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

Cipro I.V. (ciprofloxacin) for Intravenous Infusion

(click product name to read prescribing information)

WARNINGS

• Cytochrome P450 (CYP450)

PRECAUTIONS

• Information for Patients
  • Tizanidine (Zanaflex)
• Drug Interactions
  • Tizanidine

CONTRAINDICATIONS

Ciprofloxacin is contraindicated in persons with a history of hypersensitivity to ciprofloxacin, any member of the quinolone class of antimicrobial agents, or any of the product components.

Concomitant administration with tizanidine is contraindicated.

WARNINGS

Ciprofloxacin is an inhibitor of the hepatic CYP1A2 enzyme pathway. Coadministration of ciprofloxacin and other drugs primarily metabolized by CYP1A2 (e.g. theophylline, methylxanthines, tizanidine) results in increased plasma concentrations of the coadministered drug and could lead to clinically significant pharmacodynamic side effects of the coadministered drug.

Cipro (ciprofloxacin hydrochloride) Tablets

Cipro (ciprofloxacin) Oral Suspension

(click product name to read prescribing information)

WARNINGS

• Cytochrome P450 (CYP450)

PRECAUTIONS

• Information for Patients
  • Tizanidine (Zanaflex)
• Drug interactions
  • Tizanidine

PATIENT PACKAGE INSERT

CONTRAINDICATIONS

Ciprofloxacin is contraindicated in persons with a history of hypersensitivity to ciprofloxacin, any member of the quinolone class of antimicrobial agents, or any of the product components.

Concomitant administration with tizanidine is contraindicated.

WARNINGS

Ciprofloxacin is an inhibitor of the hepatic CYP1A2 enzyme pathway. Coadministration of ciprofloxacin and other drugs primarily metabolized by CYP1A2 (e.g. theophylline, methylxanthines, tizanidine) results in increased plasma concentrations of the coadministered drug and could lead to clinically significant pharmacodynamic side effects of the coadministered drug.

Cipro XR (ciprofloxacin extended-release tablets)

(click product name to read prescribing information)

WARNINGS

• Cytochrome P450 (CYP450)

PRECAUTIONS

• Information for Patients
  • Tizanidine (Zanaflex)
• Drug Interactions
  • Tizanidine

PATIENT PACKAGE INSERT

CONTRAINDICATIONS

Ciprofloxacin is contraindicated in persons with a history of hypersensitivity to ciprofloxacin, any member of the quinolone class of antimicrobial agents, or any of the product components.

Concomitant administration with tizanidine is contraindicated.

WARNINGS

Ciprofloxacin is an inhibitor of the hepatic CYP1A2 enzyme pathway. Coadministration of ciprofloxacin and other drugs primarily metabolized by CYP1A2 (e.g. theophylline, methylxanthines, tizanidine) results in increased plasma concentrations of the coadministered drug and could lead to clinically significant pharmacodynamic side effects of the coadministered drug.

DDAVP Injection (desmopressin acetate) 

(click product name to read prescribing information)

PRECAUTIONS

• Geriatric Use

. . . DDAVP is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50ml/min).

DDAVP Nasal Spray (desmopressin acetate)

(click product name to read prescribing information)

PRECAUTIONS

• Geriatric Use

CONTRAINDICATIONS

. . . DDAVP is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50ml/min).

DDAVP Rhinal Tube (desmopressin acetate)

(click product name to read prescribing information)

PRECAUTIONS

• Geriatric Use

. . . DDAVP is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50ml/min).

DDAVP Tablets (desmopressin acetate)

(click product name to read prescribing information)

PRECAUTIONS

• Geriatric Use

. . . DDAVP is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50ml/min).

Norvir (ritonavir capsules) Soft Gelatin & (ritonavir oral solution)

(click product name to read prescribing information)

• Voriconazole
• Table 4
  • Antifungal
    • Voriconazole

• Drug Interactions

PRECAUTIONS

• Immune Reconstitution Syndrome
• Information for Patients
  • PDE5 Inhibitors
• Drug Interactions
  • Table 5:  Drugs That Should Not Be Co-administered with Norvir
  • Table 6:  Established and Other Potentially Significant Drug Interactions.....

