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.

Brand (Generic) Name

Summary of Changes to Contraindications and Warnings

Carbatrol (carbamazepine) Extended-Release Capsules

Prescribing Information

For the most recent safety information on carbamazepine, see the MedWatch Safety Alert posted 12/12/2007.

BOXED WARNING

• Serious Dermatologic Reactions and HLA-B*1502 Allele

WARNINGS

• Serious Dermatologic Reactions
• SJS/TEN and HLA-B*1502 Allele

PRECAUTIONS

• Laboratory Tests

BOXED WARNING

Serious Dermatologic Reactions and HLA-B*1502 Allele

Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS), have been reported during treatment with carbamazepine. These reactions are estimated to occur in 1 to 6 per 10,000 new users in countries with mainly caucasian populations, but the risk in some Asian countries is estimated to be about 10 times higher. Studies in patients of Chinese ancestry have found a strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA-B gene. HLA-B*1502 is found almost exclusively in patients with ancestry across broad areas of Asia. Patients with ancestry in genetically at risk populations should be screened for the presence of HLA-B*1502 prior to initiating treatment with Carbatrol. Patients testing positive for the allele should not be treated with Carbatrol unless the benefit clearly outweighs the risk (see WARNINGS and PRECAUTIONS/Laboratory Tests).

WARNINGS

See highlighted prescribing information for new text.

Equetro (carbamazepine) Extended-Release Capsules

Prescribing Information

For the most recent safety information on carbamazepine, see the MedWatch Safety Alert posted 12/12/2007.

BOXED WARNING

• Serious Dermatologic Reactions and HLA-B*1502 Allele

WARNINGS

• Serious Dermatologic Reactions
• SJS/TEN and HLA-B*1502 Allele
• General
  • Patients with a history of adverse hematologic reaction to any drug may be particularly at risk of bone marrow depression.

PRECAUTIONS

• Laboratory Tests
  • For genetically at-risk patients [see WARNINGS], high-resolution 'HLA-B*1502 typing' is recommended. The test is positive if either one or two HLA-B*1502 alleles are detected and negative if no HLA-B*1502 alleles are detected.

ADVERSE REACTIONS

• General
  • The most severe adverse reactions previously observed with carbamazepine were reported in the hemopoietic system and skin (see BOXED WARNING) and in the cardiovascular system.
• Skin

BOXED WARNING

Serious Dermatologic Reactions and HLA-B*1502 Allele

Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS), have been reported during treatment with carbamazepine. These reactions are estimated to occur in 1 to 6 per 10,000 new users in countries with mainly caucasian populations, but the risk in some Asian countries is estimated to be about 10 times higher. Studies in patients of Chinese ancestry have found a strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA-B gene. HLA-B*1502 is found almost exclusively in patients with ancestry across broad areas of Asia. Patients with ancestry in genetically at-risk populations should be screened for the presence of HLA-B*1502 prior to initiating treatment with Equetro. Patients testing positive for the allele should not be treated with Equetro unless the benefit clearly outweighs the risk (see WARNINGS and PRECAUTIONS, Laboratory Tests).

WARNINGS

See highlighted prescribing information for new text.

Omniscan (gadodiamide) Injection for Intravenous Use

Prescribing Information (in new labeling format)

BOXED WARNING

WARNINGS AND PRECAUTIONS

• Hypersensitivity Reactions
• Acute Renal Failure
• Not for Intrathecal Use
• Impaired Visualization of Lesions Detectable with Non-contrast MRI

ADVERSE REACTIONS

• Initial Section
• Clinical Studies Experience (Adults)

USE IN SPECIFIC POPULATIONS

• Pregnancy
• Pediatric Use
• Geriatric Use

NONCLINICAL TOXICOLOGY

• Carcinogenesis, Mutagenesis, Impairment of Fertility

PATIENT COUNSELING INFORMATION

BOXED WARNING

WARNING: NOT FOR INTRATHECAL USE...

Inadvertent intrathecal use of Omniscan has caused convulsions, coma, sensory and motor neurologic deficits [see WARNINGS and PRECAUTIONS (5.4)].

WARNINGS AND PRECAUTIONS

See highlighted prescribing information for new text.

