MedWatch - November 2007 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 2007

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
Abilify (aripiprazole) Tablets Abilify Discmelt (aripiprazole) Orally Disintegrating Tablets Abilify (aripiprazole) Oral Solution Abilify (aripiprazole) Injection For Intramuscular Use Only Prescribing Information (in new labeling format) Medication Guide	BOXED WARNING WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS WARNINGS & PRECAUTIONS Clinical Worsening and Suicide Risk Suicide ADVERSE REACTIONS Overall Adverse Event Profile Clinical Studies Experience Adult Patients Receiving Abilify as Adjunctive Treatment of Major Depressive Disorde Table 8 PATIENT COUNSELING INFORMATION Clinical Worsening and Suicide Risk MEDICATION GUIDE Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions	BOXED WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of adjunctive Abilify or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Abilify is not approved for use in pediatric patients with depression [see WARNINGS AND PRECAUTIONS (5.2)]. WARNINGS & PRECAUTIONS See highlighted prescribing information for new text.

Aranesp (darbepoetin alfa) For Injection Prescribing Information Patient Package Insert: Single-use Prefilled SureClick Autoinjector Patient Package Insert: Single-dose Vial/Single-dose Prefilled Syringe (SingleJet)	BOXED WARNING WARNINGS: Increased Mortality, Serious Cardiovascular and Thromboembolic Events, and Tumor Progression Renal Failure Cancer WARNINGS Increased Mortality, Serious Cardiovascular and Thromboembolic Events Initial Section Increased Mortality and/or Tumor Progression Initial Section Table 1 Decreased Overall Survival Decreased Locoregional Progression-Free Survival and Overall Survival Decreased Locoregional Control PATIENT PACKAGE INSERT Single-dose Vial/Single-dose Prefilled Syringe (SingleJect) Single-use Prefilled SureClick Autoinjector	BOXED WARNING WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR and THROMBOEMBOLIC EVENTS, and TUMOR PROGRESSION Renal failure: Patients experienced greater risks for death and serious cardiovascular events when administered erythropoiesis-stimulating agents (ESAs) to target higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies. Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL. Cancer: ESAs shortened overall survival and/or time-to-tumor progression in clinical studies in patients with advanced breast, head and neck, lymphoid, and non-small cell lung malignancies when dosed to target a hemoglobin of ≥ 12 g/dL. The risks of shortened survival and tumor progression have not been excluded when ESAs are dosed to target a hemoglobin of < 12 g/dL. To minimize these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusions. Use only for treatment of anemia due to concomitant myelosuppressive chemotherapy. Discontinue following the completion of a chemotherapy course... WARNINGS See highlighted prescribing information for revised text.

Avandia (rosiglitazone maleate) Tablets Prescribing Information (in new labeling format) Patient Package Insert For the most recent safety information on Avandia, see the MedWatch Safety Alert posted 2/26/2008 which includes a Medication Guide.	BOXED WARNING: CONGESTIVE HEART FAILURE AND MYOCARDIAL ISCHEMIA WARNINGS & PRECAUTIONS Cardiac Failure Myocardial Ischemia Meta-Analysis of Myocardial Ischemia in a Group of 42 Clinical Trials Figure 1 Myocardial Ischemic Events in Large Long-Term Prospective Randomized Controlled Trials of Avandia Figure 2 Congestive Heart Failure and Myocardial Ischemia During Coadministration of Avandia with Insulin Table 2 Diabetes and Blood Glucose Control ADVERSE REACTIONS Clinical Trial Experience Pediatric Laboratory Abnormalities Hematologic PATIENT COUNSELING INFORMATION Patient Advice PATIENT PACKAGE INSERT What is the most important information I should know about Avandia? What is Avandia? Who should not take Avandia? What should I tell my doctor before taking Avandia? What should I avoid while taking Avandia? What are the possible side effects of Avandia?	BOXED WARNING: CONGESTIVE HEART FAILURE AND MYOCARDIAL ISCHEMIA ...A meta-analysis of 42 clinical studies (mean duration 6 months; 14,237 total patients), most of which compared Avandia to placebo, showed Avandia to be associated with an increased risk of myocardial ischemic events such as angina or myocardial infarction. Three other studies (mean duration 41 months; 14,067 patients), comparing Avandia to some other approved oral antidiabetic agents or placebo, have not confirmed or excluded this risk. In their entirety, the available data on the risk of myocardial ischemia are inconclusive. WARNINGS & PRECAUTIONS Cardiac Failure ...Patients experiencing acute coronary syndromes have not been studied in controlled clinical trials. In view of the potential for development of heart failure in patients having an acute coronary event, initiation of Avandia is not recommended for patients experiencing an acute coronary event, and discontinuation of Avandia during this acute phase should be considered. Patients with NYHA Class III and IV cardiac status (with or without CHF) have not been studied in controlled clinical trials. Avandia is not recommended in patients with NYHA Class III and IV cardiac status. Myocardia Ischemia See highlighted prescribing information for revised text.

