Lesovir-C90 mg+400 mg

Lesovir-C is a fixed-dose combination of two direct-acting antiviral (DAA) agents indicated for the treatment of chronic hepatitis C virus (HCV) infection in adults and select pediatric patients. Evidence and approval status vary by clinical scenario:

Established / Approved Uses

• Chronic HCV genotype 1, 4, 5, or 6 infection in adults and pediatric patients ≥3 years of age, without cirrhosis or with compensated (Child-Pugh A) cirrhosis, used alone.
• Chronic HCV genotype 1 infection with decompensated cirrhosis, used in combination with ribavirin.
• Chronic HCV genotype 1 or 4 infection in liver transplant recipients without cirrhosis or with compensated cirrhosis, used in combination with ribavirin.
• HCV/HIV-1 co-infected patients with chronic HCV genotype 1, 4, 5, or 6 infection, using the same regimen as HCV mono-infected patients.

Uses Requiring Combination Therapy

In patients with decompensated cirrhosis or in certain liver transplant recipients, Lesovir-C is not used alone; it must be combined with ribavirin as directed by a hepatologist/gastroenterologist experienced in HCV management.

Not Recommended / Not Indicated

Lesovir-C is not recommended for HCV genotypes for which adequate efficacy data are lacking (e.g., genotype 2 or 3 monoinfection), and it does not treat other viral hepatitis infections (hepatitis A or B) or non-HCV liver disease.

Each film-coated tablet of Ledipasvir + Sofosbuvir typically contains:

• Ledipasvir 90 mg (an HCV NS5A inhibitor)
• Sofosbuvir 400 mg (an HCV NS5B nucleotide polymerase inhibitor)

Lower-strength pediatric tablets and oral granules (ledipasvir 33.75 mg/sofosbuvir 150 mg and ledipasvir 45 mg/sofosbuvir 200 mg) are also available for weight-based dosing in children.

Lesovir-C is an oral fixed-dose combination antiviral medicine used to treat chronic hepatitis C virus (HCV) infection. It combines two direct-acting antivirals with complementary mechanisms of action — ledipasvir, an NS5A replication complex inhibitor, and sofosbuvir, a nucleotide analog NS5B polymerase inhibitor — into a single once-daily tablet.

By targeting two distinct steps of the HCV replication cycle, Lesovir-C achieves high rates of sustained virologic response (functional cure) in appropriately selected patients, without the need for interferon or, in most regimens, ribavirin.

Lesovir-C belongs to the therapeutic class of direct-acting antiviral agents (DAAs) for chronic hepatitis C, specifically a combination of an NS5A inhibitor and an NS5B polymerase inhibitor.

Ledipasvir + Sofosbuvir combines two antiviral agents that act at different points in the hepatitis C virus (HCV) lifecycle:

• Ledipasvir inhibits the HCV NS5A protein, which is essential for viral RNA replication and assembly of virions.
• Sofosbuvir is a prodrug that is metabolized intracellularly to its active triphosphate form, which acts as a chain terminator when incorporated by the HCV NS5B RNA-dependent RNA polymerase, thereby inhibiting viral RNA synthesis.

The combination has demonstrated activity against HCV genotypes 1, 4, 5, and 6, with variable and generally lower activity against genotypes 2 and 3. Following oral administration, sofosbuvir is absorbed and rapidly converted to its predominant circulating metabolite (GS-331007); ledipasvir has a longer elimination half-life. Sofosbuvir and its metabolite are predominantly renally eliminated, while ledipasvir is eliminated mainly via biliary excretion of unchanged drug.

Lesovir-C tablets should be swallowed whole with or without food; they should not be chewed, crushed, or split, as this has not been evaluated. Oral granules (for younger/smaller pediatric patients) should be administered by mixing with a small amount of non-acidic soft food (e.g., pudding, mashed potato) or given directly into the mouth, followed immediately by swallowing without chewing.

Dosing with acid-reducing agents requires attention to timing (see Interactions).

Lesovir-C has several clinically significant drug interactions:

• Potent P-glycoprotein (P-gp) inducers / CYP inducers (e.g., rifampin, rifabutin, rifapentine, carbamazepine, phenytoin, phenobarbital, oxcarbazepine, St. John's Wort): significantly decrease ledipasvir and sofosbuvir plasma concentrations, risking loss of therapeutic effect and treatment failure. Coadministration with rifampin is contraindicated (see Contraindications); other strong inducers should generally be avoided.
• Amiodarone: coadministration (with or without other HCV DAAs) has been associated with serious symptomatic bradycardia, including fatal cases, particularly in patients also taking beta-blockers or with underlying cardiac disease. Concomitant use is not recommended; if unavoidable, cardiac monitoring is required, especially during the first weeks of treatment.
• Acid-reducing agents (antacids, H2-receptor antagonists, proton pump inhibitors): increasing gastric pH reduces ledipasvir solubility and absorption. Antacids should be separated by 4 hours; H2-blockers should not exceed doses comparable to famotidine 40 mg twice daily and should be taken simultaneously with or 12 hours apart from the dose; proton pump inhibitor doses should not exceed omeprazole 20 mg equivalent and should be taken simultaneously with food.
• Tenofovir disoproxil fumarate-containing antiretroviral regimens (especially with a boosted HIV protease inhibitor): coadministration increases tenofovir concentrations; renal function should be monitored.
• Rosuvastatin and other statins: increased statin exposure raises the risk of myopathy, including rhabdomyolysis; dose limitation or careful monitoring is advised.
• Digoxin: concentrations may increase; monitoring of digoxin levels is recommended if coadministered.

Patients should inform their physician of all prescription drugs, over-the-counter medicines, and herbal products they are taking before starting Lesovir-C.

