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Interactions between Ambrisentan and Venclexta

1 drug interaction and 12 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

ambrisentan venetoclax

Applies to: ambrisentan and Venclexta (venetoclax)
Generally avoid

Coadministration with venetoclax may increase the plasma concentrations and effects of drugs that are substrates of the P-glycoprotein (P-gp) efflux transporter. The proposed mechanism involves increased absorption and/or decreased clearance of the P-gp substrate due to inhibition of P-gp-mediated drug efflux in the intestine, liver, and/or kidney by venetoclax. In healthy female volunteers (n=10), coadministration of a single dose of oral digoxin (0.5 mg) was coadministered with a single dose of venetoclax (100 mg) increased digoxin's peak plasma concentration (Cmax) and systemic exposure (AUC) by 35% and 9%, respectively. Clinical data with parenterally administered P-gp substrates are not available.

Management

Concomitant use of venetoclax with drugs that are substrates of P-gp, particularly sensitive substrates or those with a narrow therapeutic index that are absorbed in the gastrointestinal tract, should generally be avoided. Alternatives should be considered whenever possible. Caution is advised if coadministration is required, and the doses of venetoclax and the P-gp substrate(s) should be separated as much as possible to minimize potential interaction. Some manufacturers recommend that drugs sensitive to P-gp inhibition in the gastrointestinal tract be administered at least 6 hours before venetoclax.

References (11)
  1. (2022) "Product Information. PMS-Digoxin (digoxin)." Pharmascience Inc
  2. (2022) "Product Information. Venclexta (venetoclax)." AbbVie Corporation
  3. (2025) "Product Information. Venclyxto (venetoclax)." AbbVie Ltd
  4. (2025) "Product Information. Venclexta (venetoclax)." AbbVie Pty Ltd
  5. (2024) "Product Information. Venclexta (venetoclax)." AbbVie US LLC
  6. (2025) "Product Information. Digoxin (digoxin)." Hikma Pharmaceuticals USA Inc.
  7. (2025) "Product Information. Lanoxin (digoxin)." Covis Pharmaceuticals
  8. (2024) "Product Information. Digoxin (digoxin)." Amneal Pharmaceuticals LLC
  9. (2025) "Product Information. Digoxin (digoxin)." Aurobindo Pharma USA Inc
  10. (2025) "Product Information. Digoxin (digoxin)." Aspen Pharma Trading Ltd
  11. (2025) "Product Information. Lanoxin (digoxin)." Aspen Pharmacare Australia Pty Ltd

Food/lifestyle interactions

Major food/lifestyle interactions

Major:

venetoclax Food/Lifestyle

Applies to: Venclexta (venetoclax)
Adjust dosing interval

Food enhances the oral bioavailability of venetoclax. Relative to fasting conditions, venetoclax systemic exposure (AUC) increased by approximately 3.4-fold when administered with a low-fat meal (approximately 512 kilocalories, 25% calories from fat) and by 5.1- to 5.3-fold when administered with a high-fat meal (approximately 753 kilocalories, 55% calories from fat).

Generally avoid

Grapefruit, grapefruit juice, Seville oranges, and starfruit may increase the plasma concentrations of venetoclax, which is primarily metabolized by the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported with potent CYP450 3A4 inhibitors. In a study of 11 previously treated non-Hodgkin lymphoma patients, when the potent CYP450 3A4 inhibitor, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) inhibitor ketoconazole (400 mg daily for 7 days) was coadministered with venetoclax (50 mg single dose), venetoclax peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.3-fold and 6.4-fold, respectively. Physiologically based pharmacokinetic modeling estimates that the moderate CYP450 3A4 inhibitors diltiazem and erythromycin may increase the Cmax and AUC of venetoclax by between 1.4- to 2- fold and 2- to 4.9-fold, respectively, while the weak CYP450 3A4 inhibitors fluoxetine and fluvoxamine appear to have no significant effect on its Cmax or AUC. 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. Increased venetoclax exposure may potentiate the risk of tumor lysis syndrome, particularly at initiation of therapy and during the dosage ramp-up phase, as well as other adverse effects such as diarrhea, nausea, vomiting, neutropenia, anemia, and thrombocytopenia.

Management

Venetoclax should be administered with a meal and water at approximately the same time each day. Patients should avoid consumption of grapefruit products, Seville oranges, and starfruit during treatment with venetoclax.

References (6)
  1. (2016) "Product Information. Venclexta (venetoclax)." AbbVie US LLC
  2. (2022) "Product Information. Venclexta (venetoclax)." AbbVie US LLC
  3. (2023) "Product Information. Venclexta (venetoclax)." AbbVie Pty Ltd
  4. (2024) "Product Information. Venclyxto (venetoclax)." AbbVie Ltd
  5. (2022) "Product Information. Venclexta (venetoclax)." AbbVie Corporation
  6. Freise K.J, Shebley M, Salem A.H (2017) "Quantitative prediction of the effect of CYP3A inhibitors and inducers on venetoclax pharmacokinetics using a physiologically based pharmacokinetic model" J Clin Pharmacol, 57, p. 796-804

Disease interactions

11 potential interactions Applies to: 9 conditions, including Heart Failure, Anemia, Fever, Liver Disease, and Infection.

Anemia

Moderate:

ambrisentan

Ambrisentan has a moderate potential interaction with Anemia.

Clinical studies have shown that most endothelin receptor antagonists decrease hemoglobin concentration and hematocrit levels. There are some postmarketing reports of anemia cases which needed blood transfusion. Hemoglobin and hematocrit levels should be measured prior to treatment initiation and should be monitored periodically thereafter. Initiation of therapy is not recommended in patients with clinically significant anemia.

