MedWatch - October 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) -- October 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
Definity Vial for (perflutren lipid microsphere) Injectable Suspension For Intravenous Use Prescribing Information	BOXED WARNING (new) Warning: Serious Cardiopulmonary Reactions CONTRAINDICATIONS WARNINGS Serious Cardiopulmonary Reactions Anaphylactoid Reactions Systemic Embolization of Definity in Patients with Cardiac Shunts High Ultrasound Mechanical Index QTc Prolongation PRECAUTIONS Information for Patients ADVERSE REACTIONS Clinical Trials Experience Postmarketing Experience	BOXED WARNING Serious cardiopulmonary reactions, including fatalities, have occurred during or within 30 minutes following Definity administration. Assess all patients for the presence of any condition that precludes Definity administration (see CONTRAINDICATIONS). Monitor patients during and for 30 minutes following Definity 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 See highlighted prescribing information for revised text. WARNINGS See highlighted prescribing information for revised text.

Elaprase (idursulfase) Solution For Intravenous Infusion Prescribing Information	BOXED WARNING Risk of Anaphylaxis WARNINGS Anaphylaxis and Allergic Reactions ADVERSE REACTIONS The most serious infusion-related adverse reactions reported with Elaprase were anaphylactic and allergic reactions. Immunogenicity Allergic Reactions	BOXED WARNING: Risk of Anaphylaxis Life-threatening anaphylactic reactions have been observed in some patients during Elaprase infusions. Therefore, appropriate medical support should be readily available when Elaprase is administered. Biphasic anaphylactic reactions have also been observed after Elaprase administration and patients who have experienced anaphylactic reactions may require prolonged observation... WARNINGS: Anaphylaxis and Allergic Reactions ...Reactions have included respiratory distress, hypoxia, hypotension, seizure, loss of consciousness, urticaria and/or angioedema of the throat or tongue. Biphasic anaphylactic reactions have also been reported to occur after administration of Elaprase approximately 24 hours after treatment and recovery from an initial anaphylactic reaction that occurred during Elaprase infusion. Interventions for biphasic reactions have included hospitalization, and treatment with epinephrine, inhaled beta-adrenergic agonists, and corticosteroids... ...Because of the potential for biphasic anaphylactic reactions after Elaprase administration, patients who experience initial severe or refractory reactions may require prolonged observation.

Erbitux (cetuximab) Solution For Intravenous Use Prescribing Information (in new labeling format)	BOXED WARNING Infusion Reactions Cardiopulmonary Arrest WARNINGS & PRECAUTIONS Infusion Reactions Cardiopulmonary Arrest Pulmonary Toxicity Dermatologic Toxicity Hypomagnesemia and Electrolyte Abnormalities Epidermal Growth Factor Receptor (EGFR) Expression and Response ADVERSE REACTIONS Clinical Trials Experience Initial Section Infusion Reactions Infections Renal Squamous Cell Carcinoma of the Head and Neck Colorectal Cancer Table 3 Immunogenicity USE IN SPECIFIC POPULATIONS Nursing Mothers Pediatric Use Geriatric Use PATIENT COUNSELING INFORMATION (new)	BOXED WARNING: Infusion Reaction Serious infusion reactions occurred with the administration of Erbitux in approximately 3% of patients in clinical trials, with fatal outcome reported in less than 1 in 1000... ...Immediately interrupt and permanently discontinue Erbitux infusion for serious infusion reactions... BOXED WARNING: Cardiopulmonary Arrest Cardiopulmonary arrest and/or sudden death occurred in 2% of 208 patients with squamous cell carcinoma of the head and neck treated with radiation therapy and Erbitux. Closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after Erbitux... WARNINGS & PRECAUTIONS See highlighted prescribing information for revised text.

