MedWatch - August 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) -- August 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.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Metadate CD (methylphenidate HCl, USP) Extended-Release Capsules Prescribing Information	CONTRAINDICATIONS Hypersensitivity To Methylphenidate Or Other Excipients Halogenated Anesthetics PRECAUTIONS Drug Testing Metadate CD contains methylphenidate which may result in a positive result during drug testing. Drug Interactions Phenylbutazone (added) In theory, there is a possibility that the clearance of methylphenidate might be affected by urinary pH... Halogenated Anesthetics ADVERSE REACTIONS Postmarketing Experience ...peripheral coldness, Raynaud’s phenomenon, reversible ischaemic neurological deficit (added)	CONTRAINDICATIONS Hypersensitivity To Methylphenidate Or Other Excipients ...Metadate CD contains sucrose. Therefore, patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency should not take this medicine. Halogenated Anesthetics There is a risk of sudden blood pressure increase during surgery. If surgery is planned, Metadate CD should not be taken on the day of the surgery.

Reyataz (atazanavir sulfate) Capsules Prescribing Information (in new labeling format) Patient Package Insert .	CONTRAINDICATIONS Table 3: Drugs That Are Contraindicated with Reyataz Benzodiazepines DRUG INTERACTIONS Potential for Reyataz to Affect Other Drugs Established and Other Potentially Significant Drug Interactions Table 10 HIV Antiviral Agents Other Agents Drugs with No Observed or Predicted Interactions with Reyataz PATIENT PACKAGE INSERT What important information should I know about taking Reytataz with other medicines? Midazolam, also known as Versed (used for sedation), when taken by mouth. Do not take the following medicines with Reyataz because they may lower the amount of Reyataz in your blood... Viramune (nevirapine, used for HIV infection). Talk to your healthcare provider about choosing an effective method of contraception...	CONTRAINDICATIONS See Table 3: Drugs That Are Contraindicated with Reyataz: Triazolam and orally administered midazolam are extensively metabolized by CYP3A4. Coadministration of triazolam or orally administered midazolam with Reyataz may cause large increases in the concentration of these benzodiazepines...

Rocephin (ceftriaxone sodium) For Injection Prescribing Information See previous MedWatch Safety Alerts originally posted 07/05/2007 notifying healthcare professionals of the potential risks associated with concomitant use of Rocephin with calcium or calcium-containing solutions or products.	CONTRAINDICATIONS Neonates ( < 28 days) WARNINGS Interaction with Calcium-Containing Products PRECAUTIONS General Cases of pancreatitis, possibly secondary to biliary obstruction, have been reported rarely in patients treated with Rocephin... The elimination of Rocephin is not altered by probenecid. As with other cephalosporins, anaphylactic shock cannot be ruled out... Geriatric Use (subsection added) ADVERSE REACTIONS Postmarketing Experience (subsection added) Gastrointestinal Genitourinary Dermatologic Cephalosporin Class Adverse Reactions	CONTRAINDICATIONS Neonates ( < 28 days) ...Rocephin 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, Rocephin 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, Rocephin and IV calcium-containing solutions should not be administered within 48 hours of each other in any patient (see CONTRAINDICATIONS and DOSAGE AND ADMINISTRATION). 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).

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Phosphocol P 32 (chromic phosphate P 32 suspension) Prescribing Information	WARNINGS Leukemia PRECAUTIONS Pediatric Use Risk of Malignancy Acute lymphocytic leukemia has been reported in children following the intra-articular administration of Phosphocol P32 (See WARNINGS). ADVERSE REACTIONS Postmarketing Experience Leukemia in Children (see WARNINGS) Radiation injury (necrosis and fibrosis) to the small bowel, cecum, and bladder following administration of P 32 into the peritoneal cavity.	WARNINGS Leukemia Phosphocol P 32 may increase the risk for leukemia in certain situations. Two children (ages 9 and 14) with hemophilia developed acute lymphocytic leukemia approximately 10 months after intra-articular injections of Phosphocol P 32 (0.6 and 1.5 mCi total dose). Phosphocol P 32 is not indicated in the intra-articular treatment of hemarthroses.

Retisert (fluocinolone acetonide intravitreal implant) Prescribing Information (in new labeling format)	WARNINGS AND PRECAUTIONS Cataract Formation Increase in Intraocular Pressure ADVERSE REACTIONS Clinical Trials Experience – Ocular Events Clinical Trials Experience – Non-Ocular Events PATIENT COUNSELING INFORMATION	WARNINGS AND PRECAUTIONS Cataract Formation Use of corticosteroids may result in posterior subcapsular cataract formation. Based on clinical trials with Retisert, during the 3-year post implantation period, nearly all phakic eyes are expected to develop cataracts and require cataract surgery. Increase in Intraocular Pressure ...Based on clinical trials with Retisert, within 3-years post implantation, approximately 77% of patients will require IOP lowering medications to control intraocular pressure and 37% of patients will require filtering procedures to control intraocular pressure...

