Products in this table are listed alphabetically by the trade name and fell within the scope of the Best Pharmaceuticals for Children Act (BPCA) and/or the Pediatric Research Equity Act (PREA), and contain new pediatric information. Some products appearing on this list may have had studies completed under both BPCA and PREA. All BPCA products participated in the pediatric incentive program. The PREA products which participated in the BPCA incentive program by the same sponsor are marked with an asterisk (*). The PREA products marked with a (#) are labeling changes that were not based on information from clinical trials in pediatric patients. All other labeling changes are based on information from clinical trials in pediatric patients.
†All products in this table, except biologicals with a solid dot (•) by the proper name, will have a link to labeling that reflects the labeling at the time of pediatric changes and may not be the latest labeling. Biologicals will always have a link to the most recent labeling. This list only serves to highlight key information affecting the pediatric population resulting from BPCA and/or PREA at the time that particular application was approved. For the most recent labeling please go to Drugs@FDA.
Pediatric
Labeling
Date† |
Trade Name |
Generic
or Proper (biologicals•) Name |
Indications Studied |
Sponsor |
Product Labeling, FDA Full Reviews or Summary Review |
Summary of Labeling Changes |
BPCA (B)/
PREA
(P) |
10/29/2007 |
Abilify |
aripiprazole |
Schizophrenia |
Otsuka |
Label
Medical Review
Clinical Pharmacology Review |
- Extended schizophrenia indication from adults to adolescents 13–17 years
- Safety and effectiveness in pediatric patients with bipolar mania or agitation associated with schizophrenia or bipolar mania have not been established
- Efficacy for the maintenance treatment of schizophrenia in the pediatric population has not been evaluated
- In 6-week placebo controlled efficacy trial in patients 13 – 17 years with Schizophrenia 30 mg/day was not shown to be more efficacious than 10 mg/day
- Common adverse events observed were extrapyramidal disorder, somnolence, and tremor; these 3 AEs appear to have a possible dose response relationship
- Information on dose, AEs, clinical studies
|
B |
2/27/2008 |
Abilify
|
aripiprazole |
Bipolar I Disorder |
Otsuka |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Extended treatment of acute Bipolar Disorder indication from adults to pediatrics 10–17 years
- The efficacy for the maintenance treatment of Bipolar Disorder in the pediatric population has not been evaluated
- The recommended target dose in Bipolar Disorder is 10 mg/day.
- In the study of pediatric patients 10 – 17 years with Bipolar Mania, 4 common adverse reactions had a possible dose response relationship at 4 weeks; extrapyramidal disorder, somnolence, akathisia and salivary hypersecretion
- Information on dose, Aes, clinical studies
|
B |
10/21/2008 |
Acanya Gel |
clindamycin/ benzoyl peroxide combination |
Acne vulgaris in patients 12 years of age and older |
Dow |
Medical
Clinical pharmacology
Statistical |
- Safety and effectiveness established in 2 clinical studies in patients 12 years of age and older
- Safety and effectiveness in pediatric patients under the age of 12 have not been evaluated
- New drug
|
P |
5/2/2002 |
Accutane |
isotretinoin |
Severe recalcitrant nodular acne |
Hoffman La-Roche
|
Label |
- Safety and effectiveness information on pediatric patients 12-17 years of age
- Identified an increased incidence of back pain, arthralgia and myalgia in pediatric patients
- New General Precautions subsection- caution when prescribing Accutane to pediatric patients with disorders of bone metabolism, such as osteoporosis and osteomalacia
- Adolescents who participate in sports with a repetitive impact may be at increased risk for bone related injuries
- In an open-label study of pediatric patients (n=217) given a single course of therapy, 16 (7.9%) had decreases in lumbar spine bone mineral density (BMD) >4% (adjusted for body mass index); 21 (10.6%) patients had decreases in total hip BMD >5% (adjusted for body mass index)
|
B |
6/30/2008 |
Aciphex Delayed Release Tablet |
rabeprazole |
Short-term treatment symptomatic GERD in adolescent patients 12 years of age and older |
Eisai Medical Research |
Label
Medical Review
Clinical Pharmacology Review |
- Use in adolescent patients 12 years of age and older is supported by extrapolation of results from studies in adults and safety and PK studies performed in adolescent patients
- Safety and effectiveness for GERD have not been established for pediatric patients <12 years of age
- Safety and effectiveness for other uses have not been established in pediatric patients
- Adverse events (AEs) similar to those seen in adults
- Information on dose, AEs, clinical studies
|
B |
2/7/2007 |
Actiq
|
fentanyl
|
Treatment of breakthrough pain in opioid tolerant children |
Cephalon |
Label
Medical Review
Clinical Pharmacology Review |
- Safety and efficacy in patients below the age of 16 years was not established in a clinical trial of 15 patients 5 to 15 years
- Information on PK parameters and clinical studies
|
B |
2/8/2002 |
Acular & Acular PF
|
ketorolac |
Relief of ocular itching due to seasonal allergic rhinitis and postoperative inflammation after cataract extraction |
Allergan |
Label |
- Safety and effectiveness established down to 3 years; previously approved down to 12 years
|
B |
7/21/2005 |
Adderall XR
|
amphetamines, mixed salts |
ADHD |
Shire |
Label
Medical Review
Clinical Pharmacology Review |
- Expanded labeling for 13-17 year olds
- On a mg/kg body weight basis children 6-12 years have a higher clearance than adolescents or adults. Body weight is the primary determinant
- There was not adequate evidence that doses greater than 20 mg/day conferred additional benefit in a placebo-controlled study conducted in adolescents aged 13-17 with ADHD
- In a single-dose PK study in adolescents, isolated increases in systolic blood pressure (SBP) were observed in patients receiving 10 mg and 20 mg Adderall XR. Higher single doses were associated with a greater increase in SBP
- Sustained increases in blood pressure should be treated with dose reduction and/or appropriate medication
- Information on dose, PK parameters, and AE profile
|
B |
1/12/2000 |
Advil
|
ibuprofen |
Fever, minor aches & pain, cold symptoms |
Whitehall |
Label |
- Extended age range from 2 years to 6 months for the over-the-counter use based on a large safety database (14,291 patients)
|
B |
4/18/2002 |
Advil Suspension
|
ibuprofen / pseudoephedrine |
Temporary relief of nasal and sinus congestion, headache, stuffy nose, sore throat, minor aches and pains, and fever |
Whitehall |
Label |
- Information on the over-the-counter use in pediatric patients 2 to 11 years of age
|
B |
9/28/2007 |
Afluria |
influenza virus vaccine• |
For active immunization of adults 18 years of age and older against influenza disease caused by influenza virus subtypes A and type B present in the vaccine |
CSL |
Package Insert
Clinical Review
Statistical Review and Evaluation |
|
P |
12/10/2004 |
Agrylin
|
anagrelide |
Myeloproliferative disorders |
Shire |
Label
Medical Review
Clinical Pharmacology Review |
- An open-label study evaluated PK/PD but not efficacy.
- Information on PK/PD profile, dosing, AEs, and safety in patients > 6 years to 17 years
- No overall difference in dosing and safety were observed between pediatric and adult patients
- Established recommended starting dose based on limited data. Dosage should be adjusted to the lowest effective dosage
|
B |
10/07/2008 |
Akten Ophthalmic gel 3.5% |
lidocaine hydrochloride
|
Ocular surface anesthesia during ophthalmologic procedures |
Akorn |
Label |
|
P |
9/24/2000 |
Alamast
|
pemirolast |
Allergic Conjunctivitis |
Santen |
Label |
- Safety and effectiveness established down to 3 years
|
B |
3/22/2007 |
Aldara
|
imiquimod
|
Molluscum contagiosum |
Graceway Pharmaceuticals |
Label
Medical Review
Clinical Pharmacology Review |
- Efficacy in patients 2 – 12 years for the treatment of molluscum contagiosum was not demonstrated in two clinical trials in 702 patients
- Information on clinical studies and AEs
|
B |
5/12/2003 |
Allegra
|
fexofenadine |
Allergic rhinitis |
Aventis |
Label |
- Three clinical safety studies in 845 children with allergic rhinitis are described in the label
|
B |
10/16/2006 |
Allegra
|
fexofenadine |
Seasonal allergic rhinitis (SAR) uncomplicated skin manifestations of chronic idiopathic urticaria (CIU) |
Aventis |
Label
Medical Review
Clinical Pharmacology Review |
- New suspension developed
- Suspension indicated for the treatment of SAR in 2 – 11 years based on the PK comparisons in adult and pediatric patients and an extrapolation of efficacy in adults; Suspension indicated for the treatment of CIU in 6 months – 11 years based on the PK comparisons in adults and children and an extrapolation of efficacy in adults
- Safety and effectiveness of suspension in pediatric patients under 6 months of age have not been established
- Additional information on dose, PK parameters, safety and AEs
|
B |
12/20/2001 |
Alphagan
|
brimonidine |
Prevention of post-operative IOP elevations |
Allergan
|
Label |
- Safety and effectiveness established down to 2 years
- Somnolence in patients 2 to 6 years (50-83%) versus patients 7 years of age or older (25%)
|
B |
4/12/2007 |
Altabax Ointment 1% |
retapamulin |
Treatment of impetigo in patients 9 months of age and older |
GlaxoSmithKline |
Label |
- Safety and effectiveness established in studies that included 588 pediatric patients from 9 months of age to 17 years of age
- Studies waived in children 0-2 months of age and deferred in children 2-9 months of age
- New active ingredient
|
P |
1/10/2008 |
Alvesco
Inhalation Aerosol, 80 mcg & 160 mcg
|
ciclesonide |
Treatment of asthma in patients 12 years of age and older. |
Nycomed US Inc. |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Not indicated for children under the age of 12 years
- Five clinical studies evaluated safety in children 12 years of age and older
- Safety and effectiveness have not been established in children under 12 years of age
- Waiver of studies in children 0 to less than 6 months of age due to too few patients with the disease
- New dosage form
|
P |
11/28/2005 |
Amaryl
|
glimepiride |
Type-2 Diabetes Mellitus |
Aventis |
Label
Medical Review
Clinical Pharmacology Review |
- Data are insufficient to recommend pediatric use of glimepiride
- In an active-controlled, single-blind, 24-week trial, 272 pediatric patients aged 8 to 17 years with Type 2 diabetes were randomized to treatment with glimepiride or metformin. Trial suggested differences favoring metformin
- AE profile in the pediatric population was similar to that for adults
- Information on PK parameters
|
B |
3/28/2007 |
Ambien
|
zolpidem |
Insomnia associated with ADHD |
Sanofi Aventis |
Label
Medical
Clinical Pharmacology |
- Safety and effectiveness have not been established in pediatric patients with insomnia associated with ADHD
- In an 8-week controlled study in 201 pediatric patients 6-17 years, psychiatric and nervous system disorders comprised > 5% of treatment emergent adverse events, including dizziness (23.5%) headache (12.5%) and hallucinations (7.4%); treatment was discontinued due to an adverse event in 7.4%
|
B |
9/29/2004 |
Amlexanox Mucoadhesive Patch
|
amlexanox |
Treatment of apthous ulcers in children 12 years of age and older |
Access Pharmaceuticals |
Label |
- Approval based on monograph and previous studies for other indication
- no new studies submitted
- Studies in children birth – 12 years of age waived
- New indication
|
P |
12/27/2007 |
AndroGel
|
testosterone |
Use in adolescent boys with delayed puberty |
Unimed |
Label
Medical Review
Clinical Pharmacology Review |
- Safety and efficacy in males < 18 years old have not been established
- Improper use may result in acceleration of bone age and premature closure of epiphyses
|
B |
7/21/2006 |
Anthelios SX Cream |
avobenzone; ecamsule; octocrylene |
Prevention of sunburn and protection from UVA and UVB rays in children 6 months of age and older
OTC |
L’Oreal USA |
Label |
- Effectiveness extrapolated from adult studies
- Safety studies included pediatric patients 6 months of age and older
- Age range based on monograph
- Deferred studies in children < 6 months of age
- New active ingredient
|
P |
10/24/2008 |
Apidra |
insulin glulisine recombinant |
Diabetes Mellitus |
Sanofi-Aventis |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Extended indication from adults to pediatric patients 4 years and older with type 1 diabetesHas not been studied in pediatric patients less than 4 years with type 1 diabetes and in pediatric patients with type 2 diabetes
- Pediatric patients had a higher incidence of severe symptomatic hypoglycemia compared to adults in the clinical study
- New indication
|
P |
6/23/2008 |
Aptivus |
tipranavir |
Co-administered with ritonavir for combination antiretroviral in patients who are treatment-experienced and infected with HIV-1 strains resistant to more than one protease inhibitor |
Boehringer Ingelheim |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Extended indication from adults to children 2 years and older
- The risk-benefit has not been established in patients <2 years of age
- Dosing is based on body weight or body surface area not to exceed adult dose
- AEs are generally similar to those seen in adults however, rash was more frequent in pediatric patients than in adults; The frequency of rash through 48 weeks of treatment was 21%. Most rashes were mild and 5% were moderate. Overall 3% interrupted treatment due to rash
- Information on dose, AEs, PK parameters, lab abnormalities, and clinical study
|
B |
3/5/2004 |
Arava
|
leflunomide |
Polyarticular Juvenile Rheumatoid Arthritis |
Aventis |
Label
Medical Review
Clinical Pharmacology Review |
- Safety and efficacy in pediatric patients with polyarticular JRA have not been fully evaluated
- 94 patients with polyarticular JRA were studied in a double-blind active controlled trial (1:1 randomization); approximately 68% of pediatric patients receiving Arava versus 89% receiving active comparator demonstrated improvement on the primary endpoint by week 16
- Pediatric patients with a body weight ≤ 40 kg have a reduced clearance relative to adult rheumatoid arthritis patients
- Information on PK of M1, the active metabolite responsible for in vivo activity in children 3-17 years old
- Most common adverse events in 74 polyarticular JRA patients 3-17 years old included abdominal pain, diarrhea, nausea, vomiting, oral ulcers, upper respiratory tract infections, alopecia, rash, headache, and dizziness
- 14 of the 74 patients experienced ALT and/or AST elevations; 5/14 were between 3 and 8 fold the upper limit of normal
|
B |
5/5/2008 |
Argatroban
|
argatroban
|
Heparin-Induced Thrombocytopenia (HIT) or HIT with Thrombosis |
Encysive |
Label
Medical Review
Clinical Pharmacology Review |
- Safety and effectiveness, including the appropriate anticoagulation goals and duration of therapy, have not been established in pediatric patients
- Population PK/PD analysis of sparse data in 15 seriously ill pediatric patients ages <6 months – 16 years diagnosed with HIT or suspected HIT requiring an alternative to heparin anticoagulation showed clearance in pediatric patients was 50% lower compared to healthy adults and led to dose recommendations
- Information on dose, AEs and PK
|
B |
12/5/2008 |
Arimidex |
anastrozole |
Male pubertal patients with gynecomastia and female pediatric patients with McCune-Albright syndrome with progressive precocious puberty |
AstraZeneca |
Label |
- Efficacy has not been demonstrated in clinical studies of anastrozole in the treatment of pubertal gynecomastia in adolescent boys 11-18 years and in the treatment of precocious puberty in girls with McCune-Albright Syndrome 2 to < 10 years
- Information on clinical studies, AEs, and PK parameters
|
B |
3/19/2008 |
ARTISS
|
fibrin sealant (human)• |
To adhere autologous skin grafts to surgically prepared wound beds resulting from burns in adult and pediatric populations |
Baxter |
Package Insert
Pharmacology / Toxicology Review
Statistical Review |
|
P |
2/1/2008 |
Asmanex Twisthaler 110mcg inhalation powder
[Label not available] |
mometasone furoate |
Maintenance treatment of asthma as prophylactic therapy in children 4 years of age and older |
Schering Corporation |
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Not indicated for relief of acute bronchospasm or in children less than 4 years of age
- Clinical studies, including 52 week safety trial conducted in children 4 – 11 years of age
- Pediatric dosing information provided
- Child may not get the most benefit for 1 to 2 weeks or longer after starting treatment
- New dosage form
|
P |
12/17/2004 |
Augmentin ES-600 Powder for Oral Suspension#
|
amoxicillin; clavulanate |
Treatment of acute bacterial sinusitis (ABS) (sinus infection) in children 3 months of age and older |
GlaxoSmithKline |
Label |
- No new pediatric studies
- Effectiveness extrapolated from adult studies for Augmentin XR for ABS and from studies in pediatric patients with otitis media and by similar pharmacokinetics in pediatric patients
- New indication
|
P |
7/29/2005 |
Avandia
|
rosiglitazone |
Type 2 Diabetes Mellitus |
SB Pharmco |
Label
Medical Review
Clinical Pharmacology Review |
- Data are insufficient to recommend pediatric use of rosiglitazone
- In a 24 week double-blind controlled trial in children with type 2 diabetes mellitus, aged 10 to 17 years, with a baseline BMI of 33 kg/m2 were randomized to treatment with rosiglitazone or metformin
- Mean change from baseline in HbA1c was -0.14% with rosiglitazone and -0.49% with metformin
- There was an insufficient number of patients to establish statistically whether these observed mean treatment effects were similar or different
- Weight gain similar to that in adults
- Information on PK parameters, and AE profile
|
B |
3/16/2006 |
Avapro
|
irbesartan
|
Hypertension |
Sanofi-Synthelabo |
Label
Medical Review
Clinical Pharmacology Review
|
- In a study at a dose up to 4.5 mg/kg once daily, irbesartan did not appear to lower blood pressure effectively in pediatric patients ages 6 to 16 years
|
B |
4/30/2009 |
Axert
|
almotriptan |
Acute treatment of pediatric migraine in adolescent patients age 12-17 years |
Ortho-McNeil |
|
|
B |
5/25/2004 |
Axid
|
nizatidine |
Esophagitis, and heartburn due to GERD |
Reliant Pharms |
Label |
- Indicated in pediatric patients 12 years and older
- Information on dose, PK parameters, and AE profile
|
B |
4/27/2007 |
Azasite Ophthalmic Solution 1%
|
azithromycin |
Treatment of bacterial conjunctivitis caused by certain microorganisms in patients down to 1 year of age |
InSite Vision |
Label |
- Effectiveness and safety were established in controlled clinical trials including patients down to 1 years of age
- Dosing information provided
- New dosage form
|
P |
9/28/2006 |
Azopt ophthalmic suspension
|
brinzolamide
|
Elevated intraocular pressure |
Alcon |
Label
Medical Review |
- IOP-lowering efficacy was not demonstrated in a 3-month controlled clinical study in which brinzolamide was dosed only twice a day in pediatric patients 4 weeks to 5 years of age
|
B |
10/1/2001 |
Betapace
|
sotalol |
Arrhythmia |
Berlex |
Label |
- Analysis of 2 trials provided information on PK and PD in children 3 days – 12 years; safety and efficacy have not been established
- Information on dose, pharmacokinetics and AE's
- Pharmacokinetics: BSA most important covariate and more relevant than age
- Smaller children (BSA < 0.33 m2) showed tendency for larger change in QTc and increased frequency of prolongation of the QTc interval as well as greater beta-blocking effects
- Individualized dosing on a mg/m2 basis
- Information on preparation of a suspension
|
B |
9/28/2006 |
Betaxon ophthalmic suspension
|
levobetaxolol |
Elevated intraocular pressure |
Alcon |
Label
Medical Review
No clin pharm |
- Extended indication from adults to pediatric patients
- The adverse event profile was comparable to that seen in adults and elderly patients
|
B |
6/8/2007 |
Betoptic S
|
betaxolol
|
Elevated intraocular pressure in patients with chronic open-angle glaucoma or ocular hypertension |
Alcon
|
Label
Medical Review |
- Extended indication from adults to pediatric patients
- The adverse reaction profile was comparable to that seen in adults
|
B |
7/19/2001 |
Buspar
|
buspirone |
General Anxiety Disorder |
Bristol-Myers Squibb |
Label |
- Safety and effectiveness were not established in patients 6 to 17 years of age for treatment of General Anxiety Disorder at doses recommended for use in adults
- PK parameters (AUC and Cmax) of buspirone and its active metabolite were found to be equal to or higher in children and adolescents than that of adults
|
B |
1/13/2003 |
Busulfex
|
busulfan |
Part of a conditioning regimen administered prior to hematopoietic progenitor cell transplantation for a variety of malignant hematologic or non-malignant diseases |
Orphan Medical |
Label |
- The population pharmacokinetic estimates of busulfan for clearance and volume of distribution were determined in an open-label, uncontrolled PK study in 24 pediatric patients 5 months to 16 years who received busulfan as part of a conditioning regimen administered prior to hematopoietic progenitor cell transplantation for a variety of malignant hematologic or non-malignant diseases
- Suggested dosing regimen
|
B |
11/16/2001 |
Calcijex
|
calcitriol
|
Management of hypocalcemia in patients undergoing chronic renal dialysis |
Abbott
|
Label |
- The safety and effectiveness of calcitriol was examined in a double-blind placebo-controlled trial of 35 pediatric patients (13-18 years of age) with end-stage renal disease and on dialysis.
