MedWatch - May 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) -- May 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

Definity (perflutren lipid microsphere) Injectable Suspension

Prescribing Information

BOXED WARNING

WARNING: Serious Cardiopulmonary Reactions

WARNINGS

Serious Cardiopulmonary Reactions
Anaphylactoid Reactions

ADVERSE REACTIONS

Postmarketing Experience

BOXED WARNING AND WARNINGS

Serious cardiopulmonary reactions, including fatalities, have occurred during or following perflutren-containing microsphere administration.

BOXED WARNING

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 Definity administration...

WARNINGS

Serious Cardiopulmonary Reactions

...In these patients, monitor vital signs, electrocardiography, and cutaneous oxygen saturation during and for at least 30 minutes after Definity administration. In the absence of these underlying conditions, observe patients closely during and following Definity administration.

In postmarketing use, uncommon but serious reactions observed during or shortly following perflutren-containing microsphere administration included fatal cardiac or respiratory arrest...

Anaphylactoid Reactions

Post-marketing reports of acute anaphylactoid reactions including shock, bronchospasm, upper airway swelling, loss of consciousness, urticaria and pruritus, have occurred in patients with no prior exposure to perflutren-containing microsphere products...

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Ambien (zolpidem tartrate) Tablets Prescribing Information (in new labeling format) Medication Guide	CONTRAINDICATIONS WARNINGS AND PRECAUTIONS Abnormal thinking and behavioral changes Special populations Use in patients with concomitant illness ADVERSE REACTIONS Clinical trials experience Adverse event incidence across the entire preapproval database Body as a whole Fatigue Central and peripheral nervous system headache anxiety nervousness Gastrointestinal system dyspepsia nausea anorexia vomiting Immunologic system Infection (infrequent) Musculoskeletal system Frequent arthralgia myalgia Respiratory system upper respiratory infection (frequent) rhinitis Urogenital system urinary tract infection (frequent) DRUG INTERACTIONS Drugs that affect drug metabolism via cytochrome P450 Drug-laboratory test interactions USE IN SPECIFIC POPULATIONS Pregnancy Nursing mothers Pediatric use Geriatric use PATIENT COUNSELING INFORMATION Severe anaphylactic and anaphylactoid reactions Sleep-driving and other complex behaviors Administration instructions MEDICATION GUIDE	CONTRAINDICATIONS ...Observed reactions include anaphylaxis and angioedema. WARNINGS AND PRECAUTIONS Abnormal thinking and behavioral changes 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 with sedative-hypnotics, including zolpidem... Special populations: Use in patients with concomitant illness ...Since sedative/hypnotics have the capacity to depress respiratory drive, precautions should be taken if Ambien is prescribed to patients with compromised respiratory function... ...Ambien should be used with caution in patients with sleep apnea syndrome or myasthenia gravis.

Ceftriaxone for Injection and Dextrose Injection Prescribing Information See MedWatch Safety Alert for Rocephin posted 09/11/2007 and 07/05/2007 for additional safety information.	CONTRAINDICATIONS Neonates (<28 days) WARNINGS Hypersensitivity Interaction with Calcium-Containing Products Clostridium difficile PRECAUTIONS Pediatric Use ...Ceftriaxone for Injection and Dextrose Injection should not be administered... ADVERSE REACTIONS Local Reactions Pain, induration and tenderness was 1% overall ... Cases of fatal reactions with ceftriaxone-calcium precipitates in lung and kidneys in neonates have been described...	CONTRAINDICATIONS Neonates (<28 days) Hyperbilirubinemic neonates, especially prematures, should not be treated with Ceftriaxone for Injection and Dextrose Injection. In vitro studies have shown that ceftriaxone can displace bilirubin from its binding to serum albumin and bilirubin encephalopathy can possibly develop in these patients. Ceftriaxone for Injection and Dextrose Injection must not be co-administered with calcium containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition, in neonates because of the risk of precipitation of ceftriaxone-calcium salt. Cases of fatal reactions with ceftriaxone-calcium precipitates in lung and kidneys in neonates have been described. In some cases the infusion lines and the times of administration of ceftriaxone and calcium-containing solutions differed. WARNINGS Interaction with Calcium-Containing Products There are no reports to date of intravascular or pulmonary precipitations in patients, other than neonates, treated with ceftriaxone and calcium-containing IV solutions. However, the theoretical possibility exists for an interaction between ceftriaxone and IV calcium-containing solutions in patients other than neonates. Therefore, Ceftriaxone for Injection and Dextrose Injection and calcium-containing solutions, including continuous calcium-containing infusions such as parenteral nutrition, should not be mixed or co-administered to any patient irrespective of age, even via different infusion lines at different sites. As a further theoretical consideration and based on 5 half-lives of ceftriaxone, Ceftriaxone for Injection and Dextrose Injection and IV calcium-containing solutions should not be administered within 48 hours of each other in any patient... No data are available on potential interaction between ceftriaxone and oral calcium-containing products or interaction between intramuscular ceftriaxone and calcium-containing products (IV or oral).

