aripiprazole

Label

• 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

aripiprazole

 Label

• 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

isotretinoin

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)

fentanyl

Label

• 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

amphetamines mixed salts

Label

• 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

ibuprofen

Label

ibuprofen/
pseudoephedrine

Label

Anagrelide

Label

• 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

pemirolast

Label

imiquimod

Label

• 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

fexofenadine

Label

fexofenadine

Label  

• 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

brimonidine

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%)

glimepiride

Label

• 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

zolpidem

Label

• 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%

testosterone

Label

• 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

tipranavir

Label

• 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

leflunomide

Label

• 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

argatroban

Label

• 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

rosiglitazone

Label

• 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

irbesartan

• 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

nizatidine

Label

• Indicated in pediatric patients 12 years and older
• Information on dose, PK parameters, and AE profile

brinzolamide

Label

• 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

sotalol

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

levobetaxolol

Label

• Extended indication from adults to pediatric patients
• The adverse event profile was comparable to that seen in adults and elderly patients

betaxolol

Label

• Extended indication from adults to pediatric patients
• The adverse reaction profile was comparable to that seen in adults

buspirone

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

busulfan

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

calcitriol

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

irinotecan

Label

• 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

caspofungin

Label

• 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

technetium tc99m sestamibi

Label

• 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

celecoxib

Label

• 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

citalopram

Label

• 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

ciprofloxacin

Label

• 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

desloratadine

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

loratadine

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

clofarabine

Label

• 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 profile

balsalazide

Label

• 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

methylphenidate

Label

• 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

carvedilol

Label

• 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%)

fenoldopam

Label

•   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

losartan

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

oxaprozin

Label

divalproex disodium

Label

• 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

tolterodine

Label

• 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

valsartan

Label

• 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

propofol

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

oxybutynin

Label

• Additional information on dose and PK parameters
• Precautions section of label updated

• Safety and effectiveness established down to 6 years of age

fentanyl

Label

• 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%)

venlafaxine

• 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

pimecrolimus

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.

mometasone

Label

• 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)

• 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

• 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

oxaliplatin

Label  

• 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

emtricitabine

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

emtricitabine

Label

• 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

lamivudine

lamivudine

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)

sodium ferric gluconate complex

Label

• 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

fluticasone

Label  

Label

• 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.

• 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

fludarabine

Label

• Fludarabine was evaluated in 62 pediatric patients and the data were insufficient to establish efficacy in any childhood malignancy

alendronate

Label

• 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

enfuvirtide

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

gemcitabine

Label

• 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

imatinib mesylate

Label

• 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

metformin

Label

glyburide/ metformin

Label

• 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

adefovir dipivoxil

Label

• 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

sumatriptan

Label

• 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

eplerenone

Label

• 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

ertapenem

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

lopinavir/ ritonavir

Label

• Extended indication from 6 months - 12 years to 14 days - 18 years
• The safety, efficacy, and pharmacokinetic profiles in pediatric patients < 14 days have not been established
• Dose should be calculated based on body weight or body surface area not to exceed adult dose
  
• Because no data exists for dosage when administered with efavirenz, nevirapine, (fos)amprenavir, or nelfinavir, it is recommended that lopinavir/ ritonavir not be administered in combination with these drugs in patients < 6 months of age
• Infants <6 months of age generally had lower lopinavir AUC12 than children 6 months - 12 years of age
• Information on dose, PK parameters, clinical studies, and AEs

levetiracetam

Label

• 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

ammonium lactate

Label

lamotrigine

Label

• 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

terbinafine

Label  

• 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

insulin glargine

Label

fluvastatin

Label

• 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

levofloxacin

Label  

• 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

atorvastatin

Label

etodolac

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

benazepril

Label

• 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

betamethason;betamethasone/ clotrimazole

Label

• 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)

• 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

• 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

fluvoxamine

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

• 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%)

atovaquone/
proguanil

Label

• 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

sibutramine

Label

• 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

lovastatin

Label

meloxicam

Label

• 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

fosinopril

Label

• 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

ibuprofen

Label

ibuprofen/
pseudoephedrine

Label

cromolyn

Label

vinorelbine

Label

gabapentin

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

esomeprazole

• 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

tamoxifen

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

amlodipine

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

ritonavir

Label

• 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

insulin aspart recombinant injection

Label

• 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

azelastine

Label

norgestimate/ ethinyl estradiol

Label

• 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

paroxetine

• 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

famotidine

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

pravastatin

Label

lansoprazole

Label

• 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

lansoprazole

Label

• Effectiveness was not established in a 4 week multicenter, double-blind, placebo-controlled study in infants between 1 month and < 12 months of age
• E profile similar to that observed in adults
• Information on PK parameters in neonates to 11 months of age, and clinical studies

omeprazole

Label

• Safety and effectiveness established in pediatric patients 2-16 years of age
• Information on dose, PK parameters, exposure/response and AE profile

lisinopril

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

modafinil

Label  

• 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 studies

fluoxetine

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

budesonide

Label

• 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

sirolimus

Label

• 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

ribavirin/intron a; ribavirin

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

mirtazapine

• 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

risperidone

Label

• 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

octreotide

Label

• 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

nefazodone

• 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

montelukast

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

atomoxetine

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

desflurane

 Label

• 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

oseltamivir

Label

• 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 yearr 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

oseltamivir

Label

oseltamivir

Label

• 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

temozolomide

Label

• 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

timolol

Label

• Extended indication from adults to pediatric patients
• The adverse reaction profile was comparable to that seen in adults

metoprolol

Label

• 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

oxcarbazepine

Label

• 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

dorzolamide

Label

• Safety and IOP-lowering effects have been demonstrated in pediatric patients
• Adverse event profile was comparable  to that seen in adults

sevoflurane

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

remifentanil

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

valacyclovir

Label

• 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
  
  

Label

• Labeling for 1 month-16 years of age
• Information on dose, efficacy and pharmacokinetics
• Information on preparation of a suspension

albuterol

Label

• 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

midazolam

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

didanosine

Label

moxifloxacin

Label

rofecoxib

Label

nelfinavir

Label

• 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

orlistat

Label

• 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

ranitidine

Label

• Small studies in newborns 0 to 1 month receiving ECMO did not demonstrate efficacy but provided information on dose and PK

paricalcitol

Label

• 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

rocuronium

Label

• 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

stavudine

Label

• Safety and effectiveness established down to birth
• Established a dose for newborns from birth to 13 days

lisinopril

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

Zetia and
Vytorin
(MSP Singapore)

ezetimibe
and ezetimibe/ simvastatin

Label

Label (6/13/2008 not available)

• 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)

abacavir

Label

• Labeling for 3 months - 12 years
• Information on dose, efficacy, PK parameters and AE profile

simvastatin

Label

ondansetron

Label

• 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

sertraline

• 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

zoledronic acid

Label

• 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

zolmitriptan

Label

• 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.

cetirizine

Label

• Extended the age range from 2 years to 6 months
• Information on dose, PK parameters and AE profile

linezolid

Label

• 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

• 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

olanzapine

Label

• 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