Sofosbuvir; velpatasvir is a combination oral product indicated for the treatment of adults and pediatric patients 3 years and older infected with chronic hepatitis C virus (HCV), including genotypes 1, 2, 3, 4, 5, and 6. Sofosbuvir; velpatasvir is the first drug approved for the treatment of all 6 HCV genotypes. For patients without cirrhosis and those with compensated cirrhosis, the drug may be administered as a monotherapy; however, patients with decompensated cirrhosis must receive sofosbuvir; velpatasvir in combination with ribavirin.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
Oral Tablets
-Administer with or without food.
-If administered with ribavirin, take ribavirin with food.
Oral Pellets
-For patients 6 years and older, administer with or without food.
-For patients younger than 6 years, administer with food to increase tolerability related to palatability.
-Inspect the packaging for damage. Do not use if the carton tamper-evident seal or the pellet packet seal is broken or damaged.
-Do not open packets until ready for use; shake the pellets packet gently to settle the pellets.
-If pellets are taken with food:
--Add 1 or more spoonfuls of non-acidic soft food (i.e., pudding, chocolate syrup, ice cream) to a bowl at or below room temperature.
-Sprinkle the entire contents of the prescribed number of pellet packets onto the food in the bowl.
-Gently mix with a spoon.
-Ingest pellets within 15 minutes of mixing with food and swallow entire contents without chewing to avoid a bitter taste. Do not store any leftover oral pellets mixed with food for use at a later time.
-If pellets are taken without food:
--Pour the entire contents of the pellet packet directly in the mouth and swallow without chewing to avoid a bitter taste.
-If needed, water may be taken after swallowing the pellets.
-Repeat the process if more than 1 pellet packet is prescribed.
-Make sure all the oral pellets are taken and that no pellets remain in the packet(s) or food.
Headache (10% to 22%), fatigue (15% to 32%), asthenia (5%), insomnia (5% to 11%), and irritability (5% or more) were commonly reported during clinical trials with sofosbuvir; velpatasvir. Depression occurred in 1% of patients during clinical trials.
Nausea (7% to 15%) and diarrhea (6% to 10%) were reported during sofosbuvir; velpatasvir clinical trials. Among 41 pediatric patients younger than 6 years of age, vomiting was reported in 15% of patients and spitting up the drug was reported in 10% of patients. Five (12%) patients discontinued treatment after vomiting or spitting up the drug.
Anemia was reported in 26% of patients during clinical trials with sofosbuvir; velpatasvir and ribavirin. Hemoglobin was decreased to less than 10 g/dL in 23% of patients and decreased to less than 8.5 g/dL in 7% of patients during clinical trials with this combination. Treatment was permanently discontinued in 17% of patients.
Rash was reported in 2% to 5% of patients during sofosbuvir; velpatasvir clinical trials. Skin rashes, sometimes with blisters or angioedema-like swelling, have also been reported in postmarketing surveillance.
Laboratory abnormalities were reported during sofosbuvir; velpatasvir clinical trials. Elevated lipase (3-times ULN) was noted in 2% to 6% of patients. Elevated creatine kinase (10-times ULN) was reported in 1% to 2% of patients. Hyperbilirubinemia, reported as indirect bilirubin increases up to 3 mg/dL above baseline, was noted among HIV-1 and HCV coinfected patients also treated with atazanavir; ritonavir-based antiretroviral regimens. Elevations in indirect bilirubin were not associated with clinical adverse events. Clinical and hepatic laboratory monitoring (including direct bilirubin) is recommended for patients with decompensated cirrhosis receiving treatment with sofosbuvir; velpatasvir and ribavirin.
Hepatitis B exacerbation (including fulminant hepatitis, hepatic failure requiring liver transplant, and death) has been reported in patients coinfected with hepatitis B and C receiving treatment with direct-acting antivirals (DAA), such as sofosbuvir; velpatasvir. The exact mechanism is unknown; however, a commonly reported sequence of events includes initiation of a DAA-based HCV regimen, rapid drop in HCV RNA to undetectable levels within 1 to 2 weeks of liver enzyme normalization, followed by a rise in HBV DNA (with or without increased transaminases) between treatment weeks 4 and 8.
Missing doses of direct-acting antiviral (DAA) therapy, such as sofosbuvir; velpatasvir, is relatively common; however, outcome data in patients with incomplete adherence is limited and the threshold at which a lack of adherence to treatment results in a reduced systemic viral response (SVR) is unknown. For treatment naive patients with or without compensated cirrhosis who miss doses during the first 28 days of therapy with sofosbuvir; velpatasvir:
-If 7 days or less are missed, restart therapy immediately and complete treatment for the originally planned duration.
-If 8 days or more are missed, restart therapy immediately and obtain HCV RNA as soon as possible (preferably on the same day treatment is restarted).
--If HCV RNA is undetectable, complete treatment for the originally planned duration; however, for genotype 3 and/or cirrhosis, recommend extending treatment for an additional 4 weeks.
-If HCV RNA is greater than 25 International units/L, or not obtained, extend the treatment duration for an additional 4 weeks.
For treatment naive patients with or without compensated cirrhosis who miss doses after receiving at least 28 days of therapy with sofosbuvir; velpatasvir:
-If 7 days or less are missed, restart therapy immediately and complete treatment for the originally planned duration.
-If 8 to 20 consecutive days are missed, restart therapy immediately and obtain HCV RNA as soon as possible (preferably on the same day treatment is restarted).
--If HCV RNA is undetectable, complete treatment for the originally planned duration; however, for genotype 3 and/or cirrhosis, recommend extending treatment for an additional 4 weeks.
-If HCV RNA is greater than 25 International units/L, or not obtained, stop treatment and retreat according to guideline recommendations for patients requiring retreatment.
-If 21 consecutive days or more are missed, stop treatment and assess for SVR12. If SVR12 has not been achieved, retreat according to guideline recommendations for patients requiring retreatment.
For treatment experienced patients or other patient populations (e.g., posttransplant, decompensated cirrhosis), the patient should be managed in consultation with an expert. Question all patients with incomplete adherence about contributing factors and counsel them regarding the importance of adherence to treatment.
No adequate human data are available to establish whether or not sofosbuvir; velpatasvir poses a risk to pregnancy outcomes. In animal studies, no adverse effects on fetal development were observed with either sofosbuvir or velpatasvir. Because animal studies are not always predictive of human response, use of the drug during pregnancy should only be considered if the benefits justify the potential risk to the fetus. In certain patient populations, sofosbuvir; velpatasvir is administered with ribavirin. The use of sofosbuvir; velpatasvir in combination with ribavirin is contraindicated in pregnant women and in the male partners of women who are pregnant. Ribavirin may cause birth defects and death of the exposed fetus. Ribavirin therapy also may cause male-mediated teratogenicity and is contraindicated for use during pregnancy, in females who may become pregnant, or in men whose female partners are pregnant. Studies of ribavirin indicate teratogenic (e.g., malformations of skull, palate, eye, jaw, limbs, skeleton, and GI tract) or embryocidal properties in all of the animal species tested. Patients and their partners are required use 2 reliable forms of effective contraception during treatment and for 6 months after use of these combination therapies. Patients who are not willing to practice strict contraception should not receive sofosbuvir; velpatasvir with ribavirin. Females must also undergo a pregnancy test immediately prior to initiation of therapy, monthly during therapy, and for 6 months post-therapy. To monitor maternal-fetal outcomes of pregnancies in female patients and female partners of male patients exposed to ribavirin during treatment and for 6 months following cessation of treatment, health care providers are encouraged to report any cases to the Ribavirin Pregnancy Registry; telephone (800) 593-2214. For patient who are also infected with HIV and taking concomitant antiretroviral agents, an Antiretroviral Pregnancy Registry is available at (800) 258-4263.
According to the manufacturer, it is not known if sofosbuvir; velpatasvir or their metabolites are excreted in human milk, affect milk production, or have an adverse effect on nursing infants. Consider the benefits of breast-feeding, the risk of infant drug exposure, and the risk of an untreated or inadequately treated condition. Boceprevir, simeprevir, or sofosbuvir may be considered as alternatives; however, their excretions into human breast milk are also unknown. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.
HIV treatment guidelines recommend all adult and adolescent patients presenting with HIV infection undergo routine screening for hepatitis C virus (HCV). Additionally, perform HCV screening in any child whose mother is known to have HCV infection. For HCV seronegative individuals who are at continued high risk of acquiring hepatitis C, specifically men who have sex with men (MSM) or persons who inject drugs, additional HCV screening is recommended annually or as indicated by clinical presentation (e.g., unexplained ALT elevation), risk activities, or exposure. Similarly, the AASLD/IDSA HCV guidelines and the CDC preexposure prophylaxis (PrEP) guidelines recommend HCV serologic testing at baseline and every 12 months for MSM, transgender women, and persons who inject drugs. Use an FDA-approved immunoassay licensed for detection of HCV antibodies (anti-HCV); in settings where acute HCV infection is suspected or in persons with known prior infection that cleared spontaneously or after treatment, use of nucleic acid testing for HCV RNA is recommended. If hepatitis C and HIV coinfection is identified, consider treating both viral infections concurrently. It is recommended to use a fully suppressive antiretroviral therapy and an HCV regimen in all patients with coinfection regardless of CD4 count, as lower CD4 counts do not appear to compromise the efficacy of HCV treatment. In most patients, a simplified pangenotypic HCV regimen (i.e., glecaprevir; pibrentasvir or sofosbuvir; velpatasvir) may be an appropriate choice; however, these regimens are NOT recommended for use in persons with HCV and HIV coinfection who: are treatment-experienced with HCV relapse (reinfection after successful therapy is not an exclusion); have decompensated cirrhosis; on a tenofovir disoproxil fumarate containing regimen with eGFR less than 60 mL/minute; on efavirenz, etravirine, nevirapine, or boosted protease inhibitor; have untreated chronic hepatitis B; are pregnant. Patients with HCV and HIV coinfection who meet these exclusion criteria should be treated for HCV following standard approaches as described in the AASLD/IDSA HCV guidelines. Treatment of HCV infection in children younger than 3 years is not usually recommended; however, treatment should be considered for all children 3 years and older with HCV and HIV coinfection who have no contraindications to treatment. Instruct patients with coinfection to avoid consuming alcohol, limit ingestion of potentially hepatotoxic medications, avoid iron supplementation in the absence of documented iron deficiency, and receive vaccinations against hepatitis A and hepatitis B as appropriate.
Use of direct-acting antivirals (DAA), such as sofosbuvir and velpatasvir, 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 sofosbuvir; velpatasvir. 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 sofosbuvir; velpatasvir recipient develops signs of HBV reactivation, initiate appropriate treatment for HBV infection as clinically indicated.
Caution is advised when prescribing sofosbuvir; velpatasvir 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.
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 sofosbuvir; velpatasvir. 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.
Baseline NS5A resistance-associated substitutions (RAS) testing is recommended for HCV genotype 3-infected, treatment-naive patients with cirrhosis and treatment-experienced patients without cirrhosis. If Y93H is present, ribavirin should be added or a different regimen should be used. RAS testing is NOT recommended for patients with genotypes 1, 2, 4, 5, or 6.
Initiation of therapy for HCV infection:
-HCV screening (i.e., HCV-antibody for initial screening, HCV-RNA for confirmation of active infection) recommended for:
-All persons 18 years and older (a 1-time, routine, opt-out test)
-All persons younger than 18 years with any of the below activities, exposures, or conditions and circumstances associated with an increased risk of HCV infection (a 1-time test)
-Each pregnancy (testing as part of routine prenatal care)
-All persons with any of the below activities, exposures, or conditions and circumstances associated with an increased risk of HCV infection (periodic repeat testing)
-All persons who inject drugs (annual testing)
-Men with HIV who have unprotected sex with men, and men who have sex with men taking HIV pre-exposure prophylaxis (annual testing)
-HCV risk-associated activities, exposures, or conditions and circumstances include:-Activities: injection drug use (current or ever, including those who injected only once); intranasal illicit drug use; use of glass crack pipes; engagement in chem sex (i.e., combining sex with nonprescription drugs to facilitate or enhance sexual encounter); men who have sex with men.
