The detailed view includes drug products with safety labeling changes to the BOXED WARNING, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSE REACTIONS, or PATIENT PACKAGE INSERT/MEDICATION GUIDE sections. Deletions or editorial revisions made to these sections are not included in this summary. Read about the new physician labeling format.

Brand (Generic) Name

Summary of Changes to Contraindications and Warnings

Aceon (perindopril erbumine) Tablets

Prescribing Information

BOXED WARNING

• USE IN PREGNANCY

WARNINGS

• Fetal/Neonatal Morbidity and Mortality

PRECAUTIONS

• Information for Patients
  • Pregnancy
• Drug Interactions
  • Gold (added)
• Pregnancy
  • Pregnancy Category D. (See WARNINGS: Fetal/Neonatal Morbidity and Mortality.)
• Geriatric Use
  • ...Perindopril should be used with caution when administered to elderly patients who are at an increased risk for falls due to age...
    

ADVERSE REACTIONS

• Potential Adverse Effects Reported with ACE Inhibitors
  • pemphigus, falls, psoriasis (added)

BOXED WARNING

USE IN PREGNANCY

When used in pregnancy, ACE inhibitors can cause injury and even death to the developing fetus...

WARNINGS

Fetal/Neonatal Morbidity and Mortality

...The use of ACE inhibitors during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation and hypoplastic lung development.

Prematurity, intrauterine growth retardation, patent ductus arteriosus, and other structural cardiac malformations, as well as neurological malformations, have been reported following exposure to ACE inhibitors during the first trimester of pregnancy.

When patients become pregnant, physicians should make every effort to discontinue the use of Aceon Tablets as soon as possible. Rarely (probably less often than once in every thousand pregnancies), no alternative to ACE inhibitors will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intra-amniotic environment...

Brand (Generic) Name

Summary of Changes to Contraindications and Warnings

Proair HFA (albuterol sulfate) Inhalation Aerosol

Prescribing Information (in new labeling format)

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

• Hypokalemia

ADVERSE REACTIONS

• Clinical Trials Experience
  • Initial Paragraph
  • Pediatric Patients 4 to 11 Years of Age
• Postmarketing Experience
  • ...In addition, albuterol, like other sympathomimetic agents, can cause adverse reactions such as:
    • hypotension, palpitations, nervousness, tremor, hypokalemia, hyperglycemia, and metabolic acidosis (added)

DRUG INTERACTIONS

• Diuretics
  • ...Consider monitoring potassium levels.
• Monoamine Oxidase Inhibitors or Tricyclic Antidepressants
  • ...Consider alternative therapy in patients taking MAO inhibitors or tricyclic antidepressants.

USE IN SPECIFIC POPULATIONS

• Pediatric Use

NONCLINICAL TOXICOLOGY

• Carcinogenesis, Mutagenesis, Impairment of Fertility

PATIENT COUNSELING INFORMATION

• Paradoxical Bronchospasm
• General Information on Use

CONTRAINDICATIONS

...Rare cases of hypersensitivity reactions, including urticaria, angioedema, and rash have been reported after the use of albuterol sulfate [see Warnings and Precautions (5.6)].

WARNINGS AND PRECAUTIONS

Hypokalemia

As with other beta-agonists, Proair HFA Inhalation Aerosol may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease is usually transient, not requiring supplementation.

Brand (Generic) Name

Summary of Changes to Contraindications and Warnings

EpiPen (epinephrine) Auto-Injector 0.3 mg

EpiPen JR (epinephrine) Auto-Injector 0.15 mg

Prescribing Information

WARNINGS

PRECAUTIONS

• General
• Information for Patients
• Drug Interactions
• Carcinogenesis, Mutagenesis, Impairment of Fertility
• Usage in Pregnancy

ADVERSE REACTIONS

• Adverse reactions to epinephrine include...

WARNINGS

See prescribing information for multiple labeling revisions, including information regarding:

• ...Injection into the buttock may not provide effective treatment of anaphylaxis...
• ...accidental injection into the digits, hands or feet, may result in loss of blood flow to the affected area...
• ...The presence of a sulfite in this product should not defer administration of the drug for treatment of serious allergic or other emergency situations even if the patient is sulfite-sensitive.
• ...epinephrine may precipitate or aggravate angina pectoris as well as produce ventricular arrhythmias...