PATIENT PACKAGE INSERT

.....Voriconazole is an exception in that coadministration of Norvir and Voriconazole results in a significant decrease in plasma concentrations of Voriconazole.

WARNINGS

Particular caution should be used when prescribing PDE5 inhibitors for erectile dysfunction (eg, sildenafil, tadalafil, or vardenafil) for patients receiving protease inhibitors, including Norvir.....

Brand (Generic) Name

Summary of Changes to Contraindications and Warnings

Strattera (atomoxetine hydrochloride) Capsules

(click product name to read prescribing information)

BOXED WARNING

• Suicidal Ideation in Children and Adolescents 

WARNINGS

• Suicidal Ideation

• Screening Patients for Bipolar Disorder

PRECAUTIONS

• Information for Patients
  • Initial Paragraph
  • Suicide Risk
• Pediatric Use

MEDICATION GUIDE

BOXED WARNING

Strattera (atomoxetine) increased the risk of suicidal ideation in short-term studies in children or adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). Anyone considering the use of Strattera in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be monitored closely for suicidality (suicidal thinking and behavior), clinical worsening, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Strattera is approved for ADHD in pediatric and adult patients. Strattera is not approved for major depressive disorder.....

WARNINGS

Suicidal Ideation

.....All pediatric patients being treated with Strattera should be monitored closely for suicidality, clinical worsening, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes. Such monitoring would generally include at least weekly face-to-face contact with patients or their family members or caregivers during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks. Additional contact by telephone may be appropriate between face-to-face visits.

.....Families and caregivers of pediatric patients being treated with Strattera should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers.....

Screening Patients for Bipolar Disorder

In general, particular care should be taken in treating ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown..... 

For additional details, see MedWatch 9/29/05 Safety Alert.

Tracleer (bosentan) Film-coated Tablets

(click product name to read prescribing information)

BOXED WARNING

• Potential Liver Injury

WARNINGS

• Potential Liver Injury

PRECAUTIONS

• Pulmonary Veno-Occlusive Disease (PVOD)
• Drug Interactions
  • CYP Isozymes
  • Sildenafil

ADVERSE REACTIONS

• Post-Marketing Experience
  • Unexplained Hepatic Cirrhosis

MEDICATION GUIDE

BOXED WARNING

.....In the post-marketing period, in the setting of close monitoring, rare cases of unexplained hepatic cirrhosis were reported after prolonged (> 12 months) therapy with Tracleer in patients with multiple co-morbidities and drug therapies. The contribution of Tracleer in these cases could not be excluded.

In at least one case the initial presentation (after > 20 months of treatment) included pronounced elevations in aminotransferases and bilirubin levels accompanied by nonspecific symptoms, all of which resolved slowly over time after discontinuation of Tracleer. This case reinforces the importance of strict adherence to the monthly monitoring schedule for the duration of treatment and the treatment algorithm, which includes stopping Tracleer with a rise of aminotransferases accompanied by signs or symptoms of liver dysfunction.....

WARNINGS 

.....Elevations of AST and/or ALT associated with bosentan are dose-dependent, occur both early and late in treatment, usually progress slowly, are typically asymptomatic, and usually have been reversible after treatment interruption or cessation. Aminotransferase elevations also may reverse spontaneously while continuing treatment with Tracleer.....

Xyrem (sodium oxybate) Oral Solution

(click product name to read prescribing information)

BOXED WARNING

WARNINGS

• Confusion/Neuropsychiatric Adverse Events

  • Depression

PRECAUTIONS

• Incontinence

• Sodium Intake

• Information for Patients

BOXED WARNING

Xyrem is available through the Xyrem Success Program, using a centralized pharmacy 1- 866-XYREM88 (1-866-997-3688). The Success Program provides educational materials to the prescriber and the patient explaining the risks and proper use of sodium oxybate, and the required prescription form. Once it is documented that the patient has read and/or understood the materials, the drug will be shipped to the patient. The Xyrem Success Program also recommends patient follow-up every 3 months. Physicians are expected to report all serious adverse events to the manufacturer.