- The primary efficacy endpoint favored the calcitriol-treated versus the placebo-treated patients
- Transient hypercalcemia was seen in 1 of 16 calcitriol-treated patients; 6 of 16 (38%) calcitriol-treated patients and 2 of 19 (11%) placebo-treated patients had Ca x P >75
|
B |
6/24/2004 |
Camptosar
|
irinotecan |
Refractory solid tumors |
Pfizer |
Label
Medical Review
Clinical Pharmacology Review |
- Effectiveness in pediatric patients has not been established
- Adverse event profile from a Phase 2 trial with 170 children with refractory solid tumors comparable to that seen in adults; Grade 3-4 neutropenia experienced by 54 (31.8%) patients, neutropenia complicated by fever in 15 (8.8%) patients, Grade 3-4 diarrhea observed in 35 (20.6%) patients.
- Accrual for phase 2 study with 21 children with previously untreated rhabdomyosarcoma halted due to high rate (23.6%) of progressive disease and early deaths (14%)
- Adverse event profile seen in the 21 children different than that observed in adults; most significant Grade 3 or 4 adverse events were dehydration experienced by 6 patients (28.6%) associated with severe hypokalemia in 5 patients (23.8%) and hyponatremia in 3 patients (14.3%); in addition Grade 3-4 infection was reported in 5 patients (23.8%)(across all courses of therapy and irrespective of causal relationship)
- PK parameters comparable to adults
- Minimal accumulation of irinotecan and SN-38 (active metabolite) observed in children on daily dosing
|
B |
7/29/2008 |
Cancidas |
caspofungin |
Empirical therapy for presumed fungal infections in febrile, neutropenic patients; Candidemia and certain Candida infections; Esophageal Candidiasis; Invasive Aspergillosis in patients who are refractory to or intolerant of other therapies |
Merck |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Extended indication from adults to children 3 months and older based upon evidence from adequate and well-controlled studies in adults and PK data in pediatric patients and additional data from pediatric studies
- The efficacy and safety have not been adequately studied in infants < 3 months
- The ability of caspofungin to penetrate the blood-brain barrier and to treat patients with meningitis and endocarditis is unknown
- Dosing should be based on the patient’s body surface area. Maximum loading dose and daily maintenance dose should not exceed 70 mg
- The safety profile in pediatrics is comparably to adults
- Information on dose, AEs, PK parameters, clinical studies and infusion preparation instructions
|
B |
4/30/2008 |
Cardiolite
|
technetium tc99m sestamibi |
Medical imaging in Kawasaki disease |
Lantheus Medical Imaging |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Safety and effectiveness have not been established in the pediatric population
- No evidence of diagnostic efficacy or clinical utility of scan was found in 3 clinical studies of children and adolescents with Kawasaki disease
- A study of 445 pediatric patients failed to demonstrate the predictive value of Cardiolite rest and stress myocardial perfusion imaging to define children with Kawasaki disease at risk of developing cardiac events 6 months after receiving Cardiolite; only 3cardiac events were observed. In all 3 cases, the scan was negative
- Adverse events similar to that of adults
- Information on dose, PK, and clinical studies
|
B |
12/19/2008 |
Casodex |
bicalutamide |
Gonadotropin-independent precocious puberty in boys with familial male-limited precocious puberty (testotoxicosis) |
AstraZeneca |
Label |
- Safety and effectiveness have not been established in pediatric patients
- Bicalutamide was studied in combination with anastrozole in an open-label, non-comparative, multi-center study that assessed the efficacy and safety of this combination regimen over 12 months in the treatment of testotoxicosis in patients ≥2 years
- Of the 14 patients exposed to study treatment, 13 had at least one adverse event. Adverse reactions considered possibly related to bicalutamide included gynecomastia (43%), central precocious puberty (14%), breast tenderness (14%), breast pain (7%), asthenia (7%), increased alanine aminotransferase (7%), increased aspartate aminotransferase (7%), and musculoskeletal chest pain (7%). Headache was the only adverse reaction considered possibly related to anastrozole
- Information on clinical studies, AEs, and PK parameters
|
B |
12/15/2006 |
Celebrex
|
celecoxib |
Relief of the signs and symptoms of juvenile rheumatoid arthritis (JRA) |
Pfizer |
Label
Medical Review
Clinical Pharmacology Review |
- New indication in 2 years and older
- Has not been studied in patients < 2 years, in patients with body weight < 10 kg, or in patients with active systemic features
- Celecoxib should be used only with caution in patients with systemic onset JRA due to the risk for serious adverse reactions including the risk of disseminated intravascular coagulation
- The long-term cardiovascular toxicity in children has not been evaluated; it is unknown if the long-term risk may be similar to that seen in adults
- New 50 mg capsule developed
- Information on adding contents of a capsule to applesauce. for patients with difficulty swallowing capsules
- Information on dose, clinical studies, PK parameters, AEs
|
B |
2/18/2005 |
Celexa
|
citalopram |
Major Depressive Disorder |
Forest |
Label
Medical Review
Clinical Pharmacology Review |
- Safety and effectiveness in the pediatric population have not been established
- FDA required boxed warning for all antidepressants: Suicidality in Children and Adolescents - Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Celexa or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Celexa is not approved for use in pediatric patients. (See Warnings and Precautions: Pediatric Use) Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials
- Two placebo-controlled trials in 407 pediatric patients with MDD have been conducted with Celexa, and the data were not sufficient to support a claim for use in pediatric patients
|
B |
12/4/2002 |
Centany Ointment 2%
|
mupirocin |
Treatment of impetigo in children 2 months of age and older |
Clay-Park Labs |
Label |
- New dosage form: ointment that differed from already approved ointment with pediatric clinical trials to demonstrate equivalence
|
P |
2/24/2004 |
Children's Advil Allergy Sinus Suspension
|
chlorpheniramine; ibuprofen*; pseudoephedrine* |
Symptoms of allergic rhinitis (runny nose) and the common cold in children 6 years of age and older |
Wyeth Consumer Healthcare |
Label |
- Effectiveness extrapolated from adult studies
- Bioequivalence studies in healthy adults
- PK and safety studies in children 6 to 12 years of age
- New dosage form
|
P |
3/25/2004 |
Cipro
|
ciprofloxacin |
Complicated UTI and pyelonephritis |
Bayer |
Label
Medical Review
Clinical Pharmacology Review
|
- Indicated for the treatment of complicated urinary tract infections (cUTIs) and pyelonephritis in pediatric patients 1 – 17 years of age
- Not drug of first choice due to increased adverse events compared to controls including events related to joints and/or surrounding tissues
- Information on PK and dose in pediatric patients 1 – 17 years of age
- The most frequent adverse events observed within 6 weeks of treatment initiation during the cUTI clinical trial were gastrointestinal 15% compared to 9% and musculoskeletal 9.3% compared to 6% in ciprofloxacin-treated compared to control-treated patients, respectively
|
B |
7/18/2003 |
Ciprodex Sterile Otic Suspension
|
ciprofloxacin*; dexamethasone |
Treatment of acute otitis media in patients with tympanostomy tubes (inner ear infection) in children 6 months of age and older treatment of acute otitis externa (outer ear infection) in children 6 months of age and older |
Alcon |
Label
Medical Review |
- Over 700 pediatric patients in safety and effectiveness studies to support both indications
- Pediatric dosing information added
- New dosage form
|
P |
9/1/2004 |
Clarinex
|
desloratadine |
Seasonal and perennial allergic rhinitis, and the symptomatic relief of pruritus, and hives |
Schering |
Label |
- Indicated for seasonal allergic rhinitis down to 2 years of age. Extended age range down to 6 months for perennial allergic rhinitis and chronic idiopathic urticaria
- Safety and effectiveness of tablets or syrup has not been established in pediatric patients less than 6 months of age
- Information on dose, PK parameters, and AE profile in pediatric patients 6 months - 11 years of age
|
B |
3/3/2005 |
Clarinex D 24 Hour Extended Release Tablets
|
desloratadine*/pseudoephedrine |
Relief of nasal and non-nasal symptoms of seasonal allergic rhinitis, including nasal congestion, in patients 12 years of age and older |
Schering |
Label |
- Two safety and effectiveness studies conducted in patients 12 years of age and older
- PK study
- Studies waived in children < 12 years of age
- New active ingredient; new dosing regimen
|
P |
2/1/2006 |
Clarinex-D 12 Hour Extended Release Tablets
|
desloratadine*/ pseudoephedrine |
Relief of nasal and non-nasal symptoms of seasonal allergic rhinitis in children 12 years of age and older |
Schering |
Label |
- Approval based on two safety and effectiveness studies in patients down to 12 years of age
- Not an appropriate dosage form for use in pediatric patients below 12 years of age.
- Studies waived in children < 12 years of age
- New dosing regimen
|
P |
12/4/2000 |
Claritin
|
loratadine |
Allergic rhinitis/Urticaria |
Schering |
Label |
- Labeling for 2 - 5 year olds including information on dose, PK parameters and AE profile
- PK parameter in 2-5 year olds given a 5mg dose was comparable to the 10mg dose in children 6 years to adolescence
|
B |
7/30/2004 |
Claritin-D 12 Hour Extended-Release Tablets#
Claritin-D 24 Hour Extended-Release Tablets# |
loratadine*; pseudoephedrine |
Temporary relief of nasal congestion due to the common cold in children 12 years of age and older
OTC |
Schering-Plough |
Label |
- Approval based on monograph and previous studies for other indication
- No new studies submitted
- Studies in children birth - 12 years of age waived
- New indication
|
P |
12/28/2004 |
Clolar
|
clofarabine
|
Relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens |
Genzyme
|
Label
Medical Review
Clinical Pharmacology Review |
- Labeling for patients 1 to 21 years old. This use is based on the induction of complete responses
- Randomized trials demonstrating increased survival or other clinical benefit have not been conducted
- Information on dose, PK parameters, and AE profihe
|
B |
6/21/2004 |
Codeprex Extended-Release Suspension#
|
chlorpheniramine; codeine |
Temporary relief of cough associated with the common cold or inhaled irritants; temporary relief of symptoms of hay fever, other upper respiratory allergies, or allergic rhinitis in children 6 years of age and older
OTC |
Celltech Pharmaceuticals |
Label |
- Approval and age range based on monograph for antitussives and antihistamine
- No clinical studies submitted
- Studies in children < 6 years of age deferred
- New dosage form; new dosing regimen
|
P |
12/20/2006 |
Colazal
|
balsalazide
|
Mildly to moderately active ulcerative colitis in patients 5 years of age and older |
Salix |
Label
Medical Review
Clinical Pharmacology Review |
- Extended indication from adults to patients 5 years and older
- Dosing can be initiated at either 6.75 or 2.25 g/day
- PK of balsalazide, and metabolites showed very large inter-patient variability similar to that seen in adults
- AEs were similar to those seen in adults
|
B |
10/30/2007 |
Combigan 0.2%/0.5% ophthalmic solution
|
brimonidine tartrate/timolol maleate |
Reduction of elevated intraocular pressure in patients with glaucoma or ocular hypertension |
Allergan |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Safety and effectiveness supported by evidence from clinical studies in adults with additional data from a study in children with glaucoma ages 2 – 7 years old
- Not recommended for use in children under the age of 2 years due to safety concerns based on reports of apnea, bradycardia, hypotension, hypothermia, hypotonia, and somnolence in infants
- Safety and effectiveness have not been studied in children below the age of two years
- New active ingredient
|
P |
10/21/2004 |
Concerta
|
methylphenidate |
ADHD |
Alza |
Label
Medical Review
Clinical Pharmacology Review |
- Expanded labeling for 13-17 year olds including information on dose, PK parameters, and AE profile
- Increase in age resulted in increased apparent oral clearance
- For patients new to methylphenidate: higher maximum recommended dosage for adolescents compared to children 6-12 years of age
- Data are inadequate to determine whether chronic use of stimulants in children may cause suppression of growth. Therefore, growth should be monitored during treatment
- Safety and efficacy in children <6 years have not been established
|
B |
2/23/2007 |
Coreg
|
carvedilol |
Heart failure |
GlaxoSmithKline |
Label
Medical Review
Clinical Pharmacology Review |
- Effectiveness has not been established in patients < 18 years
- In a double-blind trial of 161 children, 2 months to 17 years with chronic heart failure receiving standard background treatment, randomized to placebo or carvedilol, carvedilol demonstrated reduction of heart rate 4-6 beats per minute
- There was no significant effect of treatment on clinical outcomes after 8 months of follow-up
- AEs occurring in ≥ 10% of patients treated with carvedilol included chest pain (17%), dizziness (13%), and dyspnea (11%)
|
B |
4/1/2004 |
Corlopam |
fenoldopam |
Indicated for the in-hospital, short-term reduction in blood pressure |
Hospira |
Label
Medical Review
Clinical Pharmacology Review |
- Indicated for the in-hospital, short-term (up to 4 hours) reduction in blood pressure in pediatric patients <1 month (at least 2 kg) to 12 years of age
- Information on PK, dose and AE profile
- Clinical studies did not include patients 12 – 16 years of age
|
B |
3/11/2004 |
Cozaar
|
losartan |
Hypertension |
Merck |
Label |
- Antihypertensive effects established in hypertensive patients 6-16 years of age
- Not recommended for pediatric patients less than 6 years or with glomerular filtration rate < 30mL/ min/1.73 m2 due to no data
- Information on PK and dose in pediatric patients 6-16 years of age.