Mirena (levonorgestrel-releasing intrauterine system) Prescribing Information Patient Package Insert	CONTRAINDICATIONS WARNINGS Ectopic Pregnancy Sepsis Perforation Ovarian Cysts Breast Cancer PRECAUTIONS Continuation and Removal Mirena should be removed for the following reasons: Pelvic Infection Endometritis Drug Interactions Nursing Mothers ADVERSE REACTIONS Other relevant reported adverse reactions occurring in less than 5% of subjects include: Vomiting Postmarketing Experience PATIENT PACKAGE INSERT What is Mirena? How does Mirena work? Who should not use Mirena? Tell your health care provider if you... How is Mirena placed? How can I check that Mirena is in place? Is it safe to breast-feed while using Mirena? What are the possible side effects of usine Mirena? When should I call my health care provider?	CONTRAINDICATIONS Mirena is contraindicated when one or more of the following conditions exist: Conditions associated with increased susceptibility to pelvic infections. WARNINGS Ectopic Pregnancy ...Up to half of pregnancies that occur with Mirena in place are ectopic. The incidence of ectopic pregnancy in clinical trials that excluded women with risk factors for ectopic pregnancy was about 1 ectopic pregnancy per 1000 users per year. Tell women who choose Mirena about the risks of ectopic pregnancy, including the loss of fertility. Teach them to recognize and report to their physician promptly any symptoms of ectopic pregnancy... Sepsis ...In some cases, severe pain occurred within hours of insertion followed by sepsis within days... Perforation Perforation or penetration of the uterine wall or cervix may occur during insertion although the perforation may not be detected until some time later... Ovarian Cysts ...Surgical intervention is not usually required. Breast Cancer ...Two observational studies have not provided evidence of an increased risk of breast cancer during the use of Mirena.

Noxafil (posaconazole) Oral Suspension Prescribing Information Patient Package Insert	CONTRAINDICATIONS PRECAUTIONS Information for Patients Drug Interactions Table 8 Efavirenz Table 9 Sirolimus Atazanavir Ritonavir Table 10 Halofantrine Digoxin PATIENT PACKAGE INSERT Who should not take Noxafil? Sirolimus Can I take other medicines with Noxafil? Ritonavir Atazanavir	CONTRAINDICATIONS ...Co-administration of Noxafil (posaconazole) with sirolimus is contraindicated ...