Tegretol (carbamazepine) USP, Chewable Tablets, and Oral Suspension

Tegretol-XR
(carbamazepine extended-release tablets)

Prescribing Information

For the most recent safety information on carbamazepine, see the MedWatch Safety Alert posted 12/12/2007.

BOXED WARNING

• Serious Dermatologic Reactions and HLA-B*1502 Allele

WARNINGS

• Serious Dermatologic Reactions
• SJS/TEN and HLA-B*1502 Allele
• Aplastic Anemia and Agranulocytosis
  • Patients with a history of adverse hematologic reaction to any drug may be particularly at risk of bone marrow depression.

PRECAUTIONS

• Laboratory Tests
  • For genetically at-risk patients [see WARNINGS], high-resolution 'HLA-B*1502 typing' is recommended. The test is positive if either one or two HLA-B*1502 alleles are detected and negative if no HLA-B*1502 alleles are detected.

ADVERSE REACTIONS

• Initial Section
  • The most severe adverse reactions have been observed in the hemopoietic system and skin (see BOXED WARNING), the liver and the cardiovascular system.
• Skin

BOXED WARNING

Serious Dermatologic Reactions and HLA-B*1502 Allele

Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS), have been reported during treatment with Tegretol. These reactions are estimated to occur in 1 to 6 per 10,000 new users in countries with mainly caucasian populations, but the risk in some Asian countries is estimated to be about 10 times higher. Studies in patients of Chinese ancestry have found a strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA-B gene. HLA-B*1502 is found almost exclusively in patients with ancestry across broad areas of Asia. Patients with ancestry in genetically at-risk populations should be screened for the presence of HLA-B*1502 prior to initiating treatment with Tegretol. Patients testing positive for the allele should not be treated with Tegretol unless the benefit clearly outweighs the risk (see WARNINGS and PRECAUTIONS, Laboratory Tests).

WARNINGS

See highlighted prescribing information for new text.

Brand (Generic) Name

Summary of Changes to Contraindications and Warnings

Ambien CR (zolpidem tartrate extended-release) Tablets

Prescribing Information (in new labeling format)

Medication Guide

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

• Severe Anaphylactic and Anaphylactoid Reactions
• Abnormal Thinking and Behavioral Changes
• Special Populations
  • Use in Pediatric Patients

DRUG INTERACTIONS

• CNS-Active Drugs
• Drugs that Affect Drug Metabolism Via Cytochrome P450
• Other Drugs with No Interaction with Zolpidem

USE IN SPECIAL POPULATIONS

• Pregnancy
• Pediatric Use
• Geriatric Use

PATIENT COUNSELING INFORMATION

• Severe Anaphylactic and Anaphylactoid Reactions
• Sleep-driving and Other Complex Behaviors

MEDICATION GUIDE (new)

CONTRAINDICATIONS

...Observed reactions include anaphylaxis and angioedema [see WARNINGS and PRECAUTIONS (5.2)].

WARNINGS AND PRECAUTIONS

Severe Anaphylactic and Anaphylactoid Reactions

Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of sedative-hypnotics, including zolpidem. Some patients have had additional symptoms such as dyspnea, throat closing or nausea and vomiting that suggest anaphylaxis...

Abnormal Thinking and Behavioral Changes

In a clinical trial, 7.4% of pediatric patients with insomnia associated with attentiondeficit/ hyperactivity disorder (ADHD), who received zolpidem reported hallucinations [see USE IN SPECIFIC POPULATIONS (8.4)].

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 Pediatric Patients

Safety and effectiveness of zolpidem has not been established in pediatric patients. In an 8-week study in pediatric patients (aged 6-17 years) with insomnia associated with ADHD given an immediate-release oral solution of zolpidem tartrate, zolpidem did not decrease sleep latency compared to placebo. Hallucinations were reported in 7.4% of the pediatric patients who received zolpidem; none of the pediatric patients who received placebo reported hallucinations [see USE IN SPECIFIC POPULATIONS (8.4)].

