MedWatch - June 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) -- June 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
Optison (Perflutren Protein -Type A Microspheres Injectable Suspension, USP) Prescribing Information See MedWatch Safety Alert posted 07/17/2008 for additional safety information.	BOXED WARNING WARNING: Serious Cardiopulmonary Reactions WARNINGS Serious Cardiopulmonary Reactions	BOXED WARNING WARNING: Serious Cardiopulmonary Reactions ...In patients with pulmonary hypertension or unstable cardiopulmonary conditions, monitor vital sign measurements, electrocardiography, and cutaneous oxygen saturation during and for at least 30 minutes after Optison administration... WARNINGS Serious Cardiopulmonary Reactions ...The risk for these reactions may be increased among patients with pulmonary hypertension or unstable cardiopulmonary conditions (acute myocardial infarction, acute coronary artery syndromes, worsening or unstable congestive heart failure, serious ventricular arrhythmias or respiratory failure, including patients receiving mechanical ventilation). In these patients, monitor vital signs, electrocardiography, and cutaneous oxygen saturation during and for at least 30 minutes after Optison administration...

Viramune (nevirapine) Tablets and Oral Suspension Prescribing Information (in new labeling format) Medication Guide	BOXED WARNING Skin Reactions Monitoring CONTRAINDICATIONS WARNINGS AND PRECAUTIONS Hepatotoxicity and Hepatic Impairment Skin Reactions Drug Interactions St. John's wort ADVERSE REACTIONS Clinical Trials in Pediatrics DRUG INTERACTIONS Table 4 USE IN SPECIFIC POPULATIONS Pediatric Use Hepatic Impairment PATIENT COUNSELING INFORMATION Hepatotoxicity and Skin Reactions ...Patients should be instructed that if any rash occurs during the two-week lead-in period, the Viramune dose should not be escalated until the rash resolves... MEDICATION GUIDE Who should not take Viramune? Do not take Viramune if you have severe liver problems. How should I take Viramune? ...Therefore, it is important to strictly follow the once daily dose for the first 14 days. If you have a skin rash during the first 14 days immediately contact your doctor and do not increase your dose to Viramune twice a day. The total duration of the once daily lead-in dosing period should not exceed 28 days at which point an alternative regimen may need to be started...	BOXED WARNING Skin Reactions ...Transaminase levels should be checked immediately for all patients who develop a rash in the first 18 weeks of treatment. The 14-day lead-in period with Viramune 200 mg daily dosing has been observed to decrease the incidence of rash and must be followed... Monitoring Patients must be monitored intensively during the first 18 weeks of therapy with Viramune to detect potentially life-threatening hepatotoxicity or skin reactions... CONTRAINDICATIONS Viramune is contraindicated in patients with moderate or severe (Child Pugh Class B or C, respectively) hepatic impairment... WARNINGS AND PRECAUTIONS Hepatotoxicity and Hepatic Impairment ...Transaminases should be checked immediately if a patient experiences signs or symptoms suggestive of hepatitis and/or hypersensitivity reaction. Transaminases should also be checked immediately for all patients who develop a rash in the first 18 weeks of treatment... ...Nevirapine should not be administered to patients with moderate or severe (Child Pugh Class B or C, respectively) hepatic impairment... Skin Reactions ...A patient experiencing a mild to moderate rash without constitutional symptoms during the 14-day lead-in period of 200 mg/day (150 mg/m2/day in pediatric patients) should not have their Viramune dose increased until the rash has resolved. The total duration of the once daily lead-in dosing period should not exceed 28 days at which point an alternative regimen should be sought... Drug Interactions Concomitant use of St. John's wort (Hypericum perforatum) or St. John's wort containing products and Viramune is not recommended. Co-administration of St. John’s wort with non-nucleoside reverse transcriptase inhibitors (NNRTIs), including Viramune, is expected to substantially decrease NNRTI concentrations and may result in sub-optimal levels of Viramune and lead to loss of virologic response and possible resistance to Viramune or to the class of NNRTIs.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Aptivus (tipranavir) Capsules and Oral Solution Prescribing Information (in new labeling format) Patient Package Insert	CONTRAINDICATIONS Drug Interactions Table 1 Sedative/hypnotics WARNINGS AND PRECAUTIONS Effects on Platelet Aggregation and Coagulation Vitamin E Intake Rash ADVERSE REACTIONS Clinical Trials in Pediatric Patients (new subsection) DRUG INTERACTIONS Potential for Aptivus/ritonavir to Affect Other Drugs ...Aptivus oral solution co-administered with ritonavir capsules demonstrated similar effects as Aptivus capsules co-administrated with ritonavir... Potential for Other Drugs to Affect Tipranavir Table 4 Benzodiazepines: Parenterally administered midazolam USE IN SPECIFIC POPULATIONS Pediatric Use PATIENT COUNSELING INFORMATION Use of Vitamin E (new subsection) Administration ...Aptivus can be taken with or without food. PATIENT PACKAGE INSERT Who should not take Aptivus? Do not take Aptivus if you take... Versed (midazolam) orally Tell your healthcare professional... If you are taking Aptivus oral solution, which contains vitamin E, you should not take additional vitamin E... How should I take Aptivus? What are the possible side effects of Aptivus? ...Rash was seen more frequently in children. How should I store Aptivus?	CONTRAINDICATIONS Drug Interactions: Oral midazolam WARNINGS AND PRECAUTIONS Effect on Platelet Aggregation and Coagulation ...In rats, tipranavir treatment alone induced dose-dependent changes in coagulation parameters, bleeding events and death. Co-administration with vitamin E significantly increased these effects [see Nonclinical Toxicology (13.2)]. However, analyses of stored plasma from adult patients treated with Aptivus capsules and pediatric patients treated with Aptivus oral solution (which contains a vitamin E derivative) showed no effect of Aptivus/ritonavir on vitamin K-dependent coagulation factors (Factor II and Factor VII), Factor V, or on prothrombin or activated partial thromboplastin times... Vitamin E Intake Patients taking Aptivus oral solution should be advised not to take supplemental vitamin E greater than a standard multivitamin as Aptivus oral solution contains 116 IU/mL of vitamin E which is higher than the Reference Daily Intake (adults 30 IU, pediatrics approximately 10 IU). Rash ...In the pediatric clinical trial, the frequency of rash (all grades, all causality) through 48 weeks of treatment was 21%. Overall, most of the pediatric patients had mild rash and 5 (5%) had moderate rash. Overall 3% of pediatric patients interrupted Aptivus treatment due to rash and the discontinuation rate for rash in pediatric patients was 0.9%...

Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate) Tablets Prescribing Information (in new labeling format) Patient Package Insert	CONTRAINDICATIONS Contraindicated Drugs Table 1 WARNINGS AND PRECAUTIONS Drug Interactions Nervous System Symptoms ADVERSE REACTIONS Adverse Reactions from Clinical Trials Experience Table 2 Effavirenz Abnormal Dreams Laboratory Abnormalities Table 3 Hepatic Events Postmarketing Experience Tenofovir Disoproxil Fumarate Hepatobiliary Disorders Increased liver enzymes (most commonly AST, ALT, gamma GT)... DRUG INTERACTIONS Emtricitabine and Tenofovir Disoproxil Fumarate Efavirenz Assay Interference Cannabinoid Test Interaction USE IN SPECIFIC POPULATIONS Hepatic Impairment PATIENT COUNSELING INFORMATION Lactic Acidosis/Severe Hepatomegaly with Steatosis Patients Coinfected with HIV-1 and HBV New Onset or Worsening Renal Impairment Decreases in Bone Mineral Density Dosing Instructions PATIENT PACKAGE INSERT Medicines You Should Not Take With Atripla ...Reyataz is not recommended with Atripla...	CONTRAINDICATIONS See Table 1 in prescribing information. WARNINGS AND PRECAUTIONS Drug Interactions Efavirenz plasma concentrations may be altered by substrates, inhibitors, or inducers of CYP3A. Likewise, efavirenz may alter plasma concentrations of drugs metabolized by CYP3A... Nervous System Symptoms Fifty-three percent (531/1008) of patients receiving efavirenz in controlled trials reported central nervous system symptoms (any grade, regardless of causality) compared to 25% (156/635) of patients receiving control regimens. These symptoms included dizziness (28.1% of the 1008 patients)...

