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    NS3/4A Protease Inhibitor Antivirals in Combination with NS5A Protein Inhibitor Antivirals for Hepatitis C

    BOXED WARNING

    Hepatitis B exacerbation

    Use of direct-acting antivirals (DAA), such as glecaprevir and pibrentasvir, to treat hepatitis C virus (HCV) infection in patients currently or previously infected with hepatitis B virus (HBV) has been associated with reactivation and hepatitis B exacerbation. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Hepatitis B reactivation has also occurred in patients receiving certain immunosuppressive or chemotherapeutic medications; the risk of HBV reactivation associated with DAA treatment may be increased in these patients. HBV reactivation is characterized as an abrupt increase in viral replication manifesting as a rapid increase in serum HBV DNA concentration. In patients with resolved HBV infection, the reappearance of HBsAg can occur. Reactivation of HBV replication may be accompanied by hepatitis (i.e., increases in aminotransferase concentrations) and, in severe cases, increases in bilirubin concentrations, liver failure, and death can occur. To decrease the risk of reactivating an HBV infection, screen all potential drug recipients for evidence of current or prior HBV infection by measuring the hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc). For those patients whose screening reveals serologic evidence of HBV infection, a baseline HBV DNA concentration should be obtained prior to starting glecaprevir; pibrentasvir. Continue to monitor coinfected patients during and after treatment for clinical and laboratory signs of hepatitis B exacerbation (i.e., HBsAg, HBV DNA, hepatic enzymes, bilirubin). In addition, instruct patients to immediately report any signs of liver toxicity (e.g., yellow eyes or skin, fatigue, weakness, loss of appetite, nausea, vomiting, or light-colored stools) to their health care provider. If a glecaprevir; pibrentasvir recipient develops signs of HBV reactivation, initiate appropriate treatment for HBV infection as clinically indicated.

    DEA CLASS

    Rx

    DESCRIPTION

    Combination oral antiviral containing an HCV NS3/4A protease inhibitor and NS5A inhibitor
    For the treatment of chronic HCV infections (all genotypes) in adults and pediatric patients (12 years and older or weighing at least 45 kg) without cirrhosis or with compensated cirrhosis (Child-Pugh A)
    Contraindicated in patients with moderate to severe hepatic impairment and in those with any history of prior hepatic decompensation

    COMMON BRAND NAMES

    Mavyret

    HOW SUPPLIED

    Glecaprevir, Pibrentasvir/Mavyret Oral Tab: 100-40mg

    DOSAGE & INDICATIONS

    For the treatment of chronic hepatitis C infection in patients without cirrhosis or with compensated cirrhosis (Child-Pugh A).
    For treatment-naive patients with HCV genotype 1, 2, 3, 4, 5, or 6 infection.
    Oral dosage
    Adults

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 8 weeks. Guidelines recommend increasing the treatment duration to 12 weeks for patients with compensated cirrhosis and HCV/HIV coinfection.

    Children and Adolescents 12 to 17 years

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 8 weeks.

    Children younger than 12 years but weighing at least 45 kg

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 8 weeks.

    For treatment-experienced patients with HCV genotype 1 infection.
    Oral dosage
    Adults previously treated with an NS5A inhibitor without prior treatment with an NS3/4A PI

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 16 weeks.

    Children and Adolescents 12 to 17 years previously treated with an NS5A inhibitor without prior treatment with an NS3/4A PI

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 16 weeks.

    Children younger than 12 years weighing 45 kg or more previously treated with an NS5A inhibitor without prior treatment with an NS3/4A PI

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 16 weeks.

    Adults previously treated with an NS3/4A PI without prior treatment with an NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 12 weeks.

    Children and Adolescents 12 to 17 years previously treated with an NS3/4A PI without prior treatment with an NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 12 weeks.

    Children younger than 12 years weighing 45 kg or more previously treated with an NS3/4A PI without prior treatment with an NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 12 weeks.

    Adults without cirrhosis previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 8 weeks. Guidelines recommend 16 weeks of treatment for patients who previously failed a sofosbuvir-based regimen that did not include an NS3/4A PI.

    Children and Adolescents 12 to 17 years without cirrhosis previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 8 weeks.

    Children younger than 12 years weighing 45 kg or more without cirrhosis previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 8 weeks.

    Adults with compensated cirrhosis previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 12 weeks. Guidelines recommend 16 weeks of treatment for patients who previously failed a sofosbuvir-based regimen that did not include an NS3/4A PI.

    Children and Adolescents 12 to 17 years with compensated cirrhosis previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 12 weeks.

    Children younger than 12 years weighing 45 kg or more with compensated cirrhosis previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 12 weeks.

    Adults with and without compensated cirrhosis who previously failed treatment with glecaprevir; pibrentasvir†

    Guidelines recommend 3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food plus sofosbuvir and weight-based ribavirin for 16 weeks.

    Adults with and without compensated cirrhosis who have multiple DAA failures (including sofosbuvir; velpatasvir; voxilaprevir or glecaprevir; pibrentasvir plus sofosbuvir)†

    Guidelines recommend 3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food plus sofosbuvir and weight-based ribavirin for 16 weeks. Increase the treatment duration to 24 weeks for patients with previous failure on glecaprevir; pibrentasvir plus sofosbuvir.

    For treatment-experienced patients with HCV genotypes 2, 4, 5, or 6.
    Oral dosage
    Adults without cirrhosis previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 8 weeks. Guidelines recommend 16 weeks of treatment for patients who previously failed a sofosbuvir-based regimen that did not include an NS3/4A PI.

    Children and Adolescents 12 to 17 years without cirrhosis previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 8 weeks.

    Children younger than 12 years weighing 45 kg or more without cirrhosis previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 8 weeks.

    Adults with compensated cirrhosis previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 12 weeks. Guidelines recommend 16 weeks of treatment for patients who previously failed a sofosbuvir-based regimen that did not include an NS3/4A PI.

    Children and Adolescents 12 to 17 years with compensated cirrhosis previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 12 weeks.

    Children younger than 12 years weighing 45 kg or more with compensated cirrhosis previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 12 weeks.

    Adults with and without compensated cirrhosis who previously failed treatment with glecaprevir; pibrentasvir†

    Guidelines recommend 3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food plus sofosbuvir and weight-based ribavirin for 16 weeks.

    Adults with and without compensated cirrhosis who have multiple DAA failures (including sofosbuvir; velpatasvir; voxilaprevir or glecaprevir; pibrentasvir plus sofosbuvir)†

    Guidelines recommend 3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food plus sofosbuvir and weight-based ribavirin for 16 weeks. Increase the treatment duration to 24 weeks for patients with previous failure on glecaprevir; pibrentasvir plus sofosbuvir.

    For treatment-experienced patients with HCV genotype 3.
    Oral dosage
    Adults previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 16 weeks.

    Children and Adolescents 12 to 17 years previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 16 weeks.

    Children younger than 12 years weighing 45 kg or more previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 16 weeks.

    Adults with and without compensated cirrhosis who previously failed treatment with glecaprevir; pibrentasvir†

    Guidelines recommend 3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food plus sofosbuvir and weight-based ribavirin for 16 weeks.

    Adults without compensated cirrhosis who have multiple DAA failures (including sofosbuvir; velpatasvir; voxilaprevir or glecaprevir; pibrentasvir plus sofosbuvir)†

    Guidelines recommend 3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food plus sofosbuvir and weight-based ribavirin for 16 weeks. Increase the treatment duration to 24 weeks for patients with previous failure on glecaprevir; pibrentasvir plus sofosbuvir.

    Adults with compensated cirrhosis who have multiple DAA failures (including sofosbuvir; velpatasvir; voxilaprevir or glecaprevir; pibrentasvir plus sofosbuvir)†

    Guidelines recommend 3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food plus sofosbuvir and weight-based ribavirin for 24 weeks.

    For treatment-naive and experienced patients who develop recurrent HCV genotypes 1, 2, 3, 4, 5, or 6 infection after liver or kidney transplantation.
    Oral dosage
    Adults

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 12 weeks. Extend the treatment duration to 16 weeks for: genotype 1 infected patients previously treated with an NS5A inhibitor without prior treatment with an NS3/4A PI; genotype 3 infected patients previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor.

    Children and Adolescents 12 to 17 years

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 12 weeks. Extend the treatment duration to 16 weeks for: genotype 1 infected patients previously treated with an NS5A inhibitor without prior treatment with an NS3/4A PI; genotype 3 infected patients previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor.[62201]

    Children younger than 12 years weighing 45 kg or more

    3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 12 weeks. Extend the treatment duration to 16 weeks for: genotype 1 infected patients previously treated with an NS5A inhibitor without prior treatment with an NS3/4A PI; genotype 3 infected patients previously treated with regimens containing interferon, ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A PI or NS5A inhibitor.[62201]

    For preemptive treatment of HCV-uninfected recipients of organ transplants from HCV-viremic donors†.
    Oral dosage
    Uninfected adults who received liver transplant from HCV-viremic donor

    Guidelines recommend 3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 12 weeks.

    Uninfected adults who received non-liver transplant from HCV-viremic donor

    Guidelines recommend 3 tablets (glecaprevir 300 mg; pibrentasvir 120 mg) PO once daily with food for 8 weeks.

    MAXIMUM DOSAGE

    Adults

    3 tablets/day PO (glecaprevir 300 mg/day PO; pibrentasvir 120 mg/day PO).

    Geriatric

    3 tablets/day PO (glecaprevir 300 mg/day PO; pibrentasvir 120 mg/day PO).

    Adolescents

    3 tablets/day PO (glecaprevir 300 mg/day PO; pibrentasvir 120 mg/day PO).

    Children

    12 years or weighing 45 kg or more: 3 tablets/day PO (glecaprevir 300 mg/day PO; pibrentasvir 120 mg/day PO).
    weighing less than 45 kg: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Dosage adjustments are not required for mild hepatic impairment (Child-Pugh A). Use is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh B or C) and in those with any history of prior hepatic decompensation.[62201]

    Renal Impairment

    No dosage adjustments are needed for any degree of renal impairment. Further, guidelines recommend glecaprevir; pibrentasvir as a preferred direct acting antiviral regimen for treatment of HCV genotypes 1a, 1b, 2, 3, 4, 5, and 6 in patients with chronic kidney disease (i.e., GFR less than 30 mL/min/1.73 m2), including kidney transplant recipients.

    ADMINISTRATION

    Oral Administration

    Take with food.

    STORAGE

    Mavyret:
    - Avoid temperatures above 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Alcoholism, ascites, hepatic decompensation, hepatic disease, hepatic encephalopathy, hepatocellular cancer, jaundice

    Glecaprevir; pibrentasvir is contraindicated for use in patients with moderate or severe hepatic disease (Child-Pugh B or C) and in those with any history of prior hepatic decompensation.[62201] The FDA has issued a Drug Safety Communication describing rare cases (n = 63) of worsening hepatic function and hepatic failure (including deaths) following the inappropriate use of certain hepatitis C treatments (including glecaprevir; pibrentasvir) in patients with advanced hepatic disease. The most frequently reported drug-associated hepatic events were hyperbilirubinemia, jaundice, ascites, and hepatic encephalopathy; and the median time to onset after drug initiation was 22 days (range 2 days to 16 weeks). Of the 63 reported cases, 21 were in patients with decompensated cirrhosis, 18 with compensated cirrhosis, 13 without cirrhosis, and 11 with unknown hepatic function at baseline. More than half of the cases that reported no or compensated cirrhosis (Child-Pugh A) were incorrectly classified and had evidence of advanced liver disease (e.g., decreased platelets, portal hypertension) or preexisting risk factors (e.g., hepatocellular cancer, alcoholism, serious hepatic medical illness). Health care professionals are advised to carefully assess patient's hepatic disease status at baseline and closely monitor for signs and symptoms of worsening hepatic function during treatment (e.g., increased hepatic enzymes, jaundice, ascites, hepatic encephalopathy, and variceal hemorrhage). Discontinue treatment in any patient who develops signs and symptoms of hepatic decompensation, as drug discontinuation can resolve symptoms or reduce hepatic biochemical values.[64589]

    Hepatitis B exacerbation

    Use of direct-acting antivirals (DAA), such as glecaprevir and pibrentasvir, to treat hepatitis C virus (HCV) infection in patients currently or previously infected with hepatitis B virus (HBV) has been associated with reactivation and hepatitis B exacerbation. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Hepatitis B reactivation has also occurred in patients receiving certain immunosuppressive or chemotherapeutic medications; the risk of HBV reactivation associated with DAA treatment may be increased in these patients. HBV reactivation is characterized as an abrupt increase in viral replication manifesting as a rapid increase in serum HBV DNA concentration. In patients with resolved HBV infection, the reappearance of HBsAg can occur. Reactivation of HBV replication may be accompanied by hepatitis (i.e., increases in aminotransferase concentrations) and, in severe cases, increases in bilirubin concentrations, liver failure, and death can occur. To decrease the risk of reactivating an HBV infection, screen all potential drug recipients for evidence of current or prior HBV infection by measuring the hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc). For those patients whose screening reveals serologic evidence of HBV infection, a baseline HBV DNA concentration should be obtained prior to starting glecaprevir; pibrentasvir. Continue to monitor coinfected patients during and after treatment for clinical and laboratory signs of hepatitis B exacerbation (i.e., HBsAg, HBV DNA, hepatic enzymes, bilirubin). In addition, instruct patients to immediately report any signs of liver toxicity (e.g., yellow eyes or skin, fatigue, weakness, loss of appetite, nausea, vomiting, or light-colored stools) to their health care provider. If a glecaprevir; pibrentasvir recipient develops signs of HBV reactivation, initiate appropriate treatment for HBV infection as clinically indicated.

    Pregnancy

    No adequate, well-controlled studies have been conducted with glecaprevir; pibrentasvir in human pregnancy, and it is unknown whether glecaprevir; pibrentasvir poses a risk to the developing fetus. In animal studies, no adverse effects on embryo-fetal development and pre/postnatal development were identified in rats (glecaprevir) and mice and rabbits (pibrentasvir) exposed to doses higher than the recommended human dose.

    Breast-feeding

    It is unknown if glecaprevir and pibrentasvir are excreted in human milk, affect milk production, or have an adverse effect on nursing infants. Animal studies showed that both components were present in milk, without an effect on growth and development in the nursing animal. Consider the benefits of breast-feeding, the risk of infant drug exposure, and the risk of an untreated or inadequately treated condition.

    Hepatitis C and HIV coinfection

    HIV treatment guidelines recommend all patients presenting with HIV infection undergo testing for hepatitis C, with continued annual screening advised for those persons considered high risk for acquiring hepatitis C. If hepatitis C and HIV coinfection is identified, consider treating both viral infections concurrently. For most patients, the benefits of concurrent therapy outweighs the potential risks (i.e., drug-induced hepatic injury, complex drug interactions, overlapping toxicities); therefore, it is recommended to initiate a fully suppressive antiretroviral (ARV) therapy and a hepatitis C regimen in all coinfected patients regardless of CD4 count. However, for antiretroviral naive patients with CD4 counts greater than 500 cells/mm3, consideration may be given to deferring ARV until the hepatitis C treatment regimen has been completed. Conversely, for patients with CD4 counts less than 200 cells/mm3, consider delaying initiation of the hepatitis C treatment regimen until the patient is stable on fully suppressive ARV regimen. Instruct coinfected patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate.

    Anticoagulant therapy

    Caution is advised when prescribing glecaprevir; pibrentasvir to patients receiving concurrent anticoagulant therapy, specifically warfarin. Fluctuations in International Normalized Ratio (INR) have been observed in warfarin recipients who were also receiving treatment for hepatitis C virus (HCV) infections. It is recommended to closely monitor these patients for changes in INR both during and after discontinuation of the HCV treatment regimen.

