Drug-Drug Interactions

• American Association for the Study of Liver Diseases (AASLD)/Infectious Diseases Society of America (IDSA): Includes charts listing all DAAs
• University of Liverpool HEP Drug Interactions: Provides guidance on managing HCV drug interactions, especially in those coinfected with HIV; may not include all medications available in the United States

• Carbamazepine: Significant decrease in glecaprevir/pibrentasvir levels expected
• Phenobarbital, phenytoin: Significant decrease in glecaprevir/pibrentasvir levels possible

• Significant decrease in glecaprevir/pibrentasvir levels expected

• Increased risk of ALT elevations

• Decreased glecaprevir/pibrentasvir levels expected

• 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

• Increased levels of atorvastatin, lovastatin, and simvastatin expected; do not co-administer
• See note below regarding use of alternative statins

• Increased digoxin levels likely; reduce digoxin dosage 50%
• Measure serum digoxin level prior to initiating therapy with glecaprevir/pibrentasvir

• Refer to dabigatran prescribing information; follow dosage recommendations for concurrent use with P-glycoprotein inhibitors

• 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

• Increased levels of glecaprevir/pibrentasvir expected; do not co-administer in patients requiring cyclosporine doses >100 mg daily

• 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

• Significant decrease in ledipasvir/sofosbuvir levels

• Significant decrease in ledipasvir/sofosbuvir levels

• Significant decrease in ledipasvir/sofosbuvir levels

• Significant increase in rosuvastatin level

• Significant increases in ledipasvir levels

• Ledipasvir solubility decreases as pH increases
• Separate administration of aluminum- and magnesium-containing antacids and ledipasvir/sofosbuvir by 4 hours

• Increase in digoxin level expected
• Monitor digoxin level

• Administer simultaneously with, or 12 hours apart from, ledipasvir/sofosbuvir
• Do not exceed doses comparable to famotidine 40 mg twice daily 

• If co-administration is required, doses comparable to omeprazole 20 mg or lower can be administered simultaneously with ledipasvir/sofosbuvir under fasting conditions

• 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

• Significant decrease in sofosbuvir level expected, leading to reduced sofosbuvir and/or velpatasvir drug levels

• Potential significant decrease in sofosbuvir and/or velpatasvir drug levels

• May significantly decrease sofosbuvir and/or velpatasvir drug levels

• May decrease concentration of velpatasvir
• Separate administration of antacid and velpatasvir/sofosbuvir by 4 hours

• Increase in digoxin level expected
• Monitor digoxin level

• Significant increase in topotecan expected

• 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

• 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

• 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

• 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

• Significant decrease in sofosbuvir/velpatasvir/voxilaprevir levels

• Significant decrease in sofosbuvir/velpatasvir/voxilaprevir levels

• Significant decrease in sofosbuvir/velpatasvir/voxilaprevir levels

• 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

• Significant increase in pitavastatin and rosuvastatin levels expected when combined with sofosbuvir/velpatasvir/voxilaprevir

• Significant increases in cyclosporine level expected

Acid reducing medications:

• Aluminum- and magnesium hydroxide- containing antacids
• H2-receptor antagonists
• Proton pump inhibitor

• 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

• Sofosbuvir/velpatasvir/voxilaprevir may increase digoxin levels; monitor digoxin levels closely prior to and during therapy

• Significant increase in TDF levels expected; monitor for tenofovir-related adverse events

• 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

• Northeast Caribbean AETC Antiretroviral Clinical Support Tools: DAA Drug Interactions Quick Guides for Clinicians:
  • Glecaprevir/pibrentasvir (Mavyret)
  • Ledipasvir/sofosbuvir (Harvoni)
  • Sofosbuvir/velpatasvir (Epclusa)
  • Sofosbuvir/velpatasvir/voxilaprevir (Vosevi)
• HCV Guidance: American Association for the Study of Liver Diseases (AASLD)/Infectious Diseases Society of America (IDSA): Includes charts listing all DAAs and their compatibility with ARVs
• University of Liverpool HEP Drug Interactions: Provides guidance on managing HCV drug interactions, especially in those who also have HIV; may not include all medications available in the United States)

• All DAA regimens are compatible.

