MedWatch - January 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) -- January 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
EstroGel 0.06% (estradiol gel) Prescribing Information Patient Package Insert	BOXED WARNING Cardiovascular and Other Risks WARNINGS Cardiovascular Disorders Stroke Coronary Heart Disease Venous Thromboembolism (VTE) Malignant Neoplasms Endometrial Cancer Breast Cancer Ovarian Cancer Dementia PRECAUTIONS General Hypertriglyceridemia Alcohol-based Gels are Flammable Laboratory Tests Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Nursing Mothers Pediatric Use Geriatric Use ADVERSE REACTIONS Genitourinary System Uterine Bleeding/Spotting Pelvic Pain Central Nervous System Exacerbation of Chorea Miscellaneous Glucose Intolerance Hypocalcemia (preexisting condition) PATIENT PACKAGE INSERT Initial Paragraph What is the most important information I should know about EstroGel (an estrogen hormone)? How is EstroGel used? Tell your healthcare provider... How should I use EstroGel? What should I avoid while using EstroGel? What are the possible side effects of estrogens? What can I do to lower my chances of having an adverse event with EstroGel? What are the ingredients in EstroGel?	BOXED WARNING Cardiovascular and Other Risks Estrogens with or without progestins should not be used for the prevention of cardiovascular disease or dementia... The Women's Health Initiative Memory Study (WHIMS), a substudy of WHI, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily CE 0.625 mg alone and during 4 years of treatment with daily CE 0.625 mg combined with MPA 2.5 mg, relative to placebo... In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA and other combinations and dosage forms of estrogens and progestins... WARNINGS See highlighted text for labeling revisions.

Herceptin (trastuzumab) Intravenous Infusion Prescribing Information (in new labeling format)	BOXED WARNING Cardiomyopathy Infusion Reactions; Pulmonary Toxicity WARNINGS AND PRECAUTIONS Cardiomyopathy Table 1 Table 2 Infusion Reactions In postmarketing reports, serious and fatal infusion reactions have been reported... HER2 Testing Embryo-Fetal Toxicity (Pregnancy Category D) ADVERSE REACTIONS Initial Section Adverse reactions requiring interruption or discontinuation of Herceptin treatment include: pulmonary toxicity (added) PATIENT COUNSELING INFORMATION	BOXED WARNING Cardiomyopathy Herceptin can result in sub-clinical and clinical cardiac failure manifesting as CHF and decreased LVEF... Infusions Reactions; Pulmonary Toxicity ...Fatal infusion reactions have been reported. ...Discontinue Herceptin for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. [see Warnings and Precautions (5.2, 5.4)] WARNINGS AND PRECAUTIONS See highlighted text for labeling revisions.

Rituxan (rituximab) Injection For Intravenous Use Prescribing Information (in new labeling format) Medication Guide	BOXED WARNING Infusion Reactions WARNINGS AND PRECAUTIONS Infusion Reactions ADVERSE REACTIONS The most common adverse reactions of Rituxan (incidence ≥25%) observed in patients with NHL are infusion reactions, fever, chills, infection, asthenia, and lymphopenia... Clinical Trials Experience Non-Hodgkin's Lymphoma Infections Cytopenias and Hypogammaglobulinemia Postmarketing Reports Pulmonary USE IN SPECIFIC POPULATIONS Pregnancy Nursing Mothers MEDICATION GUIDE (new - previously Patient Package Insert)	BOXED WARNING Infusion Reactions Rituxan administration can result in serious, iucluding fatal infusion reactions. Deaths within 24 hours of Rituxan infusion have occurred... ...Carefully monitor patients during infusions. Discontinue Rituxan infusion and provide medical treatment for Grade 3 or 4 infusion reactions... WARNINGS AND PRECAUTIONS Infusion Reactions ...Premedicate patients with an antihistamine and acetaminophen prior to dosing. Institute medical management (e.g. glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion reactions as needed. Depending on the severity of the infusion reaction and the required interventions, consider resumption of the infusion at a minimum 50% reduction in rate after symptoms have resolved...

