The detailed view includes drug products with safety labeling changes to the CONTRAINDICATIONS, BOXED WARNING, WARNINGS, PRECAUTIONS, or ADVERSE REACTIONS sections. The prescribing information may be accessed by clicking on the drug name.

Brand (Generic) Name

Summary of Changes to Contraindications and Warnings

Fluvoxamine Maleate Tablets

(click product name to read prescribing information)

WARNINGS

• Potential Tizanidine Interaction
• Potential Alosetron Interaction

PRECAUTIONS

• Concomitant Medication
• Drug Interactions
  • Potential Interactions with Drugs that Inhibit or are Metabolized by Cytochrome P450 Isozymes
• Other Drugs
  • Alosetron

CONTRAINDICATIONS

Co-administration of thioridazine, terfenadine, astemizole, cisapride, pimozide, alosetron or tizanidine with fluvoxamine maleate is contraindicated. Fluvoxamine maleate tablets are contraindicated in patients with a history of hypersensitivity to fluvoxamine maleate.

^WARNINGS

^{Potential Tizanidine Interaction}

Fluvoxamine is a potent inhibitor of CYP1A2 and tizanidine is a CYP1A2 substrate. The effect of fluvoxamine (100 mg daily for 4 days) on the pharmacokinetics and pharmacodynamics of a single 4 mg dose of tizanidine has been studied in 10 healthy subjects. Tizanidine C_max was increased approximately 12-fold (range 5-fold to 32-fold), elimination half-life was increased by almost 3-fold, and AUC increased 33-fold (range 14-fold to 103-fold). The mean maximal effect on blood pressure was a 35 mm Hg decrease in systolic blood pressure, a 20 mm Hg decrease in diastolic blood pressure, and a 4 beat/min decrease in heart rate. Drowsiness was significantly increased and performance on a psychomotor task was significantly impaired. Fluvoxamine and tizanidine should not be used together.

Potential Alosetron Interaction

Fluvoxamine, an inhibitor of several CYP isozymes, has been shown to increase mean alosetron plasma concentrations (AUC) approximately 6-fold and prolonged the half-life by approximately 3-fold. Consequently, it is recommended that fluvoxamine not be used in combination with alosetron.

Norvir (ritonavir capsules) Soft Gelatin 

Norvir (ritonavir oral solution)

(click product name to read prescribing information)

• Table 4
  • Alpha₁-adrenoreceptor Antagonist
    • Alfuzosin HCL

WARNINGS

• Drug Interactions
  • Fluticasone Propionate

PRECAUTIONS

• Drug Interactions
  • Table 6
    • Trazodone
    • Fluticasone Propionate
     

CONTRAINDICATIONS

Alfuzosin HCL as member of Alpha₁-adrenoreceptor antagonist, is contraindicated with Norvir.

WARNINGS

A drug interaction study in healthy subjects has shown that ritonavir significantly increases plasma fluticasone propionate exposures, resulting in significantly decreased serum cortisol concentrations. Systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression have been reported during postmarketing use in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate. Therefore, coadministration of fluticasone propionate and Norvir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects. 

Tev-Tropin [somatropin (rDNA origin) for injection]

(click product name to read prescribing information)

WARNINGS

CONTRAINDICATIONS

Growth hormone is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment. Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, Tev-Tropin is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.

WARNINGS

 There have been reports of fatalities after initiating therapy with growth hormone in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstructions or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. Patients with Prader-Willi syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with growth hormone. If during treatment with growth hormone, patients show signs of upper airway obstruction (including onset of or increased snoring) and/or new onset sleep apnea, treatment should be interrupted. All patients with Prader-Willi syndrome treated with growth hormone should also have effective weight control and be monitored for signs of respiratory infection, which should be diagnosed as early as possible and treated aggressively.

Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, Tev-Tropin is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.

Brand (Generic) Name

Summary of Changes to Contraindications and Warnings

Ellence (epirubicin hydrochloride injection) 

(click product name to read prescribing information)

BOXED WARNING

WARNINGS

• Secondary Leukemia
  • Figure 6
  • Table 4

PRECAUTIONS

• General

ADVERSE REACTIONS

• Table 6

 BOXED WARNING

The cumulative risk of developing treatment-related AML or myelodysplastic syndrome (MDS), in 7110 patients with breast cancer who received adjuvant treatment with epirubicin-containing regimens, was estimated as 0.27% at 3 years, 0.46% at 5 years, and 0.55% at 8 years.