Lesovir-C is generally well tolerated. The most commonly reported adverse effects (used alone, without ribavirin) include:

• Fatigue
• Headache

Other reported adverse effects include nausea, diarrhea, insomnia, and asthenia. When Lesovir-C is given together with ribavirin, additional adverse effects associated with ribavirin — most notably anemia — are more frequent. Serious adverse effects are uncommon but include hepatitis B reactivation and serious bradyarrhythmias with concomitant amiodarone (see Precautions and Interactions). Patients should report any unusual or severe symptoms to their physician promptly.

Pregnancy: Data on the use of Lesovir-C in pregnant women are limited. It should be used during pregnancy only if clearly needed and the potential benefit justifies the potential risk to the fetus; use only under close physician supervision. If Lesovir-C is used in combination with ribavirin, pregnancy is an absolute contraindication for that combination due to ribavirin's known teratogenic and embryocidal effects — pregnancy must be excluded before starting, and effective contraception is required during treatment and for a defined period afterward, for female patients and for female partners of male patients.

Lactation: It is not known whether ledipasvir or sofosbuvir/its metabolites are excreted in human breast milk. Because many drugs are excreted in breast milk and the potential for adverse effects on the infant is unknown, a decision should be made whether to discontinue breastfeeding or discontinue the drug, taking into account the importance of treatment to the mother; consult a physician before breastfeeding while taking Lesovir-C.

Hepatitis B virus (HBV) reactivation: Cases of HBV reactivation, some fatal, have been reported in HCV/HBV co-infected patients treated with direct-acting antivirals, including Lesovir-C. All patients should be screened for current or prior HBV infection before starting treatment, and HBV-coinfected patients should be monitored during and after treatment as clinically indicated.

Serious bradycardia with amiodarone: Life-threatening bradyarrhythmias have occurred when amiodarone is coadministered with Lesovir-C, particularly with concurrent beta-blocker use or in patients with cardiac comorbidities. This combination is not recommended; if no alternative exists, cardiac monitoring is required, especially during the first 48 hours and continuing closely for the first two weeks.

Renal impairment: Caution is advised in patients with severe renal impairment (eGFR <30 mL/min/1.73m²) or end-stage renal disease, as sofosbuvir and its metabolite may accumulate; use only if the potential benefit outweighs the risk and under specialist supervision.

Use with other HCV regimens: Lesovir-C should not be combined with other medicines containing sofosbuvir.

Risk of resistance: Missing doses or stopping treatment early increases the risk of virologic relapse and development of resistance-associated substitutions; patients must complete the full prescribed course exactly as directed and not stop, extend, skip doses, or share this medicine with others without medical advice.

There is limited clinical experience with overdose of Lesovir-C. In available reports, high doses of the individual components have been generally well tolerated without evidence of serious adverse effects. There is no specific antidote for overdose. In case of suspected overdose, seek immediate medical attention or contact a poison control center. Management should be supportive, monitoring the patient's vital signs and clinical status. Hemodialysis can efficiently remove the predominant circulating metabolite of sofosbuvir, but is unlikely to result in significant removal of ledipasvir 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.

Elderly: No dosage adjustment is required based on age alone; clinical studies did not identify overall differences in safety or efficacy between elderly and younger adult patients, though limited data are available for patients over 65 years.

Renal impairment: No dosage adjustment is needed for mild or moderate renal impairment. See Precautions for severe renal impairment/ESRD.

Hepatic impairment: No dosage adjustment is required for patients with mild, moderate, or severe (compensated or decompensated) hepatic impairment; decompensated cirrhosis requires combination with ribavirin per specialist guidance.

HIV-1 co-infection: The same dosing regimen used for HCV mono-infection applies; attention should be paid to interactions with antiretroviral therapy (see Interactions).

Post-liver transplant patients: Used in combination with ribavirin; duration depends on cirrhosis status (see Dosage and Administration).

Pediatric patients: See Pediatric Uses.

Treatment duration with Lesovir-C ranges from 8 to 24 weeks depending on HCV genotype, prior treatment experience, presence and severity of cirrhosis, and whether ribavirin is co-administered (see the duration table under Dosage and Administration). The exact duration must be determined by the prescribing physician and the full course must be completed even if the patient feels well before finishing, to maximize the chance of cure and reduce the risk of viral relapse or resistance.

Ledipasvir + Sofosbuvir is classified as a combination direct-acting antiviral (DAA): an HCV NS5A inhibitor (ledipasvir) plus an HCV NS5B nucleotide polymerase inhibitor (sofosbuvir).

Ledipasvir + Sofosbuvir works through the complementary mechanisms of its two components. Ledipasvir binds to and inhibits the HCV NS5A protein, blocking viral RNA replication and virion assembly. Sofosbuvir, after intracellular activation to its triphosphate form, is incorporated into the growing HCV RNA chain by the viral NS5B RNA-dependent RNA polymerase, causing chain termination and halting viral RNA synthesis. Together, these actions suppress HCV replication at two distinct steps of the viral lifecycle, leading to sustained virologic response (undetectable viral RNA, indicating cure) in most treated patients.

Lesovir-C is approved for the treatment of chronic HCV genotype 1, 4, 5, or 6 infection in pediatric patients ≥3 years of age, without cirrhosis or with compensated cirrhosis, using weight-based dosing (see Dosage). Safety and efficacy in children younger than 3 years of age have not been established, and Lesovir-C should not be used in this age group. In eligible pediatric patients, the treatment duration is generally 12 weeks; use in children with decompensated cirrhosis or those requiring ribavirin combination has more limited data, and such use should be directed by a pediatric hepatology specialist.