Rifampin/Isoniazid/Pyrazinamide

DEA Class; Rx

Common Brand Names; Rifater (DSC)

• Antitubercular Agents

Hypersensitivity to isoniazid, pyrazinamide, rifamycins

Acute liver disease, severe hepatic damage, acute gout

Rifampin contraindicated in patients receiving ritonavir-boosted saquinavir due to an increased risk of severe hepatocellular toxicity

Many CYP substrates are contraindicated with rifampin owing to risk for decreased systemic exposure

Rifampin is contraindicated with atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir because of the potential to substantially decrease plasma concentrations of these antiviral drugs, which may result in loss of antiviral efficacy for HIV infection and/or development of viral resistance

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Systemic hypersensitivity reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, may occur; signs and symptoms may include fever, rash, urticaria, angioedema, hypotension, acute bronchospasm, conjunctivitis, thrombocytopenia, neutropenia, elevated liver transaminases or flu-like syndrome (weakness, fatigue, muscle pain, nausea, vomiting, headache, chills, aches, itching, sweats, dizziness, shortness of breath, chest pain, cough, syncope, palpitations;. reactions may be severe and fatal; monitor for signs and/or symptoms of hypersensitivity reactions; discontinue therapy and administer supportive measures if symptoms occur

Rifampin is not recommended for intermittent therapy; caution patient against intentional or accidental interruption of daily dosage regimen since rare renal hypersensitivity reactions have been reported when therapy was resumed in such cases

Rifampin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones, and vitamin D

Patient should be told that rifampin may produce a discoloration (yellow, orange, red, brown) of teeth, urine, sweat, sputum, and tears, and should be forewarned of this; soft contact lenses may be permanently stained

Heartburn, epigastric distress, anorexia, nausea, vomiting, jaundice, flatulence, cramps, and diarrhea reported; although Clostridium difficile shown in vitro to be sensitive to rifampin, pseudomembranous colitis reported with use of rifampin (and other broad spectrum antibiotics); consider this diagnosis in patients who develop diarrhea in association with antibiotic use

Isoniazid has some monoamine oxidase inhibiting activity; interaction with tyramine- containing foods (cheese, red wine) may occur; diamine oxidase may also be inhibited, causing exaggerated response (e.g., headache, sweating, palpitations, flushing, hypotension) to foods containing histamine (e.g., skipjack, tuna, other tropical fish); tyramine and histamine- containing foods should be avoided in patients receiving therapy

The reliability of oral or other systemic hormonal contraceptives may be affected by rifampin; consideration should be given to using alternative contraceptive measures

Patients should abstain from alcohol, hepatotoxic medications or herbal products while receiving therapy

Emphasize compliance with full course of therapy, and stress importance of not missing any doses

Isoniazid: Embryocidal effects reported in both rats and rabbits, although no congenital abnormalities observed in mammalian offspring when given during pregnancy

Pyrazinamide: Animal reproductive studies have not been conducted

Isoniazid is known to be secreted into breast milk

Because of potential for tumorigenicity shown for rifampin in animal studies, a decision should be made whether to discontinue nursing or discontinue drug, taking into account importance of drug to mother

Rifampin/isoniazid/pyrazinamide

tablet

• 120mg/50mg/300mg