AndroGel (testosterone gel) 1%

Prescribing Information (in new labeling format)

Patient Package Insert

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

• Worsening of BPH and Potential Risk of Prostate Cancer
• Potential for Testosterone Transfer to Others
• Use in Women
• Potential for Adverse Effects on Spermatogenesis
• Hepatic Adverse Effects
• Gynecomastia
• Sleep Apnea
• Laboratory Tests
• Flammable until Dry

ADVERSE REACTIONS

• Clinical Trial Experience
  • Clinical Trials in Hypogonadal Men
• Postmarketing Experience

DRUG INTERACTIONS

• Corticosteroids
• Oral Anticoagulants

USE IN SPECIFIC POPULATIONS

• Pregnancy
• Nursing Mothers
• Geriatric Use
• Renal or Hepatic Impairment

PATIENT COUNSELING INFORMATION

• Potential Adverse Reactions with Androgens
• Instructions for Use of AndroGel

PATIENT PACKAGE INSERT

• What Disease or Condition Does AndroGel Treat?
• How to use the AndroGel Pump?
• The Major Risks of AndroGel include...

CONTRAINDICATIONS

AndroGel should not be used in any of the following patients:

• Men with carcinoma of the breast or known or suspected carcinoma of the prostate...

• Women who are or may become pregnant, or who are breastfeeding. AndroGel can cause fetal harm when administered to a pregnant woman. Androgel may cause serious adverse reactions in nursing infants. Exposure of a female fetus or nursing infant to androgens may result in varying degrees of virilization. Pregnant women or those who may become pregnant need to be aware of the potential for transfer of testosterone from men treated with AndroGel...

• Men with known hypersensitivity to any of its ingredients, including alcohol and soy products.

WARNINGS AND PRECAUTIONS

See highlighted prescribing information for new text.

Dostinex (cabergoline) Tablets

Prescribing Information

CONTRAINDICATIONS

WARNINGS

• Valvulopathy

PRECAUTIONS

• Fibrosis
  • ...Erythrocyte sedimentation rate (ESR) has been found to be abnormally increased in association with pleural effusion/fibrosis. Chest x-ray examination is recommended in cases of unexplained ESR increases to abnormal values. Serum creatinine measurements can also be used to help in the diagnosis of fibrotic disorder.

ADVERSE REACTIONS

• Postmarketing Surveillance Data
  • ...Others events have been reported in association with cabergoline: hypersexuality, increased libido, pathological gambling (See PRECAUTIONS, Psychiatric). In addition, during postmarketing surveillance, cases of alopecia, aggression and psychotic disorder have been reported in patients taking Dostinex. Some of these reports have been in patients who have had prior adverse reactions to dopamine agonist products.

CONTRAINDICATIONS

Dostinex Tablets are contraindicated in patients with:

• History of pulmonary, pericardial, cardiac valvular, or retroperitoneal fibrotic disorders. (See PRECAUTIONS, Fibrosis)

WARNINGS: Valvulopathy

Postmarketing cases of cardiac valvulopathy have been reported in patients receiving Dostinex. These cases have generally occurred during long-term administration of high doses of Dostinex (>2 mg/day) used for the treatment of Parkinson’s disease. Rare cases have been reported associated with short-term treatment (< 6 months) or in patients receiving lower doses for the treatment of hyperprolactinemia.

Physicians should use the lowest effective dose of Dostinex for the treatment of hyperprolactinemia and should periodically reassess the need for continuing therapy with Dostinex. In addition, patients receiving long term treatment with Dostinex should undergo periodic reassessment of their cardiac status, and echocardiography should be considered. Any patient who develops signs or symptoms of cardiac disease, including dyspnea, edema, congestive heart failure, or a new cardiac murmur, while being treated with Dostinex should be evaluated for possible valvulopathy.

Dostinex should be used with caution in patients who have hemodynamically significant valvular disease or have been exposed to other medications associated with valvulopathy.

Brand (Generic) Name

Summary of Changes to Warnings

Aredia (pamidronate disodium for injection)

Prescribing Information

For the most recent safety information on Aredia, see the MedWatch Safety Alert posted 10/01/2007.

WARNINGS

• Deterioration in Renal Function

PRECAUTIONS

• General
  • Patients with a history of thyroid surgery may have relative hypoparathyroidism that may predispose to hypocalcemia with Aredia.
• Renal Insufficiency
  • In clinical trials, patients with real impairment (serum creatinine >3.0 mg/dL) have not been
    studied. Limited pharmacokinetic data exist in patients with creatinine clearance <30 ml/min...
• Drug Interactions
  • In multiple myeloma patients, the risk of renal dysfunction may be increased when Aredia is used in combination with thalidomide.
• Animal Toxicology (new subsection)

ADVERSE REACTIONS

• Postmarketing Experience
  • The following adverse reactions have been reported in postmarketing use...

