MedWatch - April 2004 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 2004

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
Cetrotide (cetrorelix acetate for injection) (click product name to read prescribing information)	CONTRAINDICATIONS PRECAUTIONS General ADVERSE REACTIONS PATIENT PACKAGE INSERT	Cetrotide is contraindicated in severe renal impairment.

Dopram Injection (doxapram hydrochloride injection, USP) (click product name to read prescribing information)	CONTRAINDICATIONS	Doxapram is contraindicated in patients with known hypersensitivity to the drug or any of the injection components. Doxapram is contraindicated in patients with mechanical disorders of ventilation such as mechanial obstruction, muscle paresis (including neuromuscular blocade), flail chest, pneumothorax, acute bronchial asthma, pulmonary fibrosis or other conditions resulting in restriction of chest wall, muscles of respiration or alveolar expansion.

Vfend (voriconazole) Injection, Oral Suspension, and Tablets (click product name to read prescribing information)	CONTRAINDICATIONS PRECAUTIONS Drug Interactions Table 8 Table 9	Coadministration of Vfend with ritonavir (400 mg Q12h) is contraindicated because ritonavir (400 mg Q12h) significantly decreases plasma voriconazole concentrations in healthy subjects. The effect of ritonavir (100 mg Q12h as used to inhibit CYP3A and increase concentrations of other antiretroviral drugs) on voriconazole concentrations has not been studied. Coadministration of Vfend with efavirenz is contraindicated because efavirenz significantly decreases voriconazole plasma concentrations while Vfend also significantly increases efavirenz plasma concentrations.

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Brand (Generic) Name

Sections Modified

Summary of Changes to Contraindications and Warnings

Premarin Intravenous (conjugated estrogens, USP for injection)

(click product name to read prescribing information)

BOXED WARNING

Estrogens Increase the Risk of Endometrial Cancer

WARNINGS

Malignant Neoplasms
- Breast Cancer

PRECAUTIONS

Ovarian Cancer
Drug/Laboratory Tests Interactions
Pregnancy
Nursing Mothers
Pediatric Use

ADVERSE REACTIONS

Gastrointestinal
- Enlargement of hepatic hemangiomas
Skin
- Pruritis
Central Nervous System
- Dementia

PATIENT PACKAGE INSERT

Extensive revisions to the prescribing information. Please see prescribing information for new text.

BOXED WARNING

There is no evidence that the use of "natural" estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen doses.

WARNINGS

These observational studies have not found significant variation in the risk of breast cancer among different estrogens or among different estrogen/progestin combinations, doses, or routes of administration.

The observational Million Women Study in Europe reported an increased risk of mortality due to breast cancer among current users of estrogens alone or estrogens plus progestins compared to never users, while the estrogen plus progestin sub-study of WHI showed no effect on breast cancer mortality with a mean follow-up of 5.6 years.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Abilify (aripiprazole) 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.

Celexa (citalopram hydrobromide) Tablets and Oral Solution (click product name to read prescribing information)	WARNINGS PRECAUTIONS General Discontinuation of Treatment with Celexa Abnormal Bleeding Information for Patients Drugs that Interfere with Hemostasis (NSAIDs, Aspirin, Warfarin, etc.) Pregnancy-Nonteratogenic Effects	Serotonin syndrome has been reported in two patients who were concomitantly receiving linezolid an antibiotic which is a reversible non-selective MAOI.

Hectorol (doxercalciferol) Capsules (click product name to read prescribing information)	WARNINGS PRECAUTIONS General Pre-dialysis Information for the Patient Laboratory Tests ADVERSE REACTIONS Dialysis Pre-dialysis	Since doxercalciferol is a precursor for 1α,25-(OH)2D2, a potent metabolite of vitamin D2, pharmacologic doses of vitamin D and its derivatives should be withheld during Hectorol treatment to avoid possible additive effects and hypercalcemia. Uncontrolled serum phosphorus exacerbates secondary hyperparathyroidism and can lessen the effectiveness of Hectorol in reducing blood PTH levels. If hypercalcemia occurs after initiating Hectorol therapy, the dose of Hectorol and/or calcium containing-phosphate binders should be decreased. If hyperphosphatemia occurs after initiating Hectorol, the dose of Hectorol should be decreased and/or the dose of phosphate binders increased.

