MedWatch - August 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) -- August 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
Saizen (somatropin [rDNA origin] for injection) (click product name to read prescribing information)	CONTRAINDICATIONS WARNINGS PRECAUTIONS General Intracranial hypertension (IH) Drug Interactions Cytochrome P450 3A4 ADVERSE REACTIONS Growth Hormone Deficient Adult Patients Table 2	CONTRAINDICATIONS Saizen is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Saizen is contraindicated in patients with proliferative or preproliferative diabetic retinopathy. Growth hormone is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment. Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, Saizen is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. WARNINGS There have been reports of fatalities after initiating therapy with growth hormone in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. Patients with Prader-Willi syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with growth hormone. If, during treatment with growth hormone, patients show signs of upper airway obstruction (including onset of or increased snoring) and/or new onset sleep apnea, treatment should be interrupted. All patients with Prader-Willi syndrome treated with growth hormone should also have effective weight control and be monitored for signs of respiratory infection, which should be diagnosed as early as possible and treated aggressively. Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, Saizen is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.

Sustiva (efavirenz) Capsules and Tablets (click product name to read prescribing information)	CONTRAINDICATIONS WARNINGS Psychiatric Symptoms Nervous System Symptoms PRECAUTIONS Immune Reconstitution Syndrome Table 5^a: Drugs That Should Not Be Coadministered with Sustiva Voriconazole Established Drug Interaction Table Atazanavir ADVERSE REACTIONS Table 9 Triglyceride Data Liver Enzymes Lipids PATIENT PACKAGE INSERT	CONTRAINDICATIONS Sustiva should not be administered concurrently with voriconazole because Sustiva significantly decreases voriconazole plasma concentrations. WARNINGS Psychiatric Symptoms Serious psychiatric adverse experiences have been reported in patients treated with Sustiva..... Other factors associated with an increase in the occurrence of these psychiatric symptoms were history of injection drug use, psychiatric history, and receipt of psychiatric medication at study entry.... (Please see details in prescribing information.) Nervous System Analysis of long-term data from Study 006 (median follow-up 180 weeks, 102 weeks, and 76 weeks for patients treated with Sustiva + zidovudine + lamivudine, Sustiva + indinavir, and indinavir + zidovudine + lamivudine, respectively) showed that, beyond 24 weeks of therapy, the incidences of new-onset nervous system symptoms among Sustiva-treated patients were generally similar to those in the indinavir-containing control arm.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Adderall XR (mixed salts of a single-entity amphetamine product) (click product name to read prescribing information)	BOXED WARNING WARNINGS Sudden Death and Pre-existing Structural Cardiac Abnormalities PRECAUTIONS Carcinogenesis/Mutagenesis and Impairment of Fertility Pregnancy ADVERSE REACTIONS Initial Paragraph Adverse events associated with discontinuation of treatment Adverse events occurring in a controlled trial Table 1 Table 2 Cardiovascular Sudden Death Myocardial Infarction Central Nervous System Depression Seizures Stroke	BOXED WARNING Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events. WARNINGS Sudden death has been reported in association with amphetamine treatment at usual doses in children with structural cardiac abnormalities. Adderall XR generally should not be used in children or adults with structural cardiac abnormalities.

Hepsera (adefovir dipivoxil) Tablets (click product name to read prescribing information)	BOXED WARNING WARNINGS Exacerbations of Hepatitis after Discontinuation of Treatment ADVERSE REACTIONS Second Paragraph PATIENT PACKAGE INSERT	BOXED WARNING Severe acute exacerbations of hepatitis have been reported in patients who have discontinued anti-hepatitis B therapy (including Hepsera). Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, resumption of anti-hepatitis B therapy may be warranted. WARNINGS Severe acute exacerbation of hepatitis has been reported in patients who have discontinued anti-hepatitis B therapy, including therapy with Hepsera. Hepatic function should be monitored at repeated intervals with both clinical and laboratory follow-up for at least several months in patients who discontinue Hepsera. If appropriate, resumption of anti-hepatitis B therapy may be warranted.