WARNINGS: Deterioration in Renal Function

Bisphosphonates, including Aredia, have been associated with renal toxicity manifested as deterioration of renal function and potential renal failure.

...Renal deterioration, progression to renal failure, and dialysis have been reported in patients after the initial or a single dose of Aredia.

Focal segmental glomerulosclerosis (including the collapsing variant) with or without nephrotic syndrome, which may lead to renal failure, has been reported in Aredia-treated patients, particularly in the setting of multiple myeloma and breast cancer. Some of these patients had gradual improvement in renal status after Aredia was discontinued.

Biaxin Filmtab (clarithromycin tablets, USP)

Biaxin XL Filmtab
(clarithromycin extended-release tablets)

Biaxin Granules
(clarithromycin for oral suspension, USP)

Prescribing Information

WARNINGS

PRECAUTIONS

• Information for Patients
  • Diarrhea is a common problem caused by antibiotics which 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 two or more months after having taken 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 Biaxin, 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.

Prescribing Information

WARNINGS

ADVERSE REACTIONS

• ...Prolonged respiratory depression or apnea may occur when administration of epidural DepoDur is associated with subarachnoid puncture.

WARNINGS

...In all cases, signs of prolonged respiratory depression were observed requiring narcotic antagonist (naloxone) administration or ventilatory support.

Prolonged and serious respiratory depression or apnea has occurred when administration of epidural DepoDur was associated with subarachnoid puncture. In these cases, respiratory depression has occurred within 12 hours of DepoDur administration following apparent recovery from anesthesia. Respiratory depression resulting from DepoDur can be treated successfully with a naloxone bolus or, more commonly, a naloxone infusion; intubation and mechanical ventilation may be necessary in some cases.

Because intrathecal leakage from the epidural space may occur through a breached dural membrane, especially when the epidural drug is administered in a bolus, DepoDur should not be administered to a patient following a recent dural puncture without vigilant monitoring of respiratory function for a prolonged period (48 hours) with provision for emergency mechanical ventilation to minimize the risk of serious respiratory depression...

Derma-Smoothe/FS (fluocinolone acetonide) Topical Oil 0.01% (Body Oil)

Prescribing Information (in new labeling format)

WARNINGS AND PRECAUTIONS

• Hypothalamic-Pituitary-Adrenal Axis Suppression

ADVERSE REACTIONS

• Clinical Studies Experience: Evaluation in Pediatric Subjects 3 months to 2 years old

USE IN SPECIFIC POPULATIONS

• Pediatric Use
  • Systemic Adverse Reactions in Pediatric Patients
  • Evaluation in Pediatric Subjects 3 months to 2 years old

PATIENT COUNSELING INFORMATION

• Instructions
  • Derma-Smoothe/FS should not be applied under occlusion unless directed by the physician. Derma-Smoothe/FS should not be applied to the diaper area as diapers or plastic pants may constitute occlusive use.
  • Do not use other corticosteriod-containing products while using Derma-Smoothe/FS without first consulting your physician.

WARNINGS AND PRECAUTIONS

...Recovery of HPA axis function is generally prompt upon discontinuation of topical corticosteroids...

Doryx (doxycycline hyclate) Capsule, Delayed Release Pellets

Prescribing Information

WARNINGS

PRECAUTIONS

• Information for Patients
  • Diarrhea is a common problem caused by antibiotics which 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 two or more months after having taken 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 Doryx Capsules, 75 mg and 100 mg, 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.

Effexor XR (venlafaxine hydrochloride) Extended-Release Capsules

Prescribing Information

Medication Guide

WARNINGS

• Sustained Hypertension
  • Table 2 (new)
  • Table 3 (new)
• Elevations in Systolic and Diastolic Blood Pressure
  • Table 4 (new)

PRECAUTIONS (Social Anxiety Disorder data updated)

• General
• Discontinuation of Treatment with Effexor XR
• Insomnia and Nervousness
  • Table 5
• Changes in Weight
  • Adult Patients
• Changes in Appetite
  • Adult Patients
• Activation of Mania/Hypomania
• Seizures
• Use in Patients With Concomitant Illness
• Drug Interactions
  • Metoprolol
• Geriatric Use