Valium (diazepam) Tablets Prescribing Information	CONTRAINDICATIONS WARNINGS Initial Section Pregnancy Labor and Delivery (new subsection) Nursing Mothers (new subsection) PRECAUTIONS General Information for Patients Drug Interactions Centrally Acting Agents Alcohol Antacids Compounds Which Inhibit Certain Hepatic Enzymes Phenytoin Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy: Category D Geriatric Use (new subsection) Hepatic Insufficiency (new subsection) ADVERSE REACTIONS Initial Section Central Nervous System Gastrointestinal System Special Senses Cardiovascular System Psychiatric and Paradoxical Reactions Urogenital System Skin and Appendages Laboratories Other Antegrade Amnesia... Minor changes in EEG patterns...	Major revisions to labeling. See highlighted labeling for revised/new text. CONTRAINDICATIONS ...Valium is also contraindicated in patients with myasthenia gravis, severe respiratory insufficiency, severe hepatic insufficiency, and sleep apnea syndrome... WARNINGS Initial Section ...As with other agents that have anticonvulsant activity, when Valium is used as an adjunct in treating convulsive disorders, the possibility of an increase in the frequency and/or severity of grand mal seizures may require an increase in the dosage of standard anticonvulsant medication. Abrupt withdrawal of Valium in such cases may also be associated with a temporary increase in the frequency and/or severity of seizures. Pregnancy See section for new text. Labor and Delivery Special care must be taken when Valium is used during labor and delivery, as high single doses may produce irregularities in the fetal heart rate and hypotonia, poor sucking, hypothermia, and moderate respiratory depression in the neonates. With newborn infants it must be remembered that the enzyme system involved in the breakdown of the drug is not yet fully developed (especially in premature infants). Nursing Mothers Diazepam passes into breast milk. Breastfeeding is therefore not recommended in patients receiving Valium.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Accolate (zafirlukast) Tablet, Film Coated Prescribing Information	WARNINGS Hepatotoxicity	WARNINGS ...In extremely rare post-marketing cases, no clinical symptoms or signs suggestive of liver dysfunction were reported to precede the latter observations.

Caduet (amlodipine besylate/atorvastatin calcium) Tablets Prescribing Information	WARNINGS Skeletal Muscle PRECAUTIONS Drug Interactions Studies with Atorvastatin The risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased...	WARNINGS Skeletal Muscle The risk of myopathy during treatment with drugs in the HMG-CoA reductase inhibitor class is increased with concurrent administration of cyclosporine, fibric acid derivatives, erythromycin, clarithromycin, combination of ritonavir plus saquinavir or lopinavir plus ritonavir, niacin, or azole antifungals...

CellCept (mycophenolate mofetil capsules) CellCept (mycophenolate mofetil tablets) CellCept Oral Suspension (mycophenolate mofetil for oral suspension) CellCept Intravenous (mycophenolate mofetil hydrochloride for injection) Prescribing Information See MedWatch Safety Alerts, most recently updated 6/26/2008, for additional safety information.	WARNINGS Lymphoma and Malignancy Infections Progressive Multifocal Leukoencephalopathy (PML) ADVERSE REACTIONS See highlighted text for revised labeling Postmarketing Experience Resistance Mechanism Disorders Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal...	WARNINGS Lymphoma and Malignancy Lymphoproliferative disease or lymphoma developed in 0.4% to 1% of patients receiving CellCept (2 g or 3 g) with other immunosuppressive agents in controlled clinical trials of renal, cardiac, and hepatic transplant patients. In pediatric patients, no other malignancies besides lymphoproliferative disorder (2/148 patients) have been observed. Infections Oversuppression of the immune system can also increase susceptibility to infection, including opportunistic infections, fatal infections, and sepsis. In patients receiving CellCept (2 g or 3 g) in controlled studies for prevention of renal, cardiac or hepatic rejection, fatal infection/sepsis occurred in approximately 2% of renal and cardiac patients and in 5% of hepatic patients. Progressive Multifocal Leukoencephalopathy (PML) Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal, have been reported in patients treated with CellCept...

Chantix (varenicline) Tablets Prescribing Information Medication Guide See MedWatch Safety Alert posted 5/16/2008 and 11/20/2007 for additional information.	WARNINGS Neuropsychiatric Symptoms PRECAUTIONS Information for Patients (see highlighted text for new information.) MEDICATION GUIDE (new)	WARNINGS Neuropsychiatric Symptoms Advise patients and caregivers that the patient should stop taking Chantix and contact a healthcare provider immediately if agitation, depressed mood, or changes in behavior that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior.

Furadantin (nitrofurantoin) Oral Suspension 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 Furadantin Oral Suspension, 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.

