Drug Interactions between clofarabine and ivacaftor / tezacaftor

Clofarabine may cause liver problems, and using it with other medications that can also affect the liver such as ivacaftor may increase that risk. You should avoid or limit the use of alcohol while being treated with these medications. Call your doctor immediately if you have fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark urine, pale stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. Talk to your doctor or pharmacist if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Consumer information for this interaction is not currently available.

GENERALLY AVOID: The liver is a known target organ for clofarabine toxicity, and concomitant use of other potentially hepatotoxic agents may increase the risk of liver injury. Severe and fatal hepatotoxicity has occurred with the use of clofarabine alone. In clinical studies, grade 3 to 4 liver enzyme elevations were frequently observed in pediatric patients during treatment, with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevations reported in 36% and 44% of patients, respectively. Liver enzyme elevations typically occurred within 10 days of clofarabine administration and returned to grade 2 or lower within 15 days. Grade 3 or 4 bilirubin elevations occurred in 13% of patients, with 2 cases reported as grade 4 hyperbilirubinemia (2%), one of which resulted in treatment discontinuation and the other in multi-organ failure and death. Eight patients (7%) had grade 3 or 4 elevations in serum bilirubin at the last time point measured, all of whom died due to sepsis and/or multi-organ failure.

MANAGEMENT: Concomitant use of clofarabine with other potentially hepatotoxic agents should be avoided whenever possible (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Hepatic function should be monitored during clofarabine administration, and therapy discontinued if grade 3 to 4 liver enzyme or bilirubin elevations occur. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice.