MedWatch - March 2009 Safety-Related Drug Labeling Changes

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Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) -- March 2009

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
Epzicom (abacavir sulfate and lamivudine) Tablets Prescribing Information and Medication Guide	BOXED WARNING CONTRAINDICATIONS WARNINGS PRECAUTIONS Myocardial Infarction In a published...the use of abacavir within the previous 6 months was correlated with an increased risk of myocardial infarction (MI)... MEDICATION GUIDE revised to include information related to myocardial infarction	BOXED WARNING Patients who carry the HLA-B5701 allele are at high risk for experiencing a hypersensitvity reaction to abacavir. Prior to initiating therapy ..... Regardless of HLA-B5701 status permanently discontinue Epzicom if hypersensitivity cannot be ruled out... Following a hypersensitivity reaction to abacavir, NEVER restart Epzicom... severe symptoms can occur within hours ..... Reintroduction of Epzicom or any other abacavir-containing product...can result in serious or fatal ..... CONTRAINDICATIONS Never restart Epzicom or any other abacavir-containing product following a hypersensitivity reaction to abacavir, regardless of HLA-B5701 status.... WARNINGS* ...Patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction to abacavir...

OsmoPrep (sodium phosphate monobasic monohydrate, USP and sodium phosphate dibasic anhydrous, USP) Tablets Prescribing Information and Medication Guide See MedWatch Safety Alert posted 12/11/2008 for additional information on OsmoPrep labeling revisions.	BOXED WARNING New ADVERSE REACTIONS Postmarketing Experience General Added (tongue) ..swelling of the lips and tongue.. Cardiovascular: Arrhythmias Nervous system: Seizures Renal acute phosphate nephropathy added MEDICATION GUIDE New	BOXED WARNING There have been rare, but serious reports of acute phosphate nephropathy in patients who received oral sodium phosphate products for colon cleansing prior to colonoscopy. Some cases have resulted in permanent impairment of renal function and some patients required long-term dialysis. While some cases have occurred in patients without identifiable risk factors, patients at increased risk of acute phosphate nephropathy may include ....

Raptiva (efalizumab) Prescribing Information and Medication Guide See MedWatch Safety Alert posted 01/19/2009 for additional information on Raptiva labeling revisions.	BOXED WARNING CONTRAINDICATIONS WARNINGS Progressive Multifocal Leukoencephalopathy (PML) PRECAUTIONS Information for Patients Healthcare providers should counsel patients about the risks and benefits of Raptiva... ADVERSE REACTIONS The most serious adverse reactions observed during treatment with Raptiva are serious infections, including PML... In postmarketing experience, serious bacterial, viral, fungal, and opportunistic infections have occurred, including JC virus infection resulting in PML... MEDICATION GUIDE Conversion of the Patient Package Insert to a Medication Guide	BOXED WARNING Warning: Risk of Progressive Mutifocal Leukoencephalopathy (PML) Raptiva increases the risk for PML, a rapidly progressive viral infection of the central nervous system that... Patients on Raptiva should be monitored frequently... Raptiva dosing should be withheld immediately at the first sign or symptom suggestive of PML... CONTRAINDICATIONS should not be administered to patients who have been diagnosed with PML WARNINGS Progressive Multifocal Leukoencephalopathy (PML) PML is a rapidly progressive infection of the central nervous system caused by the JC virus that leads to death or severe disability. Raptiva increases the risk for PML and this risk may markedly increase with longer duration ..... Post-marketing cases... The effect of intermittent use of Raptiva... Healthcare providers treating patients with Raptiva should consider...