    Diabetes mellitus, hyperglycemia, hypoglycemia

    A safety review of direct-acting antivirals (DAAs) was conducted and it was determined that there is an association between these medications and episodes of dysglycemia (both hypoglycemia and hyperglycemia). At the time of the safety review, 36 case reports describing a possible link between the use of DAAs and dysglycemia were identified. Of the 36 reports, 24 were related to hyperglycemia or new-onset diabetes (including 1 death), 8 were related to hypoglycemia or improved diabetes, and 4 were reported as other (1 abnormal blood glucose, 2 loss of blood glucose control, 1 both hyperglycemia and hypoglycemia). A further evaluation concluded that 27 of the case reports (including the 1 fatality) were possibly linked to the use of a DAA, 3 were not likely associated with DAA use, and the rest could not be assessed due to insufficient data. Closely monitor blood glucose concentrations during treatment with glecaprevir; pibrentasvir. For patients with diabetes mellitus who are receiving concurrent treatment with antidiabetic agents, dose adjustments of the antidiabetic agents may be needed in order to prevent the occurrence of hypoglycemia.

    ADVERSE REACTIONS

    Severe

    hepatitis B exacerbation / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    hepatic decompensation / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known

    Moderate

    hyperbilirubinemia / Delayed / 3.5-3.5
    jaundice / Delayed / 0-1.0

    Mild

    headache / Early / 5.0-17.0
    pruritus / Rapid / 6.0-17.0
    fatigue / Early / 6.0-16.0
    nausea / Early / 5.0-12.0
    asthenia / Delayed / 7.0-7.0
    diarrhea / Early / 3.0-7.0