Vivelle (estradiol transdermal system) (click product name to read prescribing information)	BOXED WARNING Cardiovascular and Other Risks Women's Health Initiative Memory Study (WHIMS) WARNINGS Dementia PRECAUTIONS Geriatric Use	BOXED WARNING 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 oral conjugated estrogens plus medroxyprogesterone acetate relative to placebo. It is unknown whether this finding applies to younger postmenopausal women or to women taking estrogen alone therapy. WARNINGS In the Women's Health Initiative Memory Study (WHIMS), 4,532 generally healthy postmenopausal women 65 years of age and older were studied, of whom 35% were 70 to 74 years of age and 18% were 75 or older. After an average follow-up of 4 years, 40 women being treated with CE/MPA (1.8%, n = 2,229) and 21 women in the placebo group (0.9%, n = 2,303) received diagnoses of probable dementia. The relative risk for CE/MPA versus placebo was 2.05 (95% confidence interval 1.21 - 3.48), and was similar for women with and without histories of menopausal hormone use before WHIMS. The absolute risk of probable dementia for CE/MPA versus placebo was 45 versus 22 cases per 10,000 women-years, and the absolute excess risk for CE/MPA was 23 cases per 10,000 women years. It is unknown whether these findings apply to younger postmenopausal women.

Vivelle-Dot (estradiol transdermal system) (click product name to read prescribing information)	BOXED WARNING Cardiovascular and Other Risks Women's Health Initiative Memory Study (WHIMS) WARNINGS Dementia PRECAUTIONS Geriatric Use	BOXED WARNING 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 oral conjugated estrogens plus medroxyprogesterone acetate relative to placebo. It is unknown whether this finding applies to younger postmenopausal women or to women taking estrogen alone therapy. WARNINGS In the Women's Health Initiative Memory Study (WHIMS), 4,532 generally healthy postmenopausal women 65 years of age and older were studied, of whom 35% were 70 to 74 years of age and 18% were 75 or older. After an average follow-up of 4 years, 40 women being treated with CE/MPA (1.8%, n = 2,229) and 21 women in the placebo group (0.9%, n = 2,303) received diagnoses of probable dementia. The relative risk for CE/MPA versus placebo was 2.05 (95% confidence interval 1.21 - 3.48), and was similar for women with and without histories of menopausal hormone use before WHIMS. The absolute risk of probable dementia for CE/MPA versus placebo was 45 versus 22 cases per 10,000 women-years, and the absolute excess risk for CE/MPA was 23 cases per 10,000 women years. It is unknown whether these findings apply to younger postmenopausal women.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Actos (pioglitazone HCl) Tablets (click product name to read prescribing information)	WARNINGS Cardiac Failure and Other Cardiac Effects In Type 2 Diabetes and Congestive Heart Failure (Systolic Dysfunction)	A 24-week post-marketing safety study was performed to compare Actos (n=262) to glyburide (n=256) in uncontrolled diabetic patients (mean HbA1C 8.8% at baseline) with NYHA Class II and III heart failure and ejection fraction less than 40% (mean EF 30% at baseline). Over the course of the study, overnight hospitalization for congestive heart failure was reported in 9.9% of patients on Actos compared to 4.7% of patients on glyburide with a treatment difference observed from 6 weeks. This adverse event associated with Actos was more marked in patients using insulin at baseline and in patients over 64 years of age. No difference in cardiovascular mortality between the treatment groups was observed. Actos should be initiated at the lowest approved dose if it is prescribed for patients with type 2 diabetes and systolic heart failure (NYHA Class II). If subsequent dose escalation is necessary, the dose should be increased gradually only after several months of treatment with careful monitoring for weight gain, edema, or signs and symptoms of CHF exacerbation.

Amicar (aminocaproic acid) Tablets, Injection and Syrup (click product name to read prescribing information)	WARNINGS PRECAUTIONS Pediatric Use	Amicar Injection contains benzyl alcohol as a preservative. The administration of medications containing benzyl alcohol as a preservative to premature neonates has been associated with fatal "Gasping Syndrome".

Geodon (ziprasidone HCl) Capsules Geodon (ziprasidone mesylate) for Injection (for IM Use Only) (click product name to read prescribing information)	WARNINGS Hyperglycemia and Diabetes Mellitus PRECAUTIONS Suicide ADVERSE REACTIONS Initial Paragraph Fifth Paragraph Adverse Findings Observed in Short-Term, Placebo-Controlled Trials with Oral Ziprasidone Adverse Events Associated with Discontinuation of Treatment in Short-Term, Placebo-Controlled Trials of Oral Ziprasidone Bipolar Mania Commonly Observed Adverse Events in Short-Term, Placebo-Controlled Trials Table 1 Table 2 Adverse Events Occurring at an Incidence of 2% or More Among Ziprasidone-Treated Patients in Short-Term, Oral, Placebo-Controlled Trials Table 3 Dose Dependency of Adverse Events in Short-Term, Fixed-Dose, Placebo-Controlled Trials Extrapyramidal Symptoms (EPS) Weight Gain ECG Changes Other Adverse Events Observed During the Premarketing Evaluation of Oral Ziprasidone Cardiovascular System Tachycardia Postural Hypotension Digestive System Anorexia Musculoskeletal System Myalgia Special Senses Fungal Dermatitis	Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. There have been few reports of hyperglycemia or diabetes in patients treated with Geodon. Although fewer patients have been treated with Geodon, it is not known if this more limited experience is the sole reason for the paucity of such reports. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of the suspect drug.

