• Rating:
  • Manufacturer:
  • Model:
    1267
  • Available:
    In stock
  • Availability date:
    2020-07-30
  • Dosage form:
    tablets
  • In stock:
    159 Items

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Composition:


active ingredients: ledipasvir, sofosbuvir;


1 film-coated tablet contains 90 mg of ledipasvir and 400 mg of sofosbuvir;


excipients: lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, colloidal anhydrous Silicon Dioxide, Magnesium Stearate, Opadry II Brown 85F565007 (polyvinyl alcohol, polyethylene glycol, titanium dioxide, talc, iron oxide red, iron oxide yellow).


Dosage form. Film-coated tablets.


Basic physical and chemical properties: Brown, capsule-shaped biconvex tablets with beveled edges, film-coated, with the inscription "H" on one side and "L18" on the opposite side.


Pharmacotherapeutic group.


Direct-acting antiviral agents.


ATX code J05A P51.


Pharmacological properties.


Pharmacodynamics.


Mechanism of action


Ledipasvir is an HCV inhibitor targeted by the HCV NS5A protein, which is essential for RNA replication and assembly of HCV virions. Since NS5A has no enzymatic activity, biochemical confirmation of NS5A inhibition by ledipasvir is currently impossible. In vitro studies on selective and cross-resistance have shown that ledipasvir acts on NS5A as an object of its influence. Sofosbuvir is a pangenotypic inhibitor of HCV-dependent NS5A RNA polymerase, which is essential for viral replication.


Sofosbuvir is a nucleotide Depot form that is converted by intracellular metabolism to pharmacologically active uridine-analog triphosphate (GS-461203), which can be incorporated into HCV RNA by NS5B polymerase and play the role of a synthesis Terminator. GS - 461203 (the active metabolite of sofosbuvir) is not an inhibitor of human DNA and RNA polymerases and is not an inhibitor of mitochondrial RNA polymerase.

Clinical characteristics.


Indications.


Sofgen-L is indicated for the treatment of chronic hepatitis C (HCG) in adult patients (see the sections "dosage and Administration", "special safety measures" and "pharmacodynamics").


For the genotype-specific activity of hepatitis C virus (HCV), see the sections "special safety measures" and "pharmacodynamics".


Contraindications.


Hypersensitivity to active ingredients or any excipient.


Concomitant use with rosuvastatin (see the section "interactions with other drugs and other types of interactions").


Use with strong P-glycoprotein inducers


Medications that are strong inducers of P‑glycoprotein (P-gp) in the gut (rifampicin, rifabutin, St. John's wort [Hypericum perforatum], carbamazepine, phenobarbital, and phenytoin). Concomitant use will significantly reduce the concentration of ledipasvir and sofosbuvir in blood plasma and may lead to a decrease in the effectiveness of Sofgen-L (see the section "interactions with other drugs and other types of interactions").


Special security measures.


Sofgen-L should not be used together with other medications that contain sofosbuvir.


Genotype - specific activity


Recommended treatment regimens for different HCV genotypes are given in the section "dosage and administration". Information on genotype-specific virological and clinical activity is provided in the section "pharmacodynamics".


Clinical data supporting the use of Sofgen-L for the treatment of patients infected with HCV genotype 3 are limited (see Section "pharmacodynamics"). The relative efficacy of the 12-week course of treatment presented by ledipasvir/sofosbuvir + ribavirin compared to the 24-week course of treatment with sofosbuvir + ribavirin has not been studied. For all patients with genotype 3 who have undergone therapy, as well as for patients with cirrhosis of the liver, patients with genotype 3 who have not undergone previous therapy, a 24-week course of conservative treatment is recommended (see the section "route of administration and doses").


Clinical data supporting the use of Sofgen-L for the treatment of patients infected with HCV genotypes 2 and 6 are limited (see the section "pharmacodynamics").


Severe bradycardia and cardiac conduction block


Cases of severe bradycardia and cardiac conduction block have been reported with or without concomitant use of Sofgen-L and amiodarone together with other drugs that slow the heart rate. The mechanism of this phenomenon is not clear.


Co-administration with Amiodarone during the clinical development period of sofosbuvir with direct-acting antiviral drugs (PPD) was limited. Such cases are life-threatening, so amiodarone should be prescribed to patients undergoing treatment with Sofgen-l only if other alternative antiarrhythmic drugs are poorly tolerated or contraindicated.


If concomitant use of Amiodarone is deemed necessary, continuous monitoring of the patient's condition is recommended after prescribing Sofgen-L. If it is determined that the patient is at high risk of developing bradycardia, it is necessary to ensure continuous monitoring for 48 hours in the appropriate conditions of the medical institution.


Due to the Long Half-Life of amiodarone, patients who have stopped taking amiodarone in the last few months and start taking Sofgen-L should be properly monitored.


All patients taking Sofgen-L in combination with or without amiodarone or other heart-lowering medications should distinguish between symptoms of bradycardia and cardiac conduction blockage and seek medical attention immediately after such symptoms occur.


Use in patients who have previously taken direct-acting antiviral drugs for the treatment of HCV infection


In patients whose treatment with ledipasvir/sofosbuvir did not work, in most cases the presence of NS5A resistance mutations is observed, which reduce sensitivity to ledipasvir (see the section "pharmacodynamics"). Some data indicate that such NS5A mutations do not reappear during long-term follow-up. Currently, there are no data confirming the effectiveness of repeated treatment with an NS5A inhibitor in patients in whom the effectiveness of ledipasvir/sofosbuvir was absent. Similarly, there are currently no data confirming the efficacy of NS3/4A proteinase inhibitors in patients whose previous course of therapy with NS3/4A proteinase inhibitors was ineffective. Accordingly, such patients may be dependent on other classes of the drug to eliminate HCV infection. Therefore, the possibility of extending the treatment period for patients with uncertain options for further therapy should be considered.