Erbitux (cetuximab) Solution for Intravenous Use

Prescribing Information (in new labeling format)

WARNINGS AND PRECAUTIONS

• Infusion Reactions
  • Initial Paragraph
    • shock, loss of consciousness, myocardial infarction (added)
• Dermatology Toxicity
  • Initial Paragraph
    • conjunctivitis, keratitis, hypertrichosis (added)

ADVERSE REACTIONS

• Clinical Trials Experience
  • Squamous Cell Carcinoma of the Head and Neck
    • Table 2
      • Metabolic/Nutritional

WARNINGS AND PRECAUTIONS

Infusion Reactions

Serious infusion reactions, requiring medical intervention and immediate, permanent discontinuation of Erbitux included rapid onset of airway obstruction (bronchospasm, stridor, hoarseness), hypotension, shock, loss of consciousness, myocardial infarction, and/or cardiac arrest. Severe (NCI CTC Grades 3 and 4) infusion reactions occurred in 2-5% of 1373 patients in clinical trials, with fatal outcome in 1 patient.

Dermatology Toxicity

Dermatologic toxicities, including acneform rash, skin drying and fissuring, paronychial inflammation, infectious sequelae (for example S. aureus sepsis, abscess formation, cellulitis, blepharitis, conjunctivitis, keratitis, cheilitis), and hypertrichosis occurred in patients receiving Erbitux therapy. Acneform rash occurred in 76-88% of 1373 patients receiving Erbitux in clinical trials. Severe acneform rash occurred in 1-17 % of patients.

Exubera (insulin human [rDNA origin]) Inhalation Powder

For current prescribing information contact Pfizer at 1-800-879-3477.

Medication Guide

WARNINGS

MEDICATION GUIDE

• What are some of the possible side effects of Exubera?
  • In studies of Exubera in people with diabetes, lung cancer occurred in a few more people who were taking Exubera than in people who were taking other diabetes medicines. All the people in these studies who developed lung cancer used to smoke cigarettes. There were too few cases to know if the lung cancer was related to Exubera.

WARNINGS

In clinical trials of Exubera, there have been 6 newly diagnosed cases of primary lung malignancies among Exubera-treated patients, and 1 newly diagnosed case among comparator-treated patients. There has also been 1 postmarketing report of a primary lung malignancy in an Exubera-treated patient. In controlled clinical trials of Exubera, the incidence of new primary lung cancer per 100 patient-years of study drug exposure was 0.13 (5 cases over 3800 patient-years) for Exubera-treated patients and 0.03 (1 case over 3900 patient-years) for comparator-treated patients. There were too few cases to determine whether the emergence of these events is related to Exubera. All patients who were diagnosed with lung cancer had a prior history of cigarette smoking.

Gleevec (imatinib mesylate) Tablets

Prescribing Information (in new labeling format)

WARNINGS AND PRECAUTIONS

• Hepatotoxicity
• Hemorrhage
• Hypothyroidism

ADVERSE REACTIONS

• Additional Data From Multiple Trials
• Postmarketing Experience

USE IN SPECIFIC POPULATIONS

• Renal Impairment

WARNINGS AND PRECAUTIONS

Hepatotoxicity

... When Gleevec is combined with chemotherapy, liver toxicity in the form of transaminase elevation and hyperbilirubinemia has been observed. Additionally, there have been reports of acute liver failure. Monitoring of hepatic function is recommended.

Hemorrhage

In the newly diagnosed CML trial, 1.8% of patients had Grade 3/4 hemorrhage. In the Phase 3 GIST studies 211 patients (12.9%) reported Grade 3/4 hemorrhage at any site. In the Phase 2 GIST study 7 patients (5%) had a total of 8 CTC Grade 3/4 hemorrhages; gastrointestinal (GI) (3 patients), intra-tumoral (3 patients) or both (1 patient). Gastrointestinal tumor sites may have been the source of GI hemorrhages. 

Hypothyroidism

Clinical cases of hypothyroidism have been reported in thyroidectomy patients undergoing levothyroxine replacement during treatment with Gleevec. TSH levels should be closely monitored in such patients.

Heparin Sodium Injection, USP [Preservative Free]

Prescribing Information

WARNINGS

The following subsections have been added:

• Fatal Medication Errors
• Heparin-Induced Thrombocytopenia (HIT) and Heparin-Induced Thrombocytopenia and Thrombosis (HITT)
• Delayed Onset of HIT and HITT
• Use in Neonates

PRECAUTIONS

• Drug Interactions
  • Other Drug Interactions
    • Intravenous nitroglycerin administered to heparinized patients may result in a decrease of the partial thromboplastin time with subsequent rebound effect upon discontinuation of nitroglycerin. Careful monitoring of partial thromboplastin time and adjustment of heparin dosage are recommended during coadministration of heparin and intravenous nitroglycerin.