ADVERSE REACTIONS

• Adverse Findings Observed in Short-Term, Placebo-Controlled Studies with Effexor XR
• Table 6 (Social Anxiety Disorder Data)
• Social Anxiety Disorder
• Table 9
• Vital Sign Changes
• Laboratory Changes
  • Serum Cholesterol
  • Serum Triglycerides
• Other Adverse Events Observed During the Premarketing Evaluation of Effexor and Effexor XR
  • Body as a Whole
  • Cardiovascular System
  • Digestive System
  • Metabolic and Nutritional
  • Nervous System
  • Special Senses
  • Urogenital System

WARNINGS

See highlighted prescribing information for new text.

Exjade (deferasirox) Tablets for Oral Suspension

Prescribing Information

For the most recent safety information on Exjade, see the MedWatch Safety Alert posted 12/13/2007.

WARNINGS

• Hepatic Dysfunction and Failure

ADVERSE REACTIONS

• Postmarketing Experience
  • Hepatic Failure

WARNINGS: Hepatic Dysfunction and Failure

In Study 1, 4 patients discontinued Exjade because of hepatic abnormalities (drug-induced hepatitis in 2 patients and increased serum transaminases in 2 additional patients). There have been postmarketing reports of hepatic failure, some with a fatal outcome, in patients treated with Exjade. Most of these events occurred in patients greater than 55 years of age. Most reports of hepatic failure involved patients with significant comorbidities, including liver cirrhosis and multi-organ failure. Liver function tests should be monitored monthly during Exjade treatment and dose modifications or interruption considered for severe or persistent elevations.

Prescribing Information

For the most recent safety information on Heparin, see the MedWatch Safety Alert posted 02/07/2007.

WARNINGS

• Fatal Medication Errors
• Use in Neonates

WARNINGS

Fatal Medication Errors

Do not use Heparin Sodium Injection as a “catheter lock flush” product. Heparin Sodium Injection is supplied in vials containing various strengths of heparin, including vials that contain a highly concentrated solution of 10,000 units in 1 mL. Fatal hemorrhages have occurred in pediatric patients due to medication errors in which 1 mL Heparin Sodium Injection vials were confused with 1 mL "catheter lock flush" vials. Carefully examine all Heparin Sodium Injection vials to confirm the correct vial choice prior to administration of the drug.

Use in Neonates

This product contains the preservative benzyl alcohol and is not recommended for use in neonates. There have been reports of fatal ‘gasping syndrome’ in neonates (children less than one month of age) following the administration of intravenous solutions containing the preservative benzyl alcohol. Symptoms include a striking onset of gasping respiration, hypotension, bradycardia, and cardiovascular collapse.

Carefully examine all Heparin Sodium Injection vials to confirm choice of the correct strength prior to administration of the drug. Pediatric patients, including neonates, have died as a result of medication errors in which Heparin Sodium Injection vials have been confused with "catheter lock flush" vials. (See WARNINGS: Fatal Medication Errors.)

Heparin Sodium Injection, USP (porcine) 5,000 U/mL

Contact Abraxis Pharmaceutical Products at 1-800-551-7176 for current prescribing information.

WARNINGS

• Thrombocytopenia
• Heparin-induced Thrombocytopenia (HIT) and Heparin-Induced Thrombocytopenia and Thrombosis (HITT)
• Delayed Onset of HIT and HITT
• Use in Neonates

PRECAUTIONS

• Increased Risk to Older Patients, Especially Women
• Drug Interactions
  • Intravenous nitroglycerin administered to heparinized patients may result in a decrease of the partial thromboplastin time with subsequent rebound effect upon discontinuation of nitroglycerin...
• Geriatric Use
  • A higher incidence of bleeding has been reported in patients over 60 years of age, especially women. Clinical studies indicate that lower doses of heparin may be indicated in these patients...

