Ketek

KETEK- telithromycin tablet, film coated
sanofi-aventis U.S. LLC

WARNING: CONTRAINDICATION IN MYASTHENIA GRAVIS

There have been reports of fatal and life-threatening respiratory failure in patients with myasthenia gravis associated with the use of KETEK. [see Contraindications (4.1)]

1 INDICATIONS AND USAGE

KETEK is indicated for the treatment of community-acquired pneumonia (of mild to moderate severity) due to Streptococcus pneumoniae , (including multi-drug resistant S. pneumoniae [MDRSP 1]), Haemophilus influenzae , Moraxella catarrhalis , Chlamydophila pneumoniae , or Mycoplasma pneumoniae , for patients 18 years or older.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of KETEK and other antibacterial drugs, KETEK should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.


1
MDRSP, Multi-drug resistant Streptococcus pneumoniae includes isolates known as PRSP (penicillin-resistant Streptococcus pneumoniae), and are isolates resistant to two or more of the following antibacterials: penicillin, 2nd generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

The dosage of KETEK tablets is 800 mg (2 tablets of 400 mg) taken orally once daily for 7–10 days in patients 18 years or older. KETEK tablets can be administered with or without food.

2.2 Dosage in Patients with Renal and/or Hepatic Impairment

In the presence of severe renal impairment (CLCR less than 30 mL/min), including patients who need dialysis, reduce the dosage of KETEK to 600 mg once daily. In patients undergoing hemodialysis, give KETEK after the dialysis session on dialysis days. [see Clinical Pharmacology (12.3)]

In the presence of severe renal impairment (CLCR less than 30 mL/min), with coexisting hepatic impairment, reduce the dosage of KETEK to 400 mg once daily. Patients with mild or moderate renal impairment (CLCR of 30 mL/min or more) with or without coexisting hepatic impairment do not require a dosage adjustment. No dosage adjustments of KETEK are necessary in patients with hepatic impairment alone. [see Clinical Pharmacology (12.3)]

3 DOSAGE FORMS AND STRENGTHS

KETEK tablets are available in two strengths:

  • Tablets: 400 mg supplied as light-orange, oval, film-coated tablets, imprinted “H3647″ on one side and “400″ on the other side.
  • Tablets: 300 mg supplied as light-orange, oval, film-coated tablets, imprinted “38AV” on one side and blank on the other side.

4 CONTRAINDICATIONS

4.1 Myasthenia Gravis

KETEK is contraindicated in patients with myasthenia gravis. Exacerbations of myasthenia gravis have been reported in patients and sometimes occurred within a few hours of the first dose of KETEK. Reports have included fatal and life-threatening acute respiratory failure with a rapid onset and progression.

4.2 Hepatitis

KETEK is contraindicated in patients with previous history of hepatitis and/or jaundice associated with the use of KETEK tablets, or any macrolide antibacterial. [see Warnings and Precautions (5.1)]

4.3 Hypersensitivity

KETEK is contraindicated in patients with a history of hypersensitivity to telithromycin, any components of KETEK tablets, or any macrolide antibacterial.[see Description (11)]

4.4 Cisapride/Pimozide

Concomitant administration of KETEK with cisapride or pimozide is contraindicated because co-administration can lead to life-threatening QT prolongation. [see Warnings and Precautions (5.2); Drug Interactions (7)]

4.5 Colchicine

Concomitant administration of KETEK and colchicine is contraindicated in patients with renal or hepatic impairment due to increased plasma concentration of colchicine leading to life-threatening colchicine toxicity. [see Warnings and Precautions (5.4); Drug Interactions (7)]

5 WARNINGS AND PRECAUTIONS

5.1 Hepatotoxicity

Acute hepatic failure and severe liver injury, in some cases fatal, have been reported in patients treated with KETEK. These hepatic reactions included fulminant hepatitis and hepatic necrosis leading to liver transplant, and were observed during or immediately after treatment. In some of these cases, liver injury progressed rapidly and occurred after administration of a few doses of KETEK.