WARNINGS

Fatal Medication Errors

Do not use Heparin Sodium Injection as a “catheter lock flush” product. Heparin Sodium Injection is supplied in vials containing various strengths of heparin, including vials that contain a highly concentrated solution of 10,000 units in 1 mL. Fatal hemorrhages have occurred in pediatric patients due to medication errors in which 1 mL Heparin Sodium Injection vials were confused with 1 mL “catheter lock flush” vials. Carefully examine all Heparin Sodium Injection vials to confirm the correct vial choice prior to administration of the drug.

Heparin-Induced Thrombocytopenia (HIT) and Heparin-Induced Thrombocytopenia and Thrombosis (HITT)

Heparin-induced Thrombocytopenia (HIT) is a serious antibody-mediated reaction resulting from irreversible aggregation of platelets. HIT may progress to the development of venous and arterial thromboses, a condition referred to as Heparin-induced Thrombocytopenia and Thrombosis (HITT). Thrombotic events may also be the initial presentation for HITT. These serious thromboembolic events include...

Delayed Onset of HIT and HITT

Heparin-induced Thrombocytopenia and Heparin-induced Thrombocytopenia and Thrombosis can occur up to several weeks after the discontinuation of heparin therapy. Patients presenting with thrombocytopenia or thrombosis after discontinuation of heparin should be evaluated for HIT and HITT.

Use in Neonates

Carefully examine all Heparin Sodium Injection vials to confirm choice of the correct strength prior to administration of the drug. Pediatric patients, including neonates, have died as a result of medication errors in which Heparin Sodium Injection vials have been confused with “catheter lock flush” vials (see WARNINGS, Fatal Medication Errors).

Heparin Sodium Injection, USP [Preserved with Parabens]

Prescribing Information

WARNINGS

The following subsections have been added:

• Fatal Medication Errors
• Heparin-Induced Thrombocytopenia (HIT) and Heparin-Induced Thrombocytopenia and Thrombosis (HITT)
• Delayed Onset of HIT and HITT
• Use in Neonates

PRECAUTIONS

• Drug Interactions
  • Other Drug Interactions
    • Intravenous nitroglycerin administered to heparinized patients may result in a decrease of the partial thromboplastin time with subsequent rebound effect upon discontinuation of nitroglycerin. Careful monitoring of partial thromboplastin time and adjustment of heparin dosage are recommended during coadministration of heparin and intravenous nitroglycerin.

WARNINGS

Fatal Medication Errors

Do not use Heparin Sodium Injection as a “catheter lock flush” product. Heparin Sodium Injection is supplied in vials containing various strengths of heparin, including vials that contain a highly concentrated solution of 10,000 units in 1 mL. Fatal hemorrhages have occurred in pediatric patients due to medication errors in which 1 mL Heparin Sodium Injection vials were confused with 1 mL “catheter lock flush” vials. Carefully examine all Heparin Sodium Injection vials to confirm the correct vial choice prior to administration of the drug.

Heparin-Induced Thrombocytopenia (HIT) and Heparin-Induced Thrombocytopenia and Thrombosis (HITT)

Heparin-induced Thrombocytopenia (HIT) is a serious antibody-mediated reaction resulting from irreversible aggregation of platelets. HIT may progress to the development of venous and arterial thromboses, a condition referred to as Heparin-induced Thrombocytopenia and Thrombosis (HITT). Thrombotic events may also be the initial presentation for HITT. These serious thromboembolic events include...

Delayed Onset of HIT and HITT

Heparin-induced Thrombocytopenia and Heparin-induced Thrombocytopenia and Thrombosis can occur up to several weeks after the discontinuation of heparin therapy. Patients presenting with thrombocytopenia or thrombosis after discontinuation of heparin should be evaluated for HIT and HITT.

Use in Neonates

Carefully examine all Heparin Sodium Injection vials to confirm choice of the correct strength prior to administration of the drug. Pediatric patients, including neonates, have died as a result of medication errors in which Heparin Sodium Injection vials have been confused with “catheter lock flush” vials (see WARNINGS, Fatal Medication Errors).