Soriatane (acitretin) Capsules Prescribing Information Medication Guide	BOXED CONTRAINDICATIONS AND WARNINGS Contraindications and Warnings Important Information for Women of Childbearing Potential PRECAUTIONS Initial Section, "A description of the Do Your P.A.R.T. materials... For Prescribers Soriatane has not been studied in and is not indicated for treatment of acne. PATIENT AGREEMENT/INFORMED CONSENT FOR FEMALE PATIENTS MEDICATION GUIDE	BOXED CONTRAINDICATIONS AND WARNINGS Because of Soriatane's teratogenicity, a program called the Do Your P.A.R.T program, Pregnancy Prevention Actively Required During and After Treatment, has been developed to educate women of childbearing potential and their healthcare providers about the serious risks associated with acitretin and to help prevent pregnancies from occurring with the use of this drug and for 3 years after its discontinuation. The Do Your P.A.R.T. program requirements are described below... Important Information for Women of Childbearing Potential See highlighted prescribing information for revised text.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Aptivus (tipranavir) Capsules Prescribing Information (in new labeling format) Patient Package Insert	CONTRAINDICATIONS Drug Interactions Initial Section Table 1: Drugs that are Contraindicated with Aptivus Co-Administered with 200 mg of Ritonavir WARNINGS & PRECAUTIONS Hepatic Impairment and Toxicity Rash Resistance/Cross Resistance ADVERSE REACTIONS Clinical Trials Experience Table 2 Less Common Adverse Reactions Laboratory Abnormalities Drug Interactions Potential for Aptivus/ritonavir to Affect Other Drugs Potential for Other Drugs to Affect Tipranavir Table 4 USE IN SPECIFIC POPULATIONS Hepatic Impairment NONCLINICAL TOXICITY Carcinogenesis, Mutagenesis, Impairment of Fertility PATIENT COUNSELING INFORMATION Rash Sulfa Allergy PATIENT PACKAGE INSERT Who Should Not Take Aptivus? What Should I Tell My Healthcare Professional Before I Take Aptivus? What Are The Possible Side Effects of Aptivus?	CONTRAINDICATIONS See highlighted prescribing information for revised/new text. WARNINGS & PRECAUTIONS See highlighted prescribing information for revised/new text.

Azithromycin for Injection For I.V. Infusion Only Prescribing Information	CONTRAINDICATIONS ADVERSE REACTIONS Postmarketing Adverse Events Special Senses ...reports of taste/smell perversion and/or loss	CONTRAINDICATIONS Azithromycin is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, or any macrolide or ketolide antibiotic.

DDAVP Injection (desmopressin acetate) 4 mcg/mL Prescribing Information See MedWatch Safety Alert posted 12/04/2007 for recent information for Healthcare Professionals.	CONTRAINDICATIONS WARNINGS PRECAUTIONS Drug Interactions ...The concomitant administration of drugs that may increase the risk of water intoxication with hyponatremia (e.g. tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine, opiate analgesics, NSAIDs, lamotrigine and carbamazepine) should be performed with caution. Pediatric Use ...Fluid restriction should be discussed with the patient and/or guardian... ADVERSE REACTIONS Postmarketing ...and rare reports of hyponatremic convulsions associated with concomitant use with the following medications: oxybutinin and imipramine.	CONTRAINDICATIONS ...DDAVP is contraindicated in patients with hyponatremia or a history of hyponatremia. WARNINGS Very rare cases of hyponatremia have been reported from world-wide postmarketing experience in patients treated with DDAVP (desmopression acetate). DDAVP is a potent antidiuretic which, when administered, may lead to water intoxication and/or hyponatremia. Unless properly diagnosed and treated hyponatremia can be fatal. Therefore, fluid restriction is recommended and should be discussed with the patient and/or guardian. Careful medical supervision is required. ...All patients receiving DDAVP therapy should be observed for the following signs of symptoms associated with hyponatremia: headache, nausea/vomiting, decreased serum sodium, weight gain, restlessness, fatigue, lethargy, disorientation, depressed reflexes, loss of appetite, irritability, muscle weakness, muscle spasms or cramps and abnormal mental status such as hallucinations, decreased consciousness and confusion. Severe symptoms may include one or a combination of the following: seizure, coma and/or respiratory arrest... ...DDAVP should be used with caution in patients with habitual or psychogenic polydipsia who may be more likely to drink excessive amounts of water, putting them at greater risk of hyponatremia.

DDAVP Nasal Spray (desmopressin acetate) Prescribing Information Patient Package Insert See MedWatch Safety Alert posted 12/04/2007 for recent information for Healthcare Professionals.	CONTRAINDICATIONS WARNINGS PRECAUTIONS General ...heart failure and renal disorders (added) Information for Patients Ensure that in children, administration is under adult supervision in order to control the dose intake... Fluid intake should be adjusted downward based upon discussion with the physician. Drug Interactions ...The concomitant administration of drugs that may increase the risk of water intoxication with hyponatremia... ADVERSE REACTIONS Postmarketing There have been rare reports of hyponatremia convulsions associated with concomitant use with the following medications: oxybutinin and imipramine. PATIENT PACKAGE INSERT Caution Ensure that in children administration is under adult supervision in order to control the dose intake. If you accidentally deliver/administer too much of a dose, immediately telephone your doctor or a certified Regional Poison Center for advice. Possible signs of overdose may include confusion, drowsiness, continued headache, problems with passing urine and rapid weight gain due to fluid retention.	CONTRAINDICATIONS ...DDAVP is contraindicated in patients with hyponatremia or a history of hyponatremia. WARNINGS ...DDAVP Nasal Spray should only be used in patients where orally administered formulations are not feasible. Very rare cases of hyponatremia have been reported from world-wide postmarketing experience in patients treated with DDAVP (desmopression acetate). DDAVP is a potent antidiuretic which, when administered, may lead to water intoxication and/or hyponatremia. Unless properly diagnosed and treated hyponatremia can be fatal. Therefore, fluid restriction is recommended and should be discussed with the patient and/or guardian. Careful medical supervision is required. ...All patients receiving DDAVP therapy should be observed for the following signs or symptoms associated with hyponatremia: headache, nausea/vomiting, decreased serum sodium, weight gain, restlessness, fatigue, lethargy, disorientation, depressed reflexes, loss of appetite, irritability, muscle weakness, muscle spasms or cramps and abnormal mental status such as hallucinations, decreased consciousness and confusion. Severe symptoms may include one or a combination of the following: seizure, coma and/or respiratory arrest... DDAVP should be used with caution in patients with habitual or psychogenic polydipsia who may be more likely to drink excessive amounts of water, putting them at greater risk of hyponatremia.