WARNINGS

In clinical trials, 3.2% of patients treated with sodium oxybate reported depressive symptoms. In the majority of cases, no change in sodium oxybate treatment was required. Four patients (<1%) discontinued because of depressive symptoms. In the controlled clinical trial where patients were randomized to fixed doses of 3, 6, 9 g/night or placebo, there was a single event of depression at the 3 g/night dose. In Trial 3, where patients were titrated from an initial 4.5 g/night starting dose, the incidence of depression was 1 (1.7%), 1 (1.5%), 2 (3.2%), and 2 (3.6%) for the placebo, 4.5g, 6 g, and 9 g/night doses respectively.

Brand (Generic) Name

Summary of Changes to Contraindications and Warnings

Agenerase (amprenavir) Oral Solution

(click product name to read prescribing information)

PRECAUTIONS

• Immune Reconstitution Syndrome
• Drug Interactions
  • Table 8
  • Other Agents
    • Antidepressant
      • Trazodone
    • Inhaled/nasal steroid
      • 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 Agenerase with ritonavir 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 Agenerase/ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects. 

(click product name to read prescribing information)

• Pure Red Cell Aplasia

ADVERSE REACTIONS

• Immunogenicity

Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported in patients treated with Aranesp. This has been reported predominantly in patients with CRF receiving Aranesp by subcutaneous administration. Any patient who develops a sudden loss of response to Aranesp, accompanied by severe anemia and low reticulocyte count, should be evaluated for the etiology of loss of effect, including the presence of neutralizing antibodies to erythropoietin. If anti-erythropoietin antibody-associated anemia is suspected, withhold Aranesp and other erythropoietic proteins. Contact Amgen (1-800-77AMGEN) to perform assays for binding and neutralizing antibodies. Aranesp should be permanently discontinued in patients with antibody-mediated anemia. Patients should not be switched to other erythropoietic proteins as antibodies may cross-react.

For additional details, see MedWatch 12/01/05 Safety Alert.

(click product name to read prescribing information)

• Sustained Hypertension

PRECAUTIONS

• General
  • Insomina/Nervousness
  • Changes in Weight
  • Changes in Appetite
  • Activation of Mania/Hypomania
  • Seizures
  • Use in Patients with Concomitant Illness
  • Geriatric Use

ADVERSE REACTIONS

• Adverse Findings Observed in Short-Term, Placebo-Controlled Studies with Effexor XR

  • Adverse Events Associated with Discontinuation of Treatment

• Adverse Events Occurring at an Incidence of 2% or More Among Effexor XR Treated Patients

  • Panic Disorder

    • Table 6

  •  Vital Sign Changes

  • Laboratory Changes

• Other Adverse Events Observed During the Premarketing Evaluation of Effexor and Effexor XR

  • Initial Section

  • Nervous System

    • Rare

      • Homicidal Ideation

.....Among patients treated with 75 to 225 mg/day of Effexor XR in premarketing panic disorder studies, 0.9% (9/973) experienced sustained hypertension.....

Mevacor (lovastatin) Tablets

(click product name to read prescribing information)

• Myopathy/Rhabdomyolysis
• Table VI

PRECAUTIONS

• Other Drug Interactions
  • Cyclosporine or Danazol

 Myopathy/Rhabdomyolysis

Lovastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma.....

Table VI

New Table added entitled "Drug Interactions Associated with Increased Risk of Myopathy/Rhabdomyolysis." (See prescribing information for table).

(click product name to read prescribing information)

ADVERSE REACTIONS

• Post-Marketing Experience

The extent of the risk of thrombotic adverse events after treatment with NovoSeven in patients with hemophilia and inhibitors is not known, but is considered to be low. Patients with disseminated intravascular coagulation (DIC), advanced atherosclerotic disease, crush injury, septicemia, or concomitant treatment with aPCCs/PCCs (activated or nonactivated prothrombin complex concentrates) may have an increased risk of developing thrombotic events due to circulating TF or predisposing coagulopathy. 

