MedWatch - April 2006 Safety-Related Drug Labeling Changes

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Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) -- April 2006

The detailed view includes drug products with safety labeling changes to the BOXED WARNING, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, or ADVERSE REACTIONS sections. Deletions or editorial revisions made to these sections are not included in this summary. The prescribing information may be accessed by clicking on the drug name.

Summary View

Brand (Generic) Name

Sections Modified

Summary of Changes to Contraindications and Warnings

Premarin (conjugated estrogens tablets, USP)

(click product name to read prescribing information)

BOXED WARNING

Cardiovascular and Other Risks

WARNINGS

Cardiovascular Disorders
- Stroke and Coronary Heart Disease
- Venous Thromboembolism (VTE)
Malignant Neoplasms
- Breast Cancer
Dementia

PRECAUTIONS

Geriatric Use

BOXED WARNING

The estrogen-alone substudy of the Women's Health Initiative (WHI) reported.....

The estrogen-plus-progestin substudy of the WHI reported increased.....

WARNINGS

See prescribing information for revised text.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Prozac (fluoxetine hydrochloride) Please contact Eli Lilly and Company at 1-800-545-5979 for prescribing information.	CONTRAINDICATIONS Pimozide PRECAUTIONS Drug Interactions Antipsychotics .....Clinical studies of pimozide with other antidepressants demonstrate an increase in drug interaction or QT_c prolongation. While a specific study with pimozide and fluoxetine has not been conducted, the potential for drug interactions or QT_c prolongation warrants restricting the concurrent use of pimozide and Prozac. Concomitant use of Prozac and pimozide is contraindicated. ADVERSE REACTIONS Postintroduction Reports Erythema Multiforme	Concomitant use in patients taking pimozide is contraindicated.

Sarafam (fluoxetine hydrochloride) Please contact Warner Chilcott at 1-800-521-8813 for prescribing information.	CONTRAINDICATIONS Pimozide PRECAUTIONS Drug Interactions Antipsychotics .....Clinical studies of pimozide with other antidepressants demonstrate an increase in drug interaction or QT_c prolongation. While a specific study with pimozide and fluoxetine has not been conducted, the potential for drug interactions or QT_c prolongation warrants restricting the concurrent use of pimozide and fluoxetine. Concomitant use of fluoxetine and pimozide is contraindicated. ADVERSE REACTIONS Postintroduction Reports Erythema Multiforme	Concomitant use in patients taking pimozide is contraindicated.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Advil (200 mg ibuprofen) Capsules and Tablets Over-the-Counter (OTC) Medication (click product name to read labeling template)	WARNINGS Allergy Alert Stomach Bleeding Warning DO NOT USE..... ASK A DOCTOR BEFORE USE IF YOU HAVE..... WHEN USING THIS PRODUCT..... STOP USE AND ASK A DOCTOR IF..... IF PREGNANT OR BREASTFEEDING.....	Please see attached labeling template. Revisions to the Drug Facts label and Principal Display Panel include more specific information for consumers, family members, and caregivers about potential risks of cardiovascular and gastrointestinal adverse effects associated with the use of non-prescription NSAIDS (excluding aspirin). In addition, the "Allergy Alert" has been revised to include a warning for aspirin sensitive individuals and a description of early symptoms associated with Stevens-Johnson Syndrome (SJS). The "Alcohol Warning" has been relocated to appear as part of the new "Stomach Bleeding Warning". The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Advil Cold & Sinus Liqui-Gels (200 mg ibuprofen/30 mg pseudoephedrine HCl capsules) Over-the-Counter (OTC) Medication Please contact Wyeth Consumer Healthcare at 1-800-322-3129 for prescribing information.	WARNINGS	ASK A DOCTOR OR PHARMACIST BEFORE USE IF YOU ARE taking aspirin for heart attack or stroke, because ibuprofen may decrease this benefit of aspirin.

Advil Cold & Sinus (200 mg ibuprofen/ 30 mg pseudoephedrine HCl) Tablets Over-the-Counter (OTC) Medication Please contact Wyeth Consumer Healthcare at 1-800-322-3129 for prescribing information.	WARNINGS	ASK A DOCTOR OR PHARMACIST BEFORE USE IF YOU ARE taking aspirin for heart attack or stroke, because ibuprofen may decrease this benefit of aspirin.