DDAVP Rhinal Tube (desmopressin acetate) Prescribing Information Patient Package Insert See MedWatch Safety Alert posted 12/04/2007 for recent information for Healthcare Professionals.	CONTRAINDICATIONS WARNINGS PRECAUTIONS General ...heart failure and renal disorders (added) Ensure that in children, administration is under adult supervision in order to control the dose intake. Drug Interactions ...The concomitant administration of drugs that may increase the risk of water intoxication with hyponatremia... Pediatric Use ...Fluid restriction should be discussed with the patient and/or guardian... Geriatric Use ...Fluid restriction should be discussed with the patient. ADVERSE REACTIONS Postmarketing There have been rare reports of hyponatremic convulsions associated with concomitant use with the following medications: oxybutinin and imipramine. PATIENT PACKAGE INSERT Ensure that in children administration is under adult supervision in order to control the dose intake If you accidentially deliver/administer too much of a dose, immediately telephone your doctor or a certified Regional Poison Center for advice. Possible signs of overdose may include confusion, drowsiness, continuing headache, problems with passing urine and rapid weight gain due to fluid retention.	CONTRAINDICATIONS ...DDAVP is contraindicated in patients with hyponatremia or a history of hyponatremia. WARNINGS ...DDAVP Rhinal Tube should only be used in patients where orally administered formulations are not feasible. Very rare cases of hyponatremia have been reported from world-wide postmarketing experience in patients treated with DDAVP (desmopression acetate). DDAVP is a potent antidiuretic which, when administered, may lead to water intoxication and/or hyponatremia. Unless properly diagnosed and treated hyponatremia can be fatal. Therefore, fluid restriction is recommended and should be discussed with the patient and/or guardian. Careful medical supervision is required. ...All patients receiving DDAVP therapy should be observed for the following signs or symptoms associated with hyponatremia: headache, nausea/vomiting, decreased serum sodium, weight gain, restlessness, fatigue, lethargy, disorientation, depressed reflexes, loss of appetite, irritability, muscle weakness, muscle spasms or cramps and abnormal mental status such as hallucinations, decreased consciousness and confusion. Severe symptoms may include one or a combination of the following: seizure, coma and/or respiratory arrest... DDAVP should be used with caution in patients with habitual or psychogenic polydipsia who may be more likely to drink excessive amounts of water, putting them at greater risk of hyponatremia.

DDAVP Tablets (desmopressin acetate) Prescribing Information See MedWatch Safety Alert posted 12/04/2007 for recent information for Healthcare Professionals.	CONTRAINDICATIONS WARNINGS PRECAUTIONS Drug Interactions ...The concomitant administration of drugs that may increase the risk of water intoxication with hyponatremia, (e.g. tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine, opiate analgesics, NSAIDs, lamotrigine and carbamazepine) should be performed with caution. Pediatric Use Central Diabetes Insipidus ...Fluid restriction should be discussed with the patient and/or guardian. Primary Nocturnal Enuresis ...Treatment with desmopressin for primary nocturnal enuresis should be interrupted during the acute intercurrent illness characterized by fluid and/or electrolyte imbalance... Geriatric Use ...Fluid restriction should be discussed with the patient. ADVERSE REACTIONS Postmarketing There have been rare reports of hyponatremia convulsions associated with concomitant use with the following medications: oxybutinin and imipramine.	CONTRAINDICATIONS ...DDAVP is contraindicated in patients with hyponatremia or a history of hyponatremia. WARNINGS Very rare cases of hyponatremia have been reported from world-wide postmarketing experience in patients treated with DDAVP (desmopression acetate). DDAVP is a potent antidiuretic which, when administered, may lead to water intoxication and/or hyponatremia. Unless properly diagnosed and treated hyponatremia can be fatal. Therefore, fluid restriction is recommended and should be discussed with the patient and/or guardian. Careful medical supervision is required. ...All patients receiving DDAVP therapy should be observed for the following signs of symptoms associated with hyponatremia: headache, nausea/vomiting, decreased serum sodium, weight gain, restlessness, fatigue, lethargy, disorientation, depressed reflexes, loss of appetite, irritability, muscle weakness, muscle spasms or cramps and abnormal mental status such as hallucinations, decreased consciousness and confusion. Severe symptoms may include one or a combination of the following: seizure, coma and/or respiratory arrest... DDAVP should be used with caution in patients with habitual or psychogenic polydipsia who may be more likely to drink excessive amounts of water, putting them at greater risk of hyponatremia.

