MedWatch - April 2008 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 2008

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. Read about the new physician labeling format.

Summary View

Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Aldurazyme (laronidase) Solution for Intravenous Infusion Only Prescribing Information	BOXED WARNING (new) Risk of Anaphylaxis WARNINGS Anaphylaxis and Allergic Reactions (see BOXED WARNING) ADVERSE REACTIONS Initial Paragraph In clinical studies, the most common adverse reactions requiring intervention... In postmarketing experience with Aldurazyme... Immunogenicity	BOXED WARNING WARNING: Risk of Anaphylaxis Life-threatening anaphylactic reactions have been observed in some patients during Aldurazyme infusions. Therefore, appropriate medical support should be readily available when Aldurazyme is administered. Patients with compromised respiratory function or acute respiratory disease may be at risk of serious acute exacerbation of their respiratory compromise due to infusion reactions, and require additional monitoring. WARNINGS: Anaphylaxis and Allergic Reactions (see BOXED WARNING) See prescribing information for revised text.

Emtriva (emtricitabine) Capsules and Oral Solution Prescribing Information Patient Package Insert	BOXED WARNING WARNINGS Patients Co-infected with HIV and Hepatitis B Virus PATIENT PACKAGE INSERT What is the most important information I should know about Emtriva? If you are also infected with the Hepatitis B Virus (HBV)... What are the possible side effects of Emtriva? "flare-ups" of Hepatitis B Virus infection...	BOXED WARNING ...Emtriva is not approved for the treatment of Chronic Hepatitis B Virus (HBV) Infection... WARNINGS: Patients Co-infected with HIV and Hepatitis B Virus ...Emtriva is not approved for the treatment of chronic HBV infection... ...In some patients infected with HBV and treated with Emtriva, the exacerbations of hepatitis B were associated with liver decompensation and liver failure...

Lotronex (alosetron hydrochloride) Tablets Prescribing Information (in new labeling format) Medication Guide	BOXED WARNING WARNING: SERIOUS GASTROINTESTINAL ADVERSE REACTIONS WARNINGS AND PRECAUTIONS Serious Complications of Constipation Ischemic Colitis Prescribing Program for Lotronex ADVERSE REACTIONS Clinical Trials Experience Initial Paragraph Women With Severe Diarrhea-Predominant Irritable Bowel Syndrome Table 2 Constipation DRUG INTERACTIONS Initial Paragraph USE IN SPECIFIC POPULATIONS Pediatric Use Geriatric Use Hepatic Impairment Renal Impairment PATIENT COUNSELING INFORMATION Physician and Patient Responsibilities MEDICATION GUIDE There is a special prescribing program for Lotronex. What is Lotronex? Who should not take Lotronex? What should I talk about with my doctor before taking Lotronex? What are the possible side effects of Lotronex? How should I store Lotronex? General information about the safe and effective use of Lotronex.	BOXED WARNING WARNING: SERIOUS GASTROINTESTINAL ADVERSE REACTIONS ...Only physicians who have enrolled in the Prometheus Prescribing Program for Lotronex based on their understanding of the benefits and risks, should prescribe Lotronex... WARNINGS AND PRECAUTIONS Serious Complications of Constipation ...Complications of constipation have been reported with use of 1 mg twice a daily and with lower doses. A dose response relationship has not been established for serious complications of constipation... Ischemic Colitis Some patients have experienced ischemic colitis without warning... ...Ischemic colitis has been reported with use of 1 mg twice daily and with lower doses. A dose-response relationship has not been established. Ischemic colitis was reported in one patient receiving placebo. Prescribing Program for Lotronex (See highlighted text for labeling revisions.)

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Advair Diskus (fluticasone propionate and salmeterol inhalation powder) Prescribing Information (in new labeling format) Medication Guide	CONTRAINDICATIONS WARNINGS AND PRECAUTIONS Deterioration of Disease and Acute Episodes Pneumonia Drug Interactions With Strong Cytochrome P450 3A4 Inhibitors ADVERSE REACTIONS Clinical Trials Experience in Asthma Adult and Adolescent Patients 12 Years of Age and Older Table 2 Clinical Trials Experience in Chronic Obstructive Pulmonary Disease Short-Term (6 Months to 1 Year) Trials Table 3 Postmarketing Experience Musculoskeletal, Connective Tissue, and Bone Disorders Arthralgia Psychiatric Disorders Behavioral changes, including hyperactivity and irritability, have been reported very rarely and primarily in children. DRUG INTERACTIONS Inhibitors of Cytochrome P450 3A4 Initial Paragraph Ketoconazole: Salmeterol Beta-Adrenergic Receptor Blocking Agents USE IN SPECIFIC POPULATIONS Pregnancy Pediatric Use Geriatric Use Hepatic Impairment Renal Impairment PATIENT COUNSELING INFORMATION Pneumonia MEDICATION GUIDE What is Advair Diskus Chronic Obstructive Pulmonary Disease Who should not use Advair Diskus? What should I tell my healthcare provider before using Advair Diskus? ...are allergic to any of the ingredients in Advair Diskus... How do I use Advair Diskus? What are the possible side effects with Advair Diskus? The most common side effects with Advair Diskus include...	CONTRAINDICATIONS Severe hypersensitivity to milk proteins... WARNINGS AND PRECAUTIONS Deterioration of Disease and Acute Episodes Advair Diskus should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma or COPD. Advair Diskus has not been studied in patients with acutely deteriorating asthma or COPD... Pneumonia Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbations frequently overlap. Lower respiratory tract infections, including pneumonia, have been reported in patients with COPD following the inhaled administration of corticosteroids, including fluticasone propionate and Advair Diskus. In 2 replicate 12-month studies of 1,579 patients with COPD, there was a higher incidence of pneumonia reported in patients receiving Advair Diskus 250/50 (7%) than in those receiving salmeterol 50 mcg (3%). The incidence of pneumonia in the patients treated with Advair Diskus was higher in patients over 65 years of age (9%) compared with the incidence in patients less than 65 years of age (4%)... Drug Interactions With Strong Cytochrome P450 3A4 Inhibitors The use of strong CYP 3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with Advair Diskus is not recommended because increased systemic corticosteroid and increased cardiovascular adverse effects may occur...

