MedWatch - December 2003 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 2003

The detailed view includes drug products with safety labeling changes to the CONTRAINDICATIONS, BOXED WARNING, WARNINGS, PRECAUTIONS, or ADVERSE REACTIONS sections. 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
Delestrogen (estradiol valerate injection) (click product name to read prescribing information)	CONTRAINDICATIONS BOXED WARNINGS WARNINGS Cardiovascular Disorders Coronary Heart Disease and Stroke Venous Thromboembolism Malignant Neoplasms Breast Cancer PRECAUTIONS General Patient Information Laboratory Tests Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, and Impairment of Fertility Pregnancy Nursing Mothers ADVERSE REACTIONS PATIENT PACKAGE INSERT	Extensive labeling changes to incorporate data from the Women's Health Initiative. Please see the prescribing information for the new text. CONTRAINDICATIONS Estrogens should not be used in individuals with any of the following conditions ... (see prescribing information). BOXED WARNINGS Estrogens increase the risk of endometrial cancer. Estrogens with and without progestins should not be used for the prevention of cardiovascular disease. WARNINGS Women's Health Initiative (WHI) data added.

Declomycin (demeclocycline hydrochloride) Tablets Please contact ESP Pharma at 1-866-437-7742 for prescribing information.	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria. CONTRAINDICATIONS WARNINGS PRECAUTIONS General Information for Patients Laboratory Tests Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects Nonteratogenic Effects Nursing Mothers Pediatric Use ADVERSE REACTIONS Gastrointestinal Skin Renal Toxicity Hypersensitivity CNS Other	CONTRAINDICATIONS This drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines or any of the components of the product formulation. WARNINGS Demeclocycline hydrochloride, like other tetracycline-class antibiotic, can cause fetal harm when administered to a pregnant women. If any tetracycline is used during pregnancy, or if the patient becomes pregnant while taking these drugs, the patient should be apprised of the potential hazard to the fetus. Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients who are experiencing central nervous system symptoms including headache, dizziness, light-headedness, vertigo or blurred vision associated with demeclocycline therapy, should be cautioned about driving vehicles or using hazardous machinery while on demeclocycline therapy.

Kayexalate (sodium polystyrene sulfonate) Powder Please contact Sanofi-Synthelabo at 1-800-446-6267 for prescribing information.	CONTRAINDICATIONS PRECAUTIONS Drug Interactions Pediatric Use ADVERSE REACTIONS	Kayexalate is contraindicated in the following conditions: patients with hypokalemia, patients with a history of hypersensitivity to polystyrene sulfonate resins, obstructive bowel disease, neonates with reduced gut motility (postoperatively or drug induced) and oral administration in neonates.

Lidocaine HCl and 5% Dextrose Injection (click product name to read prescribing information)	CONTRAINDICATIONS	Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

Tazorac (tazarotene) Gel (click product name to read prescribing information)	CONTRAINDICATIONS PRECAUTIONS Carcinogenesis, Mutagenesis, Impairment of Fertility Geriatric Use ADVERSE REACTIONS Acne PATIENT PACKAGE INSERT Before You Use This Medicine How To Use This Product	As with other retinoids, when tazarotene was given orally to experimental animals, developmental delays were seen in rats, and teratogenic effects and post-implantation loss were observed in rats and rabbits at AUCde values that were 0.55 and 13.2 times, respectively, the AUC0-24h observed in psoriatic patients treated with 2 mg/cm2 of tazarotene gel 0.1% (extrapolated for topical application over 20% body surface area), and 0.68 and 16.4 times, respectively, the maximum AUC0-24h in acne patients treated with 2 mg/cm2 of tazarotene gel 0.1% over 15% (targeted) body surface area.

Theophylline in 5% Dextrose Injection (click product name to read prescribing information)	CONTRAINDICATIONS	Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

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Brand (Generic) Name

Sections Modified

Summary of Changes to Contraindications and Warnings

Viramune (nevirapine) Tablets and Oral Suspension

(click product name to read prescribing information)

BOXED WARNINGS

WARNINGS

Hepatic Events

BOXED WARNINGS

The greatest risk of severe rash or hepatic events associated with rash occurs in the first 6 weeks of therapy. Women and patients with higher CD4 counts are at increased risk of these hepatic events.

