Drug Interaction Report

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.

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.