HCV Guideline Committee, May 2019
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 Treatment of Patients with HIV/HCV Coinfection > Drug-Drug Interactions between DAAs and ARVs section of this guideline.
| KEY POINT |
- Although significant interactions associated with the use of direct-acting antivirals (DAAs) and drugs used commonly in the treatment of substance use disorders are unlikely, care providers should always monitor for excess sedation when making alterations to a patient’s drug therapy while he/she is taking methadone, buprenorphine, naltrexone, and naloxone.
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The links below open pages with tables for each of the following drugs:
| Box 2: Online Resources for Identifying Drug-Drug Interactions between DAAs and Common Medications |
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Note: As of May 2019, the following DAAs are no longer used in the United States: PIs: paritaprevir, simeprevir, telaprevir, boceprevir; NS5A inhibitors: daclatasvir, ombitasvir; NS5V inhibitor: dasabuvir.
Elbasvir/Grazoprevir
HCV Guideline Committee, May 2019
| Table 34: Elbasvir/Grazoprevir (Zepatier) Drug-Drug Interactions |
| Avoid co-administration; see clinical comments |
| Class (medications) |
Clinical Comments |
| Anticonvulsants (carbamazepine, phenytoin) |
- Significant decrease in elbasvir/grazoprevir levels
|
| Antimycobacterial (rifampin) |
- Significant decrease in elbasvir/grazoprevir levels
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| Herbal product (St. John’s wort) |
- Significant decrease in elbasvir/grazoprevir levels
|
| HIV medications (efavirenz, atazanavir, darunavir, lopinavir, saquinavir, tipranavir) |
- Efavirenz: Significant decrease in elbasvir/grazoprevir levels
- Atazanavir, darunavir, lopinavir, saquinavir, tipranavir: Significant increase in grazoprevir level
- May lead to ALT elevation
|
| Immunosuppressant (cyclosporine) |
- Significant increase in grazoprevir level
- May lead to ALT elevation
|
| Co-administration possible; see clinical comments |
| Class (medications) |
Clinical Comments |
| Antibiotic (nafcillin) |
- Decreased concentrations of elbasvir/grazoprevir levels
|
| Antifungal (ketoconazole) |
- Significant increase in elbasvir/grazoprevir levels
- Increased risk of hepatotoxicity
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| Endothelin antagonist (bosentan) |
- Significant decrease in elbasvir/grazoprevir levels
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| HMG-CoA reductase inhibitors (atorvastatin, fluvastatin, lovastatin, rosuvastatin, simvastatin) |
- Increase in statin drug levels expected
- Atorvastatin: Maximum daily dose 20 mg
- Fluvastatin, lovastatin, or simvastatin: Use lowest doses possible; titrate with close monitoring
- Rosuvastatin: Maximum daily dose 10 mg
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| Immunosuppressant (tacrolimus) |
- Significant increase in tacrolimus level expected
- Frequent monitoring required for tacrolimus level, changes in renal function, and tacrolimus-associated adverse events
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| Wakefulness-promoting agent (modafinil) |
- Significant decrease in elbasvir/grazoprevir levels
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| Source: U.S. Food and Drug Administration. Zepatier (elbasvir and grazoprevir) tablets, for oral use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208261Orig1s000lbl.pdf [accessed 2019 May 9] |
Glecaprevir/Pibrentasvir
HCV Guideline Committee, May 2019
| Table 35: Glecaprevir/Pibrentasvir (Mavyret) Drug-Drug Interactions |
| Avoid co-administration; see clinical comments |
| Class (medications) |
Clinical Comments |
| Anticonvulsants (carbamazepine, phenobarbital, phenytoin) |
- Carbamazepine: Significant decrease in glecaprevir/pibrentasvir levels expected
- Phenobarbital, phenytoin: Significant decrease in glecaprevir/pibrentasvir levels possible
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| Antimycobacterial (rifampin) |
- Significant decrease in glecaprevir/pibrentasvir levels expected
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| Ethinyl estradiol |
- Increased risk of ALT elevations
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| Herbal therapy (St. John’s Wort) |
- Decreased glecaprevir/pibrentasvir levels expected
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| HIV medications (efavirenz, atazanavir, darunavir, lopinavir, saquinavir, tipranavir) |
- Efavirenz: Significant decrease in glecaprevir/pibrentasvir levels expected
- Atazanavir: Significant increase in glecaprevir/pibrentasvir levels expected; increased ALT elevations
- Darunavir, lopinavir/ritonavir, other HIV protease inhibitors: Significant increase in glecaprevir/pibrentasvir levels expected
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| HMG-CoA reductase inhibitors (atorvastatin, lovastatin, simvastatin) |
- Increased levels of atorvastatin, lovastatin, and simvastatin expected; do not co-administer
