MedWatch - February 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) -- February 2005

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
Copegus (ribavirin, USP) Tablets (click product name to read prescribing information)	CONTRAINDICATIONS WARNINGS Initial Paragraph Hepatic Failure PRECAUTIONS Laboratory Tests Drug Interactions Nucleoside Analogues NRTIs Lamivudine, Stavudine, and Zidovudine ADVERSE REACTIONS Initial Section Table 4 Common Adverse Reactions in CHC With HIV Coinfection Laboratory Test Values	CONTRAINDICATIONS Copegus and Pegasys combination therapy is contraindicated in patients with: Autoimmune hepatitis Hepatic decompensation (Child-Pugh score greater than 6; class B and C) in cirrhotic CHC monoinfected patients before or during treatment Hepatic decompensation with Child-Pugh score greater than or equal to 6 in cirrhotic CHC patients coinfected with HIV before or during treatment WARNINGS Initial Paragraph Copegus must not be used alone because ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus infection. Hepatic Failure Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including Pegasys. Cirrhotic CHC patients coinfected with HIV receiving highly active antiretroviral therapy (HAART) and interferon alfa-2a with or without ribavirin appear to be at increased risk for the development of hepatic decompensation compared to patients not receiving HAART.

Duragesic (fentanyl transdermal system) (click product name to read prescribing information)	CONTRAINDICATIONS BOXED WARNING WARNINGS General Hypoventilation (Respiratory Depression) Interactions with other CNS Depressants PRECAUTIONS General Tolerance Physical Dependence Information for Patients Drug Interactions Central Nervous System Depressants ADVERSE REACTIONS Pre-Marketing Clinical Trial Experience Drug Abuse and Addiction	CONTRAINDICATIONS Because serious or life-threatening hypoventilation could occur, Duragesic (fentanyl transdermal system) is contraindicated in patients who are not opioid-tolerant..... Duragesic (fentanyl transdermal system) is contraindicated in patients with known hypersensitivity to fentanyl or any components of this product. Statement, "FOR USE IN OPIOID-TOLERANT PATIENTS ONLY" added above boxed warning. BOXED WARNING Duragesic contains a high concentration of a potent Schedule II opioid agonist, fentanyl. Schedule II opioid substances which include fentanyl, hydromorphone, methadone, morphine, oxycodone, and oxymorphone have the highest potential for abuse and associated risk of fatal overdose due to respiratory depression. Fentanyl can be abused and is subject to criminal diversion. Duragesic is indicated for management of persistent, moderate to severe chronic pain that requires continuous, around-the-clock opioid administration for an extended period of time. Because serious or life-threatening hypoventilation could occur, Duragesic (fentanyl transdermal system) is contraindicated in patients who are not opioid-tolerant. WARNINGS General All patients and their caregivers should be advised to avoid exposing the Duragesic application site to direct external heat sources, such as heating pads or electric blankets, heat lamps, saunas, hot tubs, and heated water beds, etc., while wearing the system. There is a potential for temperature-dependent increases in fentanyl released from the system resulting in possible overdose and death. Hypoventilation Serious or life-threatening hypoventilation may occur at any time during the use of Duragesic especially during the initial 24-72 hours following initiation of therapy and following increases in dose. Interactions with other CNS Depressants The concomitant use of Duragesic (fentanyl transdermal system) with other central nervous system depressants, including but not limited to other opioids, sedatives, hypnotics, tranquilizers (e.g., benzodiazepines), general anesthetics, phenothiazines, skeletal muscle relaxants, and alcohol, may cause respiratory depression, hypotension, and profound sedation or potentially result in coma. When such combined therapy is contemplated, the dose of one or both agents should be significantly reduced.