Fever

Moderate:

Venclexta

The venetoclax in Venclexta has a moderate potential interaction with Fever.

Venetoclax can cause neutropenia. It is recommended to monitor for fever and signs suggestive of an infection. Monitor complete blood count during the course of therapy and reduce dose or interrupt treatment for severe neutropenia. Therapy with this agent should be administered cautiously in patients with preexisting bone marrow depression or blood dyscrasias.

Heart Failure

Moderate:

ambrisentan

Ambrisentan has a moderate potential interaction with Heart Failure.

Peripheral edema and fluid retention are known clinical consequences of pulmonary hypertension and also known effects of endothelin receptor antagonists. Caution and monitoring is recommended if these agents are used in patients with underlying left ventricular dysfunction or underlying heart failure, as they have an increased risk for developing significant fluid retention that may need treatment or require discontinuation.

Infection

Moderate:

Venclexta

The venetoclax in Venclexta has a moderate potential interaction with Infection.

Venetoclax can cause neutropenia. It is recommended to monitor for fever and signs suggestive of an infection. Monitor complete blood count during the course of therapy and reduce dose or interrupt treatment for severe neutropenia. Therapy with this agent should be administered cautiously in patients with preexisting bone marrow depression or blood dyscrasias.

Liver Disease

Major:

ambrisentan

Ambrisentan has a major potential interaction with Liver Disease.

Endothelin receptor antagonists (ERAs) have been associated with aminotransferase elevations, hepatotoxicity, and cases of liver failure. Hepatic function should be assessed before treatment initiation and closely monitored during treatment. Therapy should be discontinued if aminotransferase elevations are accompanied by increases in bilirubin, or clinical symptoms of hepatotoxicity such as nausea, vomiting, fever, abdominal pain or jaundice. Treatment should be avoided in patients with elevated aminotransferases at baseline as monitoring for hepatotoxicity may be more difficult. In general, the use of ERAs is not recommended for patients with moderate to severe hepatic impairment.

Moderate:

Venclexta

The venetoclax in Venclexta has a moderate potential interaction with Liver Disease.

In vitro studies demonstrated that venetoclax is predominantly metabolized in the liver by CYP450 3A4/5. Based on pharmacokinetic analysis with subjects with mild and moderate hepatic impairment, the venetoclax exposures were similar to those with normal hepatic function; therefore, no dose adjustment is recommended in patients with mild or moderate hepatic impairment. Based on the drug metabolism, an increase in adverse events might result in patients with moderate to severe hepatic impairment. It is recommended to monitor patients with moderate to severe hepatic impairment carefully for signs of toxicity during the initiation and the weekly dose ramp-up phase. Caution is advised when using this agent in patients with severe hepatic impairment as it pharmacokinetics has not been studied.

Neutropenia

Moderate:

Venclexta

The venetoclax in Venclexta has a moderate potential interaction with Neutropenia.

Venetoclax can cause neutropenia. It is recommended to monitor for fever and signs suggestive of an infection. Monitor complete blood count during the course of therapy and reduce dose or interrupt treatment for severe neutropenia. Therapy with this agent should be administered cautiously in patients with preexisting bone marrow depression or blood dyscrasias.

Renal Dysfunction

Moderate:

ambrisentan

Ambrisentan has a moderate potential interaction with Renal Dysfunction.

There is no information on the exposure to ambrisentan in patients with severe renal impairment. Additionally, the impact of hemodialysis on the disposition of ambrisentan has not been studied, hence caution is advised. No dosage adjustment is required in patients with mild or moderate renal impairment.

Moderate:

Venclexta

The venetoclax in Venclexta has a moderate potential interaction with Renal Dysfunction.

Based on pharmacokinetic analysis with subjects with mild and moderate renal impairment, the venetoclax exposures were similar to those with normal renal function; therefore, no dose adjustment is recommended in these patients. The pharmacokinetics of venetoclax has not been studied in subjects with severe renal impairment. Patients with reduced renal function are at increased risk of tumor lysis syndrome (TLS) and these patients may require more intensive monitoring and care to reduce the risk of TLS at the start of treatment. Patients should be assessed for risk factor that may contribute to an increase risk for TLS and complete blood chemistries should be monitored regularly. Dose interruption is recommended if needed based on clinical findings.

Tumor Lysis Syndrome

Moderate:

Venclexta

The venetoclax in Venclexta has a moderate potential interaction with Tumor Lysis Syndrome.

Based on pharmacokinetic analysis with subjects with mild and moderate renal impairment, the venetoclax exposures were similar to those with normal renal function; therefore, no dose adjustment is recommended in these patients. The pharmacokinetics of venetoclax has not been studied in subjects with severe renal impairment. Patients with reduced renal function are at increased risk of tumor lysis syndrome (TLS) and these patients may require more intensive monitoring and care to reduce the risk of TLS at the start of treatment. Patients should be assessed for risk factor that may contribute to an increase risk for TLS and complete blood chemistries should be monitored regularly. Dose interruption is recommended if needed based on clinical findings.

Vaccination

Moderate:

Venclexta

The venetoclax in Venclexta has a moderate potential interaction with Vaccination.

The administration of live attenuated vaccines should be avoided prior to, during, and after therapy with venetoclax until B-cell recovery occurs. It is recommended to be up-to-date with all required immunizations, as recommended by current immunization guidelines, before initiating therapy. The safety and efficacy of immunization with live attenuated vaccines during or following venetoclax therapy have not been studied. Venetoclax may interfere with the response to immunization and the vaccinations may be less effective.

More resources

ambrisentan

A total of 186 drugs are known to interact with ambrisentan.

Venclexta

A total of 535 drugs are known to interact with Venclexta.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.