HCV Guideline Committee, updated August 2020
The charts contained in this section are meant to provide guidance on significant interactions between DAAs and common primary care medications. While these guidelines can be helpful, they are not a substitute for sound clinical judgment and practice.
In some cases, the medications listed below are contraindicated in the U.S. Food and Drug Administration (FDA) labeling for the medication, or the label may state elsewhere that co-administration is not recommended. For some, the recommendation may be to “Avoid Co-administration,” but in some clinical situations it may be necessary to use the medications concurrently. When this is the case, clinicians are encouraged to consult additional references or a liver disease specialist for additional guidance.
For more information on drug-drug interactions in patients with HIV/HCV coinfection see the Drug-Drug Interactions Between DAAs and ARVs section of this guideline.
KEY POINT |
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The links below open pages with tables for each of the following drugs:
- Glecaprevir/Pibrentasvir
- Ledipasvir/Sofosbuvir
- Sofosbuvir/Velpatasvir
- Sofosbuvir/Velpatasvir/Voxilaprevir
Box 2: Online Resources for Identifying Drug-Drug Interactions between DAAs and Common Medications |
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Note: As of August 2020, the following DAAs are no longer used in the United States: Boceprevir, daclatasvir, dasabuvir, elbasvir, grazoprevir, ombitasvir, paritaprevir, simeprevir, and telaprevir.
Glecaprevir/Pibrentasvir
HCV Guideline Committee, May 2019
Table 34: Glecaprevir/Pibrentasvir (Mavyret) Drug-Drug Interactions | |
Avoid co-administration; see clinical comments | |
Class (medications) | Clinical Comments |
Anticonvulsants (carbamazepine, phenobarbital, phenytoin) |
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Antimycobacterial (rifampin) |
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Ethinyl estradiol |
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Herbal therapy (St. John’s Wort) |
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HIV medications (efavirenz, atazanavir, darunavir, lopinavir, saquinavir, tipranavir) |
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HMG-CoA reductase inhibitors (atorvastatin, lovastatin, simvastatin) |
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Co-administration possible; see clinical comments | |
Class (medications) | Clinical Comments |
Antiarrhythmic (digoxin) |
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Anticoagulant (dabigatran etexilate) |
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HMG-CoA reductase inhibitors (fluvastatin, pitavastatin, pravastatin, rosuvastatin) |
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Immunosuppressant (cyclosporine) |
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Source: FDA. Mavyret (glecaprevir and pibrentasvir) tablets, for oral use. http://www.natap.org/2017/HCV/mavyret_pi.pdf [accessed 2019 May 9] |
Ledipasvir/Sofosbuvir
HCV Guideline Committee, May 2019
Table 35: Ledipasvir/Sofosbuvir (multiple brands) Drug-Drug Interactions | |
Avoid co-administration; see clinical comments | |
Class (medications) | Clinical Comments |
Antiarrhythmic (amiodarone) |
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Herbal product (St. John’s wort) |
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Anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin) |
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Antimycobacterials (rifampin, rifabutin, rifapentine) |
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HMG-CoA reductase inhibitor (rosuvastatin) |
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NS3/4A HCV protease inhibitor (simeprevir) |
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Co-administration possible; see clinical comments | |
Class (medications) | Clinical Comments |
Antacids |
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Antiarrhythmic (digoxin) |
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H2-receptor antagonists |
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Proton-pump inhibitors |
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Source: FDA. Harvoni (ledipasvir and sofosbuvir) tablets, for oral use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205834s024lbl.pdf [accessed 2019 May 9] |
Sofosbuvir/Velpatasvir
HCV Guideline Committee, May 2019
Table 36: Sofosbuvir/Velpatasvir (multiple brands) Drug-Drug Interactions |
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Avoid co-administration; see clinical comments | |
Class (medications) | Clinical Comments |
Antiarrhythmic (amiodarone) |
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Anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin) |