ADVERSE REACTIONS

• Hemorrhage
  • Thrombocytopenia, Heparin-induced Thrombocytopenia (HIT) and Heparin-induced Thrombocytopenia and Thrombosis (HITT) and Delayed Onset of HIT and HITT (See WARNINGS)

WARNINGS

Thrombocytopenia

Thrombocytopenia has been reported to occur in patients receiving heparin with a reported incidence of up to 30%. Platelet counts should be obtained at baseline and periodically during heparin administration. Mild thrombocytopenia (count greater than 100,000/mm³) may remain stable or reverse even if heparin is continued. However, thrombocytopenia of any degree should be monitored closely. If the count falls below 100,000/mm³ or if recurrent thrombosis develops (see Heparin-induced thrombocytopenia and Heparin-induced Thrombocytopenia and Thrombosis), the heparin product should be discontinued and, if necessary, an alternative anticoagulant administered.

Hepsera (adefovir
dipivoxil) Tablets

Prescribing Information

WARNINGS AND PRECAUTIONS

• Nephrotoxicity
  • Pediatric Patients

ADVERSE REACTIONS

• Pediatric Patients

USE IN SPECIFIC POPULATIONS

• Pediatric Use

WARNINGS AND PRECAUTIONS

See highlighted prescribing information for new text.

Invega (paliperidone) Extended-Release Tablets

Prescribing Information (in new labeling format)

WARNINGS AND PRECAUTIONS

• QT Prolongation

DRUG INTERACTIONS

• Potential for Other Drugs to Affect Invega
  • Paroxetine

WARNINGS AND PRECAUTIONS

QT Prolongation

See highlighted prescribing information for new text..

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)

WARNINGS AND PRECAUTIONS

• Photosensitivity/Phototoxicity

ADVERSE REACTIONS

• Serious and Otherwise Important Adverse Reactions
  • Photosensitivity/Phototoxicity
• Postmarketing Experience
  • Table 7
  • Skin and Subcutaneous Tissue Disorders - Photosensitivity/Phototoxicity Reaction [see WARNINGS and PRECAUTIONS (5.10)]

PATIENT COUNSELING INFORMATION

• Serious and Potentially Serious Adverse Reactions
  • Photosensitivity/Phototoxicity
• What are possible side effects of Levaquin?
  • Sun sensitivity (photosensitivity)...

WARNINGS AND PRECAUTIONS

Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (e.g., burning, erythema, exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, “V” area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with the use of quinolones after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Drug therapy should be discontinued if photosensitivity/ phototoxicity occurs [See ADVERSE REACTIONS (6.3); PATIENT COUNSELING INFORMATION (17.3)]

Monodox (doxycycline monohydrate) Capsules

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. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken 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 Monodox, 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.

Sonata (zaleplon) Capsules

Prescribing Information

Medication Guide

WARNINGS

• Abnormal Thinking and Behavioral Changes
• Severe Anaphylactic and Anaphylactoid Reactions

PRECAUTIONS

• Information for Patients
• Special Concerns - "Sleep-Driving" and Other Complex Behaviors

MEDICATION GUIDE (new)

WARNINGS

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. These events can occur in sedative-hypnotic-naive as well as in sedative-hypnotic-experienced persons. Although behaviors such as sleep-driving may occur with Sonata alone at therapeutic doses, the use of alcohol and other CNS depressants with Sonata appears to increase the risk of such behaviors, as does the use of Sonata at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of Sonata should be strongly considered for patients who report a “sleep-driving” episode. Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative-hypnotic. As with sleep-driving, patients usually do not remember these events. Amnesia and other neuropsychiatric symptoms may occur unpredictably. In primarily depressed patients, worsening of depression, including suicidal thoughts and actions (including completed suicides), has been reported in association with the use of sedative/hypnotics...

Severe Anaphylactic and Anaphylactoid Reactions

Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of sedative-hypnotics, including Sonata. Some patients have had additional symptoms such as dyspnea, throat closing, or nausea and vomiting that suggest anaphylaxis. Some patients have required medical therapy in the emergency department. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with Sonata should not be rechallenged with the drug.