Avandamet (rosiglitazone maleate/metformin HCl) (click product name to read prescribing information)	WARNINGS Rosiglitazone Maleate Cardiac Failure and Other Cardiac Effects	Avandamet is not recommended in patients with NYHA Class 3 and 4 cardiac status.

Avandia (rosiglitazone maleate) Tablets (click product name to read prescribing information)	WARNINGS Cardiac Failure and Other Cardiac Effects Table 7: Emergent Cardiovascular Adverse Events in Patients with Congestive Heart Failure (NYHA Class 1 and 2) treated New or Worsening Edema New or Worsening Dyspnea	Patients with congestive heart failure (CHF) New York Heart Association (NYHA) Class 1 and 2 treated with Avandia have an increased risk of cardiovascular events. 52-week, double-blind, placebo-controlled echocardiographic study was conducted in 224 patients with type 2 diabetes mellitus and NYHA Class 1 or 2 CHF (ejection fraction ≤45%) on background antidiabetic and CHF therapy.....

Avastin (bevacizumab) for Intravenous Use (click product name to read prescribing information)	WARNINGS Gastrointestinal Perforations/Wound Healing Complications	Gastrointestinal perforation and wound dehiscence, complicated by intra-abdominal abscesses, occurred at an increased incidence in patients receiving Avastin as compared to controls. Avastin has also been shown to impair wound healing in pre-clinical animal models.....

Children's Advil Cold (100 mg/5 ml ibuprofen and 15 mg/5 ml pseudoephedrine) Suspension Over-the-Counter (OTC) Medication (click product name to read labeling template)	WARNINGS Allergy Alert Stomach Bleeding Warning Sore Throat Warning DO NOT USE..... ASK A DOCTOR BEFORE USE IF THE CHILD HAS..... ASK A DOCTOR OR PHARMACIST BEFORE USE IF THE CHILD IS..... WHEN USING THIS PRODUCT..... STOP USE AND ASK A DOCTOR.....	Please see attached labeling template. Revisions to the Drug Facts label and Principal Display Panel include more specific information for consumers, family members, and caregivers about potential risks of cardiovascular and gastrointestinal adverse effects associated with the use of non-prescription NSAIDS (excluding aspirin). In addition, the "Allergy Alert" has been revised to include a warning for aspirin sensitive individuals and a description of early symptoms associated with Stevens-Johnson Syndrome (SJS). The "Alcohol Warning" has been relocated to appear as a part of the new "Stomach Bleeding Warning". The labeling template includes the recommended general changes and not the specific approved product labeling For additional details, see MedWatch 6/15/05 Safety Alert.

Children's Advil Allergy Sinus (100 mg ibuprofen, 15 mg pseudoephedrine, and 1mg chlorpheniramine per 5 mL) Suspension Over-the-Counter (OTC) Medication (click product name to read labeling template)	WARNINGS Allergy Alert Stomach Bleeding Warning Sore Throat Warning DO NOT USE..... ASK A DOCTOR BEFORE USE IF THE CHILD HAS..... ASK A DOCTOR OR PHARMACIST BEFORE USE IF THE CHILD IS..... WHEN USING THIS PRODUCT..... STOP USE AND ASK A DOCTOR.....	Please see attached labeling template. Revisions to the Drug Facts label and Principal Display Panel include more specific information for consumers, family members, and caregivers about potential risks of cardiovascular and gastrointestinal adverse effects associated with the use of non-prescription NSAIDS (excluding aspirin). In addition, the "Allergy Alert" has been revised to include a warning for aspirin sensitive individuals and a description of early symptoms associated with Stevens-Johnson Syndrome (SJS). The "Alcohol Warning" has been relocated to appear as a part of the new "Stomach Bleeding Warning". The labeling template includes the recommended general changes and not the specific approved product labeling For additional details, see MedWatch 6/15/05 Safety Alert.