Kidney failure


Dose adjustment of Sofgen-L is not required for patients with mild to moderate renal insufficiency. The safety of using Sofgen-L in patients with severe renal insufficiency (estimated glomerular filtration rate [rscf] 2) or end-stage renal insufficiency (TSNN) with the need for hemodialysis has not been studied. When using Sofgen-L with ribavirin in patients with creatinine clearance (CrCl)


Patients with decompensated cirrhosis of the liver and/or patients awaiting liver transplantation or undergoing liver transplantation


The efficacy of ledipasvir/sofosbuvir in patients infected with HCV genotype 5 and genotype 6, with decompensated cirrhosis of the liver and/or those awaiting liver transplantation or undergoing liver transplantation has not been studied. Treatment with Sofgen-L should be carried out taking into account the ratio of potential benefits and risks for each individual patient.

Interactions with other drugs and other types of interactions.


Since Sofgen-L contains ledipasvir and sofosbuvir, any interactions established for these components may occur with Sofgen-L treatment.


Ability of Sofgen-L to influence the action of other drugs


Ledipasvir in vitro acts as an inhibitor of the drug transporter P‑gp and a protein that determines breast cancer resistance (BCRP), and can enhance intestinal uptake of simultaneously used substrates of these transporters. In vitro data suggest that ledipasvir may act as a weak inducer of metabolizing enzymes, such as CYP3A4, CYP2C, and UGT1A1. When using substances that are substrates of such enzymes simultaneously with ledipasvir/sofosbuvir, their concentration in blood plasma may decrease. Ledipasvir in vitro resulted in inhibition of intestinal CYP3A4 and UGT1A1. Drugs with a narrow therapeutic range, as well as those that are metabolized by these enzymes, should be prescribed with caution and constantly monitored.


Ability of other drugs to influence the effect of Sofgen-L


Ledipasvir and sofosbuvir are substrates of drug carriers P‑gp and BCRP, in contrast to GS-331007.


Drugs that are strong Inducers of P‑gp (rifampicin, rifabutin, St. John's wort, carbamazepine, phenobarbital and phenytoin) can significantly reduce the concentration of ledipasvir and sofosbuvir in blood plasma, with a corresponding decrease in the therapeutic effectiveness of ledipasvir/sofosbuvir, and, thus, their use with Sofgen-L is contraindicated (see the section "contraindications"). Drugs that are moderate inducers of P-gp in the intestine (for example, oxcarbazepine) may reduce the concentration of ledipasvir and sofosbuvir in blood plasma, which leads to a decrease in the therapeutic effect of Sofgen-L. concomitant use of such drugs together with Sofgen-L is not recommended (see the section "special safety measures"). Concomitant use with drugs that inhibit P-gp and/or BCRP may lead to an increase in the concentration of ledipasvir and sofosbuvir without an increase in the concentration of GS-331007 in blood plasma; concomitant use of Sofgen-L with P‑gp and/or BCRP inhibitors is not excluded. Clinically significant drug interactions with ledipasvir/sofosbuvir mediated by CYP450 or UGT1A1 enzymes are unlikely.


Patients receiving vitamin K antagonists


Due to the fact that liver function may change during treatment with Sofgen-L, it is recommended to closely monitor the values of the international normalized ratio (INR) for such patients.

Application features.


Use during pregnancy or lactation.


Women of reproductive age/contraception in men and women


When using Sofgen-L with ribavirin, it is necessary to make every effort to prevent pregnancy of patients and partners of male patients. Significant teratogenic and/or embryocidal effects have been reported in animals treated with ribavirin. Women of reproductive age or their partners should use effective methods of contraception during treatment and after completion of treatment, according to the recommendations given in the instructions for medical use of ribavirin. For more information, see the instructions for use of ribavirin. 


Pregnancy


There are no data on the use of ledipasvir, sofosbuvir or Sofgen-L in pregnant women, or there are very few such data (less than 300 pregnancy consequences).


No signs of reproductive toxicity were observed in animal studies. In rats and rabbits, there was no significant effect on fetal development when using ledipasvir or sofosbuvir. It was not possible to fully establish the limits of sofosbuvir exposure in rats relative to human exposure at the recommended clinical dose.


As a preventive measure, it is recommended to avoid the use of Sofgen-L during pregnancy.


Breast-feeding


It is not known whether ledipasvir or sofosbuvir and its metabolites pass into breast milk.


Available animal pharmacokinetic data have shown that ledipasvir and sofosbuvir metabolites are present in breast milk.


Risk for newborns/infants is not excluded. Accordingly, Sofgen-L should not be used during breast-feeding.


Fertility


There are no data on the effect of Sofgen-L on Human Fertility. The results of animal studies did not show a negative effect of ledipasvir or sofosbuvir on fertility.


In the case of simultaneous use of Ribavirin and Sofgen-L, contraindications are imposed regarding the appointment of ribavirin during pregnancy or lactation (See also the instructions for medical use of ribavirin).


Ability to influence the reaction rate when driving vehicles or other mechanisms.


Sofgen-L (when used independently or in combination with ribavirin) does not adversely affect the ability to drive a vehicle and work with other mechanisms. However, patients should note that among patients treated with ledipasvir/sofosbuvir, fatigue was more common than in patients treated with placebo.


Dosage and administration.


Prescribing Sofgen-L and monitoring its administration should be carried out by a doctor who has experience in treating patients with CHD.

Tags: Sofgen-L® [Ledipasvir, Sofosbuvir]