WARNINGS

An analysis of 7110 patients who received adjuvant treatment with epirubicin in controlled clinical trials as a component of polychemotherapy regimens for early breast cancer, showed a cumulative risk of secondary acute myelogenous leukemia or myelodysplastic syndrome (AML/MDS) of about 0.27% (approximate 95% CI, 0.14-0.40) at 3 years, 0.46% (approximate 95% CI, 0.28-0.65) at 5 years and 0.55% (approximate 95% CI, 0.33-0.78) at 8 years. The risk of developing AML/MDS increased with increasing epirubicin cumulative doses as shown in Figure 6.

Brand (Generic) Name

Summary of Changes to Contraindications and Warnings

(click product name to read prescribing information)

• Cerebrovascular Adverse Events, Including Stroke, in Elderly Patients with Dementia

In placebo-controlled clinical studies (two flexible dose and one fixed dose study) of dementia-related psychosis, there was an increased incidence of cerebrovascular adverse events (eg, stroke, transient ischemic attack), including fatalities, in aripiprazole-treated patients (mean age: 84 years; range: 78-88 years). In the fixed-dose study, there was a statistically significant dose response relationship for cerebrovascular adverse events in patients treated with aripiprazole. Aripiprazole is not approved for the treatment of patients with dementia-related psychosis.

Crestor (rosuvastatin calcium) Tablets

(click product name to read prescribing information)

• Myopathy/Rhabdomyolysis

PRECAUTIONS

• General
  • Asian subjects
• Pregnancy
  • Pregnant rats given oral gavage dosages

ADVERSE REACTIONS

• Clinical Adverse Experiences
  • Laboratory Abnormalities
    • Elevated Creatine Phosphokinase
• Postmarketing Experience
  • Very Rare Cases of Jaundice

In clinical trials, the incidence of myopathy and rhabdomyolysis increased at doses of rosuvastatin above the recommended dosage range (5 to 40 mg). In postmarketing experience, effects on skeletal muscle, e.g. uncomplicated myalgia, myopathy and, rarely, rhabdomyolysis have been reported in patients treated with HMG-CoA reductase inhibitors including rosuvastatin. As with other HMG-CoA reductase inhibitors, reports of rhabdomyolysis with rosuvastatin are rare, but higher at the highest marketed dose (40 mg). Factors that may predispose patients to myopathy with HMG-CoA reductase inhibitors include advanced age (≥65 years), hypothyroidism, and renal insufficiency.

Rosuvastatin should be prescribed with caution in patients with predisposing factors for myopathy, such as, renal impairment, advanced age, and inadequately treated hypothyroidism.

The 40 mg dose of rosuvastatin is reserved only for those patients who have not achieved their LDL-C goal utilizing the 20 mg dose of rosuvastatin once daily.

Rosuvastatin therapy should also be temporarily withheld in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis, hypotension, dehydration, major surgery, trauma, severe metabolic, endocrine, and electrolyte disorders, or uncontrolled seizures).

Diamox Sequels (acetazolamide extended-release capsules)

(click product name to read prescribing information)

PRECAUTIONS

• Information for Patients
• Drug Interactions
  • Lithium
• Drug/Laboratory Test Interactions
• Geriatric Use

ADVERSE REACTIONS

• Body as a Whole
  • Fever

Femring (estradiol acetate vaginal ring) 

(click product name to read prescribing information)

• Coronary Heart Disease and Stroke
• Venous Thromboembolism (VTE)

PATIENT PACKAGE INSERT

• What Is The Most Important Information I Should Know About Femring (an Estrogen Product)?

Coronary Heart Disease and Stroke

In the Women's Health Initiative (WHI) study, an increase in the number of strokes was observed in women receiving CE alone compared to placebo.

Venous Thromboembolism (VTE)

In the Women's Health Initiative (WHI) study, an increased risk of deep vein thrombosis was observed in women receiving CE alone compared to placebo.

Kaletra (lopinavir/ritonavir) Capsules and Oral Solution

(click product name to read prescribing information)

• Drug Interactions
  • Fluticasone Propionate

PRECAUTIONS

• Drug Interactions
  • Table 9
    • Trazodone
    • Fluticasone

A drug interaction study in healthy subjects has shown that ritonavir significantly increases plasma fluticasone propionate exposures, resulting in significantly decreased serum cortisol concentrations. Concomitant use of Kaletra and fluticasone propionate is expected to produce the same effects. Systemic corticosteroid effects including Cushing's syndrome and adrenal suppression have been reported during postmarketing use in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate. Therefore, coadministration of fluticasone propionate and Kaletra is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.