- No relevant differences between the AE profile for pediatric patients compared to reported AEs for adults
- Information on preparation of a suspension
|
B |
3/12/2008 |
Daptacel
|
diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed• |
Active immunization against diphtheria, tetanus & pertussis as a five dose series in children 6 weeks through 6 years of age (prior to 7th birthday) |
Sanofi Pasteur |
Package Insert
Committee Chair Approval Memo
Clinical Review |
|
P |
1/25/2002 |
Daypro
|
oxaprozin |
Relief of signs and symptoms of Juvenile Rheumatoid Arthritis |
Searle |
Label |
- New indication in 6 years -16 years
|
B |
10/10/2003 |
Denavir Cream
|
penciclovir |
Treatment of recurrent herpes labialis (cold sores) in children 12 years of age and older |
Novartis |
Label |
- Extended indication down from 18 years of age to 12 years of age
- Effectiveness extrapolated from adult studies
- Safety study in patients 12-17 years of age
- Pediatric submission
|
P |
3/24/2008 |
Depakote ER Depakote Sprinkles
|
divalproex disodium |
Pediatric Bipolar Disorder; Prophylaxis of Migraine |
Abbott |
Label
Medical Review
Medical Review
Medical Review
Clinical Pharmacology Review
Medical Review Sprinkles
Clinical Pharmacology Review Sprinkles |
- Efficacy was not established in a double-blind, placebo controlled study of patients 10-17 years conducted to evaluate efficacy in the treatment of pediatric bipolar disorder
- Efficacy was not established in a double-blind, placebo-controlled study of patients 12 – 17 years conducted to evaluate the efficacy in the prophylaxis of migraine
- The safety and tolerability was similar to adults in 5 long-term safety studies
- Additional information on clinical studies, AE profile in Depakote ER labeling
|
B |
12/12/2007 |
Derma-Smoothe/FS Topical Oil, 0.01% (Body Oil)
|
fluocinolone acetonide |
Treatment of atopic dermatitis in pediatric patients 3 months and older for up to 4 weeks. |
Hill Dermaceuticals, Inc. |
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Extended age range down to 3 months
- Effectiveness and safety are not established in children less than 3 months old
- Safety was evaluated in two pediatric clinical studies (including facial use)
- Pediatric dosing and administration information provided
- Studies waived in children under 3 months of age due to safety concerns of adrenal suppression
- New indication
|
P |
5/8/2008 |
Desmopressin acetate Tablets, 0.1 mg and 0.2 mg |
desmopressin acetate |
Determine the capacity of the kidney to concentrate urine in pediatric patients (Renal Concentration Capacity Test or RCCT) and management of primary nocturnal enuresis (PNE) |
Ferring |
Medical
Clinical pharmacology |
- Eficacy in RCCT was evaluated in a single trial with children 3 to 18 years old
- Three studies evaluated efficacy in children 5 to 17 years old with PNE; an additional study evaluated efficacy in adolescents 12 to 17 years old
- Fluid intake should be adjusted downward in children to decrease the potential occurrence of water intoxication and hyponatremia
- Dosing information provided for children 3 to 18 years old for RCCT
- Dosing information provided for pediatric patients 6 years of age and older with PNE
- Tablet dosage and administration information provided for children with central diabetes insipidus
- Pharmacokinetics and pharmacodynamics were evaluated in children
- New indications and dosing regimen
|
P |
10/20/2006 |
Desonate Gel
|
desonide |
Treatment of mild to moderate atopic dermatitis in children 3 months of age and older |
Dow |
Label |
- Effectiveness established from two studies in patients 3 months to 18 years of age
- Not recommended for use in patients under 3 months of age
- Treatment should not exceed 4 consecutive weeks
- HPA axis suppression studied in patients 6 months of age to 6 years of age
- New dosage form
|
P |
4/14/2004 |
Detrol LA
|
tolterodine |
Urinary frequency and urge incontinence due to neurogenic conditions |
Pfizer |
Label
Medical Review
Clinical Pharmacology Review
|
- Efficacy in pediatric population has not been demonstrated
- The dose-plasma concentration relationship is linear in patients from 11 to 15 years
- Parent/ metabolite ratios differed according to CYP2D6 metabolizer status
- 710 pediatric patients ages 5 -10 years with urinary frequency and urge incontinence were studied in 2 randomized placebo controlled trials. Urinary tract infections were higher in patients treated with Detrol LA (6.6%) compared to placebo (4.5%)
- Aggressive, abnormal and hyperactive behavior and attention disorders occurred in 2.9% of children treated with Detrol LA compared to 0.9% treated with placebo
|
B |
11/29/2007 |
Diovan
|
valsartan |
Hypertension
|
Novartis |
Label
Medical Review
Clinical Pharmacology
Statistical |
- Labeling for 6-16 years of age
- Not recommended for pediatric patients less than 6 years due to safety findings possibly related to treatment or with glomerular filtration rate < 30mL/min/1.73m2
- Information on dose, clinical studies in 1-16 years and pharmacokinetics
- No relevant differences were identified between adverse experience profile for pediatric patients and that previously reported for adult patients
- Information on preparation of a suspension
|
B |
2/23/2001 |
Diprivan |
propofol |
Induction and/or maintenance of anesthesia |
AstraZeneca |
Label |
- Maintenance of anesthesia- age decreased down to 2 months from 3 years
- Induction of anesthesia remains the same- 3 years of age and above
- Concomitant administration with fentanyl may result in serious bradycardia
- Abrupt discontinuation following prolonged infusion may result in flushing of hands and feet, agitation, tremulousness and hyperirritability
- Propofol is not indicated for pediatric ICU sedation as safety has not been established. In a single multicenter trial of ICU sedation in critically ill pediatric patients (patients with upper respiratory tract infections excluded), the incidence of mortality (causality not established) was 9% in the propofol arm versus 4% in the standard sedative agents arm
|
B |
10/3/2001 |
Diprolene AF,
Diprosone,
Lotrisone
|
betamethasone |
Diprolene AF and Diprosone - Relief of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses Lotrisone- Treatment of symptomatic inflammatory tinea pedis, tinea cruris and tinea corporis |
Schering |
Label |
Diprolene AF Cream
- In an open-label study for the treatment of atopic dermatitis, 19 of 60 (32%) evaluable patients (ages 3 mo-12 years) showed HPA axis suppression. The younger the age group, the greater the proportion of patients with adrenal suppression.
- Indicated in patients 13 years and older. Not recommended in pediatric patients 12 years and younger
- Strengthened labeling in Clinical Pharmacology, Precautions- General and Pediatric Use subsections
- Local adverse reactions including signs of skin atrophy (telengiectasia, bruising, shininess) occurred in 10% of pediatric patients (3mo-12 years)
Diprosone Cream, Ointment, Lotion
- A separate open-label study was performed in pediatric patients with atopic dermatitis for each Diprosone formulation
- Testing for HPA axis suppression was positive with each formulation in the age groups studied: Cream - 23% (ages 2yr-12yr); Ointment - 28% (ages 6mo-12yr); and Lotion - 73% (ages 6yr-12yr)
- Indicated in patients 13 years and older. Not recommended in pediatric patients 12 years and younger
- Strengthened labeling in Clinical Pharmacology, Precautions- General and Pediatric Use subsections
- Local adverse reactions including signs of skin atrophy (telengiectasia, bruising, shininess) occurred in the cream and ointment studies
Lotrisone
- Not recommended for patients under the age of 17 years and not recommended for diaper dermatitis; previously not recommended for patients under the age of 12 years
- In an open-label study of Lotrisone cream for the treatment of tinea pedis, 17 of 43 (39.5%) evaluable patients (ages 12-16 years) demonstrated adrenal suppression as determined by cosyntropin testing
- In an open-label study of Lotrisone cream for the treatment of tinea cruris, 8 of 17 (47.1%) evaluable patients (ages 12-16 years) demonstrated adrenal suppression by cosyntropin testing
- Indicated in patients 17 years and older
|
B |
4/15/2003 |
Ditropan & Ditropan XL
|
oxybutynin |
Detrusor Overactivity Associated with a Neurological Condition |
Johnson & Johnson |
Label
Medical Review
Clinical Pharmacology Review |
Ditropan
- Additional information on dose and PK parameters
- Precautions section of label updated
Ditropan XL
- Safety and effectiveness established down to 6 years of age
|
B |
5/6/2005 |
Doryx Delayed-Release Tablets#
|
doxycycline |
Treatment of infections |
Warner Chilcott |
Label
Medical Review
No Clin Pharm |
- No new clinical studies submitted
- PK data
- Dosing information for new dosage form (to decrease esophagitis seen from capsules)
- New dosage form
|
P |
5/23/2003 |
Duocaine Injection#
|
bupivacaine; lidocaine |
Local regional anesthesia for ophthalmologic surgery by peripheral nerve block techniques in children 12 years of age and older |
Amphastar |
Label |
- Safety and effectiveness extrapolated from existing clinical database
- Safety and effectiveness not established in patients < 12 years of age
- Partial waiver 0-12 years of age because general anesthesia is preferred in that population
- New active ingredient
|
P |
5/20/2003 |
Duragesic
|
fentanyl |
Management of chronic pain |
Alza |
Label
Medical Review
Clinical Pharmacology Review |
- Safety evaluated in three open-label trials in 291 patients 2 years through 18 years of age with chronic pain
- New Warning: Duragesic should be administered to children only if they are opioid-tolerant and age 2 years or older
- New information on pharmacokinetics, dosage and administration and patient information
- Precaution to guard against accidental ingestions by children
- Adverse Events: no apparent pediatric-specific risk associated with Duragesic use in children as young as 2 years old when used as directed. Most common adverse events were fever (35%), vomiting (33%), and nausea (24%)
|
B |
9/29/2006 |
DuraPrep Surgical Solution#
|
iodine; isopropyl alcohol |
Preoperative skin preparation for use in children 2 months of age and older
OTC |
3M Health |
Review |
- Effectiveness based on determination that permeability of skin in children > 2 months of age is essentially that of adult skin
- Studies waived in children under 2 months of age for safety reasons and includes the following statement in the label: Do not use in children under 2 months of age due to excessive skin irritation and transient hypothyroidism.
- New active ingredient
|
P |
5/5/2004 and 2/18/2005 |
Effexor and Effexor XR |
venlafaxine |
Major Depressive Disorder |
Wyeth |
Label
Medical Review
Clinical Pharmacology Review |
- Effectiveness in pediatric patients has not been established
- FDA required boxed warning for all antidepressants: Suicidality in Children and Adolescents - Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Effexor or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Effexor is not approved for use in pediatric patients. (See Warnings and Precautions: Pediatric Use) Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials.
- 18% of Effexor XR treated patients (6-17 years) versus 3.6 % of placebo treated patients experienced a weight loss of at least 3.5 % in both MDD and the GAD studies
- In an open-label study increases in weight were less than expected based on data from age and sex matched peers. The difference between observed weight gain was larger for children less than 12 years than for adolescents older than 12 years
- During an 8 week placebo controlled GAD trial, Effexor XR treated patients ages 6-17 years grew an average of 0.3 cm, while placebo treated patients grew an average of 1 cm. In a 6 month open-label study, height increases that were less than expected based on data from age and sex matched pairs. The difference between observed and expected growth rates were larger for children less than 12 years than for adolescents older than 12 years
- Decreased appetite observed in 10% of patients ages 6-17 years old receiving Effexor XR
- Occurrence of blood pressure and cholesterol increases considered clinically relevant in pediatric patients similar to that observed in adults
|
B |
12/1/2005 |
Effexor XR Extended-Release Capsules
|
venlafaxine* |
Social anxiety disorder |
Wyeth |
Label
Medical Review
Clinical Pharmacology Review |
- Provided additional safety data for changes in weight, height, and appetite occurring in pediatric patient
- Information based on a clinical study of patients with SAD
- New indication (not approved in pediatric patients)
|
P |
10/16/2003 |
Elestat Ophthalmic Solution
|
epinastine |
Prevention of itching associated with allergic conjunctivitis in children 3 years of age and older |
Allergan |
Label |
- Based on effectiveness and safety studies that included children down to 10 years of age
- Partial waiver for children < 3 years of age because the condition does not exist in the age group
- New drug
|
P |
12/13/2001 |
Elidel
|
pimecrolimus |
Treatment of mild/moderate atopic dermatitis |
Novartis |
Label |
- Indicated for short-term and intermittent long-term therapy for mild to moderate atopic dermatitis in non-immunocompromised patients 2 years and older
- Not recommended for use in pediatric patients less than 2 years of age. Infants on Elidel Cream had an increased incidence of some adverse events compared to vehicle which included pyrexia, URI, nasopharyngitis, gastroenteritis, otitis media, and diarrhea.
|
B |
1/10/2007 |
Eloxatin
|
oxaliplatin |
Solid tumors |
Sanofi-Aventis |
Label
Medical Review
Clinical Pharmacology Review
|
- The effectiveness of oxaliplatin in children has not been established
- No significant activity observed in 2 Phase I and 2 Phase II trials in 159 patients ages 7 months to 22 years with solid tumors
- Information on clinical studies and AEs
|
B |
9/28/2005 |
Emtriva
|
emtricitabine |
HIV-1 infection in combination with other antiretroviral agents |
Gilead Sciences |
Label
|
- Safety and effectiveness in pediatric patients 3 months and older supported by data from 3 open-label, nonrandomized clinical studies
- Safety and effectiveness in patients < 3 months have not been established
- Relative bioavailability of Emtriva oral solution is approximately 80% of Emtriva capsules. Thus, maximum dosage is different for these 2 formulations: Solution max - 240 mg once daily; Capsules max - children weighing > 33 kg one 200 mg capsule once daily
- The AE profile in pediatric patients was comparable to that observed in adults
- Information on dose, PK parameters, AE profile and clinical studies
|
B |
12/22/2006 |
Emtriva
|
emtricitabine |
HIV-1 infection in combination with other antiretroviral agents |
Gilead Sciences |
Label
Medical Review 1
Medical Review 2
Clinical Pharmacology Review |
- Efficacy in preventing or treating HIV in neonates to 3 month olds could not be determined after a PK study in 20 neonates born to HIV positive mothers
- Information on dose in 0-3 months, additional safety and PK parameters
|
B |
12/17/2008 |
Epiduo |
adapalene and benzoyl peroxide |
Topical treatment of acne vulgaris in patients 12 years of age and older |
Galderma |
Label |
- Safety and effectiveness established in patients 12 years of age and older
- Safety and effectiveness in pediatric patients under the age of 12 have not been established
- New drug
|
P |
10/8/2002 |
Epivir
|
lamivudine |
HIV |
GlaxoSmithKline |
Label |
- Lamivudine clearance substantially reduced in 1-week-old neonates relative to pediatric patients >3 months of age
|
B |
8/16/2001 |
Epivir-HBV
|
lamivudine |
Treatment of Chronic Hepatitis B |
GlaxoSmithKline |
Label |
- Safety and effectiveness established down to 2 years
- Established a dose of 3mg/kg/day up to a maximum of 100mg/day (adult dose)
|
B |
12/10/2003 |
Ertaczo Cream
|
sertaconazole |
Treatment of interdigital tinea pedis (athlete's foot) in children 12 years of age and older |
Mylan |
Label |
- Safety and effectiveness established in clinical trials involving adolescent patients
- Studies in patients less than 12 years of age waived because there are too few children with the disease to study
- New drug
|
P |
1/2/2008 |
EVICEL
|
fibrin sealant (human)• |
Adjunct to hemostasis for use in patients undergoing surgery, when control of bleeding by standard surgical techniques is ineffective or impractical |
Johnson/Johnson Wound Management |
Package Insert
Clinical Review
Statistical Review |
|
P |
6/12/2007 |
Extina Foam, 2%
|
ketoconazole |
Topical treatment of seborrheic dermatitis in immunocompetent patients 12 years of age and older |
Stiefel Laboratories |
Label |
- Effectiveness and safety were established in a clinical study that included 44 patients from 12-17 years of age
- Studies waived in children 0-12 years of age
- New dosage form
|
P |
8/13/2004 |
Ferrlecit
|
sodium ferric gluconate complex |
Iron deficiency anemia in chronic hemodialysis patients receiving supplemental erythropoietin therapy |
Watson |
Label
Medical Review
Clinical Pharmacology Review |
- Safety and effectiveness established in pediatric patients 6 -15 years old
- Patients <6 years of age not studied
- Information on dose, PK parameters and AE profile
|
B |
5/1/2003 and 1/18/2002 |
Flonase Nasal Spray & Cutivate Ointment
|
fluticasone |
Flonase - nasal symptoms of seasonal and perennial allergic and nonallergic rhinitis
Cutivate Ointment - corticosteroid-responsive dermatoses |
GlaxoSmithKline |
Label - Flonase
Label - Cutivate
Medical Review
No clin pharm |
Flonase
- New data from 1-year placebo-controlled clinical growth study in pediatric patients 3-9 years of age; no statistically significant effect on growth was noted compared to placebo. No evidence of clinically relevant changes in HPA axis function or bone mineral density was observed as assessed by 12-hour urinary cortisol excretion and dual-energy x-ray absorptiometry, respectively.