The extent of the risk of arterial and venous thromboembolic adverse events after treatment with NovoSeven in patients without hemophilia is also not known. A clinical study in elderly non-hemophilia intracerebral hemorrhage patients indicated a potential increased risk of arterial thromboembolic adverse events with use of NovoSeven, including myocardial ischemia, myocardial infarction, cerebral ischemia and/or infarction.

For additional details, see MedWatch 12/01/05 Safety Alert.

Ortho Evra (norelgestromin /ethinyl estradiol transdermal system)

(click product name to read prescribing information)

• Pharmacokinetic Profile
• .....There is limited epidemiologic data available to determine whether safety with the transdermal route of administration is different than the oral route.....

PATIENT PACKAGE INSERT

Tarceva (erlotinib) Tablets

(click product name to read prescribing information)

• Pulmonary Toxicity

The overall incidence of ILD-like events in approximately 4900 Tarceva-treated patients from all studies (including uncontrolled studies and studies with concurrent chemotherapy) was approximately 0.7%.....

Amaryl (glimepiride tablets)

(click product name to read prescribing information)

• Pediatric Use

• Pediatric Patients

Aredia (pamidronate disodium for injection) for Intravenous Infusion 

(click product name to read prescribing information)

• Geriatric Use

Avelox (moxifloxacin hydrochloride) Tablets

Avelox I.V. (moxifloxacin hydrochloride in sodium chloride injection) 

(click product name to read prescribing information)

• Information for Patients
  • That phototoxicity has been reported in patients receiving certain quinolones, and infrequently moxifloxacin.....
• Pregnancy: Teratogenic Effects. Pregnancy Category C:
  • Cynomolgus Monkeys

• Initial Paragraph
  • Body as a Whole
    • Malaise
  • Cardiovascular
    • QT interval Prolonged
  • Digestive
  • Hemic and Lymphatic
    • Thrombocythemia
  • Nervous System
    • Insomnia
    • Nervousness
    • Vertigo
    • Somnolence
    • Anxiety
    • Tremor
  • Additional Clinically Relevant Rare Events.....
    • Anemia
    • Hypertension
    • Kidney Function Abnormal
    • Leg Pain
    • Paraesthesia
• Post-Marketing Adverse Event Reports
  • Phototoxicity

Bicillin C-R (penicillin G benzathine and penicillin G procaine injectable suspension) Disposable Syringe 4 mL for deep IM injection only

(click product name to read prescribing information)

• Geriatric Use

Bicillin C-R (penicillin G benzathine and penicillin G procaine injectable suspension) Tubex 1 mL and 2 mL for deep IM injection only

(click product name to read prescribing information)

• Geriatric Use

Bicillin C-R 900/300 (penicillin G benzathine and penicillin G procaine injectable suspension) Tubex 2 mL for deep IM Injection only

(click product name to read prescribing information)

• Geriatric Use

(click product name to read prescribing information)

• Geriatric Use

(click product name to read prescribing information)

• Geriatric Use

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

(click product name to read prescribing information)

• General
  • .....One peanut sensitive child experienced a flare of his atopic dermatitis after 5 days of twice daily treatment with Derma-Smoothe/FS.
  • .....Physicians should use caution in prescribing Derma-Smoothe/FS for peanut-sensitive individuals.

• Initial Paragraph
  • ....One peanut sensitive child experienced a flare of his atopic dermatitis after 5 days of twice daily treatment with Derma-Smoothe/FS.
• A post marketing (open-label) safety study was conducted in 58 children to evaluate the local safety of Derma-Smoothe/FS when applied twice daily for 4 weeks to the face in children (2 to 12 years) with moderate to severe atopic dermatitis.
  • Table:  Incidence of Adverse Events (%)

(click product name to read prescribing information)

• General
  • Changes in Weight
    • Pediatric Patients
  • Changes in Height
    • Pediatric Patients
  • Changes in Appetite
    • Pediatric Patients

Fosamax (alendronate sodium) Tablets and Oral Solution

(click product name to read prescribing information)

• Dental
  • Osteonecrosis of the Jaw

• Post-Marketing Experience
  • Localized Osteonecrosis of the Jaw.....