WARNINGS

Increased AST or ALT levels and/or co-infection with hepatitis B or C at the start of antiretroviral therapy are associated with a greater risk of hepatic adverse events. Women appear to have a three fold higher risk than men for rash-associated hepatic events (4.6% versus 1.5%). Patients with higher CD4 counts may also be at higher risk for rash-associated hepatic events with Viramune. In a retrospective review, women with CD4 counts >250 cells/mm3 had a 9 fold higher risk of rash associated hepatic adverse events compared to women with CD4 counts <250 cells/mm3 (8.4% versus 0.9%). An increased risk was observed in men with CD4 counts >400 cells/mm3 (4.5% versus 0.7% for men with CD4 counts <400 cells/mm).

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Carac (fluorauracil cream) (click product name to read prescribing information)	WARNINGS PATIENT PACKAGE INSERT Who Should Not Use Carac? What Are The Possible Side Effects Of Carac?	Rarely, unexpected, systemic toxicity (e.g., stomatitis, diarrhea, neutropenia, and neurotoxicity) associated with parenteral administration of fluorouracil has been attributed to deficiency of dihydropyrimidine dehydrogenase "DPD" activity.

Clozaril (clozapine) Tablets (click product name to read prescribing information)	WARNINGS Hyperglycemia and Diabetes Mellitus	Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics including Clozaril.

Lexapro (escitalopram oxalate) Tablets and Oral Solution (click product name to read prescribing information)	WARNINGS PRECAUTIONS General Abnormal Bleeding Activation of Mania/Hypomania Seizures Interference with Cognitive and Motor Performance Information for Patients Drug Interactions Drugs that Interfere With Hemostasis (NSAIDS, Aspirin, Warfarin, etc.) Metoprolol Pregnancy-Nonteratogenic Effects Geriatric Use ADVERSE REACTIONS Generalized Anxiety Disorder Incidence of Adverse Events in Placebo-Controlled Clinical Trials Generalized Anxiety Disorder Table 2 Male and Female Sexual Dysfunction with SSRIs Table 4 Other Event Observed During the Premarketing Evaluation of Lexapro Central and Peripheral Nevous System Disorders Gastrointestinal Disorders General Hemic and Lymphatic Disorders Metabolic and Nutritional Disorders Musculoskeletal System Disorders Psychiatric Disorders Reproductive Disorders/Female Skin and Appendages Disorders Special Senses Urinary System Disorders	Serotonin syndrome has been reported in two patients who were concomitantly receiving linezolid an antibiotic which is a reversible non-selective MAOI.

Prefest (estradiol and norgestimate) Tablets Please contact King Pharmaceuticals at 1-888-358-6436 for prescribing information.	WARNINGS Cardiovascular Disorders Coronary Heart Disease and Stroke Venous Thromboembolism Malignant Neoplasms Breast Cancer PRECAUTIONS General Addition of a Progestin when a Woman has not had a Hysterectomy ADVERSE REACTIONS Genitourinary System PATIENT PACKAGE INSERT	Extensive labeling changes to prescribing information and patient package insert. Women's Health Initiative (WHI) data added.

ProcalAmine (3% amino acid and 3% glycerin injection with electrolytes) (click product name to read prescribing information)	WARNINGS PRECAUTIONS General Laboratory Tests Drug Interactions Pediatric Use Geriatric Use	Care should be taken to avoid circulatory overload, particularly in patients with cardiac insufficiency. Blood sugar levels should be monitored frequently in diabetic patients.

Tabloid (thioguanine) Tablets (click product name to read prescribing information)	WARNINGS PRECAUTIONS Laboratory Tests	There are individuals with an inherited deficiency of the enzyme thiopurine methyltransferase (TPMT) who may be unusually sensitive to the myelosuppressive effects of thioguanine and prone to developing rapid bone marrow suppression following the initiation of treatment. Substantial dosage reductions may be required to avoid the development of life-threatening bone marrow suppression in these patients.

Topamax (topiramate) Tablets and Sprinkle Capsules (click product name to read prescribing information)	WARNINGS Metabolic Acidosis PRECAUTIONS Adjustment of Dose in Renal Failure Laboratory Tests Pediatric Use Geriatric Use ADVERSE REACTIONS Incidence in Study 119 - Add-On Therapy- Adults with Partial Onset Seizures Table 5	Hyperchloremic, non-anion gap, metabolic acidosis (i.e. decreased serum bicarbonate below the normal reference range in the absence of chronic respiratory alkalosis) is associated with topiramate treatment. This metabolic acidosis is caused by renal bicarbonate loss due to the inhibitory effect of topiramate on carbonic anhydrase. Such electrolyte imbalance has been observed with the use of topiramate in placebo controlled clinical trials and in the post-marketing period. Generally, topiramate induced metabolic acidosis occurs early in treatment although cases can occur at any time during treatment.