    DRUG INTERACTIONS

    Acalabrutinib: (Moderate) Coadministration of acalabrutinib and glecaprevir may increase glecaprevir exposure and increase the risk of glecaprevir toxicity. Acalabrutinib is a substrate and inhibitor of the breast cancer resistance protein (BCRP) transporter in vitro; it may inhibit intestinal BCRP. Glecaprevir is a substrate and inhibitor of BCRP. (Moderate) Coadministration of acalabrutinib and pibrentasvir may increase pibrentasvir exposure and increase the risk of pibrentasvir toxicity. Acalabrutinib is a substrate and inhibitor of the breast cancer resistance protein (BCRP) transporter in vitro; it may inhibit intestinal BCRP. Pibrentasvir is a substrate and inhibitor of BCRP.
    Acarbose: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Acetohexamide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Afatinib: (Moderate) If the concomitant use of glecaprevir and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of glecaprevir. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-glycoprotein (P-gp) substrate and glecaprevir is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib. (Moderate) If the concomitant use of pibrentasvir and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of pibrentasvir. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-glycoprotein (P-gp) substrate and pibrentasvir is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib.
    Albiglutide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Aliskiren: (Moderate) Caution is advised with the coadministration of glecaprevir and aliskiren as coadministration may increase serum concentrations of aliskiren and increase the risk of adverse effects. Aliskiren is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and aliskiren as coadministration may increase serum concentrations of aliskiren and increase the risk of adverse effects. Aliskiren is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
    Aliskiren; Amlodipine: (Moderate) Caution is advised with the coadministration of glecaprevir and aliskiren as coadministration may increase serum concentrations of aliskiren and increase the risk of adverse effects. Aliskiren is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and aliskiren as coadministration may increase serum concentrations of aliskiren and increase the risk of adverse effects. Aliskiren is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advised with the coadministration of glecaprevir and aliskiren as coadministration may increase serum concentrations of aliskiren and increase the risk of adverse effects. Aliskiren is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and aliskiren as coadministration may increase serum concentrations of aliskiren and increase the risk of adverse effects. Aliskiren is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advised with the coadministration of glecaprevir and aliskiren as coadministration may increase serum concentrations of aliskiren and increase the risk of adverse effects. Aliskiren is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and aliskiren as coadministration may increase serum concentrations of aliskiren and increase the risk of adverse effects. Aliskiren is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
    Aliskiren; Valsartan: (Moderate) Caution is advised with the coadministration of glecaprevir and aliskiren as coadministration may increase serum concentrations of aliskiren and increase the risk of adverse effects. Aliskiren is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and aliskiren as coadministration may increase serum concentrations of aliskiren and increase the risk of adverse effects. Aliskiren is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
    Alogliptin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Alogliptin; Metformin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Alogliptin; Pioglitazone: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Alpelisib: (Major) Avoid coadministration of alpelisib with glecaprevir due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and glecaprevir is a BCRP inhibitor. (Major) Avoid coadministration of alpelisib with pibrentasvir due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and pibrentasvir is a BCRP inhibitor.
    Amiodarone: (Moderate) Caution is advised with the coadministration of glecaprevir and amiodarone as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); amiodarone is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and amiodarone as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); amiodarone is an inhibitor of P-gp.
    Amlodipine; Atorvastatin: (Major) Avoid the concurrent use of atorvastatin and glecaprevir due to an increased risk of myopathy/rhabdomyolysis. Coadministration may increase the plasma concentrations of atorvastatin. Atorvastatin is a substrate of the drug transporters P-glycoprotein (P-gp) and OATP1B1/3; glecaprevir is an inhibitor of these transporters. In drug interaction studies, coadministration of atorvastatin with glecaprevir; pibrentasvir resulted in an approximately 8-fold increase in the AUC of atorvastatin. (Major) Avoid the concurrent use of atorvastatin and pibrentasvir due to an increased risk of myopathy/rhabdomyolysis. Coadministration may increase the plasma concentrations of atorvastatin. Atorvastatin is a substrate of the drug transporters P-glycoprotein (P-gp) and OATP1B1; pibrentasvir is an inhibitor of these transporters. In drug interaction studies, coadministration of atorvastatin with glecaprevir; pibrentasvir resulted in an approximately 8-fold increase in the AUC of atorvastatin.
    Amoxicillin; Clarithromycin; Lansoprazole: (Moderate) Caution is advised with the coadministration of glecaprevir and clarithromycin as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) 1B1/3; clarithromycin is an inhibitor of P-gp and OATP1B1/3. (Moderate) Caution is advised with the coadministration of pibrentasvir and clarithromycin as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); clarithromycin is an inhibitor of P-gp.
    Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Caution is advised with the coadministration of glecaprevir and clarithromycin as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) 1B1/3; clarithromycin is an inhibitor of P-gp and OATP1B1/3. (Moderate) Caution is advised with the coadministration of pibrentasvir and clarithromycin as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); clarithromycin is an inhibitor of P-gp.
    Antidiabetic Agents: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Apalutamide: (Major) Coadministration of glecaprevir with apalutamide is not recommended as apalutamide may significantly decrease plasma concentrations of glecaprevir resulting in loss of efficacy. Glecaprevir is a CYP3A4 and P-glycoprotein (P-gp) substrate. Apalutamide is a strong CYP3A4 inducer and a weak inducer of P-gp. Coadministration with another strong CYP3A4 and P-gp inducer decreased glecaprevir exposure by 66%. (Moderate) Monitor for decreased efficacy of pibrentasvir if coadministration with apalutamide is necessary. Pibrentasvir is a P-glycoprotein (P-gp) and BCRP substrate. Apalutamide is a weak P-gp and BCRPP inducer. Concomitant use may decrease pibrentasvir plasma concentrations.
    Aspirin, ASA; Pravastatin: (Major) Reduce pravastatin dose by 50% when coadministered with glecaprevir due to an increased risk of myopathy, including rhabdomyolysis. Pravastatin is a substrate of the drug transporters OATP1B1 and OATP1B3; glecaprevir is an inhibitor of these transporters. Coadministration may increase the plasma concentrations of pravastatin. In drug interaction studies, coadministration of pravastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of pravastatin. (Major) Reduce pravastatin dose by 50% when coadministered with pibrentasvir due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of pravastatin. Pravastatin is a substrate of the drug transporters OATP1B1 and OATP1B3; pibrentasvir is an inhibitor of these transporters. In drug interaction studies, coadministration of pravastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of pravastatin.
    Atazanavir: (Contraindicated) Coadministration of glecaprevir with atazanavir is contraindicated due to an increased risk of ALT elevations. (Contraindicated) Coadministration of pibrentasvir with atazanavir is contraindicated due to an increased risk of ALT elevations.
    Atazanavir; Cobicistat: (Contraindicated) Coadministration of glecaprevir with atazanavir is contraindicated due to an increased risk of ALT elevations. (Contraindicated) Coadministration of pibrentasvir with atazanavir is contraindicated due to an increased risk of ALT elevations. (Moderate) Caution is advised with the coadministration of glecaprevir and cobicistat as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); cobicistat is an inhibitor of all these transporters. (Moderate) Caution is advised with the coadministration of pibrentasvir and cobicistat as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); cobicistat is an inhibitor of P-gp and BCRP.
    Atorvastatin: (Major) Avoid the concurrent use of atorvastatin and glecaprevir due to an increased risk of myopathy/rhabdomyolysis. Coadministration may increase the plasma concentrations of atorvastatin. Atorvastatin is a substrate of the drug transporters P-glycoprotein (P-gp) and OATP1B1/3; glecaprevir is an inhibitor of these transporters. In drug interaction studies, coadministration of atorvastatin with glecaprevir; pibrentasvir resulted in an approximately 8-fold increase in the AUC of atorvastatin. (Major) Avoid the concurrent use of atorvastatin and pibrentasvir due to an increased risk of myopathy/rhabdomyolysis. Coadministration may increase the plasma concentrations of atorvastatin. Atorvastatin is a substrate of the drug transporters P-glycoprotein (P-gp) and OATP1B1; pibrentasvir is an inhibitor of these transporters. In drug interaction studies, coadministration of atorvastatin with glecaprevir; pibrentasvir resulted in an approximately 8-fold increase in the AUC of atorvastatin.
    Atorvastatin; Ezetimibe: (Major) Avoid the concurrent use of atorvastatin and glecaprevir due to an increased risk of myopathy/rhabdomyolysis. Coadministration may increase the plasma concentrations of atorvastatin. Atorvastatin is a substrate of the drug transporters P-glycoprotein (P-gp) and OATP1B1/3; glecaprevir is an inhibitor of these transporters. In drug interaction studies, coadministration of atorvastatin with glecaprevir; pibrentasvir resulted in an approximately 8-fold increase in the AUC of atorvastatin. (Major) Avoid the concurrent use of atorvastatin and pibrentasvir due to an increased risk of myopathy/rhabdomyolysis. Coadministration may increase the plasma concentrations of atorvastatin. Atorvastatin is a substrate of the drug transporters P-glycoprotein (P-gp) and OATP1B1; pibrentasvir is an inhibitor of these transporters. In drug interaction studies, coadministration of atorvastatin with glecaprevir; pibrentasvir resulted in an approximately 8-fold increase in the AUC of atorvastatin.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Caution is advised with coadministration of glecaprevir and phenobarbital as decreased plasma concentrations of glecaprevir may occur resulting in the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); phenobarbital is a CYP3A4/P-gp inducer. (Moderate) Caution is advised with coadministration of pibrentasvir and phenobarbital due to the potential loss of efficacy of pibrentasvir. Coadministration may decrease plasma concentrations of pibrentasvir. Pibrentasvir is a substrate of P-glycoprotein (P-gp); phenobarbital is a P-gp inducer.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Caution is advised with coadministration of glecaprevir and phenobarbital as decreased plasma concentrations of glecaprevir may occur resulting in the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); phenobarbital is a CYP3A4/P-gp inducer. (Moderate) Caution is advised with coadministration of pibrentasvir and phenobarbital due to the potential loss of efficacy of pibrentasvir. Coadministration may decrease plasma concentrations of pibrentasvir. Pibrentasvir is a substrate of P-glycoprotein (P-gp); phenobarbital is a P-gp inducer.
    Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking glecaprevir. Concurrent use may increase berotralstat exposure and the risk of adverse effects. The exposure of glecaprevir may also be increased resulting in increased risk of glecaprevir-related adverse events. Berotralstat is a P-gp and BCRP substrate and P-gp inhibitor; glecaprevir is a P-gp substrate and P-gp and BCRP inhibitor. Coadministration with another P-gp and BCRP inhibitor increased berotralstat exposure by 69%. (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking pibrentasvir. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Additionally, monitor for increased toxicity of pibrentasvir as concurrent use may also increase the exposure of pibrentasvir. Berotralstat is a P-gp and BCRP substrate and P-gp inhibitor; pibrentasvir is a P-gp substrate and P-gp and BCRP inhibitor. Coadministration with another P-gp and BCRP inhibitor increased berotralstat exposure by 69%.
    Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving glecaprevir. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving glecaprevir. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; glecaprevir inhibits P-gp. (Major) Avoid betrixaban use in patients with severe renal impairment receiving pibrentasvir. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving pibrentasvir. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; pibrentasvir inhibits P-gp.
    Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is advised with the coadministration of glecaprevir and tenofovir alafenamide as coadministration may increase serum concentrations of tenofovir alafenamide and increase the risk of adverse effects. Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of all these drug transporters. (Moderate) Caution is advised with the coadministration of pibrentasvir and tenofovir alafenamide as coadministration may increase serum concentrations of tenofovir alafenamide and increase the risk of adverse effects. Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of all these drug transporters.
    Bosentan: (Moderate) Caution is advised with the coadministration of glecaprevir and bosentan as coadministration may increase serum concentrations of bosentan and increase the risk of adverse effects. Bosentan is a substrate of organic anion transporting polypeptide (OATP) 1B1/3; glecaprevir is an inhibitor of OATP1B1/3. (Moderate) Caution is advised with the coadministration of pibrentasvir and bosentan as coadministration may increase serum concentrations of bosentan and increase the risk of adverse effects. Bosentan is a substrate of organic anion transporting polypeptide (OATP) 1B1/3; pibrentasvir is an inhibitor of OATP1B1/3.
    Brigatinib: (Moderate) Monitor for an increase in glecaprevir-related adverse reactions if coadministration with brigatinib is necessary. Glecaprevir is a substrate of P-glycoprotein (P-gp) and BCRP. Brigatinib inhibits both P-gp and BCRP in vitro and may have the potential to increase concentrations of substrates of these transporters. (Moderate) Monitor for an increase in pibrentasvir-related adverse reactions if coadministration with brigatinib is necessary. Pibrentasvir is a substrate of P-glycoprotein (P-gp) and BCRP. Brigatinib inhibits both P-gp and BCRP in vitro and may have the potential to increase concentrations of substrates of these transporters.
    Budesonide: (Moderate) Caution is advised with the coadministration of glecaprevir and budesonide as coadministration may increase serum concentrations of budesonide and increase the risk of adverse effects. Glecaprevir is a P-glycoprotein (P-gp) inhibitor; budesonide is a P-gp substrate. (Moderate) Caution is advised with the coadministration of pibrentasvir and budesonide as coadministration may increase serum concentrations of budesonide and increase the risk of adverse effects. Pibrentasvir is a P-glycoprotein (P-gp) inhibitor; budesonide is a P-gp substrate.
    Budesonide; Formoterol: (Moderate) Caution is advised with the coadministration of glecaprevir and budesonide as coadministration may increase serum concentrations of budesonide and increase the risk of adverse effects. Glecaprevir is a P-glycoprotein (P-gp) inhibitor; budesonide is a P-gp substrate. (Moderate) Caution is advised with the coadministration of pibrentasvir and budesonide as coadministration may increase serum concentrations of budesonide and increase the risk of adverse effects. Pibrentasvir is a P-glycoprotein (P-gp) inhibitor; budesonide is a P-gp substrate.
    Budesonide; Glycopyrrolate; Formoterol: (Moderate) Caution is advised with the coadministration of glecaprevir and budesonide as coadministration may increase serum concentrations of budesonide and increase the risk of adverse effects. Glecaprevir is a P-glycoprotein (P-gp) inhibitor; budesonide is a P-gp substrate. (Moderate) Caution is advised with the coadministration of pibrentasvir and budesonide as coadministration may increase serum concentrations of budesonide and increase the risk of adverse effects. Pibrentasvir is a P-glycoprotein (P-gp) inhibitor; budesonide is a P-gp substrate.
    Cabozantinib: (Minor) Monitor for an increase in glecaprevir-related adverse reactions if coadministration with cabozantinib is necessary. Glecaprevir is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown. (Minor) Monitor for an increase in pibrentasvir-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of pibrentasvir may be necessary. Pibrentasvir is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
    Canagliflozin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Canagliflozin; Metformin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Capmatinib: (Moderate) Caution is advised with coadministration of glecaprevir and capmatinib as increased plasma concentrations of glecaprevir may occur resulting in increased risk of glecaprevir-related adverse events. Glecaprevir is a substrate of P-glycoprotein (P-gp) and BCRP and capmatinib is a P-gp and BCRP inhibitor. (Moderate) Caution is advised with coadministration of pibrentasvir and capmatinib as increased plasma concentrations of pibrentasvir may occur resulting in increased risk of pibrentasvir-related adverse events. Pibrentasvir is a substrate of P-glycoprotein (P-gp) and BCRP. Capmatinib is a P-gp and BCRP inhibitor.
    Carbamazepine: (Major) Coadministration of glecaprevir with carbamazepine is not recommended due to the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); carbamazepine is a CYP3A4/P-gp inducer. In drug interaction studies, coadministration of carbamazepine with glecaprevir resulted in a 66% decrease in the AUC of glecaprevir. (Major) Coadministration of pibrentasvir with carbamazepine is not recommended due to the potential loss of efficacy of pibrentasvir. Pibrentasvir is a substrate of P-glycoprotein (P-gp); carbamazepine is an inducer of P-gp. Coadministration may decrease plasma concentrations of pibrentasvir. In drug interaction studies, coadministration of carbamazepine with pibrentasvir resulted in a 51% decrease in the AUC of pibrentasvir.
    Carvedilol: (Moderate) Caution is advised with the coadministration of glecaprevir and carvedilol as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and carvedilol are both substrates and inhibitors of P-glycoprotein (P-gp). (Moderate) Caution is advised with the coadministration of pibrentasvir and carvedilol as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Both pibrentasvir and carvedilol are substrates and inhibitors of P-glycoprotein (P-gp).
    Cenobamate: (Major) Coadministration of glecaprevir with cenobamate is not recommended due to the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4; cenobamate is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of glecaprevir.
    Chlorpropamide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Clarithromycin: (Moderate) Caution is advised with the coadministration of glecaprevir and clarithromycin as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) 1B1/3; clarithromycin is an inhibitor of P-gp and OATP1B1/3. (Moderate) Caution is advised with the coadministration of pibrentasvir and clarithromycin as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); clarithromycin is an inhibitor of P-gp.
    Cobicistat: (Moderate) Caution is advised with the coadministration of glecaprevir and cobicistat as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); cobicistat is an inhibitor of all these transporters. (Moderate) Caution is advised with the coadministration of pibrentasvir and cobicistat as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); cobicistat is an inhibitor of P-gp and BCRP.
    Cobimetinib: (Moderate) Caution is advised with the coadministration of glecaprevir and cobimetinib as coadministration may increase serum concentrations of cobimetinib and increase the risk of adverse effects. Cobimetinib is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and cobimetinib as coadministration may increase serum concentrations of cobimetinib and increase the risk of adverse effects. Cobimetinib is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
    Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and glecaprevir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Glecaprevir can inhibit colchicine's metabolism via P-glycoprotein (P-gp), resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a P-gp inhibitor like glecaprevir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day. (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and pibrentasvir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Pibrentasvir can inhibit colchicine's metabolism via P-glycoprotein (P-gp), resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a P-gp inhibitor like pibrentasvir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Colchicine; Probenecid: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and glecaprevir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Glecaprevir can inhibit colchicine's metabolism via P-glycoprotein (P-gp), resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a P-gp inhibitor like glecaprevir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day. (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and pibrentasvir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Pibrentasvir can inhibit colchicine's metabolism via P-glycoprotein (P-gp), resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a P-gp inhibitor like pibrentasvir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Conivaptan: (Moderate) Caution is advised with the coadministration of glecaprevir and conivaptan as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); conivaptan is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and conivaptan as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); conivaptan is an inhibitor of P-gp.
    Cyclosporine: (Major) Coadministration of glecaprevir in patients requiring stable cyclosporine doses more than 100 mg per day is not recommended as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is partially metabolized by CYP3A4, and is a substrate of the drug transporters P-glycoprotein (P-gp), OATP1B1, and BCRP; cyclosporine is an inhibitor of CYP3A4, P-gp, OATP1B1, and BCRP. Additionally, cyclosporine is a P-gp substrate and glecaprevir is a P-gp inhibitor; concentrations of cyclosporine may also be increased. In drug interaction studies, coadministration of cyclosporine with glecaprevir resulted in an approximately 5-fold increase in the AUC of glecaprevir. (Major) Coadministration of pibrentasvir in patients requiring stable cyclosporine doses more than 100 mg per day is not recommended as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of the drug transporters P-glycoprotein (P-gp) and BCRP; cyclosporine is an inhibitor of P-gp and BCRP. Additionally, cyclosporine is a P-gp substrate and pibrentasvir is a P-gp inhibitor; concentrations of cyclosporine may also be increased. In drug interaction studies, coadministration of cyclosporine with pibrentasvir resulted in an approximately 2-fold increase in the AUC of pibrentasvir.
    Dabigatran: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with glecaprevir, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like glecaprevir in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with glecaprevir, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. In drug interaction studies, coadministration of dabigatran with glecaprevir; pibrentasvir resulted in over a 2-fold increase in the AUC of dabigatran. (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with pibrentasvir, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like pibrentasvir in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with pibrentasvir, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. In drug interaction studies, coadministration of dabigatran with glecaprevir; pibrentasvir resulted in over a 2-fold increase in the AUC of dabigatran.
    Daclatasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and daclatasvir as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of organic anion transporting polypeptide (OATP) 1B1/3, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP); daclatasvir is an inhibitor of all these drug transporters. (Moderate) Caution is advised with the coadministration of pibrentasvir and daclatasvir as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); daclatasvir is an inhibitor of P-gp and BCRP.
