Drug-Drug Interaction Profile of Sofosbuvir/Velpatasvir Fixed-Dose Combination

Mogalian, Erik; McNally, John; Shen, Gong; Moorehead, Lisa; Sajwani, K.; Smith, Brandon; Ling, J.; Mathias, Anita

doi:10.1016/s0168-8278(16)01136-3

Cited by 7 publications

(18 citation statements)

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“…These findings correspond with a previous DDI study, which resulted in the restrictions for the use of PPIs. Although the effect was more pronounced in the study with SOF/VEL 400/100 mg and omeprazole 20 mg simultaneously (−37%), we observed an effect of −27% (90% CI 55.6–96.8) that fell out of the PK equivalence boundaries . This difference might be explained by study design (e.g., fasting conditions and omeprazole intake) and patient characteristics (e.g., CYP2C19 genotype and stomach acidity).…”

Section: Discussioncontrasting

confidence: 58%

“…Although the effect was more pronounced in the study with SOF/VEL 400/100 mg and omeprazole 20 mg simultaneously (−37%), we observed an effect of −27% (90% CI 55.6-96.8) that fell out of the PK equivalence boundaries. 5 This difference might be explained by study design (e.g., fasting conditions and omeprazole intake) and patient characteristics (e.g., CYP2C19 genotype and stomach acidity). For example, we found no decrease in VEL exposure for all rapid CYP2C19 metabolizers after intake of omeprazole.…”

Section: Discussionmentioning

confidence: 99%

“…This increase in gastric pH impairs VEL absorption. It has been shown that, in subjects treated with omeprazole, the absorption of VEL is reduced by 26–56%, depending on the dose of omeprazole, concomitant food intake, and timing/sequence of VEL vs. omeprazole intake . This is the reason why concomitant use of SOF/VEL with PPIs (such as omeprazole) is not recommended.…”

mentioning

confidence: 99%

“…It has been shown that, in subjects treated with omeprazole, the absorption of VEL is reduced by 26-56%, depending on the dose of omeprazole, concomitant food intake, and timing/sequence of VEL vs. omeprazole intake. 5,6 This is the reason why concomitant use of SOF/VEL with PPIs (such as omeprazole) is not recommended. The package insert recommends the administration of SOF/VEL with food and taken 4 hours before PPI at maximum doses comparable to omeprazole 20 mg, if PPI use is necessary.…”

mentioning

confidence: 99%

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Concomitant Intake of Coca‐Cola to Manage the Drug–Drug Interaction Between Velpatasvir and Omeprazole Studied in Healthy Volunteers

Seyen¹,

Colbers²,

Abbink

et al. 2019

Clin Pharma and Therapeutics

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We aimed to evaluate the effect of the acid beverage Coca‐Cola on the pharmacokinetics of velpatasvir (VEL) when given with omeprazole. This was an open‐label, randomized, crossover trial in 11 healthy adults. A single dose of sofosbuvir/velpatasvir (SOF/VEL) 400/100 mg was administered alone (reference) or with omeprazole 40 mg once daily with water (intervention I); in the intervention II arm, omeprazole 40 mg was combined with 250 mL of Coca‐Cola. Geometric mean ratios (GMRs) were calculated for VEL area under the concentration‐time curve from zero to infinity (AUC 0−inf) and maximum plasma concentration (Cmax). VEL exposure was reduced by 26.7% when SOF/VEL was coadministered with omeprazole vs. reference: GMRs (90% confidence interval (CI)) were 73.3% (55.6–96.8) and 69.1% (52.3–91.2) for AUC 0‐inf and Cmax, respectively. Intake of SOF/VEL with Coca‐Cola compensated for the interaction with omeprazole and resulted in a higher VEL exposure. GMRs (90% CI) were 161.6% (122.4–213.3) for AUC 0‐inf and 143.9% (109.0–190.0) for Cmax. Therefore, Coca‐Cola can be used to overcome the drug–drug interaction between VEL and omeprazole.

