Adult Dosing

Initial phase of the short-course treatment of pulmonary tuberculosis (treatment usually continued for 2 months)

• Patients weighing = < 44 kg: 4 tablets PO qd
• Patients weighing between 45-54 kg: 5 tablets PO qd
• Patients weighing = > 55 kg: 6 tablets PO qd

Pediatric Dosing

• Safety and efficacy have not been established in pediatric patients < 15 years have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Initial phase of the short-course treatment of pulmonary tuberculosis

• Hypersensitivity to any of the ingredients of the product or to any of the rifamycins
• Rifampin is contraindicated in patients who are also receiving ritonavir-boosted saquinavir due to an increased risk of severe hepatocellular toxicity
• Rifampin is contraindicated in patients who are also receiving atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir due to the potential of rifampin to substantially decrease plasma concentrations of these antiviral drugs
• Severe hepatic damage
• Acute liver disease
• Acute gout

• Therapy with isoniazid may lead to severe and sometimes fatal hepatitis. Risk of developing hepatitis is age related. Approximate case rates by age are: 0 per 1,000 for persons under 20 years of age, 3 per 1,000 for persons in the 20 to 34 year age group, 12 per 1,000 for persons in the 35 to 49 year age group, 23 per 1,000 for persons in the 50 to 64 year age group, and 8 per 1,000 for persons over 65 years of age. Risk is increased with daily consumption of alcohol
• 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
• Patients should be instructed to report immediately any of the 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, therapy should be discontinued promptly
• If therapy 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 The drug should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is any indication of recurrent liver involvement

Renal Dose Adjustment

• Renal impairment: Dose adjustments not defined; caution advised

Hepatic Dose Adjustment

• Hepatic impairment: Dose adjustments not defined; caution advised

• Therapy with isoniazid may lead to severe and sometimes fatal hepatitis. Risk of developing hepatitis is age related. Approximate case rates by age are: 0 per 1,000 for persons under 20 years of age, 3 per 1,000 for persons in the 20 to 34 year age group, 12 per 1,000 for persons in the 35 to 49 year age group, 23 per 1,000 for persons in the 50 to 64 year age group, and 8 per 1,000 for persons over 65 years of age. Risk is increased with daily consumption of alcohol [US blackbox warning]
• 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 [US blackbox warning]
• Patients should be instructed to report immediately any of the 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, therapy should be discontinued promptly [US blackbox warning]
• If therapy 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 [US blackbox warning]
• Fatalities associated with jaundice have occurred in patients with liver disease and in patients taking rifampin with other hepatotoxic agents
• Closely monitoring liver function, especially serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) prior to therapy and then every 2 to 4 weeks during therapy. If signs of hepatocellular damage occur, discontinue therapy
• Rifampin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones, and vitamin D
• Ophthalmologic examinations should be done before treatment is started and periodically thereafter, even without occurrence of visual symptoms
• Because it contains pyrazinamide, patients should have baseline serum uric acid and liver function determinations
• If signs of hepatocellular damage or hyperuricemia accompanied by an acute gouty arthritis appear, therapy should be discontinued
• Use cautiously in patients with a history of diabetes mellitus
• Rifampin is not recommended for intermittent therapy; the patient should be cautioned against intentional or accidental interruption of the daily dosage regimen since rare renal hypersensitivity reactions have been reported
• Adults treated for tuberculosis should have baseline measurements of hepatic enzymes, bilirubin, serum creatinine, a complete blood count (CBC) and platelet count (or estimate), and blood uric acid

Pregnancy Category:C

Breastfeeding: Rifampin, isoniazid, and pyrazinamide are known to pass into maternal breast milk, a decision should be made whether to discontinue nursing or to discontinue therapy, taking into account the importance of the drug to the mother.

• CNS: Vertigo, sweating, headache, insomnia, fever, diffuse paresthesia of the legs, anxiety, diabetic coma
• GI: Nausea, vomiting, digestive pain, diarrhea
• MUSC: Arthralgia, long bones pain, phlebitis, localized joint pain, diffuse joint pain, edema of the legs
• DERM: Rash, erythroderma, erythema, exfoliative dermatitis, lyell syndrome, urticaria, localized skin rash, diffuse skin rash, pruritus
• EENT: Tinnitus, coughing, hemoptysis, total pneumothorax
• CV: Tightness in chest, diffuse chest pain, angina, palpitation
• HEPA: Hepatitis with conjunctival jaundice, hepatitis with deep jaundice
• HYPERSENSITIVITY: Generalized hypersensitivity

Isoniazid

• Antitubercular; inhibits mycobacterial cell wall synthesis and interferes with metabolism of Mycobacterium tuberculosis
• 50% metabolized by the liver
• Excreted in urine (50% unchanged)
• Half-life: 1–4 hrs

Rifampin

• Rifamycin; inhibits DNA-dependent RNA polymerase activity in susceptible Mycobacterium tuberculosis organisms
• Extensively metabolized by the liver
• Excreted in urine; feces
• Half-life: Approx 2-3 hrs

Pyrazinamide

• Antituberculous agent; bacteriostatic or bactericidal action against susceptible strains of Mycobacterium tuberculosis
• Metabolized by liver
• Renally excreted 70%
• Half-life: 9-10 hrs

US Trade Name(s)

• Rifater

US Availability

Rifater (isoniazid/pyrazinamide/rifampin)

• TABS: 50 /300/ 120 mg

Canadian Trade Name(s)

• Rifater

Canadian Availability

Rifater (isoniazid/pyrazinamide/rifampin)

• TABS: 50 /300/ 120 mg

UK Trade Name(s)

• Rifater

UK Availability

Rifater (isoniazid/pyrazinamide/rifampin)

• TABS: 50 /300/ 120 mg

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Antimicrobials

Antituberculosis Agents

Drug Name: Rifater 120/50/300 (rifampin / isoniazid / pyrazinamide) Oral Tablet

Ingredient(s): Isoniazid mixture with Pyrazinamide and Rifampin

Imprint: RIFATER

Color(s): White

Shape: Round

Size (mm): 10.00

Score: 1

Inactive Ingredient(s): povidone / carboxymethylcellulose sodium / calcium stearate / sodium lauryl sulfate / sucrose / talc / acacia / titanium dioxide / kaolin / magnesium carbonate / colloidal silicon dioxide / dried aluminum hydroxide gel / ferric oxide / black iron oxide / carnauba wax / white beeswax / colophony / hard paraffin / lecithin / shellac / propylene glycol

Drug Label Author:
sanofi-aventis U.S. LLC

DEA Schedule:
Non-Scheduled