Lotronex (alosetron HCl) Tablets (click product name to read prescribing information)	CONTRAINDICATIONS BOXED WARNING WARNINGS Constipation Ischemic Colitis PRECAUTIONS Information for Patients Drug Interactions Fluvoxamine Ketoconazole MEDICATION GUIDE PATIENT-PHYSICIAN AGREEMENT FOR LOTRONEX PRESCRIBING PROGRAM FOR LOTRONEX: PHYSICIAN ENROLLMENT FORM	CONTRAINDICATIONS Concomitant administration of alosetron with fluvoxamine is contraindicated. Fluvoxamine, a known strong inhibitor of CYP1A2, has been shown to increase mean alosetron plasma concentrations (AUC) approximately 6-fold and prolong the half-life by approximately 3-fold. BOXED WARNING Infrequent but serious gastrointestinal adverse events have been reported with the use of Lotronex. WARNINGS Constipation Serious complications of constipation including obstruction, ileus, impaction, toxic megacolon, and secondary bowel ischemia have been reported with use of Lotronex during clinical trials. In addition, rare cases of perforation and death have been reported from postmarketing clinical practice. In some cases,complications of constipation required intestinal surgery, including colectomy. In IBS clinical trials, approximately 10% of patients on Lotronex withdrew prematurely because of constipation. The incidence of serious complications of constipation was approximately 0.1% (1 per 1,000 patients) in women receiving either Lotronex or placebo. Patients who are elderly, debilitated, or taking additional medications that decrease gastrointestinal motility may be at greater risk for complications of constipation. Ischemic Colitis Ischemic colitis has been reported in patients receiving Lotronex in clinical trials as well as during marketed use of the drug. In IBS clinical trials, the cumulative incidence of ischemic colitis in women receiving Lotronex was 0.2% (2 per 1,000 patients, 95% confidence interval 1 to 3) through 3 months and was 0.3% (3 per 1,000 patients, 95% confidence interval 1 to 4) through 6 months. Ischemic colitis was not reported in women receiving placebo. The patient experience in controlled clinical trials is insufficient to estimate the incidence of ischemic colitis in patients taking Lotronex for longer than 6 months.

Malarone (atovaquone and proguanil hydrochloride) Tablets Malarone (atovaquone and proguanil hydrochloride) Pediatric Tablets (click product name to read prescribing information)	CONTRAINDICATIONS PRECAUTIONS Carcinogenesis, Mutagenesis, Impairment of Fertility Proguanil ADVERSE REACTIONS Post-Marketing Adverse Reactions Skin/Hypersensitivity Angioedema Anaphylaxis	Malarone is contraindicated in individuals with known hypersensitivity to atovaquone or proguanil hydrochloride or any component of the formulation. Rare cases of anaphylaxis following treatment with atovaquone/proguanil have been reported.

Serostim LQ (somatropin [rDNA origin] injection) (click product name to read prescribing information)	CONTRAINDICATIONS	Serostim LQ should not be used in any patient with a known hypersensitivity to somatropin or any of the excipients.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Celexa (citalopram hydrobromide) Tablets and Oral Solution (click product name to read prescribing information)	BOXED WARNING Suicidality in Children and Adolescents WARNINGS Clinical Worsening and Suicide Risk PRECAUTIONS Information for Patients Clinical Worsening and Suicide Risk Pediatric Use MEDICATION GUIDE	Please see prescribing information. Class labeling changes for all of the drugs approved to treat major depressive disorder (MDD) and to caution practitioners, patients, family members or caregivers about an increased risk of suicidal thinking and behavior (suicidality) in children and adolescents with MDD and other psychiatric disorders who are taking antidepressant medications. See FDA Public Health Advisory 10/15/04 - Suicidality in Children and Adolescents Being Treated With Antidepressant Medications