Amitiza (lubiprostone) Capsules Prescribing Information (in new labeling format)	CONTRAINDICATIONS WARNINGS AND PRECAUTIONS Dyspnea ADVERSE REACTIONS Clinical Studies Experience Chronic Idiopathic Constipation Table 1 Nausea Diarrhea Less common adverse reactions Irritable Bowel Syndrome with Constipation Table 2 Less common adverse reactions Postmarketing Experience USE IN SPECIFIC POPULATIONS Pregnancy Geriatric Use Irritable Bowel Syndrome with Constipation NONCLINICAL TOXICITY Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Impairment of Fertility PATIENT COUNSELING INFORMATION Dosing Instructions Irritable Bowel Syndrome with Constipation	CONTRAINDICATIONS Amitiza is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. WARNINGS AND PRECAUTIONS: Dyspnea In clinical trials conducted to study Amitiza in treatment of chronic idiopathic constipation and IBS-C there were reports of dyspnea. This was reported at 2.5% of the treated chronic idiopathic constipation population and at 0.4% in the treated IBS-C population. Although not classified as serious adverse events, some patients discontinued treatment on study because of this event. There have been postmarketing reports of dyspnea when using Amitiza 24 mcg... ...These events have usually been described as a sensation of chest tightness and difficulty taking in a breath, and generally have an acute onset within 30-60 minutes after taking the first dose. They generally resolve within a few hours after taking the dose, but recurrence has been frequently reported with subsequent doses.

Crixivan (indinavir sulfate) Capsules Prescribing Information Patient Package Insert	CONTRAINDICATIONS Table 7 Oral Midazolam WARNINGS Drug Interactions Rosuvastatin (added) ...Dosage reduction for midazolam... PRECAUTIONS Drug Interactions Table 8: Drugs That Should Not Be Coadministered with Crixivan Sedative/hypnotics Oral Midazolam Table 9: Established and Other Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction HMG-CoA Reductase Inhibitors Rosuvastatin Midazolam (parenteral administration) PATIENT PACKAGE INSERT Can Crixivan be taken with other medications? Medicines you should not take with Crixivan Oral Versed (midazolam) In addition, you should not take Crixivan with the following: Crestor (rosuvastatin) Medicines you can take with Crixivan Intravenous Versed (midazolam) - If you take Crixivan with Intravenous Versed, your doctor may adjust the does of Versed.	CONTRAINDICATIONS Table 7: Drug Interactions With Crixivan: Contraindicated Drugs Drug Class: Sedative/hypnotics Oral midazolam (added as contraindicated drug) (See highlighted text for labeling revisions.) WARNINGS Drug Interactions Caution should be exercised if HIV protease inhibitors, including Crixivan, are used concurrently with other HMG-CoA reductase inhibitors that are also metabolized by the CYP3A4 pathway (e.g., atorvastatin or rosuvastatin). ...If Crixivan with or without ritonavir is co-administered with parenteral midazolam, it should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered.

Tigan (trimethobenzamide hydrochloride) Injectable for Intramuscular Use Only Prescribing Information	CONTRAINDICATIONS PRECAUTIONS General Adjustment of Dose in Renal Failure Geriatric Use	CONTRAINDICATIONS The injectable form of Tigan is contraindicated in pediatric patients and in patients with known hypersensitivity to trimethobenzamide.

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Brand (Generic) Name	Sections Modified
Cardiolite Kit for the Preparation of Technetium Tc99m Sestamibi for Injection Prescribing Information (in new labeling format)	USE IN SPECIFIC PATIENTS Pediatric Use

Cetrotide (cetrorelix acetate for injection) Prescribing Information	PRECAUTIONS General Cases of hypersensitivity reactions, including anaphylactoid reactions with the first dose, have been reported during postmarketing surveillance…

Dibenzyline (phenoxybenzamine hydrochloride capsules, USP) Prescribing Information	PRECAUTIONS Carcinogenesis and Mutagenesis Case reports of carcinoma in humans after long-term treatment with phenoxybenzamine have been reported. Hence long-term use of phenoxybenzamine is not recommended. Carefully weigh the benefits and risks before prescribing this drug...