HepatAmine (8% amino acid injection) (click product name to read prescribing information)	WARNINGS PRECAUTIONS General Laboratory Tests Drug Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use	This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Frequent clinical evaluation and laboratory determinations are necessary for proper monitoring of parenteral nutrition.

Intralipid 10% Intravenous Fat Emulsion Intralipid 20% Intravenous Fat Emulsion Intralipid 30% Intravenous Fat Emulsion Please contact Baxter Healthcare at 1-800-422-9837 for prescribing information.	WARNINGS PRECAUTIONS	This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 µg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

Lexapro (escitalopram oxalate) Tablets and Oral Solution (click product name to read prescribing information)	WARNINGS PRECAUTIONS General Discontinuation of Treatment with Lexapro Abnormal Bleeding Information for Patients Drugs that Interfere with Hemostasis (NSAIDs, Aspirin, Warfarin, etc.) Pregnancy-Nonteratogenic Effects	Serotonin syndrome has been reported in two patients who were concomitantly receiving linezolid an antibiotic which is a reversible non-selective MAOI.

Premarin (conjugated estrogens tablets, USP) (click product name to read prescribing information)	WARNINGS Malignant Neoplasms Breast Cancer Dementia PRECAUTIONS Ovarian Cancer Drug/Laboratory Test Interactions Geriatric Use PATIENT PACKAGE INSERT	These observational studies have not found significant variation in the risk of breast cancer among different estrogens or among different estrogen/progestin combinations, doses, or routes of administration. The observational Million Women Study in Europe reported an increased risk of mortality due to breast cancer among current users of estrogens alone or estrogens plus progestins compared to never users, while the estrogen plus progestin sub-study of WHI showed no effect on breast cancer mortality with a mean follow-up of 5.6 years. The results of the estrogen alone sub-study of the Women's Health Initiative Memory Study have not been reported. It is unknown whether these findings apply to estrogen alone therapy.

Premarin (conjugated estrogens) Vaginal Cream (click product name to read prescribing information)	WARNINGS Malignant Neoplasms Breast Cancer Dementia PRECAUTIONS Ovarian Cancer Drug/Laboratory Test Interactions Geriatric Use ADVERSE REACTIONS PATIENT PACKAGE INSERT	These observational studies have not found significant variation in the risk of breast cancer among different estrogens or among different estrogen/progestin combinations, doses, or routes of administration. The observational Million Women Study in Europe reported an increased risk of mortality due to breast cancer among current users of estrogens alone or estrogens plus progestins compared to never users, while the estrogen plus progestin sub-study of WHI showed no effect on breast cancer mortality with a mean follow-up of 5.6 years. The results of the estrogen-alone sub-study of the Women's Health Initiative Memory Study have not been reported.

Prempro/Premphase (conjugated estrogens/medroxyprogesterone acetate) Tablets (click product name to read prescribing information)	WARNINGS Malignant Neoplams Breast Cancer Dementia PRECAUTIONS Ovarian Cancer Drug/Laboratory Test Interactions ADVERSE REACTIONS Genitourinary System Dysmenorrhea PATIENT PACKAGE INSERT	These observational studies have not found significant variation in the risk of breast cancer among different estrogens or among different estrogen/progestin combinations, doses, or routes of administration. The observational Million Women Study in Europe reported an increased risk of mortality due to breast cancer among current users of estrogens alone or estrogens plus progestins compared to never users, while the estrogen plus progestin sub-study of WHI showed no effect on breast cancer mortality with a mean follow-up of 5.6 years. The results of the estrogen alone sub-study of the Women's Health Initiative Memory Study have not been reported.

Reglan (metoclopromide injection, USP) (click product name to read prescribing information)	WARNINGS Neuroleptic Malignant Syndrome (NMS) PRECAUTIONS General Pediatric Use Geriatric Use Other Special Populations ADVERSE REACTIONS Neuroleptic Malignant Syndrome	There have been rare reports of an uncommon but potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) associated with metoclopramide. Clinical manifestations of NMS include hyperthermia, muscle rigidity, altered consciousness, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac arrhythmias).

Ultracet (tramadol hydrochloride/acetaminophen tablets) (click product name to read prescribing information)	WARNINGS Withdrawal	Withdrawal symptoms may occur if Ultracet is discontinued abruptly. These symptoms may include: anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely hallucinations. Other symptoms that have been seen less frequently with Ultracet discontinuation include: panic attacks, severe anxiety, and paresthesias. Clinical experience suggests that withdrawal symptoms may be avoided by tapering Ultracet at the time of discontinuation.