    Dapagliflozin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Dapagliflozin; Metformin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Dapagliflozin; Saxagliptin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Darolutamide: (Moderate) Monitor for an increase in glecaprevir-related adverse reactions if coadministration with darolutamide is necessary. Concomitant use may increase glecaprevir exposure. Glecaprevir is a BCRP and OATP1B1/3 substrate; darolutamide is a BCRP and OATP1B1/3 inhibitor. (Moderate) Monitor for an increase in pibrentasvir-related adverse reactions if coadministration with darolutamide is necessary. Concomitant use may increase plasma concentrations of pibrentasvir. Pibrentasvir is a BCRP substrate. Darolutamide is a BCRP inhibitor.
    Darunavir: (Major) Coadministration of glecaprevir with darunavir is not recommended as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of CYP3A4; darunavir is an inhibitor of CYP3A4. Additionally, darunavir is a P-gp substrate and glecaprevir is a P-gp inhibitor; concentrations of darunavir may also be increased. In drug interaction studies, coadministration of darunavir boosted with ritonavir with glecaprevir; pibrentasvir resulted in an approximately 5-fold increase in the AUC of glecaprevir and a 29% increase in the AUC of darunavir. (Major) Coadministration of pibrentasvir with darunavir is not recommended as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of the drug transporter P-glycoprotein (P-gp); darunavir is an inhibitor of P-gp. Additionally, darunavir is a P-gp substrate and pibrentasvir is a P-gp inhibitor; concentrations of darunavir may also be increased. In drug interaction studies, coadministration of darunavir boosted with ritonavir with glecaprevir; pibrentasvir resulted in a 29% increase in the AUC of darunavir.
    Darunavir; Cobicistat: (Major) Coadministration of glecaprevir with darunavir is not recommended as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of CYP3A4; darunavir is an inhibitor of CYP3A4. Additionally, darunavir is a P-gp substrate and glecaprevir is a P-gp inhibitor; concentrations of darunavir may also be increased. In drug interaction studies, coadministration of darunavir boosted with ritonavir with glecaprevir; pibrentasvir resulted in an approximately 5-fold increase in the AUC of glecaprevir and a 29% increase in the AUC of darunavir. (Major) Coadministration of pibrentasvir with darunavir is not recommended as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of the drug transporter P-glycoprotein (P-gp); darunavir is an inhibitor of P-gp. Additionally, darunavir is a P-gp substrate and pibrentasvir is a P-gp inhibitor; concentrations of darunavir may also be increased. In drug interaction studies, coadministration of darunavir boosted with ritonavir with glecaprevir; pibrentasvir resulted in a 29% increase in the AUC of darunavir. (Moderate) Caution is advised with the coadministration of glecaprevir and cobicistat as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); cobicistat is an inhibitor of all these transporters. (Moderate) Caution is advised with the coadministration of pibrentasvir and cobicistat as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); cobicistat is an inhibitor of P-gp and BCRP.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of glecaprevir with darunavir is not recommended as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of CYP3A4; darunavir is an inhibitor of CYP3A4. Additionally, darunavir is a P-gp substrate and glecaprevir is a P-gp inhibitor; concentrations of darunavir may also be increased. In drug interaction studies, coadministration of darunavir boosted with ritonavir with glecaprevir; pibrentasvir resulted in an approximately 5-fold increase in the AUC of glecaprevir and a 29% increase in the AUC of darunavir. (Major) Coadministration of pibrentasvir with darunavir is not recommended as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of the drug transporter P-glycoprotein (P-gp); darunavir is an inhibitor of P-gp. Additionally, darunavir is a P-gp substrate and pibrentasvir is a P-gp inhibitor; concentrations of darunavir may also be increased. In drug interaction studies, coadministration of darunavir boosted with ritonavir with glecaprevir; pibrentasvir resulted in a 29% increase in the AUC of darunavir. (Moderate) Caution is advised with the coadministration of glecaprevir and cobicistat as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); cobicistat is an inhibitor of all these transporters. (Moderate) Caution is advised with the coadministration of glecaprevir and tenofovir alafenamide as coadministration may increase serum concentrations of tenofovir alafenamide and increase the risk of adverse effects. Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of all these drug transporters. (Moderate) Caution is advised with the coadministration of pibrentasvir and cobicistat as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); cobicistat is an inhibitor of P-gp and BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and tenofovir alafenamide as coadministration may increase serum concentrations of tenofovir alafenamide and increase the risk of adverse effects. Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of all these drug transporters.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Coadministration of glecaprevir with ritonavir is not recommended as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); ritonavir is an inhibitor of CYP3A4 and P-gp. Additionally, ritonavir is a P-gp substrate and glecaprevir is a P-gp inhibitor; concentrations of ritonavir may also be increased. (Major) Coadministration of pibrentasvir with ritonavir is not recommended as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of the drug transporter P-glycoprotein (P-gp); ritonavir is an inhibitor of P-gp. Additionally, ritonavir is a P-gp substrate and pibrentasvir is a P-gp inhibitor; concentrations of ritonavir may also be increased. (Moderate) Caution is advised with the coadministration of glecaprevir and dasabuvir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Dasabuvir is a substrate of P-glycoprotein (P-gp) and a substrate and inhibitor of breast cancer resistance protein (BCRP); glecaprevir is a substrate and inhibitor of P-gp and BCRP. (Moderate) Caution is advised with the coadministration of glecaprevir and ombitasvir as coadministration may increase serum concentrations of ombitasvir and increase the risk of adverse effects. Ombitasvir is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of P-gp and BCRP. (Moderate) Caution is advised with the coadministration of glecaprevir and paritaprevir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and paritaprevir are both substrates and inhibitors of organic anion transporting polypeptide (OATP) 1B1/3. Additionally, paritaprevir is a substrate of P-glycoprotein (P-gp) and substrate and inhibitor of breast cancer resistance protein (BCRP); glecaprevir is a P-gp inhibitor and a substrate and inhibitor of BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and dasabuvir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Dasabuvir is a substrate of P-glycoprotein (P-gp) and a substrate and inhibitor of breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of P-gp and a substrate and inhbitor of BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and ombitasvir as coadministration may increase serum concentrations of ombitasvir and increase the risk of adverse effects. Ombitasvir is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of P-gp and BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and paritaprevir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Paritaprevir is a substrate of of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide (OATP)1B1/3; pibrentasvir is an inhibitor of all these drug transporters. Additionally, pibrentasvir is a substrate of BCRP while paritaprevir is an inhibitor of BCRP.
    Daunorubicin Liposomal: (Moderate) Caution is advised with the coadministration of glecaprevir and daunorubicin liposomal as coadministration may increase serum concentrations of daunorubicin and increase the risk of adverse effects. Daunorubicin is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of P-gp and BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and daunorubicin liposomal as coadministration may increase serum concentrations of daunorubicin and increase the risk of adverse effects. Daunorubicin is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of P-gp and BCRP.
    Daunorubicin Liposomal; Cytarabine Liposomal: (Moderate) Caution is advised with the coadministration of glecaprevir and daunorubicin liposomal as coadministration may increase serum concentrations of daunorubicin and increase the risk of adverse effects. Daunorubicin is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of P-gp and BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and daunorubicin liposomal as coadministration may increase serum concentrations of daunorubicin and increase the risk of adverse effects. Daunorubicin is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of P-gp and BCRP.
    Dexamethasone: (Moderate) Caution is advised with the coadministration of glecaprevir and dexamethasone as coadministration may increase serum concentrations of dexamethasone and increase the risk of adverse effects. Dexamethasone is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and dexamethasone as coadministration may increase serum concentrations of dexamethasone and increase the risk of adverse effects. Dexamethasone is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
    Dextromethorphan; Quinidine: (Moderate) Caution is advised with the coadministration of glecaprevir and quinidine as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and quinidine are both substrates and inhibitors of P-glycoprotein (P-gp). (Moderate) Caution is advised with the coadministration of pibrentasvir and quinidine as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Both pibrentasvir and quinidine are substrates and inhibitors of P-glycoprotein (P-gp).
    Digoxin: (Major) Coadministration of glecaprevir with digoxin may increase the serum concentrations of digoxin. Measure serum digoxin concentrations prior to initiating glecaprevir; reduce digoxin concentrations by decreasing digoxin dose by approximately 50% or by modifying the dosing frequency; continue monitoring during therapy. Digoxin is a substrate of P-glycoprotein (P-gp); glecaprevir is an inhibitor of P-gp. In drug interaction studies, coadministration of digoxin with glecaprevir; pibrentasvir resulted in a 48% increase in the AUC of digoxin. (Major) Coadministration of pibrentasvir with digoxin may increase the serum concentrations of digoxin. Measure serum digoxin concentrations prior to initiating pibrentasvir; reduce digoxin concentrations by decreasing digoxin dose by approximately 50% or by modifying the dosing frequency; continue monitoring during therapy. Digoxin is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp. In drug interaction studies, coadministration of digoxin with glecaprevir; pibrentasvir resulted in a 48% increase in the AUC of digoxin.
    Docetaxel: (Moderate) Caution is advised with the coadministration of glecaprevir and docetaxel as coadministration may increase serum concentrations of docetaxel and increase the risk of adverse effects. Docetaxel is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and docetaxel as coadministration may increase serum concentrations of docetaxel and increase the risk of adverse effects. Docetaxel is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Doxorubicin Liposomal: (Moderate) Caution is advised with the coadministration of glecaprevir and doxorubicin liposomal as coadministration may increase serum concentrations of doxorubicin and increase the risk of adverse effects. Doxorubicin is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of P-gp and BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and doxorubicin liposomal as coadministration may increase serum concentrations of doxorubicin and increase the risk of adverse effects. Doxorubicin is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of P-gp and BCRP.
    Doxorubicin: (Moderate) Caution is advised with the coadministration of glecaprevir and doxorubicin as coadministration may increase serum concentrations of doxorubicin and increase the risk of adverse effects. Doxorubicin is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of P-gp and BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and doxorubicin as coadministration may increase serum concentrations of doxorubicin and increase the risk of adverse effects. Doxorubicin is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of P-gp and BCRP.
    Dronedarone: (Moderate) Caution is advised with the coadministration of glecaprevir and dronedarone as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); dronedarone is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and dronedarone as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); dronedarone is an inhibitor of P-gp.
    Drospirenone; Ethinyl Estradiol: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Dulaglutide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Efavirenz: (Major) Coadministration of glecaprevir with efavirenz is not recommended due to the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4; efavirenz is a CYP3A4 inducer. Coadministration may decrease plasma concentrations of glecaprevir.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Coadministration of glecaprevir with efavirenz is not recommended due to the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4; efavirenz is a CYP3A4 inducer. Coadministration may decrease plasma concentrations of glecaprevir.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of glecaprevir with efavirenz is not recommended due to the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4; efavirenz is a CYP3A4 inducer. Coadministration may decrease plasma concentrations of glecaprevir.
    Elagolix: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as glecaprevir is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Glecaprevir inhibits both OATP1B1 and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as pibrentasvir is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Pibrentasvir inhibits both OATP1B1 and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
    Elagolix; Estradiol; Norethindrone acetate: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as glecaprevir is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Glecaprevir inhibits both OATP1B1 and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as pibrentasvir is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Pibrentasvir inhibits both OATP1B1 and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
    Elbasvir; Grazoprevir: (Moderate) Caution is advised with the coadministration of glecaprevir and elbasvir as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of breast cancer resistance protein (BCRP); elbasvir is an inhibitor of BCRP. (Moderate) Caution is advised with the coadministration of glecaprevir and grazoprevir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Grazoprevir is a substrate of organic anion transporting polypeptide (OATP) 1B1/3; glecaprevir is an inhibitor of OATP1B1/3. Additionally, glecaprevir is a substrate of BCRP and grazoprevir is an inhibitor of BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and elbasvir as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of breast cancer resistance protein (BCRP); elbasvir is an inhibitor of BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and grazoprevir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Grazoprevir is a substrate of organic anion transporting polypeptide (OATP) 1B1/3 and an inhibitor of breast cancer resistance protein (BCRP); pibrentasvir is a substrate of BCRP and an inhibitor of OATP1B1/3.
    Eletriptan: (Moderate) Caution is advised with the coadministration of glecaprevir and eletriptan as coadministration may increase serum concentrations of eletriptan and increase the risk of adverse effects. Eletriptan is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor.
    Elexacaftor; tezacaftor; ivacaftor: (Moderate) Caution is advised with the coadministration of glecaprevir and ivacaftor as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); ivacaftor is a P-gp inhibitor. (Moderate) Monitor for glecaprevir-related adverse reactions during coadministration of elexacaftor; tezacaftor; ivacaftor as concurrent use may increase exposure of glecaprevir. Glecaprevir is a substrate for the transporters OATP1B1 and OATP1B3; elexacaftor; tezacaftor; ivacaftor may inhibit uptake of OATP1B1 and OATP1B3.
    Eliglustat: (Moderate) Caution is advised with the coadministration of glecaprevir and eliglustat as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); eliglustat is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and eliglustat as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); eliglustat is an inhibitor of P-gp.
    Eltrombopag: (Moderate) Caution is advised with the coadministration of glecaprevir and eltrombopag as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of organic anion transporting polypeptide (OATP) 1B1 and breast cancer resistance protein (BCRP); eltrombopag is an inhibitor of OATP1B1 and BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and eltrombopag as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of breast cancer resistance protein (BCRP); eltrombopag is an inhibitor of BCRP.
    Eluxadoline: (Major) Reduce the dose of eluxadoline to 75 mg PO twice daily and monitor for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity) if coadministered with glecaprevir. Advise patients against driving or operating machinery until the combined effects of these drugs on the individual patient is known. Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); glecaprevir is an OATP1B1/1B3 inhibitor. This specific interaction has not been evaluated; however, administration of eluxadoline with another OATP inhibitor resulted in elevated exposure (AUC) and maximum plasma concentration of eluxadoline by 4.4- and 6.2-fold, respectively. (Major) Reduce the dose of eluxadoline to 75 mg PO twice daily and monitor for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity) if coadministered with pibrentasvir. Advise patients against driving or operating machinery until the combined effects of these drugs on the individual patient is known. Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); pibrentasvir is an OATP1B1/1B3 inhibitor. This specific interaction has not been evaluated; however, administration of eluxadoline with another OATP inhibitor resulted in elevated exposure (AUC) and maximum plasma concentration of eluxadoline by 4.4- and 6.2-fold, respectively.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is advised with the coadministration of glecaprevir and cobicistat as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); cobicistat is an inhibitor of all these transporters. (Moderate) Caution is advised with the coadministration of glecaprevir and tenofovir alafenamide as coadministration may increase serum concentrations of tenofovir alafenamide and increase the risk of adverse effects. Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of all these drug transporters. (Moderate) Caution is advised with the coadministration of pibrentasvir and cobicistat as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); cobicistat is an inhibitor of P-gp and BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and tenofovir alafenamide as coadministration may increase serum concentrations of tenofovir alafenamide and increase the risk of adverse effects. Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of all these drug transporters.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised with the coadministration of glecaprevir and cobicistat as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); cobicistat is an inhibitor of all these transporters. (Moderate) Caution is advised with the coadministration of pibrentasvir and cobicistat as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); cobicistat is an inhibitor of P-gp and BCRP.
    Empagliflozin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Empagliflozin; Linagliptin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Empagliflozin; Linagliptin; Metformin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Empagliflozin; Metformin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Caution is advised with the coadministration of glecaprevir and tenofovir alafenamide as coadministration may increase serum concentrations of tenofovir alafenamide and increase the risk of adverse effects. Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of all these drug transporters. (Moderate) Caution is advised with the coadministration of pibrentasvir and tenofovir alafenamide as coadministration may increase serum concentrations of tenofovir alafenamide and increase the risk of adverse effects. Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of all these drug transporters.
    Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is advised with the coadministration of glecaprevir and tenofovir alafenamide as coadministration may increase serum concentrations of tenofovir alafenamide and increase the risk of adverse effects. Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of all these drug transporters. (Moderate) Caution is advised with the coadministration of pibrentasvir and tenofovir alafenamide as coadministration may increase serum concentrations of tenofovir alafenamide and increase the risk of adverse effects. Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of all these drug transporters.
    Enasidenib: (Moderate) Monitor for an increase in glecaprevir-related adverse effects if coadministration with enasidenib is necessary. Concomitant use may increase glecaprevir exposure. Glecaprevir is a substrate of P-gp, BCRP, and OATP1B1/3 and enasidenib is a P-gp, BCRP, and OATP1B1/3 inhibitor. (Moderate) Monitor for an increase in pibrentasvir-related adverse effects if concomitant use of enasidenib is necessary. Concomitant use may increase pibrentasvir exposure. Pibrentasvir is a substrate of P-gp and BCRP and enasidenib is a P-gp and BCRP inhibitor.
    Enzalutamide: (Major) Coadministration of glecaprevir with enzalutamide is not recommended as enzalutamide may significantly decrease plasma concentrations of glecaprevir resulting in loss of efficacy. Glecaprevir is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer.
    Ertugliflozin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Ertugliflozin; Metformin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Ertugliflozin; Sitagliptin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Erythromycin: (Moderate) Caution is advised with the coadministration of glecaprevir and erythromycin as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and erythromycin are both substrates and inhibitors of P-glycoprotein (P-gp). Additionally, glecaprevir is a substrate of organic anion transporting polypeptide (OATP) 1B1/3 and erythromycin is an inhibitor of OATP1B1/3. (Moderate) Caution is advised with the coadministration of pibrentasvir and erythromycin as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Both pibrentasvir and erythromycin are substrates and inhibitors of P-glycoprotein (P-gp).
    Erythromycin; Sulfisoxazole: (Moderate) Caution is advised with the coadministration of glecaprevir and erythromycin as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and erythromycin are both substrates and inhibitors of P-glycoprotein (P-gp). Additionally, glecaprevir is a substrate of organic anion transporting polypeptide (OATP) 1B1/3 and erythromycin is an inhibitor of OATP1B1/3. (Moderate) Caution is advised with the coadministration of pibrentasvir and erythromycin as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Both pibrentasvir and erythromycin are substrates and inhibitors of P-glycoprotein (P-gp).
    Ethinyl Estradiol: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Ethinyl Estradiol; Desogestrel: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Ethinyl Estradiol; Etonogestrel: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Ethinyl Estradiol; Levonorgestrel: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Ethinyl Estradiol; Norelgestromin: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Ethinyl Estradiol; Norethindrone Acetate: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Ethinyl Estradiol; Norethindrone: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Ethinyl Estradiol; Norgestimate: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Ethinyl Estradiol; Norgestrel: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Etravirine: (Moderate) Caution is advised with the coadministration of glecaprevir and etravirine as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); etravirine is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and etravirine as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); etravirine is an inhibitor of P-gp.
    Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with glecaprevir is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-glycoprotein (P-gp) substrate and glecaprevir is a P-gp inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations. (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with pibrentasvir is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-glycoprotein (P-gp) substrate and pibrentasvir is a P-gp inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations.
    Exenatide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Ezetimibe; Simvastatin: (Major) Coadministration of glecaprevir with simvastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of simvastatin. Simvastatin is a substrate of OATP1B1/3; glecaprevir is an inhibitor of OATP1B1/3. In drug interaction studies, coadministration of simvastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of simvastatin. (Major) Coadministration of pibrentasvir with simvastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of simvastatin. Simvastatin is a substrate of the drug transporters OATP1B1/3; pibrentasvir is an inhibitor of OATP1B1/3. In drug interaction studies, coadministration of simvastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of simvastatin.
    Fexofenadine: (Moderate) Caution is advised with the coadministration of glecaprevir and fexofenadine as coadministration may increase serum concentrations of fexofenadine and increase the risk of adverse effects. Fexofenadine is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and fexofenadine as coadministration may increase serum concentrations of fexofenadine and increase the risk of adverse effects. Fexofenadine is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Fexofenadine; Pseudoephedrine: (Moderate) Caution is advised with the coadministration of glecaprevir and fexofenadine as coadministration may increase serum concentrations of fexofenadine and increase the risk of adverse effects. Fexofenadine is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and fexofenadine as coadministration may increase serum concentrations of fexofenadine and increase the risk of adverse effects. Fexofenadine is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Caution is advised with the coadministration of glecaprevir and umeclidinium as coadministration may increase serum concentrations of umeclidinium and increase the risk of adverse effects. Umeclidinium is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and umeclidinium as coadministration may increase serum concentrations of umeclidinium and increase the risk of adverse effects. Umeclidinium is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
    Fluvastatin: (Major) Use the lowest approved fluvastatin dose (i.e., 20 mg PO once daily) when coadministered with glecaprevir due to an increased risk of myopathy, including rhabdomyolysis. If a higher dose is necessary, use the lowest necessary dose based on a risk/benefit assessment. Coadministration may increase the plasma concentrations of fluvastatin. Fluvastatin is a substrate of the drug transporters OATP1B1 and BRCP; glecaprevir is an inhibitor of these transporters. Additionally, glecaprevir is a P-gp substrate and fluvastatin is a P-gp inhibitor; concentrations of glecaprevir may also be increased. (Major) Use the lowest approved fluvastatin dose (i.e., 20 mg PO once daily) when coadministered with pibrentasvir due to an increased risk of myopathy, including rhabdomyolysis. If a higher dose is necessary, use the lowest necessary dose based on a risk/benefit assessment. Coadministration may increase the plasma concentrations of fluvastatin. Fluvastatin is a substrate of the drug transporters OATP1B1 and BRCP; pibrentasvir is an inhibitor of these transporters. Additionally, pibrentasvir is a P-gp substrate and fluvastatin is a P-gp inhibitor; concentrations of pibrentasvir may also be increased.
    Fosamprenavir: (Moderate) Caution is advised with the coadministration of pibrentasvir and fosamprenavir as coadministration may decrease serum concentrations of pibrentasvir and/or increase serum concentrations of fosamprenavir. This may result in decreased efficacy of pibrentasvir and/or increased fosamprenavir-related adverse effects. Pibrentasvir is a substrate and inhibitor of P-glycoprotein (P-gp); fosamprenavir is a substrate and inducer of P-gp.
    Fosphenytoin: (Moderate) Caution is advised with coadministration of glecaprevir and fosphenytoin as decreased plasma concentrations of glecaprevir may occur resulting in the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); fosphenytoin is a CYP3A4/P-gp inducer. (Moderate) Caution is advised with coadministration of pibrentasvir and fosphenytoin due to the potential loss of efficacy of pibrentasvir. Coadministration may decrease plasma concentrations of pibrentasvir. Pibrentasvir is a substrate of P-glycoprotein (P-gp); fosphenytoin is a P-gp inducer.
    Fostamatinib: (Moderate) Monitor for glecaprevir toxicities that may require glecaprevir dose reduction if given concurrently with fostamatinib. Concomitant use of fostamatinib with a BCRP or P-gp substrate may increase the concentration of the BCRP or P-gp substrate. Fostamatinib is a P-gp inhibitor, and the active metabolite of fostamatinib, R406, is a BCRP inhibitor; glecaprevir is a substrate for BCRP and P-gp. Coadministration of fostamatinib with another BCRP substrate increased the substrate AUC by 95% and Cmax by 88%. Coadministration of fostamatinib with another P-gp substrate increased the substrate AUC by 37% and Cmax by 70%. (Moderate) Monitor for pibrentasvir toxicities that may require pibrentasvir dose reduction if given concurrently with fostamatinib. Concomitant use of fostamatinib with a BCRP or P-gp substrate may increase the concentration of the BCRP or P-gp substrate. Fostamatinib is a P-gp inhibitor, and the active metabolite of fostamatinib, R406, is a BCRP inhibitor; pibrentasvir is a substrate for BCRP and P-gp. Coadministration of fostamatinib with another BCRP substrate increased the substrate AUC by 95% and Cmax by 88%. Coadministration of fostamatinib with another P-gp substrate increased the substrate AUC by 37% and Cmax by 70%.
    Fostemsavir: (Moderate) Caution is advised with coadministration of glecaprevir and fostemsavir as increased plasma concentrations of glecaprevir may occur resulting in increased risk of glecaprevir-related adverse events. Glecaprevir is a substrate of BCRP and OATP1B1/3; fostemsavir is a BCRP and OATP1B1/3 inhibitor. (Moderate) Caution is advised with coadministration of pibrentasvir and fostemsavir as increased plasma concentrations of pibrentasvir may occur resulting in increased risk of pibrentasvir-related adverse events. Pibrentasvir is a substrate of BCRP and fostemsavir is a BCRP inhibitor.
    Gemfibrozil: (Moderate) Caution is advised with the coadministration of glecaprevir and gemfibrozil as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of organic anion transporting polypeptide (OATP)1B1; gemfibrozil is an inhibitor of OATP1B1.
    Glimepiride: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Glimepiride; Pioglitazone: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Glimepiride; Rosiglitazone: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Glipizide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Glipizide; Metformin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Glyburide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Glyburide; Metformin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Grapefruit juice: (Moderate) Caution is advised with the coadministration of glecaprevir and grapefruit juice as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); grapefruit juice is a P-gp inhibitor.
    Imatinib: (Moderate) Caution is advised with the coadministration of glecaprevir and imatinib as coadministration may increase serum concentrations of imatinib and increase the risk of adverse effects. Imatinib is a substrate of the breast cancer resistance protein (BCRP) transporter; glecaprevir is an inhibitor of BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and imatinib as coadministration may increase serum concentrations of imatinib and increase the risk of adverse effects. Imatinib is a substrate of the breast cancer resistance protein (BCRP) transporter; pibrentasvir is an inhibitor of BCRP.
    Indinavir: (Moderate) Caution is advised with the coadministration of glecaprevir and indinavir as coadministration may increase serum concentrations of indinavir and increase the risk of adverse effects. Indinavir is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and indinavir as coadministration may increase serum concentrations of indinavir and increase the risk of adverse effects. Indinavir is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Insulin Aspart: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Insulin Aspart; Insulin Aspart Protamine: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Insulin Degludec; Liraglutide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Insulin Detemir: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Insulin Glargine: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Insulin Glargine; Lixisenatide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Insulin Glulisine: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Insulin Lispro: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Insulin Lispro; Insulin Lispro Protamine: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Insulin, Inhaled: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Irinotecan Liposomal: (Major) Avoid administration of glecaprevir during treatment with irinotecan unless there are no therapeutic alternatives. Irinotecan is a P-glycoprotein (P-gp) substrate and its active metabolite, SN-38, is a UGT1A1 substrate. Glecaprevir is a P-gp and UGT1A1 inhibitor. Concomitant use may increase systemic exposure to irinotecan and SN-38. (Major) Avoid administration of pibrentasvir during treatment with irinotecan unless there are no therapeutic alternatives. Irinotecan is a P-glycoprotein (P-gp) substrate and its active metabolite, SN-38, is a UGT1A1 substrate. Pibrentasvir is a P-gp and UGT1A1 inhibitor. Concomitant use may increase systemic exposure to irinotecan and SN-38.
    Irinotecan: (Major) Avoid administration of glecaprevir during treatment with irinotecan unless there are no therapeutic alternatives. Irinotecan is a P-glycoprotein (P-gp) substrate and its active metabolite, SN-38, is a UGT1A1 substrate. Glecaprevir is a P-gp and UGT1A1 inhibitor. Concomitant use may increase systemic exposure to irinotecan and SN-38. (Major) Avoid administration of pibrentasvir during treatment with irinotecan unless there are no therapeutic alternatives. Irinotecan is a P-glycoprotein (P-gp) substrate and its active metabolite, SN-38, is a UGT1A1 substrate. Pibrentasvir is a P-gp and UGT1A1 inhibitor. Concomitant use may increase systemic exposure to irinotecan and SN-38.
    Isavuconazonium: (Moderate) Caution is advised with the coadministration of glecaprevir and isavuconazonium as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); isavuconazonium is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and isavuconazonium as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); isavuconazonium is an inhibitor of P-gp.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Contraindicated) Coadministration of glecaprevir with rifampin is contraindicated due to the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate for CYP3A4 and P-glycoprotein (P-gp); rifampin is a CYP3A4 and P-gp inducer. Coadministration decreases the plasma concentrations of glecaprevir by 88%. (Contraindicated) Coadministration of pibrentasvir with rifampin is contraindicated due to the potential loss of efficacy of pibrentasvir. Pibrentasvir is a substrate for P-glycoprotein (P-gp); rifampin is an inducer of P-gp. Coadministration decreases the plasma concentrations of pibrentasvir by 87%.
    Isoniazid, INH; Rifampin: (Contraindicated) Coadministration of glecaprevir with rifampin is contraindicated due to the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate for CYP3A4 and P-glycoprotein (P-gp); rifampin is a CYP3A4 and P-gp inducer. Coadministration decreases the plasma concentrations of glecaprevir by 88%. (Contraindicated) Coadministration of pibrentasvir with rifampin is contraindicated due to the potential loss of efficacy of pibrentasvir. Pibrentasvir is a substrate for P-glycoprotein (P-gp); rifampin is an inducer of P-gp. Coadministration decreases the plasma concentrations of pibrentasvir by 87%.
    Isophane Insulin (NPH): (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Itraconazole: (Moderate) Caution is advised with the coadministration of glecaprevir and itraconazole as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and itraconazole are both substrates and inhibitors of P-glycoprotein (P-gp). In addition, itraconazole inhibits breast cancer resistance protein (BCRP); glecaprevir is a BCRP substrate. (Moderate) Caution is advised with the coadministration of pibrentasvir and itraconazole as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Both pibrentasvir and itraconazole are substrates and inhibitors of P-glycoprotein (P-gp). In addition, itraconazole inhibits breast cancer resistance protein (BCRP); pibrentasvir is a BCRP substrate.
    Ivacaftor: (Moderate) Caution is advised with the coadministration of glecaprevir and ivacaftor as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); ivacaftor is a P-gp inhibitor.
    Ketoconazole: (Moderate) Caution is advised with the coadministration of glecaprevir and ketoconazole as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); ketoconazole is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and ketoconazole as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); ketoconazole is an inhibitor of P-gp.
    Lapatinib: (Moderate) Monitor for an increase in treatment-related adverse reactions if coadministration of lapatinib with glecaprevir is necessary. Both drugs are P-glycoprotein (P-gp) substrates and inhibitors. Increased plasma concentrations of lapatinib are likely. Exposure to glecaprevir may also occur. (Moderate) Monitor for an increase in treatment-related adverse reactions if coadministration with lapatinib is necessary. Both drugs are P-glycoprotein (P-gp) substrates and inhibitors. Increased plasma concentrations of lapatinib are likely when administered with P-gp inhibitors. Exposure to pibrentasvir may also increase.
    Ledipasvir; Sofosbuvir: (Moderate) Caution is advised with the coadministration of glecaprevir and ledipasvir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and ledipasvir are both substrates and inhibitors of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). (Moderate) Caution is advised with the coadministration of pibrentasvir and ledipasvir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Pibrentasvir and ledipasvir are both substrates and inhibitors of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).
    Lefamulin: (Moderate) Monitor for lefamulin-related adverse effects if oral lefamulin is administered with glecaprevir as concurrent use may increase exposure from lefamulin tablets; an interaction is not expected with intravenous lefamulin. Lefamulin is a CYP3A4 and P-gp substrate and glecaprevir is a P-gp inhibitor. (Moderate) Monitor for lefamulin-related adverse effects if oral lefamulin is administered with pibrentasvir as concurrent use may increase exposure from lefamulin tablets; an interaction is not expected with intravenous lefamulin. Lefamulin is a CYP3A4 and P-gp substrate and pibrentasvir is a P-gp inhibitor.
    Lente Insulin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Letermovir: (Moderate) Administering glecaprevir concurrently with letermovir may result in elevated concentrations of both drugs. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine. Closely monitor for adverse events, including tachycardia, atrial fibrillation, hepatotoxicity, and gastrointestinal events. Glecaprevir and letermovir are substrates and inhibitors of the organic anion-transporting polypeptides (OATP1B1/3). Glecaprevir is also a substrate of CYP3A4, while letermovir is a moderate CYP3A4 inhibitor. When given with cyclosporine, the combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. In addition, cyclosporine is an OATP1B1 inhibitor, which could further amplify this interaction. (Moderate) Closely monitor for letermovir-related adverse events (i.e., tachycardia, atrial fibrillation, and gastrointestinal events) if administered with pibrentasvir, as use of these drugs together may result in elevated letermovir plasma concentration. Letermovir is a substrate of the organic anion-transporting polypeptides (OATP1B1/3); pibrentasvir is an inhibitor of OATP1B1/3.
    Linagliptin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Linagliptin; Metformin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Liraglutide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Lixisenatide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Lonafarnib: (Moderate) Caution is advised with coadministration of glecaprevir and lonafarnib as increased plasma concentrations of glecaprevir may occur resulting in increased risk of glecaprevir-related adverse events. Glecaprevir is a P-gp substrate and lonafarnib is a P-gp inhibitor. (Moderate) Caution is advised with coadministration of pibrentasvir and lonafarnib as increased plasma concentrations of pibrentasvir may occur resulting in increased risk of pibrentasvir-related adverse events. Pibrentasvir is a substrate of P-glycoprotein (P-gp) and lonafarnib is a P-gp inhibitor.
    Loperamide: (Moderate) Caution is advised with the coadministration of glecaprevir and loperamide as coadministration may increase serum concentrations of loperamide and increase the risk of adverse effects. Monitor for depressed respiratory ventilation and adverse cardiac effects if these drugs are to be coadministered. Loperamide is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. In-vivo, single dose pharmacokinetic studies suggest that oral coadministration of loperamide (16 mg) and other known P-gp inhibitors resulted in a 2- to 3-fold increase in loperamide plasma concentrations. (Moderate) Caution is advised with the coadministration of pibrentasvir and loperamide as coadministration may increase serum concentrations of loperamide and increase the risk of adverse effects. Monitor for depressed respiratory ventilation and adverse cardiac effects if these drugs are to be coadministered. Loperamide is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp. In-vivo, single dose pharmacokinetic studies suggest that oral coadministration of loperamide (16 mg) and other known P-gp inhibitors resulted in a 2- to 3-fold increase in loperamide plasma concentrations.
    Loperamide; Simethicone: (Moderate) Caution is advised with the coadministration of glecaprevir and loperamide as coadministration may increase serum concentrations of loperamide and increase the risk of adverse effects. Monitor for depressed respiratory ventilation and adverse cardiac effects if these drugs are to be coadministered. Loperamide is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. In-vivo, single dose pharmacokinetic studies suggest that oral coadministration of loperamide (16 mg) and other known P-gp inhibitors resulted in a 2- to 3-fold increase in loperamide plasma concentrations. (Moderate) Caution is advised with the coadministration of pibrentasvir and loperamide as coadministration may increase serum concentrations of loperamide and increase the risk of adverse effects. Monitor for depressed respiratory ventilation and adverse cardiac effects if these drugs are to be coadministered. Loperamide is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp. In-vivo, single dose pharmacokinetic studies suggest that oral coadministration of loperamide (16 mg) and other known P-gp inhibitors resulted in a 2- to 3-fold increase in loperamide plasma concentrations.
    Lopinavir; Ritonavir: (Major) Coadministration of glecaprevir with lopinavir is not recommended as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of the organic anion transporting protein (OATP1B1); lopinavir is an inhibitor of OATP1B1. In drug interaction studies, coadministration of lopinavir; ritonavir with glecaprevir; pibrentasvir resulted in an approximately 4-fold increase in the AUC of glecaprevir. (Major) Coadministration of glecaprevir with ritonavir is not recommended as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); ritonavir is an inhibitor of CYP3A4 and P-gp. Additionally, ritonavir is a P-gp substrate and glecaprevir is a P-gp inhibitor; concentrations of ritonavir may also be increased. (Major) Coadministration of pibrentasvir with ritonavir is not recommended as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of the drug transporter P-glycoprotein (P-gp); ritonavir is an inhibitor of P-gp. Additionally, ritonavir is a P-gp substrate and pibrentasvir is a P-gp inhibitor; concentrations of ritonavir may also be increased.
    Lorlatinib: (Moderate) Caution is advised with coadministration of glecaprevir and lorlatinib as decreased plasma concentrations of glecaprevir may occur resulting in the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp). Lorlatinib is a moderate CYP3A4 inducer as well as an inducer of P-gp. (Moderate) Caution is advised with coadministration of pibrentasvir and lorlatinib as decreased plasma concentrations of pibrentasvir may occur resulting in the potential loss of efficacy of pibrentasvir. Pibrentasvir is a substrate of P-glycoprotein (P-gp) and lorlatinib is a P-gp inducer.
    Lovastatin: (Major) Coadministration of glecaprevir with lovastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of lovastatin. Lovastatin is a substrate of the drug transporter OATP1B1; glecaprevir is an inhibitor of this transporter. In drug interaction studies, coadministration of lovastatin with glecaprevir; pibrentasvir resulted in 70% increase in the AUC of lovastatin. (Major) Coadministration of pibrentasvir with lovastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of lovastatin. Lovastatin is a substrate of the drug transporter OATP1B1; pibrentasvir is an inhibitor of this transporter. In drug interaction studies, coadministration of lovastatin with glecaprevir; pibrentasvir resulted in 70% increase in the AUC of lovastatin.
    Lovastatin; Niacin: (Major) Coadministration of glecaprevir with lovastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of lovastatin. Lovastatin is a substrate of the drug transporter OATP1B1; glecaprevir is an inhibitor of this transporter. In drug interaction studies, coadministration of lovastatin with glecaprevir; pibrentasvir resulted in 70% increase in the AUC of lovastatin. (Major) Coadministration of pibrentasvir with lovastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of lovastatin. Lovastatin is a substrate of the drug transporter OATP1B1; pibrentasvir is an inhibitor of this transporter. In drug interaction studies, coadministration of lovastatin with glecaprevir; pibrentasvir resulted in 70% increase in the AUC of lovastatin.
    Lumacaftor; Ivacaftor: (Moderate) Caution is advised with coadministration of glecaprevir and lumacaftor; ivacaftor as decreased plasma concentrations of glecaprevir may occur resulting in the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); lumacaftor is a CYP3A4 inducer as well as an inhibitor and inducer of P-gp. The net effect on P-gp substrates is unknown. (Moderate) Caution is advised with coadministration of pibrentasvir and lumacaftor; ivacaftor as altered plasma concentrations of pibrentasvir may occur resulting in the potential loss of efficacy of pibrentasvir and/or increased adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); lumacaftor is an inhibitor and inducer of P-gp. The net effect on P-gp substrates is unknown. (Moderate) Caution is advised with the coadministration of glecaprevir and ivacaftor as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); ivacaftor is a P-gp inhibitor.
    Lumacaftor; Ivacaftor: (Moderate) Caution is advised with coadministration of glecaprevir and lumacaftor; ivacaftor as decreased plasma concentrations of glecaprevir may occur resulting in the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); lumacaftor is a CYP3A4 inducer as well as an inhibitor and inducer of P-gp. The net effect on P-gp substrates is unknown. (Moderate) Caution is advised with coadministration of pibrentasvir and lumacaftor; ivacaftor as altered plasma concentrations of pibrentasvir may occur resulting in the potential loss of efficacy of pibrentasvir and/or increased adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); lumacaftor is an inhibitor and inducer of P-gp. The net effect on P-gp substrates is unknown.
    Lumateperone: (Major) Avoid coadministration of lumateperone and glecaprevir as concurrent use may increase lumateperone exposure and the risk of adverse effects. Lumateperone is a UGT1A1 substrate; glecaprevir is a UGT1A1 inhibitor.
    Maraviroc: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and glecaprevir as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1B1); glecaprevir is an inhibitor of P-gp and OATP1B1. The effects of these transporters on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible. (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and pibrentasvir as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1B1); pibrentasvir is an inhibitor of P-gp and OATP1B1. The effects of these transporters on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Mefloquine: (Moderate) Caution is advised with the coadministration of glecaprevir and mefloquine as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and mefloquine are both substrates and inhibitors of P-glycoprotein (P-gp). (Moderate) Caution is advised with the coadministration of pibrentasvir and mefloquine as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Pibrentasvir and mefloquine are both substrates and inhibitors of P-glycoprotein (P-gp).