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Alesse 28 Tablets (levonorgestrel and ethinyl estradiol tablets) Prescribing Information Patient Package Insert	CONTRAINDICATIONS WARNINGS Thromboembolic Disorders and Other Vascular Problems Figure II: Circulatory Disease Mortality Rates Per 100,000 Woman Years By Age, Smoking Status and Oral-Contraceptive Use Venous Thrombosis and Thromboembolism Carcinoma of the Reproductive Organs and Breasts PATIENT PACKAGE INSERT:DETAILED PATIENT LABELING Who Should Not Take Oral Contraceptives Risks of Taking Oral Contraceptives Risk of Developing Blood Clots Lipid Metabolism and Pancreatitis	CONTRAINDICATIONS Valvular heart disease with thrombogenic complications WARNINGS Venous Thrombosis and Thromboembolism ...Since the immediate postpartum period is also associated with an increased risk of thromboembolism, oral contraceptives should be started no earlier than four weeks after delivery in women who elect not to breast-feed or after a midtrimester pregnancy termination. Carcinoma of the Reproductive Organs and Breasts See highlighted text for labeling revisions.

Janumet (sitagliptin/metformin HCl) Tablets Prescribing Information (in new labeling format) Patient Package Insert	CONTRAINDICATIONS WARNINGS AND PRECAUTIONS Hypersensitivity Reactions ADVERSE REACTIONS Postmarketing Experience ...Hypersensitivity reactions include anaphylaxis, angioedema, rash, urticaria and exfoliative skin conditions including Stevens-Johnson syndrome [see Warnings and Precautions (5.13)]; upper respiratory tract infection. PATIENT COUNSELING INFORMATION Instructions Patients should be informed that allergic reactions have been reported during postmarketing use of sitagliptin, one of the components of Janumet... PATIENT PACKAGE INSERT Do not take Janumet if you: ...have had an allergic reaction to Janumet or sitagliptin (Januvia), one of the components of Janumet. What should I tell my doctor before and during treatment with Janumet? What are the possible side effects of Janumet? Allergic reactions, which may be serious... Upper respiratory infection	CONTRAINDICATIONS Janumet (sitagliptin/metformin HCl) is contraindicated in patients with: History of a serious hypersensitivity reaction to Janumet or sitagliptin, (one of the components of Janumet), such as anaphylaxis or angioedema. [See Warnings and Precautions (5.13) and Adverse Reactions (6.2).] WARNINGS AND PRECAUTIONS: Hypersensitivity Reactions There have been postmarketing reports of serious hypersensitivity reactions in patients treated with sitagliptin, one of the components of Janumet. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome... ...Onset of these reactions occurred within the first 3 months after initiation of treatment with sitagliptin, with some reports occurring after the first dose. If a hypersensitivity reaction is suspected, discontinue Janumet, assess for other potential causes for the event, and institute alternative treatment for diabetes. [See Adverse Reactions (6.2).]

Mycamine (micafungin sodium) For Injection Prescribing Information (in new labeling format)	CONTRAINDICATIONS ADVERSE REACTIONS Clinical Trials Experience Candidemia and Other Candida Infections Table 2 Esophageal Candidiasis Table 3 Prophylaxis of Candida Infections in Hematopoietic Stem Cell Transplant Recipients Table 4 Overall Mycamine Safety Experience in Clinical Trials Blood and Lymphatic System Disorders Gastrointestinal Disorders Table 5 DRUG INTERACTIONS USE IN SPECIFIC POPULATIONS Geriatric Use Race and Gender	CONTRAINDICATIONS Mycamine is contraindicated in persons with known hypersensitivity to micafungin, any component of Mycamine, or other echinocandins.

Omnitrope [somatropin (rDNA origin) injection] For Subcutaneous Use Prescribing Information (in new labeling format) Patient Package Insert	CONTRAINDICATIONS Acute Critical Illness Prader-Willi Syndrome in Children Active Malignancy Diabetic Retinopathy Hypersensitivity Benzyl Alcohol Sensitivity WARNINGS AND PRECAUTIONS Acute Critical Illness Neoplasms Glucose Intolerance Intracranial Hypertension (IH) Fluid Retention Hypothyroidism Slipped Capital Femoral Epiphysis in Pediatric Patients Local and Systemic Reactions Laboratory Tests ADVERSE REACTIONS Most Serious and/or Most Frequently Observed Adverse Reactions Clinical Trials Experience Clinical Trials in Pediatric GHD Patients Table 1 Postmarketing Surveillance DRUG INTERACTIONS Inhibition of 11ß-Hydroxysteroid Dehydrogenase Type 1 (11ßHSD-1) Glucocorticoid Replacement Cytochrome P450-Metabolized Drugs Oral Estrogen Insulin and/or Oral Hypoglycemic Agents USE IN SPECIFIC POPULATIONS Pregnancy Geriatric Use PATIENT COUNSELING INFORMATION If patients are prescribed Omnitrope Cartridge 5 mg/1.5 mL (to be inserted into Omnitrope Pen 5 delivery systems)... PATIENT PACKAGE INSERT Instructions for Use: Omnitrope Pen 5 (new)	CONTRAINDICATIONS See highlighted text for labeling revisions. WARNINGS AND PRECAUTIONS See highlighted text for labeling revisions.