-Exposures: persons on long-term hemodialysis (ever); persons with percutaneous or parenteral exposures in an unregulated setting; healthcare, emergency medical, and public safety workers after needlestick, sharps, or mucosal exposure to HCV-infected blood; children born to mothers with HCV; persons who were ever incarcerated; certain recipients of a prior transfusion or organ transplant (i.e., received blood from a donor who later tested positive for HCV; received a blood transfusion or blood component, or underwent an organ transplant before July 1992; received clotting factor concentrates produced before 1987).
-Conditions and Circumstances: HIV or HBV infection; sexually active persons about to start pre-exposure prophylaxis for HIV; chronic hepatic disease or chronic hepatitis, including unexplained elevated ALT concentrations; solid organ donors and recipients.
-Treatment is recommended for all patients with acute or chronic HCV infection, except those with short life expectancy that cannot be remediated by HCV therapy, liver transplantation or other direct therapy.
-Laboratory tests recommended prior to initiating antiviral therapy: quantitative HCV-RNA test to document baseline viral load; HCV genotype and subtype test (if starting a non-pangenotypic direct-acting antiviral [DAA]); HBsAg test for active HBV coinfection, and anti-HBs and anti-HBc test for prior HBV coinfection (if starting DAA); test for HIV coinfection (if starting DAA); testing for presence of resistance-associated substitutions (RAS).
Place in therapy for HCV infection:
-A simplified pangenotypic HCV regimen of sofosbuvir; velpatasvir can be used in treatment-naive patients with or without compensated cirrhosis who do NOT have any of the following characteristics:
--genotype 3 with cirrhosis if RAS Y93H is present
-current or prior episode of decompensated cirrhosis (Child-Pugh 7 or more)
-end-stage renal disease (eGFR less than 30 mL/minute/m2)
-hepatocellular carcinoma
-prior liver transplant
-pregnant
-hepatitis B positive
-HIV positive IF receiving a tenofovir disoproxil fumarate containing regimen AND have an eGFR less than 60 mL/minute
-Recommended therapy for adults who are:
-treatment-naive with genotypes 1, 2, 4, 5, 6 with or without compensated cirrhosis.
-treatment-naive with genotype 3 without cirrhosis.
-treatment-naive with genotype 3 with compensated cirrhosis if RAS Y93H negative.
-treatment-naive and experienced with genotypes 1, 2, 3, 4, 5, 6 with decompensated cirrhosis (given with or without ribavirin).
-treatment-naive and experienced liver transplant patients with genotypes 1, 2, 3, 4, 5, 6 with or without compensated cirrhosis.
-treatment-naive and experienced liver transplant patients with genotypes 1, 2, 3, 4, 5, 6 with decompensated cirrhosis (must be given with ribavirin).
-treatment-naive and non-DAA-experienced kidney transplant patients with genotypes 1, 2, 3, 4, 5, 6 with or without compensated cirrhosis.
-HCV-uninfected recipients of liver transplants from HCV-viremic donors.
-HCV-uninfected recipients of non-liver transplants from HCV-viremic donors.
-Alternative therapy for adults who are:-treatment-naive with genotype 3 with compensated cirrhosis if RAS Y93H positive (must be given with ribavirin)
-Pediatric guidelines are also available.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: hepatitis C virus
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of chronic hepatitis C infection in treatment-naive and experienced persons:
-for the treatment of chronic hepatitis C genotypes 1, 2, 3, 4, 5, and 6 infection in persons without cirrhosis or with compensated cirrhosis (Child-Pugh A), including those who have undergone liver transplant:
NOTE: Guidelines recommend testing those with genotype 3 HCV for NS5A resistance-associated substitutions (RAS) prior to initiating therapy.
Oral dosage:
Adults: 400 mg sofosbuvir; 100 mg velpatasvir PO once daily for 12 weeks. If a treatment-naive person with compensated cirrhosis has RAS Y93H at baseline, either add ribavirin or consider use of an alternative regimen.
Children and Adolescents 3 to 17 years weighing 30 kg or more: 400 mg sofosbuvir; 100 mg velpatasvir PO once daily for 12 weeks.
Children 3 to 12 years weighing 17 to 29 kg: 200 mg sofosbuvir; 50 mg velpatasvir PO once daily for 12 weeks.
Children 3 to 12 years weighing less than 17 kg: 150 mg sofosbuvir; 37.5 mg velpatasvir PO once daily for 12 weeks.
-for the treatment of chronic hepatitis C genotypes 1, 2, 3, 4, 5, and 6 infection in persons with decompensated cirrhosis (Child-Pugh B or C) who are ribavirin eligible:
Oral dosage:
Adults: 400 mg sofosbuvir; 100 mg velpatasvir PO once daily for 12 weeks in combination with ribavirin.
Children and Adolescents 3 to 17 years weighing 30 kg or more: 400 mg sofosbuvir; 100 mg velpatasvir PO once daily for 12 weeks in combination with ribavirin.
Children 3 to 12 years weighing 17 to 29 kg: 200 mg sofosbuvir; 50 mg velpatasvir PO once daily for 12 weeks in combination with ribavirin.
Children 3 to 12 years weighing less than 17 kg: 150 mg sofosbuvir; 37.5 mg velpatasvir PO once daily for 12 weeks in combination with ribavirin.
-for the treatment of chronic hepatitis C genotypes 1, 2, 3, 4, 5, and 6 infection in persons with decompensated cirrhosis (Child-Pugh B or C) who are ribavirin ineligible*:
Oral dosage:
Adults: 400 mg sofosbuvir; 100 mg velpatasvir PO once daily for 24 weeks. Recommendation includes patients who may or may not be candidates for liver transplant, including those with hepatocellular carcinoma.
-for the treatment of chronic hepatitis C genotypes 1, 2, 3, 4, 5, and 6 infection in persons with decompensated cirrhosis (Child-Pugh B or C) in whom prior sofosbuvir- or NS5A-based treatment failed*:
Oral dosage:
Adults: 400 mg sofosbuvir; 100 mg velpatasvir PO once daily for 24 weeks in combination with ribavirin. Recommendation includes patients who may or may not be candidates for liver transplant, including those with hepatocellular carcinoma.
-for the treatment of chronic hepatitis C genotypes 1, 2, 3, 4, 5, and 6 infection in treatment-naive persons with decompensated cirrhosis (Child-Pugh B or C) who have undergone a liver transplant*:
Oral dosage:
Adults: 400 mg sofosbuvir; 100 mg velpatasvir PO once daily for 12 weeks in combination with ribavirin.
-for the treatment of chronic hepatitis C genotypes 1, 2, 3, 4, 5, and 6 infection in treatment-experienced persons with decompensated cirrhosis (Child-Pugh B or C) who have undergone a liver transplant*:
Oral dosage:
Adults: 400 mg sofosbuvir; 100 mg velpatasvir PO once for 24 weeks in combination with ribavirin.
-for the treatment of chronic hepatitis C genotypes 1, 2, 3, 4, 5, and 6 infection in treatment-naive and non-DAA-experienced patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have undergone a kidney transplant*:
Oral dosage:
Adults: 400 mg sofosbuvir; 100 mg velpatasvir PO once daily for 12 weeks.
-for preemptive treatment of HCV-uninfected recipients of organ transplants from HCV-viremic donors*:
Oral dosage:
Adults: 400 mg sofosbuvir; 100 mg velpatasvir PO once daily for 12 weeks.
Maximum Dosage Limits:
-Adults
400 mg/day PO for sofosbuvir; 100 mg/day PO for velpatasvir.
-Geriatric
400 mg/day PO for sofosbuvir; 100 mg/day PO for velpatasvir.
-Adolescents
400 mg/day PO for sofosbuvir; 100 mg/day PO for velpatasvir.
-Children
3 to 12 years weighing 30 kg or more: 400 mg/day PO for sofosbuvir; 100 mg/day PO for velpatasvir.
3 to 12 years weighing 17 to 29 kg: 200 mg/day PO for sofosbuvir; 50 mg/day PO for velpatasvir.
3 to 12 years weighing less than 17 kg: 150 mg/day PO for sofosbuvir; 37.5 mg/day PO for velpatasvir (oral pellets only).
1 to 2 years: Safety and efficacy not established.
-Infants
Safety and efficacy not established.
-Neonates
Safety and efficacy not established.
Patients with Hepatic Impairment Dosing
No dosage adjustments are needed for patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, or C).
Patients with Renal Impairment Dosing
No dosage adjustments are needed for any degree of renal impairment, including end stage renal disease requiring hemodialysis.
*non-FDA-approved indication
Acalabrutinib: (Moderate) Coadministration of acalabrutinib and sofosbuvir may increase the exposure and the risk of toxicity of sofosbuvir. Acalabrutinib is a substrate and inhibitor of the breast cancer resistance protein (BCRP) transporter in vitro; it may inhibit intestinal BCRP. Sofosbuvir is a BCRP transporter substrate. (Moderate) Coadministration of acalabrutinib and velpatasvir may increase the exposure and the risk of toxicity of either drug. Both acalabrutinib and velpatasvir are a substrate and inhibitor of the breast cancer resistance protein (BCRP) transporter; acalabrutinib may inhibit intestinal BCRP.
Acarbose: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Afatinib: (Moderate) If the concomitant use of velpatasvir 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 velpatasvir. 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 velpatasvir 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.
Alogliptin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Alogliptin; Metformin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Alogliptin; Pioglitazone: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Alpelisib: (Major) Avoid coadministration of alpelisib with velpatasvir 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 velpatasvir is a BCRP inhibitor.
Aluminum Hydroxide: (Moderate) Separate the use of antacids and velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Separate the use of antacids and velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Separate the use of antacids and velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Separate the use of antacids and velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Separate the use of antacids and velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Amiodarone: (Major) Coadministration of amiodarone with sofosbuvir is not recommended due to the potential for serious symptomatic bradycardia. Cases of symptomatic bradycardia, including cases requiring pacemaker intervention, have been reported with the concurrent use of amiodarone with sofosbuvir-containing regimens; additionally, a fatal cardiac arrest was reported in a patient receiving a sofosbuvir-containing regimen (ledipasvir; sofosbuvir). The mechanism of this effect is unknown. If coadministration is required, cardiac monitoring in an inpatient setting for the first 48 hours of coadministration is recommended, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment. Due to the long half-life of amiodarone, patients discontinuing amiodarone just prior to starting sofosbuvir should also undergo similar cardiac monitoring as outlined above.
Amlodipine: (Moderate) Use caution when administering velpatasvir with amlodipine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Amlodipine; Atorvastatin: (Major) Monitor patients closely when atorvastatin is coadministered with velpatasvir as this may significantly increase the serum concentrations of atorvastatin, which may increase the risk of myopathy and rhabdomyolysis. Atorvastatin is a substrate of the P-glycoprotein (P-gp) and OATP1B1 transporters as well as CYP3A4, while velpatasvir inhibits P-gp, OATP1B1, and CYP3A4. (Moderate) Use caution when administering velpatasvir with amlodipine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Amlodipine; Benazepril: (Moderate) Use caution when administering velpatasvir with amlodipine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Amlodipine; Celecoxib: (Moderate) Use caution when administering velpatasvir with amlodipine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Amlodipine; Olmesartan: (Moderate) Use caution when administering velpatasvir with amlodipine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Amlodipine; Valsartan: (Moderate) Use caution when administering velpatasvir with amlodipine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Use caution when administering velpatasvir with amlodipine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy. (Moderate) Use caution when administering velpatasvir with clarithromycin. Taking these medications together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of P-glycoprotein (P-gp) and CYP3A4. Clarithromycin is a CYP3A4 and P-gp inhibitor.
Antacids: (Moderate) Separate the use of antacids and velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Antidiabetic Agents: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Apalutamide: (Major) Avoid coadministration of sofosbuvir with inducers of P-glycoprotein (P-gp) and BCRP, such as apalutamide. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. (Major) Coadministration of velpatasvir with apalutamide is not recommended due to the potential for loss of antiviral efficacy. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer.
