Drug Interactions between calcitriol and Tuinal

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

MONITOR: Coadministration with potent CYP450 3A4 inducers and certain anticonvulsants, which are also capable of CYP450 3A4 induction, may decrease the pharmacologic effects of vitamin D and/or vitamin D analogs. In general, vitamin D is primarily biotransformed into inactive metabolites via CYP450 3A4 in the liver. Increases in the inactivation of vitamin D may be accompanied by reduced serum calcium and increased parathyroid hormone levels. Patients on long-term anticonvulsant therapy have occasionally developed osteomalacia, presumably due to interference with vitamin D and calcium metabolism. Clinical studies have documented widely varying rates of vitamin D deficiency in pediatric patients being treated with anticonvulsants, ranging from as low as 10% to as high as 79%. Case reports of low vitamin D levels associated with symptomatic hypocalcemia also exist in patients on the potent CYP450 3A4 inducer, rifampin.

MANAGEMENT: Patients receiving vitamin D and/or vitamin D analogs with potent CYP450 3A4 inducers or anticonvulsants capable of CYP450 3A4 induction should be monitored more closely for reduced vitamin D effects. Higher doses of vitamin D and/or the vitamin D analog may be necessary to achieve the desired therapeutic effect.

MONITOR: Coadministration with potent CYP450 3A4 inducers and certain anticonvulsants, which are also capable of CYP450 3A4 induction, may decrease the pharmacologic effects of vitamin D and/or vitamin D analogs. In general, vitamin D is primarily biotransformed into inactive metabolites via CYP450 3A4 in the liver. Increases in the inactivation of vitamin D may be accompanied by reduced serum calcium and increased parathyroid hormone levels. Patients on long-term anticonvulsant therapy have occasionally developed osteomalacia, presumably due to interference with vitamin D and calcium metabolism. Clinical studies have documented widely varying rates of vitamin D deficiency in pediatric patients being treated with anticonvulsants, ranging from as low as 10% to as high as 79%. Case reports of low vitamin D levels associated with symptomatic hypocalcemia also exist in patients on the potent CYP450 3A4 inducer, rifampin.

MANAGEMENT: Patients receiving vitamin D and/or vitamin D analogs with potent CYP450 3A4 inducers or anticonvulsants capable of CYP450 3A4 induction should be monitored more closely for reduced vitamin D effects. Higher doses of vitamin D and/or the vitamin D analog may be necessary to achieve the desired therapeutic effect.