Avodart (dutasteride) Soft Gelatin Capsules Prescribing Information (in new labeling format)	CONTRAINDICATIONS Pregnancy WARNINGS AND PRECAUTIONS Evaluation for Other Urological Diseases Effects on Prostate-Specific Antigen (PSA) and the Use of PSA in Prostate Cancer Detection ADVERSE REACTIONS Clinical Trials Experience Combination with Alpha-Blocker Therapy (CombAT) Table 2 DRUG INTERACTIONS Alpha-Adrenergic Blocking Agents ...The effect of administration of tamsulosin or terazosin on dutasteride pharmacokinetic parameters has not been evaluated. USE IN SPECIFIC POPULATIONS Pregnancy Hepatic Impairment ...in a clinical study where 60 subjects received 5 mg (10 times the therapeutic dose) daily for 24 weeks, no additional adverse events were observed compared with those observed at the therapeutic dose of 0.5 mg... PATIENT COUNSELING INFORMATION Exposure of Women - Risk to Male Fetus ...Dutasteride is absorbed through the skin and could result in unintended fetal exposure. If a pregnant woman or woman of childbearing potential comes in contact with leaking Avodart Capsules, the contact area should be washed immediately with soap and water... Blood Donation ...Serum levels of dutasteride are detectable for 4 to 6 months after treatment ends...	CONTRAINDICATIONS Pregnancy - Dutasteride inhibits the activity of 5α-reductase, which prevents conversion of testosterone to dihydrotesterone, a hormone necessary for normal development of male genitalia. In animal reproduction and developmental toxicity studies, dutasteride inhibited development of male fetus external genitalia. Therefore, Avodart may cause fetal harm when administered to a pregnant woman. If Avodart is used during pregnancy or if the patient becomes pregnant while taking Avodart, the patient should be apprised of the potential hazard to the fetus... WARNINGS AND PRECAUTIONS Evaluation for Other Urological Diseases ...Patients should be assessed to rule out prostate cancer and other urological diseases prior to treatment with Avodart and periodically thereafter... Effects on Prostate-Specific Antigen (PSA) and the Use of PSA in Prostate Cancer Detection Coadministration of tamsulosin with dutasteride resulted in similar changes to total PSA as dutasteride monotherapy.

Concerta (methylphenidate HCl) Extended-Release Tablets Prescribing Information (in new labeling format) Medication Guide	CONTRAINDICATIONS Hypersensitivity to Methylphenidate WARNINGS AND PRECAUTIONS Psychiatric Adverse Events Pre-Existing Psychosis Emergence of New Psychotic or Manic Symptoms Aggression ADVERSE REACTIONS Initial Section Table 3 Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials Children and Adolescents Table 4 Adults Table 5 Blood Pressure and Heart Rate Increases Postmarketing Experience PATIENT COUNSELING INFORMATION Information for Patients Stimulants may impair the ability to operate potentially hazardous machinery... MEDICATION GUIDE What are possible side effects of Concerta? Common side effects include...	CONTRAINDICATIONS Hypersensitivity to Methylphenidate Hypersensitivity reactions, such as angioedema and anaphylactic reactions, have been observed in patients treated with Concerta. Therefore, Concerta is contraindicated in patients known to be hypersensitive to methylphenidate or other components of the product... WARNINGS AND PRECAUTIONS Psychiatric Adverse Events Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder...

Kaletra (lopinavir and ritonavir) Tablet, Film Coated for Oral Use Kaletra (lopinavir and ritonavir) Solution for Oral Use Prescribing Information (in new labeling format) Patient Package Insert	CONTRAINDICATIONS Initial Statement Table 3: Drugs That Are Contraindicated With Kaletra ADVERSE REACTIONS Pediatric Patients - Clinical Trials Experience DRUG INTERACTIONS Table 9 Benzodiazepines: Parenterally Administered Midazolam USE IN SPECIFIC POPULATIONS Pediatric Use PATIENT PACKAGE INSERT What is Kaletra and how does it work? ...Kaletra is for adults and for children age 14 days and older. How should I take Kaletra? Dosing in children greater than 14 days of age...	CONTRAINDICATIONS Kaletra is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme) to any of its ingredients, including ritonavir. Table 3: Drugs That Are Contraindicated With Kaletra Sedative/Hyponotics: Orally Administered Midazolam (added)