Aprepitant, Fosaprepitant: (Moderate) Use caution when administering velpatasvir with aprepitant. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a substrate of CYP3A4. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and weak inducer. Plasma concentrations of another CYP3A4 substrate, midazolam, increased from 1.25-fold to 3.3-fold after administration of a 3 to 5-day oral aprepitant regimen; midazolam concentrations were subsequently decreased by 19% and 4% on days 8 and 15, respectively. However, as a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, IV fosaprepitant (single dose) is rapidly converted to aprepitant and shares some of the same drug interactions but it only weakly inhibits CYP3A4 for a duration of 2 days, increasing the midazolam AUC by approximately 1.8-fold on day 1 with no effect by day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important. There is no evidence of CYP3A4 induction with fosaprepitant.
Armodafinil: (Major) Avoid coadministration of velpatasvir with armodafinil. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; armodafinil is an in vitro inducer of CYP3A4.
Aspirin, ASA; Omeprazole: (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Atazanavir: (Moderate) Monitor for velpatasvir-related adverse events when administering velpatasvir with atazanavir. In an interaction study, use of these drugs together resulted in a 142% increase in velpatasvir exposure; however, because data have not correlated velpatasvir exposure with toxicity, no dose adjustments are recommended. Velpatasvir is a substrate of organic anion transporting polypeptide (OATP1B1), and to a lesser extent CYP3A and CYP2C8; atazanavir is an inhibitor of OATP1B1, CYP3A4, and CYP2C8.
Atazanavir; Cobicistat: (Moderate) In an interaction study, use of cobicistat with sofosbuvir resulted in a 37% increase in sofosbuvir exposure; however, no dose adjustments are required. Clinical monitoring for adverse effects is recommended during coadministration. Cobicistat is an inhibitor of the transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Sofosbuvir is a substrate of P-gp and BCRP. (Moderate) Monitor for velpatasvir-related adverse events when administering velpatasvir with atazanavir. In an interaction study, use of these drugs together resulted in a 142% increase in velpatasvir exposure; however, because data have not correlated velpatasvir exposure with toxicity, no dose adjustments are recommended. Velpatasvir is a substrate of organic anion transporting polypeptide (OATP1B1), and to a lesser extent CYP3A and CYP2C8; atazanavir is an inhibitor of OATP1B1, CYP3A4, and CYP2C8. (Moderate) Monitor for velpatasvir-related adverse events when administering velpatasvir with cobicistat. In an interaction study, use of these drugs together resulted in a 50% increase in velpatasvir exposure; however, because data have not correlated velpatasvir exposure with toxicity, no dose adjustments are recommended. Velpatasvir is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP1B1), Breast Cancer Resistance Protein (BCRP), and CYP3A; cobistat is an inhibitor of P-gp, OATP1B1, BCRP, and CYP3A4.
Atogepant: (Major) Limit the dose of atogepant to 10 or 30 mg PO once daily for episodic migraine or 30 mg PO once daily for chronic migraine if coadministered with velpatasvir. Concurrent use may increase atogepant exposure and the risk of adverse effects. Atogepant is a substrate of OATP1B1 and OATP1B3 and velpatasvir is an OATP inhibitor. Coadministration with an OATP1B1/3 inhibitor resulted in a 2.85-fold increase in atogepant overall exposure and a 2.23-fold increase in atogepant peak concentration.
Atorvastatin: (Major) Monitor patients closely when atorvastatin is coadministered with velpatasvir as this may significantly increase the serum concentrations of atorvastatin, which may increase the risk of myopathy and rhabdomyolysis. Atorvastatin is a substrate of the P-glycoprotein (P-gp) and OATP1B1 transporters as well as CYP3A4, while velpatasvir inhibits P-gp, OATP1B1, and CYP3A4.
Basiliximab: (Moderate) Use caution when administering velpatasvir with basiliximab. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a substrate of CYP3A4. Basiliximab may cause a down-regulation of 3A4 activity by increasing IL-2 binding to IL-2 receptors on hepatic and intestinal cells.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving velpatasvir. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving velpatasvir. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; velpatasvir inhibits P-gp.
Bexagliflozin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Bexarotene: (Major) Avoid coadministration of velpatasvir with bexarotene. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a substrate of CYP3A4; bexarotene is a moderate inducer of CYP3A.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir alafenamide and velpatasvir due to potential increases in tenofovir serum concentrations. Tenofovir alafenamide is a substrate of the breast cancer resistance protein (BCRP),P-glycoprotein (P-gP), OATP1B1, and OATB1B3 transporters, while velpatasvir inhibits these transporters.
Bosentan: (Major) Avoid coadministration of velpatasvir with bosentan. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; bosentan is an inducer of CYP3A4. Additionally, velpatasvir is an inhibitor of the organic anion transporting polypeptides OATP1B1 and OATP1B3. Coadministration with substrates of these transporters, such as bosentan, may increase their exposure.
Brincidofovir: (Moderate) Postpone the administration of velpatasvir for at least three hours after brincidofovir administration and increase monitoring for brincidofovir-related adverse reactions (i.e., elevated hepatic enzymes and bilirubin, diarrhea, other gastrointestinal adverse events) if concomitant use of brincidofovir and velpatasvir is necessary. Brincidofovir is an OATP1B1/3 substrate and velpatasvir is an OATP1B1/3 inhibitor. In a drug interaction study, the mean AUC and Cmax of brincidofovir increased by 374% and 269%, respectively, when administered with another OATP1B1/3 inhibitor.
Calcium Carbonate: (Moderate) Separate the use of antacids (e.g., calcium carbonate) and sofosbuvir; velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) H2-blockers may be administered simultaneously with or 12 hours apart from velpatasvir. H2-blocker doses should not exceed doses comparable to famotidine 40 mg twice daily. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy. (Moderate) Separate the use of antacids (e.g., calcium carbonate) and sofosbuvir; velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Separate the use of antacids (e.g., calcium carbonate) and sofosbuvir; velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Separate the use of antacids (e.g., calcium carbonate) and sofosbuvir; velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Calcium Carbonate; Simethicone: (Moderate) Separate the use of antacids (e.g., calcium carbonate) and sofosbuvir; velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Calcium; Vitamin D: (Moderate) Separate the use of antacids (e.g., calcium carbonate) and sofosbuvir; velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Canagliflozin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Canagliflozin; Metformin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Carbamazepine: (Major) Avoid coadministration of sofosbuvir with inducers of P-glycoprotein (P-gp), such as carbamazepine. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. (Major) Avoid coadministration of velpatasvir with inducers of P-glycoprotein (P-gp) and CYP 3A4 and 2B6 isoenzymes, such as carbamazepine. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is metabolized by P-gp and CYP3A4 and 2B6.
Carvedilol: (Moderate) Use caution when administering velpatasvir with carvedilol. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). (Minor) Coadministration of sofosbuvir and carvedilol may result in elevated sofosbuvir plasma concentrations. Sofosbuvir is a substrate for the drug transporter P-glycoprotein (P-gp); carvedilol is a P-gp inhibitor. According to the manufacturer, no dosage adjustments are required when sofosbuvir is administered concurrently with P-gp inhibitors; however, if these drugs are given together, consider increased monitoring for potential adverse effect.
Cenobamate: (Major) Avoid coadministration of velpatasvir with cenobamate due to the potential for loss of antiviral efficacy. Concurrent use may significantly decrease velpatasvir plasma concentrations. Velpatasvir is a CYP3A4 substrate; cenobamate is a moderate CYP3A4 inducer.
Chloramphenicol: (Moderate) Use caution when administering velpatasvir with chloramphenicol. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Chloramphenicol is a potent CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Chlorpropamide: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Cimetidine: (Major) H2-blockers may be administered simultaneously with or 12 hours apart from velpatasvir. H2-blocker doses should not exceed doses comparable to famotidine 40 mg twice daily. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Ciprofloxacin: (Moderate) Use caution when administering velpatasvir with ciprofloxacin. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Ciprofloxacin is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Clarithromycin: (Moderate) Use caution when administering velpatasvir with clarithromycin. Taking these medications together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of P-glycoprotein (P-gp) and CYP3A4. Clarithromycin is a CYP3A4 and P-gp inhibitor.
Cobicistat: (Moderate) In an interaction study, use of cobicistat with sofosbuvir resulted in a 37% increase in sofosbuvir exposure; however, no dose adjustments are required. Clinical monitoring for adverse effects is recommended during coadministration. Cobicistat is an inhibitor of the transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Sofosbuvir is a substrate of P-gp and BCRP. (Moderate) Monitor for velpatasvir-related adverse events when administering velpatasvir with cobicistat. In an interaction study, use of these drugs together resulted in a 50% increase in velpatasvir exposure; however, because data have not correlated velpatasvir exposure with toxicity, no dose adjustments are recommended. Velpatasvir is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP1B1), Breast Cancer Resistance Protein (BCRP), and CYP3A; cobistat is an inhibitor of P-gp, OATP1B1, BCRP, and CYP3A4.
Cocaine: (Moderate) Use caution when administering velpatasvir with cocaine. Cocaine may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Cocaine is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Colchicine: (Major) Avoid concomitant use of colchicine and velpatasvir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and velpatasvir is a P-gp inhibitor.
Conivaptan: (Moderate) Caution is warranted when conivaptan is administered with sofosbuvir as there is a potential for elevated concentrations of sofosbuvir. Conivaptan is P-glycoprotein (P-gp) inhibitor. Sofosbuvir is a substrate of P-gp. According to the manufacturer, no dosage adjustments are required when sofosbuvir is administered concurrently with P-gp inhibitors; however, if these drugs are given together, consider increased monitoring for potential adverse effects. (Moderate) Use caution when administering velpatasvir with conivaptan. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); conivaptan is an inhibitor of P-gp. Conivaptan is also a potent inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Cyclosporine: (Moderate) Use caution when administering velpatasvir with cyclosporine. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). Velpatasvir is also a substrate for the Breast Cancer Resistance Protein (BCRP). Cyclosporine is a BCRP inhibitor. In addition, cyclosporine is an inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Dabrafenib: (Major) Avoid coadministration of velpatasvir with dabrafenib. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; dabrafenib is an inducer of CYP3A4.
Daclatasvir: (Contraindicated) Do not coadminister velpatasvir with daclatasvir. Taking these drugs together is a duplication of therapy, and may result in adverse effects.
Danazol: (Moderate) Use caution when administering velpatasvir with danazol. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Danazol is a CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Dapagliflozin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Dapagliflozin; Metformin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Dapagliflozin; Saxagliptin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Darunavir; Cobicistat: (Moderate) In an interaction study, use of cobicistat with sofosbuvir resulted in a 37% increase in sofosbuvir exposure; however, no dose adjustments are required. Clinical monitoring for adverse effects is recommended during coadministration. Cobicistat is an inhibitor of the transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Sofosbuvir is a substrate of P-gp and BCRP. (Moderate) Monitor for velpatasvir-related adverse events when administering velpatasvir with cobicistat. In an interaction study, use of these drugs together resulted in a 50% increase in velpatasvir exposure; however, because data have not correlated velpatasvir exposure with toxicity, no dose adjustments are recommended. Velpatasvir is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP1B1), Breast Cancer Resistance Protein (BCRP), and CYP3A; cobistat is an inhibitor of P-gp, OATP1B1, BCRP, and CYP3A4.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) In an interaction study, use of cobicistat with sofosbuvir resulted in a 37% increase in sofosbuvir exposure; however, no dose adjustments are required. Clinical monitoring for adverse effects is recommended during coadministration. Cobicistat is an inhibitor of the transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Sofosbuvir is a substrate of P-gp and BCRP. (Moderate) Monitor for velpatasvir-related adverse events when administering velpatasvir with cobicistat. In an interaction study, use of these drugs together resulted in a 50% increase in velpatasvir exposure; however, because data have not correlated velpatasvir exposure with toxicity, no dose adjustments are recommended. Velpatasvir is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP1B1), Breast Cancer Resistance Protein (BCRP), and CYP3A; cobistat is an inhibitor of P-gp, OATP1B1, BCRP, and CYP3A4. (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir alafenamide and velpatasvir due to potential increases in tenofovir serum concentrations. Tenofovir alafenamide is a substrate of the breast cancer resistance protein (BCRP),P-glycoprotein (P-gP), OATP1B1, and OATB1B3 transporters, while velpatasvir inhibits these transporters.
