Usual Adult Dose for Tuberculosis - Resistant

Weeks 1 and 2: 400 mg orally once a day
Weeks 3 to 24: 200 mg orally 3 times a week, with at least 48 hours between doses
Duration of therapy: 24 weeks

Comments:

• Alcohol should be avoided during treatment.
• Treatment should be given by directly observed therapy (DOT).
• This drug was approved based on sputum culture conversion time in clinical trials; continued approval may be based upon verification and clinical benefit in confirmatory trials.
• Use of this drug should be limited to infections where effective treatment regimens cannot otherwise be provided.
• Treatment should be used with at least 3 other drugs to which the in-vitro multidrug resistant tuberculosis (MDR-TB) isolate has been shown to be susceptible OR with at least 4 other drugs to which the isolate is likely to be susceptible if in-vitro results are unavailable.

Usual Pediatric Dose for Tuberculosis - Resistant

12 years and older:
30 kg and over:

• Weeks 1 and 2: 400 mg orally once a day
• Weeks 3 to 24: 200 mg orally 3 times a week, with at least 48 hours between doses
• Duration of therapy: 24 weeks

• Alcohol should be avoided during treatment.
• Treatment should be given by DOT, and should be given in combination with other antimycobacterial agents.
• This drug was approved based on sputum culture conversion time in clinical trials; continued approval may be based upon verification and clinical benefit in confirmatory trials.
• Use of this drug should be limited to infections where effective treatment regimens cannot otherwise be provided.
• Treatment should be used with at least 3 other drugs to which the in-vitro MDR-TB isolate has been shown to be susceptible OR with at least 4 other drugs to which the isolate is likely to be susceptible if in-vitro results are unavailable.

Renal Dose Adjustments

Mild to moderate renal dysfunction: No adjustment recommended.
Severe renal dysfunction: Use with caution; frequent monitoring recommended.

Liver Dose Adjustments

All patients: Frequent liver function test and hepatotoxicity sign/symptom monitoring recommended.

Mild to moderate liver dysfunction: No adjustment recommended.
Severe liver dysfunction: Use is recommended only if clearly needed and the benefit outweighs the risk. Frequent monitoring recommended.

New/worsening liver dysfunction: Patients should be tested for viral hepatitis, and other hepatotoxic medications should be discontinued.

Treatment Discontinuation:
This drug should be discontinued if the patient develops:

• AST elevations accompanied by total bilirubin elevations exceeding 2 times the upper limit of normal (2 x ULN)
• AST elevations greater than 8 x ULN
• AST elevations greater than 5 x ULN AND persisting longer than 2 weeks

Dose Adjustments

Missed Doses:

• Weeks 1 and 2: Skip the missed dose, then continue the daily dosing regimen; do not administer the missed dose the following day as a double dose.
• Weeks 3 to 24: Administer the missed dose as soon as possible, then resume the 3 times a week regimen.

• Clinically significant ventricular arrhythmia
• QT interval of greater than 500 msec (confirmed with repeated ECG)

Precautions

CONTRAINDICATIONS:

• None.

• An increased risk of death was seen in the active component treatment group (11.4%) compared to the placebo treatment group (2.5%) in 1 placebo-controlled trial in adults.

• This drug should be limited for use in patients 12 years of age and older when an effective treatment regimen cannot otherwise be provided.

• QT prolongation can occur with use.
• Use with drugs that prolong the QT interval may cause additive prolongation.

• Monitoring should include ECG.
• Use should be discontinued in patients who develop significant ventricular arrhythmias and/or in patients with significant QTcF interval prolongation (greater than 500 msec).

Dialysis

End-stage renal disease (ESRD) requiring hemodialysis: Use with caution; frequent monitoring recommended.
ESRD requiring peritoneal dialysis: Use with caution; frequent monitoring recommended.

Other Comments

Administration advice:

• This drug should be taken with food.
• Doses should be swallowed whole with water.

• Protect from light.

• Limitations of use: This drug should not be used in the treatment of drug-sensitive tuberculosis, extrapulmonary tuberculosis, infections caused by non-tuberculous mycobacteria, and/or latent infections due to M tuberculosis.
• There are limited safety and efficacy data for use in the treatment of MDR-TB in patients with HIV.

• CARDIOVASCULAR: ECG at baseline, and regularly thereafter
• HEPATIC: Liver function tests and signs/symptoms of hepatotoxicity at baseline and regularly thereafter
• IMMUNOLOGIC: Susceptibility information for the background regimen (if possible)
• METABOLIC: Calcium, potassium, and magnesium levels at baseline and follow-up if QT prolongation occurs

• Patients should be advised to avoid missing doses and to complete the entire course of therapy, even if they feel better.
• Patients should be told to report any unusual or severe side effects, including signs/symptoms of hepatotoxicity and/or QT prolongation.
• Patients should be instructed to tell their healthcare provider about all the medicines that they take, including prescription and non-prescription medicines.
• Inform patients that this drug may cause dizziness, and they should avoid driving or operating machinery if these side effects occur.
• Advise patients to speak to their healthcare provider if they become pregnant, intend to become pregnant, or are breastfeeding.