    Metformin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Metformin; Pioglitazone: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Metformin; Repaglinide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Metformin; Rosiglitazone: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Metformin; Saxagliptin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Metformin; Sitagliptin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Methotrexate: (Moderate) Caution is advised with the coadministration of glecaprevir and methotrexate as coadministration may increase serum concentrations of methotrexate and increase the risk of adverse effects. Methotrexate is a substrate of breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and methotrexate as coadministration may increase serum concentrations of methotrexate and increase the risk of adverse effects. Methotrexate is a substrate of breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of BCRP.
    Mifepristone: (Moderate) Caution is advised with the coadministration of glecaprevir and mifepristone as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); mifepristone is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and mifepristone as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); mifepristone is an inhibitor of P-gp.
    Miglitol: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Mitotane: (Major) Coadministration of glecaprevir with mitotane is not recommended as mitotane may significantly decrease plasma concentrations of glecaprevir resulting in loss of efficacy. Glecaprevir is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer.
    Mitoxantrone: (Moderate) Caution is advised with the coadministration of glecaprevir and mitoxantrone as coadministration may increase serum concentrations of mitoxantrone and increase the risk of adverse effects. Mitoxantrone is a substrate of breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and mitoxantrone as coadministration may increase serum concentrations of mitoxantrone and increase the risk of adverse effects. Mitoxantrone is a substrate of breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of BCRP.
    Morphine: (Moderate) Caution is advised with the coadministration of glecaprevir and morphine as coadministration may increase serum concentrations of morphine and increase the risk of adverse effects. Morphine is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and morphine as coadministration may increase serum concentrations of morphine and increase the risk of adverse effects. Morphine is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Morphine; Naltrexone: (Moderate) Caution is advised with the coadministration of glecaprevir and morphine as coadministration may increase serum concentrations of morphine and increase the risk of adverse effects. Morphine is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and morphine as coadministration may increase serum concentrations of morphine and increase the risk of adverse effects. Morphine is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions if coadministered with glecaprevir. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a P-gp substrate; glecaprevir is a moderate P-gp inhibitor.
    Nateglinide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Nelfinavir: (Moderate) Caution is advised with the coadministration of glecaprevir and nelfinavir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and nelfinavir are both substrates and inhibitors of P-glycoprotein (P-gp). (Moderate) Caution is advised with the coadministration of pibrentasvir and nelfinavir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Pibrentasvir and nelfinavir are both substrates and inhibitors of P-glycoprotein (P-gp).
    Neratinib: (Moderate) Caution is advised with the coadministration of glecaprevir and neratinib as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); neratinib is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and neratinib as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); neratinib is an inhibitor of P-gp.
    Niacin; Simvastatin: (Major) Coadministration of glecaprevir with simvastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of simvastatin. Simvastatin is a substrate of OATP1B1/3; glecaprevir is an inhibitor of OATP1B1/3. In drug interaction studies, coadministration of simvastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of simvastatin. (Major) Coadministration of pibrentasvir with simvastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of simvastatin. Simvastatin is a substrate of the drug transporters OATP1B1/3; pibrentasvir is an inhibitor of OATP1B1/3. In drug interaction studies, coadministration of simvastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of simvastatin.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Coadministration of glecaprevir with ritonavir is not recommended as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); ritonavir is an inhibitor of CYP3A4 and P-gp. Additionally, ritonavir is a P-gp substrate and glecaprevir is a P-gp inhibitor; concentrations of ritonavir may also be increased. (Major) Coadministration of pibrentasvir with ritonavir is not recommended as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of the drug transporter P-glycoprotein (P-gp); ritonavir is an inhibitor of P-gp. Additionally, ritonavir is a P-gp substrate and pibrentasvir is a P-gp inhibitor; concentrations of ritonavir may also be increased. (Moderate) Caution is advised with the coadministration of glecaprevir and ombitasvir as coadministration may increase serum concentrations of ombitasvir and increase the risk of adverse effects. Ombitasvir is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of P-gp and BCRP. (Moderate) Caution is advised with the coadministration of glecaprevir and paritaprevir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and paritaprevir are both substrates and inhibitors of organic anion transporting polypeptide (OATP) 1B1/3. Additionally, paritaprevir is a substrate of P-glycoprotein (P-gp) and substrate and inhibitor of breast cancer resistance protein (BCRP); glecaprevir is a P-gp inhibitor and a substrate and inhibitor of BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and ombitasvir as coadministration may increase serum concentrations of ombitasvir and increase the risk of adverse effects. Ombitasvir is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of P-gp and BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and paritaprevir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Paritaprevir is a substrate of of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide (OATP)1B1/3; pibrentasvir is an inhibitor of all these drug transporters. Additionally, pibrentasvir is a substrate of BCRP while paritaprevir is an inhibitor of BCRP.
    Omeprazole; Amoxicillin; Rifabutin: (Major) When possible, avoid concurrent administration of glecaprevir and rifabutin; consider use of an alternative hepatitis C treatment. Use of these drugs together may decrease the plasma concentration of glecaprevir. Use of another rifamycin with glecaprevir resulted in an 88% decrease in the plasma concentration of glecaprevir. (Major) When possible, avoid concurrent administration of pibrentasvir and rifabutin; consider use of an alternative hepatitis C treatment. Use of these drugs together may decrease the plasma concentration of pibrentasvir. Use of another rifamycin with pibrentasvir resulted in an 87% decrease in the plasma concentration of pibrentasvir.
    Ondansetron: (Moderate) Caution is advised with the coadministration of glecaprevir and ondansetron as coadministration may increase serum concentrations of ondansetron and increase the risk of adverse effects. Ondansetron is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and ondansetron as coadministration may increase serum concentrations of ondansetron and increase the risk of adverse effects. Ondansetron is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
    Osimertinib: (Moderate) Caution is advised with the coadministration of glecaprevir and osimertinib as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp). Osimertinib is a BCRP and P-gp inhibitor. (Moderate) Monitor for an increase in pibrentasvir-related adverse reactions if coadministration with osimertinib is necessary. Pibrentasvir is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor. Concomitant use may increase plasma concentrations of pibrentasvir.
    Ozanimod: (Major) Coadministration of ozanimod with glecaprevir is not recommended. Coadministration may increase the exposure of the active metabolites of ozanimod, which may increase the risk of adverse reactions. Ozanimod is a BCRP substrate and glecaprevir is a BCRP inhibitor. Coadministration with another BCRP inhibitor had no effect on ozanimod exposure, but doubled the exposure of the minor active metabolites, RP101988 and RP101075 (the direct precursor of the major active metabolite CC112273). Coadministration of ozanimod with BCRP inhibitors may also increase exposure of CC112273 and CC1084037. (Major) Coadministration of ozanimod with pibrentasvir is not recommended. Coadministration may increase the exposure of the active metabolites of ozanimod, which may increase the risk of adverse reactions. Ozanimod is a BCRP substrate and pibrentasvir is a BCRP inhibitor. Coadministration with another BCRP inhibitor had no effect on ozanimod exposure, but doubled the exposure of the minor active metabolites, RP101988 and RP101075 (the direct precursor of the major active metabolite CC112273). Coadministration of ozanimod with BCRP inhibitors may also increase exposure of CC112273 and CC1084037.
    Paclitaxel: (Moderate) Caution is advised with the coadministration of glecaprevir and paclitaxel as coadministration may increase serum concentrations of paclitaxel and increase the risk of adverse effects. Paclitaxel is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and paclitaxel as coadministration may increase serum concentrations of paclitaxel and increase the risk of adverse effects. Paclitaxel is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
    Panobinostat: (Moderate) Caution is advised with the coadministration of glecaprevir and panobinostat as coadministration may increase serum concentrations of panobinostat and increase the risk of adverse effects. Panobinostat is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and panobinostat as coadministration may increase serum concentrations of panobinostat and increase the risk of adverse effects. Panobinostat is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Pazopanib: (Moderate) Caution is advised with the coadministration of glecaprevir and pazopanib as coadministration may increase serum concentrations of pazopanib and increase the risk of adverse effects. Pazopanib is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of P-gp and BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and pazopanib as coadministration may increase serum concentrations of pazopanib and increase the risk of adverse effects. Pazopanib is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of P-gp and BCRP.
    Pexidartinib: (Major) Avoid coadministration of pexidartinib with glecaprevir as concurrent use may increase pexidartinib exposure. Concurrent use may also result in decreased plasma concentrations of glecaprevir resulting in the potential loss of efficacy of glecaprevir. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If glecaprevir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of glecaprevir. Pexidartinib is a UGT substrate and moderate CYP3A4 inducer; glecaprevir is a CYP3A4 substrate and UGT inhibitor. Coadministration with another UGT inhibitor increased pexidartinib exposure by 60%. (Major) Avoid coadministration of pexidartinib with pibrentasvir as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If pibrentasvir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of pibrentasvir. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a UGT substrate; pibrentasvir is a UGT inhibitor. Coadministration with another UGT inhibitor increased pexidartinib exposure by 60%.
    Phenobarbital: (Moderate) Caution is advised with coadministration of glecaprevir and phenobarbital as decreased plasma concentrations of glecaprevir may occur resulting in the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); phenobarbital is a CYP3A4/P-gp inducer. (Moderate) Caution is advised with coadministration of pibrentasvir and phenobarbital due to the potential loss of efficacy of pibrentasvir. Coadministration may decrease plasma concentrations of pibrentasvir. Pibrentasvir is a substrate of P-glycoprotein (P-gp); phenobarbital is a P-gp inducer.
    Phenytoin: (Moderate) Caution is advised with coadministration of glecaprevir and phenytoin as decreased plasma concentrations of glecaprevir may occur resulting in the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); phenytoin is a CYP3A4/P-gp inducer. (Moderate) Caution is advised with coadministration of pibrentasvir and phenytoin due to the potential loss of efficacy of glecaprevir. Coadministration may decrease plasma concentrations of pibrentasvir. Pibrentasvir is a substrate of P-glycoprotein (P-gp); phenytoin is a P-gp inducer.
    Pioglitazone: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Pitavastatin: (Major) Use the lowest approved pitavastatin dose (i.e., 1 mg PO once daily) when coadministered with glecaprevir due to an increased risk of myopathy, including rhabdomyolysis. If a higher dose is necessary, use the lowest necessary dose based on a risk/benefit assessment. Coadministration may increase the plasma concentrations of pitavastatin. Pitavastatin is a substrate of the drug transporters OATP1B1 and OATP1B3. Glecaprevir is an inhibitor of these transporters. (Major) Use the lowest approved pitavastatin dose (i.e., 1 mg PO once daily) when coadministered with pibrentasvir due to an increased risk of myopathy, including rhabdomyolysis. If a higher dose is necessary, use the lowest necessary dose based on a risk/benefit assessment. Coadministration may increase the plasma concentrations of pitavastatin. Pitavastatin is a substrate of the drug transporters OATP1B1 and OATP1B3; pibrentasvir is an inhibitor of these transporters.
    Posaconazole: (Moderate) Caution is advised with the coadministration of glecaprevir and posaconazole as coadministration may increase serum concentrations of posaconazole and increase the risk of adverse effects. Posaconazole is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and posaconazole as coadministration may increase serum concentrations of posaconazole and increase the risk of adverse effects. Posaconazole is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
    Pramlintide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Pravastatin: (Major) Reduce pravastatin dose by 50% when coadministered with glecaprevir due to an increased risk of myopathy, including rhabdomyolysis. Pravastatin is a substrate of the drug transporters OATP1B1 and OATP1B3; glecaprevir is an inhibitor of these transporters. Coadministration may increase the plasma concentrations of pravastatin. In drug interaction studies, coadministration of pravastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of pravastatin. (Major) Reduce pravastatin dose by 50% when coadministered with pibrentasvir due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of pravastatin. Pravastatin is a substrate of the drug transporters OATP1B1 and OATP1B3; pibrentasvir is an inhibitor of these transporters. In drug interaction studies, coadministration of pravastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of pravastatin.
    Prednisone: (Moderate) Caution is advised with the coadministration of glecaprevir and prednisone as coadministration may increase serum concentrations of prednisone and increase the risk of adverse effects. Prednisone is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and prednisone as coadministration may increase serum concentrations of prednisone and increase the risk of adverse effects. Prednisone is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
    Primidone: (Moderate) Caution is advised with coadministration of glecaprevir and primidone as decreased plasma concentrations of glecaprevir may occur resulting in the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); phenobarbital, the active metabolite of primidone, is a CYP3A4/P-gp inducer. (Moderate) Caution is advised with coadministration of pibrentasvir and primidone due to the potential loss of efficacy of pibrentasvir. Coadministration may decrease plasma concentrations of pibrentasvir. Pibrentasvir is a substrate of P-glycoprotein (P-gp); phenobarbital, the active metabolite of primidone, is a P-gp inducer.
    Propafenone: (Moderate) Caution is advised with the coadministration of glecaprevir and propafenone as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); propafenone is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and propafenone as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); propafenone is a P-gp inhibitor.
    Quinidine: (Moderate) Caution is advised with the coadministration of glecaprevir and quinidine as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and quinidine are both substrates and inhibitors of P-glycoprotein (P-gp). (Moderate) Caution is advised with the coadministration of pibrentasvir and quinidine as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Both pibrentasvir and quinidine are substrates and inhibitors of P-glycoprotein (P-gp).
    Quinine: (Moderate) Caution is advised with the coadministration of glecaprevir and quinine as coadministration may increase serum concentrations of quinine and increase the risk of adverse effects. Quinine is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and quinine as coadministration may increase serum concentrations of quinine and increase the risk of adverse effects. Quinine is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Ranolazine: (Moderate) Caution is advised with the coadministration of glecaprevir and ranolazine as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and ranolazine are both substrates and inhibitors of P-glycoprotein (P-gp). (Moderate) Caution is advised with the coadministration of pibrentasvir and ranolazine as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Both pibrentasvir and ranolazine are substrates and inhibitors of P-glycoprotein (P-gp).
    Regorafenib: (Moderate) Caution is advised with the coadministration of glecaprevir and regorafenib as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of breast cancer resistance protein (BCRP); regorafenib is an inhibitor of BCRP. (Moderate) Monitor for an increase in pibrentasvir-related adverse reactions if coadministration with regorafenib is necessary. Pibrentasvir is a BCRP substrate and regorafenib is a BCRP inhibitor.
    Regular Insulin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Regular Insulin; Isophane Insulin (NPH): (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Relugolix: (Major) Avoid concomitant use of relugolix and oral glecaprevir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer glecaprevir at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and glecaprevir is a P-gp inhibitor. (Major) Avoid concomitant use of relugolix and oral pibrentasvir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer pibrentasvir at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and pibrentasvir is a P-gp inhibitor.
    Repaglinide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Revefenacin: (Major) Coadministration of revefenacin is not recommended with glecaprevir because it could lead to an increase in systemic exposure of the active metabolite of revefenacin and an increased potential for anticholinergic adverse effects. The active metabolite of revefenacin is a substrate of OATP1B1 and OATP1B3; glecaprevir is an inhibitor of OATP1B1 and OATP1B3. (Major) Coadministration of revefenacin is not recommended with pibrentasvir because it could lead to an increase in systemic exposure of the active metabolite of revefenacin and an increased potential for anticholinergic adverse effects. The active metabolite of revefenacin is a substrate of OATP1B1 and OATP1B3; pibrentasvir is an inhibitor of OATP1B1 and OATP1B3.
    Rifabutin: (Major) When possible, avoid concurrent administration of glecaprevir and rifabutin; consider use of an alternative hepatitis C treatment. Use of these drugs together may decrease the plasma concentration of glecaprevir. Use of another rifamycin with glecaprevir resulted in an 88% decrease in the plasma concentration of glecaprevir. (Major) When possible, avoid concurrent administration of pibrentasvir and rifabutin; consider use of an alternative hepatitis C treatment. Use of these drugs together may decrease the plasma concentration of pibrentasvir. Use of another rifamycin with pibrentasvir resulted in an 87% decrease in the plasma concentration of pibrentasvir.
    Rifampin: (Contraindicated) Coadministration of glecaprevir with rifampin is contraindicated due to the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate for CYP3A4 and P-glycoprotein (P-gp); rifampin is a CYP3A4 and P-gp inducer. Coadministration decreases the plasma concentrations of glecaprevir by 88%. (Contraindicated) Coadministration of pibrentasvir with rifampin is contraindicated due to the potential loss of efficacy of pibrentasvir. Pibrentasvir is a substrate for P-glycoprotein (P-gp); rifampin is an inducer of P-gp. Coadministration decreases the plasma concentrations of pibrentasvir by 87%.
    Rifapentine: (Major) When possible, avoid concurrent administration of glecaprevir and rifapentine; consider use of an alternative hepatitis C treatment. Use of these drugs together may decrease the plasma concentration of glecaprevir. Use of another rifamycin with glecaprevir resulted in an 88% decrease in the plasma concentration of glecaprevir. (Major) When possible, avoid concurrent administration of pibrentasvir and rifapentine; consider use of an alternative hepatitis C treatment. Use of these drugs together may decrease the plasma concentration of pibrentasvir. Use of another rifamycin with pibrentasvir resulted in an 87% decrease in the plasma concentration of pibrentasvir.
    Rifaximin: (Moderate) Caution is advised with the coadministration of glecaprevir and rifaximin as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and rifaximin are both substrates and inhibitors of organic anion transporting polypeptide (OATP) 1B1/3 and P-glycoprotein (P-gp). (Moderate) Caution is advised with the coadministration of pibrentasvir and rifaximin as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Rifaximin is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) 1B1/3; pibrentasvir is an inhibitor of these drug transporters. Additionally, pibrentasvir is a substrate of P-gp while rifaximin is an inhibitor of P-gp.
    Rimegepant: (Major) Avoid coadministration of rimegepant with glecaprevir; concurrent use may increase rimegepant exposure. Rimegepant is a substrate of P-gp and BCRP and glecaprevir is a P-gp and BCRP inhibitor. (Major) Avoid coadministration of rimegepant with pibrentasvir; concurrent use may increase rimegepant exposure. Rimegepant is a substrate of P-gp and BCRP and pibrentasvir is a P-gp and BCRP inhibitor.
    Ritonavir: (Major) Coadministration of glecaprevir with ritonavir is not recommended as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); ritonavir is an inhibitor of CYP3A4 and P-gp. Additionally, ritonavir is a P-gp substrate and glecaprevir is a P-gp inhibitor; concentrations of ritonavir may also be increased. (Major) Coadministration of pibrentasvir with ritonavir is not recommended as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of the drug transporter P-glycoprotein (P-gp); ritonavir is an inhibitor of P-gp. Additionally, ritonavir is a P-gp substrate and pibrentasvir is a P-gp inhibitor; concentrations of ritonavir may also be increased.
    Romidepsin: (Moderate) Caution is advised with the coadministration of glecaprevir and romidepsin as coadministration may increase serum concentrations of romidepsin and increase the risk of adverse effects. Romidepsin is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and romidepsin as coadministration may increase serum concentrations of romidepsin and increase the risk of adverse effects. Romidepsin is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Rosiglitazone: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Rosuvastatin: (Major) Initiate rosuvastatin at a reduced dosage of 5 mg once daily if coadministered with glecaprevir; do not exceed a rosuvastatin dosage of 10 mg once daily. Concurrent use results in elevated rosuvastatin serum concentrations; thereby increasing the risk for myopathy, including rhabdomyolysis. Closely monitor for statin-associated adverse reactions, such as myopathy and rhabdomyolysis. Rosuvastatin is a substrate of the drug transporters OATP1B1, OATP1B3, and BRCP; glecaprevir is an inhibitor of these transporters. In drug interaction studies, coadministration of rosuvastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of rosuvastatin. (Major) Initiate rosuvastatin at a reduced dosage of 5 mg once daily if coadministered with pibrentasvir; do not exceed a rosuvastatin dosage of 10 mg once daily. Concurrent use results in elevated rosuvastatin serum concentrations; thereby increasing the risk for myopathy, including rhabdomyolysis. Closely monitor for statin-associated adverse reactions, such as myopathy and rhabdomyolysis. Rosuvastatin is a substrate of the drug transporters OATP1B1, OATP1B3, and BRCP; pibrentasvir is an inhibitor of these transporters. In drug interaction studies, coadministration of rosuvastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of rosuvastatin.