Deferasirox: (Major) Avoid coadministration of velpatasvir with deferasirox. Taking these drugs together may significantly alter velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy or adverse effects. Velpatasvir is a substrate of CYP3A4 and CYP2C8; deferasirox is an inducer of CYP3A4 and an inhibitor of CYP2C8.
Delavirdine: (Moderate) Use caution when administering velpatasvir with delavirdine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Delavirdine is a potent CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Desogestrel; Ethinyl Estradiol: (Moderate) Use caution when administering velpatasvir with ethinyl estradiol. Taking these drugs together may increase the plasma concentrations velpatasvir and ethinyl estradiol, potentially resulting in adverse events. Velpatasvir is a CYP2B6 and CYP3A4 substrate; ethinyl estradiol is an in vitro inhibitor of CYP2B6 and CYP3A4. In addition, ethinyl estradiol is a substrate for the drug transporter P-glycoprotein (P-gp); velpatasvir is a P-gp inhibitor.
Dexlansoprazole: (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Dextromethorphan; Quinidine: (Moderate) Use caution when administering velpatasvir with quinidine. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp).
Digoxin: (Moderate) Therapeutic serum concentration monitoring of digoxin is recommended when coadministered with velpatasvir due to the potential for increased digoxin serum concentrations. A digoxin dose modification may be necessary. A single-dose pharmacokinetic study showed increases in the Cmax (188%) and AUC (134%) of digoxin when administered with velpatasvir compared to no coadministration. Digoxin is a P-glycoprotein (P-gp) substrate and velpatasvir inhibits P-gp.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir disoproxil fumarate and velpatasvir due to potential increases in tenofovir serum concentrations. When administered concurrently with velpatasvir, the peak concentration (Cmax), systemic exposure (AUC), and the trough concentration (Cmin) of tenofovir increased by 44%, 40%, and 84%, respectively. Tenofovir is a substrate of the breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) transporters, while velpatasvir inhibits both BCRP and P-gp. Consider use of tenofovir alafenamide in place of tenofovir disoproxil fumarate.
Dronedarone: (Moderate) Use caution when administering velpatasvir with dronedarone. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); dronedarone is an inhibitor of P-gp. Dronedarone is also an inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Drospirenone; Ethinyl Estradiol: (Moderate) Use caution when administering velpatasvir with ethinyl estradiol. Taking these drugs together may increase the plasma concentrations velpatasvir and ethinyl estradiol, potentially resulting in adverse events. Velpatasvir is a CYP2B6 and CYP3A4 substrate; ethinyl estradiol is an in vitro inhibitor of CYP2B6 and CYP3A4. In addition, ethinyl estradiol is a substrate for the drug transporter P-glycoprotein (P-gp); velpatasvir is a P-gp inhibitor.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Use caution when administering velpatasvir with ethinyl estradiol. Taking these drugs together may increase the plasma concentrations velpatasvir and ethinyl estradiol, potentially resulting in adverse events. Velpatasvir is a CYP2B6 and CYP3A4 substrate; ethinyl estradiol is an in vitro inhibitor of CYP2B6 and CYP3A4. In addition, ethinyl estradiol is a substrate for the drug transporter P-glycoprotein (P-gp); velpatasvir is a P-gp inhibitor.
Dulaglutide: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Efavirenz: (Major) Avoid coadministration of velpatasvir with efavirenz, as concurrent administration significantly decreases velpatasvir plasma concentrations and may result in loss of antiviral efficacy. In a drug interaction study, use of these drugs together resulted in an approximate 50% reduction in velpatasvir exposure. Velpatasvir is substrate of P-glycoprotein (P-gp) and to a lesser extent CYP3A; efavirenz induces P-gp and CYP3A.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of velpatasvir with efavirenz, as concurrent administration significantly decreases velpatasvir plasma concentrations and may result in loss of antiviral efficacy. In a drug interaction study, use of these drugs together resulted in an approximate 50% reduction in velpatasvir exposure. Velpatasvir is substrate of P-glycoprotein (P-gp) and to a lesser extent CYP3A; efavirenz induces P-gp and CYP3A. (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir disoproxil fumarate and velpatasvir due to potential increases in tenofovir serum concentrations. When administered concurrently with velpatasvir, the peak concentration (Cmax), systemic exposure (AUC), and the trough concentration (Cmin) of tenofovir increased by 44%, 40%, and 84%, respectively. Tenofovir is a substrate of the breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) transporters, while velpatasvir inhibits both BCRP and P-gp. Consider use of tenofovir alafenamide in place of tenofovir disoproxil fumarate.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of velpatasvir with efavirenz, as concurrent administration significantly decreases velpatasvir plasma concentrations and may result in loss of antiviral efficacy. In a drug interaction study, use of these drugs together resulted in an approximate 50% reduction in velpatasvir exposure. Velpatasvir is substrate of P-glycoprotein (P-gp) and to a lesser extent CYP3A; efavirenz induces P-gp and CYP3A. (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir disoproxil fumarate and velpatasvir due to potential increases in tenofovir serum concentrations. When administered concurrently with velpatasvir, the peak concentration (Cmax), systemic exposure (AUC), and the trough concentration (Cmin) of tenofovir increased by 44%, 40%, and 84%, respectively. Tenofovir is a substrate of the breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) transporters, while velpatasvir inhibits both BCRP and P-gp. Consider use of tenofovir alafenamide in place of tenofovir disoproxil fumarate.
Elagolix: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as velpatasvir 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. Velpatasvir is an inhibitor of OATP1B1. 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 velpatasvir 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. Velpatasvir is an inhibitor of OATP1B1. 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: (Contraindicated) Concomitant use of grazoprevir and velpatasvir is contraindicated due to the potential for increased grazoprevir exposure. Grazoprevir is a substrate of OATP1B1/3; velpatasvir is an inhibitor of OATP1B1/3.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Use caution when administering velpatasvir with ivacaftor. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); ivacaftor is a weak inhibitor of P-gp. Ivacaftor is also a weak inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Eliglustat: (Moderate) Use caution when administering velpatasvir with eliglustat. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); eliglustat is an inhibitor of P-gp.
Eluxadoline: (Major) When administered concurrently with velpatasvir, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); velpatasvir is an OATP1B1 inhibitor. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) In an interaction study, use of cobicistat with sofosbuvir resulted in a 37% increase in sofosbuvir exposure; however, no dose adjustments are required. Clinical monitoring for adverse effects is recommended during coadministration. Cobicistat is an inhibitor of the transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Sofosbuvir is a substrate of P-gp and BCRP. (Moderate) Monitor for velpatasvir-related adverse events when administering velpatasvir with cobicistat. In an interaction study, use of these drugs together resulted in a 50% increase in velpatasvir exposure; however, because data have not correlated velpatasvir exposure with toxicity, no dose adjustments are recommended. Velpatasvir is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP1B1), Breast Cancer Resistance Protein (BCRP), and CYP3A; cobistat is an inhibitor of P-gp, OATP1B1, BCRP, and CYP3A4. (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir alafenamide and velpatasvir due to potential increases in tenofovir serum concentrations. Tenofovir alafenamide is a substrate of the breast cancer resistance protein (BCRP),P-glycoprotein (P-gP), OATP1B1, and OATB1B3 transporters, while velpatasvir inhibits these transporters.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) In an interaction study, use of cobicistat with sofosbuvir resulted in a 37% increase in sofosbuvir exposure; however, no dose adjustments are required. Clinical monitoring for adverse effects is recommended during coadministration. Cobicistat is an inhibitor of the transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Sofosbuvir is a substrate of P-gp and BCRP. (Moderate) Monitor for velpatasvir-related adverse events when administering velpatasvir with cobicistat. In an interaction study, use of these drugs together resulted in a 50% increase in velpatasvir exposure; however, because data have not correlated velpatasvir exposure with toxicity, no dose adjustments are recommended. Velpatasvir is a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP1B1), Breast Cancer Resistance Protein (BCRP), and CYP3A; cobistat is an inhibitor of P-gp, OATP1B1, BCRP, and CYP3A4. (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir disoproxil fumarate and velpatasvir due to potential increases in tenofovir serum concentrations. When administered concurrently with velpatasvir, the peak concentration (Cmax), systemic exposure (AUC), and the trough concentration (Cmin) of tenofovir increased by 44%, 40%, and 84%, respectively. Tenofovir is a substrate of the breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) transporters, while velpatasvir inhibits both BCRP and P-gp. Consider use of tenofovir alafenamide in place of tenofovir disoproxil fumarate.
Empagliflozin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Empagliflozin; Linagliptin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Empagliflozin; Linagliptin; Metformin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Empagliflozin; Metformin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir alafenamide and velpatasvir due to potential increases in tenofovir serum concentrations. Tenofovir alafenamide is a substrate of the breast cancer resistance protein (BCRP),P-glycoprotein (P-gP), OATP1B1, and OATB1B3 transporters, while velpatasvir inhibits these transporters.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir disoproxil fumarate and velpatasvir due to potential increases in tenofovir serum concentrations. When administered concurrently with velpatasvir, the peak concentration (Cmax), systemic exposure (AUC), and the trough concentration (Cmin) of tenofovir increased by 44%, 40%, and 84%, respectively. Tenofovir is a substrate of the breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) transporters, while velpatasvir inhibits both BCRP and P-gp. Consider use of tenofovir alafenamide in place of tenofovir disoproxil fumarate.
Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir alafenamide and velpatasvir due to potential increases in tenofovir serum concentrations. Tenofovir alafenamide is a substrate of the breast cancer resistance protein (BCRP),P-glycoprotein (P-gP), OATP1B1, and OATB1B3 transporters, while velpatasvir inhibits these transporters.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir disoproxil fumarate and velpatasvir due to potential increases in tenofovir serum concentrations. When administered concurrently with velpatasvir, the peak concentration (Cmax), systemic exposure (AUC), and the trough concentration (Cmin) of tenofovir increased by 44%, 40%, and 84%, respectively. Tenofovir is a substrate of the breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) transporters, while velpatasvir inhibits both BCRP and P-gp. Consider use of tenofovir alafenamide in place of tenofovir disoproxil fumarate.
Encorafenib: (Major) Concomitant use of velpatasvir with encorafenib is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a CYP3A substrate and encorafenib is a strong CYP3A inducer.
Enzalutamide: (Major) Coadministration of velpatasvir with enzalutamide is not recommended due to the potential for loss of antiviral efficacy. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer.
Ertugliflozin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Ertugliflozin; Metformin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Ertugliflozin; Sitagliptin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Erythromycin: (Moderate) Use caution when administering velpatasvir with erythromycin. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). In addition, erythromycin is an inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Eslicarbazepine: (Major) Avoid coadministration of velpatasvir with eslicarbazepine. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; eslicarbazepine is an inducer of CYP3A4.
Esomeprazole: (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Ethinyl Estradiol; Norelgestromin: (Moderate) Use caution when administering velpatasvir with ethinyl estradiol. Taking these drugs together may increase the plasma concentrations velpatasvir and ethinyl estradiol, potentially resulting in adverse events. Velpatasvir is a CYP2B6 and CYP3A4 substrate; ethinyl estradiol is an in vitro inhibitor of CYP2B6 and CYP3A4. In addition, ethinyl estradiol is a substrate for the drug transporter P-glycoprotein (P-gp); velpatasvir is a P-gp inhibitor.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Use caution when administering velpatasvir with ethinyl estradiol. Taking these drugs together may increase the plasma concentrations velpatasvir and ethinyl estradiol, potentially resulting in adverse events. Velpatasvir is a CYP2B6 and CYP3A4 substrate; ethinyl estradiol is an in vitro inhibitor of CYP2B6 and CYP3A4. In addition, ethinyl estradiol is a substrate for the drug transporter P-glycoprotein (P-gp); velpatasvir is a P-gp inhibitor.