Sporanox (itraconazole) Oral Solution, 10 mg/mL Prescribing Information	BOXED WARNING Drug Interactions CONTRAINDICATIONS Congestive Heart Failure Drug Interactions WARNINGS Cardiac Dysrhythmias Cardiac Disease Treatment of Severely Neutropenic Patients PRECAUTIONS Hearing Loss Transient or permanent hearing loss has been reported ..... Information for Patients Instruct patients that hearing loss can occur... Drug Interactions Table additions ...disopyramide..(including nisoldipine)..levacetylmethadol (levomethadyl), ergot alkaloids, halofantrine..budesonide, dexamethasone, fluticasone..warfarin, cilostazol, eletriptan, fentanyl... Antiarrhythmics The class IA antiarrhythmic disopyramide has the potential to increase the QT interval... ...via inhibition of P glycoprotein. Calcium Channel Blockers ...due to an increased risk of CHF. Concomitant administration of Sporanox and nisoldipine results in... Other Levacetylmethadol (levomethadyl) is known to prolong the QT... Elevated concentrations of ergot alkaloids can cause ergotism... Halofantrine has the potential to prolong the QT interval... Sporanox may..."glucocorticosteroids such as budesonide, dexamethasone, fluticasone and"... Cilostazol and eletriptan are CYP3A4 metabolized... Fentanyl plasma concentrations could... Pregnancy:Teratogenic Effects, Pregnancy Category C During post-marketing experience, cases of congenital abnormalities have been reported. Geriatric Use (new section) Renal Impairment (new section) Hepatic Impairment (new section) ADVERSE REACTIONS Postmarketing Experience Revised and table updated Transient or permanent hearing loss	BOXED WARNING Drug Interactions Coadministration of "levacetylmethadol (levomethadyl)" addition ..sudden death have occurred in patients using "levacetylmethadol (levomethadyl)"... CONTRAINDICATIONS Congestive Heart Failure (new section) Drug Interactions nisoldipine levacetylmethadol (levomethadyl) Ergot alkaloids metabolized... WARNINGS Cardiac Dysrhythmias levacetylmethadol (levomethadyl) Cardiac Disease Itraconazole has been shown to have a negative inotropic effect. Sporanox has been associated with reports of congestive heart failure. In post-marketing... Calcium channel blockers can have negative inotropic effects Treatment of Severely Neutropenic Patients (new section)

Trizivir (abacavir sulfate, lamivudine, and zidovudine) Tablets Prescribing Information	BOXED WARNING CONTRAINDICATIONS WARNINGS Hypersensitivity Reaction PRECAUTIONS Myocardial Infarction MEDICATION GUIDE Observed During Clinical Practice Cardiovascular: Myocardial infarction.	BOXED WARNING Patients who carry the HLA-B5701 allele are at high risk for experiencing a hypersensitvity reaction to abacavir... CONTRAINDICATIONS* Trizivir tablets are contraindicated in patients with previously demonstrated hypersensitivity to abacavir or to any other component of the product... Never restart Trizivir or any other abacavir-containing product... WARNINGS Hypersensitivity Reaction Serious and sometimes fatal hypersensitivity reactions have been associated with Trizivir... HLA-B*5701-negative patients may develop a hypersensitivity reaction to abacavir...

Visicol Tablets (sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Prescribing Information and Medication Guide See MedWatch Safety Alert posted 12/11/2008 for additional information on Visicol labeling revisions.	BOXED WARNING New ADVERSE REACTIONS Postmarketing Experience Rewritten to match OsmoPrep format MEDICATION GUIDE New Medication Guide	BOXED WARNING There have been rare, but serious reports of acute phosphate nephropathy in patients who received oral sodium phosphate products for colon cleansing prior to colonoscopy. Some cases have resulted in permanent impairment of renal function and some patients required long-term dialysis. While some cases have occurred in patients without identifiable risk factors, patients at increased risk of acute phosphate nephropathy may include ...

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Diabeta (glyburide) Tablets Prescribing Information	CONTRAINDICATIONS PRECAUTIONS Hemolytic anemia There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction Drug Interactions Clarithromycin (hypoglycemic action of sulfonylureas may be potentiated) bosentan and cyclosporine	CONTRAINDICATIONS hypersensitivity to any of the drug’s excipients and patients treated with bosentan

Macrobid (nitrofurantoin monohydrate/macrocrystals) Capsules, 100 mg Prescribing Information	CONTRAINDICATIONS WARNINGS	CONTRAINDICATIONS Macrodantin is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin. WARNINGS Added subheadings for readability of the following reactions: Pulmonary reactions Hepatoxicity Neuropathy Hemolytic anemia Clostridium difficile-associated diarrhea

Macrodantin (nitrofurantoin monohydrate/macrocrystals) Capsules, 25, 50 and 100 mg Prescribing Information	CONTRAINDICATIONS WARNINGS	CONTRAINDICATIONS Macrodantin is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin. WARNINGS Added subheadings for readability of the following reactions: Pulmonary reactions Hepatoxicity Neuropathy Hemolytic anemia Clostridium difficile-associated diarrhea

Rocephin (ceftriaxone sodium) for injection, 250 mg, 500 mg, 1 g and 2 g Prescribing Information	CONTRAINDICATIONS Neonates WARNINGS Interaction with Calcium-Containing Products ADVERSE REACTIONS Postmarketing Experience A small number of cases of fatal outcomes in which a crystalline material was observed in the lungs and kidneys at autopsy have been reported...	CONTRAINDICATIONS Neonates (section edited) Rocephin is contraindicated in neonates if they require... A small number of cases of fatal outcomes in which a crystalline material was observed in the lungs and kidneys at autopsy... WARNINGS Interaction with Calcium-Containing Products Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute Rocephin vials...