Tysabri (natalizumab) Injection For Intravenous Use Prescribing Information (in new labeling format) Medication Guide	CONTRAINDICATIONS WARNINGS AND PRECAUTIONS Progressive Multifocal Leukoencephalopathy (PML) Distribution Program for Tysabri Hypersensitivity/Antibody Formation Immunosuppression/Infections Hepatotoxicity ADVERSE REACTIONS Clinical Trials Experience Initial Section Multiple Sclerosis Clinical Studies Crohn's Disease Clinical Studies Table 2 Table 3 Infections Infusion-related Reactions Immunogenicity DRUG INTERACTIONS USE IN SPECIFIC POPULATIONS Pregnancy Geriatric Use PATIENT COUNSELING INFORMATION General Counseling Information Progressive Multifocal Leukoencephalopathy Immunosuppression/Infections Hepatotoxicity MEDICATION GUIDE	CONTRAINDICATIONS Tysabri should not be administered to a patient who has had a hypersensitivity reaction to Tysabri. Observed reactions range from urticara to anaphylaxis [see Warnings and Precautions (5.3)]. WARNINGS AND PRECAUTIONS See highlighted text for labeling revisions.

WelChol (colesevelam hydrochloride) Tablets Prescribing Information (in new labeling format)	CONTRAINDICATIONS WARNINGS AND PRECAUTIONS General Serum Triglycerides (TG) Drug Interactions ADVERSE REACTIONS Clinical Studies Experience Type 2 Diabetes Mellitus Table 2 Hypertriglyceridemia Cardiovascular Adverse Events Hypoglycemia USE IN SPECIFIC POPULATIONS Geriatric Use Type 2 Diabetes Mellitus Renal Impairment Type 2 Diabetes Mellitus PATIENT COUNSELING INFORMATION Type 2 Diabetes Mellitus General Hypertriglyceridemia and Cardiovascular Disease	CONTRAINDICATIONS WelChol is contraindicated in patients with: • A history of bowel obstruction • Serum TG concentrations >500 mg/dL • A history of hypertriglyceridemia-induced pancreatitis WARNINGS AND PRECAUTIONS See highlighted text for labeling revisions.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Azactam (aztreonam for injection, USP) Prescribing Information	WARNINGS Clostridium difficile associated disease (CDAD) 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 Azactam, 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.

Azactam (aztreonam injection) in GALAXY Plastic Container (PL 2040) For Intravenous Use Prescribing Information	WARNINGS Clostridium difficile associated disease (CDAD) 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 Azactam, 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.

Chantix (varenicline) Tablets Prescribing Information See MedWatch Safety Alert posted 11/20/2007 for additional information on Chantix.	WARNINGS Neuropsychiatric Symptoms PRECAUTIONS Information for Patients (see highlighted text for new or revised labeling)	WARNINGS: Neuropsychiatric Symptoms Serious neuropsychiatric symptoms have occurred in patients being treated with Chantix. Some cases may have been complicated by the symptoms of nicotine withdrawal in patients who stopped smoking; however, some of these symptoms have occurred in patients who continued to smoke. All patients being treated with Chantix should be observed for neuropsychiatric symptoms including changes in behavior, agitation, depressed mood, suicidal ideation and suicidal behavior. These symptoms, as well as worsening of pre-existing psychiatric illness, have been reported in patients attempting to quit smoking while taking Chantix in the postmarketing experience. Patients with serious psychiatric illness such as schizophrenia, bipolar disorder, and major depressive disorder did not participate in the pre-marketing studies of Chantix and the safety and efficacy of Chantix in such patients has not been established. Patients attempting to quit smoking with Chantix and their families and caregivers should be alerted about the need to monitor for these symptoms and to report such symptoms immediately to the patient’s healthcare provider.