Ethinyl Estradiol; Norgestrel: (Moderate) Use caution when administering velpatasvir with ethinyl estradiol. Taking these drugs together may increase the plasma concentrations velpatasvir and ethinyl estradiol, potentially resulting in adverse events. Velpatasvir is a CYP2B6 and CYP3A4 substrate; ethinyl estradiol is an in vitro inhibitor of CYP2B6 and CYP3A4. In addition, ethinyl estradiol is a substrate for the drug transporter P-glycoprotein (P-gp); velpatasvir is a P-gp inhibitor.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Use caution when administering velpatasvir with ethinyl estradiol. Taking these drugs together may increase the plasma concentrations velpatasvir and ethinyl estradiol, potentially resulting in adverse events. Velpatasvir is a CYP2B6 and CYP3A4 substrate; ethinyl estradiol is an in vitro inhibitor of CYP2B6 and CYP3A4. In addition, ethinyl estradiol is a substrate for the drug transporter P-glycoprotein (P-gp); velpatasvir is a P-gp inhibitor.
Etonogestrel; Ethinyl Estradiol: (Moderate) Use caution when administering velpatasvir with ethinyl estradiol. Taking these drugs together may increase the plasma concentrations velpatasvir and ethinyl estradiol, potentially resulting in adverse events. Velpatasvir is a CYP2B6 and CYP3A4 substrate; ethinyl estradiol is an in vitro inhibitor of CYP2B6 and CYP3A4. In addition, ethinyl estradiol is a substrate for the drug transporter P-glycoprotein (P-gp); velpatasvir is a P-gp inhibitor.
Etravirine: (Major) Avoid coadministration of velpatasvir with etravirine due to the potential for loss of antiviral efficacy. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; etravirine is a moderate CYP3A4 inducer.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with velpatasvir is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-glycoprotein (P-gp) substrate and velpatasvir 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 sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Ezetimibe; Simvastatin: (Moderate) Initiate simvastatin at the lowest approved dose if coadministration of velpatasvir is necessary due the potential for increased simvastatin exposure and risk for adverse events, such as myopathy or rhabdomyolysis. If higher doses are needed, use the lowest necessary dose based on risk and benefit assessment. Simvastatin is a substrate of OATP1B1/3; velpatasvir is an inhibitor of OATP1B1/3.
Famotidine: (Major) H2-blockers may be administered simultaneously with or 12 hours apart from velpatasvir. H2-blocker doses should not exceed doses comparable to famotidine 40 mg twice daily. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Felodipine: (Moderate) Use caution when administering velpatasvir with felodipine. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); felodipine is an inhibitor of P-gp.
Fexinidazole: (Major) Concomitant use of velpatasvir with fexinidazole is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a CYP2B6 substrate and fexinidazole is a CYP2B6 inducer.
Flibanserin: (Moderate) Use caution when administering velpatasvir with flibanserin. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); flibanserin is an inhibitor of P-gp.
Fluconazole: (Moderate) Use caution when administering velpatasvir with fluconazole. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Fluconazole is a CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Fluoxetine: (Moderate) Use caution when administering velpatasvir with fluoxetine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Fluoxetine is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Flutamide: (Major) Avoid coadministration of velpatasvir with flutamide. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; flutamide is an inducer of CYP3A4.
Fluvoxamine: (Moderate) Use caution when administering velpatasvir with fluvoxamine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Fluvoxamine is a CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Fosamprenavir: (Major) Avoid coadministration of velpatasvir with fosamprenavir. Taking these drugs together may significantly reduce the plasma concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); fosamprenavir is a P-gp inducer. Velpatasvir is also a substrate for CYP3A4; fosamprenavir is an inducer/inhibitor of CYP34. (Moderate) Caution is advised when administering sofosbuvir with fosamprenavir, as concurrent use may result in reduced sofosbuvir plasma concentrations. Sofosbuvir is a substrate for the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is a P-gp inducer.
Fosphenytoin: (Major) Avoid coadministration of sofosbuvir with fosphenytoin. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. (Major) Avoid coadministration of velpatasvir with inducers of P-glycoprotein (P-gp) and CYP3A4, such as fosphenytoin. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a P-gp and CYP3A4 substrate.
Glecaprevir; Pibrentasvir: (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.
Glimepiride: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Glipizide: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Glipizide; Metformin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Glyburide: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Glyburide; Metformin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Grapefruit juice: (Moderate) Taking velpatasvir with grapefruit juice may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); grapefruit is an inhibitor of P-gp. Grapefruit is also an inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
H2-blockers: (Major) H2-blockers may be administered simultaneously with or 12 hours apart from velpatasvir. H2-blocker doses should not exceed doses comparable to famotidine 40 mg twice daily. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Ibuprofen; Famotidine: (Major) H2-blockers may be administered simultaneously with or 12 hours apart from velpatasvir. H2-blocker doses should not exceed doses comparable to famotidine 40 mg twice daily. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Idelalisib: (Moderate) Use caution when administering velpatasvir with idelalisib. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Idelalisib is a potent CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Imatinib: (Moderate) Use caution when administering velpatasvir with imatinib. Taking these medications together may increase the plasma concentrations of imatinib, potentially resulting in adverse events. Imatinib is a substrate for the drug transporter Breast Cancer Resistance Protein (BCRP). Velpatasvir is an inhibitor of BCRP.
Indinavir: (Moderate) Use caution when administering velpatasvir with indinavir. Taking these medications together may increase the plasma concentrations of velpatasvir and indinavir, potentially resulting in adverse events. Indinavir is a substrate for the drug transporters P-glycoprotein (P-gp). Velpatasvir is an inhibitor of P-gp. Indinavir is also a potent CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Insulin Aspart: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Insulin Aspart; Insulin Aspart Protamine: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Insulin Degludec; Liraglutide: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Insulin Detemir: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Insulin Glargine: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Insulin Glargine; Lixisenatide: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Insulin Glulisine: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Insulin Lispro: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Insulin Lispro; Insulin Lispro Protamine: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Insulin, Inhaled: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Isavuconazonium: (Moderate) Use caution when administering velpatasvir with isavuconazonium. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); isavuconazonium is a weak inhibitor of P-gp. Isavuconazonium is also an inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of sofosbuvir, a P-glycoprotein (P-gp) substrate, with inducers of P-gp, such as rifampin. Taking these drugs together may significantly decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. In a single-dose study, coadministration reduced the sofosbuvir Cmax and AUC to 23% and 28% of normal concentrations, respectively. (Major) Avoid coadministration of velpatasvir with inducers of P-glycoprotein (P-gp), CYP3A4, CYP2B6, and CYP2C8, such as rifampin. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. In a single-dose study, coadministration reduced the velpatasvir Cmax and AUC to 29% and 18% or normal concentrations, respectively. Velpatasvir is a substrate of P-gp, CYP3A4, CYP2B6, and CYP2C8.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of sofosbuvir, a P-glycoprotein (P-gp) substrate, with inducers of P-gp, such as rifampin. Taking these drugs together may significantly decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. In a single-dose study, coadministration reduced the sofosbuvir Cmax and AUC to 23% and 28% of normal concentrations, respectively. (Major) Avoid coadministration of velpatasvir with inducers of P-glycoprotein (P-gp), CYP3A4, CYP2B6, and CYP2C8, such as rifampin. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. In a single-dose study, coadministration reduced the velpatasvir Cmax and AUC to 29% and 18% or normal concentrations, respectively. Velpatasvir is a substrate of P-gp, CYP3A4, CYP2B6, and CYP2C8.
Isophane Insulin (NPH): (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Itraconazole: (Moderate) Use caution when administering velpatasvir with itraconazole. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). In addition, itraconazole is a potent inhibitor of the hepatic enzyme CYP3A4 and the breast cancer resistance protein (BCRP) transporter. Velpatasvir is a CYP3A4 and BCRP substrate. (Minor) Itraconazole and sofosbuvir may be given together with caution. Taking these drugs together may increase plasma concentrations of sofosbuvir, without increasing GS-331007 plasma concentrations. Sofosbuvir is a substrate of the drug transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) inhibitor; itraconazole is a P-gp and BCRP inhibitor.
Ivacaftor: (Moderate) Use caution when administering velpatasvir with ivacaftor. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); ivacaftor is a weak inhibitor of P-gp. Ivacaftor is also a weak inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Ketoconazole: (Moderate) Use caution when administering velpatasvir with ketoconazole. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); ketoconazole is an inhibitor of P-gp. Ketoconazole is also a potent inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir disoproxil fumarate and velpatasvir due to potential increases in tenofovir serum concentrations. When administered concurrently with velpatasvir, the peak concentration (Cmax), systemic exposure (AUC), and the trough concentration (Cmin) of tenofovir increased by 44%, 40%, and 84%, respectively. Tenofovir is a substrate of the breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) transporters, while velpatasvir inhibits both BCRP and P-gp. Consider use of tenofovir alafenamide in place of tenofovir disoproxil fumarate.
Lansoprazole: (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy. (Moderate) Use caution when administering velpatasvir with clarithromycin. Taking these medications together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of P-glycoprotein (P-gp) and CYP3A4. Clarithromycin is a CYP3A4 and P-gp inhibitor.
Lapatinib: (Moderate) Monitor for an increase in lapatinib-related adverse reactions if coadministration with velpatasvir is necessary. Lapatinib is a P-glycoprotein (P-gp) substrate and velpatasvir is a P-gp inhibitor. Increased plasma concentrations of lapatinib are likely.
Ledipasvir; Sofosbuvir: (Contraindicated) Taking these drugs together is a duplication of therapy, and may result in adverse effects.
Lefamulin: (Moderate) Monitor for lefamulin-related adverse effects if oral lefamulin is administered with velpatasvir 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 velpatasvir is a P-gp inhibitor.
Letermovir: (Moderate) Administering velpatasvir concurrently with letermovir may result in elevated concentrations of letermovir. Monitor for increased letermovir adverse effects. Velpatasvir is an inhibitor of the organic anion-transporting polypeptides (OATP1B1/3). Letermovir is an OATP1B1/3 substrate.
Levamlodipine: (Moderate) Use caution when administering velpatasvir with amlodipine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Levoketoconazole: (Moderate) Use caution when administering velpatasvir with ketoconazole. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); ketoconazole is an inhibitor of P-gp. Ketoconazole is also a potent inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Levonorgestrel; Ethinyl Estradiol: (Moderate) Use caution when administering velpatasvir with ethinyl estradiol. Taking these drugs together may increase the plasma concentrations velpatasvir and ethinyl estradiol, potentially resulting in adverse events. Velpatasvir is a CYP2B6 and CYP3A4 substrate; ethinyl estradiol is an in vitro inhibitor of CYP2B6 and CYP3A4. In addition, ethinyl estradiol is a substrate for the drug transporter P-glycoprotein (P-gp); velpatasvir is a P-gp inhibitor.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Use caution when administering velpatasvir with ethinyl estradiol. Taking these drugs together may increase the plasma concentrations velpatasvir and ethinyl estradiol, potentially resulting in adverse events. Velpatasvir is a CYP2B6 and CYP3A4 substrate; ethinyl estradiol is an in vitro inhibitor of CYP2B6 and CYP3A4. In addition, ethinyl estradiol is a substrate for the drug transporter P-glycoprotein (P-gp); velpatasvir is a P-gp inhibitor.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Use caution when administering velpatasvir with ethinyl estradiol. Taking these drugs together may increase the plasma concentrations velpatasvir and ethinyl estradiol, potentially resulting in adverse events. Velpatasvir is a CYP2B6 and CYP3A4 substrate; ethinyl estradiol is an in vitro inhibitor of CYP2B6 and CYP3A4. In addition, ethinyl estradiol is a substrate for the drug transporter P-glycoprotein (P-gp); velpatasvir is a P-gp inhibitor.
Linagliptin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Linagliptin; Metformin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Liraglutide: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Lixisenatide: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with velpatasvir. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and velpatasvir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with velpatasvir. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and velpatasvir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lorlatinib: (Major) Coadministration of velpatasvir with lorlatinib is not recommended due to the potential for loss of antiviral efficacy. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 and P-glycoprotein (P-gp) substrate. Lorlatinib is a moderate CYP3A4 inducer as well as a P-gp inducer.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of velpatasvir with lumacaftor; ivacaftor. Taking these drugs together may significantly decrease plasma concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy. Lumacaftor is a potent inducer of CYP3A4; velpatasvir is a CYP3A4 substrate. In addition, velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); lumacaftor is an inducer/inhibitor of P-gp. (Minor) Although the clinical significance of this interaction is unknown, concurrent use of sofosbuvir and lumacaftor; ivacaftor may alter sofosbuvir exposure; caution and close monitoring are advised if these drugs are used together. Sofosbuvir is a substrate of the drug transporter P-glycoprotein (P-gp). In vitro data suggest that lumacaftor; ivacaftor has the potential to both induce and inhibit P-gp. The net effect of lumacaftor; ivacaftor on P-gp transport is not clear, but substrate exposure may be affected leading to decreased efficacy or increased or prolonged therapeutic effects and adverse events. FDA-approved labeling for sofosbuvir recommends to avoid coadministration with potent P-gp inducers.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of velpatasvir with lumacaftor; ivacaftor. Taking these drugs together may significantly decrease plasma concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy. Lumacaftor is a potent inducer of CYP3A4; velpatasvir is a CYP3A4 substrate. In addition, velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); lumacaftor is an inducer/inhibitor of P-gp. (Moderate) Use caution when administering velpatasvir with ivacaftor. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); ivacaftor is a weak inhibitor of P-gp. Ivacaftor is also a weak inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate. (Minor) Although the clinical significance of this interaction is unknown, concurrent use of sofosbuvir and lumacaftor; ivacaftor may alter sofosbuvir exposure; caution and close monitoring are advised if these drugs are used together. Sofosbuvir is a substrate of the drug transporter P-glycoprotein (P-gp). In vitro data suggest that lumacaftor; ivacaftor has the potential to both induce and inhibit P-gp. The net effect of lumacaftor; ivacaftor on P-gp transport is not clear, but substrate exposure may be affected leading to decreased efficacy or increased or prolonged therapeutic effects and adverse events. FDA-approved labeling for sofosbuvir recommends to avoid coadministration with potent P-gp inducers.
Magnesium Hydroxide: (Moderate) Separate the use of antacids and velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Maraviroc: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and velpatasvir as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1B1); velpatasvir 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.
Mavacamten: (Major) Concomitant use of velpatasvir with mavacamten is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Mefloquine: (Moderate) Use caution when administering velpatasvir with mefloquine. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp).
Meropenem: (Major) Coadministration of sofosbuvir with meropenem is not recommended. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Sofosbuvir is a P-gp substrate and meropenem is a P-gp inducer. (Major) Concomitant use of velpatasvir with meropenem is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a P-gp substrate and meropenem is a P-gp inducer.
Meropenem; Vaborbactam: (Major) Coadministration of sofosbuvir with meropenem is not recommended. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Sofosbuvir is a P-gp substrate and meropenem is a P-gp inducer. (Major) Concomitant use of velpatasvir with meropenem is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a P-gp substrate and meropenem is a P-gp inducer.
Metformin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Metformin; Repaglinide: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Metformin; Saxagliptin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Metformin; Sitagliptin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Midostaurin: (Major) Concomitant use of velpatasvir with midostaurin is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a CYP2B6 substrate and midostaurin is a CYP2B6 inducer.
Mifepristone: (Moderate) Use caution when administering velpatasvir with mifepristone. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); mifepristone is an inhibitor of P-gp. Mifepristone is also an inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Miglitol: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Mitotane: (Major) Avoid coadministration of velpatasvir with mitotane. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; mitotane is a potent inducer of CYP3A4.
Modafinil: (Major) Avoid coadministration of velpatasvir with inducers of CYP3A4 and CYP2B6, such as modafinil. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 and CYP2B6 substrate.
Momelotinib: (Moderate) Monitor for an increase in momelotinib-related adverse reactions if coadministration with velpatasvir is necessary. Concomitant use may increase momelotinib exposure. Momelotinib is an OATP1B1/3 substrate; velpatasvir is an OATP1B1/3 inhibitor. Coadministration with another OATP1B1/1B3 inhibitor increased momelotinib exposure by 57%; exposure of its active M21 metabolite increased by 12%.
Nafcillin: (Major) Avoid coadministration of velpatasvir with nafcillin. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; nafcillin is an in vitro inducer of CYP3A4.
Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions if coadministered with velpatasvir. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a P-gp substrate; velpatasvir is a moderate P-gp inhibitor.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and velpatasvir. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and velpatasvir is a P-gp inhibitor.
Naproxen; Esomeprazole: (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Nateglinide: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Nefazodone: (Moderate) Use caution when administering velpatasvir with nefazodone. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Nefazodone is a potent CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Nelfinavir: (Moderate) Use caution when administering velpatasvir with nelfinavir. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). In addition, nelfinavir is a potent inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Use caution when administering velpatasvir with netupitant. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Netupitant is a CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Nevirapine: (Major) Avoid concurrent use of nevirapine and velpatasvir. Concomitant use may decrease plasma concentrations of velpatasvir, resulting in decreased virologic response. Velpatasvir is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Nilotinib: (Moderate) Use caution when administering velpatasvir with nilotinib. Taking these medications together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Nilotinib is a moderate inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Nizatidine: (Major) H2-blockers may be administered simultaneously with or 12 hours apart from velpatasvir. H2-blocker doses should not exceed doses comparable to famotidine 40 mg twice daily. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Use caution when administering velpatasvir with ethinyl estradiol. Taking these drugs together may increase the plasma concentrations velpatasvir and ethinyl estradiol, potentially resulting in adverse events. Velpatasvir is a CYP2B6 and CYP3A4 substrate; ethinyl estradiol is an in vitro inhibitor of CYP2B6 and CYP3A4. In addition, ethinyl estradiol is a substrate for the drug transporter P-glycoprotein (P-gp); velpatasvir is a P-gp inhibitor.
Norethindrone; Ethinyl Estradiol: (Moderate) Use caution when administering velpatasvir with ethinyl estradiol. Taking these drugs together may increase the plasma concentrations velpatasvir and ethinyl estradiol, potentially resulting in adverse events. Velpatasvir is a CYP2B6 and CYP3A4 substrate; ethinyl estradiol is an in vitro inhibitor of CYP2B6 and CYP3A4. In addition, ethinyl estradiol is a substrate for the drug transporter P-glycoprotein (P-gp); velpatasvir is a P-gp inhibitor.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Use caution when administering velpatasvir with ethinyl estradiol. Taking these drugs together may increase the plasma concentrations velpatasvir and ethinyl estradiol, potentially resulting in adverse events. Velpatasvir is a CYP2B6 and CYP3A4 substrate; ethinyl estradiol is an in vitro inhibitor of CYP2B6 and CYP3A4. In addition, ethinyl estradiol is a substrate for the drug transporter P-glycoprotein (P-gp); velpatasvir is a P-gp inhibitor.
Norgestimate; Ethinyl Estradiol: (Moderate) Use caution when administering velpatasvir with ethinyl estradiol. Taking these drugs together may increase the plasma concentrations velpatasvir and ethinyl estradiol, potentially resulting in adverse events. Velpatasvir is a CYP2B6 and CYP3A4 substrate; ethinyl estradiol is an in vitro inhibitor of CYP2B6 and CYP3A4. In addition, ethinyl estradiol is a substrate for the drug transporter P-glycoprotein (P-gp); velpatasvir is a P-gp inhibitor.
Olanzapine; Fluoxetine: (Moderate) Use caution when administering velpatasvir with fluoxetine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Fluoxetine is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Use caution when administering velpatasvir with amlodipine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Omeprazole: (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid coadministration of sofosbuvir with rifabutin. Taking these drugs together may decrease sofosbuvir plasma concentration, potentially resulting in loss of antiviral efficacy. (Major) Avoid coadministration of velpatasvir with inducers of CYP3A4, such as rifabutin. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate. (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Omeprazole; Sodium Bicarbonate: (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Oritavancin: (Major) Use caution when administering velpatasvir with oritavancin. Taking these drugs together may decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; oritavancin is a weak inducer of CYP3A4.
Osimertinib: (Moderate) Monitor for an increase in sofosbuvir-related adverse reactions if coadministration with osimertinib is necessary. Sofosbuvir is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Oxcarbazepine: (Major) Avoid coadministration of sofosbuvir with oxcarbazepine. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy.
Pantoprazole: (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Pazopanib: (Moderate) Use caution when administering velpatasvir with pazopanib. Taking these medications together may increase the plasma concentrations of velpatasvir and pazopanib, potentially resulting in adverse events. Pazopanib is a substrate of the drug transporters P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP); velpatasvir is a P-gp and BCRP inhibitor. Pazopanib is also a weak inhibitor of the hepatic enzymes CYP3A4 and CYP2C8. Velpatasvir is a substrate of both enzymes.
Perampanel: (Major) Use caution when administering velpatasvir with perampanel. Taking these drugs together may decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; perampanel is a weak in vitro inducer of CYP3A4.
Perindopril; Amlodipine: (Moderate) Use caution when administering velpatasvir with amlodipine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Pexidartinib: (Major) Concomitant use of velpatasvir with pexidartinib is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
Phenobarbital: (Major) Avoid coadministration of sofosbuvir with inducers of P-glycoprotein (P-gp), such as phenobarbital. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. (Major) Avoid coadministration of velpatasvir with inducers of P-glycoprotein (P-gp) and CYP3A4, such as phenobarbital. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a P-gp and CYP3A4 substrate.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of sofosbuvir with inducers of P-glycoprotein (P-gp), such as phenobarbital. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. (Major) Avoid coadministration of velpatasvir with inducers of P-glycoprotein (P-gp) and CYP3A4, such as phenobarbital. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a P-gp and CYP3A4 substrate.
Phentermine; Topiramate: (Major) Use caution when administering velpatasvir with topiramate. Taking these drugs together may decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; topiramate is a weak inducer of CYP3A4.
Phenytoin: (Major) Avoid coadministration of sofosbuvir with inducers of P-glycoprotein (P-gp), such as phenytoin. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. (Major) Avoid coadministration of velpatasvir with inducers of P-glycoprotein (P-gp) and CYP3A4, such as phenytoin. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy.
Pioglitazone: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Pioglitazone; Glimepiride: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Pioglitazone; Metformin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Pirfenidone: (Moderate) Use caution when administering velpatasvir with pirfenidone. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); pirfenidone is a weak inhibitor of P-gp. Pirfenidone is also a weak in vitro inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Posaconazole: (Moderate) Use caution when administering velpatasvir with posaconazole. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). In addition, posaconazole is a potent inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Pralsetinib: (Major) Avoid concomitant use of velpatasvir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and velpatasvir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Pramlintide: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Primidone: (Major) Avoid coadministration of sofosbuvir with inducers of P-glycoprotein, such as primidone. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. (Major) Avoid coadministration of velpatasvir with inducers of P-glycoprotein (P-gp) and CYP3A4, such as primidone. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a P-gp and CYP3A4 substrate.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and velpatasvir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and velpatasvir is a P-gp inhibitor.
Propafenone: (Moderate) Use caution when administering velpatasvir with propafenone. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); propafenone is an inhibitor of P-gp.
Proton pump inhibitors: (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Quinidine: (Moderate) Use caution when administering velpatasvir with quinidine. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp).
Quinine: (Major) Avoid coadministration of velpatasvir with quinine. Taking these drugs together may significantly alter velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy or adverse effects. Velpatasvir is a CYP3A4 substrate, while quinine is a mixed inducer/inhibitor or CYP3A4. Additionally, velpatasvir is an inhibitor of the drug transporter P-glycoprotein (P-gp). Coadministration with substrates of this transporter, such as quinine, may increase their exposure.
Rabeprazole: (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Ranitidine: (Major) H2-blockers may be administered simultaneously with or 12 hours apart from velpatasvir. H2-blocker doses should not exceed doses comparable to famotidine 40 mg twice daily. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Ranolazine: (Moderate) Monitor for an increase in ranolazine-related adverse reactions if coadministration with velpatasvir is necessary; a dose adjustment of ranolazine may be necessary. Ranolazine is a P-gp substrate. Velpatasvir is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates.
