Buviren400 mg

Buviren is a direct-acting antiviral (DAA), specifically a nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. It is indicated for the treatment of chronic hepatitis C virus infection in adults and pediatric patients, always as part of a combination antiviral regimen — Buviren is never used as monotherapy.

Established / approved combination regimens

• Genotype 1 or 4: Buviren with peginterferon alfa and ribavirin.
• Genotype 2: Buviren with ribavirin.
• Genotype 3: Buviren with ribavirin (with or without peginterferon alfa, per treatment history and guideline recommendation).
• HCV/HIV-1 co-infection: Buviren-based combination regimens selected as for HCV mono-infected patients, per current guidelines.

Guideline-supported interferon-free combinations

Current international treatment guidelines (e.g. AASLD-IDSA, WHO) also support interferon-free, all-oral regimens that combine Buviren with another direct-acting antiviral such as ledipasvir, velpatasvir, or daclatasvir, chosen according to HCV genotype and prior treatment history. These fixed or co-administered combinations are the preferred standard of care in many settings but must be prescribed and dispensed as directed by a qualified physician.

Buviren is not indicated for acute hepatitis C, hepatitis B, or hepatitis A, and is not effective against non-HCV viral infections.

Each film-coated tablet contains Sofosbuvir 400 mg as the active ingredient, along with standard pharmaceutical excipients.

Buviren is a prodrug of a nucleotide analog that, once inside hepatocytes, is metabolized to its active triphosphate form. It belongs to the direct-acting antiviral (DAA) class used in modern, largely interferon-free treatment of chronic hepatitis C. Buviren is supplied as an oral film-coated tablet (400 mg) and, in some markets, as oral pellets for weight-based pediatric dosing.

Buviren revolutionized hepatitis C therapy by enabling shorter, better-tolerated, higher cure-rate regimens compared with older interferon-based treatment, when used correctly in combination with other antiviral agents.

Antiviral agent – Direct-Acting Antiviral (DAA); HCV NS5B nucleotide analog polymerase inhibitor. Buviren belongs to this class.

Sofosbuvir is a nucleotide prodrug. After cellular uptake, it is metabolized through a series of enzymatic steps to form the pharmacologically active nucleoside analog triphosphate, GS-461203. This active metabolite acts as an alternative substrate for the HCV NS5B RNA-dependent RNA polymerase, the enzyme responsible for viral RNA replication.

Incorporation of GS-461203 into the growing viral RNA chain by the NS5B polymerase results in chain termination, because the metabolite lacks the structural feature required for continued RNA synthesis. This directly inhibits HCV replication. GS-461203 is a weak inhibitor of human DNA and RNA polymerases and of mitochondrial RNA polymerase, which underlies the relatively favorable tolerability profile of Sofosbuvir compared with older antivirals.

Sofosbuvir itself has minimal antiviral activity; efficacy depends on intracellular activation, and clinical benefit requires co-administration with a second (and sometimes third) antiviral agent active against a different step of the HCV lifecycle, to reduce the risk of resistance and treatment failure.

Buviren tablets are taken orally, once daily, with or without food, swallowed whole with water. It must always be taken together with the other antiviral medicine(s) prescribed as part of the combination regimen, at the times and for the full duration instructed by the physician.

Amiodarone: See Contraindications — coadministration of amiodarone with Buviren-containing regimens can cause serious, symptomatic bradycardia, including fatal cases, and is contraindicated/not recommended.

Potent P-glycoprotein (P-gp) inducers: See Contraindications — rifampin, rifabutin, rifapentine, carbamazepine, phenytoin, phenobarbital, and St. John's Wort significantly reduce plasma concentrations of Buviren, which may result in loss of antiviral efficacy.

Other HCV antiviral combination products: When Buviren is used within a specific fixed-dose or co-packaged combination product (e.g. with ledipasvir or velpatasvir), the complete interaction profile of the companion drug(s) also applies and must be reviewed in that product's own labeling.

HIV protease inhibitors (e.g. tipranavir/ritonavir): May significantly decrease Buviren plasma concentrations; coadministration is not recommended.

Other anticonvulsants (e.g. oxcarbazepine): May reduce Buviren concentrations through similar P-gp/enzyme induction mechanisms; avoid concurrent use where possible.

Always inform the prescribing physician of all other prescription medicines, over-the-counter drugs, and herbal supplements being used before starting Buviren.

The most commonly reported adverse effects with Buviren-based regimens include:

• Fatigue
• Headache
• Nausea
• Insomnia

When Buviren is combined with ribavirin and/or peginterferon alfa, additional effects commonly seen include anemia, rash, diarrhea, irritability, and neutropenia — these are generally attributable to the companion drugs rather than Buviren itself.

Hepatitis B virus (HBV) reactivation has been reported in patients coinfected with HBV and HCV who were treated with Buviren-containing regimens, in some cases with serious or fatal outcomes. See Precautions and Warnings for required screening before starting treatment.

