Drug Interactions between emtricitabine / lopinavir / ritonavir / tenofovir disoproxil and nebivolol

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.

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 2D6 may increase the plasma concentrations of nebivolol, which is primarily metabolized by the isoenzyme The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity. Several studies have shown that coadministration of CYP450 2D6 inhibitors increases the peak plasma concentration (Cmax) and systemic exposure (AUC) of nebivolol. When the potent CYP450 2D6 inhibitor paroxetine (20-40 mg daily) was coadministered with nebivolol (5 mg) in 23 healthy subjects, nebivolol's Cmax and AUC increased by 5.7-fold and 6.1-fold, respectively. Similarly, when bupropion (300 mg), a potent CYP450 2D6 inhibitor, was coadministered with nebivolol in 18 healthy volunteers, the Cmax and AUC increased by 2.3-fold and 7.2-fold, respectively. Fluoxetine (20 mg daily), a potent CYP450 2D6 inhibitor, increased nebivolol's Cmax and AUC by approximately 2.3-fold and 6-fold in 10 patients. Fluvoxamine, a mild CYP450 2D6 inhibitor, increased Cmax and AUC by 1.41-fold and 1.44-fold in 18 healthy volunteers. However, no data resulted in significant changes to heart rate or blood pressure.

MANAGEMENT: Caution is advised when nebivolol is used concomitantly with CYP450 2D6 inhibitors. Additional caution and monitoring are advised if the coadministered CYP450 2D6 inhibitor may potentiate the blood pressure lowering effects of nebivolol (e.g., phenothiazines, tricyclic antidepressants (TCAs), and some antipsychotic (neuroleptic) agents). Patients should be monitored closely for adverse effects such as bradycardia, diarrhea, nausea, fatigue, chest pain, peripheral edema, headache, dizziness, insomnia, dyspnea and rash, and the nebivolol dose should be adjusted according to blood pressure response.

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.

Using lopinavir together with nebivolol can increase the risk of an irregular heart rhythm that may be serious. You may need a dose adjustment or special tests to safely use both medications. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, or irregular heartbeat during treatment with these drugs, whether together or alone. 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.