HCV CARE

Hepatitis C Virus Infection Guideline Committee, July 2017

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 judgement 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 an experienced HCV care provider for additional guidance.

KEY POINT
  • Though 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.

The links below open pages with tables for each of the following drugs:

Daclatasvir

Hepatitis C Virus Infection Guideline Committee, July 2017

Table 35. Daclatasvir Drug-Drug Interactions
Avoid co-administration; see clinical comments
Class (medications) Clinical comments
Antiarrhythmics (amiodarone)
  • Serious symptomatic bradycardia may occur if used concomitantly with sofosbuvir and daclatasvir
  • Concurrent use not recommended
Anticonvulsants (carbamazepine, phenytoin) Significant decrease in daclatasvir level
Antimycobacterial (rifampin) Significant decrease in daclatasvir level
Herbal product (St. John’s wort) Significant decrease in daclatasvir level
Co-administration possible; see clinical comments
Class (medications) Clinical comments

Strong inhibitors of cytochrome 3A metabolic system (CYP3A):

  • Antibiotics (clarithromycin, telithromycin)
  • Antifungals (itraconazole, ketoconazole, posaconazole, voriconazole)
  • Antidepressant (nefazodone)
  • Strong CYP3A inhibitors are expected to increase daclatasvir levels
  • Decrease daclatasvir dose to 30 mg once daily

Moderate inducers of CYP3A:

  • Antibiotic (nafcillin)
  • Antimycobacterial (rifapentine)
  • Corticosteroid (dexamethasone)
  • Endothelin antagonist (bosentan)
  • Wakefulness-promoting agent (modafinil)
  • Moderate CYP3A inducers are expected to decrease daclatasvir levels
  • Increase daclatasvir dose to 90 mg once daily
Anticoagulant (dabigatran)
  • Potential for increased dabigatran level in patients with renal impairment
  • See dabigatran label for further information
Antiarrhythmics (digoxin)
  • If already taking daclatasvir and initiating digoxin:
    • Use lowest digoxin dose possible
    • Monitor level
    • Titrate as needed
  • If already taking digoxin and initiating daclatasvir:
    • Measure serum digoxin level prior to starting daclatasvir
    • Reduce digoxin dose by 15% to 30%
    • Monitor level
    • Titrate as needed

HMG-CoA reductase inhibitors (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin)

  • Increased HMG-CoA reductase inhibitor drug levels
  • Monitor for adverse events such as myopathy
Narcotic analgesics (buprenorphine, buprenorphine/naloxone)
  • Increased narcotic analgesic drug levels expected
  • No dose adjustment required
  • Clinical monitoring recommended
Source: FDA. Highlights of Prescribing Information: Daklinza (daclatasvir) tablets, for oral use. Accessed July 3, 2017.

Elbasvir/Grazoprevir

Hepatitis C Virus Infection Guideline Committee, July 2017

Table 34. Elbasvir/Grazoprevir 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
Herbal product (St. John’s wort) Significant decrease in elbasvir/grazoprevir levels
IV 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
Endothelin antagonist (bosentan) Significant decrease in elbasvir/grazoprevir levels
HMG-CoA reductase inhibitors (atorvastatin, fluvastatin, lovastatin, rosuvastatin, simvastatin)
  • Increase in statin drug levels expected
  • Atorvastatin: Max daily dose 20 mg
  • Fluvastatin, lovastatin, or simvastatin: Use lowest doses possible; titrate with close monitoring
  • Rosuvastatin: Max daily dose 10 mg 
Immunosuppressant (tacrolimus)
  • Significant increase in tacrolimus level expected
  • Frequent monitoring required for tacrolimus level, changes in renal function, and tacrolimus-associated adverse events
Wakefulness-promoting agent (modafinil) Significant decrease in elbasvir/grazoprevir levels
Source: FDA. Highlights of Prescribing Information: Zepatier (elbasvir and grazoprevir) tablets, for oral use.  Accessed July 3, 2017.