Maxaquin (lomefloxacin hydrochloride tablets)

(click product name to read prescribing information)

• Peripheral Neuropathy
• Tendon Effects

PRECAUTIONS

• Information for Patients

ADVERSE REACTIONS

• Post-Marketing Adverse Events
  • Quinolone-Class Adverse Events
    • Peripheral Neuropathy
    • Torsades de Pointes

Rare cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving quinolones, including lomefloxacin. Lomefloxacin should be discontinued if the patient experiences symptoms of neuropathy including pain, burning, tingling, numbness, and /or weakness, or is found to have deficits in light touch, pain, temperature, position sense, vibratory sensation, and/or motor strength in order to prevent the development of an irreversible condition.

Tendon Effects

Ruptures of the shoulder, hand, Achilles tendon or other tendons that require surgical repair or resulted in prolonged disability have been reported in patients receiving quinolones, including lomefloxacin. Post-marketing surveillance reports indicate that this risk may be increased in patients receiving concomitant corticosteroids, especially the elderly. Lomefloxacin should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon. Patients should rest and refrain from exercise until diagnosis of tendonitis or tendon rupture had been excluded. Tendon rupture can occur during or after therapy with quinolones, including lomefloxacin.

(click product name to read prescribing information)

ADVERSE REACTIONS IN ADULTS

• Newly Diagnosed Glioblastoma Multiforme

(click product name to read prescribing information)

• Serious Dermatological Reactions

PRECAUTIONS

• Multi-organ Hypersensitivity
• Information for Patients

Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in both children and adults in association with Trileptal use. The median time of onset for reported cases was 19 days. Such serious skin reactions may be life-threatening, and some patients have required hospitalization with very rare reports of fatal outcome. Recurrence of the serious skin reactions following re-challenge with Trileptal has also been reported.

The reporting rate of TEN and SJS associated with Trileptal use, which is generally accepted to be an underestimate due to underreporting, exceeds the background incidence rate estimates by a factor of 3 to 10 fold. Estimates of the background incidence rate for these serious skin reactions in the general population range between 0.5 to 6 cases per million person years. Therefore, if a patient develops a skin reaction while taking Trileptal, consideration should be given to discontinuing Trileptal use and prescribing another anti-epileptic medication.

Boniva (ibandronate sodium) Tablets

(click product name to read prescribing information)

• General
  • Jaw Osteonecrosis
  • Musculoskeletal Pain
• Information for Patients
• Drug Interactions
  • H2 Blockers and Proton Pump Inhibitors (PPIs)
  • Aspirin/Nonsteroidal Antiinflammatory Drugs (NSAIDs)
• Carcinogenesis, Mutagenesis, Impairment of Fertility
  • Carcinogenesis
  • Impairment of Fertility
• Pregnancy
• Geriatric Use

ADVERSE REACTIONS

• Daily Dosing
• Treatment and Prevention of Postmenopausal Osteoporosis
• Table 3
• Once Monthly Dosing
• Table 4
• Ocular Adverse Events
• Laboratory Test Findings

PATIENT PACKAGE INSERT

• What Is My Boniva Schedule?
• Common Side Effects With Boniva Are:

Children's Advil (100 mg/5 mL ibuprofen) Suspension

(click product name to read prescribing information)

• Not Been Drinking Fluids
• Lost a Lot of Fluid Due to Continued Vomiting or Diarrhea
• Ulcers
• Bleeding Problems
• Problems or Serious Side Effects from Taking Fever Reducers or Pain Relievers
• Stomach Problems that Last or Come Back, such as Heartburn, Upset Stomach or Pain
• High Blood Pressure, Heart or Kidney Disease or is Taking a Diuretic

Alcohol Free statement added to carton of the fruit flavored product to maintain consistency with the grape and blue raspberry products.