• All DAA regimens are compatible.

• All DAA regimens are compatible, but see note [g] regarding concomitant use of LED or VEL and tenofovir.

• All DAA regimens are compatible, but see note [g] regarding concomitant use of LED or VEL and tenofovir.

• All DAA regimens are compatible.
• GLE/PIB may increase the serum concentration of RAL but no action is needed.
• See note [g] regarding concomitant use of LED or VEL and tenofovir.

• Do not co-administer with GLE/PIB.
• When combining SOF/VEL/VOX with COBI-boosted DRV, levels of VOX may be increased. Until more safety data become available, patients who are taking the combination should be monitored for hepatotoxicity during therapy.
• See note [g] regarding concomitant use of LED or VEL and tenofovir.

• When combining GLE/PIB with COBI-boosted EVG, levels of GLE/PIB may be increased. Until more safety data become available, patients who are taking the combination should be monitored for hepatotoxicity during therapy.
• See note [g] regarding concomitant use of LED or VEL and tenofovir.

• All DAA regimens are compatible, but see note [g] regarding concomitant use of LED or VEL and tenofovir.

• All DAA regimens are considered to be compatible, but there are limited data evaluating the use of DOR with SOF/VEL or GLE/PIB.
• See note [g] regarding concomitant use of LED or VEL and tenofovir.

• All DAA regimens are considered to be compatible, but there are limited data evaluating the use of DOR with SOF/VEL or GLE/PIB.

• All DAA regimens are considered to be compatible, but there are limited data evaluating the use of DOR with SOF/VEL or GLE/PIB.
• See note [g] regarding concomitant use of LED or VEL and tenofovir.

• All DAA regimens are compatible, but see note [g] regarding concomitant use of LED or VEL and tenofovir.

Abbreviations: 3TC, lamivudine; ABC, abacavir; BIC, bictegravir; COBI, cobicistat; DRV, darunavir; DTG, dolutegravir; EVG, elvitegravir; FTC, emtricitabine; RAL, raltegravir; RPV, rilpivirine; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.

Notes:

1. Refer to DHHS for ART regimens for individuals of childbearing potential: Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the United States.
2. See the NYSDOH AI guideline Selecting an Initial ART Regimen.
3. Available DAA regimens as of October 2021: Glecaprevir/pibrentasvir (GLE/PIB; Mavyret); ledipasvir/sofosbuvir (LED/SOF; multiple brands); sofosbuvir/velpatasvir (SOF/VEL; multiple brands); sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX; Vosevi).
4. See Use of Dolutegravir in Individuals of Childbearing Capacity.
5. Substitutions: In all cases, FTC and 3TC are interchangeable; TAF 10 mg and TAF 25 mg are not interchangeable.
6. For dose adjustments, refer to the NYSDOH AI guideline Selecting an Initial ART Regimen > Table 9: Recommended Dose Adjustments for Use of Selected Fixed-Dose Combination Antiretroviral Medications in Patients With Hepatic or Renal Impairment.
7. Concomitant use of LED or VEL and tenofovir: When using TAF or TDF concurrently with a DAA regimen containing LED or VEL, renal function should be evaluated with CrCl testing at baseline and 4 weeks after the start of DAA treatment. When LED or VEL is taken with TDF or TAF, the serum concentration of tenofovir may be increased, which may lead to tenofovir-related renal side effects. Concurrent use of a LED- or VEL-containing DAA and TDF should be avoided in patients with a CrCl < 50 mL/min. Options include switching TDF to TAF [c], substituting ABC if patient is HLAB*5701 negative and has no evidence of ABC resistance, or using a different DAA regimen.