Hepsera (adefovir dipivoxil) Tablets Prescribing Information (in new labeling format)	WARNINGS AND PRECAUTIONS Clinical Resistance (new subsection) ADVERSE REACTIONS Clinical Trials Experience For 65 patients who chose to continue Hepsera for up to 240 weeks in Study 437, 6 had a confirmed increase in serum creatinine of >0.5 mg/dL from baseline with 2 patients discontinuing from the study due to the elevated serum creatinine concentration. Postmarketing Experience (new subsection) PATIENT COUNSELING INFORMATION Lamivudine-resistant patients should use Hepsera in combination with lamivudine and not as Hepsera monotherapy [See Warnings and Precautions. (5.5)]	WARNINGS AND PRECAUTIONS Clinical Resistance Resistance to adefovir dipivoxil can result in viral load rebound which may result in exacerbation of hepatitis B and, in the setting of diminished hepatic function, lead to liver decompensation and possible fatal outcome. In order to reduce the risk of resistance in patients with lamivudine resistant HBV, adefovir dipivoxil should be used in combination with lamivudine and not as adefovir dipivoxil monotherapy. Long-term (144 week) data from Study 438 (n=124) show that patients with HBV DNA levels greater than 1000 copies/mL at Week 48 of treatment with Hepsera were at greater risk of developing resistance than patients with serum HBV DNA levels below 1000 copies/mL at Week 48 of therapy.

Herceptin (trastuzumab) Intravenous Infusion Prescribing Information (in new labeling format) See MedWatch Safety Alert posted 07/10/2008 for additional information.	WARNINGS AND PRECAUTIONS Cardiomyopathy Cardiac Monitoring Table 1 Table 2 ADVERSE REACTIONS Clinical Trials Experience Adjuvant Breast Cancer Studies Safety data from Study 4 ... Metastatic Breast Cancer Studies Cardiomyopathy Table 5 Figure 3	WARNINGS AND PRECAUTIONS Cardiac Monitoring ...In Study 4, a total of 2.9% (31/1056) patients in the TCH arm (1.5% during the chemotherapy phase and 1.4% during the monotherapy phase) and 5.7% (61/1068) patients in the AC-TH arm (1.5% during the chemotherapy phase and 4.2% during the monotherapy phase) discontinued Herceptin due to cardiac toxicity... See highlighted prescribing information for additional new text.

Intron A (interferon alfa-2b, recombinant) For Injection Prescribing Information Medication Guide - Intron A Multidose Pen for Injection Medication Guide - Intron A Solution for Injection Medication Guide - Intron A Powder for Injection	WARNINGS Cerebrovascular Disorders MEDICATION GUIDE - Intron A Multidose Pen for Injection The most serious possible side effects of Intron A include: Body Organs Problems Call your doctor for medical advice about side effects. You may report side effects to FDA at 1–800–FDA–1088. MEDICATION GUIDE - Intron A Solution for Injection The most serious possible side effects of Intron A include: Body Organs Problems Call your doctor for medical advice about side effects. You may report side effects to FDA at 1–800–FDA–1088. For Intramuscular Injection ...If after using a multidose vial (18 million IU or 25 million IU) there is enough solution... MEDICATION GUIDE - Intron A Powder for Injection The most serious possible side effects of Intron A include: Body Organs Problems Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.	WARNINGS Cerebrovascular Disorders Ischemic and hemorrhagic cerebrovascular events have been observed in patients treated with interferon alpha-based therapies, including Intron A. Events occurred in patients with few or no reported risk factors for stroke, including patients less than 45 years of age. Because these are spontaneous reports, estimates of frequency cannot be made and a causal relationship between interferon alpha-based therapies and these events is difficult to establish.

Keflex (cephalexin) Capsules Prescribing Information	WARNINGS Clostridium difficile associated diarrhea (CDAD) PRECAUTIONS Information for Patients Diarrhea is a common problem caused by antibiotics...	WARNINGS Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Keflex, 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.

