Label Changes for:

Biaxin Filmtabs (clarithromycin tablets, USP) Biaxin Filmtabs (clarithromycin tablets, USP) Biaxin Granules (clarithromycin for oral suspension, USP) Biaxin XL Filmtabs (clarithromycin extended release tablets) 

September 2013

Changes have been made to the WARNINGS and PRECAUTIONS sections of the safety label.

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) –  

 

September 2013

WARNINGS

Hepatotoxicity
  •  ..... Symptoms of hepatitis can include anorexia, jaundice, dark urine, pruritus, or tender abdomen....
Drug Interactions
  • .....Clarithromycin should be used with caution when administered concurrently with medications that induce the cytochrome CYP3A4 enzyme (see PRECAUTIONS – Drug Interactions).
Benzodiazepines:
  • Increased sedation and prolongation of sedation have been reported with concomitant administration of clarithromycin and triazolobenzodiazepines, such as triazolam, and midazolam.
Oral Hypoglycemic Agents/Insulin
  • The concomitant use of clarithromycin and oral hypoglycemic agents and/or insulin can result in significant hypoglycemia. With certain hypoglycemic drugs such as nateglinide, pioglitazone, repaglinide and rosiglitazone, inhibition of CYP3A enzyme by clarithromycin may be involved and could cause hypoglycemia when used concomitantly. Careful monitoring of glucose is recommended.
Oral Anticoagulant
  • There is a risk of serious hemorrhage and significant elevations in INR and prothrombin time when clarithromycin is co-administered with warfarin. INR and prothrombin times should be frequently monitored while patients are receiving clarithromycin and oral anticoagulants concurrently.
HMG-CoA Reductase Inhibitors (statins)
  • Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated (see CONTRAINDICATIONS) as these statins are extensively metabolized by CYP3A4, and concomitant treatment with clarithromycin increases their plasma concentration, which increases the risk of myopathy, including rhabdomyolysis. Cases of rhabdomyolysis have been reported in patients taking clarithromycin concomitantly with these statins. If treatment with clarithromycin cannot be avoided, therapy with lovastatin or simvastatin must be suspended during the course of treatment.
  • Caution should be exercised when prescribing clarithromycin with statins. In situations where the concomitant use of clarithromycin with atorvastatin or pravastatin cannot be avoided, atorvastatin dose should not exceed 20 mg daily and pravastatin dose should not exceed 40 mg daily. Use of a statin that is not dependent on CYP3A metabolism (e.g.fluvastatin) can be considered. It is recommended to prescribe the lowest registered dose if concomitant use cannot be avoided.
Combination therapy with other drugs
  • For information about warnings of other drugs indicated in combination with BIAXIN, refer to the WARNINGS section of their package inserts.

PRECAUTIONS

Efavirenz, Nevirapine, Rifampicin, Rifabutin, and Rifapentine
  • Concomitant administration of rifabutin and clarithromycin resulted in an increase in rifabutin, and decrease in clarithromycin serum levels together with an increased risk of uveitis.
Etravirine
  • Clarithromycin exposure was decreased by etravirine; however, concentrations of the active metabolite, 14- OH-clarithromycin, were increased. Because 14-OH-clarithromycin has reduced activity against Mycobacterium avium complex (MAC), overall activity against this pathogen may be altered; therefore alternatives to clarithromycin should be considered for the treatment of MAC.
  • There have been spontaneous or published reports of CYP3A based interactions of erythromycin and/or clarithromycin with cyclosporine, carbamazepine, tacrolimus, alfentanil, disopyramide, rifabutin, quinidine, methylprednisolone, cilostazol, bromocriptine, vinblastine, phenobarbital and St. John’s Wort. 

 

July 2012

CONTRAINDICATIONS

  • Clarithromycin should not be given to patients with history of QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes.
  • Clarithromycin should not be used concomitantly with HMG-CoA reductase inhibitors (statins) that are extensively metabolized by CYP3A4 (lovastatin or simvastatin), due to the increased risk of myopathy, including rhabdomyolysis

WARNINGS

QT Prolongation
  • Clarithromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving clarithromycin. Fatalities have been reported. Clarithromycin should be avoided in patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia (see CONTRAINDICATIONS) and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval
Drug Interactions

Acute Hypersensitivity Reactions

  • In the event of severe acute hypersensitivity reactions, such as anaphylaxis, Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS), and Henoch-Schonlein purpura clarithromycin therapy should be discontinued immediately and appropriate treatment should be urgently initiated.

Oral Hypoglycemic Agents/Insulin

  • The concomitant use of clarithromycin and oral hypoglycemic agents and/or insulin can result in significant hypoglycemia. With certain hypoglycemic drugs such as nateglinide, pioglitazone, repaglinide and rosiglitazone, inhibition of CYP3A enzyme by clarithromycin may be involved and could cause hypolgycemia when used concomitantly. Careful monitoring of glucose is recommended.

Oral Anticoagulants

  • There is a risk of serious hemorrhage and significant elevations in INR and prothrombin time when clarithromycin is co-administered with warfarin. INR and prothrombin times should be frequently monitored while patients are receiving clarithromycin and oral anticoagulants concurrently.

HMG-CoA Reductase Inhibitors (statins)

  • Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated (see CONTRAINDICATIONS) as these statins are extensively metabolized by CYP3A4, and concomitant treatment with clarithromycin increases their plasma concentration, which increases the risk of myopathy, including rhabdomyolysis. Cases of rhabdomyolysis have been reported in patients taking clarithromycin concomitantly with these statins. If treatment with clarithromycin cannot be avoided, therapy with lovastatin or simvastatin must be suspended during the course of treatment.
  • Caution should be exercised when prescribing clarithromycin with statins. In situations where the concomitant use of clarithromycin with atorvastatin or pravastatin cannot be avoided, atorvastatin dose should not exceed 20 mg daily and pravastatin dose should not exceed 40 mg daily. Use of a statin that is not dependent on CYP3A metabolism (e.g.fluvastatin) can be considered. It is recommended to prescribe the lowest registered dose if concomitant use cannot be avoided.

ADVERSE REACTIONS

Post-Marketing Experience
  • There have been cases of rhabdomyolysis reported with clarithromycin use. In some cases, clarithromycin was administered concomitantly with other drugs known to be associated with rhabdomyolysis (such as statins, fibrates, colchicine or allopurinol). 

 

May 2012

WARNINGS

QT Prolongation
  • section added

PRECAUTIONS 

Geriatric Use
  • Elderly patients may be more susceptible to development of torsades de pointes arrhythmias than younger patients

 

May 2011

CONTRAINDICATIONS

  • Clarithromycin is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of clarithromycin.

WARNINGS

Hepatotoxicity
  • Hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been reported with clarithromycin. This hepatic dysfunction may be severe and is usually reversible. In some instances, hepatic failure with fatal outcome has been reported and generally has been associated with serious underlying diseases and/or concomitant medications. Discontinue clarithromycin immediately if signs and symptoms of hepatitis occur.

ADVERSE REACTIONS

Postmarketing Experience
  • Adverse reactions related to hepatic dysfunction have been reported in postmarketing experience with clarithromycin.

 

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