Fiorinal with Codeine (butalbital, aspirin, caffeine, and codeine phosphate) Capsules Prescribing Information	PRECAUTIONS Ultra-rapid Metabolizers of Codeine

Maxitrol (neomycin and polymyxin B sulfates and dexamethasone ophthalmic suspension) Prescribing Information	PRECAUTIONS Geriatric Use (new subsection)

Pilopine HS (pilocarpine hydrochloride ophthalmic gel) 4% Prescribing Information	PRECAUTIONS Geriatric Use

Propranolol Hydrochloride Injection, USP Prescribing Information	PRECAUTIONS General ...Withdrawal may lead to a return of elevated intraocular pressure.

Pulmicort Flexhaler (budesonide inhalation powder) For Oral Inhalation Only Prescribing Information Patient Package Insert	PRECAUTIONS General Initial Paragraph Pulmicort Flexhaler contains small amounts of lactose... Information for Patients ADVERSE REACTIONS Adverse Event Reports from Other Sources Postmarketing Experience PATIENT PACKAGE INSERT Before Using Your Pulmicort Flexhaler What are the ingredients in Pulmicort Flexhaler?

Synthroid (levothyroxine sodium tablets, USP) Prescribing Information	PRECAUTIONS Information for Patients Agents such as iron and calcium supplements and antacids can decrease the absorption of levothyroxine sodium tablets. Therefore, levothyroxine sodium tablets should not be administered within 4 hours of these agents.

Tenormin (atenolol) Tablets Prescribing Information	PRECAUTIONS Drug Interactions Disopyramide is a Type I antiarrhythmic drug with potent negative inotropic and chronotropic effects... Amiodarone is an antiarrhythmic agent with negative chronotropic properties that may be additive to those seen with beta blockers... Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate...

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Brand (Generic) Name	Sections Modified
Copegus (ribavirin, USP) Tablets Prescribing Information	ADVERSE REACTIONS Postmarketing Experience Dehydration

Enablex (darifenacin) Extended-Release Tablets Prescribing Information	ADVERSE REACTIONS Postmarketing Experience (new subsection)

Flomax (tamsulosin hydrochloride) Capsules Prescribing Information	ADVERSE REACTIONS Postmarketing Experience Respiratory Symptoms

Lexiva (fosamprenavir calcium) Tablets and Oral Suspension Prescribing Information (in new labeling format) Patient Package Insert	ADVERSE REACTIONS Postmarketing Experience Skin and Subcutaneous Tissue Disorders Angioedema PATIENT PACKAGE INSERT What are the possible side effects of Lexiva? ...Swelling of the face, lips, and tongue (angioedema) has also been reported. Tell your healthcare provider if you get a rash or develop facial swelling after starting Lexiva.

Navane (thiothixene) Capsules Navane (thiothixene hydrochloride) Concentrate Prescribing Information	ADVERSE REACTIONS Extrapyramidal Symptoms Dystonia, Class Effect (new subsection)

RotaTeq (rotavirus vaccine, live, oral, pentavalent) Oral Solution Prescribing Information (in new labeling format) Patient Package Insert	ADVERSE REACTIONS Postmarketing Experience Gastrointestinal Disorders Intussusception (including death) PATIENT COUNSELING INFORMATION PATIENT PACKAGE INSERT What other important information should I know? ...Death due to intussusception has also occurred...

Singulair (montelukast sodium) Granule Singulair (montelukast sodium) Tablet, Chewable Singulair (montelukast sodium) Tablet, Film Coated Prescribing Information Patient Package Insert See MedWatch Safety Alert posted 03/27/2008 for additional information on Singulair	ADVERSE REACTIONS Postmarketing Experience Psychiatric Disorders Anxiousness Suicidal thinking and behavior (including suicide) PATIENT PACKAGE INSERT Less common side effects that have happened with Singulair include: Behavior and Mood related changes Feeling anxious Suicidal thoughts and actions (including suicide)...

Theophylline in 5% Dextrose Injections, USP Prescribing Information	ADVERSE REACTIONS ...Hypercalcemia has been reported in a patient with hyperthyroid disease at therapeutic theophylline concentrations.

Zerit (stavudine) Capsules Zerit (stavudine) for Oral Solution Prescribing Information Patient Package Insert	ADVERSE REACTIONS Observed During Clinical Practice Metabolic Disorders Diabetes Mellitus and Hyperglycemia PATIENT PACKAGE INSERT What are the possible side effects of Zerit? Other Side Effects ...high blood sugar (hyperglycemia or diabetes)...

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NuvaRing (etonogestrel/ethinyl estradiol vaginal ring)

Patient Package Insert

Prescribing Information

PATIENT PACKAGE INSERT

How do I insert NuvaRing?
How do I remove NuvaRing?
Call your healthcare provider right away if you get any of the symptoms listed below...

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