Seek prompt medical attention for any signs of an allergic reaction (rash, swelling, difficulty breathing), unusually slow or irregular heartbeat, dizziness, or fainting.

Pregnancy: Buviren should be used during pregnancy only if clearly needed and if the potential benefit to the mother justifies the potential risk to the fetus; a physician must be consulted before use. Data on Buviren alone in human pregnancy are limited. Important: when Buviren is used in combination with ribavirin (with or without peginterferon alfa), that combination is contraindicated in pregnant women and in male patients whose female partners are pregnant, because ribavirin has significant teratogenic and/or embryocidal potential (see Contraindications).

Lactation: It is not known whether Buviren or its metabolites pass into human breast milk. Because many drugs are excreted in breast milk and the effect on a nursing infant is not established, a decision should be made, in consultation with a physician, to either discontinue breastfeeding or discontinue the medicine, taking into account the importance of the treatment to the mother.

Hepatitis B virus (HBV) reactivation

Test all patients for evidence of current or prior HBV infection (HBsAg and anti-HBc) before starting Buviren-containing treatment. Patients coinfected with HBV and HCV are at risk of HBV reactivation, which can result in fulminant hepatitis, hepatic failure, and death. Monitor coinfected patients for clinical and laboratory signs of hepatitis flare or HBV reactivation during and after treatment, and manage appropriately with anti-HBV therapy if indicated.

Not for use as monotherapy

Buviren must always be prescribed and taken together with another antiviral agent as part of a complete combination regimen; using it alone is not effective and promotes viral resistance.

Serious bradycardia with amiodarone

See Contraindications — do not combine Buviren-containing regimens with amiodarone. If no alternative exists, this should only occur under close cardiac monitoring in an in-patient setting.

Adherence

Complete the full course of therapy exactly as prescribed. Do not stop, skip doses, alter the dose, or share this medicine with another person without medical advice — incomplete or interrupted treatment increases the risk of treatment failure and development of drug-resistant HCV.

Renal and hepatic impairment

See Use in Special Populations for details on dosing in renal and hepatic impairment.

Limited data are available on Buviren overdose. In clinical studies, single doses up to three times the recommended dose were generally well tolerated. There is no specific antidote for Buviren overdose.

In case of suspected overdose, seek immediate medical attention or contact the nearest hospital emergency department or a poison control center. Management consists of general supportive care, monitoring of vital signs and clinical status, and treatment of symptoms as they arise. Hemodialysis can remove a portion of the circulating metabolite, and may be considered by treating physicians in significant overdose.

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

Renal impairment

No dose adjustment of Buviren is required for patients with mild or moderate renal impairment. For patients with severe renal impairment or end-stage renal disease, safety and dosing have not been fully established due to substantially increased levels of the main circulating metabolite; such use requires specialist supervision.

Hepatic impairment

No dose adjustment of Buviren is required for patients with mild, moderate, or severe hepatic impairment (including decompensated cirrhosis), based on available pharmacokinetic data, though close monitoring by a physician is advised in decompensated disease.

Elderly patients

Limited data are available specifically in elderly patients; no dedicated dose adjustment based on age alone is established, but treatment should be individualized considering overall health and concomitant medications.

HIV/HCV coinfection

Buviren-based combination regimens may be used in patients coinfected with HIV, selecting the companion antiviral(s) and regimen as for HCV mono-infected patients, with attention to interactions with antiretroviral therapy.

Treatment duration with Buviren-containing regimens typically ranges from 12 to 24 weeks, depending on the HCV genotype, the companion antiviral agent(s) used, presence of cirrhosis, and prior treatment history. Some modern interferon-free combination regimens may be as short as 8 weeks in selected patients. The treating physician determines the exact duration; the full course must be completed even if symptoms are not apparent, since hepatitis C is often asymptomatic.

Direct-Acting Antiviral (DAA); HCV NS5B nucleotide analog polymerase inhibitor. Sofosbuvir is the prototype and most widely used member of this drug class.

Sofosbuvir is a nucleotide prodrug that undergoes intracellular metabolism to its active triphosphate form, GS-461203. This active metabolite is incorporated by the HCV NS5B RNA-dependent RNA polymerase into the nascent viral RNA chain in place of the natural nucleotide, acting as a chain terminator and halting further viral RNA synthesis. Because it targets the essential HCV replication enzyme directly, Sofosbuvir exerts pangenotypic antiviral activity when combined with a suitable companion agent.

B

Buviren, in combination with ribavirin, is approved for the treatment of chronic HCV genotype 2 or 3 infection in pediatric patients 3 years of age and older, using weight-based dosing (150 mg, 200 mg, or 400 mg once daily depending on body weight — see Dosage and Administration).

Safety and efficacy of Buviren have not been established in children younger than 3 years of age, or for genotypes/regimens outside those specifically studied and approved in the pediatric population. Use in younger children or unapproved regimens should occur only under the direct supervision of a pediatric hepatology/infectious disease specialist.