MedWatch - March 2007 Safety-Related Drug Labeling Changes

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Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) -- March 2007

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

Summary View

Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Cyclessa (desogestrel/ethinyl estradiol) Tablets Prescribing Information Patient Package Insert	CONTRAINDICATIONS WARNINGS Initial Overview Thromboembolic Disorders and Other Vascular Problems Cerebrovascular Diseases Estimates of Mortality from Contraceptive Use Carcinoma of the Reproductive Organs and Breasts Oral Contraceptive Use Before Or During Early Pregnancy Elevated Blood Pressure Bleeding Irregularities PRECAUTIONS Sexually Transmitted Diseases Lipid Disorders Emotional Disorders Drug Interactions Anti-HIV Protease Inhibitors Herbal Products Nursing Mothers ADVERSE REACTIONS The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related..... The following adverse reactions have been reported in users of oral contraceptives and the association has been neither confirmed nor refuted..... PACKAGE PACKAGE INSERT Brief Summary Instructions to Patients How to Take Cyclessa Detailed Patient Package Insert Who Should Not Take Oral Contraceptives? Other Considerations Before Taking Oral Conceptives Risks of Taking Oral Conceptives Cancer of the Reproductive Organs and Breasts Lipid Metabolism and Inflammation of the Pancreas Side Effects of Oral Conceptives Irregular Vaginal Bleeding Fluid Retention or Raised Blood Pressure General Precautions How to Take Cyclessa	CONTRAINDICATIONS Oral contraceptives should not be used in women who currently have the following conditions: Hepatic tumors (benign or malignant) or active liver disease Heavy smoking (>15 cigarettes per day) and over age 35 WARNINGS See highlighted labeling for revised text.

Genotropin (somatropin [rDNA origin] for injection) Prescribing Information	CONTRAINDICATIONS PRECAUTIONS General Pediatric Patients Adult Patients Information for Patients Laboratory Tests Drug Interactions Geriatric Use	CONTRAINDICATIONS Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. In general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor..... Extensive labeling revisions. See highlighted prescribing information for revised text.

Saizen (somatropin [rDNA origin] for injection) for Subcutaneous or Intramuscular Injection Prescribing Information	CONTRAINDICATIONS WARNINGS PRECAUTIONS General Pediatric Patients Adult Patients Information for Patients Laboratory Tests Drug Interactions Geriatric Use	CONTRAINDICATIONS Saizen reconstituted with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) should not be administered to patients with a known sensitivity to Benzyl Alcohol..... Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. In general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin..... See highlighted prescribing information for revised text.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Ambien (zolpidem tartrate) Tablets Prescribing Information (in new labeling format) See MedWatch Safety Alert posted on 3/14/2007 regarding sedative-hypnotic drug products.	WARNINGS & PRECAUTIONS Special Populations Pediatric Patients USE IN SPECIFIC POPULATIONS Pediatric Use .....Ten patients on zolpidem (7.4%) discontinued treatment due to an adverse event. PATIENT COUNSELING INFORMATION Special Concerns Children	WARNINGS & PRECAUTIONS: Special Populations/Pediatric Patients .....Hallucinations were reported in 7.4% of the pediatric patients who received zolpidem; none of the pediatric patients who received placebo reported hallucinations.

Aristospan (triamcinolone hexacetonide injectable suspension, USP) 5 mg/mL Prescribing Information	WARNINGS General PRECAUTIONS General .....Atrophy at the site of injection has been reported. Pediatric Use This product contains benzyl alcohol as a preservative. Benzyl alcohol, a component of this product, has been associated with serious adverse events and death, particularly in pediatric patients..... The “gasping syndrome”.....	WARNINGS: General .....Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants. There have been rare reports of deaths, primarily in preterm infants, associated with exposure to excessive amounts of benzyl alcohol.....