Keppra (levetiracetam) Injection for Intravenous Use Prescribing Information (in new labeling format)	WARNINGS AND PRECAUTIONS Neuropsychiatric Adverse Reactions Primary Generalized Tonic-Clonic Seizures ADVERSE REACTIONS Clinical Studies Experience Primary Generalized Tonic-Clonic Seizures (located after Table 4) Table 5 Discontinuation Or Dose Reduction In Well-Controlled Clinical Studies Primary Generalized Tonic-Clonic Seizures (located after Table 7)	WARNINGS AND PRECAUTIONS Neuropsychiatric Adverse Reactions: Primary Generalized Tonic-Clonic Seizures ...As in the partial seizure patients, behavioral symptoms appeared to be associated with Keppra treatment. Gait disorders and somnolence were also described in the study in primary generalized seizures, but with no difference between placebo and Keppra treatment groups and no appreciable discontinuations... In some patients experiencing primary generalized tonic-clonic seizures, Keppra causes behavioral abnormalities. In the double-blind, controlled trial in patients with idiopathic generalized epilepsy experiencing primary generalized tonic-clonic seizures, irritability was the most frequently reported psychiatric adverse event occurring in 6.3% of Keppra-treated patients compared to 2.4% of placebo patients... Non-psychotic mood disorders (reported as anger, apathy, depression, mood altered, mood swings, negativism, suicidal ideation, and tearfulness) occurred in 12.7% of Keppra-treated patients compared to 8.3% of placebo patients...

Levaquin (levofloxacin) Tablets and Oral Solution Levaquin (levofloxacin) Injection, for Intravenous Use Levaquin (levofloxacin in 5% dextrose) Injection, for Intravenous Use Prescribing Information (in new labeling format) Patient Package Insert	WARNINGS AND PRECAUTIONS Tendon Effects Musculoskeletal Disorders in Pediatric Patients and Arthropathic Effects in Animals USE IN SPECIFIC POPULATIONS Pediatric Use Inhalational Anthrax (Post-Exposure) Adverse Events PATIENT COUNSELING INFORMATION Serious and Potentially Serious Adverse Reactions Musculoskeletal Disorders in Pediatric Patients PATIENT PACKAGE INSERT Who should not take Levaquin? What if I have been prescribed Levaquin for possible anthrax exposure?	WARNINGS AND PRECAUTIONS Tendon Effects ...Postmarketing surveillance reports indicate that this risk is increased in patients receiving concomitant corticosteroids and in patients over 65 years of age. Levaquin should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon... Musculoskeletal Disorders in Pediatric Patients and Arthropathic Effects in Animals Levaquin is indicated in pediatric patients (less than 18 years of age) only for the prevention of inhalational anthrax (post-exposure)...

Mycobutin (rifabutin capsules, USP) Prescribing Information	WARNINGS Clostridium difficile associated diarrhea (CDAD) PRECAUTIONS Information for Patients Diarrhea is a common problem caused by antibiotics...	WARNINGS Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Mycobutin (rifabutin capsules, USP), 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.

Myfortic (mycophenolic acid) Delayed-Release Tablets Prescribing Information See MedWatch Safety Alerts, most recently updated 05/16/2008, for additional safety information.	WARNINGS Lymphoma and Other Malignancies Progressive Multifocal Leukoencephalopathy (PML) ADVERSE REACTIONS Postmarketing Experience (new subsection) Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal... Congenital malformations have been reported in offspring of patients...	WARNINGS Lymphoma and Other Malignancies ...The rates for lymphoproliferative disease or lymphoma in Myfortic-treated patients were comparable to the mycophenolate mofetil group in the de novo and maintenance studies. As usual for patients with increased risk for skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing and using a sunscreen with a high protection factor. Progressive Multifocal Leukoencephalopathy (PML) Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal, have been reported in patients treated with mycophenolate mofetil (MMF)...

Primaxin I.M. (imipenem and cilastatin for injectable suspension) Prescribing Information	WARNINGS Seizure Potential PRECAUTIONS Drug Interactions A clinically significant reduction in serum valproic acid concentration has been reported in patients receiving carbapenem antibiotics and may result in loss of seizure control...	WARNINGS Seizures and other CNS adverse experiences, such as myoclonic activity, have been reported during treatment with Primaxin I.M. Carbapenems, including imipenem, may reduce serum valproic acid concentrations to subtherapeutic levels, resulting in loss of seizure control. Serum valproic acid concentrations should be monitored frequently after initiating carbapenem therapy. Alternative antibacterial or anticonvulsant therapy should be considered if serum valproic acid concentrations drop below the therapeutic range or a seizure occurs.

