Rifadin (rifampin, isoniazid and pyrazinamide)

Brand name: Rifadin

Generic: rifampin, isoniazid and pyrazinamide

Rifadin is an antibiotic used to treat tuberculosis (TB).

Common side effects of Rifadin include:

• upset stomach,
• heartburn,
• nausea,
• menstrual changes,
• headache,
• drowsiness,
• tired feeling, or
• dizziness.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Rifadin (rifampin capsules USP) and Rifadin IV (rifampin for injection USP) and other antibacterial drugs, rifampin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

No information provided

Pharmacodynamic Interactions

• Healthy subjects who received rifampin 600 mg once daily concomitantly with saquinavir 1000 mg/ritonavir 100 mg twice daily (ritonavir-boosted saquinavir) developed severe hepatocellular toxicity. Therefore, concomitant use of these medications is contraindicated.
• When rifampin is given concomitantly with other hepatotoxic medications such as halothane or isoniazid, the potential for hepatotoxicity is increased. The concomitant use of rifampin and halothane should be avoided. Patients receiving both rifampin and isoniazid should be monitored closely for hepatotoxicity.

Effect Of Rifampin On Other Drugs

Induction Of Drug Metabolizing Enzymes And Transporters

Drug metabolizing enzymes and transporters affected by rifampin include cytochromes P450 (CYP) 1A2, 2B6, 2C8, 2C9, 2C19, and 3A4, UDP-glucuronyltransferases (UGT), sulfotransferases, carboxylesterases, and transporters including P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2).

Most drugs are substrates for one or more of these enzyme or transporter pathways and these pathways may be induced by rifampin simultaneously. Therefore, rifampin may increase the metabolism and decrease the activity of certain coadministered drugs or increase the activity of a coadministered pro-drug (where metabolic activation is required) and has the potential to perpetuate clinically important drug drug interactions against many drugs and across many drug classes (Table 1).

Table 1 summarizes the effect of rifampin on other drugs or drug classes. Adjust dosages of concomitant drugs based on approved drug labeling and if applicable, therapeutic drug monitoring, unless otherwise specified.

Table 1: Drug Interactions with Rifampin that Affect Concomitant Drug Concentrations^a

Effect Of Other Drugs On Rifampin

• Concomitant antacid administration may reduce the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids.
• Concomitant use with probenecid and cotrimoxazole increases the concentration of rifampin which may increase the risk of Rifadin toxicities. Monitor for adverse reactions associated with Rifadin during coadministration.

Other Interactions

Atovaquone

• Concomitant use of rifampin with atovaquone decrease concentrations of atovaquone and increase concentrations of rifampin which may increase the risk of Rifadin toxicities. Coadministration of rifampin with atovaquone is not recommended.

Rifampin can be administered by the oral route or by IV infusion. IV doses are the same as those for oral.

See prescribing information for dosing information in patients with renal failure.

Tuberculosis

Adults

• 10 mg/kg, in a single daily administration, not to exceed 600 mg/day, oral or IV

Pediatric Patients

• 10-20 mg/kg, not to exceed 600 mg/day, oral or IV
• It is recommended that oral rifampin be administered once daily, either 1 hour before or 2 hours after a meal with a full glass of water.
• Rifampin is indicated in the treatment of all forms of tuberculosis. A three-drug regimen consisting of rifampin, isoniazid, and pyrazinamide (e.g., Rifater) is recommended in the initial phase of short-course therapy which is usually continued for 2 months. The Advisory Council for the Elimination of Tuberculosis, the American Thoracic Society, and the Centers for Disease Control and Prevention recommend that either streptomycin or ethambutol be added as a fourth drug in a regimen containing isoniazid (INH), rifampin, and pyrazinamide for initial treatment of tuberculosis unless the likelihood of INH resistance is very low. The need for a fourth drug should be reassessed when the results of susceptibility testing are known. If community rates of INH resistance are currently less than 4%, an initial treatment regimen with less than four drugs may be considered.
• Following the initial phase, treatment should be continued with rifampin and isoniazid for at least 4 months. Treatment should be continued for longer if the patient is still sputum or culture positive, if resistant organisms are present, or if the patient is HIV positive.

Preparation Of Solution For IV Infusion

• Reconstitute the lyophilized powder by transferring 10 mL of sterile water for injection to a vial containing 600 mg of rifampin for injection. Swirl vial gently to completely dissolve the antibiotic. The reconstituted solution contains 60 mg rifampin per mL and is stable at room temperature for up to 30 hours. Prior to administration, withdraw from the reconstituted solution a volume equivalent to the amount of rifampin calculated to be administered and add to 500 mL of infusion medium. Mix well and infuse at a rate allowing for complete infusion within 3 hours. Alternatively, the amount of rifampin calculated to be administered may be added to 100 mL of infusion medium and infused in 30 minutes.
• Dilutions in dextrose 5% for injection (D5W) are stable at room temperature for up to 8 hours and should be prepared and used within this time. Precipitation of rifampin from the infusion solution may occur beyond this time. Dilutions in normal saline are stable at room temperature for up to 6 hours and should be prepared and used within this time. Other infusion solutions are not recommended.

Incompatibilities

• Physical incompatibility (precipitate) was observed with undiluted (5 mg/mL) and diluted (1 mg/mL in normal saline) diltiazem hydrochloride and rifampin (6 mg/mL in normal saline) during simulated Y-site administration.

Meningococcal Carriers

Adults

• For adults, it is recommended that 600 mg rifampin be administered twice daily for two days.

Pediatric Patients

• Pediatric patients 1 month of age or older: 10 mg/kg (not to exceed 600 mg per dose) every 12 hours for two days.

Pediatric Patients Under 1 Month Of Age

• 5 mg/kg every 12 hours for two days.

• Rifadin should be used with caution in patients with a history of diabetes mellitus, as diabetes management may be more difficult.
• When administered during the last few weeks of pregnancy, rifampin can cause postnatal hemorrhages in the mother and infant for which treatment with vitamin K may be indicated.
• Because of the potential for tumorigenicity shown for rifampin in animal studies, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.