Nasacort AQ (triamcinolone acetonide) Nasal Spray

Prescribing Information (in new labeling format)

Patient Package Insert (new)

WARNINGS AND PRECAUTIONS

• Local Nasal Effects
  • Epistaxis
  • Nasal Septal Perforation
    • In clinical trials, nasal septum perforation was reported in one adult patient treated with Nasacort AQ Nasal Spray.
  • Candida Infection
• Glaucoma and Cataracts
• Immunosuppression
• Hypothalamic-Pituitary-Adrenal Axis Effects
  • Hypercorticism and Adrenal Suppression
• Effect on Growth

ADVERSE REACTIONS

• Clinical Trials Experience
  • Table 2
  • A total of 474 children 2 to 5 years of age were studied in a 4-week double-blind, placebocontrolled clinical trial...
    • Table 3
• Postmarketing Experience

USE IN SPECIFIC POPULATIONS

• Pediatric Use
• Geriatric Use

PATIENT COUNSELING INFORMATION

• Local Nasal Effects
• Cataracts and Glaucoma
• Immunosuppression
• Use Daily for Best Effect
• Keep Spray Out of Eyes
• Patient Package Information

PATIENT PACKAGE INSERT (new)

WARNINGS AND PRECAUTIONS

Local Nasal Effects: Epistaxis

In clinical studies of 2 to 12 weeks duration, epistaxis was observed more frequently in patients treated with Nasacort AQ Nasal Spray than those who received placebo [see Adverse Reactions (6)].

Local Nasal Effects: Candida Infection

...Therefore, patients using Nasacort AQ Nasal Spray over several months or longer should be examined periodically for evidence of Candida infection or other signs of adverse effects on the nasal mucosa.

Glaucoma and Cataracts

Nasal and inhaled corticosteroids may result in the development of glaucoma and/or cataracts. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma and/or cataracts.

Immunosuppression

Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In children or adults who have not had these diseases or have not been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known...

Hypothalamic-Pituitary-Adrenal Axis Effects: Hypercorticism and Adrenal Suppression

When intranasal steroids are used at higher than recommended dosages or in susceptible individuals at recommended dosages, systemic corticosteroid effects such as hypercoticism and adrenal suppression may appear...

Effect on Growth

Corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth routinely of pediatric patients receiving Nasacort AQ Nasal Spray. To minimize the systemic effects of intranasal corticosteroids, including Nasacort AQ Nasal Spray, titrate each patient’s dose to the lowest dosage that effectively controls his/her symptoms [see Use in Specific Populations (8.4)].

Noroxin (norfloxacin) Tablets

Prescribing Information

Patient Package Insert (new)

WARNINGS

• Hypersensitivity Reactions

PRECAUTIONS

• General
  • Moderate to severe photosensitivity/phototoxicity reactions...
• Information for Patients
  • Patients should be advised:
    • ...The risk of serious tendon disorders with quinolones is
      higher in those over 65 years of age and those on corticosteroids.
• Geriatric Use
  • In general, elderly patients may be more susceptible to drug-associated effects of the QTc interval...
  • Patients over 65 years of age are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone antibiotic such as Noroxin...

ADVERSE REACTIONS

• Postmarketing
  • Skin
    • ...photosensitivity/phototoxicity reactions (see PRECAUTIONS)
  • Hepatic
    • Hepatic failure, including fatal cases

PATIENT PACKAGE INSERT (new)

WARNINGS

Hypersensitivity Reactions

...Other serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain etiology, have been reported rarely in patients receiving therapy with quinolones, including Noroxin. These events may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following:

• fever, rash or severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson
  syndrome);
• vasculitis; arthralgia; myalgia; serum sickness;
• allergic pneumonitis;
• interstitial nephritis; acute renal insufficiency or failure;
• hepatitis; jaundice; acute hepatic necrosis or failure;
• anemia, including hemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic abnormalities.

The drug should be discontinued immediately at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity, and supportive measures should be instituted (see PRECAUTIONS, Information for Patients and ADVERSE REACTIONS).

Photofrin (porfimer sodium) Injection

Prescribing Information (in new labeling format)

WARNINGS AND PRECAUTIONS

• High-Grade Dysplasia (HGD) in Barrett’s Esophagus (BE)
• Photosensitivity
• Esophageal Strictures
  • Table 5: Esophageal Dilations in Patients with Treatment-Related Strictures
• Hepatic and Renal Impairment (new subsection)

ADVERSE REACTIONS

• Overall Adverse Reaction Profile
• Adverse Reactions in Clinical Trials
  • High-Grade Dysplasia (HGD) in Barrett’s Esophagus (BE)

DRUG INTERACTIONS

• Concomitant Therapy
  • Photodynamic therapy (PDT) with Photofrin causes direct intracellular damage...

