MedWatch - Novemver 2006 Safety-Related Drug Labeling Changes

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Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) -- November 2006

The detailed view includes drug products with safety labeling changes to the BOXED WARNING, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSE REACTIONS, or PATIENT PACKAGE INSERT/MEDICATION GUIDE sections. Deletions or editorial revisions made to these sections are not included in this summary.

Summary View

Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Dolophine Hydrochloride (methadone hydrochloride tablets, USP) Prescribing Information Patient Package Insert	BOXED WARNING (new) CONTRAINDICATIONS WARNINGS Respiratory Depression, Incomplete Cross-tolerance, and Iatrogenic Overdose Cardiac Conduction Effects Misuse, Abuse, and Diversion of Opioids Interactions with other CNS Depressants Interactions with Alcohol and Drugs of Abuse Head Injury and Increased Intracranial Pressure Acute Abdominal Conditions Hypotensive Effect PRECAUTIONS General Drug Interactions Opioid Antagonists, Mixed Agonist/Antagonists, and Partial Agonists Anti-retroviral Agents Cytochrome P450 Inducers Cytochrome P450 Inhibitors Potentially Arrhythmogenic Agents Interactions with Alcohol and Drugs of Abuse Anxiety Acute Pain Risk of Relapse in Patients on Methadone Maintenance Treatment of Opioid Addiction Tolerance and Physical Dependence Special Risk Patients Information for Patients Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use Renal Impairment Hepatic Impairment Gender ADVERSE REACTIONS Heroin Withdrawal Initial Administration Other Adverse Reactions Include the Following..... Maintenance on a Stabilized Dose PATIENT PACKAGE INSERT (new)	See highlighted prescribing information for extensive labeling revisions.

Herceptin (trastuzumab) Prescribing Information	BOXED WARNING Cardiomyopathy Infusion Reaction/Pulmonary Toxicity WARNINGS Cardiomyopathy PRECAUTIONS HER2 Testing Pregnancy Category B Geriatric Use ADVERSE REACTIONS Initial Section Cardiomyopathy Table 5: Per Patient Incidence of New Onset Myocardial Dysfunction..... Table 6: Incidence of Clnical Cardiac Events in Adjuvant Breast Cancer Table 7: Incidence and Severity of Cardiac Dysfunction in Metastatic Breast Cancer Infusion Reactions Anemia Neutropenia Infection Pulmonary Toxicity Thrombosis/Embolism Diarrhea Immunogenicity Adjuvant Breast Cancer Table 8: Selected Non-Cardiac Adverse Events with Higher Incidence (≥2%)..... Metastatic Breast Cancer Initial Section	BOXED WARNING: Cardiomypathy .....The incidence and severity of left ventricular cardiac dysfunction/CHF was highest in patients who received Herceptin concurrently with anthracycline-containing chemotherapy regimens. Discontinue Herceptin treatment in patients receiving adjuvant therapy for breast cancer and strongly consider discontinuation of Herceptin in patients with metastatic breast cancer who develop a clinically significant decrease in left ventricular function. BOXED WARNING: Infusion Reactions/Pulmonary Toxicity Herceptin administration can result in serious infusion reactions and pulmonary toxicity. .....Discontinuation of Herceptin should be strongly considered for infusion reactions manifesting as anaphylaxis, angioedema, pneumonitis, or acute respiratory distress syndrome. WARNINGS: Cardiomyopathy See WARNINGS section for revised prescribing information.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Diovan (valsartan) Tablets Prescribing Information	WARNINGS Fetal/Neonatal Morbidity and Mortality ADVERSE REACTIONS Post-marketing Experience Blood and Lymphatic There are very rare reports of thrombocytopenia.	WARNINGS: Fetal/Neonatal Morbidity and Mortality There have been reports of spontaneous abortion, oligohydramnios and newborn renal dysfunction when pregnant women have inadvertently taken valsartan.

Diovan HCT (valsartan and hydrochlorothiazide, USP) Combination Tablets Prescribing Information	WARNINGS Fetal/Neonatal Morbidity and Mortality	WARNINGS: Fetal/Neonatal Morbidity and Mortality There have been reports of spontaneous abortion, oligohydramnios and newborn renal dysfunction when pregnant women have inadvertently taken valsartan.

