MedWatch - December 2005 Safety-Related Drug Labeling Changes

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Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) -- December 2005

The detailed view includes drug products with safety labeling changes to the CONTRAINDICATIONS, BOXED WARNING, 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

Climara Pro (estradiol/levonorgestrel) Transdermal System)

(click product name to read prescribing information)

CONTRAINDICATIONS

BOXED WARNING

WARNINGS

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

PRECAUTIONS

Geriatric Use

ADVERSE REACTIONS

Miscellaneous
- Urticaria
- Angioedema
- Anaphylactoid/Anaphylactic Reactions

PATIENT PACKAGE INSERT

CONTRAINDICATIONS

Known hypersensitivity to the ingredients of Climara Pro.

BOXED WARNING

The WHI study reported increased risks of stroke and deep vein thrombosis in postmenopausal women (50 to 70 years of age) during 6.8 years of treatment with oral conjugated estrogens (CE0.625 mg) relative to placebo.

The Women's Health Initiative Memory Study (WHIMS), a substudy of WHI, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with CE 0.625 mg combined with MPA 2.5 mg and during 5.2 years of treatment with CE 0.625 mg alone, relative to placebo.....

WARNINGS

Cardiovascular Disorders

Coronary Heart Disease and Stroke

In the WHI estrogen-alone substudy, an increased risk of stroke was observed in women receiving CE compared to placebo (44 versus 32 per 10,000 women-years). The increase in risk was observed in year 1 and persisted.

.....Participation in an open label extension of the original HERS trial (HERS II) was agreed to by 2,321 women.....

Venous Thromboembolism (VTE)

In the WHI estrogen-alone substudy, an increased risk of deep vein thrombosis was observed in women receiving CE compared to placebo (21 versus 15 per 10,000 women-years). The increase in deep vein thrombosis risk was observed during the first year.

Malignant Neoplasms

Endometrial Cancer

.....The reported endometrial cancer risk among unopposed estrogen users is about 2 to 12 times greater than in nonusers, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with use of estrogens for less than one year. The greatest risk appears associated with prolonged use, with increased risks of 15- to 24-fold for 5 to 10 years or more.....

Dementia

.....In the estrogen-alone substudy, after an average follow-up of 5.2 years, 28 women in the estrogen-alone group and 19 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for estrogen alone versus placebo was 1.49 (95 percent CI, 0.83-2.66). The absolute risk of probable dementia for estrogen alone versus placebo was 37 versus 25 cases per 10,000 women-years.....

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Advil Cold & Sinus Liquigels (200 mg ibuprofen/ 30 mg pseudoephedrine HCl capsules) 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...... ASK A DOCTOR OR PHARMACIST BEFORE USE IF YOU ARE..... WHEN USING THIS PRODUCT..... STOP USE AND ASK A DOCTOR IF..... IF PREGNANT OR BREAST-FEEDING.....	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.

Children's Advil (100 mg/5 mL ibuprofen) 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 IF.....	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.

Children's Motrin (100 mg/5 mL ibuprofen) 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 IF.....	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.

Children's Motrin Cold (100 mg/5 mL ibuprofen and 15 mg/5 mL pseudoephedrine HCl) 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 IF.....	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.

Emla (lidocaine 2.5% and prilocaine 2.5%) Cream (click product name to read prescribing information)	WARNINGS PRECAUTIONS General Emla cream should not be applied to open wounds. Care should be taken not to allow Emla Cream to come in contact with the eye..... Information for Patients Emla Cream should not be applied near the eyes..... Drug Interactions Specific interaction studies with lidocaine/prilocaine and class III anti-arrhythmic drugs..... Should Emla cream be used concomitantly with other products containing lidocaine..... Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Labor and Delivery Pediatric Use	Patients treated with class III anti-arrhythmic drugs (eg, amiodarone, bretylium, sotalol, defetilide) should be under close surveillance and ECG monitoring considered, because cardiac effects may be additive. .....In these same studies, animals exposed to Emla Cream only in the external auditory canal, showed no abnormality. Emla cream should not be used in any clinical situation when its penetration or migration beyond the tympanic membrane into the middle ear is possible.

Ibuprofen Capsules 200 mg 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...... ASK A DOCTOR OR PHARMACIST BEFORE USE IF YOU ARE..... WHEN USING THIS PRODUCT..... STOP USE AND ASK A DOCTOR IF..... IF PREGNANT OR BREAST-FEEDING.....	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.