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Antimycobacterials (rifampin, rifabutin, rifapentine) |
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Herbal product (St. John’s wort) |
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Co-administration possible; see clinical comments | |
Class (medications) | Clinical Comments |
Antacids (aluminum and magnesium hydroxide) |
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Antiarrhythmic (digoxin) |
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Anticancer (topotecan) |
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H2-receptor antagonist (famotidine) |
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HMG-CoA reductase inhibitor (rosuvastatin) |
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Proton-pump inhibitor (omeprazole) |
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Source: FDA. Epclusa (sofosbuvir and velpatasvir) tablets, for oral use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208341s000lbl.pdf [accessed 2019 May 9] |
Sofosbuvir/Velpatasvir/Voxilaprevir
HCV Guideline Committee, May 2019
Table 37: Sofosbuvir/Velpatasvir/Voxilaprevir (Vosevi) Drug-Drug Interactions |
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Avoid co-administration; see clinical comments | |
Class (medications) | Clinical Comments |
Antiarrhythmic (amiodarone) |
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Herbal product (St. John’s wort) |
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Anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin) |
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Antimycobacterials (rifampin, rifabutin, rifapentine) |
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HIV medications (efavirenz, atazanavir, tipranavir) |
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HMG-CoA reductase inhibitor (pitavastatin, rosuvastatin) |
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Immunosuppressant (cyclosporine) |
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Co-administration possible; see clinical comments | |
Class (medications) | Clinical Comments |
Acid reducing medications:
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Antiarrhythmic (digoxin) |
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HIV medication (tenofovir disoproxil fumarate [TDF]) |
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HMG-CoA reductase inhibitor (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin) |
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Source: FDA. Vosevi (sofosbuvir and velpatasvir and voxilaprevir) tablets, for oral use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209195s000lbl.pdf [accessed 2019 May 9] |
Drug-Drug Interactions Between DAAs and ARVs
HCV Guideline Committee, August 2020
Use of DAAs concurrently with ART may lead to clinically relevant drug interactions. Table 38, below, lists the potential drug-drug interactions between DAA regimens and select ART regimens and Box 3, below, lists other resources on drug-drug interactions in patients with HIV/HCV coinfection.
Tenofovir is a nucleoside reverse transcriptase inhibitor used extensively in the treatment of HIV and HBV. Tenofovir drug concentrations, when taken in the disoproxil fumarate form (TDF), are increased in the setting of renal failure and when taken with elvitegravir and cobicistat and are highest with concurrent ritonavir use [German et al. 2015]. Use of TDF with velpatasvir or ledipasvir also increases the level of tenofovir [FDA 2015, 2016a]. When ledipasvir/sofosbuvir is administered with TDF concurrently with efavirenz or ritonavir-boosted atazanavir or darunavir, the TDF exposure may increase even further, raising concern for development of TDF-related nephrotoxicity [German et al. 2014, 2015]. These interactions are also likely to occur with the sofosbuvir/velpatasvir combination [FDA 2016a]. In addition, the use of TDF with sofosbuvir/velpatasvir/voxilaprevir may also increase tenofovir levels; switching from TDF to TAF, changing TDF to ABC, or monitoring for adverse renal effects would be appropriate in this setting [FDA 2017].
Close monitoring of creatinine clearance is recommended when ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, or sofosbuvir/velpatasvir/voxilaprevir must be co-administered with TDF and efavirenz or a ritonavir-boosted protease inhibitor. Care providers should consider changing the patient’s ART regimen by switching from TDF to TAF or abacavir if the HIV virus is susceptible to these drugs. TAF is associated with much lower peak serum tenofovir concentrations [Garrison et al. 2015]. The current FDA label allows TAF formulations to be used in patients whose CrCl is as low as 30 mL/min [FDA 2016a].