Cutivate
- Indicated for use only in adult patients
- In a study of 35 pediatric patients treated for atopic dermatitis, subnormal adrenal function was observed with cosyntropin stimulation testing
|
B |
9/30/2003 |
Floxin Otic Solution
|
ofloxacin |
Treatment of otitis externa (outer ear infection) in children 6 months of age and older |
Daiichi |
Label
Medical Review |
- Dosing change from 2 times daily to 1 time daily for 7 days based on effectiveness and safety studies that included pediatric patients
- New dosing regimen
|
P |
8/1/2003 |
Fludara |
fludarabine |
Refractory acute leukemia and solid tumors |
Berlex
|
Label
Medical Review
Clinical Pharmacology Review |
- Fludarabine was evaluated in 62 pediatric patients and the data were insufficient to establish efficacy in any childhood malignancy
|
B |
11/9/2005 |
Fluocinolone
Acetonide Oil
|
fluocinolone |
Chronic eczematous external otitis (outer ear) in children 2 years of age and older |
Hill Dermaceuticals |
Label |
- Effectiveness established in studies of patients 2 years of age and older
- New indication
|
P |
5/26/2005 |
Focalin XR Extended-Release Capsules
|
dexmethylphenidate |
Treatment of Attention-Deficit Hyperactivity Disorder in children 6 years of age and older |
Novartis |
Label |
- Should not be used in children under 6 years of age
- Effectiveness in patients age 6 years of age and older was established in clinical studies
- PK studies also conducted
- Long-term effects in children have not been established
- New dosage form
|
P |
7/21/2006 |
Formoterol
Symbicort Inhalation Aerosol
|
budesonide* |
Long-term maintenance treatment of asthma in children 12 years of age and older |
AstraZeneca |
Label
Medical Review |
- Effectiveness and safety in patients 12 years of age and older established in studies up to 12 months long
- PK studies in patients 6-11 years of age
- Effectiveness in patients 6 to < 12 years of age has not been established
- Overall safety profile in patients 6 to < 12 years of age was similar to that observed in patients 12 years of age and older
- Studies waived in children 0-6 years of age; deferred in children 6-12 years of age
- New active ingredient
|
P |
12/21/2005 |
Fosamax
|
alendronate |
Severe osteogenesis imperfecta
|
Merck |
Label
Medical Review
Clinical Pharmacology Review |
- Alendronate is not indicated for use in children
- The efficacy and safety were examined in a randomized, double-blind, placebo-controlled two-year study of 139 patients, 4-18 years old, with severe osteogenesis imperfecta
- Treatment with alendronate did not reduce the risk of fracture
- There were no statistically significant differences between the alendronate and placebo groups in reduction of bone pain
- Information on PK parameters, AE profile, and clinical studies
|
B |
9/29/2006 |
Fuzeon
|
enfuvirtide
|
HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy |
Hoffmann-La Roche |
Label |
- Additional safety and efficacy data and AE information from clinical study in 5-16 year olds
- Insufficient data to provide dosing recommendations in patients < 6 years
|
B |
9/12/2008 |
Gardasil
|
human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant• |
Prevention of vulvar and vaginal cancer |
Merck |
Package Insert
Clinical Review
Statistical Review |
|
P |
4/26/2005 |
Gemzar
|
gemcitabine
|
Refractory leukemia |
Lilly |
Label
Medical Review |
- Effectiveness in pediatric patients has not been demonstrated
- Phase 1 trial in pediatric patients with refractory leukemia demonstrated a maximum tolerated dose; however, no meaningful clinical activity observed in a Phase 2 trial of gemcitabine in 22 patients with relapsed acute lymphoblastic leukemia and 10 patients with acute myelogenous leukemia
- Toxicities observed were similar to those reported in adults
|
B |
4/27/2006 |
Genotropin Injection
|
somatropin |
Long-term treatment of growth failure associated with Turner syndrome |
Pharmacia & Upjohn |
Label
|
- Indicated for use in pediatric patients with open epiphyses
- Effectiveness and safety based on studies in pediatric patients
- New indication
|
P |
9/27/2006 |
Gleevec
|
imatinib mesylate |
Treatment of newly diagnosed pediatric patients with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase |
Novartis
|
Label
Medical Review
Clinical Pharmacology Review |
- Extended age range for the treatment of newly diagnosed CML down to pediatric patients
- There are no data in children < 2 years of age
- Follow-up in children with newly diagnosed Ph+ chronic phase CML is limited
- Information on hematologic toxicities, AE profile, clinical studies and dosing guidelines new for newly diagnosed pediatric patients
|
B |
12/15/2000 |
Glucophage
(immediate release)
|
metformin |
Diabetes Mellitus |
Bristol-Myers
Squibb |
Label |
- Safety and effectiveness as monotherapy established in patients 10-16 years of age
|
B |
3/15/2004 |
Glucovance
|
glyburide / metformin |
Type 2 Diabetes Mellitus |
Bristol-Myers Squibb |
Label
Medical Review
Clinical Pharmacology Review |
- As studied in active-controlled, double blind trial in pediatric patients (9 – 16 years of age), Glucovance was not statistically superior to either metformin or glyburide in reducing HbA1C from baseline
- No unexpected safety findings
|
B |
12/19/2007 |
Hepsera
|
adefovir dipivoxil |
Chronic hepatitis B virus infection |
Gilead |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Extended indication from adults to pediatric patients 12 years and older
- Not recommended for children <12 years of age. Efficacy was not significantly different from placebo in a clinical study in children <12 years
- Safety ≥12 – < 18 years was similar to that observed in adults
- Information on PK, AEs, clinical study, clinical resistance
|
B |
6/2/2004 |
Humalog Injection
|
insulin lispro |
Treatment of patients with diabetes mellitus for the control of hyperglycemia (high blood sugar) in children 3-11 years of age |
Lilly |
Label |
- Safety and effectiveness established from studies in patients 3-11 years of age
- Dosing information added for external insulin pumps
- New route of administration
|
P |
11/1/2006 |
Humatrope for injection
|
somatropin [rDNA origin] |
Treatment of short stature or growth failure in children with short stature homeobox-containing gene (SHOX) deficiency |
Lilly |
Label |
- Effectiveness established from one 2-year study for SHOX in 52 pediatric patients
- Information on adverse events provided
- Dosing information provided
- New indication
|
P |
2/21/2008 |
Humira |
adalimumab |
Treatment of juvenile idiopathic arthritis |
Abbott |
Label
Medical
Clinical pharmacology
Statistical |
|
P |
10/13/2004 |
Imitrex Nasal Spray
|
sumatriptan |
Migraine |
Glaxo |
Label
Medical Review
Clinical Pharmacology Review
|
- Five clinical trials evaluating oral sumatriptan in pediatric patients ages 12 -17 years did not establish the safety and effectiveness when compared to placebo
- Postmarketing experience documents that serious AEs rarely reported in adults, including stroke, visual loss, and death have occurred in the pediatric population after use of subcutaneous, oral, and/ or nasal sumatriptan.
- Since clinical data to determine the frequency of serious adverse events in pediatric patients who might receive injectable, oral, and/ or intranasal sumatriptan are not presently available, the use of sumatriptan in patients aged younger than 18 years is not recommended
|
B |
1/31/2008 |
Inspra
|
eplerenone |
Hypertension |
Pfizer |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Effectiveness was not established in a study of 304 hypertensive pediatric patients 4 - 17 years; eplerenone, at doses up to 100 mg/ day, did not lower blood pressure effectively
- Therefore, it has not been studied in hypertensive patients <4 years old
- Eplerenone has not been studied in hypertensive patients < 4 years or in pediatric patients with heart failure
- Adverse events similar to that of adults
|
B |
5/18/2005 |
Invanz
|
ertapenem
|
Complicated Intra-abdominal Infections; Complicated Skin and Skin Structure Infections; Community Acquired Pneumonia; Complicated Urinary Tract Infections; Acute Pelvic Infections |
Merck |
Label |
- Approved for use down to 3 months of age. Efficacy extrapolated from studies in adults and supported by PK and safety studies in pediatric patients
- Not recommended in infants under 3 months of age as no data are available
- Not recommended in the treatment of meningitis in the pediatric population due to lack of sufficient CSF penetration
- Information on dose, PK parameters, AE profile and clinical studies
|
B |
5/18/2005 |
Invanz
|
ertapenem
|
Complicated Intra-abdominal Infections; Complicated Skin and Skin Structure Infections; Community Acquired Pneumonia; Complicated Urinary Tract Infections; Acute Pelvic Infections |
Merck |
Label |
- Approved for use down to 3 months of age. Efficacy extrapolated from studies in adults and supported by PK and safety studies in pediatric patients
- Not recommended in infants under 3 months of age as no data are available
- Not recommended in the treatment of meningitis in the pediatric population due to lack of sufficient CSF penetration
- Information on dose, PK parameters, AE profile and clinical studies
|
B |
3/30/2009 |
Ixiaro |
Japanese Encephalitis Vaccine, Inactivated, Adsorbed• |
Active immunization for the prevention of disease caused by Japanese encephalitis virus in persons 17 year of age and older |
Intercell Biomedical |
Package Insert - Military
Package Insert - Commercial |
|
P |
11/9/2007 |
Kaletra Oral Solution, 80 mg/20 mg &
Kaletra (1opinavir/ritonavir) Tablets, 200 mg/50 mg
|
lopinavir/ ritonavir |
HIV -1 protease inibitor indicated in combination with other antiretroviral agents for the treatment of HIV -1 infection. |
Abbott Laboratories |
Label |
- Dosing and administration information provided for children
- Use of a lower strength tablet in a twice daily dosing regimen for pediatric patients weighing greater than 15 kg
- New dosing regimen
|
P |
6/21/2005 |
Keppra
|
levetiracetam
|
Adjunctive therapy in the treatment of partial onset seizures in patients with epilepsy
|
UCB Pharma |
Label
Medical Review
Clinical Pharmacology Review
|
- Extended indication from adults to patients 4 years and older
- Safety and effectiveness have not been established in patients less than 4 years of age
- PK analysis showed that clearance increased with an increase in body weight
- Approximately 22% increase of apparent total body clearance of levetiracetam when co-administered with enzyme-inducing Anti-Epileptic Drugs (AEDs). Dose adjustment not necessary
- 37.6% of pediatric patients reported behavioral symptoms compared to 13.3% in adults
- Somnolence occurred in 22.8% in pediatric patients compared to 14.8% in adults
- Information on dose, PK parameters, AE profile and clinical studies
|
B |
3/19/2007 |
Keppra Tablets
Keppra Oral Solution
(levetiracetam*) |
levetiracetam*
|
Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in children 6 years of age and older with idiopathic generalized epilepsy |
UCB |
Label |
- Safety and effectiveness established in study that included patients down to 4 years of age
- Pediatric dosing information added
- Studies waived in children 1 month to 2 years of age and deferred in children 2-6 years of age
- New indication
|
P |
6/24/2008 |
Kinrix
|
diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine• |
Active immunization against diphtheria, tetanus, pertussis, & poliomyelitis as the fifth dose in the diphtheria, tetanus, & acellular pertussis (DTaP) series & the fourth dose in the inactivated poliovirus vaccine (IPV) in children 4 - 6 years of age whose previous DTaP vaccine doses have been INFANRIX and/or PEDIARIX for the first three doses & INFANRIX for the fourth dose |
GlaxoSmithKline Biologicals |
Package Insert
Clinical Review
Statistical Review |
|
P |
10/10/2008 |
Kogenate FS
|
antihemophilic factor (recombinant)•
|
Routine prophylaxis to reduce the frequency of bleeding episodes and the risk of joint damage in children with hemophilia A with no pre-existing joint damage |
Bayer |
Package Insert
Final review |
|
P |
8/25/2000 |
Lac-Hydrin
|
ammonium lactate |
Xerosis, ichthyosis |
Westwood-Squibb |
Label |
- Safety and effectiveness established in patients 2 – 11 years of age; previously approved ³12 years of age
|
B |
1/17/2003 |
Lamictal
|
lamotrigine
|
Adjunctive therapy for partial seizures |
GlaxoSmithKline |
Label
Medical Review
Clinical Pharmacology Review
|
- Extended indication from adults to pediatric patients ≥ 2 years
- Patients aged 2 - 18 years had clearance influenced predominantly by total body weight and concurrent antiepileptic drug (AED) therapy. The oral clearance was higher, on a body weight basis, in pediatric patients than in adults
- Because of increased clearance in pediatrics, maintenance doses in patients weighing < 30 kg may need an increase of as much as 50% based upon clinical response
- Evidence shows that the inclusion of VPA in a multi-drug regimen increases the risk of serious, potentially life-threatening rash in pediatric patients
- Approximately 11.5% of the 1,081 pediatric patients who received the drug as adjunctive therapy in clinical trials discontinued treatment because of an AE
|
B |
9/22/2006 |
Lamictal Tablets
Lamictal Chewable Dispersible Tablets
|
lamotrigine* |
Adjunctive therapy for primary generalized tonic-clonic seizures in children 2 years of age and older |
GlaxoSmithKline |
Label |
- Effectiveness established in study with patients down to 2 years of age
- Revised boxed warning to remove restrictions on use in pediatric patients
- New indication
|
P |
9/28/2007 |
Lamisil
Oral Granules
|
terbinafine |
Tinea capitis
|
Novartis |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- New indication in 4 years and older
- Two randomized safety and efficacy trials were conducted in patients 4 to 12 years old with tinea capitis. Terbinafine was dosed on a mg/kg basis and treated for 6 weeks
- Although no hepatotoxicity was seen during trials, pre-treatment serum transaminases tests are advised.