Epogen (epoetin alfa) For Injection Prescribing Information Patient Package Insert	BOXED WARNING (new) WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR and THROMBOEMBOLIC EVENTS, and TUMOR PROGRESSION Renal Failure Cancer Perisurgery WARNINGS Adults Increased Mortality, Serious Cardiovascular and Thromboembolic Events Increased Mortality and/or Tumor Progression Table 1 Chronic Renal Failure Patients Hypertension ...the dose of Epogen should be carefully adjusted to achieve and maintain hemoglobin levels between 10-12 g/dl... Zidovudine-treated HIV-infected Patients PRECAUTIONS Information for Patients PATIENT PACKAGE INSERT (revised)	BOXED WARNING (new) See highlighted prescribing information for new text. WARNINGS See highlighted prescribing information for revised/new text.

Myfortic (mycophenolic acid) Delayed-Release Tablets as mycophenolate sodium Prescribing Information	BOXED WARNING WARNINGS Pregnancy: Teratogenic Effects: Pregnancy Category D (new) Pregnancy Exposure Prevention (new) PRECAUTIONS Information for Patients Pregnancy Teratogenic Effects: Pregnancy Category D. See WARNINGS section.	BOXED WARNING Immunosuppression may lead to increased susceptibility to infection and possible development of lymphoma and other neoplasms... Female users of childbearing potential must use contraception. Use of Myfortic during pregnancy is associated with increased risks of pregnancy loss and congenital malformations. WARNINGS: Teratogenic Effects: Pregnancy Category D Mycophenolate mofetil (MMF) can cause fetal harm when administered to a pregnant woman... WARNINGS: Pregnancy Exposure Prevention Women of childbearing potential should have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 1 week prior to beginning therapy. Myfortic therapy should not be initiated until a negative pregnancy test report is obtained. Women of childbearing potential (including pubertal girls and peri-menopausal women) taking Myfortic must receive contraceptive counseling and use effective contraception...

Optison (Perflutren Protein-Type A Microspheres Injectable Suspension, USP) Prescribing Information	BOXED WARNING (new) WARNING: Serious Cardiopulmonary Reactions CONTRAINDICATIONS WARNINGS Serious Cardiopulmonary Reactions Anaphylactoid Reactions Systemic Embolization of Optison in Patients with Cardiac Shunts High Ultrasound Mechanical Index PRECAUTIONS Information for Patients	BOXED WARNING (new) Serious cardiopulmonary reactions, including fatalities, have occurred during or within 30 minutes following perflutren-containing microsphere administration. Assess all patients for the presence of any of the conditions that preclude Optison administration... Monitor patients during and for 30 minutes following Optison administration, including vital sign measurements and electrocardiography in all patients and cutaneous oxygen saturation in patients at risk for hypoxemia. Always have resuscitation equipment and trained personnel readily available (see WARNINGS). CONTRAINDICATIONS Do not administer Optison to patients with known or suspected: Right-to-Ieft, bi-directional, or transient right-to-left cardiac shunts, Worsening or clinically unstable congestive hear failure, Acute myocardial infarction or acute coronary syndromes, Serious ventricular arrhythmias or high risk for arrhythmias due to prolongation of the QT interval, Respiratory failure, as manifest by signs or symptoms of carbon dioxide retention or hypoxemia, Severe emphysema, pulmonary emboli or other conditions that cause pulmonary hypertension due to compromised pulmonary arterial vasculature, Hypersensitivity to perflutren, blood, blood products or albumin (see WARNINGS). Do not administer Optison by intra-arterial injection. WARNINGS See highlighted prescribing information for revised text.