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Brand (Generic) Name	Sections Modified
Amoxil (amoxicillin capsules, tablets, chewable tablets and powder for oral suspension) (click product name to read prescribing information)	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria. PRECAUTIONS General Information for Patients

Azmacort (triamcinolone acetonide) Inhalation Aerosol (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Bethine (terbutaline sulfate) Injection and Tablets Please contact aaiPharma at 1-800-575-4224 for prescribing information.	PRECAUTIONS Geriatric Use

Duricef (cefadroxil monohydrate) Capsules, Tablets and Oral Suspension Please contact Warner Chilcott Laboratories at 1-800-521-8813 for prescribing information.	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria. PRECAUTIONS General Information for Patients

Eryc (erythromycin delayed-release capsules) Please contact Warner Chilcott Laboratories at 1-800-521-8813 for prescribing information.	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria. PRECAUTIONS General Information for Patients

Florone (diflorasone diacetate cream) (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Fragmin (dalteparin sodium injection) (click product name to read prescribing information)	PRECAUTIONS Geriatric Use ADVERSE REACTIONS Medical Patients with Severely Restricted Mobility During Acute Illness Table 10 Other Ongoing Safety Surveillance

Gleevec (imatinib mesylate) Tablets (click product name to read prescribing information)	PRECAUTIONS General Dermatologic Toxicities ADVERSE REACTIONS Additional Data from Multiple Clinical Trials

Invirase (saquinavir mesylate) Capsules (click product name to read prescribing information)	PRECAUTIONS Table 5 Ergot Derivatives Table 6 HIV Fusion Inhibitor Enfuvirtide Antimycobacterial Rifampin PATIENT PACKAGE INSERT What Are The Side Effects of Invirase? Are There Other Medications That I Should Not Take With Invirase/Norvir (ritonavir)? Antiarrhythmics

Kaletra (lopinavir/ritonavir) Capsules and Oral Solution (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Table 9

Lupron (leuprolide acetate) injection (click product name to read prescribing information)	PRECAUTIONS Pediatric Use Geriatric Use

Malarone (atovaquone and proguanil hydrochloride) Tablets and Pediatric Tablets (click product name to read prescribing information)	PRECAUTIONS Pediatric Use: Treatment of Malaria ADVERSE REACTIONS Oral Ulceration Vivid Dreams Blurred Vision

Myleran (busulfan) Tablets (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Nasacort AQ (triamcinolone acetonide) Nasal Spray (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Penlac Nail Lacquer (ciclopirox) Topical Solution (click product name to read prescribing information)	PRECAUTIONS Pediatric Use

Protonix (pantoprazole) Delayed-Release Tablets (click product name to read prescribing information)	PRECAUTIONS General ADVERSE REACTIONS Postmarketing Reports

0.9% Sodium Chloride Injection Please contact Abbott Laboratories at 1-800-633-9110 for prescribing information.	PRECAUTIONS Pediatric Use The safety and effectiveness in the pediatric population are based on the similarity of the clinical conditions of the pediatric and adult populations. However, in neonates or very small infants the volume of fluid may affect fluid and electrolyte balance.

Vfend (voriconazole) I.V., Tablets, and Oral Suspension (click product name to read prescribing information)	PRECAUTIONS Information for Patients

Visipaque (iodixonal) Injection (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Xenical (orlistat) Capsules (click product name to read prescribing information)	PRECAUTIONS Pediatric Use ADVERSE REACTIONS Pediatric Patients

Zithromax (azithromycin) Tablets and Oral Suspension (click product name to read prescribing information)	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria. PRECAUTIONS General Information for Patients

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Brand (Generic) Name	Sections Modified
Nasonex (mometasone furoate monohydrate) Nasal Spray (click product name to read prescribing information)	ADVERSE REACTIONS Disturbances of Taste and Smell

Singulair (montelukast sodium) Tablets, Chewable Tablets, and Oral Granules (click product name to read prescribing information)	ADVERSE REACTIONS Postmarketing Experience Very Rarely Cholestatic Hepatitis PATIENT PACKAGE INSERT What Are The Possible Side Effects of Singulair?

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