Junior Strength Advil (100 mg ibuprofen) Tablets (click product name to read prescribing information)	WARNINGS Stomach Bleeding Warning ASK A DOCTOR BEFORE USE IF THE CHILD HAS Ulcers Bleeding problems Stomach problems that last or come back, such as heartburn, upset stomach or pain High blood pressure, heart or kidney disease or is taking a diuretic ASK A DOCTOR OR PHARMACIST BEFORE USE IF THE CHILD IS Taking a prescription drug for anticoagulation (blood thinning)	Taking more than recommended may cause stomach bleeding.

Lotrel (amlodipine besylate and benazepril hydrochloride) Combination Capsules (click product name to read prescribing information)	WARNINGS Intestinal Angioedema	Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with and without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

Naropin (ropivacaine HCl) Injection (click product name to read prescribing information)	WARNINGS PRECAUTIONS Use in Brachial Plexus Block Use in Peripheral Nerve Block Drug Interactions Class III Antiarrhythmic Drugs	Prior to receiving major blocks the general condition of the patient should be optimized and the patient should have an IV line inserted. All necessary precautions should be taken to avoid intravascular injection. Patients treated with class III antiarrhythmic drugs (eg. amiodarone) should be under close surveillance and ECG monitoring considered, since cardiac effects may be additive.

Orudis KT (ketoprofen) Tablets (click product name to read prescribing information)	WARNINGS Stomach Bleeding Warning ASK A DOCTOR BEFORE USE IF YOU HAVE Stomach problems that last or come back, such as heartburn, upset stomach, or pain Ulcers Bleeding problems High blood pressure, heart or kidney disease, are taking a diuretic, or are over 65 years of age ASK A DOCTOR OR PHARMACIST BEFORE USE IF YOU ARE Under a doctor's care for any serious medical condition Taking a prescription drug for anticoagulation (blood thinning) Taking any other drug When using this product take with food or milk if stomach upset occurs STOP USE AND ASK A DOCTOR IF Stomach pain or upset gets worse or lasts Redness or swelling is present in the painful area Any new symptoms appear	Taking more than recommended may cause stomach bleeding.

Pexeva (paroxetine mesylate) Tablets (click product name to read prescribing information)	WARNINGS Clinical Worsening and Suicide Risk PRECAUTIONS General Discontinuation of Treatment with Paroxetine Abnormal Bleeding Information for Patients Drug Interactions Drugs That Interfere With Hemostasis (NSAIDs, Aspirin, Warfarin, etc.) Pregnancy Nonteratogenic Effects	Patients with major depressive disorder, both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality), whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Although there has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients, a causal role for antidepressants in inducing such behaviors has not been established. Nevertheless, patients being treated with antidepressants should be observed closely for clinical worsening and suicidality, especially at the beginning of a course of drug therapy, or at the time of dose changes, either increases or decreases. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or whose emergent suicidality is severe, abrupt in onset, or was not part of the patient's presenting symptoms.

Prozac (fluoxetine hydrochloride) Pulvules, Tablets, Solution and Delayed-Release Capsules (click product name to read prescribing information)	WARNINGS Clinical Worsening and Suicide Risk PRECAUTIONS General Abnormal Bleeding Discontinuation of Treatment with Prozac Information for Patients Drug Interactions Drugs That Interfere With Hemostasis (NSAIDs, Aspirin, Warfarin, etc.) Pregnancy Nonteratogenic Effects	Patients with major depressive disorder, both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality), whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Although there has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients, a causal role for antidepressants in inducing such behaviors has not been established. Nevertheless, patients being treated with antidepressants should be observed closely for clinical worsening and suicidality, especially at the beginning of a course of drug therapy, or at the time of dose changes, either increases or decreases. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or whose emergent suicidality is severe, abrupt in onset, or was not part of the patient's presenting symptoms.