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Brand (Generic) Name	Sections Modified
Avodart (dutasteride) Soft Gelatin Capsules (click product name to read prescribing information)	PRECAUTIONS Drug/Laboratory Test Interactions Reproductive Function

Clozaril (clozapine) Tablets (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Pharmacokinetic-Related Interactions Ciprofloxacin

Emtriva (emtricitabine) Capsules and Oral Solution (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Coadministration of Emtricitabine/Zidovudine Immune Reconstitution Syndrome

Enlon-Plus (edrophonium chloride, USP and atropine sulfate, USP) Injection (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Femara (letrozole tablets) (click product name to read prescribing information)	PRECAUTIONS Laboratory Tests In the adjuvant setting, total cholesterol in the Femara arm..... Bone Effects Geriatric Use ADVERSE REACTIONS Initial Paragraph Adjuvant Treatment of Early Breast Cancer in Postmenopausal women Table 13: Patients with Adverse Events (CTC 1-4 grades Irrespective to Relationship of Study Drug) in the Adjuvant Study BIG 1-98 Extended Adjuvant Treatment of Early Breast Cancer in Postmenopausal Women who have Received 5 Years of Adjuvant Tamoxifen Therapy Table 14: Percentage of Patients with Adverse Events First-Line Breast Cancer Table 15: Percentage (%) of Patients with Adverse Events

Fosamax (alendronate sodium) Tablets and Oral Solution (click product name to read prescribing information)	PRECAUTIONS Pediatric Use ADVERSE REACTIONS Osteogenesis Imperfecta

Meridia (sibutramine hydrochloride monohydrate) Capsules (click product name to read prescribing information)	PRECAUTIONS Pediatric Use

Prozac (fluoxetine hydrochloride) (click product name to read prescribing information)	PRECAUTIONS Carcinogenesis, Mutagenesis, Impairment of Fertility Initial Paragraph Impairment of Fertility Adult Rats Pediatric Use

Rowasa (mesalamine) Rectal Suspension Enema (click product name to read prescribing information)	PRECAUTIONS Worsening of colitis or symptoms of inflammatory bowel disease, including melena..... Carcinogenesis, Mutagenesis, Impairment of Fertility The oligospermia and infertility in men associated with sulfasalazine have..... ADVERSE REACTIONS Pancytopenia Neutropenia Oligospermia Infertility in Men

Sarafem (fluoxetine hydrochloride) (click product name to read prescribing information)	PRECAUTIONS Carcinogenesis, Mutagenesis, Impairment of Fertility Initial Paragraph Impairment of Fertility Adult Rats Pediatric Use

Tamiflu (oseltamivir phosphate) Capsules and Oral Suspension (click product name to read prescribing information)	PRECAUTIONS General Safety and efficacy of repeated treatment or prophylaxis courses have not been studied. Serious Skin/Hypersensitivity Reaction ADVERSE REACTIONS Prophylaxis Studies in Adult Patients Table 3: Most Frequent Adverse Events in Studies in Naturally Acquired Influenza in Patients 13 Years of Age and Older Prophylaxis in Pediatric Patients Table 4: Most Frequent Adverse Events Occurring in Children Aged 1 to 12 Years in Studies in Naturally Acquired Influenza PATIENT PACKAGE INSERT

Velcade (bortezomib) for Injection (click product name to read prescribing information)	PRECAUTIONS Cardiac Disorders Hepatic Events ADVERSE REACTIONS Hepatobiliary Disorders Liver Failure

Zovirax (acyclovir) Capsules, Tablets and Suspension (click product name to read prescribing information)	PRECAUTIONS Initial Paragraph Maintaining Adequate Hydration

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Brand (Generic) Name	Sections Modified
Evoxac (cevimeline hydrochloride) Capsules Please contact Daiichi Pharmaceutical Co., Ltd at 1-877-324-4222 for prescribing information.	ADVERSE REACTIONS Initial Paragraph Cevimeline was administered to 1777 patients during clinical trials worldwide, including Sjogren's patients and patients with other conditions. In placebo-controlled Sjogren's studies in the U.S. 320 patients received cevimeline doses ranging from 15 mg tid to 60 mg tid, of whom 93% were women and 7% were men. Demographic distribution was 90% Caucasian, 5% Hispanic, 3% Black and 2% of other origin. In these studies 14.6 % of patient discontinued treatment with cevimeline due to adverse events. Post-marketing Adverse Events The following adverse reaction has been identified during post approval use of Evoxac. Because post marketing adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Liver and Biliary Systems Disorders Cholecystitis

Flovent HFA (fluticasone propionate) Inhalation Aerosol (click product name to read prescribing information)	ADVERSE REACTIONS Psychiatry Anxiety Behavioral changes, including hyperactivity and irritability, have been reported very rarely and primarily in children

Prograf (tacrolimus capsules) Prograf (tacrolimus injection) [for intravenous infusion only] (click product name to read prescribing information)	ADVERSE REACTIONS Less Frequently Reported Adverse Events Nervous System Gastrointestinal Cardiovascular Urogenital Hemic/Lymphatic Miscellaneous Respiratory Post-marketing Post-marketing Adverse Events Other Events Include.....

Spectracef (cefditoren pivoxil) Tablets (click product name to read prescribing information)	ADVERSE REACTIONS Post-marketing Experience Erythema Multiforme Stevens-Johnson Syndrome Toxic Epidermal Necrolysis

Zofran (ondansetron hydrochloride) Injection Zofran (ondansetron hydrochloride) Injection Premixed (click product name to read prescribing information)	ADVERSE REACTIONS Observed During Clinical Practice Eye Disorders.....

Zofran (ondansetron hydrochloride) Tablets Zofran ODT (ondansetron) Orally Disintegrating Tablets Zofran (ondansetron hydrochloride) Oral Solution (click product name to read prescribing information)	ADVERSE REACTIONS Observed During Clinical Practice Special Senses: Eye Disorders.....

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