USE IN SPECIFIC POPULATIONS

• Pregnancy
• Nursing Mothers

NONCLINICAL TOXICOLOGY

• Carcinogenesis, Mutagenesis, and Impairment of Fertility

PATIENT COUNSELING INFORMATION

• Photosensitivity (subsection added)
• Common Adverse Reactions (subsection added)

WARNINGS AND PRECAUTIONS

High-Grade Dysplasia (HGD) in Barrett’s Esophagus (BE)

...The follow-up period of the randomized study at the time of analysis was a minimum of two years (ranging from 2 to 5.6 years).

Photosensitivity

Conventional ultraviolet (UV) sunscreens will only protect against UV light-related photosensitivity and will be of no value in protecting against induced photosensitivity reactions caused by visible light.

Esophageal Strictures

See Table 5, located after Section 5.10.

Table 5: Esophageal Dilations in Patients with Treatment-Related Strictures

The “Number of Patients with Strictures” has changed from 122 to 114. The number of patients and percentage in each row has also changed.

Hepatic and Renal Impairment

Hepatic or Renal impairment will likely prolong the elimination of porfimer sodium leading to higher rates of toxicity. Patients with severe renal impairment or mild to severe hepatic impairment should be clearly informed that the period requiring the precautionary measures for photosensitivity may be longer than 90 days.

Reyataz (atazanavir sulfate) Capsules

Prescribing Information (in new labeling format)

Patient Package Insert

WARNINGS AND PRECAUTIONS

• Rash

ADVERSE REACTIONS

• Clinical Trial Experience in Adults
  • Treatment-Emergent Adverse Reactions in Treatment-Naive Patients
    • Initial Section
    • Table 4
    • Laboratory Abnormalities in Treatment-Naive Patients
      • Table 7
    • Lipids, Change from Baseline in Treatment-Naive Patients
      • Table 10
• Patients Co-infected With Hepatitis B and/or Hepatitis C Virus

PATIENT PACKAGE INSERT

• How should I take Reyataz (atazanavir sulfate)?
  • For adults who have never taken anti-HIV medicines before...

WARNINGS AND PRECAUTIONS

Rash

In controlled clinical trials, rash (all grades, regardless of causality) occurred in approximately 20% of patients treated with Reyataz (atazanavir sulfate). The median time to onset of rash in clinical studies was 7.1 weeks and the median duration of rash was 1.3 weeks. Rashes were generally mild-to-moderate maculopapular skin eruptions. Treatment-emergent adverse reactions of moderate or severe rash (occurring at a rate of >2%) are presented for the individual clinical studies [see Adverse Reactions (6.1)]. Dosing with Reyataz was often continued without interruption in patients who developed rash. The discontinuation rate for rash in clinical trials was <1%...

Rituxan (rituximab) Injection for Intravenous Use

Prescribing Information (in new labeling format)

See MedWatch safety alert posted 9/11/2008.

WARNINGS AND PRECAUTIONS

• Progressive Multifocal Leukoencephalopathy (PML)

USE IN SPECIFIC POPULATIONS

• Pregnancy
  • ...Postmarketing data indicate that B-cell lymphocytopenia generally lasting less than six months can occur in infants exposed to rituximab in-utero. Rituximab was detected postnatally in the serum of infants exposed in-utero...

WARNINGS AND PRECAUTIONS

Progressive Multifocal Leukoencephalopathy (PML)

JC virus infection resulting in PML and death can occur in Rituxan-treated patients with hematologic malignancies or with autoimmune diseases. The majority of patients with hematologic malignancies diagnosed with PML received Rituxan in combination with chemotherapy or as part of a hematopoietic stem cell transplant. The patients with autoimmune diseases had prior or concurrent immunosuppressive therapy. Most cases of PML were diagnosed within 12 months of their last infusion of Rituxan...

Tarceva (erlotinib) Tablets

Prescribing Information

See MedWatch safety alert posted 9/23/2008.

WARNINGS

• Patients with Hepatic Impairment
• Hepatotoxicity
• Renal Failure

PRECAUTIONS

• Drug Interactions
  • When Tarceva was co-administered with ciprofloxacin...
  • Drugs that alter the pH of the upper GI tract may alter the solubility of erlotinib and reduce its bioavailability...
• Information for Patients
  • Onset or worsening of skin rash

ADVERSE REACTIONS

• Non-Small Cell Lung Cancer
  • Tarceva dosing should be interrupted or discontinued if changes in liver function are severe...
• Pancreatic Cancer
  • Tarceva dosing should be interrupted or discontinued if changes in liver function are severe...
• NSCLC and Pancreatic Cancer Indications
  • Hair and nail disorders...
  • Hepatic failure...