Primaxin I.V. (imipenem and cilastatin) For Injection Prescribing Information	WARNINGS Seizure Potential PRECAUTIONS Drug Interactions A clinically significant reduction in serum valproic acid concentration has been reported in patients receiving carbapenem antibiotics and may result in loss of seizure control...	WARNINGS Seizures and other CNS adverse experiences, such as confusional states and myoclonic activity, have been reported during treatment with Primaxin I.V. Carbapenems, including imipenem, may reduce serum valproic acid concentrations to subtherapeutic levels, resulting in loss of seizure control. Serum valproic acid concentrations should be monitored frequently after initiating carbapenem therapy. Alternative antibacterial or anticonvulsant therapy should be considered if serum valproic acid concentrations drop below the therapeutic range or a seizure occurs.

Strattera (atomoxetine hydrochloride) Capsules Prescribing Information (in new labeling format)	WARNINGS AND PRECAUTIONS Effects on Blood Pressure and Heart Rate Effects on Urine Outflow from the Bladder Concomitant Use of Potent CYP2D6 Inhibitors or Use in patients who are known to be CYP2D6 PMs ADVERSE REACTIONS Clinical Trials Experience Initial Section Child and Adolescent Clinical Trials Reasons for discontinuation of treatment due to adverse reactions in child and adolescent clinical trials Commonly observed adverse reactions in acute child and adolescent, placebo-controlled trials Table 1 Table 2 The following adverse reactions occurred in at least 2%... Adult Clinical Trials Reasons for discontinuation of treatment due to adverse reactions in acute adult placebo-controlled trials Commonly observed adverse reactions in acute adult placebo-controlled trials Table 3 Postmarketing Spontaneous Reports Urogenital System Male Pelvic Pain	WARNINGS AND PRECAUTIONS Effects on Blood Pressure and Heart Rate See highlighted text for revised labeling. Effects on Urine Outflow from the Bladder In adult ADHD controlled trials, the rates of urinary retention (1.7%, 9/540) and urinary hesitation (5.6%, 30/540) were increased among atomoxetine subjects compared with placebo subjects (0%, 0/402 ; 0.5%, 2/402, respectively)... Concomitant Use of Potent CYP2D6 Inhibitors or Use in patients who are known to be CYP2D6 PMs Atomoxetine is primarily metabolized by the CYP2D6 pathway to 4-hydroxyatomoxetine. Dosage adjustment of Strattera may be necessary when coadministered with potent CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, and quinidine) or when administered to CYP2D6 PMs...

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Brand (Generic) Name	Sections Modified
Abilify (aripiprazole) Tablets and Oral Solution Abilify Discmelt (aripiprazole) Orally Disintegrating Tablets Abilify (aripiprazole) Injection for Intramuscular Use Only Prescribing Information (in new labeling format)	DRUG INTERACTIONS Drugs Having No Clinically Important Interactions with Abilify Lamotrigine

Aranesp (darbopoetin alfa) For Injection Prescribing Information	PRECAUTIONS Hematology Patients Transitioning to Dialysis ADVERSE REACTIONS Chronic Renal Failure Patients Adult Patients Table 2 Table 3 Pediatric Patients

Argatroban Injection Prescribing Information	PRECAUTIONS Pediatric Use

Biaxin Filmtab (clarithromycin tablets, USP) Biaxin XL Filmtab (clarithromycin extended-release tablets) Biaxin Granules (clarithromycin for oral suspension, USP) Prescribing Information	PRECAUTIONS General Exacerbation of symptoms of myasthenia gravis and new onset of symptoms of myasthenic syndrome has been reported in patients receiving clarithromycin therapy.

Dexedrine (dextroamphetamine sulfate) Spansule Sustained-Release Capsules Prescribing Information Medication Guide	PRECAUTIONS Pediatric Use Dexedrine is not recommended for use in pediatric patients younger than 6 years of age with Attention Deficit Disorder with Hyperactivity... MEDICATION GUIDE Who should not take Dexedrine? Dexedrine is not recommended for use in children less than 6 years old.

E.E.S. (erythromycin ethylsuccinate) Prescribing Information	PRECAUTIONS General Exacerbation of symptoms of myasthenia gravis and new onset of symptoms of myasthenic syndrome has been reported in patients receiving erythromycin therapy.

