Enfuvirtide Injection and Tipranavir: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Tipranavir
Enfuvirtide Injection
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
Increased tipranavir/ritonavir trough levels
Interaction Deep Dive
Coadministration of enfuvirtide and tipranavir/ritonavir (TPV/RTV) resulted in significantly increased TPV/RTV trough levels. While the exact mechanism is unknown, the Vd and half-life are the principally affected pharmacokinetic parameters1. Caution is advised if these agents are coadministered, particularly in patients with hepatitis co-infection. Patients should be monitored for tipranavir/ritonavir toxicity, including increased levels of lipid profiles, increased levels of liver function tests, nausea, vomiting or diarrhea, fatigue, headache, and rash. Because the incidence of clinically significant hepatotoxicity does not seem to correspond with increased tipranavir concentrations, dose adjustment or discontinuation of tipranavir/ritonavir or enfuvirtide is not recommended for most patients, as this may result in subtherapeutic effects and increased drug resistance 2.
Why it happens (mechanism)
Unknown
Literature reports
2 reports — tap to read
a) In a sub-analysis of the Randomized Evaluation of Strategic Intervention in multidrug reSistant patients with Tipranavir (RESIST) trial, concurrent use of enfuvirtide with tipranavir/ritonavir (n=154) increased tipranavir trough concentrations by 31% compared to tipranavir/ritonavir without enfuvirtide (n=507), without a corresponding increase in rates of grade 3/4 ALT elevations or clinical hepatotoxicity. Tipranavir concentrations above 120 micromoles were associated with increased risk of grade 3/4 ALT elevations in prior analyses. In this study, only 1.3% and 1.2% of patients on tipranavir/ritonavir with enfuvirtide and tipranavir without enfuvirtide, respectively, had tipranavir concentrations above that level. Grade 3/4 ALT elevations occurred in 6.5% of patients treated with tipranavir/ritonavir and enfuvirtide compared to 12.9% of patients treated with tipranavir/ritonavir over 96 weeks. There were 5.9 hepatic adverse events per 100 patient exposure years in the tipranavir/ritonavir with enfuvirtide group, while patients treated with tipranavir/ritonavir without enfuvirtide experienced 9.3 events per 100 patient exposure years. The administration of enfuvirtide with ritonavir-boosted comparator protease inhibitors also increased the trough concentrations of those protease inhibitors, specifically lopinavir and saquinavir, and there was a slightly higher incidence of hepatic events in patients treated with ritonavir-boosted lopinavir or saquinavir with enfuvirtide (3.9 events per 100 patient exposure years) than without enfuvirtide (2.9 events per 100 patient exposure years) 2.
b) In a prospective, cohort study, coadministration of tipranavir/ritonavir (TPV/RTV) with enfuvirtide resulted in significantly higher trough concentrations of TPV/RTV compared to treatment with TPV/RTV alone. Patients received TPV/RTV 500/200 mg orally twice daily (plus 2 nucleoside reverse transcriptase inhibitors) either with enfuvirtide 90 mg given subcutaneously twice daily (n=27; group A) or without enfuvirtide (n=28; group B). Among 194 trough samples measured between 11 and 13 hours (h) after the last TPV/RTV dose, the mean (+/- standard deviation (SD)) TPV trough concentrations were 41,069 +/- 20,174 ng/mL and 27,261 +/- 17,516 ng/mL for groups A and B, respectively (p=0.011). The mean (+/- SD) RTV trough concentrations were 371 +/- 333 ng/mL and 188 +/- 139 ng/mL for groups A and B, respectively (p=0.017). Discontinuation of enfuvirtide in 2 patients led to decreases in TPV trough levels by 50.8% and 25.6%, respectively. In 1 patient, addition of enfuvirtide to a tipranavir-based regimen resulted in a 72.3% increase in the TPV trough level. A comparison of pharmacokinetic parameters of the 2 groups with historical data revealed a similar constant of absorption for TPV/RTV in both groups. However, group A patients displayed higher Vd and lower rates of elimination of TPV/RTV compared to group B patients. For both TPV and RTV, the half-life values were higher in group A compared to group B (TPV: 9.69 hours versus 5.36 hours; RTV: 3.17 hours versus 2 hours). The exact mechanism for this interaction is unknown and further investigation is warranted 1.
Common questions
Can I take Enfuvirtide Injection and Tipranavir together?
Increased tipranavir/ritonavir trough levels Always confirm with your pharmacist or prescriber before making any change.
How serious is the Enfuvirtide Injection and Tipranavir interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Enfuvirtide Injection or Tipranavir 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 anything you'd monitor while I'm on both?
References (2)
- GonzalezdeRequena D, Calcagno A, & et al: Unexpected drug-drug interaction between tipranavir/ritonavir and enfuvirtide. AIDS 2006; 20(15):1977-1979. DOI
- Raffi F, Battegay M, Rusconi S, et al: Combined tipranavir and enfuvirtide use associated with higher plasma tipranavir concentrations but not with increased hepatotoxicity: sub-analysis from RESIST. AIDS 2007; 21(14):1977-1980. PubMed
Keep reading about Tipranavir
Keep reading about Enfuvirtide Injection
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