Sporanox (itraconazole) Capsules, 100 mg Prescribing Information and Patient Package Insert	CONTRAINDICATIONS Drug Interactions WARNINGS Cardiac Disease PRECAUTIONS Hearing Loss Transient or permanent hearing loss has been reported ..... Information for Patients Instruct patients that hearing loss can occur... Antiarrhythmics Concomitant administration of digoxin...added "via inhibition of P-glycoprotein" Drug Interactions/Calcium Channel Blockers added...due to an increased risk of CHF. Concomitant administration of Sporanox and nisoldipine results in... Drug Interactions/Other fluticasone Fentanyl plasma concentrations could be increased or prolonged by concomitant use of Sporanox and may cause potentially fatal respiratory depression Geriatric Use Transient or permanent hearing loss has been reported... Renal Impairment (new) Hepatic Impairment (new) ADVERSE REACTIONS Post-marketing Experience (replaced with table) Adverse drug reactions that have been identified during post-approval use of Sporanox (all formulations) are listed ... PATIENT PACKAGE INSERT Who Should Not Take Sporanox and What Are The Possible Side Effects Of Sporanox section	CONTRAINDICATIONS Drug Interactions nisoldipine WARNINGS Cardiac Disease Sporanox has been associated with reports of congestive heart failure. In post-marketing... Calcium channel blockers can have negative inotropic effects

Sporanox (itraconazole) Injection, 10 mg/mL Prescribing Information	CONTRAINDICATIONS Drug Interactions WARNINGS Cardiac Disease PRECAUTIONS Hearing Loss Transient or permanent hearing loss has been reported ... Information for Patients Instruct patients that hearing loss can occur... Antiarrhythmics Concomitant administration of digoxin...added "via inhibition of P-glycoprotein" Drug Interactions/Calcium Channel Blockers added...due to an increased risk of CHF. Concomitant administration of Sporanox and nisoldipine results in... Drug Interactions/Other fluticasone Fentanyl plasma concentrations could be increased or prolonged by concomitant use of Sporanox and may cause potentially fatal respiratory depression Geriatric Use Transient or permanent hearing loss has been reported... Renal Impairment (new) Hepatic Impairment (new) ADVERSE REACTIONS Post-marketing Experience (replaced with table) Adverse drug reactions that have been identified during post-approval use of Sporanox (all formulations) are listed... PATIENT PACKAGE INSERT Who Should Not Take Sporanox and What Are The Possible Side Effects Of Sporanox section	CONTRAINDICATIONS Drug Interactions nisoldipine Sporanox IV cannot be used when administration of Sodium Chloride Injection is contraindicated. WARNINGS Cardiac Disease Itraconazole has been shown to have a negative inotropic effect. Sporanox has been associated with reports of congestive heart failure. In post-marketing... Calcium channel blockers can have negative inotropic effects

Theophylline in 5% Dextrose injection, USP, Flexible Plastic Container Prescribing Information	CONTRAINDICATIONS WARNINGS When Signs and Symptoms of Theophylline Toxicity are Present PRECAUTIONS Monitoring Serum Theophylline Concentrations "Saliva concentrations of theophylline cannot be used reliably to adjust dosage without special techniques... Clinical evaluation and periodic laboratory determinations are necessary to monitor changes... ..Do not use plastic container in series connection... ..These solutions are intended for intravenous administration... ..Use only if solution is clear and container and seals are intact. ADVERSE REACTIONS Hypercalcemia has been reported in a patient with hyperthyroid disease at therapeutic theophylline concentrations. “Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia.	CONTRAINDICATIONS Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products WARNINGS When Signs and Symptoms of Theophylline Toxicity are Present “Solutions containing dextrose without electrolytes should not be administered simultaneously with blood through the same infusion set... ...Because dosages of these drugs are titrated to response, no additives should be made to Theophylline in 5% Dextrose Injection USP."