Reclast (zoledronic acid) Injection Prescribing Information (in new labeling format) Patient Package Insert	CONTRAINDICATIONS Hypersensitivity to zoledronic acid or any components of Reclast WARNINGS AND PRECAUTIONS Hypocalcemia and Mineral Metabolism Renal Impairment Musculoskeletal Pain Patients with Asthma ADVERSE REACTIONS Clinical Studies Experience Treatment of Osteoporosis Table 1 Renal Impairment Acute Phase Reaction Laboratory Findings Injection Site Reactions Osteonecrosis of the Jaw Atrial Fibrillation Ocular Adverse Events Postmarketing Experience (new subsection) DRUG INTERACTIONS Initial Section Nephrotoxic Drugs ...such as nonsteroidal anti-inflammatory drugs. USE IN SPECIFIC POPULATIONS Pediatric Use Geriatric Use PATIENT COUNSELING INFORMATION Information for Patients PATIENT PACKAGE INSERT What is the most important information I should know about Reclast? What is Reclast? What should I tell my doctor before getting Reclast? Tell your doctor about all the medicines you take... How will I receive Reclast? What are the possible side effects of Reclast? What is Osteoporosis?	CONTRAINDICATIONS Hypersensitivity to zoledronic acid or any components of Reclast Hypersensitivity reactions including rare cases of urticaria, angioedema, and anaphylactic reaction/shock have been reported... WARNINGS AND PRECAUTIONS Hypocalcemia and Mineral Metabolism ...Clinical monitoring of calcium and mineral levels (phosphorus and magnesium) is highly recommended... All osteoporosis patients should be instructed on the importance of calcium and vitamin D supplementation in maintaining serum calcium levels... Renal Impairment ...Monitor serum creatinine before each Reclast dose. Transient increase in serum creatinine may be greater in patients with impaired renal function; consider interim monitoring of serum creatinine in at-risk patients. Musculoskeletal Pain In post-marketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain have been infrequently reported in patients taking bisphosphonates, including Reclast. The time to onset of symptoms varied from one day to several months after starting the drug. Consider withholding future Reclast treatment if severe symptoms develop. Most patients had relief of symptoms after stopping. A subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate... Patients with Asthma ...Use Reclast with caution in aspirin-sensitive patients.

Zyvox (linezolid) Injection Zyvox (linezolid) Tablets Zyvox (linezolid) for Oral Suspension Prescribing Information	CONTRAINDICATIONS Monoamine Oxidase Inhibitors Potential Interactions Producing Elevation of Blood Pressure Potential Serotonergic Interactions	CONTRAINDICATIONS Monoamine Oxidase Inhibitors Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g. phenelzine, isocarboxazid) or within two weeks of taking any such medicinal product. Potential Interactions Producing Elevation of Blood Pressure Unless patients are monitored for potential increases in blood pressure, linezolid should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis and/or patients taking any of the following types of medications: directly and indirectly acting sympathomimetic agents (e.g. pseudoephedrine), vasopressive agents (e.g. epinephrine, norepinephrine), dopaminergic agents (e.g. dopamine, dobutamine)... Potential Serotonergic Interactions Unless patients are carefully observed for signs and/or symptoms of serotonin syndrome, linezolid should not be administered to patients with carcinoid syndrome and/or patients taking any of the following medications: serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine or buspirone...

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Advil Allergy Sinus Caplets (ibuprofen, pseudoephedrine HCl, chlorpheniramine maleate) Over-the-Counter For current prescribing information, contact Wyeth Consumer Healthcare at 1-800-882-3845.	WARNINGS	WARNINGS Ask a doctor before use if you have: asthma (added) Do not use: in children under 12 years of age 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...

Advil Cold & Sinus (ibuprofen and pseudoephedrine HCl) Caplets Over-the-Counter For current prescribing information, contact Wyeth Consumer Healthcare at 1-800-882-3845.	WARNINGS	WARNINGS Ask a doctor before use if you have: asthma (added) Do not use: in children under 12 years of age

Advil Cold & Sinus Liqui-Gels (ibuprofen and pseudoephedrine HCl) Capsules Over-the-Counter For current prescribing information, contact Wyeth Consumer Healthcare at 1-800-882-3845.	WARNINGS	WARNINGS Ask a doctor before use if you have: asthma Do not use: in children under 12 years of age

Advil Liqui-Gels (ibuprofen) Capsules Over-the-Counter For current prescribing information, contact Wyeth Consumer Healthcare at 1-800-882-3845.	WARNINGS	WARNINGS Ask a doctor before use if you have: asthma (added)

Advil Migraine (ibuprofen) Capsules Over-the-Counter Prescribing Information	WARNINGS	WARNINGS Ask a doctor before use if you have: asthma (added)

