Digoxin with Ritonavir Interaction Details
Brand Names Associated with Digoxin
- Cardoxin®
- Digitek®
- Digoxin
- Lanoxicaps®
- Lanoxin®
Brand Names Associated with Ritonavir
- Norvir®
- Ritonavir
- RTV
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Jan 08, 2024
Interaction Effect
Increased digoxin plasma concentrations and increased risk of digoxin toxicity (nausea, vomiting, arrhythmias); additive increase of PR interval
Interaction Summary
In healthy subjects who received daily doses of ritonavir, a single IV dose of digoxin significantly increased digoxin AUC by 86%, and a single oral dose of digoxin significantly increased AUC by 22%. Digoxin is a P-gp substrate and ritonavir is a P-gp inhibitor. Additionally, both ritonavir and digoxin increase the PR interval . If coadministration is required, measure serum digoxin concentrations before initiation. To reduce digoxin concentrations, decrease the digoxin dose by 30% to 50% or modify the dosing frequency and monitor digoxin levels . A digoxin dose adjustment is not required when coadministered with ritonavir as a component of copackaged ombitasvir/paritaprevir/ritonavir/dasabuvir .
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Coadministration of digoxin and ritonavir may increase digoxin levels. If coadministration is required, measure serum digoxin concentrations before initiation. To reduce digoxin concentrations, decrease the digoxin dose by 30% to 50% or modify the dosing frequency and monitor digoxin levels . A digoxin dose adjustment is not required when coadministered with ritonavir as a component of copackaged ombitasvir/paritaprevir/ritonavir/dasabuvir . Digoxin is a P-gp substrate and ritonavir is a P-gp inhibitor. Additionally, both ritonavir and digoxin increase the PR interval .
Mechanism Of Interaction
Decreased nonrenal clearance of digoxin due to ritonavir-mediated inhibition of P-gp in the liver; additive increase of PR interval
Literature Reports
A) Concomitant administration of ritonavir with IV digoxin significantly reduced digoxin total clearance and increased digoxin bioavailability. In a randomized, double-blind, cross-over study, healthy men (N=12) received either ritonavir 300 mg twice daily or placebo on study days 1 through 11. Twenty minutes after an oral dose of ritonavir 300 mg was given on study day 3, each subject received a single IV dose of digoxin 0.5 mg, after which digoxin pharmacokinetics were assessed in a serial manner over the next 216 hours. An oral water overload (200 mL/hr) was imposed over the first 12 hours after dosing in order to minimize renal tubular reabsorption of digoxin. Each subject crossed over the opposing study arm after a minimum washout period of 20 days. Concurrent administration of ritonavir with digoxin significantly decreased digoxin renal clearance by 35% and nonrenal clearance by 48% and significantly increased digoxin AUC (0 to infinity) by 86%, steady-state Vd by 77%, and t(1/2) by 156% .
B) In a 2 treatment, 2 period, single sequence, longitudinal drug interaction study lasting 32 days, 9 out of 12 healthy subjects showed decreased nonrenal clearance of a 0.4 mg single oral dose of digoxin by 30% after 13 days of ritonavir 200 mg twice daily. In the 72 hours after the digoxin dose, ritonavir significantly increased the digoxin AUC by 22%, from 26.2 to 31.96 nanograms x hour/mL. Renal clearance of digoxin was not significantly affected by the presence of ritonavir. The effects of ritonavir-associated P-glycoprotein inhibition on digoxin pharmacokinetics were comparable across the Multiple Drug Resistance Gene (MDR1) genotypes of the 12 subjects .
Digoxin Overview
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Digoxin is used to treat heart failure and abnormal heart rhythms (arrhythmias). It helps the heart work better and it helps control your heart rate.
Ritonavir Overview
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Ritonavir is used along with other medications to treat human immunodeficiency virus (HIV) infection. Ritonavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although ritonavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other lifestyle changes may decrease the risk of transmitting the HIV virus to other people.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.