Atrovent (ipratropium bromide) Nasal Spray 0.03%, 21 mcg/spray

Prescribing Information

PRECAUTIONS

• General
  • Effects Seen with Anticholinergic Drugs
    • Prostatic Hyperplasia

Brovana (arformoterol tartrate) Solution For Oral Inhalation Only

Prescribing Information

Medication Guide

PRECAUTIONS

• Information for Patients

MEDICATION GUIDE

• How Should I Store Brovana?
• Instructions for Using Brovana (arformoterol tartrate) Inhalation Solution

CellCept (mycophenolate mofetil capsules and tablets)

CellCept Oral Suspension (mycophenolate mofetil for oral suspension)

CellCept Intravenous (mycophenolate mofetil hydrochloride for injection)

Prescribing Information

PRECAUTIONS

• Drug Interactions
  • Initial Paragraph
    • Sevelamer, Norfloxacin, and Metronidazole (drugs added)
  • Cyclosporine
    • In renal transplant patients, mean MPA exposure (AUC0-12h) was approximately 30-50% greater when mycophenolate mofetil is administered without cyclosporine compared with when mycophenolate mofetil is coadministered with cyclosporine...
  • Sevelamer (new subsection)
  • Norfloxacin and Metronidazole (new subsection)
  • Rifampin (new subsection)

Factive (gemifloxacin) Tablets

Prescribing Information

Patient Package Insert

PRECAUTIONS

• Rash
  • Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions...
• Information for Patients
  • that photosensitivity/phototoxicity has been reported in patients receiving quinolones...

ADVERSE REACTIONS

• Adverse Events with a Frequency of Less than 1%
  • Other adverse events reported from clinical trials which have potential clinical significance and which were considered to have a suspected relationship to the drug...
    • Photosensitivity/Phototoxicity Reactions
• Postmarketing Adverse Reactions
  • Photosensitivity/Phototoxicity Reaction

PATIENT PACKAGE INSERT

• Factive and other quinolone antibiotics may cause the following serious side effects:
  • Sun sensitivity (photosensitivity), which can appear as skin eruption or severe sunburn can occur...

Floxin (ofloxacin) Tablets

Prescribing Information

Patient Package Insert

PRECAUTIONS

• General
  • Moderate to severe photosensitivity/phototoxicity reactions...
• Information for Patients
  • ...that photosensitivity/phototoxicity has been reported in patients receiving quinolone antibiotics...

ADVERSE REACTIONS

• Postmarketing Adverse Events
  • Skin/Hypersensitivity
    • Photosensitivity/Phototoxicity Reaction

PATIENT PACKAGE INSERT

• What are possible side effects of Floxin?
  • Sun sensitivity (photosensitivity), which can appear as skin eruption or severe sunburn can occur...

INOmax (nitric oxide) for Inhalation

Contact INO Therapeutics, Inc. at 1-877-566-9466 for current prescribing information.

PRECAUTIONS

• Carcinogenesis, Mutagenesis, Impairment of Fertility
  • No evidence of a carcinogenic effect was apparant, at inhalation exposures up to the recommended dose (20 ppm), in rats for 20 hr/day for up to two years. Higher exposures have not been investigated.
  • Nitric oxide has demonstrated genotoxicity in Salmonella (Ames Test), human lymphocytes, and after in vivo exposure to rats. There are no animal or human studies to evaluate nitric oxide for effects on fertility.

Prescribing Information (in new labeling format)

DRUG INTERACTIONS

• Established and Other Potentially Significant Drug Interactions
  • Table 6: Established and Other Potentially Significant Drug Interactions
    • Anticonvulsants
      • Phenytoin
        • Plasma phenytoin concentrations should be monitored and phenytoin dose should be increased as appropriate. No change in Lexiva/ritonavir dose is recommended.
    • Antidepressant
      • Paroxetine
        • Coadministration of paroxetine with Lexiva/ritonavir significantly decreased plasma levels of paroxetine. Any paroxetine dose adjustment should be guided by clinical effect (tolerability and efficacy).

Malarone (atovaquone and proguanil hydrochloride) Tablets

Malarone (atovaquone and proguanil hydrochloride) Pediatric Tablets

Prescribing Information

PRECAUTIONS

• General
  • Elevated liver function tests and rare cases of hepatitis have been reported with prophylactic use of Malarone. A single case of hepatic failure requiring liver transplantation has also been reported with prophylactic use.
• Information for Patients
  • ...rare serious adverse events such as hepatitis, severe skin reactions, neurological, and hematological events have been reported when Malarone was used for the prophylaxis or treatment of malaria.