Children's Advil Chewables (50 mg ibuprofen) Chewable Tablet Junior Strength Advil Chewables (100 mg ibuprofen) Chewable Tablet Over-the-Counter (OTC) Medication (click product name to read labeling template)	WARNINGS Allergy Alert Stomach Bleeding Warning Sore Throat Warning DO NOT USE..... ASK A DOCTOR BEFORE USE IF THE CHILD HAS..... ASK A DOCTOR OR PHARMACIST BEFORE USE IF THE CHILD IS..... WHEN USING THIS PRODUCT..... STOP USE AND ASK A DOCTOR.....	Please see attached labeling template. Revisions to the Drug Facts label and Principal Display Panel include more specific information for consumers, family members, and caregivers about potential risks of cardiovascular and gastrointestinal adverse effects associated with the use of non-prescription NSAIDS (excluding aspirin). In addition, the "Allergy Alert" has been revised to include a warning for aspirin sensitive individuals and a description of early symptoms associated with Stevens-Johnson Syndrome (SJS). The "Alcohol Warning" has been relocated to appear as a part of the new "Stomach Bleeding Warning". The labeling template includes the recommended general changes and not the specific approved product labeling For additional details, see MedWatch 6/15/05 Safety Alert.

Infant's Advil (50 mg ibuprofen/1.25 mL) Concentrated Drops* grape flavored 1/2 oz package size and white grape-flavored 1/4 and 1/2 oz package sizes Over-the-Counter (OTC) Medication* (click product name to read labeling template)	WARNINGS Allergy Alert Stomach Bleeding Warning Sore Throat Warning DO NOT USE..... ASK A DOCTOR BEFORE USE IF THE CHILD HAS..... ASK A DOCTOR OR PHARMACIST BEFORE USE IF THE CHILD IS..... WHEN USING THIS PRODUCT..... STOP USE AND ASK A DOCTOR.....	Please see attached labeling template. Revisions to the Drug Facts label and Principal Display Panel include more specific information for consumers, family members, and caregivers about potential risks of cardiovascular and gastrointestinal adverse effects associated with the use of non-prescription NSAIDS (excluding aspirin). In addition, the "Allergy Alert" has been revised to include a warning for aspirin sensitive individuals and a description of early symptoms associated with Stevens-Johnson Syndrome (SJS). The "Alcohol Warning" has been relocated to appear as a part of the new "Stomach Bleeding Warning". The labeling template includes the recommended general changes and not the specific approved product labeling For additional details, see MedWatch 6/15/05 Safety Alert.

Focalin XR (dexmethylphenidate HCl) Extended-Release Capsules (click product name to read prescribing information)	WARNINGS Sudden Death and Pre-Existing Structural Cardiac Abnormalities	Sudden death has been reported in association with CNS stimulant treatment at usual doses in children with structural cardiac abnormalities. Although some structural cardiac abnormalities alone may carry an increased risk of sudden death, stimulant products generally should not be used in children, adolescents, or adults with known structural cardiac abnormalities.

Lidoderm (lidocaine 5%) Patch (click product name to read prescribing information)	WARNINGS Accidental Exposure in Children ADVERSE REACTIONS Application Site Reactions Irritation Allergic Reactions Hypersensitivity Other Adverse Events Pain Exacerbated HANDLING AND DISPOSAL	It is important for patients to store and dispose of Lidoderm out of the reach of children, pets and others. (See HANDLING AND DISPOSAL)

Razadyne (galantamine HBr) Extended-Release Capsules Razadyne (galantaine HBr) Tablets and Oral Solution (click product name to read prescribing information)	WARNINGS Cardiovascular Conditions PRECAUTIONS Information for Patients and Caregivers Drug-Drug Interactions Memantine ADVERSE REACTIONS Pre-Marketing Clinical Trial Experience Other Adverse Events Observed During Clinical Trials Body as a Whole Asthenia Fever Malaise Cardiovascular System Disorders Myocardial Ischemia or Infarction Central & Peripheral Nervous System Disorders Leg Cramps Tinnitus Transient Ischemic Attack or Cerebrovascular Accident Heart Rate & Rhythm Disorders Atrial Arrhythmias..... Severe Bradycardia Psychiatric Disorders Suicidal Ideation Suicide	In randomized controlled trials, bradycardia was reported more frequently in galantamine-treated patients than in placebo-treated patients, but was rarely severe and rarely led to treatment discontinuation.....