Cialis (tadalafil) Tablets

(click product name to read prescribing information)

• Alpha-blockers
• Information for Patients
• Drug Interactions
  • Effects of Cialis on Other Drugs
    • Alpha Blockers
    • Tamsulosin
      • Table 7
    • Doxazosin
      • Table 8
      • Table 9

Cosopt (dorzolamide hydrochloride-timolol maleate ophthalmic solution)

(click product name to read prescribing information)

• Pediatric Use

ADVERSE REACTIONS

Gleevec (imatinib mesylate) Tablets

(click product name to read prescribing information)

• General
  • Fluid Retention and Edema
  • Hemorrhage

ADVERSE REACTIONS

• Chronic Myeloid Leukemia
• Table 4
• Table 6

Indocin (Indomethacin) Capsules, Oral Suspension and Suppositories

(click product name to read prescribing information)

• Drug Interactions
  • Anticoagulants

Levoxyl (levothyroxine sodium, USP) Tablets

(click product name to read prescribing information)

• Information for Patients

ADVERSE REACTIONS

• Tablet Stuck in Throat & Dysphagia

(click product name to read prescribing information)

• Nursing Mothers
  • Reduction in Breast Cancer Incidence in High Risk Women and Women with DCIS

Rapamune (sirolimus) Oral Solution and Tablets

(click product name to read prescribing information)

• Pediatric Use

ADVERSE REACTIONS

• Pediatrics

Velcade (bortezomib) for Injection

(click product name to read prescribing information)

• Peripheral Neuropathy
• Hypotension
• Cardiac Disorders
• Gastrointestinal Adverse Events
• Thrombocytopenia
  • Table 5
• Tumor Lysis Syndrome
• Patients with Renal Impairment
• Information for Patients
• Drug Interactions
• Pregnancy Category D
  • Pregnancy/Nursing
• Geriatric Use

ADVERSE REACTIONS

• Randomized Open-Label Phase 3 Clinical Study
  • Serious Adverse Events (SAEs)
  • Table 6
• Non-randomized Phase 2 Clinical Studies
  • Serious Adverse Events (SAEs)
  • Table 7
• The Phase 2 Open-Label Extension Study
  • Description of Selected Adverse Events from the Phase 3 and Phase 2 Studies
    • Gastrointestinal Events
    • Thrombocytopenia
    • Peripheral Neuropathy
    • Hypotension
    • Neutropenia
    • Asthenic Conditions (Fatigue, Malaise, Weakness)
    • Pyrexia
    • Additional Serious Adverse Events from Clinical Studies and Post-Marketing
    • Cardiac Disorders
    • Ear and Labyrinth Disorders
    • Eye Disorders
    • Gastrointestinal Disorders
    • General Disorders and Administration Site Conditions
    • Hepatobiliary Disorders
    • Infections and Infestations
    • Metabolism and Nutrition Disorders
    • Nervous System Disorders
    • Psychiatric Disorders
    • Renal and Urinary Disorders
    • Respiratory, Thoracic and Mediastinal Disorders
    • Skin and Subcutaneous Tissue Disorders
    • Vascular Disorders
  • Post-Marketing Experience

Vfend I.V. (voriconazole) for Injection

Vfend (voriconazole) Tablets

Vfend (voriconazole) for Oral Suspension

(click product name to read prescribing information)

• Drug Interactions
  • Table 10
    • Methadone (CYP3A4 Inhibition)

Vytorin (ezetimibe/simvastatin) Tablets

(click product name to read prescribing information)

PRECAUTIONS

• Drug Interactions

  • Cyclosporine

(click product name to read prescribing information)

• Drug Interactions 
  • HMG Co-A Reductase Inhibitors
    • Rosuvastatin
  • Cyclosporine

ADVERSE REACTIONS

• Postmarketing Experience

  • Myalgia

  • Elevated Creatine Phosphokinase

  • Myopathy/Rhabdomyolysis

  • Elevations in Liver Transaminases

  • Hepatitis

  • Thrombocytopenia

PATIENT PACKAGE INSERT

• What are the Possible Side Effects of Zetia?

Zofran (ondansetron hydrochloride) Injection Premixed

(click product name to read prescribing information)

• Pediatric Use

ADVERSE REACTIONS

• Postoperative Nausea and Vomiting
  • Pediatric Use
  • Table 14
  • Table 15

Zosyn (piperacillin and tazobactam for injection)

(click product name to read prescribing information)

PRECAUTIONS

• General
• Information for Patients
• Drug/Laboratory Test Interactions

Prilosec (omeprazole) Delayed-Release Capsules

(click product name to read prescribing information)

• Gastrointestinal
  • Stomatitis
• Nervous System/Psychiatric
  • Agitation
• Skin
  • Photosensitivity
• Hematologic
  • Leukopenia

Visudyne (verteporfin for injection)

(click product name to read prescribing information)

• Ocular Treatment Site
  • Severe Vision Decrease

FDA/CDER/OCD/Safety Policy and Communication Staff
Web page last revised by jlw May 13, 2005