Velatas400 mg+100 mg

Velatas is a fixed-dose combination direct-acting antiviral (DAA) indicated for the treatment of chronic hepatitis C virus (HCV) infection.

FDA-approved / Established Indications

• Treatment of chronic HCV genotype 1, 2, 3, 4, 5, or 6 infection in adults and pediatric patients 3 years of age and older, without cirrhosis or with compensated (Child-Pugh A) cirrhosis, as a 12-week course of Velatas alone.
• Treatment of chronic HCV genotype 1-6 infection in patients with decompensated (Child-Pugh B or C) cirrhosis, when Velatas is used in combination with ribavirin for 12 weeks.

Velatas is pangenotypic, meaning it is active against all major HCV genotypes (1 through 6), which is one of its principal clinical advantages over earlier genotype-specific regimens.

Not Indicated For

Velatas is not indicated for the treatment of hepatitis B virus (HBV) infection or other viral hepatitis. It has no role in acute (non-chronic) hepatitis C outside of specialist-directed use.

Each film-coated tablet of Sofosbuvir + Velpatasvir contains:

• Sofosbuvir 400 mg (a nucleotide analogue NS5B polymerase inhibitor)
• Velpatasvir 100 mg (an NS5A inhibitor)

Pediatric oral pellet formulations of lower strength are also available for weight-based dosing in younger children.

Velatas is a fixed-dose combination antiviral tablet that pairs two direct-acting agents with complementary mechanisms against hepatitis C virus. Sofosbuvir inhibits the HCV NS5B RNA-dependent RNA polymerase, while velpatasvir inhibits the HCV NS5A protein, which is essential for viral replication and assembly.

Together, Velatas provides a pangenotypic, interferon-free, once-daily oral treatment option for chronic HCV infection, and has significantly simplified hepatitis C therapy compared with older interferon- and ribavirin-based regimens.

Velatas belongs to the class of direct-acting antivirals (DAAs) used for chronic hepatitis C, specifically combining an NS5B polymerase inhibitor (sofosbuvir) with an NS5A inhibitor (velpatasvir).

Mechanism of Action

Sofosbuvir + Velpatasvir combines two antiviral components that act at different steps of the HCV replication cycle:

• Sofosbuvir is a prodrug that is metabolized intracellularly to its active triphosphate form, which acts as an alternate substrate for the HCV NS5B RNA-dependent RNA polymerase, causing chain termination and inhibiting viral RNA replication.
• Velpatasvir inhibits the HCV NS5A protein, which is required for viral RNA replication and virion assembly.

Pharmacokinetics

Following oral administration, sofosbuvir is rapidly absorbed and extensively metabolized to its predominant circulating metabolite (GS-331007); velpatasvir is absorbed with peak plasma concentrations reached a few hours after dosing. Sofosbuvir and its metabolite are primarily renally eliminated, whereas velpatasvir is eliminated mainly via biliary/fecal excretion as unchanged drug. Sofosbuvir + Velpatasvir achieves high sustained virologic response (SVR) rates across HCV genotypes 1-6 with a 12-week regimen.

Take Velatas orally once daily at approximately the same time each day, with or without food. Swallow the tablet whole; do not chew or crush. Complete the full prescribed treatment duration even if feeling well, as stopping early risks treatment failure and resistance.

Velatas has clinically significant interactions with drugs that affect P-glycoprotein (P-gp) and certain cytochrome P450/drug transporter pathways. Only well-established, clinically significant interactions are listed below.

Avoid / Not Recommended

• Potent P-gp inducers and moderate-to-strong CYP inducers (e.g., rifampin, rifabutin, St. John's Wort, carbamazepine, phenytoin, oxcarbazepine): significantly reduce plasma concentrations of Velatas, risking loss of antiviral efficacy and treatment failure. Coadministration should be avoided.
• Amiodarone: coadministration with Velatas is not recommended due to risk of serious symptomatic bradycardia, particularly when Velatas is combined with another NS5B inhibitor; if unavoidable, cardiac monitoring is required (see Contraindications/Precautions).
• Efavirenz-containing antiretroviral regimens and tipranavir/ritonavir: reduce sofosbuvir/velpatasvir exposure — avoid coadministration.

Dose Adjustment or Monitoring Needed

• Acid-reducing agents: velpatasvir absorption decreases as gastric pH rises. Antacids should be separated by 4 hours; H2-receptor antagonists may be used at doses comparable to famotidine 40 mg twice daily, administered simultaneously with or 12 hours apart from Velatas; proton pump inhibitors are not recommended, but if necessary should be taken under fasting conditions simultaneously with Velatas.
• Statins (e.g., rosuvastatin, atorvastatin): Velatas can significantly increase statin levels, raising myopathy/rhabdomyolysis risk — dose limitation (e.g., rosuvastatin ≤10 mg/day) or close monitoring is advised.
• Digoxin: levels may increase; therapeutic monitoring recommended.

Velatas is generally well tolerated. Most reported adverse effects are mild-to-moderate.

Common Side Effects

• Headache
• Fatigue
• Nausea
• Diarrhea
• Insomnia

In patients with decompensated cirrhosis receiving Velatas plus ribavirin, fatigue, anemia, nausea, and headache are more frequent, largely attributable to ribavirin.