- See note below regarding use of alternative statins
|
| Co-administration possible; see clinical comments |
| Class (medications) |
Clinical Comments |
| Antiarrhythmic (digoxin) |
- Increased digoxin levels likely; reduce digoxin dosage 50%
- Measure serum digoxin level prior to initiating therapy with glecaprevir/pibrentasvir
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| Anticoagulant (dabigatran etexilate) |
- Refer to dabigatran prescribing information; follow dosage recommendations for concurrent use with P-glycoprotein inhibitors
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| HMG-CoA reductase inhibitors (fluvastatin, pitavastatin, pravastatin, rosuvastatin) |
- Fluvastatin, pitavastatin: Increased statin levels likely; use lowest statin dosage and monitor for adverse events (e.g., myopathy)
- Pravastatin: Increased statin level likely; reduce pravastatin dosage by 50% prior to initiating therapy with glecaprevir/pibrentasvir
- Rosuvastatin: Increased statin level likely; do not exceed rosuvastatin 10 mg daily when combined with glecaprevir/pibrentasvir
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| Immunosuppressant (cyclosporine) |
- Increased levels of glecaprevir/pibrentasvir expected; do not co-administer in patients requiring cyclosporine doses >100 mg daily
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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 36: Ledipasvir/Sofosbuvir (multiple brands) Drug-Drug Interactions |
| Avoid co-administration; see clinical comments |
| Class (medications) |
Clinical Comments |
| Antiarrhythmic (amiodarone) |
- Significant bradycardia, especially in patients who are taking beta-blockers, have underlying cardiac abnormalities, or have advanced liver disease
- If concurrent use is required, cardiac monitoring is recommended
- See package insert for additional information
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| Herbal product (St. John’s wort) |
- Significant decrease in ledipasvir/sofosbuvir levels
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| Anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin) |
- Significant decrease in ledipasvir/sofosbuvir levels
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| Antimycobacterials (rifampin, rifabutin, rifapentine) |
- Significant decrease in ledipasvir/sofosbuvir levels
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| HMG-CoA reductase inhibitor (rosuvastatin) |
- Significant increase in rosuvastatin level
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| NS3/4A HCV protease inhibitor (simeprevir) |
- Significant increases in ledipasvir levels
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| Co-administration possible; see clinical comments |
| Class (medications) |
Clinical Comments |
| Antacids |
- Ledipasvir solubility decreases as pH increases
- Separate administration of aluminum- and magnesium-containing antacids and ledipasvir/sofosbuvir by 4 hours
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| Antiarrhythmic (digoxin) |
- Increase in digoxin level expected
- Monitor digoxin level
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| H2-receptor antagonists |
- Administer simultaneously with, or 12 hours apart from, ledipasvir/sofosbuvir
- Do not exceed doses comparable to famotidine 40 mg twice daily
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| Proton-pump inhibitors |
- If co-administration is required, doses comparable to omeprazole 20 mg or lower can be administered simultaneously with ledipasvir/sofosbuvir under fasting conditions
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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
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Table 37: Sofosbuvir/Velpatasvir (multiple brands) Drug-Drug Interactions
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| Avoid co-administration; see clinical comments |
| Class (medications) |
Clinical Comments |
| Antiarrhythmic (amiodarone) |
- Significant bradycardia, especially in patients who are taking beta-blockers, have underlying cardiac abnormalities, or have advanced liver disease
- If concurrent use is required, cardiac monitoring is recommended
- See package insert for additional information
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| Anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin) |
- Significant decrease in sofosbuvir level expected, leading to reduced sofosbuvir and/or velpatasvir drug levels
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| Antimycobacterials (rifampin, rifabutin, rifapentine) |
- Potential significant decrease in sofosbuvir and/or velpatasvir drug levels
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| Herbal product (St. John’s wort) |
- May significantly decrease sofosbuvir and/or velpatasvir drug levels
|
| Co-administration possible; see clinical comments |
| Class (medications) |
Clinical Comments |
| Antacids (aluminum and magnesium hydroxide) |
- May decrease concentration of velpatasvir
