SOLERON 100

INSTRUCTIONS for medical use of the medicinal product KYURLED

KYURLED is used in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adult patients.

Composition

Active substance: sofosbuvir; 1 film-coated tablet contains 400 mg of sofosbuvir; excipients: mannitol 60 (E 421), microcrystalline cellulose, sodium croscarmellose, colloidal silicon dioxide, magnesium stearate; tablet coating: Opadry II Blue (85F505068).

Pharmaceutical form

Film-coated tablets.

Main physical and chemical properties

Blue, capsule-shaped, biconvex film-coated tablets with engraving "400" on one side and smooth on the other.

Pharmacotherapeutic group

Antiviral agents for systemic use. Direct-acting antiviral agents. Antiviral agents for the treatment of hepatitis C virus (HCV).

ATC code

J05A P08.

Pharmacological properties

Pharmacodynamics

Mechanism of action

Sofosbuvir is a pan-genotypic inhibitor of the HCV NS5B RNA polymerase, which is essential for the replication of the virus. Sofosbuvir is a nucleotide prodrug that, after intracellular metabolism, forms the pharmacologically active uridine analog triphosphate (GS-461203), which can be incorporated into the HCV RNA by the NS5B polymerase and acts as a chain terminator.

Antiviral activity

In HCV replicon analyses, the effective concentrations (EC50) of sofosbuvir against full-length replicons of genotypes 1a, 1b, 2a, 3a, and 4a were 0.04, 0.11, 0.05, 0.05, and 0.04 μM, respectively, and the EC50 values of sofosbuvir against chimeric replicons of 1b, which encode NS5B from genotypes 2b, 5a, or 6a, were between 0.014 and 0.015 μM.

Resistance

Cell culture. HCV replicons with reduced susceptibility to sofosbuvir were selected in cell culture for multiple genotypes, including 1b, 2a, 2b, 3a, 4a, 5a, and 6a.

Pharmacokinetics

Sofosbuvir is a nucleotide prodrug that undergoes extensive metabolism. The active metabolite is formed in hepatocytes and is not detected in plasma.

Absorption

The pharmacokinetic properties of sofosbuvir and its main circulating metabolite GS-331007 were evaluated in healthy adult subjects and patients with chronic hepatitis C.

Distribution

Sofosbuvir is not a substrate for the uptake transporters OATP1B1 or OATP1B3, or the efflux transporters P-glycoprotein or BCRP.

Metabolism

Sofosbuvir is extensively metabolized in the liver to form the pharmacologically active nucleoside analog triphosphate GS-461203.

Elimination

Following a single oral dose of 400 mg [14C]-sofosbuvir, the mean total recovery of the dose was greater than 92%, consisting of approximately 80%, 14%, and 2.5% recovered in urine, feces, and expired air, respectively.

Clinical characteristics

Indications

KYURLED is used in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adult patients.

Contraindications

Hypersensitivity to the active substances or to any of the excipients of the medicinal product.

Special warnings and precautions for use

Special precautions. KYURLED should not be used as monotherapy and should be used in combination with other medicinal products for the treatment of hepatitis C virus infection.

Severe bradycardia and heart block

When KYURLED is used in combination with other direct-acting antiviral agents (DAAs) (including daclatasvir, simeprevir, and ledipasvir) and concomitantly with amiodarone, cases of severe bradycardia and heart block have been reported.

Patient with HCV genotype 1, 4, 5, or 6 infection who have previously failed treatment

The efficacy of KYURLED in patients with HCV genotype 1, 4, 5, or 6 infection who have previously failed treatment has not been studied.

Patient with HCV genotype 5 or 6 infection who have previously failed treatment

Data on the use of KYURLED in patients with HCV genotype 5 or 6 infection who have previously failed treatment are very limited.

Concomitant use with other direct-acting antiviral agents against HCV

KYURLED can be used in combination with other direct-acting antiviral agents, only if the available data indicate that their efficacy outweighs the risks.

Pregnancy and concomitant use with ribavirin

When KYURLED is used in combination with ribavirin or peginterferon alfa-2/ribavirin, women of childbearing potential or their male partners should use effective contraception during treatment and for a period after treatment.

Use with moderate P-glycoprotein inducers

Medicinal products that are moderate inducers of P-glycoprotein in the intestine (such as oxcarbazepine and modafinil) may decrease the plasma concentration of sofosbuvir, leading to reduced therapeutic effect of KYURLED.

Renal impairment

The safety of KYURLED has not been assessed in patients with severe renal impairment (eGFR <30 mL/min/1.73 m2) or in patients with chronic kidney disease requiring hemodialysis.

HCV/HBV co-infection (hepatitis B virus)

During or after treatment with direct-acting antiviral agents, cases of hepatitis B virus (HBV) reactivation have been reported, some of which were fatal.

Pediatric population

KYURLED is not recommended for use in children (under 18 years of age), as the safety and efficacy have not been established in this population.

Interaction with other medicinal products and other forms of interaction

Sofosbuvir is a nucleotide prodrug that undergoes extensive metabolism. After administration of KYURLED, sofosbuvir is rapidly absorbed and undergoes intensive first-pass metabolism in the liver and stomach.

Interaction table

Special instructions

Women of childbearing potential/contraception for men and women

When KYURLED is used in combination with ribavirin or peginterferon alfa-2/ribavirin, special attention should be paid to preventing pregnancy in female patients and their male partners.

Use during pregnancy or breastfeeding

There are no or limited data (less than 300 pregnancy outcomes) on the use of sofosbuvir in pregnant women.

Ability to influence the speed of reaction when driving vehicles or operating other mechanisms

KYURLED has a moderate influence on the ability to drive vehicles and work with complex mechanisms.

Method of administration and dosage

Adults

Recommended dose - 400 mg in the form of a tablet, which should be taken orally once a day during meals.

Table of recommendations for concomitant use of medicinal products and duration of comprehensive therapy with KYURLED

Dose adjustment

Dose reduction of KYURLED is not recommended.

Elderly patients

Dose adjustment for elderly patients is not required.

Renal impairment

No dose adjustment of KYURLED is required for patients with mild or moderate renal impairment.

Hepatic impairment

No dose adjustment of KYURLED is required for patients with mild, moderate, or severe hepatic impairment.

Overdose

The maximum reported dose of sofosbuvir is a single dose of 1200 mg, which was administered to 59 healthy subjects.

Adverse reactions

Brief overview of the safety profile. During treatment with sofosbuvir in combination with ribavirin or with peginterferon alfa-2 and ribavirin, the most common adverse reactions were those expected based on the safety profiles of sofosbuvir and peginterferon alfa-2.

Table of adverse reactions

Shelf life

3 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 30 °C.

Packaging

White high-density polyethylene bottle with an aluminum foil and a polypropylene child-resistant cap.

Release category

Prescription only.

Manufacturer

Strides Pharma Science Limited.

Manufacturer's location and address

No. 36/7, Suragajakkanahalli, Indlawadi Cross, Anekal Taluk, Bangalore, Karnataka 562106, India.

Applicant

Strides Pharma Science Limited.

Applicant's location

201, Devawrata Sector 17, Vashi, Navi Mumbai – 400 703, India.