Less Common but Serious

• Serious symptomatic bradycardia (especially with concomitant amiodarone — see Contraindications/Precautions)
• Reactivation of hepatitis B virus in HCV/HBV coinfected patients (see Precautions)
• Elevated liver enzymes
• Skin rash

Patients should seek prompt medical attention for symptoms such as slow or irregular heartbeat, severe dizziness, fainting, extreme fatigue, or shortness of breath while taking Velatas.

Pregnancy: Human data on Velatas use in pregnancy are limited. Animal reproduction studies have not shown adverse developmental effects, but this does not guarantee human safety. Velatas should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus; consult a physician before use. When Velatas is used in combination with ribavirin, this combination is contraindicated in pregnant women and in male patients whose female partners are pregnant, due to ribavirin's known teratogenic and embryolethal effects — extreme care must be taken to avoid pregnancy during and for months after such therapy.

Lactation: It is not known whether sofosbuvir or velpatasvir passes into human breast milk. Because many drugs are excreted in breast milk, a decision should be made whether to discontinue breastfeeding or discontinue Velatas, taking into account the importance of treatment to the mother; consult a physician before breastfeeding while using Velatas.

Hepatitis B Virus (HBV) Reactivation

Cases of HBV reactivation, some resulting in fulminant hepatitis, hepatic failure, and death, have been reported in HCV/HBV coinfected patients treated with direct-acting antivirals such as Velatas. All patients should be screened for HBV infection (HBsAg and anti-HBc) before starting Velatas, and HBV-coinfected patients should be monitored during and after treatment.

Serious Bradycardia with Amiodarone

Coadministration of Velatas with amiodarone is not recommended due to risk of serious, symptomatic bradycardia (see Contraindications/Interactions). If no alternative exists, this should only be done with close cardiac monitoring, ideally in an inpatient setting for the initial days of coadministration.

Renal Impairment

Use with caution and appropriate monitoring in patients with severe renal impairment, as sofosbuvir metabolite exposure may increase; data in end-stage renal disease are limited.

Use With Ribavirin

When Velatas is combined with ribavirin for decompensated cirrhosis, all ribavirin-specific warnings and precautions (hemolytic anemia, teratogenicity, contraindication in pregnancy) apply to that combination regimen.

Treatment Adherence

Patients should complete the full prescribed course of Velatas exactly as directed and should not stop, skip doses, or share this medicine with others, as incomplete therapy risks treatment failure and development of resistance.

There is no specific antidote for Velatas overdose. The highest documented doses have not been associated with unique acute toxicity, but data are limited. In case of suspected overdose, seek immediate medical attention or contact a poison control center. Management is supportive, including monitoring of vital signs and clinical status. Hemodialysis can remove the major circulating sofosbuvir metabolite to a meaningful extent, but is not expected to significantly remove velpatasvir due to its high plasma protein binding.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Pediatric Use

Velatas is approved for use in pediatric patients 3 years of age and older with chronic HCV genotype 1-6 infection, using appropriate weight-based tablet or pellet dosing. Safety and efficacy in children younger than 3 years have not been established.

Elderly

No dose adjustment is required based on age alone. Clinical studies did not show significant differences in safety or efficacy between elderly and younger adult patients, though age-related decline in renal/hepatic function should be considered.

Renal Impairment

No dose adjustment needed for mild-to-moderate impairment; use with caution and monitoring in severe renal impairment (see Precautions).

Hepatic Impairment

No dose adjustment required across Child-Pugh A, B, or C; decompensated cirrhosis requires the ribavirin-containing regimen.

The standard duration of treatment with Velatas is 12 weeks, whether used alone (no cirrhosis or compensated cirrhosis) or in combination with ribavirin (decompensated cirrhosis). The full course must be completed as prescribed to achieve sustained virologic response and reduce the risk of relapse or resistance.

Direct-acting antiviral (DAA) combination: NS5B polymerase inhibitor (sofosbuvir) + NS5A inhibitor (velpatasvir), used for chronic hepatitis C. Sofosbuvir + Velpatasvir is pangenotypic (active against HCV genotypes 1-6).

Sofosbuvir + Velpatasvir works by simultaneously blocking two proteins essential to hepatitis C virus replication: sofosbuvir inhibits the NS5B RNA-dependent RNA polymerase (causing premature termination of viral RNA synthesis), while velpatasvir inhibits the NS5A protein (disrupting viral RNA replication and virion assembly). This dual mechanism gives Sofosbuvir + Velpatasvir potent, pangenotypic antiviral activity with a high barrier to treatment failure when used for the recommended duration.

Velatas is indicated for chronic HCV genotype 1-6 infection in pediatric patients 3 years of age and older, using weight-based dosing with tablet or oral pellet formulations. Safety and efficacy have not been established in children younger than 3 years. In pediatric clinical trials, vomiting and product-use issues (e.g., spitting out pellets) were reported more frequently in younger children; caregivers should follow the specific administration instructions for pellet formulations closely and consult a pediatric specialist for dosing.