Isoniazid / Pyrazinamide / Rifampin Dosage

This dosage information may not include all the information needed to use Isoniazid / Pyrazinamide / Rifampin safely and effectively. See additional information for Isoniazid / Pyrazinamide / Rifampin.

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Usual Adult Dose for:

Usual Pediatric Dose for:

Additional dosage information:

Usual Adult Dose for Tuberculosis - Active

44 kg or less: 4 tablets (200 mg isoniazid, 1200 mg pyrazinamide, and 480 mg rifampin total dose) orally once a day
45 to 54 kg: 5 tablets (250 mg isoniazid, 1500 mg pyrazinamide, and 600 mg rifampin total dose) orally once a day
55 kg or more: 6 tablets (300 mg isoniazid, 1800 mg pyrazinamide, and 720 mg rifampin total dose) orally once a day

Usual Pediatric Dose for Tuberculosis - Active

14 years or younger: The ratio of isoniazid, pyrazinamide, and rifampin in the combination tablet may not be appropriate; for example, isoniazid mg/kg doses are typically higher in pediatric patients than adults.

15 years or older:
44 kg or less: 4 tablets (200 mg isoniazid, 1200 mg pyrazinamide, and 480 mg rifampin total dose) orally once a day
45 to 54 kg: 5 tablets (250 mg isoniazid, 1500 mg pyrazinamide, and 600 mg rifampin total dose) orally once a day
55 kg or more: 6 tablets (300 mg isoniazid, 1800 mg pyrazinamide, and 720 mg rifampin total dose) orally once a day

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Isoniazid/pyrazinamide/rifampin is contraindicated in patients with severe liver damage and in patients with acute liver disease, regardless of etiology.

Patients with impaired liver function should only be given isoniazid/pyrazinamide/rifampin in cases of necessity and then with caution and under strict medical supervision.

Precautions

Severe and sometimes fatal hepatitis associated with isoniazid therapy may occur or develop after months of treatment. There were 8 deaths among 174 cases of hepatitis reported among 13,838 persons taking isoniazid. The risk is age related with a greater occurrence reported in patients who are 35 years or older. The risk of hepatitis is also increased in patients who consume alcohol daily, in women, and in minorities. Monthly monitoring and interviewing of patients should take place. Baseline laboratory values should be obtained in patients over 35 years of age and in patients with a history of liver illness or heavy alcohol consumption. Elevated liver function tests per se are not a contraindication to the use of isoniazid unless they indicate worsening or acute liver disease. Strict monitoring of these patients, however, is crucial. Patients should be fully informed regarding the risk of hepatotoxicity associated with isoniazid, educated about the prodromal symptoms of hepatitis (such as anorexia, nausea, vomiting, fatigue, weakness, or malaise), and instructed to contact their physician immediately if they develop signs or symptoms. Isoniazid should be discontinued at once if these symptoms occur or signs indicative of liver damage are detected; continued use of isoniazid in such cases has been reported to cause a more severe form of liver damage.

Patients with tuberculosis who have hepatitis attributed to isoniazid should be administered appropriate treatment with alternative drugs. If isoniazid must be reinstated, it should be reinstituted only after symptoms and laboratory abnormalities have resolved. Isoniazid should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is any indication of recurrent liver involvement. Therapy should be deferred in persons with acute hepatic diseases.

Isoniazid/pyrazinamide/rifampin is contraindicated in patients with severe adverse reactions (such as drug fever, chills, and arthritis) associated with isoniazid and in patients with acute gout.

Each component of isoniazid/pyrazinamide/rifampin has been associated with hepatic dysfunction. Patients with preexisting liver disease or at increased risk for drug-related hepatitis (such as alcoholics) should be closely monitored.

Rifampin has been shown to produce hepatotoxicity in patients with preexisting liver dysfunction and in patients with normal liver function who are also taking other hepatotoxic agents. Some cases have been fatal. Patients with impaired liver function should only be given isoniazid/pyrazinamide/rifampin in cases of necessity and then with caution and under strict medical supervision. Careful monitoring of liver function (especially SGPT and SGOT) should be done prior to and then every 2 to 4 weeks throughout treatment in patients with liver dysfunction. Isoniazid/pyrazinamide/rifampin should be discontinued if signs of hepatocellular damage occur.

Isoniazid/pyrazinamide/rifampin is contraindicated in patients receiving ritonavir-boosted saquinavir due to an increased risk of severe hepatocellular toxicity. Isoniazid/pyrazinamide/rifampin is contraindicated in patients receiving atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir due to the potential of rifampin to substantially decrease plasma concentrations of these antiviral drugs, which may result in loss of antiviral efficacy and/or development of viral resistance.