Synarel (nafarelin acetate) Nasal Solution (click product name to read prescribing information) Note: New indication for treatment of endometriosis approved in April 2006.	WARNINGS PRECAUTIONS General Information for Patients Drug/Laboratory Tests Interactions Pediatric Use ADVERSE REACTIONS Initial Section Postmarketing Pituitary Apoplexy [section also added to Central Precocious Puberty product insert.] Changes in Bone Density Changes in Laboratory Values During Treatment Other Changes	Safe use of nafarelin acetate in pregnancy has not been established clinically. Before starting treatment with Synarel, pregnancy must be excluded. When used regularly at the recommended dose, Synarel usually inhibits ovulation and stops menstruation. Contraception is not insured, however, by taking Synarel, particularly if patients miss successive doses. Therefore, patients should use nonhormonal methods of contraception. Patients should be advised to see their physician if they believe they may be pregnant. If a patient becomes pregnant during treatment, the drug must be discontinued and the patient must be apprised of the potential risk to the fetus.

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Brand (Generic) Name	Sections Modified
Catapres-TTS (clonidine) Transdermal Therapeutic System (click product name to read prescribing information)	PRECAUTIONS MRI PATIENT INSTRUCTIONS General Information Skin burns have been reported at the patch site in several patients wearing aluminized transdermal system during a magnetic resonance imaging scan (MRI)..... CARTON & POUCH LABELS To avoid possible burns, remove the Catapres-TTS patch before undergoing an MRI (magnetic resonance imaging) procedure.

Cosopt (dorzolomide hydrochloride-timolol maleate ophthalmic solution) Sterile Ophthalmic Solution (click product name to read prescribing information)	PRECAUTIONS Drug Interactions CYP2D6 Inhibitors SSRIs INSTRUCTIONS FOR USE

Desoxyn (methamphetamine HCl tablets, USP) (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Emla (lidocaine 2.5% and prilocaine 2.5%) Cream (click product name to read prescribing information)	PRECAUTIONS Carcinogenesis, Mutagenesis, Impairment of Fertility INSTRUCTIONS FOR APPLICATION

Gemzar (gemcitabine HCl) for Injection (click product name to read prescribing information)	PRECAUTIONS Patients with Renal or Hepatic Impairment .....as there is insufficient information from clinical studies to allow clear dose recommendations..... Radiation Therapy ADVERSE REACTIONS Postmarketing Experience Vascular Disorders Skin Severe skin reactions, including desquamation and bullous skin eruptions..... Hepatic Increased liver function tests including elevations in AST, ALT, GGT, alkaline phosphatase, and bilirubin levels..... Injury, Poisoning, and Procedural Complications

Genotropin (somatropin [rDNA origin] for injection) (click product name to read prescribing information)	PRECAUTIONS General ADVERSE REACTIONS In two clinical studies with Genotropin in pediatric patients with Turner Syndrome the most frequently reported adverse events were respiratory illnesses (influenza, tonsillitis, otitis, sinusitis), joint pain, and urinary tract infection. The only treatment-related adverse event that occurred in more than 1 patient was joint pain.

Hyzaar (losartan potassium-hydrochlorothiazide tablets) (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Losartan Potassium Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors Hydrochlorothiazide Non-Steroidal Anti-Inflammatory Drugs including Selective Cyclooxygenase-2 Inhibitors Pediatric Use

Klor-Con (potassium chloride extended-release tablets, USP) (click product name to read prescribing information)	PRECAUTIONS Nursing Mothers ADVERSE REACTIONS Skin rash has been reported rarely