Sustiva (efavirenz) Capsules and Tablets Prescribing Information	WARNINGS Reproductive Risk Potential: Pregnancy Category D ADVERSE REACTIONS Postmarketing Experience Central and Peripheral Nervous System Cerebellar coordination and balance disturbances (added)	WARNINGS Reproductive Risk Potential: Pregnancy Category D ...Because of the long half-life of efavirenz, use of adequate contraceptive measures for 12 weeks after discontinuation of Sustiva is recommended... ...As of July 2007, the Antiretroviral Pregnancy Registry has received prospective reports of 373 pregnancies exposed to efavirenz-containing regimens, nearly all of which were first-trimester exposures (359 pregnancies). Birth defects occurred in 7 of 295 live births (first-trimester exposure) and 1 of 26 live births (second/third-trimester exposure). None of these prospectively reported defects were neural tube defects. However, there have been five retrospective reports of findings consistent with neural tube defects, including meningomyelocele. All mothers were exposed to efavirenz-containing regimens in the first trimester...

Vidaza (azacitidine for injection) For SC or IV Use Prescribing Information (in new labeling format)	WARNINGS AND PRECAUTIONS Anemia, Neutropenia and Thrombocytopenia Pregnancy: Pregnancy Category D Use in Males ADVERSE REACTIONS Overview Adverse Reactions Described in Other Labeling Sections Anemia (added) Adverse Reactions Most Frequently (>2%) Resulting in Clinical Intervention (SC or IV Route) Dose Held ...thrombocytopenia, pyrexia, pneumonia (added) Adverse Reactions in Clinical Trials Initial Section Table 1 Table 2 In clinical studies of either SC or IV Vidaza, the following serious adverse reactions occurring at a rate of < 5% (and not described in Tables 1 or 2) were reported: Blood and Lymphatic System Disorders Bone marrow failure Pancytopenia Eye Disorders Eye Hemorrhage Infections and Infestations Cellulitis Neutropenic sepsis Septic shock Nervous System Disorders Cerebral hemorrhage Postmarketing Experience USE IN SPECIFIC POPULATIONS Pregnancy - Pregnancy Category D ...Female partners of male patients receiving Vidaza should not become pregnant [see Nonclinical Toxicology (13)]... Nursing Mothers ...a decision should be made whether to discontinue nursing or to discontinue the drug, taking into consideration the importance of the drug to the mother. Geriatric Use Gender Race PATIENT COUNSELING INFORMATION ...For nursing mothers, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into consideration the importance of the drug to the mother.	WARNINGS AND PRECAUTIONS Anemia, Neutropenia and Thrombocytopenia Treatment with Vidaza is associated with anemia, neutropenia and thrombocytopenia... (anemia added) Pregnancy: Pregnancy Category D ...Azacitidine caused congenital malformations in animals...[see Use in Specific Populations (8.1)]. Use in Males ...In animal studies, pre-conception treatment of male mice and rats resulted in increased embryofetal loss in mated females [see Nonclinical Toxicology (13)].

Zemuron (rocuronium bromide) Injection Solution For Intravenous Use Prescribing Information (in new labeling format)	WARNINGS AND PRECAUTIONS Appropriate Administration and Monitoring Residual Paralysis Long-term Use in an Intensive Care Unit QT Interval Prolongation USE IN SPECIFIC POPULATIONS Pediatric Use	WARNINGS AND PRECAUTIONS Appropriate Administration and Monitoring ...It is recommended that clinicians administering neuromuscular blocking agents such as Zemuron employ a peripheral nerve stimulator to monitor drug effect, need for additional doses, adequacy of spontaneous recovery or antagonism, and to decrease the complications of overdosage if additional doses are administered. Residual Paralysis In order to prevent complications resulting from residual paralysis, it is recommended to extubate only after the patient has recovered sufficiently from neuromuscular block. Other factors which could cause residual paralysis after extubation in the post-operative phase (such as drug interactions or patient condition) should also be considered. If not used as part of standard clinical practice the use of a reversal agent should be considered, especially in those cases where residual paralysis is more likely to occur. Long-term Use in an Intensive Care Unit ...Myopathy after long term administration of other non-depolarizing neuromuscular blocking agents in the ICU alone or in combination with corticosteroid therapy has been reported. Therefore, for patients receiving both neuromuscular blocking agents and corticosteroids, the period of use of the neuromuscular blocking agent should be limited as much as possible and only used in the setting where in the opinion of the prescribing physician, the specific advantages of the drug outweigh the risk. QT Interval Prolongation The overall analysis of ECG data in pediatric patients indicates that the concomitant use of Zemuron with general anesthetic agents can prolong the QTc interval [see Clinical Studies (14.3)].