Advil PM (ibuprofen, diphenhydramine citrate) Caplets Over-the-Counter For current prescribing information, contact Wyeth Consumer Healthcare at 1-800-882-3845.	WARNINGS	WARNINGS Ask a doctor before use if you have: asthma (added)

Advil PM Liqui-Gels (ibuprofen, diphenhydramine HCl) Capsules Over-the-Counter For current prescribing information, contact Wyeth Consumer Healthcare at 1-800-882-3845.	WARNINGS	WARNINGS Ask a doctor before use if you have: asthma (added)

Advil (ibuprofen) Tablets Over-the-Counter For current prescribing information, contact Wyeth Consumer Healthcare at 1-800-882-3845.	WARNINGS	WARNINGS Ask a doctor before use if you have: asthma (added)

Agrylin (anagrelide hydrochloride) Capsules Prescribing Information	WARNINGS Interstitial Lung Diseases PRECAUTIONS Carcinogenesis, Mutagenesis, Impairment of Fertility In a two year rat carcinogenicity study a higher incidence of uterine adenocarcinoma... Pregnancy ...There are however, no adequate and well controlled studies with anagrelide hydrochloride in pregnant women. Nonclinical Toxicology Initial Paragraph ADVERSE REACTIONS Postmarketing Reports (new subsection)	WARNINGS Interstitial Lung Diseases Interstitial lung diseases (including allergic alveolitis, eosinophilic pneumonia and interstitial pneumonitis) have been reported to be associated with the use of anagrelide in post-marketing reports. Most cases presented with progressive dyspnea with lung infiltrations. The time of onset ranged from 1 week to several years after initiating anagrelide. In most cases, the symptoms improved after discontinuation of anagrelide...

Antara (fenofibrate) Capsules Prescribing Information	WARNINGS Other Considerations PRECAUTIONS Venothromboembolic Disease	WARNINGS: Other Considerations The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was a 5- year randomized, placebo-controlled study of 9795 patients with type 2 diabetes mellitus treated with fenofibrate. Fenofibrate demonstrated a non-significant 11 % relative reduction in the primary outcome of coronary heart disease events (hazard ratio (HR) 0.89, 95% CI 0.75-1.05, p=0.16) and a significant 11% reduction in the secondary outcome of total cardiovascular disease events (HR 0.89 (0.89-0.99), p=0.04). There was a non-significant 11 % (HR 1.11 (0.95, 1.29), p=0.18) and 19% (HR 1.19 (0.90, 1.57), p=0.22) increase in total and coronary heart disease mortality, respectively, with fenofibrate as compared to placebo.

Celestone Soluspan (betamethasone sodium phosphate and betamethasone acetate Injectable Suspension, USP) Prescribing Information	WARNINGS Neurologic	WARNINGS Neurologic Results from one multicenter, randomized, placebo controlled study with methylprednisolone hemisuccinate, an IV corticosteroid, showed an increase in early mortality (at 2 weeks) and late mortality (at 6 months) in patients with cranial trauma who were determined not to have other clear indications for corticosteroid treatment. High doses of corticosteroids, including Celestone Soluspan, should not be used for the treatment of traumatic brain injury.

Children’s Advil Chewables (50 ibuprofen) Chewable Tablets Junior Strength Advil Chewables (100 mg ibuprofen) Chewable Tablets Over-the-Counter For current prescribing information, contact Wyeth Consumer Healthcare at 1-800-882-3845.	WARNINGS	WARNINGS Ask a doctor before use if the child has: asthma (added)

Children’s Advil (ibuprofen) Suspension Over-the-Counter For current prescribing information, contact Wyeth Consumer Healthcare at 1-800-882-3845.	WARNINGS	WARNINGS Ask a doctor before use if the child has: asthma (added)

Clozaril (clozapine) Tablets Prescribing Information	WARNINGS Tardive Dyskinesia ADVERSE REACTIONS Extrapyramidal Symptoms Dystonia	WARNINGS Tardive Dyskinesia ...There are several reasons for predicting that Clozaril may be different from other antipsychotic drugs in its potential for inducing tardive dyskinesia, including the preclinical finding that it has a relatively weak dopamine-blocking effect and the clinical finding of a low incidence of certain acute extrapyramidal symptoms, e.g., dystonia...