Tracleer (bosentan) 62.5 and 125 mg Tablets Prescribing Information and Medication Guide	CONTRAINDICATIONS Lopinavir/ritonavir or other ritonavir-containing HIV regimens PRECAUTIONS Drug Interactions (section reworded) Bosentan is metabolized by CYP2C9 and CYP3A4. Inhibition of these enzymes may increase the plasma concentration of bosentan... Lopinavir/ritonavir or other ritonavir-containing HIV regimens Co-administration of Tracleer in healthy subjects resulted in initial and steady... MEDICATION GUIDE Do not take Tracleer if... lopinavir/ritonavir or other ritonavir-containing HIV regimens Tell your doctor about all the medicines you use.. lopinavir/ritonavir or other ritonavir-containing HIV regimens What should I avoid.. Do not take cyclosporine-A...increase your chance of side effects Do not take lopinavir/ritonavir or other ritonavir-containing HIV regimens	CONTRAINDICATIONS Lopinavir/ritonavir or other ritonavir-containing HIV regimens Co-administration of lopinavir/ritonavir and bosentan resulted in markedly increased plasma concentrations of bosentan.Therefore, concomitant use of Tracleer and lopinavir/ritonavir or other ritonavir-containing HIV regimens is contraindicated...

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Advair Diskus (fluticasone propionate and salmeterol xinafoate inhalation powder) The latest label (3/31/2009) is not available on this site	WARNINGS AND PRECAUTIONS Reduction in Bone Mineral Density	WARNINGS and PRECAUTIONS Reduction in Bone Mineral Density 2-Year Fluticasone Propionate Study 3-Year Bone Mineral Density Study 3-Year Survival Study

Altace (ramipril) 1.25, 2.5, 5, and 10 Capsules Altace (ramipril) 1.25, 2.5, 5 and 10 mg Tablets The latest label (approved 03/04/2009) is not available on this site	WARNINGS Fetal/Neonatal Morbidity and Mortality PRECAUTIONS Information for Patients/Pregnancy Female patients of childbearing age should be told about the consequences of exposure to ACE inhibitors during pregnancy. These patients should be asked to report pregnancies to their physicians as soon as possible.	WARNINGS Fetal/Neonatal Morbidity and Mortality In a published retrospective epidemiological study, infants whose mothers had taken an ACE inhibitor during their first trimester of pregnancy appeared to have an increased risk of major congenital malformations...findings of this study have not yet been confirmed.

Axert (almotriptan malate) Tablets 6.25 and 12.5 mg Prescribing Information	WARNINGS Serotonin Syndrome PRECAUTIONS Drug Interactions Selective Serotonin Reuptake Inhibitors/Serotonin Norephinephrine Reuptake Inhibitors and Serotonin Syndrome Information for Patients separate leaflet provided for patients Patients should be cautioned about the risk of serotonin syndrome... ADVERSE REACTIONS Postmarketing Experience Includes reports of seizure in close temporal association with triptan use PATIENT PACKAGE INSERT Includes information concerning serotonin syndrome with concomitant use of triptans and SSRIs/SNRIs	WARNINGS Serotonin Syndrome

Cymbalta (duloxetine hydrochloride) Delayed- Release Capsules 20, 30 and 60 mg Prescribing Information	WARNINGS AND PRECAUTIONS Discontinuation of Treatment with Cymbalta ADVERSE REACTIONS Other Adverse Reactions observed during the premarketing and postmarketing clinical trial evaluation of Duloxetine Ear and Labyrinth Disorders ... and tinnitus General Disorders and Administration Site Conditions ... gait disturbance Nervous System Disorders ...and poor quality sleep Renal and Urinary Disorders polyuria Reproductive System and Breast Disorders ...and sexual dysfunction Skin and Subcutaneous Tissue Disorders dermatitis contact Postmarketing Spontaneous Reports aggression and anger (particularly early in treatment or after treatment discontinuation) gynecological bleeding muscle spasm restless legs syndrome, seizures upon treatment discontinuation tinnitus (upon treatment discontinuation) MEDICATION GUIDE Toll free number	WARNINGS and PRECAUTIONS Discontinuation of Treatment with Cymbalta words "tapered" and "fatigue" inserted in the section

Frova (frovatriptan succinate) Tablets 2.5 mg Prescribing Information	WARNINGS AND PRECAUTIONS ADVERSE REACTIONS Postmarketing Experience reports of seizure in close temporal association with triptan use PATIENT PACKAGE INSERT information concerning serotonin syndrome with concomitant use of triptans and SSRIs/SNRIs	WARNINGS AND PRECAUTIONS Includes information concerning serotonin syndrome with concomitant use of triptans and SSRIs/SNRIs

Lexiscan (regadenoson) Injection Prescribing Information	WARNINGS AND PRECAUTIONS ADVERSE REACTIONS (6.1) Clinical Trials Experience (6.2) Post Marketing Experience Cardiovascular Gastrointestinal Musculoskeletal Respiratory	WARNINGS AND PRECAUTIONS Sinoatrial and Atrioventricular Nodal Block In postmarketing experience, third degree heart block and asystole within minutes of Lexiscan administration have occurred Hypotension In postmarketing experience, syncope and transient ischemic attacks have been observed