Physicians and patients should monitor for the appearance of signs or symptoms of hepatitis, such as fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, alcoholic stools, liver tenderness, or hepatomegaly. Patients with signs or symptoms of hepatitis must be advised to discontinue KETEK and immediately seek medical evaluation, which should include liver function tests. If clinical hepatitis or transaminase elevations combined with other systemic symptoms occur, KETEK should be permanently discontinued.

KETEK is contraindicated in patients with a previous history of hepatitis and/or jaundice associated with the use of KETEK tablets, or any macrolide antibacterial. [see Contraindications (4.2)]

In addition, less severe hepatic dysfunction associated with increased liver enzymes, hepatitis and in some cases jaundice was reported with the use of KETEK. These events associated with less severe forms of liver toxicity were reversible.

5.2 QTc Prolongation

KETEK can prolong the QTc interval of the electrocardiogram in some patients leading to an increased risk for ventricular arrhythmias, including ventricular tachycardia and torsades de pointes with fatal outcomes. Thus, KETEK should be avoided in patients with congenital prolongation of the QTc interval, and in patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (e.g., quinidine and procainamide) or Class III (e.g., dofetilide) antiarrhythmic agents.

Cases of ventricular arrhythmias (including ventricular tachycardia and torsades de pointes) have been reported post-marketing with KETEK and sometimes occurred within a few hours of the first dose. In clinical trials, no cardiovascular morbidity or mortality attributable to QTc prolongation occurred with KETEK treatment in 4780 patients, including 204 patients having a prolonged QTc at baseline.

5.3 Visual Disturbances and Loss of Consciousness

KETEK may cause visual disturbances particularly in slowing the ability to accommodate and the ability to release accommodation. Visual disturbances, some of them severe, included blurred vision, difficulty focusing, and diplopia. [see Adverse Reactions (6.1)]

There have been post-marketing reports of transient loss of consciousness including some cases associated with vagal syndrome.

Because of potential visual difficulties or loss of consciousness, patients should attempt to minimize activities such as driving a motor vehicle, operating heavy machinery or engaging in other hazardous activities during treatment with KETEK. If patients experience visual disorders or loss of consciousness while taking KETEK, patients should not drive a motor vehicle, operate heavy machinery or engage in other hazardous activities.

5.4 Serious Adverse Reactions with Concomitant Drugs

Serious adverse reactions have been reported in patients taking KETEK concomitantly with CYP3A4 substrates [see Drug Interactions (7)]:

  • Colchicine: colchicine toxicity
  • Simvastatin, lovastatin, and atorvastatin: rhabdomyolysis
  • Calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, amlodipine, diltiazem): hypotension

Colchicine Toxicity

Life-threatening and fatal drug interactions have been reported in patients treated with colchicine and strong CYP3A4 inhibitors. KETEK is a strong CYP3A4 inhibitor and this interaction may occur while using both drugs at their recommended dosages. If co-administration of KETEK and colchicine is necessary in patients with normal renal and hepatic function, reduce the dosage of colchicine. Monitor patients for clinical symptoms of colchicine toxicity. Concomitant administration of KETEK and colchicine is contraindicated in patients with renal or hepatic impairment. [see Contraindications (4.5); Drug Interactions (7)]

Rhabdomyolysis

Simvastatin, lovastatin and atorvastatin are metabolized by CYP3A4. High levels of HMG-CoA reductase inhibitors increase the risk of myopathy and rhabdomyolysis. Avoid use of statins which are metabolized by CYP3A4 concomitantly with KETEK; suspend therapy with simvastatin, lovastatin, or atorvastatin during the course of treatment with KETEK. [see Drug Interactions (7)]

Hypotension

Hypotension, bradyarrhythmia and loss of consciousness have been observed in patients receiving concomitant treatment with calcium channel blockers that are substrates of CYP3A4 (e.g., verapamil, amlodipine, diltiazem). Monitor for these adverse reactions and toxicity related to calcium channel blockers and adjust calcium channel blocker dosage as necessary. [see Drug Interactions (7)]

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