WARNINGS

Patients with Hepatic Impairment

In a pharmacokinetic study in patients with moderate hepatic impairment (Child-Pugh B) associated with significant liver tumor burden, 10 out of 15 patients died on treatment or within 30 days of the last Tarceva dose. One patient died from hepatorenal syndrome, 1 patient died from rapidly progressing liver failure and the remaining 8 patients died from progressive disease. Six out of the 10 patients who died had baseline total bilirubin > 3 x ULN suggesting severe hepatic impairment. Treatment with Tarceva should be used with extra caution in patients with total bilirubin > 3 x ULN. Patients with hepatic impairment (total bilirubin > ULN or Child-Pugh A, B and C) should be closely monitored during therapy with Tarceva. Tarceva dosing should be interrupted or discontinued if changes in liver function are severe such as doubling of total bilirubin and/or tripling of transaminases in the setting of pretreatment values outside normal range...

Hepatotoxicity

Cases of hepatic failure and hepatorenal syndrome (including fatalities) have been reported during use of Tarceva, particularly in patients with baseline hepatic impairment. Therefore, periodic liver function testing (transaminases, bilirubin, and alkaline phosphatase) is recommended. In the setting of worsening liver function tests, dose interruption and/or dose reduction with frequent liver function test monitoring should be considered. Tarceva dosing should be interrupted or discontinued if total bilirubin is >3 x ULN and/or transaminases are >5 x ULN in the setting of normal pretreatment values...

Renal Failure

Cases of hepatorenal syndrome, acute renal failure (including fatalities), and renal insufficiency have been reported. Some were secondary to baseline hepatic impairment while others were associated with severe dehydration due to diarrhea, vomiting, and/or anorexia or concurrent chemotherapy use. In the event of dehydration, particularly in patients with contributing risk factors for renal failure (eg, pre-existing renal disease, medical conditions or medications that may lead to renal disease, or other predisposing conditions including advanced age), Tarceva therapy should be interrupted and appropriate measures should be taken to intensively rehydrate the patient. Periodic monitoring of renal function and serum electrolytes is recommended in patients at risk of dehydration...

Uroxatral (alfuzosin HCl extended-release tablets)

Prescribing Information

WARNINGS

The following sentence was added to the WARNINGS section:

There may be an increased risk of hypotension/postural hypotension and syncope when taking Uroxatral concomitantly with anti-hypertensive medication or nitrates.

Capoten (captopril tablets, USP)

Prescribing Information

PRECAUTIONS

• Drug Interactions
  • Gold
    • Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including Capoten.

Prescribing Information

PRECAUTIONS

• General
  • Abnormal Bleeding
  • Hyponatremia
• Information for Patients
  • Patients should be cautioned about the concomitant use of Celexa and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation since combined use of psychotropic drugs that interfere with serotonin reuptake and these agents has been associated with an increased risk of bleeding.
• Drug Interactions
  • Drugs That Interfere With Hemostasis (NSAIDs, Aspirin, Warfarin, etc.)
• Geriatric Use
  • SSRIs and SNRIs, including Celexa, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event (see PRECAUTIONS, Hyponatremia).

Detrol (tolterodine tartrate tablets)

Prescribing Information

Patient Package Insert

PRECAUTIONS

• General
  • Decreased Gastrointestinal Motility
  • Myasthenia Gravis

PATIENT PACKAGE INSERT

• What should I tell my doctor before starting Detrol?
  • Before starting Detrol, tell your doctor about all of your medical conditions, including if you:
• have a condition called myasthenia gravis

Detrol LA (tolterodine tartrate extended release capsules)

Prescribing Information

Patient Package Insert

PRECAUTIONS

• General
  • Decreased Gastrointestinal Motility
  • Myasthenia Gravis

PATIENT PACKAGE INSERT

• What should I tell my doctor before starting Detrol LA?
  • Before starting Detrol LA, tell your doctor about all of your medical conditions, including if you:
    • have a condition called myasthenia gravis

Glucovance (glyburide and metformin HCl tablets)

Prescribing Information

PRECAUTIONS

• General
  • Macrovascular Outcomes
    
    • There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Glucovance or any other anti-diabetic drug.

Invega (paliperidone) Extended-Release Tablets

Prescribing Information (in new labeling format)

DRUG INTERACTIONS

• Potential for Invega to Affect Other Drugs
  • Paliperidone is a weak inhibitor of P-glycoprotein (P-gp) at high concentrations. No in vivo data are available and the clinical relevance is unknown.
• Potential for Other Drugs to Affect Invega
  • In vitro studies have shown that paliperidone is a P-gp substrate.
  • Co-administration of Invega 6 mg once daily with carbamazepine 200 mg twice daily caused a decrease of approximately 37% in the mean steady-state Cmax and AUC of paliperidone...