Ledipasvir/Sofosbuvir

Hepatitis C Virus Infection Guideline Committee, July 2017

Table 31. Ledipasvir/Sofosbuvir 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
Herbal product (St. John’s wort) Significant decrease in ledipasvir/sofosbuvir level
Anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin) Significant decrease in ledipasvir/sofosbuvir level
Antimycobacterials (rifampin, rifabutin, rifapentine) Significant decrease in ledipasvir/sofosbuvir level
HMG-CoA reductase inhibitor (rosuvastatin) Significant increase in rosuvastatin level
NS3/4A HCV protease inhibitor (simeprevir) Significant increases in ledipasvir and simeprevir level
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
Antiarrhythmic (digoxin)
  • Increase in digoxin level expected
  • Monitor digoxin level
H2-receptor antagonists 
  • Administer simultaneously with, or 12 hours apart from, ledipasvir/ sofosbuvir
  • Do not exceed doses comparable to famotidine 40 mg twice daily 
Proton-pump inhibitors  If coadministration is required, doses comparable to omeprazole 20 mg or lower can be administered simultaneously with ledipasvir/sofosbuvir under fasting conditions
Source: FDA. Highlights of prescribing information: Harvoni (ledipasvir and sofosbuvir) tablets, for oral use. Accessed July 2, 2017.

Ombitasvir/Paritaprevir/ Ritonavir/Dasabuvir

Hepatitis C Virus Infection Guideline Committee, July 2017

Table 30. Ombitasvir/Paritaprevir/Ritonavir/Dasabuvir (PrOD) Drug-Drug Interactions
Avoid co-administration; see clinical comments 
Class (medications) Clinical Comments
Alpha 1-antagonist (alfuzosin)
  • Significant increase in alfuzosin level
  • Potential for severe hypotension
Antianginal (ranolazine) Significant increase in ranolazine level
Antiarrhythmics (amiodarone, dronedarone, dofetilide, disopyramide, flecainide, lidocaine, mexiletine, propafenone, quinidine)
  • Increased antiarrhythmic drug levels, potential for cardiac arrhythmias
  • Therapeutic concentration monitoring of antiarrhythmic drug level recommended if available
Anticonvulsants (carbamazepine, oxcarbazepine, phenytoin, phenobarbital)  Significant decrease in PrOD levels 
Antigout (colchicine)
  • Significant increase in colchicine level
  • Potential for renal impairment and pancytopenia 
 Antihyperlipidemic (gemfibrozil)  Significant (10-fold) increase in dasabuvir level leading to increased risk of QT prolongation 
Antimycobacterial (rifampin)
  • Significant decrease in PrOD levels
  • Potential for HCV treatment failure 
Antipsychotics, 1st generation, typical (pimozide, lurasidone)