Sarafem (fluoxetine hydrochloride tablets) Prescribing Information Medication Guide	BOXED WARNING Suicidality and Antidepressant Drugs WARNINGS Clinical Worsening and Suicide Risk Table 2 PRECAUTIONS Hyponatremia MEDICATION GUIDE (revised) Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions	BOXED WARNING: Suicidality and Antidepressant Drugs Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of Sarafem or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Sarafem is not approved for use in pediatric patients... WARNINGS See highlighted prescribing information for revised text.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Crestor (rosuvastatin calcium) Tablets Prescribing Information (in new labeling format)	CONTRAINDICATIONS WARNINGS & PRECAUTIONS Liver Enzyme Abnormalities and Monitoring ADVERSE REACTIONS Initial Section Clinical Studies Experience Table 1 Table 2 Postmarketing Experience Arthralgia Hepatitis Jaundice DRUG INTERACTIONS Cyclosporine Gemfibrozil Lopinavir/Ritonavir Niacin USE IN SPECIFIC POPULATIONS Pregnancy Nursing Mothers Pediatric Use Geriatric Use Hepatic Impairment Asian Patients PATIENT COUNSELING INFORMATION Pregnancy Liver Enzymes	CONTRAINDICATIONS ...Hypersensitivity reactions including rash, pruritus, urticaria and angioedema have been reported with Crestor [see Adverse Reactions, (6.1)]. ...Because another drug in this class passes into breast milk, and because HMG-CoA reductase inhibitors have the potential to cause serious adverse reactions in nursing infants, women who require Crestor treatment should be advised not to nurse their infants [see Use in Specific Populations, (8.3)]. WARNINGS & PRECAUTIONS Liver Enzyme Abnormalities and Monitoring ...In a pooled analysis of placebo-controlled trials, increases in serum transaminases to >3 times the upper limit of normal occurred in 1.1% of patients taking Crestor versus 0.5% of patients treated with placebo...

Cymbalta (duloxetine hydrochloride) Delayed-Release Capsules Prescribing Information (in new labeling format)	CONTRAINDICATIONS Monoamine Oxidase Inhibitors WARNINGS & PRECAUTIONS Hepatotoxicity Abnormal Bleeding Discontinuation of Treatment with Cymbalta Fatigue (added) ADVERSE REACTIONS Postmarketing Spontaneous Reports Serious skin reactions including Stevens-Johnson Syndrome that have required drug discontinuation and/or hospitalizations...	CONTRAINDICATIONS: Monoamine Oxidase Inhibitors Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of serious, sometimes fatal, drug interactions with serotonergic drugs. These interactions may include hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have recently discontinued serotonin reuptake inhibitors and are then started on an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome...

Kaletra (Iopinavir/ritonavir) Tablets and Solution Prescribing Information and Patient Package Insert (in new labeling format)	CONTRAINDICATIONS Table 3 Antimycobacterial Rifampin Herbal Products HMG-CoA Reductase Inhibitors WARNINGS & PRECAUTIONS Hepatotoxicity ADVERSE REACTIONS Adults - Clinical Trials Experience Initial Section Pediatric Patients - Clinical Trials Experience DRUG INTERACTIONS Table 9 USE IN SPECIFIC POPULATIONS Pediatric Use PATIENT PACKAGE INSERT How should I take Kaletra? Medicines You Should Not Take With Kaletra? Crestor (rosuvastatin)	CONTRAINDICATIONS Co-administration of Kaletra is contraindicated with potent CYP3A inducers where significantly reduced lopinavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance and cross-resistance. These drugs are listed in Table 3... WARNINGS & PRECAUTIONS: Hepatotoxicity ...Appropriate laboratory testing should be conducted prior to initiating therapy with Kaletra and patients should be monitored closely during treatment...

Lac-Hydrin (ammonium lactate) Lotion, 12% Prescribing Information	CONTRAINDICATIONS WARNINGS	CONTRAINDICATIONS Lac-Hydrin Lotion is contraindicated in those patients with a history of hypersensitivity to any of the label ingredients. WARNINGS ...The use of Lac-Hydrin Lotion should be discontinued if hypersensitivity is observed.