Cialis (tadalafil) Tablets Prescribing Information (in new labeling format) Patient Package Insert	WARNINGS AND PRECAUTIONS Potential for Drug Interactions When Taking Cialis for Once Daily Use Renal Insufficiency Cialis for Once Daily Use Hepatic Impairment Cialis for Once Daily Use Alcohol Concomitant Use of Potent Inhibitors of Cytochrome P450 3A4 (CYP3A4) Effects on Bleeding ADVERSE REACTIONS Clinical Studies Experience Table 2 Table 3 Postmarketing Experience Nervous Seizure and Seizure Recurrence USE IN SPECIFIC POPULATIONS Geriatric Use Hepatic Impairment Renal Insufficiency PATIENT COUNSELING INFORMATION Potential for Drug Interactions When Taking Cialis for Once Daily Use Recommended Administration PATIENT PACKAGE INSERT What Is The Most Important Information I Should Know About Cialis? What Is Cialis? Can Other Medicines Affect Cialis? How Should I Take Cialis? Cialis for once daily use...	WARNINGS AND PRECAUTIONS Potential for Drug Interactions When Taking Cialis for Once Daily Use Physicians should be aware that Cialis for once daily use provides continuous plasma tadalafil levels and should consider this when evaluating the potential for interactions with medications (e.g., nitrates, alpha-blockers, anti-hypertensives and potent inhibitors of CYP3A4) and with substantial consumption of alcohol... Renal Insufficiency: Cialis for Once Daily Use Due to increased tadalafil exposure (AUC), limited clinical experience, and the lack of ability to influence clearance by dialysis, Cialis for once daily use is not recommended in patients with severe renal insufficiency. No dose adjustment is required in patients with mild or moderate renal insufficiency [see Use in Specific Populations (8.7)]. Hepatic Impairment: Cialis for Once Daily Use Cialis for once daily use has not been extensively evaluated in patients with mild or moderate hepatic insufficiency. Therefore, caution is advised if Cialis for once daily use is prescribed to these patients. Because of insufficient information in patients with severe hepatic impairment, use of Cialis in this group is not recommended [see Use In Specific Populations (8.6)]. See highlighted text for labeling revisions in WARNINGS AND PRECAUTIONS section.

E.E.S. (erythromycin ethylsuccinate) Prescribing Information	WARNINGS Clostridium difficile associated disease (CDAD) 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 Ery-Ped, 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.

Ery-Ped (erythromycin ethylsuccinate, USP) Prescribing Information	WARNINGS Clostridium difficile associated diarrhea (CDAD) 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 Ery-Ped, 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.

Humira (adalimumab) Injection, Solution For Subcutaneous Use Prescribing Information (in new labeling format) Medication Guide	WARNINGS AND PRECAUTIONS Malignancies ADVERSE REACTIONS Immunogenicity Plaque Psoriasis Clinical Studies PATIENT COUNSELING INFORMATION Medication Guide MEDICATION GUIDE (new)	WARNINGS AND PRECAUTIONS See highlighted text for labeling revisions.

Lunesta (eszopiclone) Tablets Prescribing Information Medication Guide	WARNINGS First paragraph (second sentence changed to a bold print type): The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Second paragraph: "Complex behaviors such as "sleep-driving"... Severe Anaphylactic and Anaphylactoid Reactions (new subsection) PRECAUTIONS SPECIAL CONCERNS “Sleep-Driving” and Other Complex Behaviors (new subsection) MEDICATION GUIDE (new)	WARNINGS (second paragraph) ...Complex behaviors such as “sleep-driving” (i.e., driving while not fully awake after ingestion of a sedative-hypnotic, with amnesia for the event) have been reported. These events can occur in sedative-hypnotic-naïve as well as in sedative-hypnotic-experienced persons. Although behaviors such as sleep-driving may occur with Lunesta alone at therapeutic doses, the use of alcohol and other CNS depressants with Lunesta appears to increase the risk of such behaviors, as does the use of Lunesta at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of Lunesta should be strongly considered for patients who report a “sleep-driving” episode. Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative-hypnotic. As with sleep-driving, patients usually do not remember these events. Amnesia and other neuropsychiatric symptoms may occur unpredictably. In primarily depressed patients, worsening of depression, including suicidal thoughts and actions (including completed suicides), have been reported in association with the use of sedative/hypnotics. Severe Anaphylactic and Anaphylactoid Reactions (new subsection) Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of sedative-hypnotics, including Lunesta... (See highlighted label for revised text.)