Inderal LA (propranolol hydrochloride) Long-Acting Capsules Prescribing Information	CONTRAINDICATIONS WARNINGS Angina Pectoris Hypersensitivity and Skin Reactions Cardiac Failure Nonallergic Bronchospasm (e.g. Chronic Bronchitis, Emphysema Major Surgery Diabetes and Hypoglycemia Thyrotoxicosis Wolff-Parkinson-White Syndrome PRECAUTIONS Clinical Laboratory Tests Drug Interactions Caution should be exercised when Inderal LA is administered with drugs that have an affect on CYP2D6, 1A2, or 2C19 metabolic pathways... Cardiovascular Drugs Antiarrhythmics Digitalis Glycosides Calcium Channel Blockers ACE Inhibitors Alpha Blockers Reserpine Inotropic Agents Isoproterenol and Dobutamine Non-Cardiovascular Drugs Nonsteroidal Anti-Inflammatory Drugs Antidepressants Anesthetic Agents Warfarin Neuroleptic Drugs Thyroxine Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy: Pregnancy Category C Pediatric Use ADVERSE REACTIONS Skin and Mucous Membranes Genitourinary	CONTRAINDICATIONS Propranolol is contraindicated in 1) cardiogenic shock; 2) sinus bradycardia and greater than first-degree block; 3) bronchial asthma; and 4) in patients with known hypersensitivity to propranolol hydrochloride. WARNINGS See highlighted prescribing information for revised text.

Januvia (sitagliptin) Tablets Prescribing Information (in new labeling format) Patient Package Insert	CONTRAINDICATIONS WARNINGS & PRECAUTIONS Use with Medications Known to Cause Hypoglycemia Hypersensitivity Reactions ADVERSE REACTIONS Clinical Trials Experience Table 1 Table 2 Postmarketing Experience USE IN SPECIFIC POPULATIONS Pediatric Use PATIENT COUNSELING INFORMATION Instructions Patients should be informed that allergic reactions have been reported during postmarketing use of Januvia... PATIENT PACKAGE INSERT What is Januvia? Who should not take Januvia? What should I tell my doctor before and during treatment with Januvia? How should I take Januvia? What are the possible side effects of Januvia?	CONTRAINDICATIONS History of a serious hypersensitivity reaction to sitagliptin, such as anaphylaxis or angioedema. [See Warnings and Precautions and Adverse Reactions.] WARNINGS & PRECAUTIONS Use with Medications Known to Cause Hypoglycemia As is typical with other antihyperglycemic agents used in combination with a sulfonylurea, when Januvia was used in combination with a sulfonylurea, a class of medications known to cause hypoglycemia, the incidence of hypoglycemia was increased over that of placebo... Hypersensitivity Reactions There have been postmarketing reports of serious hypersensitivity reactions in patients treated with Januvia. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Onset of these reactions occurred within the first 3 months after initiation of treatment with Januvia, with some reports occurring after the first dose. If a hypersensitivity reaction is suspected, discontinue Januvia, assess for other potential causes for the event, and institute alternative treatment for diabetes...

Lodine (etodolac capsules and tablets) Please contact Wyeth Pharmaceuticals at 1-800-934-5556 for prescribing information.	CONTRAINDICATIONS WARNINGS Renal Effects PRECAUTIONS Cyclosporine, Digoxin, Methotrexate ...NSAIDs, such as Lodine, should not be administered prior to or concomitantly with high doses of methotrexate... Diuretics ...Lodine can reduce the natriuretic effect of furosemide and thiazides in some patients with possible loss of blood pressure control... ...During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal insufficiency or failure... Lithium ...Careful monitoring of lithium levels is advised in the event NSAID dosage adjustments are required. Warfarin ...Close monitoring of such patients is therefore recommended. Nursing Mothers Trace amounts of some NSAIDs have been reported in human milk... ADVERSE REACTIONS Incidence Greater Than or Equal to 1% - Probably Causally Related: Digestive System Abdominal Distension Epigastric Pain Abnormal Stools Nervous System Fatigue Musculoskeletal Arthralgia Incidence Less Than 1% - Probably Causally Related: Hemic and Lymphatic System Aplastic Anemia Skin and Appendages Exfoliative Dermatitis Leukocytoclastic Vasculitis Incidence Less Than 1% - Causal Relationship Unknown: Digestive System GI Discomfort Burning Sensation Blood in Stools Gastralgia Upper Abdominal Discomfort Nervous System Irritability Respiratory System Bronchospasm Special Senses Loss of Taste Urogenital System Renal Impairment Musculoskeletal Muscle Pain	CONTRAINDICATIONS Lodine is contraindicated in patients with known hypersensitivity to etodolac or other ingredients in Lodine. WARNINGS: Renal Effects Caution is recommended in patients with pre-existing kidney disease.