- Separate administration of antacid and velpatasvir/sofosbuvir by 4 hours
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| Antiarrhythmic (digoxin) |
- Increase in digoxin level expected
- Monitor digoxin level
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| Anticancer (topotecan) |
- Significant increase in topotecan expected
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| H2-receptor antagonist (famotidine) |
- Velpatasvir solubility decreases as pH increases
- May decrease concentration of velpatasvir
- H2-receptor antagonists may be administered simultaneously with, or 12 hours apart from velpatasvir/sofosbuvir, at a dose that does not exceed doses comparable to famotidine 40 mg twice daily
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| HMG-CoA reductase inhibitor (rosuvastatin) |
- May significantly increase the concentration of rosuvastatin, which is associated with increased risk of myopathy, including rhabdomyolysis
- Rosuvastatin may be administered at a dose not greater than 10 mg daily
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| Proton-pump inhibitor (omeprazole) |
- May decrease concentration of velpatasvir
- Proton-pump inhibitor doses comparable to omeprazole 20 mg or lower can be administered simultaneously with velpatasvir/sofosbuvir under fasting conditions
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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
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Table 38: Sofosbuvir/Velpatasvir/Voxilaprevir (Vosevi) Drug-Drug Interactions
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| Avoid co-administration; see clinical comments |
| Class (medications) |
Clinical Comments |
| Antiarrhythmic (amiodarone) |
- Potential for significant bradycardia, especially in patients who are taking beta-blockers, have underlying cardiac abnormalities, or have advanced liver disease If concurrent use is required, cardiac monitoring is recommended
|
| Herbal product (St. John’s wort) |
- Significant decrease in sofosbuvir/velpatasvir/voxilaprevir levels
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| Anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin) |
- Significant decrease in sofosbuvir/velpatasvir/voxilaprevir levels
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| Antimycobacterials (rifampin, rifabutin, rifapentine) |
- Significant decrease in sofosbuvir/velpatasvir/voxilaprevir levels
|
| HIV medications (efavirenz, atazanavir, tipranavir) |
- Efavirenz: Significant decrease in velpatasvir and voxilaprevir levels expected
- Atazanavir: Significant increase in voxilaprevir level expected
- Tipranavir: Significant decrease in sofosbuvir and voxilaprevir levels expected
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| HMG-CoA reductase inhibitor (pitavastatin, rosuvastatin) |
- Significant increase in pitavastatin and rosuvastatin levels expected when combined with sofosbuvir/velpatasvir/voxilaprevir
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| Immunosuppressant (cyclosporine) |
- Significant increases in cyclosporine level expected
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| Co-administration possible; see clinical comments |
| Class (medications) |
Clinical Comments |
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Acid reducing medications:
- Aluminum- and magnesium hydroxide- containing antacids
- H2-receptor antagonists
- Proton pump inhibitor
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- Separate administration of antacids and sofosbuvir/velpatasvir/voxilaprevir by 4 hours
- H2-receptor antagonists may be administered simultaneously with or staggered from sofosbuvir/velpatasvir/voxilaprevir at a dose that does not exceed a comparable dose of famotidine 40 mg twice daily
- Omeprazole 20 mg can be administered with sofosbuvir/velpatasvir/voxilaprevir:
- Use with other proton pump inhibitors has not been studied
- Use with lowest doses of other proton pump inhibitors is unlikely to interact
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| Antiarrhythmic (digoxin) |
- Sofosbuvir/velpatasvir/voxilaprevir may increase digoxin levels; monitor digoxin levels closely prior to and during therapy
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| HIV medication (tenofovir disoproxil fumarate [TDF]) |
- Significant increase in TDF levels expected; monitor for tenofovir-related adverse events
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| HMG-CoA reductase inhibitor (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin) |
- Atorvastatin, fluvastatin, lovastatin, simvastatin: Potential increase levels of statins when combined with sofosbuvir/velpatasvir/voxilaprevir; use lowest statin dosage
- Pravastatin: Potential increased levels of pravastatin when combined with sofosbuvir/velpatasvir/voxilaprevir; do not exceed pravastatin 40 mg daily when combined
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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] |