Lariam (mefloquine hydrochloride) Tablets

Prescribing Information

Medication Guide (including reprint of information wallet card)

PRECAUTIONS

• Central and Peripheral Nervous System Effects
  • ...In a small number of patients, dizziness and loss of balance have been reported to continue for months after mefloquine has been stopped (see ADVERSE REACTIONS: Postmarketing).
• Information for Patients
  • Patients should be advised:
    • that in a small percentage of cases, patients are unable to take this medication because of side effects, including dizziness and loss of balance, and it may be necessary to change medications. Although side effects of dizziness and loss of balance are usually mild and do not cause people to stop taking the medication, in a small number of patients it has been reported that these symptoms may continue for months after discontinuation of the drug.

ADVERSE REACTIONS

• Postmarketing
  • ...In a small number of patients it has been reported that dizziness or vertigo and loss of balance may continue for months after discontinuation of the drug.

MEDICATION GUIDE

• What should I avoid while taking Lariam?
  • Lariam can cause dizziness or loss of balance, even after you stop taking Lariam (see “What are the possible side effects of Lariam?”).
• What are the possible side effects of Lariam?
  • Loss of balance (added)
  • ...However, in a small number of patients, it has been reported that dizziness and loss of balance may continue for months after stopping Lariam.
  • Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

INFORMATION WALLET CARD

• Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Lexapro (escitalopram oxalate) Tablets and Oral Solution

Prescribing Information

PRECAUTIONS

• General
  • Abnormal Bleeding
  • Hyponatremia
• Information for Patients
  • Patients should be cautioned about the concomitant use of Lexapro and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation since combined use of psychotropic drugs that interfere with serotonin reuptake and these agents has been associated with an increased risk of bleeding.
• Drug Interactions
  • Drugs That Interfere With Hemostasis (NSAIDs, Aspirin, Warfarin, etc.)
• Geriatric Use
  • SSRIs and SNRIs, including Lexapro, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event (see PRECAUTIONS, Hyponatremia).

Stromectol (ivermectin) Tablets

Prescribing Information

PRECAUTIONS

• Information for Patients
• Drug Interactions (new subsection)
  • Post-marketing reports of increased INR (International Normalized Ratio) have been rarely reported when ivermectin was co-administered with warfarin.

Vaseretic (enalapril maleate and hydrochlorothiazide) Tablets

Prescribing Information

PRECAUTIONS

• Drug Interactions
  • Enalapril Maleate
    • Gold
      • Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including Vaseretic.

Vasotec (enalapril maleate) Tablets

Prescribing Information

PRECAUTIONS

• Drug Interactions
  • Gold
    • Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including Vasotec.

Ventavis (iloprost) Inhalation Solution

Prescribing Information

PRECAUTIONS

• General
  • Ventavis inhalation can induce bronchospasm, especially in susceptible patients with hyperreactive airways. Ventavis has not been evaluated in patients with chronic obstructive pulmonary disease (COPD), severe asthma, or with acute pulmonary infections. Such patients should be carefully monitored during therapy with Ventavis.

ADVERSE REACTIONS

• Postmarketing Experience
  • Cases of bronchospasm and wheezing have been reported, particularly in susceptible patients with hyperreactive airways, such as patients with comorbid diseases affecting the airways (see PRECAUTIONS). Cases of epistaxis and gingival bleeding have been reported within one month of starting iloprost treatment. Cases of dizziness and diarrhea have also been reported with the use of Ventavis.

Videx EC (didanosine, USP) Delayed-Release Capsules (Enteric-Coated Beadlets)

Prescribing Information (in new labeling format)

Patient Package Insert

USE IN SPECIFIC POPULATIONS

• Pediatric Use
  • Use of didanosine in pediatric patients from 2 weeks of age through adolescence is supported by evidence from adequate and well-controlled studies of didanosine in adult and pediatric patients [see Dosage and Administration (2), Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14)]. Additional pharmacokinetic studies in pediatric patients support use of Videx EC in pediatric patients who weigh at least 20 kg.

PATIENT PACKAGE INSERT

The following language was added:

...Dispose of unused medicines through community take-back disposal programs when available or place Videx EC in an unrecognizable closed container in the household trash.