Spiriva HandiHaler inhalation powder Prescribing Information and New Patient Package Insert	WARNINGS ADVERSE REACTIONS added "(new onset or worsening)" to glaucoma PATIENT PACKAGE INSERT New	WARNINGS section updated symptoms of angioedema: (including swelling of the lips, tongue or throat), itching, and rash

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Brand (Generic) Name	Sections Modified
NegGram (nalidixic acid) Caplets Prescribing Information	PRECAUTIONS General subsection text modified Caution should be used in patients with renal insufficiency (term "severe" & "failure" removed) and subsequent sentence removed

Novothyrox (levothyroxine sodium) Tablets Prescribing Information	PRECAUTIONS agents such as iron and calcium supplements and antacids can decrease the absorption of levothyroxine tablets instructions for reporting side effects to FDA drug-drug interaction between levothyroxine and orlistat

Tarka (trandolopril/verapamil hydrochloride) 2/180, 1/240, 2/240, 4/240 mg ER Tablets The latest label (approved 3/5/2009) is not available on this site	PRECAUTIONS Drug Interactions (the following interactions have been added): Clarithromycin Hypotension, bradyarrhythmias, and lactic acidosis have been observed in patients receiving concurrent clarithromycin. Erythromycin Hypotension, bradyarrhythmias, and lactic acidosis have been observed in patients receiving concurrent erythromycin ethylsuccinate. Gold Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including Tarka.

Zithromax (azithromcyin) for Oral Suspension, 200 mg, 500 mg, Single Dose Packet, 600 mg, IV Prescribing Information	PRECAUTIONS General Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving azithromycin therapy. Precautions -Drug Interactions Although, in a study of 22 healthy men, a 5-day course of azithromycin did not affect the prothrombin time from a subsequently administered dose of warfarin, spontaneous post-marketing reports suggest that concomitant administration of azithromycin may potentiate the effects of oral anticoagulants. Prothrombin times should be carefully monitored while patients are receiving azithromycin and oral anticoagulants concomitantly.

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Brand (Generic) Name	Sections Modified
Clinoril (sulindac) Tablets Prescribing Information	ADVERSE REACTIONS Hypersensitivity Reactions

Cosmegen (dactinomycin) for Injection Prescribing Information	ADVERSE REACTIONS Hematologic Section addition of neutropenia and febrile neutropenia

Crestor (rosuvastatin calcium) Tablets Prescribing Information	ADVERSE REACTIONS Postmarketing Experience hepatic failure

Demerol (meperidine hydrochloride) Tablets and Oral Solution Prescribing Information	ADVERSE REACTIONS Hypersensitivity reactions including anaphylaxis

Eloxatin (oxaliplatin) powder for solution for intravenous use Eloxatin (oxaliplatin) concentrate for solution for intravenous use Prescribing Information	ADVERSE REACTIONS Postmarketing Experience after other interstitial lung diseases added "sometimes fatal" transient vision loss (reversible following therapy discontinuation) Information for Patients Updated ... vision abnormalities that may affect patients’ ability to drive and use machines.

Lipitor (atorvastatin calcium) Tablets Prescribing Information	ADVERSE REACTIONS Postintroduction Reports hepatic failure

Niaspan (niacin extended release) tablet The latest label (approved 03/26/2009) is not available on this site	ADVERSE REACTIONS Post-marketing adverse event blurred vision, hepatitis, myopathy, creatine kinase increase, and skin discoloration

Vancocin Hcl (vancomycin for injection, USP) 500 mg/100mL and 1g/200mL Prescribing Information	ADVERSE REACTIONS Post Marketing Reports Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)

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Brand (Generic) Name	Sections Modified
Dalmane (flurazepam hydrochloride), 15 mg and 30 mg oral Capsules Prescribing Information	MEDICATION GUIDE New Medication Guide

Prozac (fluoxetine hydrochloride) capsules Prescribing Information and Medication Guide	MEDICATION GUIDE

Symbyax (olanzapine/fluoxetine) capsules Prescribing Information and Medication Guide	MEDICATION GUIDE New Medication Guide

Synagis (palivizumab) Patient Package Insert	PATIENT PACKAGE INSERT New PPI

Zyprexa (olanzapine) Tablet Zyprexa Zydis (olanzapine) Tablet, Orally Disintegrating Prescribing Information and Medication Guide	MEDICATION GUIDE New Medication Guide

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