ADVERSE REACTIONS

• Postmarketing Adverse Reactions
  • Blood and Lymphatic System Disorders
  • Immune System Disorders
  • Nervous System Disorders
  • Hepatobiliary Disorders
  • Skin and Subcutaneous Tissue Disorders

Protonix I.V. (pantoprazole sodium) for Injection

Prescribing Information

PRECAUTIONS

• Drug Interactions
  • Concomitant use of atazanavir and proton pump inhibitors is not recommended. Coadministration of atazanavir with proton pump inhibitors is expected to substantially decrease atazanavir plasma concentrations and thereby reduce its therapeutic effect.

Protonix (pantoprazole sodium) Delayed-Release Tablets

Protonix (pantoprazole sodium) For Delayed-Release Oral Suspension

Prescribing Information

PRECAUTIONS

• Drug Interactions
  • Concomitant use of atazanavir and proton pump inhibitors is not recommended. Coadministration of atazanavir with proton pump inhibitors is expected to substantially decrease atazanavir plasma concentrations and thereby reduce its therapeutic effect.

Ranexa (ranolazine) Extended-Release Tablets

Prescribing Information

PRECAUTIONS

• Ranolazine is primarily metabolized by CYP 3A and is a substrate of P-glycoprotein. Coadministration of Ranexa and an inducer of CYP 3A metabolism and P-glycoprotein (rifampin, and structurally related rifabutin and rifapentin, phenobarbital, phenytoin, carbamazepine, and St. John’s wort) should be avoided (See Drug-Drug Interactions).
• Drug-Drug Interactions
  • Rifampin
    • Rifampin 600 mg q.d. decreases the plasma concentration of ranolazine by approximately 95%. Coadministration of Ranexa and rifampin should be avoided.

Rebetol (ribavirin, USP) Capsules and Oral Solution

Prescribing Information

Medication Guide

PRECAUTIONS

• Animal Toxicology

MEDICATION GUIDE

• How Should I Take Rebetol Capsules or Oral Solution?
  • Under no circumstances should Rebetol Capsules be opened, crushed, or broken.

Prescribing Information

Patient Package Insert

PRECAUTIONS

• Information for Patients
  • Physicians should advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking all PDE5 inhibitors, including Revatio...

ADVERSE REACTIONS

• Clinical Trials
• Postmarketing Experience
  • Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including Revatio...
  • Other Events
  • Nervous
    • Seizure
    • Seizure Recurrence

PATIENT PACKAGE INSERT

• What are the possible side effects of Revatio (sildenafil citrate)?
  • The following side effects were reported rarely in patients taking sildenafil...
    • Sudden decrease or loss of hearing...

Reyataz (atazanavir) Capsules

Prescribing Infomation

PRECAUTIONS

• Drug Interactions
  • Table 11
    • Proton-Pump Inhibitors
      • Omeprazole

Thyrogen (thyrotropin alfa for injection)

Prescribing Information

PRECAUTIONS

• General
  • There have been reports of deaths in which events leading to death occurred within 24 hours after administration of Thyrogen...

ADVERSE REACTIONS

• ...In post-marketing experience, there have been rare reports of events leading to death that occurred within 24 hours of administration of Thyrogen in patients with multiple serious medical problems...

Prescribing Information

PRECAUTIONS

• Table 2: Drugs that may decrease T4 absorption, which may result in hypothyroidism
  • Patients treated concomitantly with orlistat and levothyroxine should be monitored for changes in thyroid function.

Prescribing Information

PRECAUTIONS

• Hypersensitivity Reactions
  • ...There are post-marketing spontaneous reports of life-threatening hypersensitivity reactions in patients receiving Venofer...

ADVERSE REACTIONS

• Hypersensitivity Reactions
  • The postmarketing spontaneous reporting system includes reports of patients who experienced serious or life-threatening reactions (anaphylactic shock, loss of
    consciousness or collapse, bronchospasm with dyspnea, or convulsion) associated with Venofer administration.

Gonal-f RFF Pen (follitropin alfa injection)

Patient Package Insert

PATIENT PACKAGE INSERT

[See highlighted patient package insert for new text.]

• Storing the Gonal-f RFF Pen Before the First Use
• How do I prepare and use the Gonal-f RFF Pen?
  • Getting Ready
  • Preparing the Pen
  • Injecting the Dose
• Where can more information about the Gonal-f RFF Pen be obtained?

FDA/CDER/Office of Drug Safety
Web page last revised by jlw February 26, 2007