- The most common adverse events observed in the trials were nasopharyngitis, headache, pyrexia, cough, vomiting, and upper respiratory tract infection
- New 125 mg and 187.5 mg oral granule formulations developed; take with food
- Information on dose, PK parameters, AE profile, and instructions for use
|
B |
3/31/2008 |
Lancôme UV Expert 40
La Roche-Posay Anthelios 40
Vichy Capital Soleil 40 |
avobenzone, ecamsule, octocrylene, titanium dioxide cream |
OTC |
L’Oreal USA |
|
|
P |
4/20/2000 |
Lantus
|
insulin glargine |
Type 1 Diabetes |
Aventis |
Label |
- Safety and effectiveness established down to 6 years
|
B |
4/10/2006 |
Lescol and
Lescol XL
|
fluvastatin |
Heterozygous familial hypercholesterolemia as an adjunct to diet |
Novartis |
Label
Medical Review |
- New indication in adolescent boys and girls (at least one year post-menarche) 10-16 years of age, with heterozygous familial hypercholesterolemia
- Information on dose, AE profile and clinical studies
|
B |
9/11/2007 |
Levaquin
|
levofloxacin
|
Community-acquired pneumonia |
Ortho-McNeil |
Label
Medical Review
Clinical Pharmacology Review |
- Levofloxacin is not indicated for pediatric patients < 18 years of age
- In a prospective, long-term, surveillance study, levofloxacin treated children had a significantly higher incidence of musculoskeletal (MS) disorders (arthralgia, arthritis, tendonopathy, and gait abnormality) compared to non-fluoroquinolone-treated children
- Information on clinical studies, AE profile
|
B |
5/5/2008 |
Levaquin Tablets, 250 mg, 500 mg, and 750 mg#
Levaquin Oral Solution, 25 mg/mL#
Levaquin Injection and Levaquin Injection, 5 mg/mL#
|
levofloxacin
levofloxacin in 5% dextrose injection |
Reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis (inhalational anthrax post-exposure) |
Ortho-McNeil-Janssen Pharmaceutical, Inc. |
|
- New indication
- Dosing information provided for children less than and greater than 50 kg
- Efficacy is based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit, and animal studies were used to evaluate survival; the product has not been tested in humans for the post-exposure prevention of inhalation anthrax
- Safety in pediatric patients treated for more than 14 days has not been studied
- Long-term safety data, including effects on cartilage, following administration in pediatric patients is limited
- Due to possible side effects, use is not recommended for pediatric patients except in the prevention of anthrax after inhalational exposure
- Pharmacokinetics were investigated in pediatric patients 6 months to 16 years old
|
P |
3/19/2009 |
Lexapro Tablets 5 mg, 10 mg, and 20 mg and Oral solution 5 mg/mL |
escitalopram oxalate |
Major depressive disorder in adolescents |
Forest Laboratories |
|
Summary pending |
B |
6/14/2007 |
Lexiva Oral Suspension
|
fosamprenavir |
Treatment of HIV infection in patients 2-18 years of age |
GlaxoSmithKline |
Label |
- Effectiveness and safety were established in two clinical studies of pediatric patients 2-18 years of age
- Adverse event profile is similar to that of adults with the exception of vomiting, which, regardless of causality, occurred more frequently among pediatric patients
- Dosing information provided
- Studies waived in children 0-1 month of age and deferred in children 1 month - 2 years of age
- New dosage form
|
P |
6/29/2006 |
Lidocaine and Tetracaine Cream
|
lidocaine; tetracaine |
Topical local analgesia for superficial dermatological procedures |
ZARS |
Label |
- Studies failed to show effectiveness over placebo in reducing the pain associated with venipuncture in pediatric patients 5-17 years of age
- New active ingredient
|
P |
5/6/2004 |
Lidosite Topical System Kit
|
epinephrine; lidocaine |
Topical local analgesia for superficial dermatological procedures in children 5 years of age and older |
Vyteris |
Label |
- 505(b)(2) with clinical studies
- Safety and effectiveness established in studies of pediatric patients 5-18 years of age
- PK study in pediatric patients 6-15 years of age dosing regimen established in clinical trials
- Studies in patients 0-5 years of age deferred
- New dosage form; new route of administration
|
P |
10/18/2002 |
Lipitor
|
atorvastatin |
Heterozygous Familial Hypercholesterolemia |
Pfizer |
Label |
- New indication in adolescent boys and girls (post-menarche) 10-17 years of age
|
B |
5/18/2007 |
Locoid Lotion 0.1%
|
hydrocortisone butyrate |
Treatment of mild to moderate atopic dermatitis in children 3 months of age and older |
Ferndale Labs |
Label |
- Effectiveness established in one study of 284 patients from 3 months to 18 years of age
- Information provided on HPA axis suppression from one safety study with Locoid Lotion of 84 pediatric patients from 3 months to 18 years of age with moderate to severe atopic dermatitis affecting at least 25% of body surface area
- Studies waived in children < 3 months of age
- New dosage form
|
P |
8/11/2000 |
Lodine
|
etodolac |
Relief of signs & symptoms of Juvenile Rheumatoid Arthritis |
Wyeth Ayerst |
Label |
- New indication in 6 years -16 years
- Higher dose (per kg basis) in younger children which is approximately 2 times the lower dose recommended for adults
|
B |
8/4/2005 |
Loperamide Hydrochloride Soft Gelatin Capsules#
|
loperamide |
Control symptoms of diarrhea in children 12 years of age and older |
Banner Pharmacaps |
Label |
- New dosage form; new dosing regimen
- No new clinical studies
- Bioequivalence study in adults compared the current OTC drug (Imodium caplet) and this drug
- Studies waived in children 0-2 years of age
|
P |
3/2/2004 |
Lotensin |
benazepril |
Hypertension |
Novartis
|
Label
Medical Review
Clinical Pharmacology Review |
- Information on dose, PK in pediatric patients 6-16 years of age
- Not recommended for pediatric patients less than 6 years or with glomerular filtration rate < 30mL/min/1.73 m2 due to insufficient data
- Infants below the age of 1 year should not be given ACE inhibitors due to concerns over possible effects on kidney development
- The clearance rate was substantially higher in hypertensive children and adolescents than that of healthy adults
- The terminal half life (t1/2) in pediatric patients was one third of that observed in adults
- Adverse event profile in pediatric patients was similar to that seen in adults
- Information on preparation of a suspension
|
B |
9/28/2000 and 2/18/2005 |
Luvox
|
fluvoxamine |
Treatment of obsessions and compulsions in patients with OCD |
Solvay |
Label |
- Determined that a dose adjustment (increased dose) may be necessary in adolescents and girls 8-11 years of age may require lower doses
- FDA required boxed warning for all antidepressants: Suicidality in Children and Adolescents - Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of fluvoxamine or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Fluvoxamine is not approved for use in pediatric patients except for patients with obsessive compulsive disorder (OCD). (See Warnings and Precautions: Pediatric Use) Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials
- The efficacy of fluvoxamine for the treatment of OCD was demonstrated in a 10-week multicenter placebo controlled study with 120 outpatients ages 8 to 17. In addition, 99 of these outpatients continued open-label fluvoxamine treatment for up to another one to three years, equivalent to 94 patient years
|
B |
12/2/2003 |
Malarone |
atovaquone/ proguanil |
Treatment of malaria |
GlaxoSmithKline
|
Label
Medical Review
Clinical Pharmacology Review |
- Safety and efficacy for treatment of malaria established down to5 kg.
- Attributable AE occurring in ≥ 5% of the pediatric patients (5-< 11 kg) was diarrhea (6%)
- Malarone tablets may be crushed and mixed with condensed milk just prior to administration for children who may have difficulty swallowing.
- The apparent clearance (CL/F) of both atovaquone and proguanil are related to body weight
|
B |
7/14/2000 |
Malarone
|
atovaquone/proguanil |
Prophylaxis and treatment of malaria |
Glaxo Wellcome |
Label |
- Safety and effectiveness established down to ³ 11kg
- Information on dose, efficacy, PK parameters and AE profile
- Elimination half-life is shorter in pediatric patients (1 to 2 days) than in adults (2 to 3 days)
- Attributable AE’s occurring in ³ 5% of the pediatric patients were vomiting (10%) and pruritus (6%)
|
B |
12/8/2005 |
Meridia
|
sibutramine |
Obesity |
Abbott |
Label
Medical Review
Clinical Pharmacology Review |
- The data are inadequate to recommend the use of sibutramine for the treatment of obesity in pediatric patients
- Efficacy in obese adolescents has not been adequately studied
- Sibutramine's mechanism of action inhibiting the reuptake of serotonin and norepinephrine is similar to that of some antidepressants
- It is unknown if sibutramine increases the risk of suicidal behavior or thinking in pediatric patients
- In a study of adolescents with obesity in which 368 patients were treated with sibutramine and 130 patients with placebo, one patient in each group attempted suicide. Suicidal ideation was reported by 2 sibutramine-treated patients and none of the placebo patients
|
B |
5/25/2005 |
Merrem I.V.
|
meropenem |
Treatment of complicated skin and skin structure infections in children 3 months of age and older |
AstraZeneca |
Label |
- Supported by extrapolating safety and effectiveness from an adequate and well-controlled adult study and additional data from pediatric PK studies
- Studies waived for children < 3 months of age
- New indication
|
P |
4/15/2003 |
Methylin Chewable Tablets#
|
methylphenidate |
Treatment of Attention-Deficit Hyperactivity Disorder in children 6 years of age and older
treatment of narcolepsy in children 6 years of age and older |
Mallinckrodt |
Label |
- Bioequivalence studies in adults
- New dosage form
|
P |
2/14/2002 |
Mevacor
|
lovastatin |
Heterozygous Familial Hypercholesterolemia |
Merck |
Label |
- New indication in adolescent boys and girls (at least one year post-menarche) 10-17 years of age
|
B |
8/11/2005 |
Mobic
|
meloxicam
|
Relief of signs and symptoms of pauciarticular or polyarticular course Juvenile Rheumatoid Arthritis |
Boehringer Ingelheim |
Label
Medical Review
Clinical Pharmacology Review |
- Safety and efficacy established in patients 2 years of age and older
- Clinical studies evaluated doses ranging from 0.125 mg/kg/day to 0.375 mg/kg/day. There was no additional benefit demonstrated by doses above 0.125 mg/kg/day in the clinical trials. The lowest effective dose should be used
- Adverse events in children were similar to those in adults including skin reactions and gastrointestinal bleed risk
- Information on dose, PK parameters, AE profile and clinical studies
|
B |
5/27/2003 |
Monopril |
fosinopril |
Hypertension |
Bristol-Myers Squibb
|
Label
Medical Review
Clinical Pharmacology Review |
- New data from a double-blind study in 252 patients 6-16 years of age
- New recommended dose in children weighing more than 50kg
- New Information on PK parameters
- An appropriate dosage strength is not available for children weighing less than 50kg
|
B |
4/15/1999 |
Motrin
|
ibuprofen |
Fever, minor aches & pain, cold symptoms |
McNeil |
Label |
- Extended age range from 2 years to 6 months for the over-the-counter use based on a large safety database (27,000 patients)
|
B |
8/1/2000 |
Motrin Suspension
|
ibuprofen / pseudoephedrine |
Temporary relief of nasal and sinus congestion, minor body aches and pains, fever, stuffy nose, headache and sore throat |
McNeil |
Label |
- Information on the over-the-counter use in pediatric patients 2 to 11 years of age
|
B |
1/23/2008 |
Moxatag |
amoxicillin |
Use for tonsillitis and/or pharyngitis secondary to Streptococcus pyogenes patients 12 years of age and older |
Middlebrook Pharmaceuticals |
Label
Medical Review
Clinical pharmacology Review
Statistical Review |
- Safety and effectiveness in pediatric patients younger than 12 years have not been established
- One clinical study evaluated safety and effectiveness in pediatric patients 12 years of age and older with no significant differences in treatment response or adverse reactions between adults and children
- A prospective study of 51 children suggested that overdosages of less than 250 mg/kg are not associated with significant clinical symptoms and do not require gastric emptying
- Waiver of studies in children ages 0 to less than two years because too few children have the disease
- New dosage form
|
P |
4/29/2004 |
Mucinex DM Extended-release Tablet#
|
guaifenesin; dextromethorphan |
Expectorant and cough suppressant in children 12 years of age and older |
Adams Respiratory Therapeutics
|
Label |
- 505(b)(2) approved with no pediatric information
- Age range based on monograph
- Do not use in children under 12 years of age
- studies waived in children < 12 years of age due to safety concerns
- New dosage form
|
P |
2/27/2004 |
Myfortic
Delayed-Release Tablets
|
mycophenolic acid |
Prevention of organ rejection in patients receiving allogeneic renal transplants in children 5-16 years of age with stable renal transplants |
Novartis |
Label |
- Approval based on extrapolation of safety and effectiveness in adult patients
- One PK study with information down to 5 years of age
- Waived studies in birth to 10 years because there are too few children to study.
- New active ingredient
|
P |
9/19/2008 |
Nasacort AQ |
triamcinolone |
Treatment of the nasal symptoms of seasonal and perennial allergic rhinitis in adults and children 2 years of age and older |
Sanofi-Aventis |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Expands pediatric use, or age range, to include patients 2 to 5 years of age
- Dosing and administration information provided
- Not recommended for children under 2 years of age
- An effect on adrenal function in children 2 to 5 years of age cannot be ruled out
- Pharmacokinetics were evaluated in children 2 to 5 years of age
- Safety and efficacy were evaluated in one clinical study involving pediatric patients 2 to 5 years old
- Studies in children >6 months and less than 2 years of age were not performed due to safety concerns since controlled clinical studies have shown that intranasal corticosteroids may cause a reduction in growth velocity in pediatric patients.
|
P |
3/27/2001 |
Nasalcrom
|
cromolyn |
Prevention and relief of nasal symptoms of hay fever and other nasal allergies |
Pharmacia & UpJohn |
Label |
- Established proper dose in 2 year - 6 year olds and provided additional safety and compliance data for this age group
|
B |
7/17/2002 |
Nasonex-nasal
Elocon-topical
|
mometasone
|
Nasonex - Perennial and seasonal allergic rhinitis
Elocon - Relief of inflammatory and pruritic manifestations of corticosteroid dermatose |
Schering |
Label - Nasonex
Label - Elocon Cream
Label - Elocon Ointment
Label - Elocon Lotion |
Nasonex Nasal Spray
- Extended age range from 3 years down to 2 years
- In a clinical study in which pediatric patients 2-5 years were treated with mometasone nasal spray for up to 42 consecutive days, no significant effect on adrenal function was found
- Upper respiratory tract infection was more common with Nasonex (2/28) compared to placebo (0/28)
Elocon Cream & Ointment
- Evidence of HPA axis suppression in pediatric patients 6-23 months of age
- Outlined local AE's as well as skin atrophy in pediatric patients 6-23 months of age
- Approved down to 2 years of age as in previous labeling
Elocon Lotion
- Safety and effectiveness have not been established in pediatric patients below 12 years of age and use <12 year old is not recommended
- Should not be used for the treatment of diaper dermatitis
|
B |
11/5/2002 |
Navelbine
|
vinorelbine |
Malignant tumors |
GlaxoSmithKline |
Label |
- New data from a single-arm study in 46 patients with recurrent solid malignant tumors, including rhabdomyosarcoma /undifferentiated sarcoma, neuroblastoma, and CNS tumors, at doses similar to those used in adults showed no meaningful clinical activity
|
B |
7/24/2008 |
Navstel Intraocular Irrigating Solution Sterile# |
balanced salt ophthalmic solution with hypromellose, dextrose and glutathione |
Use as an intraocular irrigating solution during surgical procedures involving perfusion of the eye |
Alcon |
Label |
- Safety and efficacy have been demonstrated in pediatric patients
- New active ingredient
|
P |
10/12/2000 |
Neurontin |
gabapentin |
Adjunctive therapy in the treatment of partial seizures |
Parke-Davis |
Label |
- Safety and effectiveness established down to 3 years
- Neuropsychiatric AE's identified in 3-12 year olds
- Oral clearance normalized per body weight increased in children <5 years
- Higher doses of gabapentin required in children <5 years
|
B |
4/28/2006 |
Nexium
|
esomeprazole |
Short-term treatment of GERD |
AstraZeneca |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Use in adolescent patients 12 to 17 years of age is supported by extrapolation from studies in adults, and safety and PK studies performed in adolescent patients
- Safety and effectiveness in patients < 12 years has not been established
- Safety and effectiveness for other pediatric uses have not been established
- Information on dose, treatment related AEs, clinical study
|
B |
2/27/2008 |
Nexium Delayed-Release Oral Suspension, 10 mg |
esomeprazole |
Short-term treatment of GERD and healing of erosive esophagitis in pediatric patients aged 1-11 years. |
AstraZeneca |
Label
Medical
Clinical pharmacology
Statistical |
- Expanded age range to include pediatric patients 1-11 years. Previously approved in 12-17 years
- Use in pediatric patients 1 to 17 years of age is supported by extrapolation from studies in adults, and safety and PK studies performed in pediatric and adolescent patients
- Safety and effectiveness in pediatric patients <1 year of age have not been established
- Safety and effectiveness for other pediatric uses have not been established
- Information on dose, treatment related adverse events (AEs), clinical study
- New formulation
|
B |
8/30/2002 |
Nolvadex
|
tamoxifen |
McCune-Albright Syndrome |
AstraZeneca |
Label |
- A study in 28 female patients aged 2-10 years with McCune-Albright Syndrome and precocious puberty did not demonstrate safety and effectiveness. Long term effects have not been established
- Mean uterine volume increased after 6 months of therapy and doubled at end of 1-year study
|
B |
9/20/2007 |
Norditropin Cartridges |
somatropin [rDNA origin] |
Treatment of short stature in
children with Turner syndrome |
Novo Nordisk |
Label |
- Safety and effectiveness based on studies in pediatric patients
- New Warning: Patients with Turner syndrome should be evaluated carefully for otitis media and other ear disorders since these patients have an increased risk of ear and hearing disorders. Somatropin treatment may increase the occurrence of otitis media in patients with Turner syndrome. In addition, patients with Turner syndrome should be monitored closely for cardiovascular disorders (e.g., stroke, aortic aneurysm/dissection, hypertension) as these patients are also at risk for these conditions
- Information on recommended dosing, adverse events (AEs) and clinical studies
- New indication
|
P |
1/08/2004 |
Norvasc
|
amlodipine |
Hypertension |
Pfizer |
Label |
- Information on dose, PK in pediatric patients 6-17 years of age
- Adverse event profile in pediatric patients was similar to that seen in adults
|
B |
10/6/2005 |
Norvir
|
ritonavir |
Treatment of HIV-infection in combination with other antiretroviral agents |
Abbott |
Label
Medical Review
Clinical Pharmacology Review |
- Extended age range from 2 years down to 1 month
- AE profile in the pediatric population was similar to that for adults
- Information on dose and PK parameters
|
B |
9/13/2005 |
NovoLog
|
insulin aspart [rDNA origin] injection
|
Diabetes Mellitus |
Novo Nordisk |
Label
Medical Review |
- In clinical studies comparing NovoLog to regular human insulin in patients 2 to 18 years with type 1 diabetes, NovoLog achieved glycemic control comparable to regular human insulin
- The incidence of hypoglycemia was similar for both treatment groups
|
B |
3/14/2008 |
NovoLog |
insulin aspart [rDNA origin] injection |
Insulin analog indicated to improve glycemic control |
Novo Nordisk |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Efficacy was demonstrated in a clinical study with pediatric patients ages 4 to 18 years using an external insulin pump
- New dosing regimen
|
P |
9/15/2006 |
Noxafil Oral Suspension
|
posaconazole |
Prevention of invasive Aspergillis and Candida infections in patients 13 years of age and older |
Schering |
Label |
- Information on PK and safety studies in patients 13-17 years of agesafety profile in patients 8-17 years of age similar to adults
- Safety and effectiveness in patients below 13 years of age have not been established
- Additional information on pharmacokinetics provided in patients down to 8 years of age
- Studies deferred in children 0-12 years of age
- New drug
|
P |
11/21/2007 |
Omnaris Nasal Spray
|
ciclesonide |
Treatment of seasonal allergic rhinitis (SAR) in patients 6 through less than 12 years of age |
Nycomed US Inc. |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Indication extended down to 6 years of age
- Pediatric dosing information provided
- Two clinical studies evaluated safety in children 6 to 11 years of age and the overall incidence of adverse events was comparable to those treated with placebo
- Efficacy in children 2 to 5 years of age was not established in clinical trials conducted in this age group.