Zometa (zoledronic acid) Injection - Concentrate for Intravenous Infusion Prescribing Information (in new labeling format	CONTRAINDICATIONS Hypersensitivity to zoledronic acid or any components of Zometa WARNINGS & PRECAUTIONS Drugs with Same Active Ingredient Reclast Osteonecrosis of the Jaw ADVERSE REACTIONS Clinical Studies Experience Injection Site Reactions Ocular Adverse Events Postmarketing Experience Osteonecrosis of the Jaw Musculoskeletal Pain Ocular Adverse Events Hypersensitivity Reactions Respiratory Bronchoconstriction PATIENT COUNSELING INFORMATION (new)	CONTRAINDICATIONS Hypersensitivity reactions including rare cases of urticaria and angioedema, and very rare cases of anaphylactic reaction/shock have been reported [see Adverse Reactions (6.2)]. WARNINGS & PRECAUTIONS Drugs with Same Active Ingredient Zometa contains the same active ingredient as found in Reclast (zoledronic acid). Patients being treated with Zometa should not be treated with Reclast. Osteonecrosis of the Jaw See highlighted prescribing information for revised text.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Arava (leflunomide) Tablets Prescribing Information	WARNINGS Immunosuppression Potential/Bone Marrow Supression (new subsection)	WARNINGS Arava is not recommended for patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections. In the event that a serious infection occurs, it may be necessary to interrupt therapy with Arava and administer cholestyramine or charcoal (see PRECAUTIONS – General – Need for Drug Elimination)...

Avalide (irbesartan-hydrochlorothiazide) Tablets Prescribing Information (in new labeling format)	WARNINGS & PRECAUTIONS Fetal/Neonatal Morbidity and Mortality ADVERSE REACTIONS Clinical Trials Experience Irbesartan-Hydrochlorothiazide ...Adverse events in Studies V and VI were similar to those described above in Studies I through IV. Initial Therapy Postmarketing Experience DRUG INTERACTIONS Irbesartan USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category D Geriatric Use PATIENT COUNSELING INFORMATION Pregnancy	WARNINGS & PRECAUTIONS: Fetal/Neonatal Morbidity and Mortality Avalide can cause fetal harm when administered to a pregnant woman. If this drug 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 [see Use in Specific Populations (8.1)]...

Celebrex (celecoxib capsules) Prescribing Information	WARNINGS Renal Effects Angiotensin II Receptor Antagonists PRECAUTIONS General The concomitant use of Celebrex with any dose of a non-aspirin NSAID should be avoided. Drug Interactions ACE-inhibitors and Angiotensin II Antagonists ADVERSE REACTIONS The following adverse events occurred in 0.1 - 1.9% of patients regardless of causality. Celebrex (100 - 200 mg BID or 200 mg QD)... Other serious adverse reactions which occur rarely (estimated <0.1%), regardless of causality... Adverse reactions from long-term, placebo-controlled polyp prevention studies... Some adverse reactions occurred in higher percentages of patients than in the arthritis pre-marketing trials (treatment durations up to 12 weeks... The following additional adverse reactions occurred in ≥0.1% and <1% of patients taking Celebrex...	WARNINGS: Renal Effects Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, angiotensin II receptor antagonists, and the elderly...

Eligard (leuprolide acetate for injectable suspension) Prescribing Information	WARNINGS PRECAUTIONS Laboratory Tests ADVERSE REACTIONS Initial Section Table 6 Table 7 General Rigors, weakness, lethargy Gastrointestinal Dyspepsia Musculoskeletal Muscle atrophy, limb pain Psychiatric Insomnia, depression, loss of libido Renal/Urinary Difficulties with urination, pain on urination, scanty urination, bladder spasm, blood in urine, urinary retention, urinary urgency, incontinence, nocturia, nocturia aggravated Reproductive/Urogenital Testicular soreness/pain, breast soreness/tenderness, testicular atrophy, erectile dysfunction, penile disorder, reduced penis size Skin Clamminess, night sweats, sweating increased Vascular Hypertension, hypotension Postmarketing Pituitary Apoplexy ADMINISTRATION PROCEDURE Allow the product to reach room temperature before using. Once mixed, the product must be used within 30 minutes ...	WARNINGS Eligard 7.5 mg 22.5 mg 30 mg, like other LH-RH agonists, causes a transient increase in serum concentrations of testosterone during the first week of treatment. Eligard 45 mg causes a transient increase in serum concentrations of testosterone during the first two weeks of treatment...

