What are the potential drug interactions with VELASOF (Sofosbuvir) / SOVIHEP V (Velpatasvir)?

From the Guidelines

Velasof and Sovihep V should be used with caution due to potential drug interactions, particularly with antacids, H2-receptor antagonists, proton pump inhibitors, and certain antiretrovirals, which can affect their efficacy and increase the risk of adverse events. When considering the use of Velasof and Sovihep V, it is essential to be aware of the potential drug interactions that can impact their effectiveness and safety. According to the EASL recommendations on the treatment of hepatitis C in 2016 1, some drugs may require dose modifications dependent on hepatic function, and the co-administration of certain medications can lead to significant interactions. Some key points to consider include:

• The co-administration of proton pump inhibitors should be avoided during sofosbuvir/velpatasvir treatment, but if necessary, the medication should be taken with food and 4 hours before the proton pump inhibitor at a maximum dose comparable to omeprazole 20 mg 1.
• In HIV-HCV coinfected patients, sofosbuvir/velpatasvir may be given with most antiretrovirals, except for the inducing drugs efavirenz, etravirine, and nevirapine, which can decrease velpatasvir exposure 1.
• Sofosbuvir/velpatasvir can increase tenofovir exposure due to P-gp inhibition, requiring monitoring for renal adverse events in patients on a regimen containing tenofovir disoproxil fumarate 1. It is crucial to consult the product label for individual drugs and refer to reliable sources, such as www.hep-druginteractions.org, for detailed pharmacokinetic interaction data and dosage adjustments to minimize the risk of adverse events and ensure the effective treatment of hepatitis C.

From the FDA Drug Label

Potentially Significant Drug Interactions Sofosbuvir is a substrate of drug transporter P-gp and breast cancer resistance protein (BCRP) while the predominant circulating metabolite GS-331007 is not. Drugs that are P-gp inducers in the intestine (e.g., rifampin or St. John's wort) may decrease sofosbuvir plasma concentration, leading to reduced therapeutic effect of SOVALDI, and thus concomitant use with SOVALDI is not recommended [see Warnings and Precautions (5. 3)] . Table 6 Potentially Significant Drug Interactions: Alteration in Dosage or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction

• Concomitant Drug Class: Drug NameEffect on Concentration †Clinical Comment
• This table is not all-inclusive. † ↓ = decrease Antiarrhythmics: amiodarone Effect on amiodarone and sofosbuvir concentrations unknownCoadministration of amiodarone with a sofosbuvir-containing regimen may result in serious symptomatic bradycardia. The mechanism of this effect is unknown Coadministration of amiodarone with SOVALDI is not recommended; if coadministration is required, cardiac monitoring is recommended [see Warnings and Precautions (5.2), Adverse Reactions (6. 2)]. Anticonvulsants: Carbamazepine phenytoin phenobarbital oxcarbazepine ↓ sofosbuvir ↓ GS-331007 Coadministration of SOVALDI with carbamazepine, phenytoin, phenobarbital or oxcarbazepine is expected to decrease the concentration of sofosbuvir, leading to reduced therapeutic effect of SOVALDI. Coadministration is not recommended Antimycobacterials: Rifabutin rifampin rifapentine ↓ sofosbuvir ↓ GS-331007 Coadministration of SOVALDI with rifabutin or rifapentine is expected to decrease the concentration of sofosbuvir, leading to reduced therapeutic effect of SOVALDI. Coadministration is not recommended. Coadministration of SOVALDI with rifampin, an intestinal P-gp inducer, is not recommended [see Warnings and Precautions (5.

Key Interactions:

• Amiodarone: Coadministration may result in serious symptomatic bradycardia. Not recommended, but if required, cardiac monitoring is necessary.
• Anticonvulsants (e.g., carbamazepine, phenytoin, phenobarbital, oxcarbazepine): Expected to decrease sofosbuvir concentration, leading to reduced therapeutic effect. Coadministration is not recommended.
• Antimycobacterials (e.g., rifabutin, rifampin, rifapentine): Expected to decrease sofosbuvir concentration, leading to reduced therapeutic effect. Coadministration is not recommended. These interactions may lead to reduced therapeutic effect of SOVALDI or increased risk of adverse reactions. 2

From the Research

Drug Interaction Studies

• The studies provided do not directly address the drug interaction between VELASOF/SOVIHEP V, however, they discuss the potential for drug interactions with other medications, particularly those that affect the cytochrome P450 enzymes and P-glycoproteins 3, 4.
• Class III antiarrhythmic drugs, such as amiodarone, have been reported to be involved in a significant number of drug interactions, mainly through pharmacodynamic and pharmacokinetic interactions 4.
• The studies on sofosbuvir and velpatasvir, components of VELASOF/SOVIHEP V, focus on their efficacy and safety in treating hepatitis C virus (HCV) infection, rather than their potential interactions with other drugs 5, 6, 7.
• It is essential to exercise caution and closely monitor patients when using VELASOF/SOVIHEP V in combination with other medications, especially those that may interact with its components, to minimize the risk of adverse drug interactions 3, 4.

Potential Interaction Mechanisms

• Pharmacodynamic interactions, where the effects of one drug are enhanced or diminished by another drug, can occur with VELASOF/SOVIHEP V, particularly with medications that have similar mechanisms of action 3, 4.
• Pharmacokinetic interactions, which affect the absorption, distribution, metabolism, or excretion of a drug, may also occur with VELASOF/SOVIHEP V, especially with medications that inhibit or induce cytochrome P450 enzymes or P-glycoproteins 3, 4.

Clinical Implications

• Healthcare providers should be aware of the potential for drug interactions with VELASOF/SOVIHEP V and take steps to minimize risks, such as closely monitoring patients and adjusting medication regimens as needed 3, 4.
• The use of drug interaction software and collaboration with pharmacists can help prevent clinically significant drug interactions and optimize drug safety 3.