Lescol (fluvastatin sodium) Capsules Lescol XL (fluvastatin sodium) Extended-Release Tablets (click product name to read prescribing information)	PRECAUTIONS Pediatric Use The safety and efficacy of Lescol and Lescol XL in children and adolescent patients 9 -16 years of age with heterozygous familial hypercholesterolemia have been evaluated in open-label, uncontrolled clinical trials of 2 years' duration..... ADVERSE REACTIONS Pediatric Patients In two open-label, uncontrolled studies, 114 patients (66 boys and 48 girls) with heterozygous familial hypercholesterolemia, 9-16 years of age, were treated for 2 years with fluvastatin sodium administered as Lescol capsules 20 mg - 40 mg bid or Lescol XL 80 mg extended-release tablets..... PATIENT PACKAGE INSERT

Nexium (esomeprazole magnesium) Delayed-Release Capsules (click product name to read prescribing information)	PRECAUTIONS Pediatric Use Use of Nexium in adolescent patients 12 to 17 years of age for short-term treatment of GERD is supported by..... ADVERSE REACTIONS The safety of Nexium was evaluated in over 15,000 patients (aged 12-84 Years).....

Prevacid (lansoprazole) Delayed-Release Capsules Prevacid (lansoprazole) for Delayed-Release Oral Suspension Prevacid SoluTab (lansoprazole) Delayed-Release Orally Disintegrating Tablets (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time. In an open-label, single-arm, eight-day, pharmacokinetic study of 28 adult rheumatoid arthritis patients (who required the chronic use of 7.5 to 15 mg of methotrexate given weekly).....

Prevacid NapraPAC (lansoprazole delayed-release capsules and naproxen tablets kit), 15 mg /250 mg, 15 mg/375 mg, and 15 mg/500 mg (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Naproysn In an open-label, single-arm, eight-day, pharmacokinetic study of 28 adult rheumatoid arthritis patients (who required the chronic use of 7.5 to 15 mg of methotrexate given weekly).....

Prograf (tacrolimus) Capsules Prograf (tacrolimus) Injection (for intravenous infusion only) (click product name to read prescribing information)	PRECAUTIONS Drugs that May Alter Tacrolimus Concentrations Drugs That May Increase Tacrolimus Blood Concentrations Other Drugs Lansoprazole

Rescriptor (delavirdine mesylate) Oral Tablets (click product name to read prescribing information)	PRECAUTIONS Immune Reconstitution Syndrome Drug Interactions Table 7: Established and Other Potentially Significant Drug Interactions..... Antidepressant Trazadone Inhaled/Nasal Steroid Fluticasone

Revex (nalmefene hydrochloride injection) (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Timoptic (timolol maleate ophthalmic solution) Sterile Ophthalmic Solution (click product name to read prescribing information)	PRECAUTIONS Drug Interactions CYP2D6 Inhibitors SSRIs INSTRUCTIONS FOR USE

Timoptic-XE (timolol maleate ophthalmic gel forming solution) Sterile Ophthalmic Gel Forming Solution (click product name to read prescribing information)	PRECAUTIONS Drug Interactions CYP2D6 Inhibitors SSRIs INSTRUCTIONS FOR USE

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Brand (Generic) Name	Sections Modified
Avalide (irbesartan-hydrochlorothiazide) Tablets (click product name to read prescribing information)	ADVERSE REACTIONS Postmarketing Experience Hepatitis

Avapro (irbesartan) Tablets (click product name to read prescribing information)	ADVERSE REACTIONS Postmarketing Experience Hepatitis

Caduet (amlodipine besylate/atorvastatin calcium) Tablets click product name to read prescribing information)	ADVERSE REACTIONS Caduet The Amlodipine Component of Caduet .....In the CAMELOT and PREVENT studies, the adverse event profile was similar to that reported previously, with the most common adverse event being peripheral edema..... The Atorvastatin Component of Caduet Clinical Adverse Experiences Collaborative Atorvastatin Diabetes Study (CARDS) Urogenital System Postintroduction Reports with Atorvastatin Fatigue

Hepsera (adefovir dipivoxil) Tablets (click product name to read prescribing information)	ADVERSE REACTIONS Special Risk Patients

Namenda (memantine hydrochloride) Tablets and Oral Solution (click product name to read prescribing information)	ADVERSE REACTIONS Events Reported Subsequent to the Marketing of Namenda Worldwide

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