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Brand (Generic) Name	Sections Modified
Corzide (nadolol and bendroflumethiazide tablets) Prescribing Information	PRECAUTIONS Drug Interactions Nadolol Digitalis glycosides—Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Glucophage (metformin hydrochloride tablets) Glucophage XR (metformin hydrochloride extended-release tablets) Prescribing Information	PRECAUTIONS General Macrovascular Outcomes There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Glucophage or Glucophage XR or any other anti-diabetic drug.

Kerlone (betaxolol hydrochloride tablets) 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.

Metaglip (glipizide and metformin HCl) Tablets Prescribing Information	PRECAUTIONS General Macrovascular Outcomes There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Metaglip or any other anti-diabetic drug.

Norvir (ritonavir capsules) Soft Gelatin Norvir (ritonavir oral solution) Prescribing Information Patient Package Insert	PRECAUTIONS PR Interval Prolongation Information for Patients Patients should be informed that Norvir may produce changes in the electrocardiogram (eg, PR prolongation)... ADVERSE REACTIONS Postmarketing Experience Cardiovascular System First–degree AV block, second-degree AV block, third-degree AV block, right bundle branch block have been reported (See PRECAUTIONS – PR Interval Prolongation). PATIENT PACKAGE INSERT What Are the Possible Side Effects of Norvir? Changes in the electrocardiogram (EKG)...

Precose (acarbose tablets) Prescribing Information	PRECAUTIONS General Macrovascular Outcomes There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Precose or any other anti-diabetic drug.

Sandostatin (octreotide acetate) Injection Prescribing Information	PRECAUTIONS General Risk of Pregnancy with Normalization of IGF-1 and GH (new subsection) Pregnancy Category B Nursing Mothers

Somavert (pegvisomant for injection) Prescribing Information Patient Package Insert	PRECAUTIONS Lipohypertrophy Lipohypertrophy has been reported in <5% of patients following pegvisomant administration. ADVERSE REACTIONS Postmarketing Experience Lipohypertrophy has been reported in <5% of patients following pegvisomant administration. Asymptomatic, transient elevations in transaminases up to 15 times ULN have been observed in <2% of patients in the post-marketing experience. These reports were not associated with an increase in bilirubin, and there were no clinical consequences for these patients... PATIENT PACKAGE INSERT INSTRUCTIONS FOR USE Giving the Injection Choose a different injection site each day so lumps do not develop...

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Brand (Generic) Name	Sections Modified
Cialis (tadalafil) Tablet, Film Coated Prescribing Information	ADVERSE REACTIONS Postmarketing Experience Nervous Transient Global Amnesia (added)

Estring (estradiol vaginal ring) Prescribing Information Patient Package Insert	ADVERSE REACTIONS Postmarketing Experience A few cases of toxic shock syndrome (TSS) have been reported... A few cases of ring adherence to the vaginal wall, making ring removal difficult, have been reported... A few cases of bowel obstruction and vaginal ring use have been reported... PATIENT PACKAGE INSERT Who should not use Estring? Currently have or have had liver problems. What are the possible side effects of Estring? Initial Paragraph What can I do to lower my chances of getting a serious side effect with Estring?

Femara (letrozole tablets) Prescribing Information	ADVERSE REACTIONS Postmarketing Experiences ...angioedema and anaphylactic reactions (added)

Megace ES (megestrol acetate oral suspension) Prescribing Information	ADVERSE REACTIONS Postmarketing Deep Vein Thrombosis (added)

Symlin (pramlintide acetate) Injection Prescribing Information	ADVERSE REACTIONS Postmarketing Experience (new subsection) General Injection Site Reactions

Synagis (palivizumab) For Intramuscular Administration Prescribing Information	ADVERSE REACTIONS Postmarketing Experience Blood and Lymphatic System Disorders Severe Thrombocytopenia (platelet count <50,000/microliter) General Disorders and Administration Site Conditions Injection Site Reactions Immune System Disorders Severe acute hypersensitivity reactions and anaphylaxis...

Viagra (sildenafil citrate) Tablets Prescribing Information	ADVERSE REACTIONS Postmarketing Experience Other Events Nervous Transient Global Amnesia (added)

Zovirax (acyclovir) Capsules and Tablets Zovirax (acyclovir) Suspension Prescribing Information	ADVERSE REACTIONS Observed During Clinical Practice Urogenital Renal Pain (may be associated with renal failure)

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Brand (Generic) Name

Sections Modified

Omnitrope Pen 10 (somatropin [rDNA origin] injection), For Subcutaneous Use

For use with Omnitrope (somatropin [rDNA origin] injection) 10 mg/1.5 mL
Cartridges

Patient Package Insert

INSTRUCTIONS FOR USE (new)

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