Drug Interaction Report

Pralsetinib may alter the blood levels and effects of tadalafil. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. Contact your doctor if your condition changes or you experience increased side effects. 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.

Pralsetinib may alter the blood levels and effects of macitentan. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. Contact your doctor if your condition changes or you experience increased side effects. 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.

Information for this minor interaction is available on the professional version.

Food should not be consumed for at least 2 hours before and at least 1 hour after taking pralsetinib. Do not consume grapefruit, grapefruit juice, any supplements that contain grapefruit, Seville oranges, or Seville orange juice as these products can increase the blood levels of pralsetinib. This may increase the risk and/or severity of serious side effects such as lung problems, liver problems, high blood pressure, fatigue, muscle and joint pain, and bleeding complications. Some sources also warn that combining these medicines could increase the risk of an irregular heart rhythm that may be serious and potentially life-threatening, although it is a relatively rare side effect. You may be more susceptible if you have a heart condition called congenital long QT syndrome, other cardiac disease, conduction abnormalities, or electrolyte disturbance (for example, magnesium or potassium loss due to severe or prolonged diarrhea or vomiting). Talk to your doctor if you have any questions or concerns. 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.

Tadalafil can lower blood pressure, and combining it with alcohol may further increase this effect. You may be more likely to experience symptoms such as dizziness, lightheadedness, fainting, flushing, headache, and heart palpitations. You should avoid or limit the use of alcohol to not more than 4 alcohol-containing drinks during a small period of time while being treated with tadalafil, and use caution when getting up from a sitting or lying position. You may also want to avoid drinking large amounts of grapefruit juice, since it may increase the blood levels and effects of tadalafil. 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.