Drug Interactions between Creon and Sirturo

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of bedaquiline. When administered with a standard meal containing approximately 22 grams of fat (558 total Kcal), the relative bioavailability of bedaquiline increased by approximately 2-fold compared to administration under fasted conditions.

GENERALLY AVOID: Coadministration with alcohol may increase the risk of hepatotoxicity associated with the use of bedaquiline. In clinical trials, hepatic adverse drug reactions developed in more bedaquiline-treated patients than in those who received other drugs used to treat tuberculosis. In patients receiving bedaquiline or placebo in combination with other drugs used to treat multidrug-resistant tuberculosis, reversible aminotransferase elevations of at least 3 times the upper limit of normal developed more frequently in the bedaquiline treatment group [10.8%] than in the placebo group [5.7%].

MANAGEMENT: To ensure maximal oral absorption, bedaquiline should be taken with food. Patients should avoid alcohol use during treatment.

MONITOR: Exogenous pancreatic enzymes may interfere with the gastrointestinal absorption of folic acid and iron. The exact mechanism of interaction is unknown. In one study, investigators compared oral iron absorption over a 3-hour period in the presence and absence of exogenous pancreatic enzymes in 13 stable young adults with cystic fibrosis and 9 age-matched controls. There was no difference between patients and controls in iron absorption in the absence of exogenous pancreatic enzymes. However, significant impairment of iron absorption was observed in both groups after administration of pancrelipase one hour prior to iron administration. In the patient group, one hour after iron administration, there was a 188% increase in serum iron level above baseline in the absence of pancrelipase but only a 62% increase in the presence of pancrelipase. In the controls, percentage increases as well as peak serum iron levels were significantly higher in the absence of pancrelipase during all 3 hours after iron administration. Clinically, at least one-third of cystic fibrosis patients reportedly have iron deficiency. In the study, mean serum iron concentration was significantly lower in patients than in controls (11.9 versus 18.9 micromoles/L), and 5 of the patients but none of the controls had a serum iron concentration lower than 9 micromoles/L at baseline, presumably due to long-term treatment with pancreatic enzyme supplements.

MANAGEMENT: Patients receiving therapeutic iron or folate therapy should be monitored for potentially reduced hematologic response if pancreatic enzymes are administered concomitantly. Separating the times of administration may be helpful.