Drug Interaction Report

Treatment with cholecalciferol may require you to adjust your dietary intake of foods which contain natural or added calcium, phosphate (organic and inorganic), and vitamin D. Ingesting too much vitamin D or having elevated calcium and/or phosphorus levels in the blood and urine can lead to toxic effects, such as having an irregular heart rhythm, seizures, kidney stones, and eventual calcification of your blood vessels, cornea and/or the soft tissues in your body. Your doctor will monitor the levels of calcium and phosphorus in your blood during treatment with cholecalciferol. Please speak with your healthcare team to determine if you require a specialized diet, particularly if you have reduced kidney function, and to discuss any other questions or concerns you have. You may require additional monitoring or a dose adjustment of cholecalciferol if your diet changes. Fortified foods will state on their labeling how much calcium, phosphate, and/or vitamin D has been added. The National Institutes of Health, Office of Dietary Supplements also provides information on which foods contain calcium, phosphorus, and vitamin D. You should avoid abrupt changes in your dietary calcium intake and seek medical attention if you experience early symptoms of vitamin D intoxication such as weakness, fatigue, headache, drowsiness, vertigo, ringing in the ears, loss of appetite, nausea, vomiting, constipation, dry mouth, metallic taste, muscle pain, bone pain, muscle incoordination, and low muscle tone. Late symptoms may include frequent urination, excessive thirst, weight loss, conjunctivitis ("pink eye"), light sensitivity, runny nose, itching, increased body temperature, and irregular heart rhythm. 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: Coadministration with grapefruit juice may increase the plasma concentrations of macitentan, which is primarily metabolized by CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. The interaction has not been studied with grapefruit juice but has been reported for ketoconazole, a potent CYP450 3A4 inhibitor. In ten healthy subjects, coadministration of a single 10 mg oral dose of macitentan on day 5 of treatment with ketoconazole (400 mg daily for 24 days) resulted in an approximately 2-fold increase in macitentan systemic exposure compared to administration alone. However, the clinical significance of the interaction is unclear. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Until further information is available, patients receiving macitentan therapy should avoid the consumption of grapefruit or grapefruit juice.