Adagen (pegademase bovine) Injection

Prescribing Information

ADVERSE REACTIONS

• First Paragraph
  • The following adverse reactions were reported during clinical trials...
• The following adverse reactions have been identified during post-approval use of Adagen (pegademase bovine) Injection...
  • Hematologic events: hemolytic anemia, auto-immune hemolytic anemia, thrombocythemia
  • Dermatological events: injection site erythema, urticaria

Alimta (pemetrexed disodium) Injection, Powder, Lyophilized, For Solution for Intravenous Use

Prescribing Information (in new labeling format)

Patient Package Insert

ADVERSE REACTIONS

• Clinical Trials Experience
  • Non-Small Cell Lung Cancer (NSCLC) — Combination with Cisplatin (new subsection)
  • Non-Small Cell Lung Cancer (NSCLC) — Single-Agent
    • ...No clinically relevant differences in adverse reactions were seen in patients based on histology...
• Postmarketing Experience
  • Injury, poisoning, and procedural complications (new subsection)
  • Respiratory (new subsection)

USE IN SPECIFIC POPULATIONS

• Geriatric Use
  • In the initial treatment non-small cell lung cancer clinical trial...

PATIENT COUNSELING INFORMATION

• FDA Approved Patient Labeling - Patients should be instructed to read the patient package insert carefully.

PATIENT PACKAGE INSERT

• What is Alimta?
  • Non-small cell lung cancer...
• How is Alimta given?
  • If you are being treated with Alimta and cisplatin for the initial treatment of either mesothelioma or non-small cell lung cancer...
  • If you are being treated because your non-small cell lung cancer has returned...

Curosurf (poractant alfa) Intratracheal Suspension

Prescribing Information

ADVERSE REACTIONS

• Pulmonary Hemmorhage (added)

Lybrel (90 mcg levonorgestrel and 20 mcg ethinyl estradiol) Tablets

Prescribing Information

Patient Package Insert

ADVERSE REACTIONS

• Focal nodular hyperplasia (added)

BRIEF SUMMARY PATIENT PACKAGE INSERT

• BEFORE YOU START TAKING LYBREL

DETAILED PATIENT LABELING

• BEFORE YOU START TAKING LYBREL

NeoProfen (ibuprofen lysine) Injection

Prescribing Information

ADVERSE REACTIONS

• Postmarketing Experience (new subsection)
  • The following adverse reactions have been identified from spontaneous postmarketing reports or published literature: gastrointestinal perforation and necrotizing enterocolitis...

Retrovir (zidovudine) Tablets, Capsules, and Syrup

Prescribing Information (in new labeling format)

ADVERSE REACTIONS

• Clinical Trials Experience
  • Adults
    • In addition to the adverse reactions listed in Table 2, adverse reactions observed at an incidence of >5% in any treatment arm in clinical studies (NUCA3001, NUCA3002, NUCB3001, and NUCB3002)...
    • ...hyperbilirubinemia was reported at an incidence of <0.8%.
  • Pediatrics
    • Macrocytosis was reported in the majority of pediatric patients receiving Retrovir 180 mg/m2 every 6 hours in open-label studies. Additionally, adverse reactions reported at an incidence of <6%...

USE IN SPECIFIC POPULATIONS

• Pregnancy
• Pediatric Use

NONCLINICAL TOXICOLOGY

• Carcinogenesis, Mutagenesis, Impairment of Fertility
• Reproductive and Developmental Toxicology Studies

Valtrex (valacyclovir hydrochloride) Caplets

Prescribing Information (in new labeling format)

Patient Package Insert

ADVERSE REACTIONS

• Clinical Trials Experience in Pediatric Patients

USE IN SPECIFIC POPULATIONS

• Pediatric Use

PATIENT COUNSELING INFORMATION

• Chickenpox
  • Patients should be advised to initiate treatment at the earliest sign or symptom of chickenpox.

PATIENT PACKAGE INSERT

• What is Valtrex?
  • Valtrex is used in children:
    • ...to treat chickenpox (for children 2 to <18 years of age).

Pegasys (peginterferon alfa-2a)

Medication Guide

MEDICATION GUIDE (provides for new information related to the green cap needles dispensed with the product.)

Instructions for Preparing and Giving a Dose with a Pegasys Prefilled Syringe

• How do I prepare and inject Pegasys?
  • Uncover the needle.
  • For safety reasons, before you dispose of the syringe and needle, place the free end of the green cap...

Instructions for Preparing and Giving a Dose with a Pegasys Vial

• How do I inject Pegasys?
  • Remove the needle and syringe from their packaging and attach the needle to the end of the syringe.
  • For safety reasons, always place used syringes and needles in a puncture-resistant container immediately after use and never reuse them.

FDA/CDER/Office of Drug Safety
Web page last revised by jlw November 04, 2008