    Sacituzumab Govitecan: (Major) Avoid coadministration of sacituzumab govitecan and glecaprevir due to the risk of increased sacituzumab govitecan exposure which may increase the risk of adverse reactions. The cytotoxic component of sacituzumab govitecan, SN-38, is metabolized by UGT1A1 and glecaprevir is a UGT1A1 inhibitor. Formal drug interaction studies with sacituzumab govitecan have not been conducted but the concomitant use of UGT1A1 inhibitors is expected to increase SN-38 exposure. (Major) Avoid coadministration of sacituzumab govitecan and pibrentasvir due to the risk of increased sacituzumab govitecan exposure which may increase the risk of adverse reactions. The cytotoxic component of sacituzumab govitecan, SN-38, is metabolized by UGT1A1 and pibrentasvir is a UGT1A1 inhibitor. Formal drug interaction studies with sacituzumab govitecan have not been conducted but the concomitant use of UGT1A1 inhibitors is expected to increase SN-38 exposure.
    Sapropterin: (Moderate) Caution is advised with the coadministration of glecaprevir and sapropterin as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); sapropterin is an inhibitor of P-gp and BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and sapropterin as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); sapropterin is an inhibitor of P-gp and BCRP.
    Saquinavir: (Moderate) Caution is advised with the coadministration of glecaprevir and saquinavir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and saquinavir are both substrates and inhibitors of P-glycoprotein (P-gp). (Moderate) Caution is advised with the coadministration of pibrentasvir and saquinavir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Pibrentasvir and saquinavir are both substrates and inhibitors of P-glycoprotein (P-gp).
    Saxagliptin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Segesterone Acetate; Ethinyl Estradiol: (Major) Coadministration of glecaprevir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol. (Major) Coadministration of pibrentasvir with ethinyl estradiol is not recommended due to an increased risk of ALT elevations associated with ethinyl estradiol. In drug interaction studies, coadministration of ethinyl estradiol-containing oral contraceptives with glecaprevir; pibrentasvir resulted in a 28% to 40% increase in the AUC of ethinyl estradiol.
    Semaglutide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Silodosin: (Moderate) Caution is advised with the coadministration of glecaprevir and silodosin as coadministration may increase serum concentrations of silodosin and increase the risk of adverse effects. Silodosin is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and silodosin as coadministration may increase serum concentrations of silodosin and increase the risk of adverse effects. Silodosin is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Simeprevir: (Moderate) Caution is advised with the coadministration of glecaprevir and simeprevir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and simeprevir are both substrates and inhibitors of organic anion transporting polypeptide (OATP) 1B1/3 and P-glycoprotein (P-gp). Additionally, glecaprevir is a substrate of breast cancer resistance protein (BCRP) while simeprevir is an inhibitor of BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and simeprevir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Simeprevir is a substrate of of P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) 1B1/3; pibrentasvir is an inhibitor of these drug transporters. Additionally, pibrentasvir is a substrate of P-gp and BCRP while simeprevir is an inhibitor of P-gp and BCRP.
    Simvastatin: (Major) Coadministration of glecaprevir with simvastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of simvastatin. Simvastatin is a substrate of OATP1B1/3; glecaprevir is an inhibitor of OATP1B1/3. In drug interaction studies, coadministration of simvastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of simvastatin. (Major) Coadministration of pibrentasvir with simvastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of simvastatin. Simvastatin is a substrate of the drug transporters OATP1B1/3; pibrentasvir is an inhibitor of OATP1B1/3. In drug interaction studies, coadministration of simvastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of simvastatin.
    Simvastatin; Sitagliptin: (Major) Coadministration of glecaprevir with simvastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of simvastatin. Simvastatin is a substrate of OATP1B1/3; glecaprevir is an inhibitor of OATP1B1/3. In drug interaction studies, coadministration of simvastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of simvastatin. (Major) Coadministration of pibrentasvir with simvastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of simvastatin. Simvastatin is a substrate of the drug transporters OATP1B1/3; pibrentasvir is an inhibitor of OATP1B1/3. In drug interaction studies, coadministration of simvastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of simvastatin. (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Sirolimus: (Moderate) Caution is advised with the coadministration of glecaprevir and sirolimus as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Sirolimus is a substrate of P-glycoprotein (P-gp); glecaprevir is an inhibitor of P-gp. Additionally, glecaprevir is a substrate of breast cancer resistance protein (BCRP) while sirolimus is an inhibitor of BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and sirolimus as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Sirolimus is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp. Additionally, pibrentasvir is a substrate of breast cancer resistance protein (BCRP) while sirolimus is an inhibitor of BCRP.
    Sitagliptin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Sofosbuvir; Velpatasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and velpatasvir as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and (OATP) 1B1/3; velpatasvir is an inhibitor of P-gp, BCRP, and (OATP) 1B1/3. (Moderate) Caution is advised with the coadministration of pibrentasvir and velpatasvir as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); velpatasvir is an inhibitor of P-gp and BCRP.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Caution is advised with the coadministration of glecaprevir and velpatasvir as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and (OATP) 1B1/3; velpatasvir is an inhibitor of P-gp, BCRP, and (OATP) 1B1/3. (Moderate) Caution is advised with the coadministration of glecaprevir and voxilaprevir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and voxilaprevir are both substrates and inhibitors of organic anion transporting polypeptide (OATP) 1B1/3 and P-glycoprotein (P-gp). Additionally, glecaprevir is a substrate of breast cancer resistance protein (BCRP) while voxilaprevir is an inhibitor of BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and velpatasvir as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); velpatasvir is an inhibitor of P-gp and BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and voxilaprevir as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Voxilaprevir is a substrate of of P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) 1B1/3; pibrentasvir is an inhibitor of these drug transporters. Additionally, pibrentasvir is a substrate of P-gp and BCRP while voxilaprevir is an inhibitor of P-gp and BCRP.
    Sorafenib: (Moderate) Monitor for an increase in glecaprevir-related adverse reactions if coadministration with sorafenib is necessary. Glecaprevir is a P-glycoprotein (P-gp) substrate and sorafenib inhibits P-gp in vitro. Sorafenib may increase the concentrations of concomitantly administered drugs that are P-gp substrates. (Moderate) Monitor for an increase in pibrentasvir-related adverse reactions if coadministration with sorafenib is necessary. Pibrentasvir is a P-glycoprotein (P-gp) substrate and sorafenib inhibits P-gp in vitro. Sorafenib may increase the concentrations of concomitantly administered drugs that are P-gp substrates.
    St. John's Wort, Hypericum perforatum: (Major) Coadministration of glecaprevir with St. John's Wort is not recommended due to the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); St. John's Wort is a CYP3A4/P-gp inducer. Coadministration may decrease plasma concentrations of glecaprevir. (Major) Coadministration of pibrentasvir with St. John's Wort is not recommended due to the potential loss of efficacy of pibrentasvir. Pibrentasvir is a substrate of P-glycoprotein (P-gp); St. John's Wort is an inducer of P-gp. Coadministration may decrease plasma concentrations of pibrentasvir.
    Sulfasalazine: (Moderate) Caution is advised with the coadministration of glecaprevir and sulfasalazine as coadministration may increase serum concentrations of sulfasalazine and increase the risk of adverse effects. Sulfasalazine is a substrate of breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and sulfasalazine as coadministration may increase serum concentrations of sulfasalazine and increase the risk of adverse effects. Sulfasalazine is a substrate of breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of BCRP.
    Tacrolimus: (Moderate) Closely monitor tacrolimus serum concentrations if coadministration with a direct acting antiviral (DAA) agent, such as glecaprevir, is necessary; dosage adjustments may be required. Changes in liver function due to clearance of the hepatitis C virus by DAA therapy may alter tacrolimus serum concentrations. (Moderate) Closely monitor tacrolimus serum concentrations if coadministration with a direct acting antiviral (DAA) agent, such as pibrentasvir, is necessary; dosage adjustments may be required. Changes in liver function due to clearance of the hepatitis C virus by DAA therapy may alter tacrolimus serum concentrations.
    Tafamidis: (Moderate) Caution is advised with the coadministration of tafamidis and glecaprevir as coadministration may increase the plasma concentrations of glecaprevir increasing the risk of adverse effects. Glecaprevir is a substrate of the breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor. (Moderate) Caution is advised with the coadministration of tafamidis and pibrentasvir due to the potential for increased plasma concentrations of pibrentasvir increasing the risk of adverse effects. Pibrentasvir dose adjustment may be needed with coadministration. Pibrentasvir is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
    Talazoparib: (Major) Avoid coadministration of glecaprevir with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; glecaprevir is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure. (Major) Avoid coadministration of pibrentasvir with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; pibrentasvir is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Tamoxifen: (Moderate) Caution is advised with the coadministration of glecaprevir and tamoxifen as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); tamoxifen is a P-gp inhibitor.
    Telithromycin: (Moderate) Caution is advised with the coadministration of glecaprevir and telithromycin as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of organic anion transporting polypeptide (OATP) 1B1/3 and P-glycoprotein (P-gp); telithromycin is an inhibitor of these drug transporters. (Moderate) Caution is advised with the coadministration of pibrentasvir and telithromycin as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); telithromycin is an inhibitor of P-gp.
    Temsirolimus: (Moderate) Caution is advised with the coadministration of pibrentasvir and temsirolimus as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Both pibrentasvir and temsirolimus are substrates and inhibitors of P-glycoprotein (P-gp). (Moderate) Monitor for an increase in adverse reactions of both glecaprevir and temsirolimus if coadministration is necessary. Both drugs are P-glycoprotein (P-gp) substrates and inhibitors. Concomitant use may lead to increased concentrations of both glecaprevir and temsirolimus.
    Teniposide: (Moderate) Caution is advised with the coadministration of glecaprevir and teniposide as coadministration may increase serum concentrations of teniposide and increase the risk of adverse effects. Teniposide is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and teniposide as coadministration may increase serum concentrations of teniposide and increase the risk of adverse effects. Teniposide is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
    Tenofovir Alafenamide: (Moderate) Caution is advised with the coadministration of glecaprevir and tenofovir alafenamide as coadministration may increase serum concentrations of tenofovir alafenamide and increase the risk of adverse effects. Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of all these drug transporters. (Moderate) Caution is advised with the coadministration of pibrentasvir and tenofovir alafenamide as coadministration may increase serum concentrations of tenofovir alafenamide and increase the risk of adverse effects. Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of all these drug transporters.
    Tenofovir Alafenamide: (Moderate) Caution is advised with the coadministration of glecaprevir and tenofovir alafenamide as coadministration may increase serum concentrations of tenofovir alafenamide and increase the risk of adverse effects. Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of all these drug transporters. (Moderate) Caution is advised with the coadministration of pibrentasvir and tenofovir alafenamide as coadministration may increase serum concentrations of tenofovir alafenamide and increase the risk of adverse effects. Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1/3, and breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of all these drug transporters.
    Tepotinib: (Moderate) Caution is advised with coadministration of glecaprevir and tepotinib as increased plasma concentrations of glecaprevir may occur resulting in increased risk of glecaprevir-related adverse events. Glecaprevir is a substrate of P-gp and BCRP and tepotinib is a P-gp inhibitor. (Moderate) Monitor for an increase in pibrentasvir-related adverse effects if concomitant use of tepotinib is necessary. Concomitant use may increase pibrentasvir exposure. Pibrentasvir is a substrate of P-gp and tepotinib is a P-gp inhibitor.
    Teriflunomide: (Moderate) Caution is advised with the coadministration of glecaprevir and teriflunomide as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of organic anion transporting polypeptide (OATP) 1B1/3 and breast cancer resistance protein (BCRP); teriflunomide is an inhibitor of these drug transporters. (Moderate) Caution is advised with the coadministration of pibrentasvir and teriflunomide as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of breast cancer resistance protein (BCRP); teriflunomide is an inhibitor of BCRP.
    Tezacaftor; Ivacaftor: (Moderate) Caution is advised with the coadministration of glecaprevir and ivacaftor as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); ivacaftor is a P-gp inhibitor.
    Ticagrelor: (Moderate) Caution is advised with the coadministration of glecaprevir and ticagrelor as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and ticagrelor are both substrates and inhibitors of P-glycoprotein (P-gp). (Moderate) Caution is advised with the coadministration of pibrentasvir and ticagrelor as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Both pibrentasvir and ticagrelor are substrates and inhibitors of P-glycoprotein (P-gp).
    Tipranavir: (Moderate) Caution is advised with the coadministration of glecaprevir and tipranavir as coadministration may decrease serum concentrations of glecaprevir and/or increase serum concentrations of tipranavir. This may result in decreased efficacy of glecaprevir and/or increased tipranavir-related adverse effects. Glecaprevir is a substrate and inhibitor of P-glycoprotein (P-gp); tipranavir is a substrate and inducer of P-gp. (Moderate) Caution is advised with the coadministration of pibrentasvir and tipranavir as coadministration may decrease serum concentrations of pibrentasvir and/or increase serum concentrations of tipranavir. This may result in decreased efficacy of pibrentasvir and/or increased tipranavir-related adverse effects. Pibrentasvir is a substrate and inhibitor of P-glycoprotein (P-gp); tipranavir is a substrate and inducer of P-gp.
    Tolazamide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Tolbutamide: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Tolvaptan: (Major) In patients receiving tolvaptan for autosomal dominant polycystic kidney disease (ADPKD), avoid coadministration of glecaprevir due to the potential for increased glecaprevir exposure. Additionally, a reduction in tolvaptan dosage for hyponatremia treatment may be necessary if coadministered due to the potential for increased tolvaptan plasma concentrations. Tolvaptan is a BCRP inhibitor and P-gp substrate, and the oxobutyric acid metabolite of tolvaptan is an OATP1B1/3 inhibitor; glecaprevir is a P-gp inhibitor and BCRP and OATP1B1/3 substrates. (Major) In patients receiving tolvaptan for autosomal dominant polycystic kidney disease (ADPKD), avoid coadministration of pibrentasvir due to the potential for increased pibrentasvir exposure. Additionally, a reduction in tolvaptan dosage for hyponatremia treatment may be necessary if coadministered due to the potential for increased tolvaptan plasma concentrations. Tolvaptan is a P-gp substrate and BCRP inhibitor; pibrentasvir is a P-gp inhibitor and BCRP substrate.
    Topotecan: (Major) Avoid coadministration of glecaprevir with oral topotecan due to increased topotecan exposure; glecaprevir may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP); glecaprevir is a P-gp and BCRP inhibitor. Following escalating doses of a dual inhibitor of BCRP and P-gp, the AUC of topotecan lactone and total topotecan increased by approximately 2.5-fold compared to topotecan alone. Coadministration of a dual P-gp/BCRP inhibitor with intravenous topotecan increased total topotecan exposure by 1.2-fold and exposure to topotecan lactone by 1.1-fold. (Major) Avoid coadministration of pibrentasvir with oral topotecan due to increased topotecan exposure; pibrentasvir may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP); pibrentasvir is a P-gp and BCRP inhibitor. Following escalating doses of a dual inhibitor of BCRP and P-gp, the AUC of topotecan lactone and total topotecan increased by approximately 2.5-fold compared to topotecan alone. Coadministration of a dual P-gp/BCRP inhibitor with intravenous topotecan increased total topotecan exposure by 1.2-fold and exposure to topotecan lactone by 1.1-fold.
    Trandolapril; Verapamil: (Moderate) Caution is advised with the coadministration of glecaprevir and verapamil as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and verapamil are both substrates and inhibitors of P-glycoprotein (P-gp). (Moderate) Caution is advised with the coadministration of pibrentasvir and verapamil as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Pibrentasvir and verapamil are both substrates and inhibitors of P-glycoprotein (P-gp).
    Tucatinib: (Moderate) Caution is advised with coadministration of glecaprevir and tucatinib as increased plasma concentrations of glecaprevir may occur resulting in increased risk of glecaprevir-related adverse events. Glecaprevir is a substrate of P-glycoprotein (P-gp) and tucatinib is a P-gp inhibitor. (Moderate) Caution is advised with coadministration of pibrentasvir and tucatinib as increased plasma concentrations of pibrentasvir may occur resulting in increased risk of pibrentasvir-related adverse events. Pibrentasvir is a substrate of P-glycoprotein (P-gp) and tucatinib is a P-gp inhibitor.
    Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with glecaprevir. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the BCRP and P-gp drug transporters; glecaprevir is a BCRP and P-gp inhibitor. (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with pibrentasvir. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the BCRP and P-gp drug transporters; pibrentasvir is a BCRP and P-gp inhibitor.
    Ultralente Insulin: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
    Umeclidinium: (Moderate) Caution is advised with the coadministration of glecaprevir and umeclidinium as coadministration may increase serum concentrations of umeclidinium and increase the risk of adverse effects. Umeclidinium is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and umeclidinium as coadministration may increase serum concentrations of umeclidinium and increase the risk of adverse effects. Umeclidinium is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
    Umeclidinium; Vilanterol: (Moderate) Caution is advised with the coadministration of glecaprevir and umeclidinium as coadministration may increase serum concentrations of umeclidinium and increase the risk of adverse effects. Umeclidinium is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and umeclidinium as coadministration may increase serum concentrations of umeclidinium and increase the risk of adverse effects. Umeclidinium is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
    Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with glecaprevir due to the potential for increased venetoclax exposure. Additionally, glecaprevir exposure may be increased. Resume the original venetoclax dose 2 to 3 days after discontinuation of glecaprevir. Both venetoclax and glecaprevir are P-glycoprotein (P-gp) substrates and inhibitors. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study. (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with pibrentasvir due to the potential for increased venetoclax exposure. Additionally, pibrentasvir exposure may be increased. Resume the original venetoclax dose 2 to 3 days after discontinuation of pibrentasvir. Both venetoclax and pibrentasvir are P-glycoprotein (P-gp) substrates and inhibitors. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
    Verapamil: (Moderate) Caution is advised with the coadministration of glecaprevir and verapamil as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and verapamil are both substrates and inhibitors of P-glycoprotein (P-gp). (Moderate) Caution is advised with the coadministration of pibrentasvir and verapamil as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Pibrentasvir and verapamil are both substrates and inhibitors of P-glycoprotein (P-gp).
    Vinblastine: (Moderate) Caution is advised with the coadministration of pibrentasvir and vinblastine as coadministration may increase serum concentrations of vinblastine and increase the risk of adverse effects. Vinblastine is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Vincristine Liposomal: (Moderate) Caution is advised with the coadministration of pibrentasvir and vincristine as coadministration may increase serum concentrations of vincristine and increase the risk of adverse effects. Vincristine is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Vincristine: (Moderate) Caution is advised with the coadministration of pibrentasvir and vincristine as coadministration may increase serum concentrations of vincristine and increase the risk of adverse effects. Vincristine is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Voclosporin: (Moderate) Monitor for an increase in glecaprevir-related adverse reactions if coadministration with voclosporin is necessary. Concomitant use may increase glecaprevir exposure. Glecaprevir is an P-gp and OATP1B1/3 substrate; voclosporin is P-gp and OATP1B1/3 inhibitor. (Moderate) Monitor for an increase in pibrentasvir-related adverse effects if concomitant use of voclosporin is necessary. Concomitant use may increase pibrentasvir exposure. Pibrentasvir is a substrate of P-gp and voclosporin is a P-gp inhibitor.
    Warfarin: (Moderate) Fluctuations in International Normalized Ratio (INR) have been observed in warfarin recipients who were also receiving treatment for hepatitis C virus (HCV) infections, including glecaprevir. It is recommended to closely monitor these patients for changes in INR both during and after discontinuation of the HCV treatment regimen. (Moderate) Fluctuations in International Normalized Ratio (INR) have been observed in warfarin recipients who were also receiving treatment for hepatitis C virus (HCV) infections, including pibrentasvir. It is recommended to closely monitor these patients for changes in INR both during and after discontinuation of the HCV treatment regimen.
    Zonisamide: (Moderate) Caution is advised with the coadministration of glecaprevir and zonisamide as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); zonisamide is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and zonisamide as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); zonisamide is an inhibitor of P-gp.