- Waiver of studies in children ages 0 to less than 2 years of age for SAR because of local and systemic safety concerns as well as lack of disease and/or diagnosis difficulties in children
- New indication
|
P |
5/22/2000 |
Optivar
|
azelastine |
Itching associated with Allergic Conjunctivitis |
Muro Pharma/Asta Medica |
Label |
- Safety and effectiveness established down to 3 years
|
B |
5/9/2008 |
OraVerse Injection 0.4 mg (0.235 mg/mL) |
phentolamine mesylate |
Reversal of soft-tissue anesthesia, i.e., anesthesia of the lip and tongue, and the associated functional deficits resulting from an intraoral submucosal injection of a local anesthetic containing a vasoconstrictor |
Novalar Pharmaceuticals, Inc. |
Medical
Clinical pharmacology
Statistical |
- Use in children less than 6 years of age or weighing less than 15 kg (33 lbs) is not recommended
- Dosing information provided for children weighing 15 to 30 kg (66 lbs)
- Safety and efficacy were established in 2 clinical trials in children 12 to 17 years old, one trial in children ages 6 to 11 years, as well as adult studies
- Safety has been evaluated in pediatric patients under the age of 6 years but not efficacy
- Pharmacokinetics have been evaluated in children weighing 15 kg or more
- New indication
|
P |
4/7/2008 |
Orencia |
abatacept |
Moderate to severe polyarticular juvenile idiopathic arthritis |
Bristol-Myers Squibb |
Medical Review
Clinical Pharmacology Review
Statistical Review |
|
P |
5/13/2005 |
Ortho Tri-Cyclen
|
norgestimate/ ethinyl estradiol
|
Evaluation of total hip bone mineral density in adolescent females with anorexia nervosa |
Ortho McNeil |
Label
Medical 1 Review
Medical 2 Review
Clinical Pharmacology Review |
- No significant difference between Ortho Tri-Cyclen and placebo in mean change in total lumbar spine (L1-L4) and total hip bone mineral density in 123 adolescent females with anorexia nervosa in a double-blind, placebo-controlled, multicenter, one-year clinical trial
|
B |
12/22/2004 |
Pataday Ophthalmic Solution
|
olopatadine |
Treatment of ocular itching associated with allergic conjunctivitis (itchy eyes) in children 3 years of age and older |
Alcon |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Based on clinical trials that included patients down to 3 years of age.
- New indication
-
|
P |
4/15/2008 |
Patanase Nasal Spray |
olopatadine hydrochloride |
Relief of symptoms of seasonal allergic rhinitis (SAR) in patients 12 years of age and older |
Alcon Research, Ltd. |
Label
Medical
Clinical pharmacology
Statistical |
- Safety and effectiveness in children below the age of 12 years have not been established
- Symptoms of antihistamine overdose in children may initially include agitation and restlessness followed by drowsiness
- Efficacy and safety were evaluated in 3 clinical trials of 2 weeks duration in adult and adolescent patients, 12 years of age and older, with symptoms of SAR
- Dosage and administration information provided for children 12 years and older
- New indication, dosage form, dosing regimen, and route of administration
|
P |
1/12/2005 |
Paxil
|
paroxetine |
Major Depressive Disorder |
Glaxo |
Label
Medical Review
Clinical Pharmacology Review |
- Safety and effectiveness in the pediatric population have not been established
- FDA required boxed warning for all antidepressants: Suicidality in Children and Adolescents - Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Paxil or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Paxil is not approved for use in pediatric patients. (See Warnings and Precautions: Pediatric Use) Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials
- Three placebo-controlled trials in 752 pediatric patients with MDD have been conducted with Paxil, and the data were not sufficient to support a claim for use in pediatric patients
|
B |
6/20/2008 |
Pentacel
|
diphtheria and tetanus toxoids and acellular pertussis adsorbed, inactivated poliovirus and haemophilus b conjugate (tetanus toxoid conjugate) vaccine• |
Active immunization against diphtheria, tetanus, pertussis, poliomyelitis and invasive disease due to Haemophilus influenzae type b |
Sanofi Pasteur |
Package Insert
Clinical Review
Statistical Review
Recommendations regarding request for partial waiver of pediatric studies |
|
P |
6/6/2002 |
Pepcid
|
famotidine |
Gastroesophageal reflux |
Merck |
Label |
- Labeling for patients less than 1 year of age including information on dose, PK/PD parameters and AE profile
- Lower dose recommended in patients <3 months of age
- Pediatric patients 0-3 months of age had clearance values 2 to 4-fold less than those in older patients and adults
- In a clinical study of 35 pediatric patients <1 year of age, agitation was observed in 5 patients on famotidine and resolved upon discontinuation of the drug
|
B |
10/29/2002 |
Pravachol
|
pravastatin |
Heterozygous Familial Hypercholesterolemia |
Bristol-Myers Squibb |
Label |
- New indication in boys and girls 8-18 years of age
|
B |
10/28/2008 |
Prevacid |
lansoprazole |
Symptomatic GERD in infants |
Takeda |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Effectiveness was not established in a 4 week multicenter, double-blind, placebo-controlled study of patients 1 month and < 12 months of age
- AE profile similar to that observed in adults
- Information on PK parameters in neonates to < 1 year, and clinical studies
|
B |
6/17/2004 |
Prevacid
|
lansoprazole |
Short-term treatment of symptomatic GERD and erosive Esophagitis |
Tap |
Label
Medical Review
Clinical Pharmacology Review |
- Expanded age range to include patients 12 -17 years of age; previously labeled only in pediatric patients 1-11 years of age
- Safety and effectiveness in pediatric patients <1 year of age have not been established
- Information on dose, PK parameters, and AE profile
|
B |
12/18/2008 |
Prezista |
darunavir
|
Treatment of HIV infection in pediatric patients 6 years and older when co-administered with ritonavir (Prezista/rtv), and with other antiretroviral agents |
Tibotec |
Label |
- Extended indication from adults to pediatric patients 6 years and older
- Safety and effectiveness in pediatric patients 3 to < 6 years of age have not been established
- Do not administer in pediatric patients below 3 years of age
- Do not administer Prezista/rtv once daily in pediatric patients
- Dosing for patients 6 to < 18 years and weighing at least 44 lbs (20 kg) is based on body weight not to exceed adult dose
- AE similar to those seen in adults
- Information on dose, AEs, PK parameters, lab abnormalities, and clinical study
|
B |
7/12/2002 |
Prilosec
|
omeprazole |
Gastroesophageal reflux and erosive esophagitis |
AstraZeneca |
Label |
- Safety and effectiveness established in pediatric patients 2-16 years of age
- Information on dose, PK parameters, exposure/response and AE profile
|
B |
3/20/2008 |
Prilosec |
omeprazole |
Maintenance healing of erosive esophagitis |
AstraZeneca |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Efficacy was extrapolated from adults and older children to 1 to 2 year olds and supported with an open-label trial
- Unique adverse reactions in pediatric patients included increased respiratory system adverse events and fever.
- Safety and effectiveness in children less than 1 year of age have not been established
- Dosing and administration information provided for patients 1 year and older weighing at least 5 kg.
- New dosage form
|
P |
5/29/2003 |
Prinivil
|
lisinopril |
Hypertension |
Merck |
Label |
- Labeling for 6-16 years of age
- Not recommended for pediatric patients with glomerular filtration rate < 30ml/min/1.73m2
- Information on dose, efficacy and pharmacokinetics
- No relevant differences were identified between adverse experience profile for pediatric patients and that previously reported for adult patients
- Information on preparation of a suspension
|
B |
2/3/2006 |
ProAir HFA Inhalation Aerosol
|
albuterol |
Prevention of exercise-induced bronchospasm in children 12 years of age and older |
IVAX |
Label |
- Expands use from previously approved bronchospasm with reversible obstructive airway disease
- Effectiveness based on study in adults and adolescents
- Safety and effectiveness in pediatric patients below 12 years of age have not been established
- New indication
|
P |
8/17/2007 |
Provigil
|
modafinil |
Narcolepsy |
Cephalon, Inc |
Label
Medical Review
Clinical Pharmacology Review |
- Modafinil is not approved for use in pediatric patients for any indication
- Safety and effectiveness were not demonstrated in a controlled 6-week study in 165 pediatric patients 5-17 years with narcolepsy
- Serious rash, including Stevens-Johnson Syndrome, requiring hospitalization and discontinuation of treatment has been reported in adults and children in association with the use of modafinil
- In the controlled and open-label clinical studies, treatment emergent adverse events of the psychiatric and nervous system included Tourettes’ syndrome, insomnia, hostility, increased cataplexy, increased hypnagogic hallucinations and suicidal ideation
- Information on safety, AEs and clinical stud
|
B |
1/3/2003 and
2/18/2005 |
Prozac
|
fluoxetine |
Major Depressive Disorder (MDD) & Obsessive Compulsive Disorder (OCD) |
Lilly |
Label |
- Effectiveness established in patients 7-17 years of age for OCD
- Effectiveness established in patients 8-17 years of age for MDD
- FDA required boxed warning for all antidepressants: Suicidality in Children and Adolescents - Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Prozac or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Prozac is approved for use in pediatric patients with MDD and obsessive compulsive disorder (OCD). (See Warnings and Precautions: Pediatric Use) Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials
- Decreased weight gain has been observed in association with the use of fluoxetine, as with other SSRIs. In one 19-week clinical trial pediatric subjects treated with fluoxetine gained an average of 1.1cm less in height (p=0.004) and 1.1 kg less in weight (p=0.008) than those treated with placebo. Therefore, height and weight should be monitored periodically in pediatric patients treated with fluoxetine
- Mania/hypomania led to discontinuation of 1.8% of fluoxetine treated patients vs. 0% of placebo controlled patients in the three placebo-controlled trials combined. Regular monitoring for the occurrence of mania/hypomania is recommended
- Higher average steady state fluoxetine and norfluoxetine concentrations were observed in children than in adolescents. These differences were almost entirely explained by differences in weight
- Separate dosing recommendations in lower weight children
|
B |
2/26/2003 |
Pulmicort
|
budesonide |
Maintenance and Prophylaxis of Asthma |
AstraZeneca |
Label
Medical Review |
- Safety information in pediatric patients 6 to 12 months of age
- A dose dependent effect on growth was observed in the 12-week trial which supports the finding that the use of Pulmicort Respules in infants 6 to 12 months of age may result in systemic effects and is consistent with the findings of growth suppression in other studies with inhaled corticosteroids
- Pneumonia was observed more frequently in patients treated with Pulmicort Respules than in patients treated with placebo
|
B |
3/11/2005 |
Rapamune
|
sirolimus |
Prophylaxis of organ rejection in patients undergoing renal transplants |
Wyeth |
Label
Medical Review
Clinical Pharmacology Review |
- Safety and efficacy established in children 13 years or older judged to be at low to moderate immunologic risk
- Safety was assessed in a controlled clinical trial in pediatric (<18 years of age) renal transplant recipients considered high immunologic risk. The use of Rapamune in combination with calcineurin inhibitors and corticosteroids was associated with an increased risk of deterioration of renal function, lipid abnormalities, and urinary tract infections
- Safety and efficacy have not been established in pediatric patients less than 13 years old or in pediatric renal transplant recipients considered at high immunologic risk
- Information on PK parameters, adverse events and safety
|
B |
12/28/2001 & 7/29/2003 |
Rebetron
|
ribavirin/intron a |
Chronic hepatitis C |
Schering |
Label |
- Labeling for 3 years to 16 years
- There are no safety and efficacy data on treatment for longer than 48 weeks in pediatric patients
- Pharmacokinetic information on patients 5 to 16 years with chronic hepatitis C virus infection
- Increased incidence of suicidal ideation or attempts (2.4% versus 1%) among pediatric patients compared to adult patients
- Decrease in rate of linear growth (mean percentile assignment decrease of 9%) and in rate of weight gain (mean percentile assignment decrease of 13%) during 48 weeks of treatment; a general reversal was noted during the 24 week post treatment period
- Patients with viral genotype 1, had a lower response rate to combination therapy compared to patients with genotype non-1, 36% versus 81%
- In general, the adverse event profile in the pediatric population was similar to that observed in adults
- New oral suspension developed
|
B |
3/29/2006 |
Relenza
|
zanamivir |
Prevention of influenza in children 5 years of age and older |
GlaxoSmithKline |
Label |
- Safety and effectiveness for prophylaxis based on 4 clinical studies in patients 5-16 years of age
- No differences in safety and effectiveness were observed between pediatric and adult subjects.
- Dosing information provided
- Studies waived in children <5 years of age
- New indication
|
P |
1/12/2005 |
Remeron
|
mirtazapine
|
Major Depressive Disorder |
Organon |
Label
Medical Review
Clinical Pharmacology Review
|
- Safety and effectiveness in the pediatric population have not been established
- FDA required boxed warning for all antidepressants: Suicidality in Children and Adolescents - Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Remeron or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Remeron is not approved for use in pediatric patients. (See Warnings and Precautions: Pediatric Use) Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials
- Two placebo-controlled trials in 258 pediatric patients with MDD have been conducted with Remeron and the data were not sufficient to support a claim for use in pediatric patients
|
B |
9/19/2008 |
Retrovir syrup, capsules and tablets# |
zidovudine |
Used in combination with 18 other antiretroviral agents for the treatment of HIV-1 infection |
GlaxoSmithKline |
Label
Medical
Clinical pharmacology |
- Dosing and administration information provided to children 6 weeks to less than 18 years of age
- Macrocytosis was reported in the majority of pediatric patients receiving Retrovir 180 mg/m2 every 6 hours in open-label studies
- New dosing regimen
|
P |
3/25/2008 |
Reyataz |
atazanavir |
Treatment of HIV - 1 in pediatric patients 6 to 18 years of age |
Bristol Myers Squibb |
Label
Medical Review
Clinical Pharmacology Review |
- Extended indication from adults to children 6 years and older
- The safety, activity, and pharmacokinetic profiles in pediatric patients ages 3 months to < 6 years have not been established. Atazanavir should not be administered to pediatric patients below the age of 3 months due to the risk of kernicterus
- Dosing is based on body weight or body surface area not to exceed adult dose
- Adverse events (AEs) are generally similar to those seen in adults
- Information on dose, AEs, PK parameters, lab abnormalities, and clinical study
|
B |
8/22/2007 |
Risperdal
|
risperidone |
Schizophrenia; short-term treatment of acute manic or mixed Episodes associated with Bipolar I Disorder |
Johnson & Johnson |
Label
Medical Review
Clinical Pharmacology Review |
- Extended schizophrenia indication from adults to adolescents 13–17 years; extended bipolar mania indication from adults to children and adolescents 10-17 years
- Safety and effectiveness in children < 13 years of age with schizophrenia have not been established; safety and effectiveness in children < 10 years of age with bipolar mania have not been established
- No additional benefit was seen above 3 mg/day in schizophrenia studies and 2.5 mg/day in the Bipolar mania study; higher doses were associated with more adverse events. Doses higher than 6 mg/day have not been studied.