Prevpac (lansoprazole 30-mg capsules, amoxicillin 500-mg capsules, USP, and clarithromycin 500-mg tablets, USP) Prescribing Information	CONTRAINDICATIONS WARNINGS Amoxicillin and/or Clarithromycin Clostridium difficile associated diarrhea (CDAD) PRECAUTIONS Drug Interactions Prevacid Carcinogenesis, Mutagenesis, Impairment of Fertility Prevacid ADVERSE REACTIONS Prevacid Incidence in Clinicial Trials Postmarketing Laboratory Values	CONTRAINDICATIONS Concomitant administration of Prevpac and any of the following drugs is contraindicated: cisapride, pimozide, astemizole, terfenadine, ergotamine or dihydroergotamine... ...For information about contraindications of other drugs that may be used in combination with amoxicillin or clarithromycin, refer to the CONTRAINDICATIONS section of their package inserts. WARNINGS: Amoxicillin and/or Clarithromycin See highlighted prescribing information for revised text.

ProQuad [Measles, Mumps, Rubella and Varicella (Oka/Merck) Virus Vaccine Live] [Frozen Formulation] Prescribing Information	CONTRAINDICATIONS ADVERSE REACTIONS Postmarketing Reports Infections and Infestations Herpes Zoster Varicella Immune System Disorders Anaphylactic Reaction Nervous System Disorders Ataxia Convulsion Febrile Seizure Skin and Subcutaneous Tissue Disorders Pruritus	CONTRAINDICATIONS ...In addition, disseminated varicella vaccine virus infection has been reported in children with underlying immunodeficiency disorders who were inadvertently vaccinated with a varicella-containing vaccine.

ProQuad [Measles, Mumps, Rubella and Varicella (Oka/Merck) Virus Vaccine Live] [Refrigerator-Stable Formulation] Prescribing Information	CONTRAINDICATIONS ADVERSE REACTIONS Postmarketing Reports Infections and Infestations Herpes Zoster Varicella Immune System Disorders Anaphylactic Reaction Nervous System Disorders Ataxia Convulsion Febrile Seizure Skin and Subcutaneous Tissue Disorders Pruritus	CONTRAINDICATIONS ...In addition, disseminated varicella vaccine virus infection has been reported in children with underlying immunodeficiency disorders who were inadvertently vaccinated with a varicella-containing vaccine.

Zithromax (azithromycin tablets and azithromycin for oral suspension) Prescribing Information	CONTRAINDICATIONS ADVERSE REACTIONS Postmarketing Adverse Events Special Senses ...reports of taste/smell perversion and/or loss	CONTRAINDICATIONS Zithromax is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, or any macrolide or ketolide antibiotic.

Zmax (azithromycin extended release) For Oral Suspension Prescribing Information	CONTRAINDICATIONS ADVERSE REACTIONS Postmarketing Adverse Events Special Senses ...reports of taste/smell perversion and/or loss	CONTRAINDICATIONS Zmax is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, or any macrolide or ketolide antibiotic.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Cubicin (daptomycin for injection) Prescribing Information	WARNINGS Clostridium difficile-associated diarrhea (CDAD) PRECAUTIONS Information for Patients Diarrhea is a common problem caused by antibiotics that usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having received the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.	WARNINGS Clostridium difficile–associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Cubicin, 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, since 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 because CDAD has been reported to occur over 2 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.

Dalmane (flurazepam hydrochloride) Capsules Prescribing Information	WARNINGS Initial Section Severe Anaphylactic and Anaphylactoid Reactions PRECAUTIONS Information for Patients "Sleep-Driving" and Other Complex Behavior	WARNINGS See highlighted prescribing information for revised text.

Doral (quazepam tablets, USP) Prescribing Information Medication Guide	WARNINGS Initial Section Severe Anaphylactic and Anaphylactoid Reactions PRECAUTIONS Information for Patients "Sleep-Driving" and Other Complex Behaviors MEDICATION GUIDE (new)	WARNINGS See highlighted prescribing information for revised text.

