Tygacil 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.

Tigecycline is primarily metabolized by the liver and excreted in the bile as unchanged drug and metabolites. In a single-dose study of subjects with varying degrees of hepatic impairment, systemic clearance of tigecycline was reduced by 25% and half-life prolonged by 23% in patients classified as having moderate hepatic impairment (Child Pugh B) compared to age- and weight-matched healthy control subjects. In patients with severe hepatic impairment (Child Pugh C), systemic clearance of tigecycline was reduced by 55% and half-life prolonged by 43% compared to controls. No significant pharmacokinetic changes were reported in patients with mild hepatic impairment (Child Pugh A). Therapy with tigecycline should be administered cautiously in patients with severe liver disease. The initial dose should be 100 mg followed by a reduced maintenance dose of 25 mg every 12 hours. No dosage adjustment is necessary in patients with mild to moderate hepatic impairment.