Ortho Evra (norelgestromin/ethinyl estradiol transdermal system) Prescribing Information Patient Package Insert See MedWatch Safety Alert posted 1/19/2008 for additional information on Ortho Evra Contraceptive Transdermal Patch.	WARNINGS Epidemiologic, case-control studies... Table 5 PATIENT PACKAGE INSERT: DETAILED PATIENT LABELING Other Considerations Before Using Ortho Evra	WARNINGS Epidemiologic, case-control studies were conducted in the U.S. using electronic healthcare claims data to evaluate the risk of venous thromboembolism (VTE) among women aged 15-44 who used Ortho Evra compared to women who used oral contraceptives containing 30-35 mcg of ethinyl estradiol (EE) and either norgestimate (NGM) or levonorgestrel (LNG). NGM is the prodrug for norelgestromin, the progestin in Ortho Evra. These studies (see Table 5) used slightly different designs and reported odds ratios ranging from 0.9 (indicating no increase in risk) to 2.4 (indicating an approximate doubling of risk). One study (i3 Ingenix) included patient chart review to confirm the VTE occurrence...

PCE (erythromycin particles in tablets) Dispertab Tablets Prescribing Information	WARNINGS Clostridium difficile associated diarrhea (CDAD) 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 PCE, 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.

Rapamune (sirolimus) Oral Solution and Tablets Prescribing Information (in new labeling format)	WARNINGS AND PRECAUTIONS Proteinuria ADVERSE REACTIONS Conversion from Calcineurin Inhibitors to Rapamune in Maintenance Renal Transplant Population	WARNINGS AND PRECAUTIONS Proteinuria ...Patients with the greatest amount of urinary protein excretion prior to Rapamune conversion were those whose protein excretion increased the most after conversion. New onset nephrosis (nephrotic syndrome) was also reported as a treatment emergent adverse event in 2.2% of the Rapamune conversion group patients in comparison to 0.4% in the CNI continuation group of patients...

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Brand (Generic) Name	Sections Modified
Byetta (exenatide) injection Prescribing Information Patient Package Insert See MedWatch Safety Alerts posted 10/16/2007 and 2/27/2008 for additional information on Byetta.	PRECAUTIONS General Postmarketing cases of acute pancreatitis have been reported... Information for Patients Patients should be informed that persistent severe abdominal pain, which may be accompanied by vomiting, is the hallmark symptom of acute pancreatitis... PATIENT PACKAGE INSERT What are the possible side effects of Byetta? ...Talk to your healthcare provider if you experience the following severe and persistent symptoms, alone or in combination, because they could be signs of a serious medical condition: abdominal pain or vomiting.

Cipro I.V. (ciprofloxacin) For Intravenous Infusion Prescribing Information	PRECAUTIONS Photosensitivity/Phototoxicity Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions... Information for Patients Patients should be advised: that photosensitivity/phototoxicity has been reported in patients receiving quinolones... ADVERSE REACTIONS Skin/Hypersensitivity Photosensitivity/Phototoxicity Reaction Postmarketing Adverse Events Photosensitivity/Phototoxicity Reaction

Cipro (ciprofloxacin hydrochloride) Tablets Cipro (ciprofloxacin) Oral Suspension Prescribing Information Patient Package Insert	PRECAUTIONS Photosensitivity/Phototoxicity Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions... Information for Patients Patients should be advised: that photosensitivity/phototoxicity has been reported in patients receiving quinolones... ADVERSE REACTIONS Skin/Hypersensitivity Photosensitivity/Phototoxicity Reaction Postmarketing Adverse Events Photosensitivity/Phototoxicity Reaction PATIENT PACKAGE INSERT What are the possible side effects of Cipro? Sun sensitivity (photosensitivity), which can appear as skin eruption or severe sunburn, can occur in some patients taking quinolone antibiotics after exposure to sunlight or artificial ultraviolet (UV) light (e.g., tanning beds). Cipro has been infrequently associated with photosensitivity...