Significant increase in antipsychotic levels

Ergot derivatives (ergotamine, dihydroergot-amine, ergonovine, methylergonovine) Significant increase in ergot derivative level leading to acute ergot toxicity
Ethinyl estradiol containing products (oral contraceptives)
  • Significant increase in PrOD level
  • Alanine transaminase (ALT) elevations associated with concurrent use of ethinyl estradiol
Herbal product (St. John’s wort) Significant decrease in PrOD levels
HIV medication (efavirenz)
  • Co-administration of efavirenz-based regimens with paritaprevir, ritonavir plus dasabuvir poorly tolerated
  • Results in liver enzyme elevation
HMG-CoA reductase inhibitors (atorvastatin, lovastatin, simvastatin)
  • Significant increase in atorvastatin, lovastatin and simvastatin levels
  • Potential for rhabdomyolysis
Immunosuppressants (everolimus, sirolimus, tacrolimus) Increased potential for immunosuppressant-associated adverse events
Phosphodiesterase-5 inhibitors (sildenafil, when used in pulmonary arterial hypertension) Increased potential for sildenafil adverse events, such as priapism, visual disturbances, and hypotension
Sedative/hypnotics (oral midazolam, triazolam) Significant increases in oral midazolam or triazolam level
Co-administration possible; see clinical comment
Class (medications) Clinical Comments
Angiotensin receptor blockers (ARBs) (candesartan, olmesartan, telmisartan)
  • Increased ARB drug levels
  • Consider ARB dose reduction
  • Monitor closely for hypotension
Antifungal (oral ketoconazole, voriconazole)
  • Oral ketoconazole: Increase in ketoconazole level; dose should not exceed 200 mg in a 24-hour period
  • Voriconazole: Significant decrease in voriconazole level
Antipsychotic, 2nd generation, atypical (quetiapine)
  • Significant increase in quetiapine level
  • Consider alternative HCV therapy or reduce quetiapine dose to 1/6 of current dose
  • Monitor for adverse events, including increased blood pressure
Beta adrenoceptor agonist (long-acting salmeterol)
  • Significant increase in salmeterol level
  • Monitor for QT prolongation, palpitations, and sinus tachycardia
Calcium channel blockers (CCBs) (amlodipine, diltiazem, felodipine, nicardipine, nifedipine, nisoldipine, verapamil) 
  • Increased CCB drug levels
  • Consider CCB drug dose reduction
  • Monitor closely for hypotension and bradycardia
Corticosteroids (inhaled or nasal fluticasone)  With nasal or inhaled use, significant increase in fluticasone level, which can lead to Cushing’s Syndrome 
Diuretic (furosemide) 
  • Possible increase in furosemide level
  • Monitor closely based upon response
HMG-CoA reductase inhibitors (atorvastatin, pravastatin, rosuvastatin)
  • Increased HMG-CoA reductase inhibitor drug levels
  • Atorvastatin: Do not exceed 20 mg in a 24-hour period
  • Pravastatin: Do not exceed 40 mg in a 24-hour period
  • Rosuvastatin: Do not exceed 10 mg in a 24-hour period
Immunosuppressants (cyclosporine, tacrolimus) 
  • Increase in cyclosporine and tacrolimus levels
  • Interactions are complex; consult PrOD package insert for additional dosing guidance
Muscle relaxants (carisoprodol, cyclobenzaprine)
  • Decrease in muscle relaxant drug levels
  • Consider increasing dose of muscle relaxant if clinically indicated
Narcotic analgesics (buprenorphine/naloxone, acetaminophen/hydrocodone)
  • Buprenorphine/naloxone: Monitor for sedation
  • Acetaminophen/hydrocodone: Reduce hydrocodone dose by 50%
    • Monitor for respiratory depression and sedation
Phosphodiesterase-5 inhibitors, when used for erectile dysfunction (sildenafil, tadalafil, vardenafil)
  • Increase in phosphodiesterase-5 inhibitor drug level
  • Sildenafil: Do not exceed 25 mg in a 48-hour period
  • Tadalafil: Do not exceed 10 mg in a 72-hour period
  • Vardenafil: Do not exceed 2.5 mg in a 72-hour period
Proton-pump inhibitor (omeprazole) 
  • Decrease in omeprazole level
  • Consider increase in omeprazole dose for patients not well controlled
  • Do not exceed omeprazole 40 mg daily equivalent 
Sedative/hypnotics (alprazolam,  diazepam)
  • Alprazolam: Increase in drug level
    • Monitor for excess sedation
    • Consider decrease in alprazolam dose
  • Diazepam: Decrease in drug level
    • Consider increase in diazepam dose if clinically indicated
Source: FDA. Highlights of Prescribing Information: Viekira XR (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets, for oral use. Accessed July 3, 2017.