Invanz (ertapenem for injection) Prescribing Information	WARNINGS PRECAUTIONS Information for Patients Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued...	WARNINGS Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ertapenem, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of Clostridium difficile. Clostridium difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of Clostridium difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against Clostridium difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of Clostridium difficile, and surgical evaluation should be instituted as clinically indicated.

Motrin IB (200 mg ibuprofen) Tablets Prescribing Information	WARNINGS (on Drug Facts Label) Ask a doctor or pharmacist before use if you are... taking aspirin for heart attack or stroke, because ibuprofen may decrease this benefit of aspirin.	WARNINGS Ask a doctor or pharmacist before use if you are: taking aspirin for heart attack or stroke, because ibuprofen may decrease this benefit of aspirin.

Nexavar (sorafenib) Tablets Prescribing Information (in new labeling format) Patient Package Insert	WARNINGS & PRECAUTIONS Risk of Cardiac Ischemia and/or Infarction Risk of Hemorrhage Risk of Hypertension Risk of Dermatologic Toxicities Interaction with Docetaxel Interaction with Doxorubicin Hepatic Impairment ADVERSE REACTIONS Initial Section Adverse Reactions in HCC Study Table 2 Laboratory Abnormalities USE IN SPECIFIC POPULATIONS Geriatric Use Patients with Hepatic Impairment PATIENT PACKAGE INSERT What is Nexavar? Nexavar is an anticancer medicine used to treat a certain type of liver or kidney cancer called... Hepatocellular carcinoma (HCC, a type of liver cancer)... What should I tell my doctor before starting Nexavar? ...Have liver problems in addition to liver cancer...	WARNINGS & PRECAUTIONS See highlighted prescribing information for revised text. Interaction with Docetaxel Sorafenib can cause increases in plasma concentrations of docetaxel. Caution is recommended when Nexavar is co-administered with docetaxel [see Drug Interactions (7.2)]. Interaction with Doxorubicin Sorafenib can cause increases in plasma concentrations of doxorubicin. Caution is recommended when Nexavar is co-administered with doxorubicin [see Drug Interactions (7.3)]. Hepatic Impairment Hepatic impairment may reduce plasma concentrations of sorafenib. Comparison of data across studies suggests that sorafenib levels are lower in HCC patients than in non-HCC patients (without hepatic impairment). The AUC of sorafenib is similar between HCC patients with mild (Child-Pugh A) and moderate (Child-Pugh B) hepatic impairment. The optimal dose in non-HCC patients with hepatic impairment is not established [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

Sprycel (dasatinib) Tablet For Oral Use Prescribing Information (in new labeling format) Patient Package Insert	WARNINGS & PRECAUTIONS Myelosuppression Bleeding Related Events ...In some trials, the use of anticoagulants, aspirin, and non-steroidal anti-inflammatory drugs (NSAIDs) was allowed concurrently with Sprycel if the platlet count was >50,000... Fluid Retention Pregnancy ...Women should be advised of the potential hazard to the fetus and to avoid becoming pregnant... ADVERSE REACTIONS Clinical Studies Experience Table 2 In a Phase 2 randomized study of chronic phase CML... Table 3 In the Phase 3 dose-optimization study in patients with chronic phase CML... Table 4 Laboratory Abnormalities In the Phase 2 randomized study, the frequency of Grade 3 or 4... Table 5 Additional Data From Clinical Trials DRUG INTERACTIONS Drugs That May Increase Dasatinib Plasma Concentrations CYP3A4 Inhibitors Drugs That May Decrease Dasatinib Plasma Concentrations CYP3A4 Inducers Antacids H2 Antagonists/Proton Pump Inhibitors Drugs That May Have Their Plasma Concentration Altered By Dasatinib CYP3A4 Substrates USE IN SPECIFIC POPULATIONS Nursing Mothers Geriatric Use PATIENT COUNSELING INFORMATION PATIENT PACKAGE INSERT How should I take Sprycel? What are the possible side effects of Sprycel?	WARNINGS & PRECAUTIONS Myelosuppression ...In a Phase 3 dose-optimization study in patients with chronic phase CML, Grade 3 or 4 myelosuppression was reported less frequently in patients treated with 100 mg once daily than in patients treated with 70 mg twice daily... Fluid Retention Sprycel is associated with fluid retention. In all clinical studies, severe fluid retention was reported in 8% of patients, including pleural and pericardial effusion reported in 5% and 1% of patients, respectively. Severe ascites and generalized edema were each reported in <1% of patients... ...In the Phase 3 dose-optimization study in patients with chronic phase CML, fluid retention events were reported less frequently in patients treated with 100 mg once daily than in patients treated with 70 mg twice daily [see Table 4, Adverse Reactions (6.1)].