Regular Insulin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Regular Insulin; Isophane Insulin (NPH): (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Relugolix: (Major) Avoid concomitant use of relugolix and oral velpatasvir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer velpatasvir at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and velpatasvir is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral velpatasvir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer velpatasvir at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and velpatasvir is a P-gp inhibitor.
Repaglinide: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Repotrectinib: (Major) Avoid coadministration of repotrectinib with velpatasvir. Concomitant use may increase repotrectinib exposure and increase the risk for repotrectinib-related adverse effects and may decrease velpatasvir exposure which may result in loss of antiviral efficacy. Repotrectinib is a P-gp substrate and moderate CYP3A inducer; velpatasvir is a CYP3A substrate and P-gp inhibitor.
Resmetirom: (Major) Avoid concomitant use of resmetirom and velpatasvir due to the risk for increased resmetirom exposure which may increase the risk for resmetirom-related adverse effects. Resmetirom is an OATP1B1/3 substrate and velpatasvir is an OATP1B1/3 inhibitor.
Revefenacin: (Major) Coadministration of revefenacin is not recommended with velpatasvir 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; velpatasvir is an inhibitor of OATP1B1 and OATP1B3.
Rifabutin: (Major) Avoid coadministration of sofosbuvir with rifabutin. Taking these drugs together may decrease sofosbuvir plasma concentration, potentially resulting in loss of antiviral efficacy. (Major) Avoid coadministration of velpatasvir with inducers of CYP3A4, such as rifabutin. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate.
Rifampin: (Major) Avoid coadministration of sofosbuvir, a P-glycoprotein (P-gp) substrate, with inducers of P-gp, such as rifampin. Taking these drugs together may significantly decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. In a single-dose study, coadministration reduced the sofosbuvir Cmax and AUC to 23% and 28% of normal concentrations, respectively. (Major) Avoid coadministration of velpatasvir with inducers of P-glycoprotein (P-gp), CYP3A4, CYP2B6, and CYP2C8, such as rifampin. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. In a single-dose study, coadministration reduced the velpatasvir Cmax and AUC to 29% and 18% or normal concentrations, respectively. Velpatasvir is a substrate of P-gp, CYP3A4, CYP2B6, and CYP2C8.
Rifapentine: (Major) Avoid coadministration of sofosbuvir with rifapentine. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. (Major) Concomitant use of velpatasvir with rifapentine is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a CYP3A4 and CYP2C8 substrate and rifapentine is a strong CYP3A4 inducer and moderate CYP2C8 inducer.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with velpatasvir is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and velpatasvir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with velpatasvir; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and velpatasvir is a P-gp inhibitor.
Rolapitant: (Moderate) Use caution if sofosbuvir and rolapitant are used concurrently, and monitor for sofosbuvir-related adverse effects. Sofosbuvir is a substrate of the Breast Cancer Resistance Protein (BCRP) and P-glycoprotein (P-gp), where an increase in exposure may significantly increase adverse effects; rolapitant is a BCRP and P-gp inhibitor. The Cmax and AUC of another BCRP substrate, sulfasalazine, were increased by 140% and 130%, respectively, on day 1 with rolapitant, and by 17% and 32%, respectively, on day 8 after rolapitant administration. When rolapitant was administered with digoxin, a P-gp substrate, the day 1 Cmax and AUC were increased by 70% and 30%, respectively; the Cmax and AUC on day 8 were not studied. (Moderate) Use caution when administering velpatasvir with rolapitant. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporters P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP); rolapitant is an inhibitor of both P-gp and BCRP.
Rosiglitazone: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Rosuvastatin: (Major) Initiate rosuvastatin at a reduced dosage of 5 mg once daily if coadministered with velpatasvir; 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 breast cancer resistance protein (BCRP) and OATP1B1 transporters, while velpatasvir inhibits both BCRP and OATP1B1.
Rosuvastatin; Ezetimibe: (Major) Initiate rosuvastatin at a reduced dosage of 5 mg once daily if coadministered with velpatasvir; 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 breast cancer resistance protein (BCRP) and OATP1B1 transporters, while velpatasvir inhibits both BCRP and OATP1B1.
Saquinavir: (Moderate) Use caution when administering velpatasvir with saquinavir. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). In addition, saquinavir is a potent inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Saxagliptin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) Use caution when administering velpatasvir with ethinyl estradiol. Taking these drugs together may increase the plasma concentrations velpatasvir and ethinyl estradiol, potentially resulting in adverse events. Velpatasvir is a CYP2B6 and CYP3A4 substrate; ethinyl estradiol is an in vitro inhibitor of CYP2B6 and CYP3A4. In addition, ethinyl estradiol is a substrate for the drug transporter P-glycoprotein (P-gp); velpatasvir is a P-gp inhibitor.
Semaglutide: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Simvastatin: (Moderate) Initiate simvastatin at the lowest approved dose if coadministration of velpatasvir is necessary due the potential for increased simvastatin exposure and risk for adverse events, such as myopathy or rhabdomyolysis. If higher doses are needed, use the lowest necessary dose based on risk and benefit assessment. Simvastatin is a substrate of OATP1B1/3; velpatasvir is an inhibitor of OATP1B1/3.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of velpatasvir. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and velpatasvir is a P-gp inhibitor.
Sitagliptin: (Moderate) Closely monitor blood glucose levels if sofosbuvir 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 sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir 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 velpatasvir.
Sodium Phenylbutyrate; Taurursodiol: (Major) Avoid coadministration of sodium phenylbutyrate; taurursodiol and velpatasvir. Concomitant use may increase plasma concentrations of sodium phenylbutyrate; taurursodiol. Sodium phenylbutyrate; taurursodiol is an OATP1B3 substrate and velpatasvir is an OATP1B3 inhibitor.
Sotorasib: (Major) Concomitant use of velpatasvir with sotorasib is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate and sotorasib is a moderate CYP3A4 inducer.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of sofosbuvir, a P-glycoprotein (P-gp) substrate with inducers of P-gp, such as St. John's Wort, Hypericum perforatum. Taking these drugs together may significantly decrease sofosbuvir plasma concentration, potentially resulting in loss of antiviral efficacy. (Major) Avoid coadministration of velpatasvir with inducers of P-glycoprotein (P-gp) and CYP3A4, such as St. John's wort, Hypericum perforatum. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a P-gp and CYP3A4 substrate.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Use caution when administering velpatasvir with trimethoprim. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a CYP2C8 substrate; trimethoprim is an inhibitor of CYP2C8.
Tacrolimus: (Moderate) Closely monitor tacrolimus serum concentrations if coadministration with a direct acting antiviral (DAA) agent, such as sofosbuvir, 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) Use caution when administering velpatasvir with tacrolimus. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporters P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP); tacrolimus is an inhibitor of both P-gp and BCRP.
Tafamidis: (Minor) Caution is advised with the coadministration of tafamidis and sofosbuvir as coadminstration may increase the plasma concentrations of sofosbuvir and increase the risk of adverse effects. Sofosbuvir is a substrate of the breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor. (Minor) Caution is advised with the coadministration of tafamidis and velpatasvir as coadministration may increase plasma concentrations of velpatasvir and increase the risk of adverse effects. Velpatasvir is a substrate of the breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of velpatasvir is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; velpatasvir is a P-gp and BCRP inhibitor.
Tedizolid: (Moderate) If possible, stop use of sofosbuvir temporarily during treatment with oral tedizolid. If coadministration cannot be avoided, closely monitor for sofosbuvir-associated adverse events. Sofosbuvir plasma concentrations may be increased when administered concurrently with oral tedizolid. Sofosbuvir is a substrate of the Breast Cancer Resistance Protein (BCRP); oral tedizolid inhibits BCRP in the intestine. (Moderate) If possible, stop use of velpatasvir temporarily during treatment with oral tedizolid. If coadministration cannot be avoided, closely monitor for velpatasvir-associated adverse events. Velpatasvir plasma concentrations may be increased when velpatasvir is administered concurrently with oral tedizolid. Velpatasvir is a substrate of the Breast Cancer Resistance Protein (BCRP); oral tedizolid inhibits BCRP in the intestine.
Telmisartan; Amlodipine: (Moderate) Use caution when administering velpatasvir with amlodipine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Temsirolimus: (Moderate) Monitor for an increase in temsirolimus-related adverse reactions if coadministration with velpatasvir is necessary. Temsirolimus is a P-glycoprotein (P-gp) substrate and velpatasvir is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of temsirolimus.
Tenofovir Alafenamide: (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir alafenamide and velpatasvir due to potential increases in tenofovir serum concentrations. Tenofovir alafenamide is a substrate of the breast cancer resistance protein (BCRP),P-glycoprotein (P-gP), OATP1B1, and OATB1B3 transporters, while velpatasvir inhibits these transporters.
Tenofovir Alafenamide: (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir alafenamide and velpatasvir due to potential increases in tenofovir serum concentrations. Tenofovir alafenamide is a substrate of the breast cancer resistance protein (BCRP),P-glycoprotein (P-gP), OATP1B1, and OATB1B3 transporters, while velpatasvir inhibits these transporters.
Tenofovir Disoproxil Fumarate: (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir disoproxil fumarate and velpatasvir due to potential increases in tenofovir serum concentrations. When administered concurrently with velpatasvir, the peak concentration (Cmax), systemic exposure (AUC), and the trough concentration (Cmin) of tenofovir increased by 44%, 40%, and 84%, respectively. Tenofovir is a substrate of the breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) transporters, while velpatasvir inhibits both BCRP and P-gp. Consider use of tenofovir alafenamide in place of tenofovir disoproxil fumarate.
Teriflunomide: (Moderate) Use caution when administering velpatasvir with teriflunomide. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the Breast Cancer Resistance Protein (BCRP); teriflunomide is an inhibitor of BCRP. Teriflunomide is also an inhibitor of the hepatic enzyme CYP2C8. Velpatasvir is a CYP2C8 substrate.
Tezacaftor; Ivacaftor: (Moderate) Use caution when administering velpatasvir with ivacaftor. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); ivacaftor is a weak inhibitor of P-gp. Ivacaftor is also a weak inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Thiotepa: (Moderate) The concomitant use of thiotepa and velpatasvir may increase the exposure of velpatasvir; however, the clinical relevance of this interaction is unknown. Thiotepa is a CYP2B6 inhibitor in vitro; velpatasvir is a CYP2B6 substrate.
Ticagrelor: (Moderate) Use caution when administering velpatasvir with ticagrelor. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). In addition, ticagrelor is a weak inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Tipranavir: (Major) Avoid coadministration of sofosbuvir with inducers of P-glycoprotein (P-gp), such as tipranavir. Taking these drugs together may significantly decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Sofosbuvir is a P-gp substrate. Tipranavir is a P-gp substrate, a weak P-gp inhibitor, and appears to be a potent P-gp inducer. The administration with ritonavir appears to result in a net P-gp induction at steady state, even though, when given alone, ritonavir is a P-gp inhibitor. (Major) Avoid coadministration of velpatasvir with inducers of P-glycoprotein (P-gp), such as tipranavir. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a P-gp substrate. Tipranavir is a P-gp substrate, a weak P-gp inhibitor, and appears to be a potent P-gp inducer. The administration with ritonavir appears to result in a net P-gp induction at steady state, even though, when given alone, ritonavir is a P-gp inhibitor.
Topiramate: (Major) Use caution when administering velpatasvir with topiramate. Taking these drugs together may decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; topiramate is a weak inducer of CYP3A4.
Topotecan: (Major) Avoid coadministration of velpatasvir with oral topotecan due to increased topotecan exposure; velpatasvir may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP); velpatasvir 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.
Trametinib: (Moderate) Use caution when administering velpatasvir with trametinib. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a CYP2C8 substrate; trametinib is a weak in vitro inhibitor of CYP2C8.
Trandolapril; Verapamil: (Moderate) Use caution when administering velpatasvir with verapamil. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). In addition, verapamil is an inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Trimethoprim: (Moderate) Use caution when administering velpatasvir with trimethoprim. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a CYP2C8 substrate; trimethoprim is an inhibitor of CYP2C8.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with velpatasvir. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the BCRP and P-gp drug transporters; velpatasvir is a BCRP and P-gp inhibitor.