    PREGNANCY AND LACTATION

    Pregnancy

    No adequate, well-controlled studies have been conducted with glecaprevir; pibrentasvir in human pregnancy, and it is unknown whether glecaprevir; pibrentasvir poses a risk to the developing fetus. In animal studies, no adverse effects on embryo-fetal development and pre/postnatal development were identified in rats (glecaprevir) and mice and rabbits (pibrentasvir) exposed to doses higher than the recommended human dose.

    It is unknown if glecaprevir and pibrentasvir are excreted in human milk, affect milk production, or have an adverse effect on nursing infants. Animal studies showed that both components were present in milk, without an effect on growth and development in the nursing animal. Consider the benefits of breast-feeding, the risk of infant drug exposure, and the risk of an untreated or inadequately treated condition.

    MECHANISM OF ACTION

    Glecaprevir; pibrentasvir is active against chronic infections caused by genotypes 1, 2, 3, 4, 5, and 6 hepatitis C virus (HCV). Glecaprevir is an HCV NS3/4A protease inhibitor. Pibrentasvir is an HCV NS5A inhibitor.
    Glecaprevir: Glecaprevir is an inhibitor of the HCV NS3/4A protease, which is necessary for the proteolytic cleavage of the HCV encoded polyprotein (into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins) and is essential for viral replication.
    In cell cultures, decreased susceptibility to glecaprevir was demonstrated in HCV genotypes 1a, 1b, 2a, 3a, 4a, and 6a with the emergence of amino acid substitutions at NS3 positions A156 and D/Q168. NS3 substitution at A156 conferred a greater than 100-fold reduction in glecaprevir susceptibility. NS3 substitutions conferring a greater than 30-fold reduction in glecaprevir susceptibility included D168F/Y in genotype 1a, Q168R in genotype 3a, and D168A/G/H/V/Y in genotype 6a. Combinations of these substitutions often resulted in greater reductions in susceptibility than single substitutions alone. An NS3 Q80R substitution in genotype 3a caused a 21-fold reduction in glecaprevir susceptibility; Q80 substitutions in genotypes 1a and 1b did not reduce glecaprevir susceptibility. Individual amino acid substitutions associated with resistance to other HCV protease inhibitors at other positions (i.e., 36, 43, 54, 55, 56, 155, 166, or 170) in NS3 generally did not show reduced susceptibility to glecaprevir. Cross-resistance is possible between glecaprevir and other HCV NS3/4A protease inhibitors; cross-resistance is not expected with sofosbuvir, pegylated interferon, or ribavirin.
     
    Pibrentasvir: Pibrentasvir prevents hepatitis C viral replication by inhibiting the HCV NS5A protein. Although the exact mechanism is unknown, data suggest NS5A inhibitors may prevent replication by blocking viral hyperphosphorylation. It has been proposed that tight control of phosphorylation versus hyperphosphorylation is needed for efficient viral function.
    In cell cultures, decreased susceptibility to pibrentasvir was demonstrated in HCV genotypes 1a, 2a, and 3a following the emergence of amino acid substitutions at known NS5A inhibitor-resistance-associated positions, including Q30D/deletion, Y93D/H/N or H58D + Y93H in genotype 1a, F28S + M31I or P29S + K30G in genotype 2a, and Y93H in genotype 3a. Most individual NS5A amino acid substitutions associated with resistance to other HCV NS5A inhibitors at positions 24, 28, 30, 31, 58, 92, or 93 did not show reduced susceptibility to pibrentasvir; however, reduced pibrentasvir susceptibility was observed with M28G and Q30D in genotype 1a (244- and 94-fold, respectively) and P32-deletion in genotype 1b (1,036-fold). Combinations of these substitutions may result in greater reductions in susceptibility than single substitutions alone. Decreased susceptibility to pibrentasvir has also been observed with genotype 3b. In the presence of naturally occurring polymorphisms, K30 and M31 in NS5A, the susceptibility of a genotype 3b replicon to pibrentasvir is reduced by 24-fold relative to the drug's activity in a genotype 3a replicon. When an NS5A Y93H substitution was introduced into genotype 3b, susceptibility was further reduced 6,336-fold. Cross-resistance is possible between pibrentasvir and other HCV NS5A inhibitors; cross-resistance is not expected with sofosbuvir, pegylated interferon, or ribavirin.

    PHARMACOKINETICS

    Glecaprevir; pibrentasvir is administered orally.
    Glecaprevir: Following administration, approximately 98% is bound to plasma protein. Metabolism is primarily via the biliary-fecal route, with secondary metabolism via hepatic isoenzyme CYP3A. Most of the drug is excreted in the feces (92%), with only 0.7% of the dose excreted in the urine. The elimination half-life is approximately 6 hours.
    Pibrentasvir: Following administration, more than 99% is bound to plasma protein. Metabolism is via the biliary-fecal route with approximately 97% of the drug excreted in the feces; no drug is excreted in the urine. The elimination half-life is approximately 13 hours.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1/3
    Both glecaprevir and pibrentasvir are substrates and inhibitors of the drug transporters P-gp and BCRP. Glecaprevir is also partially metabolized by CYP3A and is a substrate of OATP1B1/3; both drugs are inhibitors of OATP1B1/3. Coadministration of glecaprevir; pibrentasvir with drugs that inhibit P-gp, BRCP, or OATP1B1/3 may increase the plasma concentrations of glecaprevir and/or pibrentasvir. Coadministration of glecaprevir; pibrentasvir with drugs that induce P-gp/CYP3A may decrease glecaprevir and pibrentasvir concentrations. Coadministration of glecaprevir; pibrentasvir with drugs that are substrates of P-gp, BRCP, OATP1B1, or OATP1B3 may increase plasma concentrations of those drugs. Glecaprevir and pibrentasvir are weak inhibitors of CYP3A, CYP1A2, and uridine glucuronosyltransferase (UGT); however, significant drug interactions are not expected when glecaprevir; pibrentasvir is coadministered with substrates of CYP3A, CYP1A2, CYP2C9, CYP2C19, CYP2D6, UGT1A1, or UGT1A4.

    Oral Route

    Glecaprevir: After oral administration, peak plasma concentrations are reached at approximately 5 hours. In clinical studies, the mean steady-state Cmax and AUC of glecaprevir were 597 ng/mL and 4,800 ng x hour/mL, respectively. Relative to healthy subjects, glecaprevir Cmax was 51% lower and AUC was similar in HCV-infected subjects without cirrhosis, respectively. Administration with food increases the mean systemic exposure by 83% to 163% relative to fasting.
    Pibrentasvir: After oral administration, peak plasma concentrations are reached at approximately 5 hours. In clinical studies, the mean steady-state Cmax and AUC of pibrentasvir were 110 ng/mL and 1,430 ng x hour/mL, respectively. Relative to healthy subjects, pibrentasvir Cmax and AUC were 63% and 34% lower, respectively, in HCV-infected subjects without cirrhosis. Administration with food increases the mean systemic exposure by 40% to 53% relative to fasting.