Isoniazid, pyrazinamide, and rifampin

Take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

Many drugs can interact with isoniazid, pyrazinamide, and rifampin. Not all possible interactions are listed here. Tell your doctor about all your medications and any you start or stop using during treatment with isoniazid, pyrazinamide, and rifampin, especially:

• antifungal medication--fluconazole, itraconazole, ketoconazole, voriconazole;

• birth control pills or hormone replacement therapy;

• a blood thinner (warfarin, Coumadin) or other medication to prevent blood clots (clopidogrel, dabigatran, Plavix, Pradaxa, rivaroxaban, ticagrelor, and others);

• vitamin D; or

• steroids (prednisone and others) or thyroid medication.

This list is not complete and many other drugs can interact with isoniazid, pyrazinamide, and rifampin. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

Age 14 Years and Younger:
-The ratio of isoniazid, pyrazinamide, and rifampin in this combination tablet may not be appropriate; for example, isoniazid mg/kg doses are typically higher in children than in adults.

Age 15 Years and Older:
Dosing Based on Patient Weight:
Isoniazid/pyrazinamide/rifampin 50 mg-300 mg pyrazinamide-120 mg oral tablet:
-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.

Duration of Therapy: 2 months (initial treatment phase)

Comments:
-This drug should be taken on an empty stomach at least 1 hour before or 2 hours after a meal with a full glass of water.
-This drug should be taken at least 1 hour before the ingestion of antacids.
-The Advisory Council for the Elimination of Tuberculosis, the American Thoracic Society, and the US CDC recommend that either streptomycin or ethambutol be added as a fourth drug in the treatment regimen, unless the likelihood of isoniazid or rifampin resistance is very low.
-Concomitant administration of pyridoxine (Vitamin B6) is recommended in adolescents, the malnourished, and in those predisposed to neuropathy (e.g., alcoholics and diabetics).

Use: Indicated in the Initial Phase of the Short-Course Treatment of Pulmonary Tuberculosis

-Impaired Liver Function: Use with caution

-Severe Liver Damage or Acute Liver Disease of Any Etiology: Contraindicated (due to isoniazid component)

Animal studies have not been conducted with this drug or pyrazinamide, but they have been conducted with rifampin and isoniazid. Congenital malformations (spina bifida and cleft palate) have been observed with rifampin at doses 0.2 to 2 times the maximum recommended human dose (MRHD); imperfect osteogenesis and embryotoxicity were also reported at doses about 3 times the MRHD. Isoniazid may exert an embryocidal effect, although no isoniazid-related congenital anomalies have been found in animals. There are no controlled data in human pregnancy. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Safety has not been established during pregnancy; this drug should be used during pregnancy only if the benefit outweighs the risk to the fetus. US FDA pregnancy category: C Comments: -When administered during the last few weeks of pregnancy, rifampin can cause post-natal hemorrhages in the mother and infant for which Vitamin K treatment may be indicated. -Occasional disturbances of the menstrual cycle have been reported in women receiving long-term anti-tuberculosis therapy containing rifampin. -Female patients of reproductive potential should be advised to consider using non-hormonal methods of birth control as this drug may affect the reliability of oral and other systemic hormonal contraceptives.