(click product name to read prescribing information)

• Dental
  • Osteonecrosis of the Jaw

• Post-Marketing Experience
  • Localized Osteonecrosis of the Jaw.....

Hiprex (methenamine hippurate tablets, USP)

(click product name to read prescribing information)

• Information for Patients

Ketek (telithromycin) Tablets

(click product name to read prescribing information)

• General
  • Visual Disturbances
• Information for Patients

• Post-Marketing Adverse Event Reports
  • Allergic
    • Face Edema
    • Rare Reports of Severe Allergic Reactions, including Angioedema and Anaphylaxis
  • Cardiovascular
    • Atrial Arrhythmias
    • Palpitations
  • Gastrointestinal System
    • Pancreatitis
  • Liver and Biliary System
    • Hepatic Dysfunction.....
  • Musculoskeletal
    • Muscle Cramps
    • Exacerbation of Myasthenia Gravis
  • Nervous System
    • Syncope.....

Kytril (granisetron hydrochloride) Injection

(click product name to read prescribing information)

• Drug Interactions
  • Ketoconazole
  • Phenobarbital

Kytril (granisetron hydrochloride) Tablets and Oral Solution

(click product name to read prescribing information)

• Initial Paragraph
• Drug Interactions
  • Ketoconazole
  • Phenobarbital

Lamisil (terbinafine hydrochloride tablets)

(click product name to read prescribing information)

• Drug Interactions
  • Initial Paragraph

• Psoriasiform Eruptions or Exacerbation of Psoriasis
• Acute Generalized Exanthematous Pustulosis

Lexiva (fosamprenavir calcium) Tablets

(click product name to read prescribing information)

• Table 13
  • Histamine H2-receptor Antagonists
    • Cimetidine, Famotidine, Nizatidine, Ranitidine
  • Proton Pump Inhibitors
    • Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole

(click product name to read prescribing information)

• General .....Neutrexin infusion should be permanently discontinued.....

Pamidronate Disodium Injection 

Pamidronate Disodium for Injection 

(click product name to read prescribing information)

• General
  • Osteonecrosis of the Jaw
  • Musculoskeletal Pain

(click product name to read prescribing information)

• Hyperprolactinemic States
• Information for Patients
• Geriatric Use

• Parkinson's Disease
  • Pleural and pericardial effusions, pleural, and pulmonary fibrosis or retroperitoneal fibrosis.....
  • Very rarely, a syndrome resembling Neuroleptic Malignant Syndrome.....

PEG-Intron (peginterferon alfa-2b) Powder for Injection

(click product name to read prescribing information)

• Drug Interactions
  • Drugs Metabolized by Cytochrome P-450

(click product name to read prescribing information)

• Hepatic Impairment
• Renal Impairment

(click product name to read prescribing information)

• Information for Patients

• When used to treat male-erectile dysfunction, non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely.....

Singulair (montelukast sodium) Tablets, Chewable Tablets, and Oral Granules

(click product name to read prescribing information)

• Pediatric Use

• Pediatric Patients 6 to 14 Years of Age with Asthma

Valtrex (valacyclovir hydrochloride) Caplets

(click product name to read prescribing information)

• Information for Patients
  • Maintain Adequate Hydration

Zyvox (linezolid) Tablets and Injection

Zyvox (linezolid) for Oral Suspension 

(click product name to read prescribing information)

• General
  • Serotonin Syndrome

Angiomax (bivalirudin)

(click product name to read prescribing information)

• AT-BAT Study (After Table 5)

  • In the AT-BAT study, 1 patient who did not undergo PCI had major bleeding.....

• AT-BAT Study (After Table 7)
  • In the AT-BAT study, 1 patient died during a bradycardic episode 46 hours after a successful PCI, another patient.....

Avalide (irbesartan-hydrochlorothiazide) Tablets

(click product name to read prescribing information)

• Post-Marketing Experience
  • Rare cases of rhabdomyolysis.....

Avapro (irbesartan) Tablets

(click product name to read prescribing information)

• Post-Marketing Experience
  • Rare cases of rhabdomyolysis.....

FDA/CDER/OCD/Safety Policy and Communication Staff
Web page last revised by jlw Feb 03, 2006