Cymbalta (duloxetine hydrochloride) Delayed-Release Capsules (click product name to read prescribing information)	BOXED WARNING Suicidality in Children and Adolescents WARNINGS Clinical Worsening and Suicide Risk PRECAUTIONS Information for Patients Clinical Worsening and Suicide Risk Pediatric Use MEDICATION GUIDE	Please see prescribing information. Class labeling changes for all of the drugs approved to treat major depressive disorder (MDD) and to caution practitioners, patients, family members or caregivers about an increased risk of suicidal thinking and behavior (suicidality) in children and adolescents with MDD and other psychiatric disorders who are taking antidepressant medications. See FDA Public Health Advisory 10/15/04 - Suicidality in Children and Adolescents Being Treated With Antidepressant Medications

Effexor (venlafaxine hydrochloride) Tablets (click product name to read prescribing information)	BOXED WARNING Suicidality in Children and Adolescents WARNINGS Clinical Worsening and Suicide Risk PRECAUTIONS Information for Patients Clinical Worsening and Suicide Risk Pediatric Use MEDICATION GUIDE	Please see prescribing information. Class labeling changes for all of the drugs approved to treat major depressive disorder (MDD) and to caution practitioners, patients, family members or caregivers about an increased risk of suicidal thinking and behavior (suicidality) in children and adolescents with MDD and other psychiatric disorders who are taking antidepressant medications. See FDA Public Health Advisory 10/15/04 - Suicidality in Children and Adolescents Being Treated With Antidepressant Medications.

Effexor XR (venlafaxine hydrochloride) Extended-Release Capsules (click product name to read prescribing information)	BOXED WARNING Suicidality in Children and Adolescents WARNINGS Clinical Worsening and Suicide Risk PRECAUTIONS Information for Patients Clinical Worsening and Suicide Risk Pediatric Use MEDICATION GUIDE	Please see prescribing information. Class labeling changes for all of the drugs approved to treat major depressive disorder (MDD) and to caution practitioners, patients, family members or caregivers about an increased risk of suicidal thinking and behavior (suicidality) in children and adolescents with MDD and other psychiatric disorders who are taking antidepressant medications. See FDA Public Health Advisory 10/15/04 - Suicidality in Children and Adolescents Being Treated With Antidepressant Medications

Lexapro (escitalopram oxalate) Tablets and Oral Solution (click product name to read prescribing information)	BOXED WARNING Suicidality in Children and Adolescents WARNINGS Clinical Worsening and Suicide Risk PRECAUTIONS Information for Patients Clinical Worsening and Suicide Risk Pediatric Use MEDICATION GUIDE	Please see prescribing information. Class labeling changes for all of the drugs approved to treat major depressive disorder (MDD) and to caution practitioners, patients, family members or caregivers about an increased risk of suicidal thinking and behavior (suicidality) in children and adolescents with MDD and other psychiatric disorders who are taking antidepressant medications. See FDA Public Health Advisory 10/15/04 - Suicidality in Children and Adolescents Being Treated With Antidepressant Medications

Nardil (phenelzine sulfate tablets, USP) (click product name to read prescribing information)	BOXED WARNING Suicidality in Children and Adolescents WARNINGS Clinical Worsening and Suicide Risk PRECAUTIONS Information for Patients Clinical Worsening and Suicide Risk Pediatric Use MEDICATION GUIDE	Please see prescribing information. Class labeling changes for all of the drugs approved to treat major depressive disorder (MDD) and to caution practitioners, patients, family members or caregivers about an increased risk of suicidal thinking and behavior (suicidality) in children and adolescents with MDD and other psychiatric disorders who are taking antidepressant medications. See FDA Public Health Advisory 10/15/04 - Suicidality in Children and Adolescents Being Treated With Antidepressant Medications

Prozac (fluoxetine hydrochloride) (click product name to read prescribing information)	BOXED WARNING Suicidality in Children and Adolescents WARNINGS Clinical Worsening and Suicide Risk PRECAUTIONS Information for Patients Clinical Worsening and Suicide Risk Pediatric Use MEDICATION GUIDE	Please see prescribing information. Class labeling changes for all of the drugs approved to treat major depressive disorder (MDD) and to caution practitioners, patients, family members or caregivers about an increased risk of suicidal thinking and behavior (suicidality) in children and adolescents with MDD and other psychiatric disorders who are taking antidepressant medications. See FDA Public Health Advisory 10/15/04 - Suicidality in Children and Adolescents Being Treated With Antidepressant Medications