Ery-Ped (erythromycin ethylsuccinate, USP) Prescribing Information	PRECAUTIONS General Exacerbation of symptoms of myasthenia gravis and new onset of symptoms of myasthenic syndrome has been reported in patients receiving erythromycin therapy.

Inderal (propranolol hydrochloride) Tablets Prescribing Information	PRECAUTIONS Drug Interactions Amiodarone is an antiarrhythmic agent with negative chronotropic properties that may be additive to those seen with β-blockers such as propranolol.

Inspra (eplerenone) Tablets Prescribing Information (in new labeling format)	USE IN SPECIFIC POPULATIONS Pediatric Use

Lotensin (benazepril hydrochloride) Tablets For current prescribing information, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682.	PRECAUTIONS Drug Interactions Lithium Anti-diabetics Carcinogenesis, Mutagenesis, Impairment of Fertility ADVERSE REACTIONS Other Frequent Urination The following adverse events of unknown frequency have been reported during post-marketing use of benazepril: small bowel angioedema, anaphylactoid reactions, hyperkalemia, agranulocytosis, and neutropenia.

Lotensin HCT (benazepril hydrochloride and hydrochlorothiazide, USP) For current prescribing information, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682.	PRECAUTIONS Drug Interactions Lithium Other ADVERSE REACTIONS Unknown Frequency Small bowel angioedema, anaphylactoid reactions, hyperkalemia, agranulocytosis, neutropenia.

Malarone (atovaquone and proguanil hydrochloride) Tablets Prescribing Information	PRECAUTIONS Drug Interactions Proguanil may potentiate the anticoagulant effect of warfarin and other coumarin-based anticoagulants. The mechanism of this potential drug interaction has not been established. Caution is advised when initiating or withdrawing malaria prophylaxis or treatment with Malarone in patients on continuous treatment with coumarin-based anticoagulants. When these products are administered concomitantly, suitable coagulation tests should be closely monitored.

Mepron (atovaquone) Suspension Prescribing Information	PRECAUTIONS General Rare cases of hepatitis, elevated liver function tests and one case of fatal liver failure have been reported in patients treated with atovaquone. A causal relationship between atovaquone use and these events could not be established because of numerous confounding medical conditions and concomitant drug therapies... ADVERSE REACTIONS Postmarketing Experience Blood and Lymphatic System Disorders Immune System Disorders: Hypersensitivity reactions including angioedema, bronchospasm, throat tightness, and urticaria. Eye Disorders Gastrointestinal Disorders: Pancreatitis Hepatobiliary Disorders: Rare cases of hepatitis and one case of fatal liver failure have been reported with atovaquone usage. Skin and Subcutaneous Tissue Disorders: ...Stevens-Johnson syndrome, and skin desquamation have been reported in patients receiving multiple drug therapy including atovaquone. Renal and Urinary Disorders

PCE (erythromycin particles in tablets) Dispertabs Tablets Prescribing Information	PRECAUTIONS General Exacerbation of symptoms of myasthenia gravis and new onset of symptoms of myasthenic syndrome has been reported in patients receiving erythromycin therapy.

Sensipar (cinacalcet) Tablets Prescribing Information	PRECAUTIONS Drug Interactions and/or Drug/Laboratory Test Interactions Effect of Sensipar on other drugs Midazolam

Tekturna (aliskiren) Tablets Prescribing Information Patient Package Insert	PRECAUTIONS Cyclosporine When aliskiren was given with cyclosporine, the blood concentrations of aliskiren were significantly increased. Concomitant use of aliskiren with cyclosporine is not recommended. PATIENT PACKAGE INSERT Tell your doctor about all the medicines you take... cyclosporine (a medicine used to suppress the immune system). potassium-containing medicines, potassium supplements, or salt substitutes containing potassium.

Timentin (ticarcillin disodium and clavulanate potassium) Injection Galaxy (PL 2040) Plastic Container Prescribing Information	PRECAUTIONS Drug/Laboratory Test Interactions ...In common with other antibiotics, ticarcillin disodium/clavulanate potassium may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.