Lexxel (enalapril maleate-felodipine ER) Tablets Prescribing Information	WARNINGS Fetal/Neonatal Morbidity and Mortality PRECAUTIONS Information for Patients Pregnancy Female patients of childbearing age should be told about the consequences of exposure to ACE inhibitors during pregnancy. These patients should be asked to report pregnancies to their physicians as soon as possible.	WARNINGS: Fetal/Neonatal Morbidity and Mortality ...In a published retrospective epidemiological study, infants whose mothers had taken an ACE inhibitor drug during the first trimester of pregnancy appeared to have an increased risk of major congenital malformations compared with infants whose mothers had not undergone first trimester exposure to ACE inhibitor drugs. The number of cases of birth defects is small and the findings of this study have not yet been repeated...

Lymphazurin 1% (isosulfan blue) Aqueous Solution Prescribing Information (in new labeling format)	WARNINGS & PRECAUTIONS Interference with Oxygen Saturation and Methemoglobin Measurements	WARNINGS & PRECAUTIONS Lymphazurin 1% interferes with measurements of oxygen saturation in peripheral blood by pulse oximetry and can cause falsely low readings. The interference effect is maximal at 30 minutes and minimal generally by four hours after administration. Arterial blood gas analysis may be needed to verify decreased arterial partial pressure of oxygen. Lymphazurin 1% may also cause falsely elevated readings of methemoglobin by arterial blood gas analyzer. Therefore, co-oximetry may be needed to verify methemoglobin level.

NuvaRing (etonogestrel/ethinyl estradiol vaginal ring) For Vaginal Use Only Prescribing Information	WARNINGS Initial Section Thromboembolic Disorders and Other Vascular Problems Cerebrovascular Diseases Dose-related Risk of Vascular Disease from Oral Contraceptives Estimates of Mortality from Contraceptive Use Carcinoma of the Reproductive Organs and Breasts Elevated Blood Pressure PRECAUTIONS Lipids Disorders Emotional Disorders Drug Interactions Anti-HIV Protease Inhibitors Vaginal Use Urinary Bladder Insertion	WARNINGS See highlighted prescribing information for revised text.

Rapamune (sirolimus) Oral Solution and Tablets Prescribing Information	WARNINGS PRECAUTIONS Fluid Accumulation and Wound Healing ADVERSE REACTIONS Other Clinical Experience Incisional Hernia (added) Pericardial Effusion... Azoospermia... ...A 5-fold increase in the reports of tuberculosis...	WARNINGS ...Oversuppression of the immune system can also increase susceptibility to infection including opportunistic infections such as tuberculosis, fatal infections, and sepsis...

Renagel (sevelamer hydrocholoride) Tablets For Oral Use Prescribing Information (in new labeing format)	WARNINGS & PRECAUTIONS Use Caution in Patients with Gastrointestinal Disorders ADVERSE REACTIONS Postmarketing Experience PATIENT COUNSELING INFORMATION Adverse Events	WARNINGS & PRECAUTIONS: Use Caution in Patients with Gastrointestinal Disorders The safety of Renagel has not been established in patients with dysphagia, swallowing disorders, severe gastrointestinal (GI) motility disorders including severe constipation, or major GI tract surgery...

Vaseretic (enalapril maleate - hydrochlorothiazide) Tablets Prescribing Information	WARNINGS General Enalapril Maleate Intestinal Angioedema Pregnancy Enalapril Maleate Fetal/Neonatal Morbidity and Mortality PRECAUTIONS Pregnancy Female patients of childbearing age should be told about the consequences of exposure to ACE inhibitors. These patients should be asked to report pregnancies to their physicians as soon as possible...	WARNINGS: Intestinal Angioedema Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain... WARNINGS: Fetal/Neonatal Morbidity and Mortality ...In a published restrospective epidemiological study, infants whose mothers had taken an ACE inhibitor during their first trimester of pregnancy appeared to have an increased risk of major congenital malformations compared with infants whose mothers had not undergone first trimester exposure to ACE inhibitor drugs. The number of cases of birth defects is small and the findings of this study have not yet been repeated...

Vasotec (enalapril maleate) Tablets Prescribing Information	WARNINGS Intestinal Angioedema Fetal/Neonatal Morbidity and Mortality PRECAUTIONS Pregnancy Female patients of childbearing age should be told about the consequences of exposure to ACE inhibitors. These patients should be asked to report pregnancies to their physicians as soon as possible...	WARNINGS: Intestinal Angioedema Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain... WARNINGS: Fetal/Neonatal Morbidity and Mortality ...In a published restrospective epidemiological study, infants whose mothers had taken an ACE inhibitor drug during the first trimestrer of pregnancy appeared to have an increased risk of major congenital malformations compared with infants whose mothers had not undergone first trimester exposure to ACE inhibitor drugs. The number of cases of birth defects is small and the findings of this study have not yet been repeated...