Sarafem (fluoxetine hydrochloride) (click product name to read prescribing information)	BOXED WARNING Suicidality in Children and Adolescents WARNINGS Clinical Worsening and Suicide Risk PRECAUTIONS Information for Patients Clinical Worsening and Suicide Risk Pediatric Use MEDICATION GUIDE	Please see prescribing information. Class labeling changes for all of the drugs approved to treat major depressive disorder (MDD) and to caution practitioners, patients, family members or caregivers about an increased risk of suicidal thinking and behavior (suicidality) in children and adolescents with MDD and other psychiatric disorders who are taking antidepressant medications. See FDA Public Health Advisory 10/15/04 - Suicidality in Children and Adolescents Being Treated With Antidepressant Medications

Sinequan (doxepin HCl) Capsules and Oral Concentrate (click product name to read prescribing information)	BOXED WARNING Suicidality in Children and Adolescents WARNINGS Clinical Worsening and Suicide Risk PRECAUTIONS Information for Patients Clinical Worsening and Suicide Risk Pediatric Use MEDICATION GUIDE	Please see prescribing information. Class labeling changes for all of the drugs approved to treat major depressive disorder (MDD) and to caution practitioners, patients, family members or caregivers about an increased risk of suicidal thinking and behavior (suicidality) in children and adolescents with MDD and other psychiatric disorders who are taking antidepressant medications. See FDA Public Health Advisory 10/15/04 - Suicidality in Children and Adolescents Being Treated With Antidepressant Medications

Symbyax (olanzapine and fluoxetine HCl capsules) (click product name to read prescribing information)	BOXED WARNING Suicidality in Children and Adolescents WARNINGS Clinical Worsening and Suicide Risk PRECAUTIONS Information for Patients Clinical Worsening and Suicide Risk Pediatric Use MEDICATION GUIDE	Please see prescribing information. Class labeling changes for all of the drugs approved to treat major depressive disorder (MDD) and to caution practitioners, patients, family members or caregivers about an increased risk of suicidal thinking and behavior (suicidality) in children and adolescents with MDD and other psychiatric disorders who are taking antidepressant medications. See FDA Public Health Advisory 10/15/04 - Suicidality in Children and Adolescents Being Treated With Antidepressant Medications

Viramune (nevirapine) Tablets and Oral Suspension (click product name to read prescribing information)	BOXED WARNING MEDICATION GUIDE	It is essential that patients be monitored intensively during the first 18 weeks of therapy with Viramune to detect potentially life-threatening hepatotoxicity or skin reactions. Extra vigilance is warranted during the first 6 weeks of therapy, which is the period of greatest risk of these events. Do not restart Viramune following severe hepatic, skin or hypersensitivity reactions. In some cases, hepatic injury has progressed despite discontinuation of treatment. In addition, the 14-day lead-in period with Viramune 200 mg daily dosing must be strictly followed.

Zoloft (sertraline hydrochloride) Tablets and Oral Concentrate (click product name to read prescribing information)	BOXED WARNING Suicidality in Children and Adolescents WARNINGS Clinical Worsening and Suicide Risk PRECAUTIONS Information for Patients Clinical Worsening and Suicide Risk Pediatric Use MEDICATION GUIDE	Please see prescribing information. Class labeling changes for all of the drugs approved to treat major depressive disorder (MDD) and to caution practitioners, patients, family members or caregivers about an increased risk of suicidal thinking and behavior (suicidality) in children and adolescents with MDD and other psychiatric disorders who are taking antidepressant medications. See FDA Public Health Advisory 10/15/04 - Suicidality in Children and Adolescents Being Treated With Antidepressant Medications