Cymbalta (duloxetine hydrochloride) Delayed-Release Capsules Prescribing Information (in new labeling format)	WARNINGS AND PRECAUTIONS Hepatotoxicity ADVERSE REACTIONS Clinical Trial Data Sources Adverse Reactions Reported as Reasons for Discontinuation of Treatment in Placebo-Controlled Trials Fibromyalgia (new subsection) Adverse Reactions Occurring at an Incidence of 2% or More Among Duloxetine-Treated Patients in Placebo-Controlled Trials Fibromyalgia (new subsection) Table 5 Weight Changes USE IN SPECIFIC POPULATIONS Geriatric Use	WARNINGS AND PRECAUTIONS Hepatotoxicity There have been reports of hepatic failure, sometimes fatal, in patients treated with Cymbalta... ...Cymbalta should be discontinued in patients who develop jaundice or other evidence of clinically significant liver dysfunction and should not be resumed unless another cause can be established..

Infants' Advil (ibuprofen) Concentrated Drops Over-the-Counter For current prescribing information, contact Wyeth Consumer Healthcare at 1-800-882-3845.	WARNINGS	WARNINGS Ask a doctor before use if child has: asthma (added)

Junior Strength Advil (ibuprofen) Tablets Over-the-Counter For current prescribing information, contact Wyeth Consumer Healthcare at 1-800-882-3845.	WARNINGS	WARNINGS Ask a doctor before use if the child has: asthma (added)

Metvixia (methyl aminolevulinate) Cream, 16.8% For Topical Use Only Prescribing Information Patient Package Insert	WARNINGS AND PRECAUTIONS Photosensitivity Aktilite Lamp ADVERSE REACTIONS Dermal Safety Studies Clinical Studies Experience Table 1 DRUG INTERACTIONS USE IN SPECIFIC POPULATIONS Geriatric Use PATIENT PACKAGE INSERT (to include use with the Aktilite CL 128 lamp)	WARNINGS AND PRECAUTIONS Photosensitivity During the time period between the application of Metvixia Cream and exposure to Aktilite red light illumination, the treatment site will become photosensitive. If for any reason the patient cannot have the Aktilite red light treatment after application of Metvixia Cream, the cream should be rinsed off, and the patient should protect the treated area from sunlight, prolonged or intense light for two days. Prolonged exposure for greater than 4 hours to Metvixia Cream should be avoided... Aktilite Lamp Before operating the Aktilite CL128 lamp, personnel should refer to the Operators Manual for specific warnings, cautions and instructions. Care should be exercised when positioning and operating the lamp. During the red light illumination period, the patient, operator and other persons present should wear protective goggles that sufficiently screen out the appropriate spectrum of red light. The protective goggles or eye shields provided for the patient are dark or of metal to block visible light...

Potassium Chloride Extended Release Tablets, USP Prescribing Information	WARNINGS Gastrointestinal Lesion PRECAUTIONS Information for Patients Physicians should consider reminding the patient of the following... Geriatric Use	WARNINGS Gastrointestinal Lesion ...Solid oral dosage forms of potassium chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract.

Pulmicort Flexhaler (budesonide inhalation powder) For Oral Inhalation Only Prescribing Information	WARNINGS PRECAUTIONS Drug Interactions Varicella Vaccine	WARNINGS ...Chicken pox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure... ... The immune responsiveness to varicella vaccine was evaluated in pediatric patients with asthma ages 12 months to 8 years with budesonide inhalation suspension...

Synercid I.V. (quinupristin and dalfopristin for injection) Prescribing Information	WARNINGS Clostridium difficile PRECAUTIONS Information for Patients Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued...	WARNINGS *Clostridium difficile* Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Synercid, 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 C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. 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 C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Vectibix (panitumumab) Injection for Intravenous Use Prescribing Information (in new labeling format	WARNINGS AND PRECAUTIONS Dermatologic Toxicity ADVERSE REACTIONS Initial Section Pulmonary Embolism CLINICAL TRIALS EXPERIENCE Table 1 Metabolic/Nutritional Immunogenicity USE IN SPECIFIC POPULATIONS Pregnancy Nursing Mothers Pediatric Use PATIENT COUNSELING INFORMATION Advise patients to contact a healthcare professional for any of the following... (see highlighted section for changes) Advise patients of the need for... (see highlighted section for changes)	WARNINGS AND PRECAUTIONS ...Withhold Vectibix for severe or life-threatening dermatologic toxicity...

