Drug Interaction Report

The side effects of levodopa may be increased when it is used in combination with entacapone. You may need a dose adjustment if you have been taking levodopa and are starting or stopping treatment with entacapone. Contact your doctor if your condition changes or if you experience movement difficulties, increased drowsiness, dizziness, lightheadedness, flushing, and/or fainting. Avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medications affect you, and use caution when getting up from a sitting or lying position. 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.

MONITOR: The hypotensive and central nervous system (CNS) depressant effects of levodopa or foslevodopa may be additive with antihypertensive agents or agents with both hypotensive properties and CNS depressant effects. Postural hypotension may occur and/or the risk of sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: Hemodynamic responses should be monitored during coadministration, especially during the first few weeks of therapy. Dose adjustments of the concomitant agent may be required. Patients should be advised to notify their doctor if they experience dizziness or syncope and/or sudden, excessive or prolonged CNS effects that interfere with their normal activities. Patients should also be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them.

Alcohol can increase the nervous system side effects of levodopa such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. You should avoid or limit the use of alcohol while being treated with levodopa. You may experience reduced effectiveness of levodopa in the presence of foods or enteral (tube) feedings with a high protein content. This may make the symptoms of Parkinson's disease worse. Talk with your doctor or nutrition counselor about the best foods to eat while you are taking this medication. Contact your doctor if your condition changes.

Alcohol can increase the nervous system side effects of entacapone such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. You should avoid or limit the use of alcohol while being treated with entacapone. Do not use more than the recommended dose of entacapone, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. Talk to your doctor or pharmacist if you have any questions or concerns.

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.

Levodopa and multivitamin with minerals should not be taken orally at the same time. Products that contain iron may interfere with the absorption of levodopa and reduce its effectiveness. You should separate the dosing of these medications by as much as possible. Contact your doctor if your Parkinson symptoms worsen. 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.