Timentin (sterile ticarcillin disodium and clavulanate potassium) for Intravenous Administration (Pharmacy Bulk Package - Not for Direct Infusion) Prescribing Information	PRECAUTIONS Drug/Laboratory Test Interactions ...In common with other antibiotics, ticarcillin disodium/clavulanate potassium may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.

Vfend I.V. (voriconazole) for Injection Vfend (voriconazole) Tablets Vfend (voriconazole) for Oral Suspension Prescribing Information	PRECAUTIONS Drug Interactions Table 12: Effect of Voriconazole on Pharmacokinetics of Other Drugs Alfentanil (CYP3A4 Inhibition)

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Brand (Generic) Name	Sections Modified
Effexor (venlafaxine hydrochloride) Tablets Prescribing Information	ADVERSE REACTIONS Postmarketing Reports Toxic Epidermal Necrolysis

Effexor XR (venlafaxine hydrochloride) Extended-Release Capsules Prescribing Information	ADVERSE REACTIONS Postmarketing Reports Adverse Events Toxic Epidermal Necrolysis

Emtriva (emtricitabine) Capsules and Oral Solution Prescribing Information (in new labeling format)	ADVERSE REACTIONS Adverse Reactions from Clinical Trials Experience Adult Patients Study 934 - Treatment Emergent Adverse Reactions Table 4 Laboratory Abnormalities Table 5

Geodon (ziprasidone HCl) Capsules Geodon (ziprasidone mesylate) for Injection For IM Use Only Prescribing Information	ADVERSE REACTIONS Extrapyramidal Symptoms (EPS) Dystonia - Class Effect

Haldol (brand of haloperidol injection) For Immediate Release Prescribing Information	ADVERSE REACTIONS CNS Effects Extrapyramidal Symptoms (EPS) Dystonia - Class Effect

Haldol Decanoate (haloperidol) For IM Injection Only Prescribing Information	ADVERSE REACTIONS CNS Effects Extrapyramidal Symptoms (EPS) Dystonia - Class Effect

Invega (paliperidone) Extended-Release Tablets Prescribing Information (in new labeling format)	ADVERSE REACTIONS Extrapyramidal Symptoms (EPS) Dystonia - Class Effect

Lariam (mefloquine hydrochloride) Tablets Prescribing Information	ADVERSE REACTIONS Postmarketing Other infrequent adverse events Respiratory Disorders Dyspnea Pneumonitis of possible allergic etiology

Levitra (vardenafil hydrochloride) Tablets Prescribing Information	ADVERSE REACTIONS Postmarketing Experience Neurologic Transient Global Amnesia

Seroquel (quetiapine fumarate) Tablets Prescribing Information (in new labeling format)	ADVERSE REACTIONS Clinical Study Experience Extrapyramidal Symptoms Dystonia - Class Effect Postmarketing Experience Anaphylactic Reaction Restless Legs DRUG INTERACTIONS P450 3A Inhibitors Protease Inhibitors

Seroquel XR (quetiapine fumarate) Extended-Release Tablets Prescribing Information (in new labeling format)	ADVERSE REACTIONS Extrapyramidal Symptoms Dystonia - Class Effect

Truvada (emtricitabine/tenofovir disoproxil fumarate) Tablets Prescribing Information (in new labeling format)	ADVERSE REACTIONS Adverse Reactions from Clinical Trials Experience Study 934 Table 2 Laboratory Abnormalities Table 3

Uroxatral (alfuzosin HCl extended-release tablets) Prescribing Information	ADVERSE REACTIONS Postmarketing Adverse Event Reports Hepatobiliary Disorders Hepatocellular and cholestatic liver injury (including cases with jaundice leading to drug discontinuation)

Viread (tenofovir disoproxil fumarate) Tablets Prescribing Information (in new labeling format)	ADVERSE REACTIONS Adverse Reactions from Clinical Trials Experience Treatment-Naive Patients Study 934 - Treatment Emergent Adverse Reactions Table 4 Laboratory Abnormalities Table 5

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Brand (Generic) Name

Sections Modified

Actos (pioglitazone HCl) Tablets

Patient Package Insert

PATIENT PACKAGE INSERT (new)

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