Humira (adalimumab) Prescribing Information	WARNINGS Malignancies ADVERSE REACTIONS Immunogenicity In patients with ankylosing spondylitis..... Psoriatic Arthritis and Ankylosing Spondylitis Clinical Trials	WARNINGS: Malignancies See highlighted WARNINGS section for revised prescribing information.
Kenalog-10 Injection (triamcinolone acetonide injectable suspension, USP) Prescribing Information	WARNINGS General Initial Paragraph Ophthalmic PRECAUTIONS Pediatric Use Initial Paragraph	WARNINGS: General Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants. There have been rare reports of deaths, primarily in preterm infants, associated with exposure to excessive amounts of benzyl alcohol. The amount of benzyl alcohol from medications is usually considered negligible compared to that received in flush solutions containing benzyl alcohol. Administration of high dosages of medications containing this preservative must take into account the total amount of benzyl alcohol administered. The amount of benzyl alcohol at which toxicity may occur is not known..... WARNINGS: Ophthalmic .....Adequate studies to demonstrate the safety of Kenalog Injection use by intraturbinal, subconjunctival, sub-Tenons, retrobulbar and intraocular (intravitreal) injections have not been performed. Endophthalmitis, eye inflammation, increased intraocular pressure and visual disturbances including vision loss have been reported with intravitreal administration. Several instances of blindness have been reported following injection of corticosteroid suspensions into the nasal turbinates and intralesional injection about the head.....

Kenalog-40 Injection (triamcinolone acetonide injectable suspension, USP) Prescribing Information	WARNINGS General Initial Paragraph Ophthalmic PRECAUTIONS Pediatric Use Initial Paragraph	WARNINGS: General Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants. There have been rare reports of deaths, primarily in preterm infants, associated with exposure to excessive amounts of benzyl alcohol. The amount of benzyl alcohol from medications is usually considered negligible compared to that received in flush solutions containing benzyl alcohol. Administration of high dosages of medications containing this preservative must take into account the total amount of benzyl alcohol administered. The amount of benzyl alcohol at which toxicity may occur is not known..... WARNINGS: Ophthalmic .....Adequate studies to demonstrate the safety of Kenalog Injection use by intraturbinal, subconjunctival, sub-Tenons, retrobulbar and intraocular (intravitreal) injections have not been performed. Endophthalmitis, eye inflammation, increased intraocular pressure and visual disturbances including vision loss have been reported with intravitreal administration. Several instances of blindness have been reported following injection of corticosteroid suspensions into the nasal turbinates and intralesional injection about the head.....

Lexiva (fosamprenavir calcium) Tablets Prescribing Information Patient Package Insert	WARNINGS PRECAUTIONS Information for Patients Drug Interactions Table 12: Drugs That Should Not Be Coadministered With Lexiva Oral Contraceptives Ethinyl Estradiol/Norethindrone PATIENT PACKAGE INSERT The use of Lexiva with Norvir (ritonavir) in combination with birth control pills may be harmful to your liver. The use of Lexiva with or without Norvir may decrease the effectiveness of birth control pills.	WARNINGS Concomitant use of Lexiva with ritonavir and oral contraceptives is not recommended. Lexiva with ritonavir and oral contraceptives may result in clinically significant hepatic transaminase elevations. Therefore, alternate methods of non-hormonal contraception are recommended.

Mirapex (pramipexole dihydrochloride) Tablets Prescribing Information Patient Package Insert	WARNINGS Hallucinations PRECAUTIONS Rebound and Augmentation in RLS Information for Patients .....In clinical trials, patients with RLS treated with pramipexole rarely reported hallucinations. Drug Interactions Amantadine Geriatric Use ADVERSE REACTIONS Restless Legs Syndrome Table 5: Treatment-Emergent Adverse Events..... Table 6: Dose Related Adverse Events..... General Adverse Events; Relationship to Age, Gender, and Race Other Adverse Events Observed During Phase 2 and 3 Clinical Trials Post-marketing Experience PATIENT PACKAGE INSERT (new)	WARNINGS In the Restless Leg Syndrome (RLS) clinical program, one pramipexole-treated patient (of 889) reported hallucinations; this patient discontinued treatment and the symptoms resolved.