Toradol (ketorolac tromethamine tablets) Prescribing Information	WARNINGS Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Skin Reactions PRECAUTIONS ACE Inhibitors/Angiotension II Receptor Antagonists Selective Serotonin Reuptake Inhibitors (SSRIs) ADVERSE REACTIONS Other rarely observed reactions (reported from postmarketing experience in patients taking Toradol or other NSAIDs) are: Dermatologic ...bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis Gastrointestinal ...ulcerative stomatitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn's disease)	WARNINGS: Gastroinestinal Effects - Risk of Ulceration, Bleeding, and Perforation NSAIDs should be given with care to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn's disease) as their condition may be exacerbated. WARNINGS: Skin Reactions ...use of the drug should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Vectibix (panitumumab) For Intravenous Use Only Prescribing Information	WARNINGS Increased Toxicity with Combination Chemotherapy (new subsection)	WARNINGS: Increased Toxicity with Combination Chemotherapy Vectibix is not indicated for use in combination with chemotherapy with or without bevacizumab. In an interim analysis of a randomized (1: 1) clinical trial of patients with previously untreated metastatic colorectal cancer, the addition of Vectibix to the combination of bevacizumab and chemotherapy, resulted in decreased progression-free survival (n=947) and increased incidence of NCI-CTC grade 3-5 (87% vs. 72%) adverse reactions (n=926)...

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Brand (Generic) Name	Sections Modified
Atrovent (ipratropium bromide) Nasal Spray Prescribing Information	PRECAUTIONS General Effects Seen with Anticholinergic Drugs Prostatic Hyperplasia

Chantix (varenicline) Tablets Prescribing Information Patient Package Insert For the most recent safety information on varenicline, see the MedWatch Safety Alert posted 2/01/2008.	PRECAUTIONS Information for Patients ...Patients should be advised to use caution driving or operating machinery until they know how quitting smoking with varenicline may affect them. ADVERSE REACTIONS Postmarketing Experience ...Smoking cessation with or without treatment is associated with nicotine withdrawal symptoms and the exacerbation of underlying psychiatric illness. Not all patients had known pre-existing psychiatric illness and not all had discontinued smoking. The role of Chantix in these reports is not known. PATIENT PACKAGE INSERT What are the possible side effects of Chantix? The most common side effects of Chantix include: ...sleep disturbance (trouble sleeping or vivid, unusual, or increased dreaming)... Use caution driving or operatory machinery until you know how quitting smoking with Chantix may affect you.

Colazal (balsalazide disodium) Capsules Prescribing Information (in new labeling format)	DRUG INTERACTIONS In an in vitro study using human liver microsomes, balsalazide and its metabolites [5- aminosalicylic acid (5-ASA), N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA), 4- aminobenzoyl-ß-alanine (4-ABA) and N-acetyl-4-aminobenzoyl- ß –alanine (N-Ac-4- ABA)] were not shown to inhibit the major CYP enzymes evaluated (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5). Therefore, balsalazide and its metabolites are not expected to inhibit the metabolism of other drugs with are substrates of CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP3A4/5. PATIENT COUNSELING INFORMATION What Patients Should Know About Taking Colazal with Other Medication Based upon limited studies conducted in a test tube, Colazal is not believed to interfere with other drugs by preventing how the liver functions. However, as the studies were limited in scope, you should always consult your doctor and discuss potential interactions prior to initiating any new drug.

Cordarone (amiodarone HCl) Tablets Prescribing Information	PRECAUTIONS Drug Interactions HMG-CoA Reductase Inhibitors HMG-CoA reductase inhibitors that are CYP3A4 substrates (including simvastatin and atorvastatin) in combination with amiodarone have been associated with reports of myopathy/rhabdomyolysis.