Cipro XR (ciprofloxacin extended-release tablets) Prescribing Information Patient Package Insert	PRECAUTIONS Photosensitivity/Phototoxicity Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions... Information for Patients Patients should be advised: that photosensitivity/phototoxicity has been reported in patients receiving quinolones... ADVERSE REACTIONS Skin/Hypersensitivity Photosensitivity/Phototoxicity Reactions Postmarketing Adverse Experience Photosensitivity/Phototoxicity Reaction PATIENT PACKAGE INSERT What are the possible side effects of Cipro XR? Sun sensitivity (photosensitivity), which can appear as skin eruption or severe sunburn, can occur in some patients taking quinolone antibiotics after exposure to sunlight or artificial ultraviolet (UV) light (e.g., tanning beds). Cipro XR has been infrequently associated with photosensitivity...

Effexor (venlafaxine hydrochloride) Tablets Contact Wyeth Pharmaceuticals, Inc. at 1-800-934-5556 for current prescribing information.	PRECAUTIONS Drug Interactions Drugs that Inhibit Cytochrome P450 Isoenzymes Ketoconazole: A pharmacokinetic study with ketoconazole 100 mg b.i.d. with a single dose of venlafaxine 50 mg in extensive metabolizers (EM; n = 14) and 25 mg in poor metabolizers (PM; n = 6) of CYP2D6 resulted in higher plasma concentrations of both venlafaxine and O-desmethylvenlafaxine (ODV) in most subjects following administration of ketoconazole. Venlafaxine Cmax increased by 26% in EM subjects and 48% in PM subjects. Cmax values for ODV increased by 14% and 29% in EM and PM subjects, respectively. Venlafaxine AUC increased by 21% in EM subjects and 70% in PM subjects (range in PMs - 2% to 206%), and AUC values for ODV increased by 23% and 33% in EM and PM (range in PMs - 38% to 105%) subjects, respectively. Combined AUCs of venlafaxine and ODV increased on average by approximately 23% in EMs and 53% in PMs, (range in PMs 4% - 134%). Concomitant use of CYP3A4 inhibitors and venlafaxine may increase levels of venlafaxine and ODV. Therefore, caution is advised if a patient’s therapy includes a CYP3A4 inhibitor and venlafaxine concomitantly.

Effexor XR (venlafaxine hydrochloride) Extended-Release Capsules Contact Wyeth Pharmaceuticals, Inc. at 1-800-934-5556 for current prescribing information.	PRECAUTIONS Drug Interactions Drugs that Inhibit Cytochrome P450 Isoenzymes Ketoconazole: A pharmacokinetic study with ketoconazole 100 mg b.i.d. with a single dose of venlafaxine 50 mg in extensive metabolizers (EM; n = 14) and 25 mg in poor metabolizers (PM; n = 6) of CYP2D6 resulted in higher plasma concentrations of both venlafaxine and O-desmethylvenlafaxine (ODV) in most subjects following administration of ketoconazole. Venlafaxine Cmax increased by 26% in EM subjects and 48% in PM subjects. Cmax values for ODV increased by 14% and 29% in EM and PM subjects, respectively. Venlafaxine AUC increased by 21% in EM subjects and 70% in PM subjects (range in PMs - 2% to 206%), and AUC values for ODV increased by 23% and 33% in EM and PM (range in PMs - 38% to 105%) subjects, respectively. Combined AUCs of venlafaxine and ODV increased on average by approximately 23% in EMs and 53% in PMs, (range in PMs 4% - 134%). Concomitant use of CYP3A4 inhibitors and venlafaxine may increase levels of venlafaxine and ODV. Therefore, caution is advised if a patient’s therapy includes a CYP3A4 inhibitor and venlafaxine concomitantly.

Flumadine (rimantadine) Tablets and Syrup Prescribing Information	PRECAUTIONS Drug Interactions Live Attenuated Influenza Vaccine (LAIV)

Inderide (propranolol hydrochloride [Inderal] and hydrochlorothiazide) Tablets Prescribing Information	PRECAUTIONS Drug/Drug Interactions Propranolol hydrochloride (Inderal) Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