Ultram (tramadol hydrochloride tablets) (click product name to read prescribing information)	WARNINGS Withdrawal	Withdrawal symptoms may occur if Ultram is discontinued abruptly. These symptoms may include: anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely hallucinations. Other symptoms that have been seen less frequently with Ultram discontinuation include: panic attacks, severe anxiety, and paresthesias. Clinical experience suggests that withdrawal symptoms may be avoided by tapering Ultram at the time of discontinuation.

Zelnorm (tegaserod maleate) Tablets (click product name to read prescribing information)	WARNINGS PRECAUTIONS Ischemic colitis Information for Patients ADVERSE REACTIONS Zelnorm-Induced Diarrhea Postmarketing Experience PATIENT PACKAGE INSERT	Serious consequences of diarrhea, including hypovolemia, hypotension, and syncope have been reported in the clinical studies and during marketed use of Zelnorm. In some cases, these complications have required hospitalization for rehydration. Zelnorm should be discontinued immediately in patients who develop hypotension or syncope. Zelnorm should not be initiated in patients who are currently experiencing or frequently experience diarrhea.

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Brand (Generic) Name	Sections Modified
Acetadote (acetylcysteine) Injection (click product name to read prescribing information)	PRECAUTIONS Initial paragraph Pediatric Patients

Advair Diskus 100/50 (fluticasone propionate 100 and salmeterol 50 mcg inhalation powder) (click product name to read prescribing information)	PRECAUTIONS Pediatric Use

Bextra (valdecoxib sodium) Tablets (click product name to read prescribing information)	PRECAUTIONS Drug Interactions General Anticonvulsants (Phenytoin) Dextromethorphan Glyburide Omeprazole Oral Contraceptives Diazepam

Corlopam (fenoldopam mesylate injection) (click product name to read prescribing information)	PRECAUTIONS Tachycardia Hypotension Intracranial Pressure Drug Interactions with Beta Blockers Drug Interactions General Pediatric Use Geriatric Use ADVERSE REACTIONS Pediatric Patients

Detrol LA (tolterodine tartrate) Extended Release Capsules (click product name to read prescribing information)	PRECAUTIONS Pediatric Use

Effexor (venlafaxine hydrochloride) Immediate Release Tablets (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Drugs Metabolized by Cytochrome P450 Isoenzymes CYP2C9

Effexor XR (venlafaxine hydrochloride) Extended Release Capsules (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Drugs Metabolized by Cytochrome P450 Isoenzymes CYP2C9

Heparin Sodium in 5% Dextrose Injection Please contact B. Braun Medical Inc. at 1-800-854-6851 for prescribing information.	PRECAUTIONS Geriatric Use A higher incidence of bleeding has been reported in patients over 60 years of age, especially women. Clinical studies indicate that lower doses of heparin may be indicated in these patients.

Heparin Sodium in 0.9% Sodium Chloride Injection Please contact B. Braun Medical Inc. at 1-800-854-6851 for prescribing information.	PRECAUTIONS Geriatric Use A higher incidence of bleeding has been reported in patients over 60 years of age, especially women. Clinical studies indicate that lower doses of heparin may be indicated in these patients.

Lac-Hydrin (ammonium lactate) Lotion (click product name to read prescribing information)	PRECAUTIONS Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects Geriatric Use

Micardis HCT (telmisartan/hydrochlorothiazide) Tablets (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Telmisartan Other Drugs Simvastatin ADVERSE REACTIONS Telmisartan

Neosporin (neomycin and polymyxin B sulfates, bacitracin zinc ophthalmic ointment, USP) (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Oxandrin (oxandrolone, USP) Tablets (click product name to read prescribing information)	PRECAUTIONS Initial Paragraph Information for Patients Drug Interactions Warfarin

Paxil (paroxetine hydrochloride) Controlled Release Tablets (click product name to read prescribing information)	PRECAUTIONS General Discontinuation of Treatment with Paxil CR Abnormal Bleeding Information for Patients Drugs that Interfere with Hemostasis (NSAIDs, Aspirin, Warfarin, etc.) Drug Interactions Drugs that Interfere with Hemostasis (NSAIDs, Aspirin, Warfarin, etc.) Pregnancy Nonteratogenic Effects