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Atacand (candesartan cilexetil) Tablets (click product name to read prescribing information)	WARNINGS Hypotension in Heart Failure Patients PRECAUTIONS Geriatric Use Heart Failure ADVERSE REACTIONS Heart Failure Laboratory Test Findings Heart Failure	Patients with heart failure given Atacand commonly have some reduction in blood pressure. In patients with symptomatic hypotension this may require temporarily reducing the dose of Atacand, or diuretic, or both, and volume repletion.

Cancidas (caspofungin acetate) for Injection (click product name to read prescribing information)	WARNINGS	Cancidas and cyclosporine should only be used concomitantly in those patients for whom the potential benefit outweighs the potential risk. Patients who develop abnormal liver function tests during concomitant therapy should be monitored and the risk/benefit of continuing therapy should be evaluated.

Gabitril (tiagabine hydrochloride) Tablets (click product name to read prescribing information)	WARNINGS Seizures in Patients Without Epilepsy	Post-marketing reports have shown that Gabitril use has been associated with new onset seizures and status epilepticus in patients without epilepsy. Dose may be an important predisposing factor in the development of seizures, although seizures have been reported in patients taking daily doses of Gabitril as low as 4 mg/day. In most cases, patients were using concomitant medications (antidepressants, antipsychotics, stimulants, narcotics) that are thought to lower the seizure threshold. Some seizures occurred near the time of a dose increase, even after periods of prior stable dosing. In nonepileptic patients who develop seizures while on Gabitril treatment, Gabitril should be discontinued and patients should be evaluated for an underlying seizure disorder.

Minocin (minocycline for Injection) Intravenous Minocin (minocycline hydrochloride) Pellet-filled Capsules and Oral Suspension Please contact Wyeth at 1-800-934-5556 for prescribing information.	WARNINGS PRECAUTIONS Pregnancy Teratogenic Effects: Pregnancy Category D Information for Patients ADVERSE REACTIONS Hepatic Toxicity Autoimmune Hepatitis Fatal Hepatic Failure	WARNINGS The anti-anabolic action of the tetracyclines may cause an increase in BUN. While this is not a problem in those with normal renal function, in patients with significantly impaired function, higher serum levels of tetracycline may lead to azotemia, hyperphosphatemia, and acidosis. Under such conditions, monitoring of creatinine and BUN is recommended, and the total daily dosage should not exceed 200 mg in 24 hours. If renal impairment exists, even usual oral or parenteral doses may lead to excessive systemic accumulation of the drug and possible liver toxicity. Pregnancy: Teratogenic Effects: Pregnancy Category D All pregnancies have a background risk of birth defect, loss, or other adverse outcome regardless of drug exposure. There are no adequate and well-controlled studies on the use of minocycline in pregnant women. Minocycline, like other tetracycline-class antibiotics, crosses the placenta and may cause fetal harm when administered to a pregnant woman. Isolated reports of congenital anomalies including limb reduction have been reported in post-marketing experience. Only limited information is available regarding these reports; therefore no conclusion on causal association can be established. If minocycline is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Strattera (atomoxetine HCl) (click product name to read prescribing information)	WARNINGS Severe Liver Injury PRECAUTIONS Drug-Drug Interaction Albuterol PATIENT PACKAGE INSERT	Severe drug-related liver injury may progress to acute liver failure resulting in death or the need for a liver transplant. Strattera should be discontinued in patients with jaundice or laboratory evidence of liver injury, and should not be restarted. Laboratory testing to determine liver enzyme levels should be done upon the first symptom or sign of liver dysfunction (e.g., pruritus, dark urine, jaundice, right upper quadrant tenderness, or unexplained "flu-like" symptoms).