InnoPran XL (propranolol hydrochloride) Extended Release Capsules Prescribing Information	PRECAUTIONS Drug Interactions Digitalis Glycosides Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Lopressor (metoprolol tartrate tablets, USP) Lopressor (metoprolol tartrate injection, USP) Prescribing Information	PRECAUTIONS Drug Interactions Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Lopressor HCT (metoprolol tartrate USP and hydrochlorothiazide USP) Tablets Prescribing Information	PRECAUTIONS Drug/Drug Interactions Lopressor Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Seroquel (quetiapine fumarate) Tablets Prescribing Information	PRECAUTIONS Leukopenia, Neutropenia and Agranulocytosis Information for Patients Laboratory Tests ADVERSE REACTIONS Vital Signs and Laboratory Studies In postmarketing clinical trials, elevations in total cholesterol (predominantly LDL cholesterol) have been observed. Postmarketing Experience Cardiomyopathy Myocarditis

Sular (nisoldipine) Extended Release Tablets [in new Geomatrix Formulation] Prescribing Information	PRECAUTIONS Information for Patients ...Sular should be taken on an empty stomach (1 hour before or 2 hours after a meal)... This product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions... Drug Interactions CYP3A4 Inhibitors and Inducers See highlighted label for revised text. ADVERSE REACTIONS See highlighted label for revised text. See Adverse Event Table with Sular, dose bioequivalent to...

Tamiflu (oseltamivir phosphate) Capsules and For Oral Suspension Prescribing Information Patient Package Insert See MedWatch Safety Alert posted 3/04/2008 for additional information on Tamiflu.	PRECAUTIONS Hepatic Impairment Neuropsychiatric Events Drug Interactions ...No pharmacokinetic interactions have been observed when coadministering oseltamivir with amoxicillin, acetaminophen, cimetidine or with antacids (magnesium and aluminum hydroxides and calcium carbonates). ADVERSE REACTIONS Observed During Clinical Practice Gastrointestinal Disorders Gastrointestinal Bleeding Hemorrhagic Colitis Psychiatric Delirium, including symptoms such as altered level of consciousness, confusion, abnormal behavior, delusions, hallucinations, agitation, anxiety, nightmares... PATIENT PACKAGE INSERT What are the possible side effects of Tamiflu? People with the flu, particularly children and adolescents, may be at an increased risk of seizures, confusion, or abnormal behavior early during their illness. These events may occur shortly after beginning Tamiflu or may occur when flu is not treated. These events are uncommon but may result in accidental injury to the patient. Therefore, patients should be observed for signs of unusual behavior and a healthcare professional should be contacted immediately if the patient shows any signs of unusual behavior.

Triglide (fenofibrate) Tablets Contact Sciele Pharma, Inc. at 1-800-461-3696 for current prescribing information.	PRECAUTIONS Information for Patients Store tablets only in the moisture protective container

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Brand (Generic) Name	Sections Modified
Celebrex (celecoxib) Capsules Prescribing Information	ADVERSE REACTIONS 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...

Climara (estradiol transdermal system) Prescribing Information	ADVERSE REACTIONS Postmarketing Experience The following adverse reactions have been identified during post approval use of Climara: a few cases in which there were a combination of the symptoms of generalized hives or rash with swelling of the throat or eyelid edema. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Lotrisone (clotrimazole and betamethasone dipropionate) Cream and Lotion Prescribing Information Patient Package Insert	ADVERSE REACTIONS The following local adverse reactions have been reported with topical corticosteroids and may occur more frequently with the use of occlusive dressings... ...capillary fragility (ecchymoses), and sensitization (local reactions upon repeated application of product)... PATIENT PACKAGE INSERT What are the possible side effects of Lotrisone Cream and Lotion? ...fragile blood vessels, sensitization (local reactions upon repeated application of product)...

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Brand (Generic) Name	Sections Modified
Avandia (rosiglitazone maleate) Tablets Prescribing Information (in new labeling format) Patient Package Insert See MedWatch Safety Alert posted 2/26/2008 for new Avandia Medication Guide.	PATIENT PACKAGE INSERT What is Avandia? ...Avandia has not been studied enough in children under 18 years of age to know if it is safe or effective in children.

Nexium (esomeprazole magnesium) Delayed-Release Capsules Nexium (esomeprazole magnesium) Delayed-Release Oral Suspension Patient Package Insert	PATIENT PACKAGE INSERT (new)

Tolectin DS (tolmetin sodium) Capsules Tolectin 600 (tolmetin sodium) Tablets For Oral Administration Medication Guide	MEDICATION GUIDE NSAID medicines that need a prescription Ibuprofen (generic name) Vicoprofen (tradename) [see footnote]

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