Isoniazid / Pyrazinamide / Rifampin Dosage

Applies to the following strengths: 50 mg-300 mg-120 mg

Usual Adult Dose for Tuberculosis - Active

Up to 44 kg: Isoniazid 200 mg-pyrazinamide 1200 mg-rifampin 480 mg orally once a day
Between 45 and 54 kg: Isoniazid 250 mg-pyrazinamide 1500 mg-rifampin 600 mg orally once a day
55 kg and greater: Isoniazid 300 mg-pyrazinamide 1800 mg-rifampin 720 mg orally once a day
Duration of therapy: 2 months

Comments:

The dose should be taken with a full glass of water 1 hour before or 2 hours after a meal.
After 2 months of using this drug combination, treatment should be continued with rifampin and isoniazid for at least 4 months.

Use: Initial phase of the short-course treatment of susceptible pulmonary tuberculosis

Usual Pediatric Dose for Tuberculosis - Active

15 Years and Older:
Up to 44 kg: Isoniazid 200 mg-pyrazinamide 1200 mg-rifampin 480 mg orally once a day
Between 45 and 54 kg: Isoniazid 250 mg-pyrazinamide 1500 mg-rifampin 600 mg orally once a day
55 kg and greater: Isoniazid 300 mg-pyrazinamide 1800 mg-rifampin 720 mg orally once a day
Duration of therapy: 2 months

Comments:

The dose should be taken with a full glass of water 1 hour before or 2 hours after a meal.
After 2 months of using this drug combination, treatment should be continued with rifampin and isoniazid for at least 4 months.

Use: Initial phase of the short-course treatment of susceptible pulmonary tuberculosis

Renal Dose Adjustments

Mild to moderate renal dysfunction: No adjustment recommended.
Severe renal dysfunction: Frequent monitoring recommended.

Liver Dose Adjustments

Acute liver disease of any etiology: Contraindicated
Patients with severe liver damage: Contraindicated

Impaired Liver Function: Use with caution and under strict medical supervision.

Comments: If this drug is given to patients with impaired liver function, carefully monitor liver function (especially AST and ALT) prior to therapy, then every 2 to 4 weeks during therapy; withdraw treatment if signs of hepatocellular damage occur.

Patients with current chronic liver disease: Frequent monitoring recommended.

During treatment:

Enzyme levels should be monitored at baseline and as necessary during treatment.
Progressive liver damage with accompanying symptoms: Immediately discontinue treatment.

Dose Adjustments

Elderly patients: Use with caution.

Patients receiving phenytoin (diphenylhydantoin): Frequent monitoring recommended.

Daily users of alcohol: Frequent monitoring recommended.

Hypersensitivity reaction: Stop treatment and evaluate the patient at the first sign/symptom of a hypersensitivity reaction.

Precautions

US BOXED WARNINGS:
HEPATITIS:

Severe and sometimes fatal hepatitis associated with isoniazid therapy may occur and may develop even after many months of treatment. The risk of developing hepatitis is age related.
Approximate case rates by age are: 0 per 1000 for persons under 20 years of age, 3 per 1000 for persons in the 20 to 34-year age group, 12 per 1000 for persons in the 35 to 49-year age group, 23 per 1000 for persons in the 50 to 64-year age group, and 8 per 1000 for persons over 65 years of age.
The risk of hepatitis is increased with daily consumption of alcohol.
Precise data to provide a fatality rate for isoniazid-related hepatitis is not available; however, in a US Public Health Service Surveillance Study of 13,838 persons taking isoniazid, there were 8 deaths among 174 cases of hepatitis.
Therefore, patients given isoniazid should be carefully monitored and interviewed at monthly intervals.
Serum transaminase concentration becomes elevated in about 10% to 20% of patients, usually during the first few months of therapy, but it can occur at any time.
Usually enzyme levels return to normal despite continuance of the drug, but in some cases, progressive liver dysfunction occurs.
Patients should be instructed to report immediately any of the prodromal symptoms of hepatitis, such as fatigue, weakness, malaise, anorexia, nausea, or vomiting.
If these symptoms appear or if signs suggestive of hepatic damage are detected, isoniazid should be discontinued promptly since continued use of the drug in these cases has been reported to cause a more severe form of liver damage.
Patients with tuberculosis should be given appropriate treatment with alternative drugs.
If isoniazid must be reinstituted, it should be reinstituted only after symptoms and laboratory abnormalities have cleared.
The drug should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is any indication of recurrent liver involvement.
Treatment should be deferred in persons with acute hepatic diseases.

CONTRAINDICATIONS:

Hypersensitivity to the active components, any of the rifamycins, or any of the ingredients

Isoniazid:

Acute gout
Patients with severe adverse reactions to this drug (e.g., drug fever, chills, arthritis)
Patients with severe liver dysfunction or acute liver disease of any etiology

Rifampin:

Patients receiving ritonavir-boosted saquinavir concomitantly
Patients who are also receiving atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir

NARROW THERAPEUTIC INDEX:

Rifampin should be considered a narrow therapeutic index (NTI) drug as small differences in dose or blood concentrations may lead to serious therapeutic failures or adverse drug reactions.

Recommendations:

Generic substitution should be done cautiously, if at all, as current bioequivalence standards are generally insufficient for NTI drugs.
Additional and/or more frequent monitoring should be done to ensure receipt of an effective dose while avoiding unnecessary toxicities.

Safety and efficacy have not been established in patients younger than 15 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration Advice:

Take 1 hour prior to OR 2 hours after a meal with a full glass of water.
Concomitant administration of pyridoxine (Vitamin B6) is recommended in the malnourished, in those predisposed to neuropathy (e.g., alcoholics and diabetics), and in adolescents.

Storage Requirements:

Store at 25C; excursions permitted to 15 to 30C.
Protect from moisture and excessive humidity.

General:

This fixed-dosage combination drug is not recommended for initial therapy of tuberculosis or for preventive therapy.
This drug is not indicated for the treatment of meningococcal infections or asymptomatic carriers of Neisseria meningitis to eliminate meningococci from the nasopharynx.

Monitoring:

DERMATOLOGIC: Signs/symptoms of cutaneous reactions
GENERAL: Follow-up with all patients with abnormalities, including laboratory testing if necessary.
HEMATOLOGIC: Complete blood count and platelet count (or estimate) at baseline and as clinically necessary thereafter
HEPATIC: Liver function tests (e.g., hepatic enzymes, blood bilirubin) at baseline and as clinically necessary thereafter
IMMUNOLOGIC: Susceptibility tests to confirm susceptibility to this combination drug prior to initiation, and repeated throughout treatment; repeat tests for persistent positive cultures
METABOLIC: Uric acid levels at baseline and as clinically necessary thereafter
OCULAR: Ophthalmologic exams (including ophthalmoscopy) before treatment initiation and periodically thereafter
RENAL: Serum creatinine at baseline and as clinically necessary thereafter

Patient Advice:

This drug may cause side effects such as vertigo, vision problems, and psychotic reactions; patients should be told to avoid potentially dangerous activities such as driving and operating machinery until they know how this drug affects them.
Patients should be told to immediately report cough, darkened urine, fever, joint pain/swelling, loss of appetite, malaise, nausea and vomiting, rash with fever/blisters with/without peeling skin, shortness of breath, swollen lymph nodes, yellowish discoloration of the skin and eyes, or wheezing.
Patients should be instructed to complete the full course of therapy, and the importance of not missing any doses should be stressed.