Due to the pyrazinamide component, isoniazid/pyrazinamide/rifampin should be permanently discontinued if signs of hepatocellular damage or hyperuricemia with an acute gouty arthritis appear. If hyperuricemia with an acute gouty arthritis occurs without liver dysfunction, the patient should be changed to a regimen without pyrazinamide.

Baseline measurements of hepatic enzymes, bilirubin, serum creatinine, a complete blood count and platelet count (or estimate), and blood uric acid are recommended. Patients should be seen at least monthly during treatment and should be specifically questioned about symptoms associated with adverse reactions. All patients with abnormalities should have follow-up, including laboratory testing, if needed. In general, routine laboratory monitoring for toxicity in patients with normal baseline measurements is not necessary.

In some cases, hyperbilirubinemia has been observed in the early days of rifampin treatment. An isolated report showing a moderate rise in bilirubin and/or transaminase level is not in itself an indication for interrupting therapy; rather, the decision should be made after repeating the laboratory tests, noting trends in the levels, and considering them in conjunction with the patient's clinical condition.

Rifampin is typically given daily for tuberculosis treatment. Rifampin doses greater than 600 mg administered once or twice weekly have resulted in a higher incidence of adverse reactions, including the "flu syndrome" (fever, chills, and malaise); hematopoietic reactions (leukopenia, thrombocytopenia, or acute hemolytic anemia); shortness of breath; shock, anaphylaxis, and renal failure; and cutaneous, gastrointestinal, and hepatic reactions. Recent studies indicate that regimens using twice-weekly doses of rifampin 600 mg plus isoniazid 15 mg/kg are much better tolerated.

Intermittent rifampin therapy is not recommended. Patients should be cautioned against intentional or accidental interruption of the daily dosage regimen since rare renal hypersensitivity reactions have been reported when therapy was resumed in such cases.

Isoniazid use should be carefully monitored in patients with the following: severe renal dysfunction, chronic liver disease, concurrent use of any chronically administered medication, or daily ingestion of alcohol.

Because of the numerous drug interactions which may occur with rifampin therapy, the usefulness and effectiveness of all medications in a patient's drug regimen should be evaluated when rifampin is added to or deleted from that regimen.

Isoniazid exhibits some monoamine oxidase inhibiting activity; therefore, an interaction with foods containing tyramine (such as cheese, red wine) may occur. Diamine oxidase may also be inhibited and may cause an exaggerated response (e.g., headache, sweating, palpitations, flushing, hypotension) to histamine-containing foods (including skipjack, tuna, other tropical fish). Patients receiving isoniazid/pyrazinamide/rifampin should avoid tyramine- and histamine-containing foods.

Ophthalmoscopic examinations are recommended periodically during isoniazid treatment when visual symptoms occur.

In the treatment of tuberculosis, small numbers of resistant cells, present within large populations of susceptible cells, can quickly become the predominating type. Since resistance can occur rapidly, culture and susceptibility tests should be performed if positive cultures persist during the course of treatment. Prior to the initiation of treatment, bacteriologic smears or cultures should be obtained to confirm the organism's susceptibility to isoniazid, pyrazinamide, and rifampin and they should be repeated throughout therapy to monitor response to the treatment. The drug regimen should be modified if test results confirm resistance to any of the components of isoniazid/pyrazinamide/rifampin and the patient is not responding to therapy.

Safety and efficacy have not been established in patients less than 15 years of age.

Dialysis

Data not available

Other Comments

Dosages should be administered at least 1 hour before or 2 hours after a meal with a full glass of water.

The isoniazid/pyrazinamide/rifampin combination tablet should only be used in the initial phase of short-course therapy which is usually continued for 2 months. Treatment should then be continued with isoniazid and rifampin for at least 4 months. Treatment duration should be extended if the patient's sputum or culture remains positive, if resistant organisms are present, or if the patient is HIV positive.

The Advisory Council for the Elimination of Tuberculosis, the American Thoracic Society, and the Centers for Disease Control and Prevention recommend adding streptomycin or ethambutol as a fourth drug in a regimen including isoniazid, pyrazinamide, and rifampin for initial treatment of tuberculosis unless the probability of isoniazid or rifampin resistance is very low. The need for a fourth drug should be reevaluated when susceptibility test results are known. If current community rates of isoniazid resistance are less than 4%, initial treatment with less than 4 drugs may be considered.

Pyridoxine, 50 mg orally once a day, may be administered concurrently to prevent the occurrence of peripheral neuropathy caused by the isoniazid component. Concomitant pyridoxine is recommended in malnourished patients, patients predisposed to neuropathy (such as alcoholics and diabetics), and adolescents.

Patients should be informed that rifampin may cause a brownish-red or orange discoloration of urine, tears, feces, saliva, sputum, and sweat. Permanent discoloration of contact lens may occur.

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