Digoxin and Ritonavir: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ritonavir
Digoxin
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Altered digoxin exposure and an increased risk of digoxin toxicity
Interaction Deep Dive
Exert caution when ritonavir is coadministered with digoxin (P-gp inhibitor) as it may increase digoxin exposure8. Concomitant use of digoxin and ritonavir (P-gp inducer) may also reduce digoxin exposure. If coadministration is required, measure serum digoxin exposure before initiation. To reduce digoxin concentrations, decrease the digoxin dose by 30% to 50% or modify the dosing frequency 124 and monitor digoxin levels 5. Also, monitor potential signs and symptoms of clinical toxicity is necessary when initiating, adjusting, or discontinuing ritonavir 3. A digoxin dose adjustment is not required when coadministered with ritonavir as a component of copackaged ombitasvir/paritaprevir/ritonavir/dasabuvir 9.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of digoxin; induction of P-gp-mediated efflux transport of digoxin
Literature reports
3 reports — tap to read
a) During pharmacokinetic studies, coadministration of ritonavir and digoxin resulted in a 86% increase in digoxin AUC 1234.
b) 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% 6.
c) 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 7.
Common questions
Can I take Digoxin and Ritonavir together?
Altered digoxin exposure and an increased risk of digoxin toxicity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Digoxin and Ritonavir interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Digoxin or Ritonavir need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (9)
- Product Information: LANOXIN(R) oral tablets, digoxin oral tablets. Concordia Pharmaceuticals Inc (per FDA), Kansas City, MO, 2019. DailyMed
- Product Information: DIGOXIN oral tablets, digoxin oral tablets. Aurobindo Pharma USA, Inc. (per Dailymed), East Windsor, NJ, May. DailyMed
- Product Information: DIGOXIN intravenous injection, digoxin intravenous injection. Hikma Pharmaceuticals USA Inc. (per Dailymed), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: LANOXIN® intravenous, intramuscular injection, digoxin intravenous, intramuscular injection. Covis Pharma (per FDA), King of Prussia, PA, 2025. DailyMed
- Product Information: NORVIR oral capsules, ritonavir oral capsules. AbbVie Inc. (per FDA), North Chicago, IL, 2013. DailyMed
- Ding R, Tayrouz Y, Riedel KD, et al: Substantial pharmacokinetic interaction between digoxin and ritonavir in healthy volunteers. Clin Pharmacol Ther 2004; 76(1):73-84.
- Penzak SR, Shen JM, Alfaro RM, et al: Ritonavir decreases the nonrenal clearance of digoxin in healthy volunteers with known MDR1 genotypes. Ther Drug Monit 2004; 26(3):322-330. PubMed
- Product Information: PAXLOVID(TM) oral tablets, nirmatrelvir oral tablets, ritonavir oral tablets. Pfizer Labs (per FDA), New York, NY, 2025. DailyMed
- Product Information: VIEKIRA PAK oral tablets, ombitasvir paritaprevir ritonavir oral tablets and dasabuvir oral tablets. AbbVie Inc. (per manufacturer), North Chicago, Il, 2014.
Keep reading about Ritonavir
Keep reading about Digoxin
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist