Rifadin (Rifampin) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

ENZYME INDUCTION

Rifampin is known to induce certain cytochrome P‑450 enzymes. Administration of rifampin with drugs that undergo biotransformation through these metabolic pathways may accelerate elimination of coadministered drugs. To maintain optimum therapeutic blood levels, dosages of drugs metabolized by these enzymes may require adjustment when starting or stopping concomitantly administered rifampin.

Rifampin has been reported to accelerate the metabolism of the following drugs: anticonvulsants (eg, phenytoin), antiarrhythmics (eg, disopyramide, mexiletine, quinidine, tocainide), oral anticoagulants, antifungals (eg, fluconazole, itraconazole, ketoconazole), barbiturates, beta-blockers, calcium channel blockers (eg, diltiazem, nifedipine, verapamil), chloramphenicol, clarithromycin, corticosteroids, cyclosporine, cardiac glycoside preparations, clofibrate, oral or other systemic hormonal contraceptives, dapsone, diazepam, doxycycline, fluoroquinolones (eg, ciprofloxacin), haloperidol, oral hypoglycemic agents (sulfonylureas), levothyroxine, methadone, narcotic analgesics, nortriptyline, progestins, quinine, tacrolimus, theophylline tricyclic antidepressants (eg, amitriptyline, nortriptyline) and zidovudine. It may be necessary to adjust the dosages of these drugs if they are given concurrently with rifampin.

Patients using oral or other systemic hormonal contraceptives should be advised to change to nonhormonal methods of birth control during rifampin therapy.

Rifampin has been observed to increase the requirements for anticoagulant drugs of the coumarin type. In patients receiving anticoagulants and rifampin concurrently, it is recommended that the prothrombin time be performed daily or as frequently as necessary to establish and maintain the required dose of anticoagulant.

Diabetes may become more difficult to control.

OTHER INTERACTIONS

When the two drugs were taken concomitantly, decreased concentrations of atovaquone and increased concentrations of rifampin were observed.

Concurrent use of ketoconazole and rifampin has resulted in decreased serum concentrations of both drugs. Concurrent use of rifampin and enalapril has resulted in decreased concentrations of enalaprilat, the active metabolite of enalapril. Dosage adjustments should be made if indicated by the patient's clinical condition.

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.

Probenecid and cotrimoxazole have been reported to increase the blood level of rifampin.

When rifampin is given concomitantly with either 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 close for hepatotoxicity.

Plasma concentrations of sulfapyridine may be reduced following the concomitant administration of sulfasalazine and rifampin. This finding may be the result of alteration in the colonic bacteria responsible for the reduction of sulfasalazine to sulfapyridine and mesalamine.

OVERDOSAGE

Signs and Symptoms

Nausea, vomiting, abdominal pain, pruritus, headache, and increasing lethargy will probably occur within a short time after ingestion; unconsciousness may occur when there is severe hepatic disease. Transient increases in liver enzymes and/or bilirubin may occur. Brownish-red or orange discoloration of the skin, urine, sweat, saliva, tears, and feces will occur, and its intensity is proportional to the amount ingested.

Facial or periorbital edema has also been reported in pediatric patients. Hypotension, sinus tachycardia, ventricular arrhythmias, seizures and cardiac arrest were reported in some fatal cases.

Acute Toxicity

The LD₅₀ of rifampin is approximately 885 mg/kg in the mouse, 1720 mg/kg in the rat, and 2120 mg/kg in the rabbit.

The minimum acute lethal or toxic dose is not well established. However, nonfatal acute overdoses in adults have been reported with doses ranging from 9 to 12 gm rifampin. Fatal acute overdoses in adults have been reported with doses ranging from 14 to 60 gm. Alcohol or a history of alcohol abuse was involved in some of the fatal and nonfatal reports. Nonfatal overdoses in pediatric patients ages 1 to 4 years old of 100 mg/kg for one to two doses has been reported.

Treatment

Intensive support measures should be instituted and individual symptoms treated as they arise. Since nausea and vomiting are likely to be present, gastric lavage is probably preferable to induction of emesis. Following evacuation of the gastric contents, the instillation of activated charcoal slurry into the stomach may help absorb any remaining drug from the gastrointestinal tract. Antiemetic medication may be required to control severe nausea and vomiting. Active diuresis (with measured intake and output) will help promote excretion of the drug. Hemodialysis may be of value in some patients.

CONTRAINDICATIONS

Rifampin is contraindicated in patients with a history of hypersensitivity to any of the rifamycins. (See WARNINGS.)

REFERENCES

1. National Committee for Clinical Laboratory Standards, Antimycobacterial Susceptibility Testing. Proposed Standard NCCLS Document M24-P, Vol. 10, No. 10, NNCLS, Villanova, PA, 1990.
2. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically -- Third Edition. Approved Standard NCCLS Document M7-A3, Vol. 13, No. 25, NCCLS, Villanova, PA, December 1993.
3. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disk Susceptibility Tests -- Fifth Edition. Approved Standard NCCLS Document M2-A5, Vol. 13, No. 24, NCCLS, Villanova, PA, December 1993.
4. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Susceptibility Testing; Fifth Informational Supplement, NCCLS Document M100-S5, Vol. 14, No. 16, NCCLS, Villanova, PA, December 1994.