Zoloft (sertraline hydrochloride) Tablets and Oral Concentrate (click product name to read prescribing information)	WARNINGS Clinical Worsening and Suicide Risk PRECAUTIONS General Discontinuation of Treatment with Zoloft Abnormal Bleeding Information for Patients Drug Interactions Drugs That Interfere With Hemostasis (Non-Selective NSAIDs, Aspirin, Warfarin, etc.) Pregnancy Nonteratogenic Effects	Patients with major depressive disorder, both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality), whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Although there has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients, a causal role for antidepressants in inducing such behaviors has not been established. Nevertheless, patients being treated with antidepressants should be observed closely for clinical worsening and suicidality, especially at the beginning of a course of drug therapy, or at the time of dose changes, either increases or decreases. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or whose emergent suicidality is severe, abrupt in onset, or was not part of the patient's presenting symptoms.

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Brand (Generic) Name	Sections Modified
Accutane (isotretinoin) Capsules (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Norethindrone/ethinyl estradiol

Anadrol -50 (oxymetholone) Tablets (click product name to read prescribing information)	PRECAUTIONS Information for the Patient Drug Interactions Warfarin

Arimidex (anastrozole) Tablets (click product name to read prescribing information)	PRECAUTIONS General First Paragraph Laboratory Tests Geriatric Use ADVERSE REACTIONS Allergic Reactions

Augmentin (amoxicillin/clavulanate potassium) 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 the Patient

Augmentin (amoxicillin/clavulanate potassium) Tablets (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

Ciloxan (ciprofloxacin hydrochloride ophthalmic solution) (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Elmiron (pentosan polysulfate sodium) Capsules (click product name to read prescribing information)	PRECAUTIONS General Rectal Hemorrhage ADVERSE REACTIONS Post-marketing Experience Rectal Hemorrhage

Ferrlecit (ferric sodium gluconate complex in sucrose injection) (click product name to read prescribing information)	PRECAUTIONS Pediatric Use ADVERSE REACTIONS Pediatric Patients

Kytril (granisetron) Injection (click product name to read prescribing information)	PRECAUTIONS Pregnancy Teratogenic Effects Pediatric Use

Persantine (dipyridamole) Tablets (click product name to read prescribing information)	PRECAUTIONS Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects

Rhinocort Aqua (budesonide) Nasal Spray (click product name to read prescribing information)	PRECAUTIONS Pregnancy

Rifadin (rifampin capsules USP) Rifadin IV (rifampin for injection USP) (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

Taxotere (docetaxel) for Injection Concentrate (click product name to read prescribing information)	PRECAUTIONS Final Paragraph ADVERSE REACTIONS Combination Therapy with Taxotere in the Adjuvant Treatment of Breast Cancer Table: Clinically Important Treatment Emergent Adverse Events Regardless of Causal Relationship in Patients Receiving Taxotere in Combination with Doxorubicin and Cyclophosphamide (TAX 316) Fever and Infection Gastrointestinal Events Cardiovascular Events Acute Myeloid Leukemia

Trobicin Sterile Powder (spectinomycin hydrochloride for injectable suspension, USP) (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

Unasyn (ampicillin sodium/sulbactam sodium) for Injection (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

Vioxx (rofecoxib) Tablets and Suspension (click product name to read prescribing information)	PRECAUTIONS Pediatric Use ADVERSE REACTIONS Pauciarticular and Polyarticular Course Juvenile Rheumatoid Arthritis

Zelnorm (tegaserod maleate) Tablets (click product name to read prescribing information)	PRECAUTIONS Geriatric Use Chronic Idiopathic Constipation ADVERSE REACTIONS Chronic Idiopathic Constipation Zelnorm-Induced Diarrhea Chronic Idiopathic Constipation

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Brand (Generic) Name	Sections Modified
Alimta (pemetrexed for injection) (click product name to read prescribing information)	ADVERSE REACTIONS Non-Small Cell Lung Cancer (NSCLC) Table 7

Topamax (topiramate) Tablets and Sprinkle Capsules (click product name to read prescribing information)	ADVERSE REACTIONS Migraine Table 8 Table 9 Other Adverse Events Observed During Migraine Clinical Trials

Ziagen (abacavir sulfate) Tablets and Oral Solution (click product name to read prescribing information)	ADVERSE REACTIONS Ziagen Once Daily versus Ziagen Twice Daily (Study CNA30021)

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