Aristospan (triamcinolone hexacetonide injectable suspension, USP) 20 mg/mL Prescribing Information	WARNINGS General PRECAUTIONS General .....Atrophy at the site of injection has been reported. Pediatric Use This product contains benzyl alcohol as a preservative. Benzyl alcohol, a component of this product, has been associated with serious adverse events and death, particularly in pediatric patients..... The “gasping syndrome”.....	WARNINGS: General .....Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants. There have been rare reports of deaths, primarily in preterm infants, associated with exposure to excessive amounts of benzyl alcohol.....

Cordarone (amiodarone HCl) Tablets Prescribing Information	WARNINGS Pulmonary Toxicity Pulmonary Alveolar Hemorrhage ADVERSE REACTIONS Post-marketing Reports Pulmonary Alveolar Hemorrhage	WARNINGS: Pulmonary Toxicity There have been postmarketing reports of acute-onset (days to weeks) pulmonary injury in patients treated with oral Cordarone with or without initial I.V. therapy. Findings have included pulmonary infiltrates and/or mass on X-ray, pulmonary alveolar hemorrhage, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia. Some cases have progressed to respiratory failure and/or death.....

Keppra (levetiracetam) Tablets and Oral Solution Prescribing Information Patient Package Insert	WARNINGS Primary Generalized Tonic-Clonic Seizures (new) PRECAUTIONS Information for Patients Patients should be advised that Keppra may cause changes in behavior..... ADVERSE REACTIONS Primary Generalized Tonic-Clonic Seizures Table 10 Discontinuation or Dose Reduction in Well-Controlled Clnical Studies Primary Generalized Tonic-Clonic Seizures Post-marketing Experience Hepatic Failure PATIENT PACKAGE INSERT Keppra may cause the following serious problems in adults. Call your healthcare provider right away if you get any of the following symptoms.....	WARNINGS: Primary Generalized Tonic-Clonic Seizures .....In patients 6 years of age and older experiencing primary generalized tonic-clonic seizures, Keppra is associated with behavioral abnormalities..... In the double-blind, controlled trial in patients with idiopathic generalized epilepsy experiencing primary generalized tonic-clonic seizures, irritability was the most frequently reported psychiatric adverse event occurring in 6.3% of Keppra-treated patients compared to 2.4% of placebo patients. Additionally, non-psychotic behavioral disorders (reported as abnormal behavior, aggression, conduct disorder, and irritability) occurred in 11.4% of the Keppra-treated patients compared to 3.6% of placebo patients. Of the Keppra-treated patients experiencing non-psychotic behavioral disorders, one patient discontinued treatment due to aggression. Non-psychotic mood disorders (reported as anger, apathy, depression, mood altered, mood swings, negativism, suicidal ideation, and tearfulness) occurred in 12.7% of Keppra-treated patients compared to 8.3% of placebo patients.....

Noroxin (norfloxacin) Tablets Prescribing Information	WARNINGS Clostridium Difficile Associated Diarrhea PRECAUTIONS Information for Patients: Patients should be advised: that diarrhea is a common problem caused by antibiotics, which usually ends when the antibiotic is discontinued. Sometimes after starting the treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.	WARNINGS: Clostridium Difficile Associated Diarrhea Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Noroxin and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile..... .....If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Prilosec OTC (omeprazole magnesium delayed-release tablet) Over-the-Counter Drug Product Prescribing Information	WARNINGS Ask a doctor or pharmacist before use if you are taking: warfarin (blood-thinning medicine) prescription antifungal or anti-yeast medicines diazepam (anxiety medicine) digoxin (heart medicine) tacrolimus (immune system medicine) atazanavir (medicine for HIV infection)	As stated in column 2.

Primaxin I.M. (imipenem and cilastatin injectable suspension) Prescribing Information	WARNINGS ADVERSE REACTIONS Systemic Adverse Reactions CNS Seizures	WARNINGS Seizures and other CNS adverse experiences, such as myoclonic activity, have been reported during treatment with Primaxin I.M.....

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Brand (Generic) Name	Sections Modified
Aldara (imiquimod) Cream, 5% for Topical Use Only Prescribing Information (in new labeling format) Patient Package Insert	USE IN SPECIFIC POPULATIONS Pediatric Use PATIENT COUNSELING INFORMATION Patient Package Insert Important: Not for mouth, eye, or vaginal use How do I store Aldara Cream?