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Section: Discussioncontrasting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Concomitant Intake of Coca‐Cola to Manage the Drug–Drug Interaction Between Velpatasvir and Omeprazole Studied in Healthy Volunteers

Seyen¹,

Colbers²,

Abbink

et al. 2019

Clin Pharma and Therapeutics

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“…During pregnancy, women often suffer from nausea and heartburn for which antacids and/or proton pump inhibitors (PPIs) may be prescribed . It has been shown that velpatasvir and ledipasvir exposure in healthy volunteers treated with PPIs such as omeprazole, is reduced up to 40% . Therefore, co‐administration of PPIs with velpatasvir or ledipasvir during pregnancy should be avoided if possible…”

Section: Effect Of Pregnancy On Maternal Exposure To Direct‐acting Anmentioning

confidence: 99%

Review article: direct‐acting antivirals for the treatment of HCV during pregnancy and lactation ‐ implications for maternal dosing, foetal exposure, and safety for mother and child

Freriksen

Seyen²,

Judd

et al. 2019

Aliment Pharmacol Ther

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Summary Background With the global efforts to eradicate hepatitis C virus (HCV), treatment during pregnancy is becoming a priority for research as this, and maternal cure should reduce vertical transmission. However, as information on the efficacy and safety of direct‐acting antivirals (DAAs) in pregnancy is generally lacking, treatment of HCV infection during pregnancy is not currently recommended. Aim To provide an overview of current knowledge regarding maternal exposure, placental handling and safety of DAAs during pregnancy and lactation Methods A literature search was performed focusing on the effect of pregnancy on maternal exposure to DAAs, the placental handling of DAAs, the safety of DAAs for mother and child during pregnancy and the safety of DAAs during lactation. Results Exposure to all DAAs studied is likely to be altered during pregnancy, mostly related to pregnancy‐induced effects on drug absorption and metabolism. Although animal studies show that most DAAs are reported to cross the placenta and transfer into breast milk, most DAA combinations show a favourable safety profile. Because of the rapid viral decline after treatment initiation, and to avoid the critical period of organogenesis, treatment may be started at the end of the second trimester or early third trimester. Conclusions Treatment of HCV infection during pregnancy is realistic, as DAAs are highly effective and treatment duration is relatively short. There is an urgent need to study DAAs during pregnancy and lactation to contribute to the goal of HCV elimination.

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Sofosbuvir/Velpatasvir: A Review in Chronic Hepatitis C

Greig

2016

Drugs

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A once-daily, single-tablet, pangenotypic regimen comprising the hepatitis C virus (HCV) NS5B polymerase inhibitor sofosbuvir and the HCV NS5A inhibitor velpatasvir (sofosbuvir/velpatasvir; Epclusa) was recently approved for the treatment of adults with chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection in the USA, EU and Canada. In the phase III ASTRAL trials, once-daily oral sofosbuvir/velpatasvir for 12 weeks provided very high rates of sustained virological response at 12 weeks post treatment (SVR12) in treatment-naive and -experienced patients with chronic HCV genotype 1-6 infection, including those with compensated cirrhosis or HIV-1 co-infection. High SVR12 rates were also observed with sofosbuvir/velpatasvir plus ribavirin for 12 weeks in patients with chronic HCV genotype 1-6 infection and decompensated cirrhosis. Sofosbuvir/velpatasvir was generally well tolerated, with low rates of adverse events. Thus, sofosbuvir/velpatasvir represents a valuable treatment option in adults with chronic HCV genotype 1-6 infection, including those with compensated or decompensated cirrhosis, previous treatment experience or HIV-1 co-infection.

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Drug-Drug Interaction Profile of Sofosbuvir/Velpatasvir Fixed-Dose Combination

Cited by 7 publications

References 0 publications

Concomitant Intake of Coca‐Cola to Manage the Drug–Drug Interaction Between Velpatasvir and Omeprazole Studied in Healthy Volunteers

Concomitant Intake of Coca‐Cola to Manage the Drug–Drug Interaction Between Velpatasvir and Omeprazole Studied in Healthy Volunteers

Review article: direct‐acting antivirals for the treatment of HCV during pregnancy and lactation ‐ implications for maternal dosing, foetal exposure, and safety for mother and child

Sofosbuvir/Velpatasvir: A Review in Chronic Hepatitis C

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