Drug Interaction Report

Talk to your doctor before using macitentan together with ritonavir. Combining these medications can significantly increase the blood levels of macitentan. This may increase the risk of side effects such as headache, anemia and liver problems, especially during prolonged treatment. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Call your doctor immediately if you have fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark colored urine, light colored stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. 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.

Ritonavir may increase the blood levels and effects of tenofovir. This can increase the risk of side effects including serious ones like kidney or liver damage and a condition known as lactic acidosis, which is a buildup of lactic acid in the blood. You should seek immediate medical attention if you develop symptoms of these conditions. Symptoms of kidney damage may include swelling, weight gain, shortness of breath, drowsiness, confusion, mood changes, increased thirst, loss of appetite, nausea, vomiting, pain in your lower back, and urinating more or less than usual or not at all. Symptoms of liver damage may include fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, dark colored urine, and/or yellowing of the skin or eyes. Symptoms of lactic acidosis may include fatigue, unusual muscle pain, difficulty breathing, stomach pain, nausea, vomiting, lightheadedness, dizziness, and a fast or irregular heartbeat. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. 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.

Lopinavir may increase the blood levels and effects of tenofovir. This can increase the risk of side effects including serious ones like kidney or liver damage and a condition known as lactic acidosis, which is a buildup of lactic acid in the blood. You should seek immediate medical attention if you develop symptoms of these conditions. Symptoms of kidney damage may include swelling, weight gain, shortness of breath, drowsiness, confusion, mood changes, increased thirst, loss of appetite, nausea, vomiting, pain in your lower back, and urinating more or less than usual or not at all. Symptoms of liver damage may include fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, dark colored urine, and/or yellowing of the skin or eyes. Symptoms of lactic acidosis may include fatigue, unusual muscle pain, difficulty breathing, stomach pain, nausea, vomiting, lightheadedness, dizziness, and a fast or irregular heartbeat. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. 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.

Ritonavir should be taken with food to lessen gastrointestinal side effects. It is important that you take this medication exactly as prescribed by your doctor. Do not change your treatment or stop treatment without first talking to your doctor.

Food may affect the absorption of lopinavir-ritonavir (brand name Kaletra) depending on whether you are taking the oral solution or the tablet. The oral solution should be taken with food to enhance absorption and help it work better. The tablet formulation can be take with or without food. Talk to your doctor or pharmacist if you have questions on how to take this or other medications you are prescribed. 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.

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