- Information on dose, clinical studies, AE profile
|
B |
10/6/2006 |
Risperdal Tablets
Risperdal Oral Solution
Risperdal M-Tabs
|
risperidone* |
Treatment of irritability associated with autistic disorder in children 5 years of age and older |
Janssen |
Label
Medical Review
Clinical Pharmacology Review
|
- Effectiveness and safety established based on two 8 week studies in patients 5-16 years of age and one long-term study of 4-6 months
- Studies waived in children under 2 years of age due to difficulty to diagnose and treat this population
- New indication
|
P |
4/3/2008 |
Rotarix
|
rotavirus vaccine, live, oral• |
Prevention of rotavirus gastroenteritis caused by G1 and non-G1 types (G3, G4, and G9) in infants and children when administered as a two-dose series between the ages of 6-24 weeks |
GlaxoSmithKline
Biolgocials |
Package Insert
Clinical Review
Statistical Review
Toxicology Review |
|
P |
5/10/2006 |
Sandostatin LAR
|
octreotide
|
Weight loss due to hypothalamic obesity from cranial insult |
Novartis |
Label
Medical Review
Clinical Pharmacology Review |
- A randomized double-blind, placebo-controlled study in 60 patients aged 6 –17 years with hypothalamic obesity from cranial insult did not demonstrate efficacy and safety of octreotide as a weight loss agent; Mean BMI increased 0.1 kg/m2 in drug treated patients compared to 0.0 kg/m2 in control-treated patients
- No unexpected AEs were observed; However, the incidence of new cholelithiasis in this pediatric population (33%) was higher than that seen in adult indications
- Information on PK parameters and AEs
|
B |
1/12/2005 |
Serzone
|
nefazodone |
Major Depressive Disorder |
Bristol-Myers Squibb |
Label
Medical Review
Clinical Pharmacology Review |
- Safety and effectiveness in the pediatric population have not been established
- FDA required boxed warning for all antidepressants: Suicidality in Children and Adolescents - Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Serzone or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Serzone is not approved for use in pediatric patients. (See Warnings and Precautions: Pediatric Use) Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials
- Two placebo-controlled trials in 286 pediatric patients with MDD have been conducted with Serzone, and the data were not sufficient to support a claim for use in pediatric patients
|
B |
7/26/2002 |
Singulair
|
montelukast |
Prophylaxis and chronic treatment of asthma |
Merck |
Label |
- Safety and effectiveness established in patients 12 months to 5 years of age
- Information on dose, PK parameters and AE profile in patients 12-23 months and 2-5 years
- New 4mg chewable tablet and 4mg oral granule formulations developed. The chewable tablets contain aspartame whereas the oral granule formulation does not
|
B |
7/27/2005 |
Singulair Oral Granules#, Tablets#, and
Chewable Tablets#
|
montelukast |
Relief of symptoms of perennial allergic rhinitis in children 6 months of age and older |
Merck |
Label |
- Effectiveness was extrapolated from a rhinitis study in patients 15 years of age and older safety and PK in patients as young as 6 months is supported by extrapolation from safety data obtained from studies in patients 6 to 23 months of age with asthma
- Studies waived in children < 6 months of age
- New indication
|
P |
12/31/2002 |
Singulair Oral Granules*, Tablets*, and
Chewable Tablets*
|
montelukast |
Seasonal allergic rhinitis in children 2 years of age and older |
Merck |
Label |
- Effectiveness extrapolated from studies in patients 15 years of age and older and supported with one pediatric safety trial in patients 2-14 years of age
- New indication
|
P |
7/27/2006 |
Sodium Chloride Injection#
|
sodium chloride |
Use in flushing compatible contrast agents through IV administration sets into indwelling intravascular access devices |
Tyco Healthcare |
Label |
- Safety of manual injection in pediatric patients is supported by reported clinical experience with IV infusion and flush safety and effectiveness of Sodium Chloride Injection, USP 0.9% administered by power injection in pediatric patients have not been established
- Administration to pediatric patients by power injection is not recommended
- To minimize the risk of fluid overload, the smallest dose necessary for manually flushing contrast agent through the vascular access line should be used
- Manual injection to pediatric patients should take into account the patient's weight, fluid status, and concomitant medical conditions to determine if use is appropriate
- New indication
|
P |
5/8/2006 |
Solodyn Extended-Release Tablets
|
minocycline |
Treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in children 12 years of age and older |
Medicis |
Label |
- Only used to treat inflammatory lesions of non-nodular moderate to severe acne vulgaris
- Safety and effectiveness established from studies in patients 12 years of age and older
- Safety and effectiveness in pediatric patients below 12 years of age has not been established
- Studies waived in children 0-11 years of age
- New dosage form
|
P |
11/26/2002 |
Strattera
|
atomoxetine |
Attention-Deficit Hyperactivity Disorder |
Lilly |
Label |
- Safety and effectiveness established down to 6 years of age
- It is unknown whether final adult height or weight is affected by treatment. Patients on long-term treatment should be monitored
- The effectiveness of atomoxetine beyond 9 weeks and safety beyond 1 year in pediatric patients, has not been systematically evaluated in controlled trials
|
B |
12/15/2006 |
Suprane
|
desflurane
|
Safety study of 2 agents used for maintenance of anesthesia in non-intubated patients |
Baxter |
Label
Medical Review |
- Not indicated for maintenance of anesthesia in non-intubated pediatric patients
- In a clinical safety trial in patients 2 - 16 years, desflurane and isoflurane were compared for maintenance of anesthesia in non-intubated patients to assess the incidence of respiratory adverse events. Desflurane was associated with higher rates of coughing, laryngospasm and secretions with an overall rate of respiratory events of 39%. 5% of pediatric patients 2-16 years old exposed to desflurane, experienced severe laryngospasm
- The incidence of respiratory events was highest in children aged 2-6 years; therefore, similar studies in children under the age of 2 years were not initiated.
- Additional information on clinical studies and AEs
|
B |
4/14/2009 |
Suprane
|
desflurane
|
Safety study of 2 agents used for maintenance of anesthesia in non-intubated patients |
Baxter |
|
|
B |
12/14/2000 |
TamiFlu
|
oseltamivir |
Treatment of uncomplicated acute illness due to influenza |
Roche |
Label
Medical Review
Clinical Pharmacology Review |
- Safety and effectiveness established for treatment in patients 1-12 years of age
- The safety and effectiveness in pediatric patients younger than 1 year of age have not been established
- Safety and effectiveness for prophylaxis in pediatric patients younger than 13 years of age have not been established (Note: labeled for prophylaxis down to 1 year due to PREA on 12/21/2005)
- The adverse event profile in adolescents is similar to that for adults and pediatric patients aged 1 to 12 years
- Information on dosing, PK parameters, AE profile, and clinical studies
|
B |
6/24/2004 |
TamiFlu
|
oseltamivir |
Treatment of uncomplicated acute illness due to influenza infection in patients 1 year and older |
Roche |
Label
Medical Review
Clinical Pharmacology Review |
- Not recommended in pediatric patients less than 1 year of age because of uncertainties regarding the rate of development of the human blood-brain barrier and the unknown clinical significance of animal toxicology data for human infants
|
B |
12/21/2005 |
TamiFlu
|
oseltamivir |
Prophylaxis in pediatric patients 1 year to <13 years of age |
Roche |
Label |
|
P |
1/17/2008 |
TamiFlu
|
oseltamivir |
Safety information resulting from studies that established treatment of uncomplicated acute illness due to influenza infection in patients 1 year and older |
Roche |
Label
Medical Review
Clinical Pharmacology Review |
- Influenza can be associated with a variety of neurologic and behavioral symptoms which can include events such as hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease.
- These events have been reported in patients receiving oseltamivir, primarily among pediatric patients, appear to be uncommon, and often had an abrupt onset and rapid resolution
- If neuropsychiatric symptoms occur, the risks and benefits of continuing treatment should be evaluated for each patient
|
B |
3/11/2003 |
Temodar
|
temozolomide |
Recurrent CNS tumors |
Schering |
Label
Medical Review
Clinical Pharmacology Review |
- Temozolomide effectiveness in children has not been demonstrated
- New data from 2 open-label Phase 2 studies in pediatric patients 3-18 years of age. In one study there were 29 patients with recurrent brain stem glioma and 34 patients with recurrent high grade astrocyoma. In a second study there were 122 patients enrolled with various types of tumors; 113 CNS tumors and 9 non-CNS tumors.
- The temozolomide toxicity profile in children is similar to adults
|
B |
6/8/2007 |
Timolol GFS
|
timolol |
Elevated intraocular pressure in patients with chronic open-angle glaucoma or ocular hypertension |
Falcon Pharmaceuticals |
Label
Medical Review |
- Extended indication from adults to pediatric patients
- The adverse reaction profile was comparable to that seen in adults
|
B |
10/13/2006 |
Tirosint capsules#
|
levothyroxine |
Replacement or supplemental therapy in hypothyroidism; treatment or prevention of euthyroid goiters |
Institute Biochimique SA |
Label |
- Contraindicated in infants, small children, or any child who may be unable to swallow a capsule.
- Dosing information provided
- Information to monitor disease provided
- No clinical studies submitted
- New dosage form
|
P |
6/29/2005 |
Topamax Tablets
and Sprinkle Capsules |
topiramate* |
Initial monotherapy for partial onset or primary generalized tonic-clonic seizures in children 10 years of age and older |
Johnson & Johnson |
Label |
- Effectiveness established in studies of patients down to 6 years of age
- Use in patients who were converted to monotherapy from a previous regimen of other anticonvulsant drugs have not been established in controlled trials
- Provides information regarding treatment-emergent decrease in serum bicarbonate and adverse events
- Some patients in the study discontinued therapy due to adverse events; however, adverse events associated with discontinuing therapy included difficulty with concentration/attention
- Studies waived in children 0-2 years of age; deferred in children 2-10 years of age
- New indication
|
P |
7/18/2007 |
Toprol XL
|
metoprolol
|
Hypertension |
AstraZeneca |
Label
Medical Review
Clinical Pharmacology Review |
- A study in 144 pediatric hypertensive pediatric patients aged 6 - 16 years did not meet its primary endpoint. However, some study endpoints demonstrated effectiveness
- Adverse event profile similar to adults
- Safety and effectiveness have not been established in patients < 6 years of age
- Information on PK parameters, clinical studies, and dose
|
B |
11/29/2007 |
Triesence 40mg/mL
|
triamcinolone acetonide injectable suspension |
Visualization during vitrectomy |
Alcon Research, Ltd. |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Efficacy and safety of corticosteroids in the pediatric population are based on the well-established course of effect of corticosteroids, which is similar in pediatric and adult populations
- Adverse effects of corticosteroids in pediatric patients are similar to those in adults
- New indication
|
P |
10/28/2005 |
Trileptal
|
oxcarbazepine |
Use as adjunctive therapy in children aged 2 years and above with epilepsy |
Novartis |
Label
Medical Review
Clinical Pharmacology Review |
- Extended adjunctive therapy age range from 4 years down to 2 years
- No evidence drug was effective as adjunctive therapy in patients < 2 years
- In clinical studies as adjunctive therapy, apparent clearance (L/hr/kg) decreased when age increased such that children 2 to <4 years of age may require up to twice the dose per body weight compared to adults; and children 4 to ≤12 years of age may require a 50% higher dose per body weight compared to adults
- Approximately 11% of pediatric patients < 4 years discontinued treatment because of adverse events including convulsions, status epilepticus and ataxia
- Information on dose, PK parameters, AE profile and clinical studies
|
B |
4/14/2004 |
Trusopt
|
dorzolamide |
Reduction in intraocular pressure |
Merck |
Label |
- Safety and IOP-lowering effects have been demonstrated in pediatric patients
- Adverse event profile was comparable to that seen in adults
|
B |
3/30/2001 |
Ultane
|
sevoflurane |
Induction and maintenance of general anesthesia |
Abbott |
Label |
- New study in pediatric patients 9 days-12 years comparing sevoflurane and halothane
- Precautions section and Adverse Events During Post-Marketing subsection updated to add information on the rare cases of seizures that have been reported in pediatric patients in association with sevoflurane use. The majority of cases were in children and young adults, most of whom had no medical history of seizures
- Pediatric information consolidated into new Pediatric Use subsection
|
B |
3/8/2004 |
Ultiva
|
remifentanil |
Maintenance of anesthesia |
Abbott |
Label |
- Safety and efficacy for the maintenance of anesthesia established from birth to 1 year of age
- Recommended dosing guidelines for maintenance of anesthesia for patients from birth to 2 months
- The clearance rate observed in neonates was highly variable – approximately 2 times higher than young healthy adults
- Individual doses for each patient should be carefully titrated
|
B |
10/5/2006 |
UV Protective Suncare#
Capital Soleil 20#
Anthelios 20#
UV Expert 20# |
avobenzone; ecamsule; octocrylene; titanium |
Prevention of sunburn and protection from UVA and UVB rays in children 6 months of age and older
OTC |
L'Oreal |
Label |
- No clinical studies submitted to support
- Age range based on monograph
- Studies deferred in children under 6 months of age
- New active ingredient
|
P |
9/3/2008 |
Valtrex |
valacyclovir |
Chickenpox; active or at risk for herpes virus infection |
GlaxoSmithKline |
Label
Medical
Clinical Pharmacology
Clinical pharmacology |
- New indication for treatment of chickenpox in pediatric patients 2 to <18 years based on single-dose pharmacokinetic and multiple-dose safety data from an open-label trial with valacyclovir and supported by safety and extrapolated efficacy data from 3 randomized, double-blind, placebo-controlled trials evaluating oral acyclovir in pediatric patients with chickenpox
- The efficacy and safety of valacyclovir have not been established in pediatric patients:
- <12 years of age with cold sores
- <18 years of age with genital herpes
- <18 years of age with herpes zoster
- <2 years of age with chickenpox,
- for suppressive therapy following neonatal HSV infection
- Adverse events similar to that of adults
- Information on PK parameters, AEs, clinical studies, and preparation of an extemporaneous formulation
|
B |
4/19/2007 |
Valtropin |
somatropin [rDNA origin] |
Short stature in children with Turner Syndrome |
LG Life |
Label |
|
P |
3/2/2006 |
Vanos Cream
|
fluocinonide |
Relief of the inflammatory and pruritic manifestations of corticosteroid responsive dermatoses in children 12 years of age and older |
Medicis |
Label |
- Use in pediatric patients younger than 12 years of age is not recommended
- Effectiveness extrapolated from adult studies
- Safety in patients 12 to 17 years of age was similar to that observed in adults
- Information provided on HPA axis suppression from safety studies with Vanos Cream in 4 cohorts of pediatric patients (3 months - 18 years of age) with atopic dermatitis
- Studies waived in children 0-11 years of age
- New indication
|
P |
2/13/2001 |
Vasotec |
enalapril |
Hypertension |
Merck |
Label |
- Labeling for 1 month-16 years of age
- Information on dose, efficacy and pharmacokinetics
- Information on preparation of a suspension
|
B |
3/26/2008 |
Ventolin HFA |
albuterol
|
Treatment of symptoms of bronchospasm associated with obstructive airway disease |
GlaxoSmithKline |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Safety and effectiveness of albuterol administered with or without a spacer device in children < 4 years of age has not been demonstrated
- 3 randomized, double-blind, placebo-controlled studies in 250 children < 4 years, in which efficacy was nor demonstrated, suggest that either the optimal dose has not been defined in this age-group or the drug is not effective in this age-group
- Information on clinical studies
|
B |
9/19/2006 |
Verdeso Foam
|
desonide |
Treatment of mild to moderate atopic dermatitis in patients 3 months of age and older |
Connetics |
Label |
- Effectiveness established from studies in 581 pediatric patients 3 months to 17 years of age
- Effect on HPA axis function was investigated in pediatric patients 6 months to 17 years of age in one study of 75 patients
- Safety has not been evaluated in patients below 3 months of age
- Use for the minimum amount of time necessary due to the potential to suppress HPA axis treatment should not exceed 4 consecutive weeks
- New dosage form
|
P |
10/15/1998 |
Versed
|
midazolam |
Sedation/anxiolysis/
amnesia |
Roche |
Label |
- Specified the effective dose, effective dose range, and time of onset
- Defined volume of distribution and similarity to adult protein binding and elimination
- Additional information on AE's and warnings about concomitant medications
- Identified a subpopulation (children with congenital heart disease and pulmonary hypertension) at higher risk for AE's and the need to start therapy at the lower end of the dosing range
|
B |
4/1/2002 |
Videx
|
didanosine |
HIV infection |
Bristol-Myers Squibb |
Label
Medical Review
Clinical Pharmacology Review |
- Safety and effectiveness established down to 2 weeks
|
B |
9/29/2008 |
Videx EC |
didanosine |
Treatment of HIV in pediatric patients >20 kg |
Bristol-Myers Squibb |
Label
Medical
Clinical pharmacology |
- Extended indication from adults to children weighing >20kg who can swallow capsules
- Dosing is based on body weight not to exceed adult dose
- Adverse events (AEs) are generally similar to those seen in adults
- Information on dose, AEs, population PK analysis, lab abnormalities, and historical clinical studies
|
B |
4/15/2003 |
Vigamox
|
moxifloxacin |
Bacterial Conjunctivitis |
Alcon |
Label |
- Safety and effectiveness established down to 1 year of age
|
B |
8/19/2004 |
Vioxx
|
rofecoxib |
Pauciarticular or polyarticular course Juvenile Rheumatoid Arthritis |
Merck |
Label
Medical Review
Clinical Pharmacology Review |
Merck announced a voluntary worldwide withdrawal of Vioxx (rofecoxib) due to safety concerns on September 30, 2004. |
B |
3/19/2004 |
Viracept
|
nelfinavir |
HIV-1 |
Pfizer |
Label
Medical Review
Clinical Pharmacology Review |
- Safety and effectiveness established in patients 2 – 13 years of age
- New twice daily dosing regimen and modified three times daily dosing for pediatric patients > 2 years
- A reliably effective dose not established in patients <2 years of age
- PK information in pediatric patients from birth to 13 years of age
- Highly variable drug exposure is a significant problem in pediatric patients
- Adverse event profile was similar to that for adults
|
B |
6/24/2008 |
Viramune Tablets 200 mg
Viramune Oral Suspension 10 mg/mL |
nevirapine |
Use in combination with other antiretroviral agents for the treatment of HIV-1 infection |
Boehringer Ingelheim |
Label
Medical Review
Clinical Pharmacology Review |
- Dosing information provided for children ages >15 days to <16 years old
- Safety was evaluated in children 2 weeks and older in 5 clinical trials and important adverse events (all causality) include rash (21%), neutropenia (8.9%), anemia (7.3%) and hepatotoxicity (2.4%)
- Safety, pharmacokinetics, and virologic and immunologic responses have been evaluated in HIV-infected pediatric patients age 3 months to 18 years
- Safety and pharmacokinetics were evaluated in HIV-infected pediatric patients age 15 days to < 3 months
- Efficacy was evaluated in one clinical study with children 3 months to 16 years of age
- Post-marketing surveillance has shown anemia to be more commonly observed in children although development of anemia due to concomitant medication use cannot be ruled out
- Potential drug interaction information is provided for children with respect to lopinavir/ritonavir
- New dosing regimen
|
P |
12/16/2004 |
VisionBlue Ophthalmic Solution#
|
trypan blue |
Aid in ophthalmic surgery by staining anterior capsule |
DORC International |
Label |
- Approved for use in all populations based on information from clinical trials in the literature
- New drug
|
P |
12/27/2007 |
Voluven
|
6% hydroxyethyl starch 130/0.4 in 0.9% sodium chloride injection•
|
Plasma volume substitute for treatment and prophylaxis of hypovolemia |
Fresenius Kabi Norge AS |
Package Insert
PREA Review Memo
Clinical Pharmacology |
|
P |
2/16/2006 |
Vusion Ointment
|
miconazole |
Adjunctive treatment of diaper dermatitis in children 4 weeks of age and older |
Barrier Therapeutics |
Label |
- Indicated for use in immunocompetent children
- Presence of candidal infection should be established by microscopic evaluation prior to initiating treatment
- Effectiveness based on three clinical studies in infants and toddlers
- Safety when used for more than 7 days is not known
- New active ingredient
|
P |
2/23/2007 |
Vyvanse Capsules |
lisdexamfetamine |
Treatment of ADHD in children 6 to 12 years of age |
New River |
Label |
- Effectiveness established in two studies of patients 6-12 years of age
- Long-term effectiveness of more than 4 weeks has not been established
- Studies waived in children 0-5 years of age and deferred in children 13-17 years of age
- New active ingredient
|
P |
12/12/2003 |
Xenical
|
orlistat |
Obesity management |
Roche |
Label
Medical Review
Clinical Pharmacology Review |
- Use in 12-16 year olds is supported by studies in adults with additional data from a 54 week safety and efficacy study in obese adolescent patients.