Box 3: Online Resources for Identifying Drug-Drug Interactions between DAAs and ARVs |
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Table 38: Compatibility of Select ART and DAA Regimens [a] for Nonpregnant Adults (August 2020) | |
ART Regimen | Concurrent DAA Regimen and Clinical Comment |
Preferred Initial ART Regimens | |
Abacavir/lamivudine/dolutegravir (ABC/3TC/DTG; Triumeq) |
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Tenofovir alafenamide/ emtricitabine/bictegravir (TAF 25 mg/FTC/BIC; Biktarvy) |
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Tenofovir alafenamide/emtricitabine and dolutegravir (TAF 25 mg/FTC and DTG; Descovy and Tivicay) |
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Tenofovir alafenamide/emtricitabine and raltegravir (TAF 25 mg/FTC and RAL HD; Descovy and Isentress HD) |
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Alternative Initial ART Regimens [b] | |
Tenofovir alafenamide/ emtricitabine/cobicistat/darunavir (TAF 10 mg/FTC/COBI/DRV; Symtuza) |
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Tenofovir alafenamide/ emtricitabine/cobicistat/elvitegravir (TAF 10 mg/FTC/COBI/EVG; Genvoya) |
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Tenofovir alafenamide/ emtricitabine/rilpivirine (TAF 25 mg/FTC/RPV; Odefsey) |
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Tenofovir disoproxil fumarate/ lamivudine/doravirine (TDF/3TC/DOR; Delstrigo) |
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Abacavir/lamivudine and doravirine (ABC/3TC and DOR; Epzicom and Pifeltro) |
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Tenofovir alafenamide/ emtricitabine and doravirine (TAF 25 mg/FTC and DOR; Descovy and Pifeltro) |
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Tenofovir disoproxil fumarate/ emtricitabine and dolutegravir (TDF/FTC and DTG; Truvada and Tivicay) |
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Tenofovir disoproxil fumarate/ emtricitabine and raltegravir (TDF/FTC and RAL HD; Truvada and Isentress HD) |
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ARV abbreviation key: Abacavir (ABC); bictegravir (BIC); cobicistat (COBI); darunavir (DRV); dolutegravir (DTG); elvitegravir (EVG); emtricitabine (FTC); lamivudine (3TC); raltegravir (RAL); rilpivirine (RPV); tenofovir alafenamide (TAF); tenofovir disoproxil fumarate (TDF). Notes:
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As new drug approvals for HIV ARVs and HCV DAAs continue, it is important that clinicians stay current on potential drug-drug interactions. Useful online resources for looking up potential drug-drug interactions and for monitoring for new information on drug-drug interactions are listed in Box 3, above.
References
FDA. Harvoni (ledipasvir and sofosbuvir) tablets, for oral use. 2015 Mar. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205834s024lbl.pdf [accessed 2017 Dec 18]
FDA. Descovy (emtricitabine/tenofovir alafenamide). 2016a Dec 30. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208215Orig1_toc.cfm [accessed 2017 Dec 18]
FDA. Vosevi (sofosbuvir, velpatasvir, and voxilaprevir) tablets, for oral use. 2017 Jul. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209195s000lbl.pdf [accessed 2017 Dec 19]
Garrison KL, Custodio JM, Pang PS, et al. Drug interactions between anti-HCV antivirals ledipasvir/sofosbuvir and integrase strand transfer inhibitor-based regimens. 16th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy; 2015 May 26-28; Washington, DC. http://www.natap.org/2015/Pharm/Pharm_32.htm
German P, Pang PS, West S, et al. Drug interactions between direct-acting anti-HCV antivirals sofosbuvir and ledipasvir and HIV antiretrovirals. 15th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy; 2014 May 19-21; Washington, DC. http://www.natap.org/2014/Pharm/Pharm_17.htm
German P, Garrison K, Pang PS, et al. Drug-drug interactions between anti-HCV regimen ledipasvir/sofosbuvir and antiretrovirals. CROI; 2015 Feb 23-26; Seattle, WA. http://www.croiconference.org/sessions/drug-drug-interactions-between-anti-hcv-regimen-ledipasvirsofosbuvir-and-antiretrovirals