Tenoretic (atenolol and chlorthalidone) (click product name to read prescribing information)	WARNINGS Pregnancy and Fetal Injury PRECAUTIONS Nursing Mothers	Neonates born to mothers who are receiving atenolol at parturition or breast-feeding may be at risk for hypoglycemia and bradycardia.

Tenormin (atenolol) I.V. Injection (click product name to read prescribing information)	WARNINGS Pregnancy and Fetal Injury PRECAUTIONS Nursing Mothers	Neonates born to mothers who are receiving Tenormin at parturition or breast-feeding may be at risk for hypoglycemia and bradycardia.

Tenormin (atenolol) Tablets (click product name to read prescribing information)	WARNINGS Pregnancy and Fetal Injury PRECAUTIONS Nursing Mothers	Neonates born to mothers who are receiving Tenormin at parturition or breast-feeding may be at risk for hypoglycemia and bradycardia.

Zantac 75 (ranitidine) Tablets Over-the-Counter Medication Please contact Pfizer Consumer Healthcare at 1-800-223-0182 for prescribing information.	DO NOT USE USES ASK A DOCTOR BEFORE USE IF YOU HAVE	DO NOT USE If you have trouble or pain swallowing food, vomiting with blood, or bloody or black stools. These may be signs of a serious condition. See your doctor. With other acid reducers USES Prevents heartburn associated with acid indigestion and sour stomach brought on by eating or drinking certain foods and beverages. ASK A DOCTOR BEFORE USE IF YOU HAVE: Frequent wheezing, particularly with heartburn Frequent chest pain Stomach pain Unexplained weight loss Nausea or vomiting Had Heartburn over 3 months. This may be sign of a more serious condition Heartburn with lightheadedness, sweating or dizziness Chest pain or shoulder pain with shortness of breath; sweating; pain spreading to arms, neck or shoulders; or lightheadedness

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Brand (Generic) Name	Sections Modified
Aredia (pamidronate disodium for injection) for Intravenous Infusion (click product name to read prescribing information)	PRECAUTIONS Osteonecrosis of the Jaw

Avandia (rosiglitazone maleate) Tablets (click product name to read prescribing information)	PRECAUTIONS Table 7 ADVERSE REACTIONS Initial Paragraph Trials of Avandia as Monotherapy and in Combination With Other Hypoglycemic Agents

Celebrex (celecoxib) Capsules (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Warfarin ADVERSE REACTIONS Other Serious Adverse Reactions Which Occur Rarely (Estimated <0.1%), Regardless Of Causality Nervous System Fatal Intracranial Hemorrhage

Ketek (telithromycin) Tablets (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Oral Anticoagulants

Prandin (repaglinide) Tablets (click product name to read prescribing information)	PRECAUTIONS General ADVERSE REACTIONS Cardiovascular Events

Visicol (sodium phosphate monobasic monohydrate, USP & sodium phosphate dibasic anhydrous, USP) Tablets (click product name to read prescribing information)	PRECAUTIONS Seizures Loss of Consciousness

Zetia (ezetimibe) Tablets (click product name to read prescribing information)	PRECAUTIONS Skeletal Muscle Drug Interactions HMG-Co A Reductase Inhibitor Warfarin ADVERSE REACTIONS Post-marketing Experience PATIENT PACKAGE INSERT

Zyvox (linezolid) Tablets, Oral Suspension, and Injection (click product name to read prescribing information)	PRECAUTIONS General Serotonin Syndrome Drug Interactions Serotonergic Agents ADVERSE REACTIONS Postmarketing Experience

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Brand (Generic) Name	Sections Modified
Neurontin (gabapentin) Capsules, Tablets and Oral Solution (click product name to read prescribing information)	ADVERSE REACTIONS Clinical Trials in Adults and Adolescents (Except Trials in Neuropathic Pain)

Penicillin G Potassium Injection, USP (click product name to read prescribing information)	ADVERSE REACTIONS Local Reactions Pain at Injection Site

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