Simepravir

Hepatitis C Virus Infection Guideline Committee, July 2017

Table 32. Simeprevir Drug-Drug Interactions
Avoid co-administration; see clinical comments
Class (medications) Clinical comments
Antiarrhythmics (amiodarone, disopyramide, flecainide, mexiletine, propafenone, quinidine)
  • 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
    • Consult package insert for additional information
  • Disopyramide, flecainide, mexiletine, propafenone, quinidine: Increase in antiarrhythmic drug levels
    • Therapeutic concentration monitoring of antiarrhythmic drug levels recommended if possible
Anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin) Significant decrease in simeprevir level leading to reduced simeprevir efficacy
Antibiotics (clarithromycin, erythromycin, telithromycin) Significant increase in simeprevir or antibiotic level due to CYP3A4 and P-glycoprotein inhibition
Antifungals (oral or IV: fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole) Significant increase in simeprevir level due to CYP3A4 inhibition from antifungals
Antimycobacterials (rifampin, rifabutin, rifapentine) Significant decrease in simeprevir level leading to reduced simeprevir efficacy
GI motility agent (cisapride; limited availability in the U.S.)
  • Significant increase in cisapride level
  • Potential for cardiac arrhythmias
Herbal products (milk thistle, St. John’s wort)
  • Milk thistle: Significant increase in simeprevir level
  • St. John’s wort: Significant decrease in simeprevir level
Immunosuppressant (cyclosporine) Significant increase in simeprevir and cyclosporine levels, leading to adverse effects of both medications
Co-administration possible; see clinical comments
Class (medications) Clinical comments
Antiarrhythmics  (digoxin)
  • Increase in digoxin level expected
  • Monitor digoxin level
Calcium channel blockers (amlodipine, diltiazem, felodipine, nicardipine, nifedipine, nisoldipine, verapamil)
  • Potential increase in CCB drug levels
  • Monitor for bradycardia and hypotension
Corticosteroid (dexamethasone) Significant decrease in simeprevir level leading to reduced simeprevir efficacy
HMG-CoA reductase inhibitors (lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin)
  • Lovastatin, pitavastatin, pravastatin, simvastatin: Use lowest dose possible; titrate carefully
  • Rosuvastatin: Increase in rosuvastatin level
    • Initiate with 5 mg daily; do not exceed 10 mg daily
Phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil)
  • Increase in phosphodiesterase-5 inhibitor levels
  • Use lowest dose possible
Sedative/hypnotics (oral midazolam, triazolam)
  • Use lowest doses possible
  • Titrate carefully
Source: FDA. Highlights of Prescribing Information: Olysio (simeprevir) capsules, for oral use. Accessed July 3, 2017.

Sofosbuvir

Hepatitis C Virus Infection Guideline Committee, July 2017

Table 33. Sofosbuvir 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
Anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin) Significant decrease in sofosbuvir level expected leading to reduced sofosbuvir efficacy
Antimycobacterials (rifampin, rifabutin, rifapentine) Significant decrease in sofosbuvir level expected leading to reduced sofosbuvir efficacy
Herbal product (St. John’s wort) Significant decrease in sofosbuvir level expected leading to reduced sofosbuvir efficacy
Source: FDA. Highlights of Prescribing Information: Sovaldi (sofosbuvir) tablets, for oral use. Accessed July 3, 2017.

Sofosbuvir and Velpatasvir

Hepatitis C Virus Infection Guideline Committee, July 2017

Table 36. Sofosbuvir and Velpatasvir 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
Anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin) Significant decrease in sofosbuvir level expected, leading to reduced sofosbuvir and/or velpatasvir drug levels
Antimycobacterials (rifampin, rifabutin, rifapentine) Potential significant decrease in sofosbuvir and/or velpatasvir drug levels
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
Antiarrhythmic (digoxin)
  • Increase in digoxin level expected
  • Monitor digoxin level
Anticancer (topotecan) Significant increase in topotecan expected
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
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
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
Source: FDA. Highlights of Prescribing Information: Epclusa (sofosbuvir and velpatasvir) tablets, for oral use. Accessed July 3, 2017.