Carnitor (levocarnitine) Tablets and Oral Solution Carnitor SF (levocarnitine) Sugar-Free Oral Solution Prescribing Information	PRECAUTIONS General ADVERSE REACTIONS Initial Paragraph

Delatestryl (testosterone enanthate injection, USP) Prescribing Information	PRECAUTIONS Geriatric Use

Detrol LA (tolterodine tartrate extended release capsules) Prescribing Information	PRECAUTIONS Information for Patients Patients should be advised to exercise caution in decisions to engage in potentially dangerous activities..... ADVERSE REACTIONS Post-marketing Surveillance Gastrointestinal Diarrhea Central/Peripheral Nervous Confusion Disorientation Memory Impairment Hallucinations Reports of aggravation of symptoms of dementia....

Flumadine (rimantadine hydrochloride tablets and syrup) Prescribing Information	PRECAUTIONS Drug Interactions Influenza Virus Vaccine Live, Intranasal (FluMist)

Focalin (dexmethylphenidate hydrochloride) Tablets Prescribing Information	PRECAUTIONS Pediatric Use In a study conducted in young rats, racemic methylphenidate was administered orally at doses of up to 100 mg/kg/day for 9 weeks.....

Fortaz (ceftazidime for injection) Fortaz (ceftazidime injection) Prescribing Information	PRECAUTIONS Drug Interactions .....In common with other antibiotics, ceftazidime may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.

Nexavar (sorafenib) Tablets Prescribing Information Patient Package Insert	PRECAUTIONS General Gastroinestinal Information for Patients .....Patients should be advised that cases of gastroinestinal perforation have been reported in patients taking Nexavar. ADVERSE REACTIONS Additional Data from Multiple Clinical Trials Cardiovascular Congestive Heart Failure Digestive Gastrointestinal Perforation General Disorders Hemorrhage (including gastrointestinal and respiratory tract and uncommon cases of cerebral hemorrhage Pain ( including mouth, bone, and tumor pain) Nervous System and Psychiatric Reversible Posterior Leukoencephalopathy Transient Ischemia Attack & Arrhythmia PATIENT PACKAGE INSERT What are possible side effects of Nexavar?

Orencia (abatacept) Prescribing Information Patient Package Insert	PRECAUTIONS Blood Glucose Testing PATIENT PACKAGE INSERT Who should not receive Orencia? What should I tell my doctor before treatment with Orencia? Can I receive Orencia if I am taking other medicines for my RA or other conditions?

Prozac (fluoxetine capsules and oral solution, USP) Prozac Weekly (fluoxetine delayed-relase capsules, USP) Prescribing Information See MedWatch Safety Alert posted on 7/19/2006 which discusses SSRIs and Treatment Challenges of Depression in Pregnancy.	PRECAUTIONS Drug Interactions Drugs metabolized by CYP2D6 Propafenone Pregnancy Nonteratogenic Effects .....Infants exposed to SSRIs in late pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality..... .....Physicians should note that in a prospective longitudinal study of 201 women with a history of major depression who were euthymic at the beginning of pregnancy, women who discontinued antidepressant medication during pregnancy were more likely to experience a relapse of major depression.....

Reyataz (atazanavir sulfate) Capsules Prescribing Information Patient Package Insert	PRECAUTIONS General Nephrolithiasis ADVERSE REACTIONS Post-marketing Experience Renal System Nephrolithiasis PATIENT PACKAGE INSERT What are the possible side effects of Reyataz?

Risperdal Consta (risperidone) Long-Acting Injection Prescribing Information	PRECAUTIONS General Administration Hyperprolactinemia Use in Patients with Concomitant Illness Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis - Oral ADVERSE REACTIONS Postintroduction Reports Pituitary Adenomas QT Prolongation Retinal Artery Occlusion.....

