Sovaldi (sofosbuvir) 400 mg, 28 tablets, India, generic Order Sovaldi (sofosbuvir) 400 mg, 28 tablets, India, generic. Medicine delivery from Europe within 4-5 days with storage conditions maintained. Payment on delivery. Order at +380996042415 via Viber or WhatsApp.

Interchangeable drugs with the same active ingredient:

Grateziano

Sovaldi

Harvoni

composition

acting substance: sofosbuvir;

1 film-coated tablet contains 400 mg sofosbuvir;

excipients: mannitol (E 421), microcrystalline cellulose, sodium croscarmellose, colloidal silicon dioxide, magnesium stearate

tablet shell: polyvinyl alcohol, titanium dioxide, macrogol, talc.

Dosage form

Film-coated tablets.

Basic physico-chemical properties:white capsule-shaped tablets, film-coated, engraved with “GSI” on one side and “7977” on the other.

Pharmacological group

Direct-acting antiviral agents.

ATC code J05A X15.

Pharmacological properties

Pharmacological

mechanism of action

Sofosbuvir is a pangenotypic inhibitor of hepatitis C virus RNA polymerase NS5B, which is important for viral replication. Sofosbuvir is a nucleotide depot form, which, after participating in intracellular metabolism, forms a pharmacologically active uridine analogue triphosphate (GS-461203), which can be introduced into the RNA of the hepatitis C virus by the NS5B polymerase, and acts as a chain-terminating agent. In a biochemical analysis, GS-461203 inhibited the polymerase activity of NS5B recombinants in hepatitis C virus genotypes 1b, 2a, 3a and 4a with 50% inhibitory concentration values ​​(IC50) in the range of 0,7 - 2,6 µm. GS-461203 (the active metabolite of sofosbuvir) is not an inhibitor of human DNA and RNA polymerase, and is also not an inhibitor of mitochondrial RNA polymerase.

antiviral effect

In HCV replication assays, the effective concentration values (EC50) of sufosbuvir against full-length REPLICON 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 hybrid REPLICON 1b, encoding NS5B genotype 2b, 5a, or 6a ranged from 0,014 to 0,015 μm. Mean ± SD EC50sofosbuvir against REPLICON hybrids encoding NS5B sequences from clinical strains was 0,068 ± 0,024 μm for genotype 1a (n = 67), 0,11 ± 0,029 μm for genotype 1b (n = 29), 0,035 ± 0,018 µm for genotype 2 (n = 15) and 0,085 ± 0,034 µm for genotype 3a (n = 106). In these analyses, the antiviral effect of sofosbuvirin vitroagainst the less common genotypes 4, 5 and 6 was similar to that observed for genotypes 1, 2 and 3.

The presence of 40% human serum had no effect on the antiviral effect sofosbuvir for HCV.

resistance

Cell culture.HCV REPLICON with reduced sensitivity to sofosbuvir has been selected in cell culture for many genotypes, including 1b, 2a, 2b, 3a, 4a, 5a and 6a. Reduced sensitivity to sofosbuvir was associated with the primary NS5B substitution S282T in all genotypes of the REPLICON analysis.Directed mutagenesis of the S282T substitution in REPLICON 8 genotypes provided a 2-18-fold decrease in sensitivity to sofosbuvir and a decrease in the possibility viral replication by 89-99% compared to the corresponding wild type. In biochemical assays, the recombinant NS5B polymerase from genotypes 1b, 2a, 3a and 4a, which expresses the S282T substitution, showed reduced sensitivity to GS-461203 compared to the corresponding wild types.

Clinical studies. In a pooled analysis of 991 patients who received sofosbuvir in the phase 3 study, 226 patients were screened for analysis of persistence of virological failure and early discontinuation of the drug, they had an HCV RNA > 1000 IU/ml. Following up, NS5B seed sequences were available for 225 of 226 patients, with deep sequencing data (1% analysis attrition) from 221 of these patients. The S282T substitution associated with sofosbuvir resistance was not detected in any of these patients by deep sequencing or population sequencing. The S282T substitution in NS5B was detected in one patient who received Sovaldi monotherapy in a phase 2 study. This patient had <1% HCV S282T at baseline and S282T (>99%) at the fourth week after treatment, which gave a 13.5-fold change in EC50of sofosbuvir and reduced the potential for viral replication. The S282T substitution reverted to wild type over the next 8 weeks and was no longer detected by deep sequencing at week 12 post-treatment.

Two NS5B substitutions, L159F and V321A, were detected in replicate post-treatment samples across multiple genotypes of 3 HCV-infected patients in phase 3 clinical trials research. No changes in phenotypical sensitivity to sofosbuvir or ribavirin were detected in isolated patients with these substitutions. In addition, substitutions S282R and L320 were detected during deep sequencing treatment in a pre-transplant patient with a partial response to treatment. The clinical significance of these findings is unknown.

Impact of HCV output polymorphisms on treatment outcome

NS5B output sequences were obtained for 1292 patients in a phase 3 study using population sequencing, and the S282T substitution was not found in any patients with the presence original sequence. When assessing the influence of baseline polymorphisms on the outcome of the assessment, there was no statistically significant association between the presence of the HCV NS5B variant at the beginning and after treatment.

Cross-resistance

HCV replicons that express the S282T substitution, associated with resistance to sofosbuvir, were completely sensitive to others classes of HCV antiviral agents. Sofosbuvir retained activity against NS5B, - L159F and L320F substitutions associated with resistance to other nucleoside inhibitors. Sofosbuvir was fully active against substitutions associated with resistance to other direct-acting antivirals with different mechanisms of action, such as non-nucleoside NS5B inhibitors, NS3 protease inhibitors and NS5A inhibitors.

Pharmacokinetics

Sofosbuvir is a nucleotide depot form that intensively participates in metabolism. The active metabolite is formed in hepatocytes and is not detected in plasma. The main (> 90%) metabolite GS-331007 is inactive. It is formed in sequential and parallel pathways leading to the formation of an active metabolite.

absorption

The pharmacokinetic properties of sofosbuvir and the main circulating metabolite GS-331007 were assessed in healthy adult patients and patients with chronic hepatitis C. After administration sofosbuvir was rapidly absorbed, and the highest plasma concentration was found ~0,5-2 hours after dosing, regardless of its level. The highest concentration of GS-331007 in plasma was found 2-4 hours after dosing. Based on population pharmacokinetic analysis in patients with genotypes 1-6 HCV infection (n = 986), the steady-state AUC0-24for sofosbuvir and GS-331007 was 1010 ng • h/ml and 7200 ng • h/ml, respectively. In healthy patients (n = 284), sofosbuvir and GS-331007 AUC0-24were 57% higher and 39% lower, respectively, than in patients infected with HCV.

Influence of food. According to diet conditions, taking one dose of sofosbuvir with a regular, high-fat meal slowed down the rate of absorption of sofosbuvir. The absorption volume of sofosbuvir was increased approximately 1,8-fold with a negligible effect on maximum concentration. The effect of GS-331007 did not change when eating a high-fat meal.

distribution

Sofosbuvir is not