Velcade (bortezomib) for Injection Prescribing Information (in new labeling format)	WARNINGS AND PRECAUTIONS Use in Pregnancy Peripheral Neuropathy Cardiac Disorders Gastrointestinal Adverse Events Thrombocytopenia/Neutropenia Table 4 ADVERSE REACTIONS Clinical Trials Safety Experience Summary of Clinical Trial in Patients with Previously Untreated Multiple Myeloma (new subsection) Table 5 (new) Description of Selected Adverse Events from the Phase 2 and 3 Relapsed Multiple Myeloma and Phase 2 Mantle Cell Lymphoma Studies Herpes Virus Infection DRUG INTERACTIONS Ketoconazole Melphalan-Prednisone Omeprazole USE IN SPECIFIC POPULATIONS Pregnancy Patients with Renal Impairment PATIENT COUNSELING INFORMATION Dehydration/Hypotension Pregnancy/Nursing Concomitant Medications Diabetic Patients Peripheral Neuropathy Other	WARNINGS AND PRECAUTIONS Use in Pregnancy ...Bortezomib administered to rabbits during organogenesis caused post-implantation loss and a decreased number of live fetuses... Peripheral Neuropathy ...Following dose adjustments, improvement in or resolution of peripheral neuropathy was reported in 51% of patients with >Grade 2 peripheral neuropathy in the relapsed multiple myeloma study... Cardiac Disorders ...In the relapsed multiple myeloma study, the incidence of any treatment-emergent cardiac disorder was 15% and 13% in the Velcade and dexamethasone groups, respectively... Gastrointestinal Adverse Events ...Ileus can occur... Thrombocytopenia/Neutropenia Velcade is associated with thrombocytopenia and neutropenia that follow a cyclical pattern with nadirs occurring following the last dose of each cycle and typically recovering prior to initiation of the subsequent cycle... ...In the relapsed multiple myeloma study, the incidence of significant bleeding events (>Grade 3) was similar on both the Velcade (4%) and dexamethasone (5%) arms. Platelet count should be monitored prior to each dose of Velcade. Patients experiencing thrombocytopenia may require change in the dose and schedule of Velcade...

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Brand (Generic) Name	Sections Modified
Amoxicillin/Clavulanate Potassium Tablets Prescribing Information	PRECAUTIONS Geriatric Use

Amoxil (amoxicillin capsules, tablets, chewable tablets, and powder for oral suspension) Prescribing Information	PRECAUTIONS General A high percentage of patients with mononucleosis who receive ampicillin develop an erythematous skin rash. Thus, ampicillin-class antibiotics should not be administered to patients with mononucleosis. Drug Interactions ...reduced efficacy of combined oral estrogen/progesterone contraceptives. ADVERSE REACTIONS Infections and Infestations Mucocutaneous Candidiasis Gastrointestinal Black Hairy Tongue Hypersensitivity Reactions Anaphylaxis (See WARNINGS)

Doryx (doxycycline hyclate) Delayed-Release Tablets Prescribing Information (in new labeling format)	DRUG INTERACTIONS Antacids and Iron Preparations USE IN SPECIFIC POPULATIONS Pediatric Use Geriatric Use Renal Impairment PATIENT COUNSELING INFORMATION All patients taking doxycycline should be advised: that the absorption of tetracyclines is reduced when taken with antacids containing aluminum, calcium or magnesium, bismuth subsalicylate, and iron containing preparations...

Ganirelix Acetate Injection Prescribing Information	PRECAUTIONS General Cases of hypersensitivity reactions, including anaphylactoid reactions with the first dose, have been reported during post-marketing surveillance... ADVERSE REACTIONS During post-marketing surveillance, rare cases of hypersensitivity reactions, including anaphylactoid reactions with the first dose, have been reported...

Levothyroxine Sodium Tablets, USP Prescribing Information	PRECAUTIONS Information for Patients ...It is very important that you take the tablet with a full glass of water. Agents such as iron and calcium supplements and antacids can decrease the absorption of levothyroxine sodium tablets... Drug Interactions Table 2: Drug-Thyroidal Axis Interactions Drugs that may decrease T4 absorption, which may result in hypothyroidism Orlistat

Ortho Micronor (norethindrone) Tablets Prescribing Information	PRECAUTIONS Nursing Mothers

Sarafem (fluoxetine hydrochloride) Capsules Prescribing Information	PRECAUTIONS Hyponatremia

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Brand (Generic) Name	Sections Modified
Aciphex (rabeprazole sodium) Delayed Release Tablets Prescribing Information (in new labeling format) Patient Package Insert	ADVERSE REACTIONS Clinical Studies Experience In a multicenter, open-label study of adolescent patients aged 12 to 16 years... USE IN SPECIFIC POPULATIONS Pediatric Use PATIENT PACKAGE INSERT What is Aciphex? Aciphex is used in adolescents 12 years of age and above...