Symmetrel (amantadine hydrochloride, USP) Tablets and Syrup Prescribing Information	PRECAUTIONS Drug Interactions The concurrent use of Symmetrel with live attenuated influenza vaccine (LAIV) intranasal has not been evaluated..... ADVERSE REACTIONS Other Adverse Reactions Reported During Post-marketing Experience..... Hematologic Agranulocytosis

Timentin (ticarcillin disodium and clavulanate potassium) Injection Prescribing Information	PRECAUTIONS Geriatric Use

Timentin (sterile ticarcillin disodium and clavulanate potassium) for Intravenous Administration Prescribing Information	PRECAUTIONS Geriatric Use

Toprol-XL (metoprolol succinate) Extended-Release Tablets Please contact AstraZeneca LP at 1-800-236-9933 for prescribing information.	PRECAUTIONS Drug Interactions Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. ADVERSE REACTIONS Post-marketing Experience Cardiovascular Cardiogenic shock in patients with acute myocardial infarction

Uroxatral (alfuzosin HCl extended-release tablets) Prescribing Information	PRECAUTIONS General Patients with Congenital or Acquired QT Prolongation A postmarketing study evaluating the effect of combining Uroxatral with another drug of comparable QT effect showed an increased effect when compared to either drug alone.....

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Brand (Generic) Name	Sections Modified
Aggrenox (aspirin/extended-release dipyridamole) Capsules Prescribing Information	ADVERSE REACTIONS Headache was most notable in the first month of treatment.

Detrol (tolterodine tartrate tablets) Prescribing Information	ADVERSE REACTIONS Post-marketing Surveillance Central/Peripheral Nervous Confusion Disorientation Memory Impairment Hallucinations Reports of aggravation of symptoms of dementia.....

Lipitor (atorvastatin calcium) Tablets Prescribing Information	ADVERSE REACTIONS Clinical Adverse Experiences Treating to New Targets Study (TNT) Incremental Decrease in Endpoints Through Aggressive Lipid Lowering Study (IDEAL)

Zelnorm (tegaserold maleate) Tablets Prescribing Information See MedWatch Safety Alert posted on 3/30/2007 regarding the market withdrawal of Zelnorm.	ADVERSE REACTIONS Post-marketing Experience Elevation in ALT, AST and Bilirubin Hepatitis Alopecia

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Brand (Generic) Name	Sections Modified
Avandaryl (rosiglitazone maleate and glimepiride) Tablets Prescribing Information Patient Package Insert	PATIENT PACKAGE INSERT What should I tell my doctor before starting Avandaryl? How should I take Avandaryl? What are the ingredients in Avanadryl?
Baraclude (entecavir) Tablets and Oral Solution Prescribing Information Patient Package Insert	PATIENT PACKAGE INSERT What should I tell my healthcare provider before I take Baraclude? How should I take Baraclude?

Dolobid (diflunisal) Tablets Prescribing Information Medication Guide	MEDICATION GUIDE (new)

Fentora (fentanyl buccal tablet) Prescribing Information Medication Guide	MEDICATION GUIDE Revised to provide for the addition of a 300-mcg strength dose.

Geodon (ziprasidone HCl) Capsules Prescribing Information Patient Package Insert	PATIENT PACKAGE INSERT What is Geodon? Who Should Take Geodon? Symptoms of manic or mixed episodes of bipolar depression may include..... What is the most important safety information I should know about Geodon? How to Take Geodon

Kaletra (lopinavir/ritonavir) Tablets and Oral Solution Prescribing Information Patient Package Insert	PATIENT PACKAGE INSERT How Do I Store Kaletra? Kaletra tablets should be stored at room temperature. Exposure of Kaletra tablets to high humidity outside the pharmacy container for longer than 2 weeks is not recommended.

Soliris (eculizumab) Prescribing Information Medication Guide	MEDICATION GUIDE (new)

Zyban (bupropion hydrochloride) Sustained-Release Tablets Prescribing Information Medication Guide	MEDICATION GUIDE See highlighted text for labeling revisions.

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