Visken (pindolol) Tablets, USP Prescribing Information	WARNINGS Cardiac Failure	WARNINGS: Cardiac Failure ...Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia...

Zestoretic (lisinopril and hydrochlorothiazide) Tablets Prescribing Information	WARNINGS Lisinopril Anaphylactoid Reactions During Membrane Exposure PRECAUTIONS Drug Interactions Gold Nitritoid Reactions... ADVERSE REACTIONS Skin Cutaneous Pseudolymphoma	WARNINGS: Anaphylactoid Reactions During Membrane Exposure Thiazide-containing combination products are not recommended in patients with severe renal dysfunction. Sudden and potentially life-threatening anaphylactoid reactions have been reported in some patients dialyzed with high-flux membranes (eg, AN69®*) and treated concomitantly with an ACE inhibitor. In such patients, dialysis must be stopped immediately, and aggressive therapy for anaphylactoid reactions must be initiated. Symptoms have not been relieved by antihistamines in these situations. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.

Zestril (lisinopril) Tablets Prescribing Information	WARNINGS Anaphylactoid Reactions During Membrane Exposure PRECAUTIONS Drug Interactions Gold Nitritoid Reactions... ADVERSE REACTIONS Skin Cutaneous Pseudolymphoma	WARNINGS: Anaphylactoid Reactions During Membrane Exposure Sudden and potentially life threatening anaphylactoid reactions have been reported in some patients dialyzed with high-flux membranes (e.g., AN69®*) and treated concomitantly with an ACE inhibitor. In such patients, dialysis must be stopped immediately, and aggressive therapy for anaphylactoid reactions must be initiated. Symptoms have not been relieved by antihistamines in these situations. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.

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Brand (Generic) Name	Sections Modified
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)	USE IN SPECIFIC POPULATIONS Pediatric Use ADVERSE REACTIONS Clinical Studies Experience Pediatric Patients (13 to 17 years) with Schizophrenia Adverse Reactions Associated with Discontinuation of Treatment Commonly Observed Adverse Reactions Less Common Adverse Reactions in Pediatric Patients (13 to 17 yrs) with Schizophrenia Table 6

Accutane (isotretinoin capsules) Prescribing Information	PRECAUTIONS Prescribers Secondary Forms of Contraception All Patients Female Patients of Childbearing Potential Pharmacists Accutane must only be dispensed...

Adagen (pegademase bovine) Injection Prescribing Information	PRECAUTIONS General Any laboratory or clinical indication of a decrease in potency of Adagen (pegademase bovine) Injection should be reported immediately by telephone to Enzon Pharmaceuticals, Inc. Telephone 866-792-5172.

Cialis (tadalafil) Tablets Prescribing Information Patient Package Insert See MedWatch Safety Alert posted 10/18//2007 for additional information on Cialis labeling revisions.	PRECAUTIONS Information for Patients Physicians should advise patients to stop taking PDE5 inhibitors, including Cialis, and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including Cialis. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors... ADVERSE REACTIONS Otologic Sudden Decrease or Loss of Hearing Tinnitus Postmarketing Surveillance Otologic Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including Cialis... PATIENT PACKAGE INSERT What are the possible side effects of Cialis? Sudden loss or decrease in hearing, sometimes with ringing in the ears and dizziness, has been rarely reported in people taking PDE5 inhibitors, including Cialis. It is not possible to determine whether these events are related directly to the PDE5 inhibitors, to other diseases or medications, to other factors, or to a combination of factors. If you experience these symptoms, stop taking Cialis and contact a doctor right away.

Coreg CR (carvedilol phosphate) Extended-release Capsules Prescribing Information	PRECAUTIONS Drug Interactions Digitalis Glycosides Pediatric Use Effectiveness of carvedilol in patients younger than 18 years of age has not been established...

Levitra (vardenafil hydrochloride) Tablets Prescribing Information Patient Package Insert See MedWatch Safety Alert posted 10/18//2007 for additional information on Levitra labeling revisions.	PRECAUTIONS Information for Patients Physicians should advise patients to stop taking PDE5 inhibitors, including Levitra, and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including Levitra. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors (see ADVERSE REACTIONS). ADVERSE REACTIONS Auditory Sudden Decrease or Loss of Hearing Tinnitus Postmarketing Experience Otologic Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including Levitra... PATIENT PACKAGE INSERT What are the possible side effects of Levitra? Sudden loss or decrease in hearing, sometimes with ringing in the ears and dizziness, has been rarely reported in people taking PDE5 inhibitors, including Levitra. It is not possible to determine whether these events are related directly to the PDE5 inhibitors, to other diseases or medications, to other factors, or to a combination of factors. If you experience these symptoms, stop taking Levitra and contact a doctor right away.

