Drug Interactions between mirvetuximab soravtansine and troleandomycin

Troleandomycin is primarily excreted by the liver and may accumulate in patients with impaired hepatic function. In addition, the use of troleandomycin has been associated with an allergic type of cholestatic hepatitis, particularly in patients receiving the drug for more than 2 weeks or given repeated courses. Therapy with troleandomycin should be administered cautiously in patients with liver and/or biliary disease. Liver function tests should be monitored during prolonged or repeated courses of therapy, and the drug discontinued if abnormalities develop.

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.

Troleandomycin is primarily excreted by the liver and may accumulate in patients with impaired hepatic function. In addition, the use of troleandomycin has been associated with an allergic type of cholestatic hepatitis, particularly in patients receiving the drug for more than 2 weeks or given repeated courses. Therapy with troleandomycin should be administered cautiously in patients with liver and/or biliary disease. Liver function tests should be monitored during prolonged or repeated courses of therapy, and the drug discontinued if abnormalities develop.

The use of mirvetuximab soravtansine should be avoided in patients with moderate or severe hepatic impairment. No dose adjustment is recommended for patients with mild hepatic impairment.

Mirvetuximab soravtansine caused peripheral neuropathy in 36% of the patients in clinical trials. Monitor patients closely for signs and symptoms of neuropathy, such as paresthesia, tingling or burning sensation, neuropathic pain, muscle weakness, or dysesthesia. For patients experiencing new or worsening peripheral neuropathy, withhold dosage, dose reduce, or permanently discontinue treatment based on the severity of the symptoms.

The effect of severe renal impairment (CrCl 15 to less than 30 mL/min) or end-stage renal disease on mirvetuximab soravtansine is unknown. Caution is advised if prescribing to these patients. No dosage adjustment is recommended for patients with mild to moderate renal impairment.

Mirvetuximab soravtansine can cause severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis. Patients should have a detailed ophthalmic exam including visual acuity and slit lamp exam prior to treatment initiation, and before every other cycle for the first 8 cycles, and then as clinically indicated. Refer patients to an eye care professional immediately for any new or worsening ocular signs and symptoms. Monitor closely for ocular toxicity and withhold, reduce, or permanently discontinue treatment based on severity and persistence of ocular adverse reactions.