Sofosvel Tablet 400 mg+100 mg

Uses

Sofosbuvir and Velpatasvir combination is used for the treatment of adult patients with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection-

• Without cirrhosis or with compensated cirrhosis
• With decompensated cirrhosis for use in combination with ribavirin

Sofosvel Tablet 400 mg+100 mg is also used to associated treatment for these conditions: Chronic Hepatitis C Genotype 1, Chronic hepatitis C genotype 2, Chronic hepatitis C genotype 3, Chronic hepatitis C genotype 4, Chronic hepatitis C genotype 5, Genotype 6 chronic hepatitis C infectionChronic Hepatitis C Genotype 1, Chronic hepatitis C genotype 2, Chronic hepatitis C genotype 3, Chronic hepatitis C genotype 4, Chronic hepatitis C genotype 5, Genotype 6 chronic hepatitis C infection

How Sofosvel Tablet 400 mg+100 mg works

Sofosbuvir is nucleotide analog inhibitor, which specifically inhibits HCV NS5B (non-structural protein 5B) RNA-dependent RNA polymerase. Following intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), sofosbuvir incorporates into HCV RNA by the NS5B polymerase and acts as a chain terminator . More specifically, Sofosbuvir prevents HCV viral replication by binding to the two Mg2+ ions present in HCV NS5B polymerase's GDD active site motif and preventing further replication of HCV genetic material .

Velpatasvir's mechanism of action is likely similar to other selective NS5A inhibitors which bind domain I of NS5A consisting of amino acids 33-202 . NS5A inhibitors compete with RNA for binding at this site. It is also thought that NS5A inhibitors bind the target during its action in replication when the binding site is exposed . Inhibition of NS5A is also known to produce redistribution of the protein to lipid droplets. The exact role of NS5A in RNA replication is not yet understood although it is known to be an important component.

Dosage

Sofosvel Tablet 400 mg+100 mg dosage

The recommended dosage is one tablet (400 mg of Sofosbuvir and 100 mg of Velpatasvir) taken orally once daily. Recommended treatment regimen:

• Patients without cirrhosis and patients with compensated cirrhosis (Child-Pugh A): one tablet once daily for 12 weeks
• Patients with decompensated cirrhosis (Child-Pugh B or C): one tablet once daily and Ribavirin for 12 weeks. The recommended dosage of Ribavirin is based on bodyweight (1000 mg/day for patients < 75 kg and 1200 mg/day for ≥ 75 kg, in two divided dose/day)

Side Effects

The most common side effects of Sofosbuvir and Velpatasvir combination include headache and tiredness. Treatment may result in slowing of the heart rate along with other symptoms when taken with amiodarone (a medicine used to treat certain heart problems).

Toxicity

Sofosbuvir, as a single agent, has very mild toxicity. The most common adverse reactions are headache and fatigue. The FDA Label currently warns of a risk of symptomatic bradycardia when Epclusa is used in combination with amiodarone .

No indication of carcinogenicity or impairment of fertility/fetal viability .

Precaution

Serious symptomatic bradycardia may occur in patients taking amiodarone, particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Coadministration of amiodarone with Sofosbuvir and Velpatasvir combination is not recommended. In patients without alternative viable treatment options, cardiac monitoring is recommended.

Interaction

Drugs may decrease the concentrations of sofosbuvir and/or velpatasvir: Antacids, H2-receptor antagonists, Proton-pump inhibitors etc.

Coadministration is not recommended with: topotecan, Carbamazepine, Phenytoin, Phenobarbital, Oxcarbazepine, Rifabutin, Rifampin, Rifapentine, efavirenz, Tipranavir, Ritonavir, Hypericum perforatum.

Coadministration of Sofosbuvir and Velpatasvir combination, with Rosuvastatin, Atorvastatin may significantly increase the concentration of Rosuvastatin, Atorvastatin.

Volume of Distribution

The volume of distribution for sofosbuvir has yet to be determined .

1.4-1.6 L/kg .

Elimination Route

When given orally, sofosbuvir reaches its maximum plasma concentration in about 0.5 to 2 hours with a maximal concentration (Cmax) of 567 ng/mL .

Oral bioavailability of 25-30% .

Half Life

Sofosbuvir has a terminal half life of 0.4 hours .

15h .

Clearance

The clearance of sofosbuvir has yet to be determined .

Estimated 0.12 L/h/kg [A19175.

Elimination Route

Sofosbuvir is eliminated by three routes: urine ( 80%), feces (14%), and respiration (2.5%); however, elimination through the kidneys is the major route .

94% excreted in feces with 77% as parent compound. 0.4% excreted in urine .

Pregnancy & Breastfeeding use

No adequate human data are available to establish whether or not Sofosbuvir and Velpatasvir combination poses a risk to pregnancy outcomes. If Sofosbuvir and Velpatasvir combination administered with Ribavirin, the combination regimen is contraindicated in pregnant women and in men whose female partner is pregnant or going to be pregnant in next six months.

Contraindication

Sofosbuvir, Velpatasvir and Ribavirin combination regimen is contraindicated in patients for whom Ribavirin is contraindicated.

Special Warning

Renal impairment patient: No dosage recommendation can be given for patients with severe renal impairment (eGFR ≤30 mL/min/1.73 m2) or with ESRD, due to higher exposures of the predominant sofosbuvir metabolite.

Acute Overdose

If overdose occurs the patient must be monitored for evidence of toxicity. Treatment of overdose includes monitoring of vital signs as well as observation of the clinical status of the patient.

Storage Condition

Store in a cool and dry place (preferably below 30° C). Keep out of reach of children.

Innovators Monograph

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