Drug Interactions between cholecalciferol / iron polysaccharide and pancrelipase

MONITOR: Additive effects and possible toxicity (e.g., hypercalcemia, hypercalciuria, and/or hyperphosphatemia) may occur when patients using vitamin D and/or vitamin D analogs ingest a diet high in vitamin D, calcium, and/or phosphorus. The biologically active forms of vitamin D stimulate intestinal absorption of calcium and phosphorus. This may be helpful in patients with hypocalcemia and/or hypophosphatemia. However, sudden increases in calcium or phosphorus consumption due to dietary changes could precipitate hypercalcemia and/or hyperphosphatemia. Patients with certain disease states, such as impaired renal function, may be more susceptible to toxic side effects like ectopic calcification. On the other hand, if dietary calcium is inadequate for the body's needs, the active form of vitamin D will stimulate osteoclasts to pull calcium from the bones. This may be detrimental in a patient with reduced bone density.

MANAGEMENT: Given the narrow therapeutic index of vitamin D and vitamin D analogs, the amounts of calcium, phosphorus, and vitamin D present in the patient's diet may need to be taken into consideration. Specific dietary guidance should be discussed with the patient and regular lab work should be monitored as indicated. Calcium, phosphorus, and vitamin D levels should be kept within the desired ranges, which may differ depending on the patient's condition. Patients should also be counseled on the signs and symptoms of hypervitaminosis D, hypercalcemia, and/or hyperphosphatemia.

ADJUST DOSING INTERVAL: Concomitant use of some oral medications may reduce the bioavailability of orally administered iron, and vice versa.

Food taken in conjunction with oral iron supplements may reduce the bioavailability of the iron. However, in many patients intolerable gastrointestinal side effects occur necessitating administration with food.

MANAGEMENT: Ideally, iron products should be taken on an empty stomach (i.e., at least 1 hour before or 2 hours after meals), but if this is not possible, administer with meals and monitor the patient more closely for a subtherapeutic effect. Some studies suggest administration of iron with ascorbic acid may enhance bioavailability. In addition, administration of oral iron products and some oral medications should be separated whenever the bioavailability of either agent may be decreased. Consult the product labeling for specific separation times and monitor clinical responses as appropriate.

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.