Paxil (paroxetine hydrochloride) Tablets and Oral Suspension (click product name to read prescribing information)	PRECAUTIONS General Discontinuation of Treatment with Paxil Abnormal Bleeding Information for Patients Drugs that Interfere with Hemostasis (NSAIDs, Aspirin, Warfarin, etc.) Drug Interactions Drugs that Interfere with Hemostasis (NSAIDs, Aspirin, Warfarin, etc.) Pregnancy Nonteratogenic Effects

Pipracil (piperacillin sodium) for Intravenous and Intramuscular Use (click product name to read prescribing information)	SYSTEMIC ANTIBACTERIAL DRUG PRODUCT STATEMENT to reduce the development of drug-resistant bacteria. PRECAUTIONS General Information for Patients

Sandostatin LAR Depot (octreotide acetate injection) (click product name to read prescribing information)	PRECAUTIONS Glucose Metabolism Drug Interactions PATIENT PACKAGE INSERT

0.45% Sodium Chloride Irrigation Solution 0.9% Sodium Chloride Irrigation Solution Please contact Abbott Laboratories at 1-800-633-9110 for prescribing information.	PRECAUTIONS Geriatric Use

Taxotere (docetaxel) for Injection Concentrate (click product name to read prescribing information)	PRECAUTIONS Geriatric Use ADVERSE REACTIONS Combination Therapy with Taxotere in Patients with Prostate Cancer

Topicort (desoximetasone) Emollient Cream Topicort (desoximetasone) LP Emollient Cream (click product name to read prescribing information)	PRECAUTIONS Carcinogenesis, Mutagenesis, and Impairment of Fertility

Topicort (desoximetasone) Gel (click product name to read prescribing information)	PRECAUTIONS Carcinogenesis, Mutagenesis, and Impairment of Fertility

Topicort (desoximetasone) Ointment (click product name to read prescribing information)	PRECAUTIONS Carcinogenesis, Mutagenesis, and Impairment of Fertility

Trusopt (dorzolamide hydrochloride ophthalmic solution) (click product name to read prescribing information)	PRECAUTIONS Pediatric Use ADVERSE REACTIONS Controlled Clinical Trials

Xanax (alprazolam) Tablets Please contact Pfizer, Inc. at 1-800-879-3477 for prescribing information.	PRECAUTIONS Suicide Laboratory Tests Drug Interactions ADVERSE REACTIONS Treatment-Emergent Adverse Events Reported in Placebo-Controlled Trials of Anxiety Disorders Adverse Events Reported as Reasons for Discontinuation in Treatment of Panic Disorder in Placebo-Controlled Trials

Xanax XR (alprazolam) Extended-Release Tablets Please contact Pfizer, Inc. at 1-800-879-3477 for prescribing information.	PRECAUTIONS Drug Interactions

Zemplar (paricalcitol) Injection (click product name to read prescribing information)	PRECAUTIONS Pediatric Use

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Brand (Generic) Name	Sections Modified
Cardizem LA (diltiazem hydrochloride) Extended Release Tablets (click product name to read prescribing information)	ADVERSE REACTIONS Initial Paragraph

Fosamax (alendronate sodium) Oral Solution (click product name to read prescribing information)	ADVERSE REACTIONS Men

Invanz (ertapenem sodium) (click product name to read prescribing information)	ADVERSE REACTIONS Post-Marketing Experience Immune System Anaphylaxis including Anaphylactoid Reactions Nervous System & Psychiatric Hallucinations

Mylotarg (gemtuzumab ozogamicin for Injection) (click product name to read prescribing information)	ADVERSE REACTIONS Acute Infusion-Related Events Table 3 Antibody Formation Neutropenia Anemia, Thrombocytopenia Table 4 Infection Bleeding Transfusions Table 5 Mucositis Hepatotoxicity Table 6 Skin Early Mortality in Clinical Studies Retreatment Events Treatment-Emergent Adverse Events (TEAE) Table 7 Table 8 Table 9

Nexium (esomeprazole magnesium) Delayed-Release Capsules (click product name to read prescribing information)	ADVERSE REACTIONS Postmarketing Reports

Proscar (finasteride) Tablets (click product name to read prescribing information)	ADVERSE REACTIONS Medical Therapy of Prostatic Symptoms (MTOPS) PATIENT PACKAGE INSERT

Ziagen (abacavir sulfate) Tablets and Oral Solution (click product name to read prescribing information)	ADVERSE REACTIONS Therapy-Naive Adults Table 3 Laboratory Abnormalities Table 6 Other Adverse Events

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