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Brand (Generic) Name	Sections Modified
Actoplus Met (pioglitazone hydrochloride + metformin hydrochloride) Prescribing Information	PRECAUTIONS Drug Interactions Pioglitazone Hydrochloride An enzyme inhibitor of CYP2C8 (such as gemfibrozil) may significantly increase the AUC of pioglitazone and an enzyme inducer of CYP2C8 (such as rifampin) may significantly decrease the AUC of pioglitazone.

Actos (pioglitazone hydrochloride) Tablets Prescribing Information	PRECAUTIONS Drug Interactions An enzyme inhibitor of CYP2C8 (such as gemfibrozil) may significantly increase the AUC of pioglitazone and an enzyme inducer of CYP2C8 (such as rifampin) may significantly decrease the AUC of pioglitazone.

Ativan (lorazepam) Injection Prescribing Information	PRECAUTIONS Pediatric Use General The “gasping syndrome”, characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites.....

Flarex (fluorometholone acetate ophthalmic suspension) Prescribing Information	PRECAUTIONS Geriatric Use

Humatrope (somatropin [rDNA origin] for injection) Prescribing Information	PRECAUTIONS General ADVERSE REACTIONS Patients with Short Stature Homeobox-Containing Gene (SHOX) Deficiency

Innohep (tinzaparin sodium) Injection Prescribing Information	PRECAUTIONS Pregnancy Pregnancy: Category B Fetal Risk Summary Clinical Considerations Data Human Data Animal Data If Innohep is used during pregnancy.....

Qvar (beclomethasone dipropionate HFA) Inhalation Aerosol Prescribing Information	PRECAUTIONS Pediatric Use

Skelid (tiludronate disodium) Tablets Prescribing Information	PRECAUTIONS General Osteonecrosis of the Jaw Musculoskeletal Pain

Symbyax (olanzapine and fluoxetine HCl) Capsules Prescribing Information	PRECAUTIONS Transaminase Elevations Rare postmarketing reports of hepatitis have been received. Very rare cases of cholestatic or mixed liver injury have also been reported in the postmarketing period. ADVERSE REACTIONS Other Events Observed with Olanzapine or Fluoxetine Monotherapy Jaundice

Tamiflu (oseltamivir phosphate) Oral Suspension and Capsules Prescribing Information Patient Package Insert See MedWatch Safety Alert posted 11/13/2006 for additional information on labeling revisions and the Dear Healthcare Professional Letter.	PRECAUTIONS Neuropsychiatric Events Drug Interactions Initial Paragraph PATIENT PACKAGE INSERT What are the possible side effects of Tamiflu?

Zyban (bupropion hydrochloride) Sustained-Release Tablets Prescribing Information	PRECAUTIONS Pregnancy Teratogenic Effects Category C (Pregnancy Category changed from Pregnancy Category B to Pregnancy Category C.)

Zyprexa (olanzapine tablets) Zyprexa Zydis (olanzapine orally disintegrating tablets) Zyprexa IntraMuscular (olanzapine for injection) Prescribing Information	PRECAUTIONS Transaminase Elevations Rare postmarketing reports of hepatitis have been received. Very rare cases of cholestatic or mixed liver injury have also been reported in the postmarketing period. ADVERSE REACTIONS Post-introduction Reports Jaundice

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Brand (Generic) Name	Sections Modified
Aggrenox (aspirin extended-release dipyridamole) Capsules Prescribing Information	ADVERSE REACTIONS Other Adverse Reactions Skin and Appendages Disorders

Natrecor (nesiritide) for Injection [for Intravenous Infusion Only] Prescribing Information	ADVERSE REACTIONS Effect on Mortality

Starlix (nateglinide) Tablets Prescribing Information	ADVERSE REACTIONS Post-marketing Experience .....Similarly, cases of jaundice, cholestatic hepatitis and elevated liver enzymes have been reported.

Uroxatral (alfuzosin HCl extended-release tablets) Prescribing Information	ADVERSE REACTIONS Post-marketing Adverse Event Reports Urticaria Angioedema Pruritis Rhinitis Diarrhea Flushing Edema Angina pectoris in patients with pre-existing coronary artery disease.

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Brand (Generic) Name

Sections Modified

Videx (didanosine)

Patient Package Insert

PATIENT PACKAGE INSERT

What should I avoid while taking Videx?
- Other Medicines
  - Antacids
    - Since Videx is mixed with an antacid, any side effects related to Videx's ingredients may get worse if you also take an antacid.

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