Rifapentine Disease Interactions

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

Although the single-dose pharmacokinetic profiles of rifapentine and its active metabolite, 25-desacetyl rifapentine, were similar in patients with various degrees of liver dysfunction and to those observed in healthy subjects, therapy with rifapentine should be administered cautiously in such patients, since the drug is primarily eliminated by the liver. Patients with abnormal liver tests and/or liver disease should only be given rifapentine in cases of necessity and under strict medical supervision; serum transaminase levels should be obtained before therapy and every 2 to 4 weeks during therapy. Rifapentine should be discontinued if liver injury occurs.

Rifapentine should be avoided in patients with porphyria. Porphyria has been reported with rifampin, attributed to induction of delta amino levulinic acid synthetase; rifapentine may have similar enzyme induction properties.