Emend (aprepitant) Capsules Prescribing Information	PRECAUTIONS General In separate pharmacokinetic studies no clinically significant change in docetaxel or vinorelbine pharmacokinetics was observed when Emend (125 mg/80 mg regimen) was co-administered. Due to the small number of patients in clinical studies who received the CYP3A4 substrates vinblastine, vincristine, or ifosfamide, particular caution and careful monitoring are advised in patients receiving these agents or other chemotherapy agents metabolized primarily by CYP3A4 that were not studied... Drug Interactions Vinorelbine

Foscavir (foscarnet sodium) Injection Prescribing Information	PRECAUTIONS General ...Cases of male and female genital irritation/ulceration have been reported in patients receiving Foscavir... Drug Interactions Since Foscavir decreases serum concentrations of ionized calcium, concurrent treatment with other drugs known to influence serum calcium concentrations should be used with particular caution. Fatalities have been reported in post-marketing surveillance during concomitant therapy with Foscavir and Pentamidine.

Levaquin (levofloxacin) Tablets and Oral Solution Levaquin (levofloxacin) Injection, for Intravenous Use Levaquin (levofloxacin in 5% dextrose) Injection, for Intravenous Use Prescribing Information (in new labeling format)	USE IN SPECIFIC POPULATIONS Geriatric Use In phase 3 clinical trials, 1,945 Levaquin-treated patients (26%) were ≥ 65 years of age. Of these, 1,081 patients (14%) were between the ages of 65 and 74 and 864 patients (12%) were 75 years or older.

Omnaris (ciclesonide) Nasal Spray For Intranasal Use Only Prescribing Information Patient Package Insert	PRECAUTIONS Pediatric Use ADVERSE REACTIONS Pediatric Patients Aged 6 to 11 Years Table 5 Pediatric Patients Aged 2 to 5 Years PATIENT PACKAGE INSERT What you should know about Omnaris Nasal Spray Dosage

Protonix (pantoprazole sodium) Delayed-Release Tablets Protonix (pantoprazole sodium) For Delayed-Release Oral Suspension Prescribing Information	PRECAUTIONS Information for Patients ADVERSE REACTIONS The adverse reaction profile for Protonix (pantoprazole sodium) For Delayed-Release Oral Suspension is similar to the established safety profile of Protonix (pantoprazole sodium) Delayed-Release Tablets...

Zevalin (ibritumomab tiuxetan) Prescribing Information	PRECAUTIONS Extravasation (new subsection) ADVERSE REACTIONS Postmarketing Experience Extravasation Radiation Injury to Adjacent Organs/Tissues

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Brand (Generic) Name	Sections Modified
Benicar HCT (olmesartan medoxomil/hydrochlorothiazide) Tablets Prescribing Information	ADVERSE REACTIONS Postmarketing Experience Metabolic and Nutritional Disorders Hyperkalemia

Diovan (valsartan) Tablets Prescribing Information (in new labeling format) Patient Package Insert	ADVERSE REACTIONS Clinicial Studies Experience Pediatric Hypertension USE IN SPECIFIC POPULATIONS Pediatric Use PATIENT PACKAGE INSERT What is Diovan? How should I take Diovan?

Pepcid (famotidine) Injection Premixed Pepcid (famotidine) Injection Prescribing Information	ADVERSE REACTIONS Nervous System/Psychiatric Convulsions, in patients with impaired renal function, have been reported very rarely. Respiratory Interstitial Pneumonia Skin Stevens-Johnson Syndrome (very rare)

Pepcid (famotidine) Tablets Pepcid (famotidine) Oral Suspension Prescribing Information	ADVERSE REACTIONS Nervous System/Psychiatric Convulsions, in patients with impaired renal function, have been reported very rarely. Respiratory Interstitial Pneumonia Skin Stevens-Johnson Syndrome (very rare)

Pletal (cilostazol) Tablets Prescribing Information	ADVERSE REACTIONS Postmarketing Experience Blood and Lymphatic System Disorders Aplastic Anemia Investigations Blood Pressure Increase

Zocor (simvastatin) Tablets Prescribing Information	ADVERSE REACTIONS Gastrointestinal Hepatic Failure

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Brand (Generic) Name

Sections Modified

Lovaza (omega-3-acid ethyl esters) Capsules*

Patient Package Insert

*Note new tradename to prevent medication errors.

PATIENT PACKAGE INSERT

What is Lovaza?
- ...Before taking Lovaza or other lipid regulating medicines, talk to your healthcare provider about how you can lower high blood fats by...
How should I store Lovaza?
- Do not freeze

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