Lexiva (fosamprenavir calcium) Tablets and Oral Suspension Prescribing Information (in new labeling format)	DRUG INTERACTIONS Established and Other Potentially Significant Drug Interactions Table 6 Oral Contraceptives ADVERSE REACTIONS Initial Paragraph Severe or life-threatening skin reactions have been reported with the use of Lexiva. The most common adverse reactions leading to discontinuation of Lexiva (increased >1% of patients) included diarrhea, nausea, vomiting, AST increased, ALT increased, and rash. Clinical Trials in Adults Initial Paragraph

Retisert (fluocinolone acetonide intravitreal implant) 0.59 mg Prescribing Information	PRECAUTIONS General In vitro stability studies show that the strength of the adhesive bond between the silicone cup reservoir and the suture tab is reduced with prolonged hydration, indicating a potential for the separation of these components. Physicians should monitor the integrity of the implant during ophthalmologic examinations.

Rhinocort Aqua (budesonide) Nasal Spray 32 mcg Prescribing Information	PRECAUTIONS Nursing Mothers

Symbicort 80/4.5 (budesonide 80 mcg and formoterol fumarate dihydrate 4.5 mcg) Inhalation Aerosol Symbicort 160/4.5 (budesonide 160 mcg and formoterol fumarate dihydrate 4.5 mcg) Inhalation Aerosol For Oral Inhalation Only Prescribing Information Medication Guide	PRECAUTIONS Nursing Mothers MEDICATION GUIDE

Tamiflu (oseltamivir phosphate) Capsules and For Oral Suspension Prescribing Information Patient Package Insert	PRECAUTIONS Information for Patients A bottle of 13 g Tamiflu for Oral Suspension contains approximately 11 g sorbitol. One dose of 75 mg Tamiflu for Oral Suspension delivers 2 g sorbitol... Carcinogenesis, Mutagenesis, and Impairment of Fertility In 2-year carcinogenicity studies in mice and rats given daily oral doses of the pro-drug oseltamivir phosphate up to 400 mg/kg and 500 mg/kg, respectively, the pro-drug oseltamivir phosphate and the active form oseltamivir carboxylate induced no statistically significant increases in tumors over controls... PATIENT PACKAGE INSERT Who Should Not Take Tamiflu?

Velcade (bortezomib) For Injection Prescribing Information (in new labeling format)	USE IN SPECIFIC POPULATIONS Patients with Renal Impairment

Viagra (sildenafil citrate) Tablets Prescribing Information Patient Package Insert See MedWatch Safety Alert posted 10/18//2007 for additional information on Viagra labeling revisions.	PRECAUTIONS Information for Patients Physicians should advise patients to stop taking PDE5 inhibitors, including Viagra, and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including Viagra. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors (see ADVERSE REACTIONS, Clinical Trials and Post-Marketing Experience). ADVERSE REACTIONS Special Senses Sudden Decrease or Loss of Hearing Postmarketing Experience Special Senses Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including Viagra... PATIENT PACKAGE INSERT Possible Side Efffects Sudden loss or decrease in hearing, sometimes with ringing in the ears and dizziness, has been rarely reported in people taking PDE5 inhibitors, including Viagra. It is not possible to determine whether these events are related directly to the PDE5 inhibitors, to other diseases or medications, to other factors, or to a combination of factors. If you experience these symptoms, stop taking Viagra and contact a doctor right away.

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Brand (Generic) Name	Sections Modified
Cordarone (amiodarone HCl) Tablets Prescribing Information	ADVERSE REACTIONS Postmarketing Reports ...parkinsonian symptoms such as akinesia and bradykinesia (sometimes reversible with discontinuation of therapy)…

Geodon (ziprasidone HCl) Capsules Geodon (ziprasidone mesylate) for Injection For IM Use Only Prescribing Information	ADVERSE REACTIONS Other Events Observed During Postmarketing Use Digestive System Disorders Swollen Tongue Nervous System Disorders Facial Droop Tardive Dyskinesia Urogenital System Disorders Enuresis Urinary Incontinence

Vivitrol (naltrexone for extended-release injectable suspension) Prescribing Information	ADVERSE REACTIONS Postmarketing Reports Reports From Other Intramuscular Drug Products Containing Polylactide-coglycolide (PLG) Microspheres – Not With Vivitrol Retinal Artery Occlusion

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Brand (Generic) Name	Sections Modified
Ambien (zolpidem tartrate) Tablets Medication Guide	MEDICATION GUIDE (new)

depo-subQ provera 104 for Subcutaneous Use Instructions for Administration	INSTRUCTIONS FOR ADMINISTRATION

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