Valproic Acid, Divalproex Sodium: (Minor) Theoretically, taking velpatasvir with valproic acid may reduce the plasma concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy. Caution is advised if these drugs are administered together. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); valproic acid is a weak P-gp inducer. Velpatasvir is also a substrate for CYP3A4; valproic acid is a weak inducer/inhibitor of CYP34.
Vemurafenib: (Moderate) Use caution when administering velpatasvir with vemurafenib. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporters P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP).
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 velpatasvir due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of velpatasvir. Venetoclax is a P-glycoprotein (P-gp) substrate; velpatasvir is a P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
Verapamil: (Moderate) Use caution when administering velpatasvir with verapamil. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). In addition, verapamil is an inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Vonoprazan: (Major) Avoid concomitant use of velpatasvir and vonoprazan. Vonoprazan reduces intragastric acidity, which may decrease the absorption of velpatasvir reducing its efficacy. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Vonoprazan; Amoxicillin: (Major) Avoid concomitant use of velpatasvir and vonoprazan. Vonoprazan reduces intragastric acidity, which may decrease the absorption of velpatasvir reducing its efficacy. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of velpatasvir and vonoprazan. Vonoprazan reduces intragastric acidity, which may decrease the absorption of velpatasvir reducing its efficacy. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy. (Moderate) Use caution when administering velpatasvir with clarithromycin. Taking these medications together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of P-glycoprotein (P-gp) and CYP3A4. Clarithromycin is a CYP3A4 and P-gp inhibitor.
Voriconazole: (Moderate) Use caution when administering velpatasvir with voriconazole. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Voriconazole is a CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
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 sofosbuvir. 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 velpatasvir. It is recommended to closely monitor these patients for changes in INR both during and after discontinuation of the HCV treatment regimen.
Zafirlukast: (Moderate) Use caution when administering velpatasvir with zafirlukast. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a CYP3A4 substrate; zafirlukast is an inhibitor of CYP3A4.
Zavegepant: (Major) Avoid concomitant use of zavegepant and velpatasvir. Concomitant use may increase zavegepant exposure and the risk for zavegepant-related adverse effects. Zavegepant is an OATP1B3 substrate and velpatasvir is an OATP1B3 inhibitor. Concomitant use with another OATP1B3 inhibitor increased zavegepant overall exposure by 2.3-fold.
Zonisamide: (Moderate) Use caution when administering velpatasvir with zonisamide. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); zonisamide is a weak in vitro inhibitor of P-gp. (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and sofosbuvir is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.
Sofosbuvir; velpatasvir is active against chronic infections caused by genotypes 1, 2, 3, 4, 5, and 6 hepatitis C virus (HCV). Sofosbuvir is a HCV nucleotide analog NS5B polymerase inhibitor. Velpatasvir is an inhibitor of the HCV NS5A protein.
Sofosbuvir: Sofosbuvir is a nucleotide prodrug that prevents hepatitis C viral (HCV) replication by inhibiting the activity of HCV NS5B RNA polymerase. It undergoes intracellular metabolism to form GS-461203, a pharmacologically active uridine analog triphosphate. Hepatitis C virus NS5B RNA polymerase incorporates this metabolite into the viral RNA, where it acts as a chain terminator. GS-461203 does not inhibit human DNA or RNA polymerase, nor does it block mitochondrial RNA polymerase.
In cell cultures, recombinant NS5B polymerase expressing a S282T substitution displayed a 2- to 18-fold decrease in susceptibility to sofosbuvir in all genotypes tested. In addition, genotype 2a, 5, and 6 replicons also developed a M289L substitution. Cross resistance is not expected with NS3/4A protease inhibitors, NS5B non-nucleoside inhibitors, or NS5A inhibitors.
Velpatasvir: Velpatasvir 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, all tested genotypes showed reduced susceptibility to velpatasvir, with variants developing amino acid substitutions at NS5A. Combinations of NS5A substitutions often showed greater reductions in susceptibility than single substitutions. Phenotypic analysis showed that single and double combinations of L31V and Y93H/N in genotype 1a, L31V plus Y93H in genotype 1b, Y93H/S in genotype 3a, and L31V and P32A/L/Q/R in genotype 6 conferred greater than 100-fold reduction in velpatasvir susceptibility. In genotype 2a, single mutants F28S and Y93H showed a 91-fold and 46-fold reduced susceptibility to velpatasvir, respectively. The single mutant Y93H conferred a 3-fold reduced susceptibility in genotype 4a. Cross resistance is not expected with NS3/4A protease inhibitors or NS5B non-nucleoside inhibitors. Efficacy has not been established in patients who have previously failed treatment with other regimens that include a NS5A inhibitor.
Sofosbuvir; velpatasvir is administered orally.
-Sofosbuvir: After administration, approximately 61% to 65% is bound to plasma protein. In the liver, sofosbuvir is converted from the nucleotide prodrug to the pharmacologically active nucleoside analog triphosphate, GS-461203. This conversion occurs via hydrolysis of the carboxy ester moiety by human cathepsin A (CatA) or carboxylesterase 1 (CES1), phosphoramidate cleavage by histidine triad nucleotide-binding protein 1 (HINT 1), and phosphorylation by pyrimidine nucleotide biosynthesis pathway. GS-461203 is then further metabolized by dephosphorylation to form GS-331007, a metabolite that lacks anti-HCV activity and cannot be rephosphorylated. GS-331007 is the predominant circulating metabolite and represents more than 90% of drug related material, while the parent drug accounts for approximately 4%. Elimination occurs primarily through the kidneys with approximately 80% of the dose recovered in the urine (78% as GS-331007, 3.5% as sofosbuvir). Other routes of elimination include the feces (14%) and expired air (2.5%). The median terminal elimination half-life of sofosbuvir and GS-331007 is 0.5 and 25 hours, respectively.
-Velpatasvir: After administration, greater than 99.5% is bound to plasma protein. Velpatasvir is metabolized by CYP2B6, CYP2C8, and CYP3A4. Biliary excretion accounts for elimination of 77% of the parent drug with 95% of the dose recovered in the feces and 0.4% of the dose recovered in the urine. The median terminal elimination half-life of velpatasvir is 15 hours.
Affected cytochrome P450 isoenzymes and drug transporters: P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), OATP1B1, OATP1B3, OAT2B1, CYP2B6, CYP2C8, CYP3A4
Sofosbuvir and velpatasvir are substrates of the drug transporters P-gp and BCRP while GS-331007 (the predominant circulating metabolite of sofosbuvir) is not. In vitro, slow metabolic turnover of velpatasvir by CYP2B6, CYP2C8, and CYP3A4 was observed. Drugs that are inducers of P-gp or moderate to potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly reduce plasma concentrations of sofosbuvir and velpatasvir, leading to potentially reduced therapeutic effects. Concomitant use is not recommended. The FDA-labeling states that sofosbuvir; velpatasvir may be administered with P-gp, BCRP, and CYP inhibitors. Additionally, velpatasvir is an inhibitor of the drug transporters P-gp, BCRP, OATP1B1, OATP1B3, and OAT2B1. Coadministration with substrates of these transporters may increase their exposure. Drug interactions with these transporters is primarily limited to the process of absorption.
Velpatasvir is not an inhibitor of OATP1A2, OCT1, OCT2, OAT1, OAT3, MATE1, or CYP or UGT1A1 enzymes. Sofosbuvir and GS-331007 are not inhibitors of P-gp, BCRP, OATP1B1, OATP1B3, and OCT1. GS-331007 is not an inhibitor of OAT1, OAT3, OCT2, and MATE1. Sofosbuvir and GS-331007 are not inhibitors or inducers of CYP or UGT1A1 enzymes.
-Route-Specific Pharmacokinetics
Oral Route
-Sofosbuvir: After oral administration, the time to reach maximum plasma concentrations (Tmax) is approximately 0.5 to 1 hours for the parent drug sofosbuvir. The mean steady-state concentrations (AUC) and the maximum plasma concentrations (Cmax) for sofosbuvir and GS-331007 in patients infected with hepatitis C are similar to those observed in healthy subjects. Administration of a single dose with a moderate-fat meal (600 kcal, 30% fat) increased the mean systemic exposure of sofosbuvir by 60%, while a high-fat meal (1,000 kcal, 50% fat) resulted in increased systemic exposure of sofosbuvir by 78%.
-Velpatasvir: After oral administration, the time to reach maximum plasma concentrations (Tmax) is approximately 3 hours. Relative to healthy subjects, the velpatasvir AUC and Cmax were 37% and 42% lower, respectively, in HCV-infected patients. Administration of a single dose with a moderate-fat meal (600 kcal, 30% fat) increased the mean systemic exposure of velpatasvir by 34%, while a high-fat meal (1,000 kcal, 50% fat) resulted in increased systemic exposure of velpatasvir by 21%.
-Special Populations
Hepatic Impairment
-Sofosbuvir: Compared to individuals with normal hepatic function, patients with moderate and severe hepatic impairment display increased exposure to the parent drug sofosbuvir (126% and 143% higher, respectively) and the major metabolite, GS-331007, (18% and 9% higher, respectively). Population pharmacokinetics analysis indicated that cirrhosis (including decompensated cirrhosis) had no clinically relevant effect on the exposure of sofosbuvir and GS-331007.
-Velpatasvir: Velpatasvir plasma exposure was similar in patients with moderate hepatic impairment, severe hepatic impairment, and control subjects with normal hepatic function. Population pharmacokinetics analysis indicated that cirrhosis (including decompensated cirrhosis) had no clinically relevant effect on the exposure of velpatasvir.
Renal Impairment
-Sofosbuvir: Compared to individuals with normal renal function, patients with mild, moderate, and severe renal impairment display increased exposure to the parent drug sofosbuvir (61%, 107%, and 171% higher, respectively) and the major metabolite, GS-331007, (55%, 88%, and 451% higher, respectively). Exposure to sofosbuvir and GS-331007 in patients with end-stage renal failure, as compared to those with normal renal function, is 28% and 1,280% higher, respectively, when dosed 1 hour before hemodialysis and 60% and 2,070% higher, respectively, when dosed 1 hour after hemodialysis. A 4-hour hemodialysis session removes approximately 18% of the administered dose. Another study evaluated the pharmacokinetics of sofosbuvir and GS-331007 in HCV-infected subjects with end-stage renal disease (ESRD) requiring dialysis treated with sofosbuvir; velpatasvir for 12 weeks. The results were generally consistent with those observed in HCV-negative subjects with ESRD requiring dialysis.
-Velpatasvir: No clinically relevant differences in velpatasvir pharmacokinetics were observed between healthy subjects and patients with severe renal impairment. Additionally, the pharmacokinetics of velpatasvir in HCV-infected subjects with end-stage renal disease (ESRD) requiring dialysis who were treated with sofosbuvir; velpatasvir for 12 weeks were generally consistent with those observed in HCV-negative subjects with ESRD requiring dialysis.
Pediatrics
The pharmacokinetics of sofosbuvir, GS-331007, and velpatasvir were evaluated in HCV genotype 1, 2, 3, 4, or 6 infected pediatric subjects 3 years of age and older receiving a daily dose of sofosbuvir; velpatasvir based on weight. Sofosbuvir AUC and Cmax and velpatasvir Cmax values were 67%, 69%, and 78% higher in pediatric subjects weighing 30 kg or more; 68%, 70%, and 96% higher in pediatric subjects weighing 17 to 29 kg; and 103%, 135%, and 92% higher in pediatric subjects weighing less than 17 kg compared to those observed in adults. This difference was not considered clinically significant. The exposures of GS-331007 and velpatasvir in pediatric subjects were similar to those observed in adults.
Geriatric
Population pharmacokinetic analysis of HCV-infected patients aged 18 to 82 years old, showed that age did not have a clinically relevant effect on the exposure to sofosbuvir, GS-331007, or velpatasvir.
Gender Differences
Population pharmacokinetics analysis indicated that gender had no clinically relevant effect on the exposure of sofosbuvir, GS-331007, or velpatasvir.
Ethnic Differences
Population pharmacokinetics analysis indicated that race had no clinically relevant effect on the exposure of sofosbuvir, GS-331007, or velpatasvir.