- Since orlistat can reduce absorption of fat soluble vitamins, all patients should take a daily multivitamin supplement containing fat soluble vitamins.
- Adverse event profile in adolescent patients was similar to that seen in adults
|
B |
7/28/2006 |
Xolegel Gel
|
ketoconazole |
Treatment of seborrheic dermatitis in children 12 years of age and older |
Barrier Therapeutics |
Label |
- Effectiveness established from studies in patients 12 years of age and older
- Safety and effectiveness in pediatric patients below 12 years of age have not been establishedstudies waived in children 0-12 years of age
- New dosage form
|
P |
3/11/2005 |
Xopenex HFA Inhalation Aerosol
|
levalbuterol |
Treatment of bronchospasm in patients with reversible obstructive airway disease in children 4 years of age and older |
Sepracor |
Label |
- Extended indication for use in children down from 6 years of age
- Pediatric patients have a lower exposure to the drug than adults
- Population PK model developed from patients down to 4 years of age
- Effectiveness and safety established from studies in adults, adolescents (12 years of age and older) and children ages 4-11 years of age with asthma.
- Deferred studies in patients < 4 years of age
- New active ingredient
|
P |
1/28/2008 |
Xyzal 0.5 mg/mL
Oral Solution# |
levocetirizine dihydrochloride |
Relief of symptoms associated with seasonal and perennial allergic rhinitis (SAR and PAR) and treatment of uncomplicated skin manifestations of chronic idiopathic urticaria (CIU) |
UCB |
Label
Medical
Clinical pharmacology |
- Dosing information provided
- Studies waived in children less than 6 months of age with PAR and CIU
- Waived in children less than 2 years of age with SAR
- New dosage form pediatric
|
P |
5/25/2007 |
Xyzal Tablets 5 mg |
levocetirizine
|
Relief of symptoms associated with seasonal allergic rhinitis and perennial allergic rhinitis in
adults and children 6 years of age or older, and for the treatment of the uncomplicated skin
manifestations of chronic idiopathic urticaria in adults and children 6 years of age or older |
UCB |
Label |
|
P |
10/19/2006 |
Zaditor ophthalmic solution#
|
ketotifen |
Temporary relief of itchy eyes in children 3 years of age and older
OTC |
Novartis |
Label |
- No new studies submitted
- New indication
|
P |
10/22/1999 |
Zantac
|
ranitidine |
Gastroesophageal Reflux |
Glaxo |
Label |
- Small studies in newborns 0 to 1 month receiving ECMO did not demonstrate efficacy but provided information on dose and PK
|
B |
3/31/2004 |
Zemplar
|
paricalcitol |
Secondary hyperparathyroidism associated with end stage renal disease |
Abbott |
Label
Medical Review |
- Safety and effectiveness were examined in a 12 week randomized, double-blind, placebo-controlled study of 29 pediatric patients aged 5-19 years old with end stage renal disease on hemodialysis; information
- Primary efficacy analysis revealed 9 of 15 patients in Zemplar group had 2 consecutive 30 % decreases from baseline intact PTH compared with 3 of 14 patients in placebo group
- No patients in either group developed hypercalcemia (defined as at least one calcium value >11.2 mg/dL) during study
|
B |
8/28/2008 |
Zemuron |
rocuronium |
adjunct
to general anesthesia |
Organon USA |
Label
Medical Review
Clinical Pharmacology Review |
- Expanded pediatric indication to include 0-17 years. Previously approved in ages 3 months – 14 years
- Not recommended for rapid sequence intubation in pediatric patients
- In clinical studies of rocuronium, onset time and clinical duration varied with dose, the age of the patient, and anesthetic technique
- The overall analysis of ECG data in pediatric patients indicates that the concomitant use of rocuronium with general anesthetic agents can prolong the QTc interval
- The time to maximum block for an intubating dose was shortest in infants and longest in neonates. The duration of clinical relaxation following an intubating dose is shortest in children > 2 years to 11 years and longest in infants
- Additional information on dose, clinical studies, and PK/PD parameters
|
B |
3/29/2002 |
Zerit
|
stavudine |
HIV infection |
Bristol-Myers Squibb |
Label |
- Safety and effectiveness established down to birth
- Established a dose for newborns from birth to 13 days
|
B |
7/1/2003 |
Zestril
|
lisinopril |
Hypertension |
AstraZeneca |
Label |
- Labeling for 6-16 years of age
- Not recommended for pediatric patients less than 6 years or with glomerular filtration rate < 30mL/min/1.73m2
- Information on dose, efficacy and pharmacokinetics
- No relevant differences were identified between adverse experience profile for pediatric patients and that previously reported for adult patients
- Information on preparation of a suspension
|
B |
6/5/2008 |
Zetia and
Vytorin |
ezetimibe
and ezetimibe/ simvastatin |
Heterozygous familial hypercholesterolemia as an adjunct to diet |
MSP Singapore |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review
Medical Review
Clinical Pharmacology
Statistical Review |
- The effects of ezetimibe co-administered with simvastatin compared to simvastatin monotherapy have been evaluated in adolescent boys and girls with heterozygous familial hypercholesterolemia (HeFH)
|
B |
12/17/1998 |
Ziagen |
abacavir |
HIV infection |
GlaxoSmithKline |
Label |
- Labeling for 3 months - 12 years
- Information on dose, efficacy, PK parameters and AE profile
|
B |
12/19/2008 |
Ziagen |
abacavir
|
Treatment of HIV-1 infection in pediatric patients weighing >14 kg |
GlaxoSmithKline |
Label
Medical
Clinical pharmacology |
- New pediatric dosing regimen using new scored tablet for pediatric patients weighing > 14 kg for whom a solid dosage form is appropriate
|
B |
11/7/2006 |
Ziana Gel
|
clindamycin; tretinoin |
Treatment of acne vulgaris in patients 12 years of age and older |
Dow |
Label
Medical
Clinical Pharmacology Review
Statistical Review |
- Effectiveness and safety based on two studies in patients 12 years of age and older
- New active ingredient
|
P |
1/15/2004 |
Zithromax Tablets
|
azithromycin |
Treatment of acute bacterial sinusitis (sinus infection) in patients 6 months of age and older |
Pfizer |
Label
Medical Review
Clinical Pharmacology Review |
- Effectiveness extrapolated from adult sinusitis studies and from pediatric acute otitis media studies
- Clinical studies conducted in pediatric patients 3 years to 16 years of age to determine PK and safety for oral suspension
- Safety and effectiveness in patients under 6 months of age have not been established
- Side effects seen in pediatric patients were comparable to those seen in adults, with different incidence rates for the dosage regimens recommended in pediatric patients
- Dosing regimen established
- Partial waiver < 6 months of age because too few patients to study
- New indication
|
P |
10/8/2008 |
Zmax Oral Susp |
azithromycin |
Community-Acquired Pneumonia |
Pfizer |
Label
Medical Review
Clinical pharmacology |
|
P |
10/18/2002 |
Zocor
|
simvastatin |
Heterozygous Familial Hypercholesterolemia |
Merck |
Label |
- New indication in adolescent boys and girls (at least one year post-menarche) 10-17 years of age
|
B |
3/25/2005 |
Zofran
|
ondansetron |
Prevention of chemotherapy-induced and postoperative induced nausea and vomiting |
GlaxoSmithKline |
Label
Medical Review
Clinical Pharmacology Review |
- Established dosing for surgical patients down to 1 month from 2 years of age
- Established dosing for cancer patients down to 6 months from 4 years of age
- Surgical and cancer patients < 18 years tend to have a higher ondansetron clearance compared to adults leading to a shorter half-life in most pediatric patients
- The clearance of ondansetron in patients 1- 4 months of age is slower and the half-life is approximately 2.5 fold longer than patients who are > 4 – 24 months of age
- Patients < 4 months of age receiving this drug should be closely monitored
- Additional information on dose, PK parameters, AE profile and safety
|
B |
2/18/2005 |
Zoloft
|
sertraline |
Major Depressive Disorder and Obsessive Compulsive Disorder |
Pfizer |
Label
Medical Review |
- Safety and effectiveness in the pediatric population other than pediatric patients with OCD have not been established
- FDA required boxed warning for all antidepressants: Suicidality in Children and Adolescents
- Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Zoloft or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Zoloft is not approved for use in pediatric patients except for patients with obsessive compulsive disorder (OCD). (See Warnings and Precautions: Pediatric Use) Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials
- Two placebo controlled trials in 373 pediatric patients with MDD have been conducted with Zoloft, and the data were not sufficient to support a claim for use in pediatric patients
|
B |
3/20/2008 |
Zometa
|
zoledronic acid |
Severe osteogenesis imperfecta |
Novartis |
Label
Medical Review
Clinical Pharmacology Review
Statistical Review |
- Zoledronic acid is not indicated for use in children
- Safety and effectiveness was studied in 152 pediatric patients with severe osteogenesis imperfecta aged 1 - 17 years. At one year, increases in BMD were observed in the zoledronic acid treatment group but the changes did not necessarily correlate with the risk for fracture or the incidence or severity of chronic bone pain
- Information on PK, clinical study, and AE profile
|
B |
11/16/2004 |
Zomig
|
zolmitriptan |
Migraine |
AstraZeneca |
Label
Medical Review
Clinical Pharmacology Review |
- Clinical trial evaluating zolmitriptan in pediatric patients ages 12 -17 years did not establish the safety and effectiveness when compared to placebo
- AEs observed in clinical trials were similar to those observed in clinical trials in adults.
|
B |
10/14/2008 |
Zomig Nasal Spray
|
zolmitriptan |
Migraine |
AstraZeneca |
|
|
B |
12/30/2002 |
Zovirax Cream
|
acyclovir |
Treatment of herpes labialis (cold sores) in children 12 years and older |
GlaxoSmithKline |
Label |
- Adolescents 12-17 years of age included in clinical safety studies.
- dosing regimen established waived in children < 12 years of age because rarely seen in that population
- New dosage form
|
P |
5/30/2007 |
Zyflo CR Extended Release Tablets
|
zileuton |
Prevention and chronic treatment of asthma in children 12 years of age and older |
Critical Therapeutics
|
Label |
- Should not be used in children under 12 years of age
- Effectiveness was established in clinical studies that included pediatric patients 12 years of age and older
- Short-term and long-term safety were established in clinical studies that included pediatric patients 12 years of age and older
- Studies waived in children 0-4 years of age and deferred in children 5-11 years of age
- New dosage form
|
P |
8/14/2008 |
Zyprexa |
olanzapine |
schizophrenia; bipolar disorder |
Lilly |
Label
Medical Review
Clinical Pharmacology Review |
- Safety and effectiveness have not been established for patients less than 18 years of age
- In an analysis of placebo-controlled olanzapine monotherapy studies of adolescent patients, including those with schizophrenia or bipolar disorder, olanzapine was associated with:
- Hyperglycemia - a statistically significantly greater mean change in fasting glucose levels compared to placebo
- Hyperlipidemia – statistically significant increases compared to placebo in fasting triglycerides, fasting total cholesterol and fasting LDL cholesterol
- Weight gain – olanzapine treated patients gained an average of 4.6 kg, compared to an average of 0.3 kg in placebo-treated patients with a median exposure of 3 weeks; Average weight gain during long-term therapy was 7.4 kg
|
B |
10/21/2002 |
Zyrtec
|
cetirizine |
Perennial Allergic Rhinitis & Chronic Urticaria |
Pfizer |
Label |
- Extended the age range from 2 years to 6 months
- Information on dose, PK parameters and AE profile
|
B |
12/19/2002 |
Zyvox
|
linezolid
|
Nosocomial pneumonia, community-acquired pneumonia, complicated and uncomplicated skin and skin structure infections,
and vancomycin-resistant infections caused by susceptible strains |
Pfizer |
Label
Medical Review
Clinical Pharmacology |
- Extended age range down to birth for nosocomial pneumonia, community-acquired pneumonia, complicated skin and skin structure infections and vancomycin-resistant infections. Safety and efficacy extrapolated from studies in adults and supported by PK and comparator-controlled studies in patients from birth to 11 years
- Extended age range down to 5 years of age for uncomplicated skin and skin structure infections based upon a comparator-controlled study in 5 to 17 year olds
- Clearance of linezolid varies as a function of age; As age of pediatric patients increases, clearance gradually decreases, and by adolescence mean clearance values approach those observed in adults
- Pediatric patients exhibit wider variability in clearance and systemic exposure (AUC) compared with adults
- New every 8 hours dosing regimen for pediatric patients birth to 11 years of age and every 12 hours dosing regimen for pediatric patients 12 years and older
- Information on PK parameters, AE profile, laboratory changes, dosing, and clinical studies
|
B |
5/12/2005 |
Zyvox
|
linezolid
|
Central nervous system infections |
Pfizer |
Label
Medical Review
Clinical Pharmacology |
- PK data in pediatric patients with ventriculoperitoneal shunts showed variable cerebrospinal fluid (CSF) concentrations; therapeutic concentrations were not consistently achieved or maintained in the CSF
- Use of linezolid for the empiric treatment of pediatric patients with central nervous system infections is not recommended
- Additional information on efficacy in pediatric patients with infectious vancomycin-resistant Enterococcus faecium
|
B |