Baraclude (entecavir) Tablets and Oral Solution Prescribing Information Patient Package Insert	ADVERSE REACTIONS Postmarketing Experience (new subsection) Skin and subcutaneous tissue disorders Rash PATIENT PACKAGE INSERT What are the possible side effects of Baraclude? There have also been occasional reports of rash (added) How should I store Baraclude? Keep Baraclude and all medicines out of the reach of children and pets at all times. Do not keep medicine that is out of date or that you no longer need. Dispose of unused medicines through community take-back disposal programs when available or place Baraclude in an unrecognizable closed container in the household trash.

Gardasil [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] Prescribing Information Patient Package Insert	ADVERSE REACTIONS Postmarketing Reports Musculoskeletal and connective tissue disorders Arthralgia Myalgia General disorders and administration site conditions Asthenia Fatigue Malaise PATIENT PACKAGE INSERT What are the possible side effects of Gardasil? ...joint pain, aching muscles, unusual tiredness or weakness, and generally feeling unwell. (added)

Genotropin (somatropin [rDNA origin] for injection) Prescribing Information (in new labeling format)	ADVERSE REACTIONS Clinical Trials Experience Clinical Trials in Children with Idiopathic Short Stature

Mobic (meloxicam) Tablets and Oral Suspension Prescribing Information	ADVERSE REACTIONS Pediatrics Pauciarticular and Polyarticular Course Juvenile Rheumatoid Arthritis (JRA) Psychiatric Alterations in mood (such as mood elevation)

OxyContin (oxycodone HCl controlled-release) Tablets Prescribing Information	ADVERSE REACTIONS The following adverse reactions occurred in less than 1% of patients involved in clinical trials or were reported in postmarketing experience. (The adverse reaction categories have been re- organized. The adverse events listed below include only the new reactions added.) Cardiac Disorders Palpitations (in the context of withdrawal) Investigations Increased hepatic enzymes

Spiriva HandiHaler (tiotropium bromide inhalation powder) Prescribing Information Patient Package Insert See MedWatch Safety Alerts posted 03/18/2008 and 02/29/2008 for additional safety information.	ADVERSE REACTIONS ...The following adverse reactions have been identified during worldwide post-approval use of Spiriva HandiHaler: application site irritation (glossitis, mouth ulceration, and pharyngolarygeal pain) PATIENT PACKAGE INSERT The following statement was added on page 1, under drug name: Do Not Swallow Capsules. For Use With HandiHaler Only. Removing a Spiriva Capsule (Figure 4): Do not swallow Spiriva Capsules.

Vytorin (ezetimibe/simvastatin) Tablets Prescribing Information (in new labeling format) Patient Package Insert	ADVERSE REACTIONS Postmarketing Experience Vytorin or ezetimibe or simvastatin Paresthesia USE IN SPECIFIC POPULATIONS Pediatric Use Table 3 PATIENT PACKAGE INSERT What are the possible side effects of Vytorin? The following side effects have been reported in general use with Vytorin or with ezetimibe or simvastatin tablets (tablets that contain the active ingredients of Vytorin): Tingling Sensation (added)

Zetia (ezetimibe) Tablets Prescribing Information (in new labeling format) Patient Package Insert	ADVERSE REACTIONS Postmarketing Experience Paresthesia USE IN SPECIFIC POPULATIONS Pediatric Use Table 3 PATIENT PACKAGE INSERT What are the possible side effects of Zetia? Tingling Sensation (added)

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Brand (Generic) Name	Sections Modified
Byetta (exenatide) Injection User Manual - 5 mcg Pen User Manual - 10 mcg Pen	PEN USER MANUALS (revised)

Forteo (teriparatide [rDNA origin]) Injection Medication Guide User Manual (for Forteo delivery device [pen])	MEDICATION GUIDE (revised) USER MANUAL (new)

PegIntron/REBETOL Combo Pack containing: PegIntron REDIPEN Single-dose Delivery System (peginterferon alfa-2b) and REBETOL (ribavirin, USP) Capsules Medication Guide	MEDICATION GUIDE (new)

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