Instructions for sofosbuvir and velpatasvir (Epclusa)

1. Generic name: sofosbuvir and velpatasvir

Product name: Epclusa

All names: Sofosbuvir Velpatasvir , Sofosbuvir and Velpatasvir, Epclusa, Bentonsa, Jisandai

2. Indications:

Sofosbuvir and velpatasvir (Epclusa) is indicated for the treatmentof patients 3 years of age and older with chronic hepatitis C virus (HCV ) Genotype Adult and pediatric patients infected with genotype 1, 2, 3, 4, 5 or 6, is also indicated for the treatment of patients without cirrhosis or compensated cirrhosis, and in patients with decompensated cirrhosis in combination with ribavirin.

3. Usage and dosage:

1. Before use: Before using sofosbuvir and velpatasvir, all patients need to be tested for evidence of current or previous hepatitis B virus (HBV) infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc).

2. Recommended dosage:

(1), adult useThe recommended dosage of sofosbuvir and velpatasvir is one tablet (40 mg of sofosbuvir and 100 mg of velpatasvir), once daily, taken orally with or without food.

(2), Recommended dosing for pediatric patients 3 years of age and older is based on body weight, take sofosbuvir and velpatasvir oral granules or tablets once daily, and for pediatric patients < 6 years of age, administer the oral granules with food to increase tolerability related to palatability. The recommended dose is 150 mg/37.5 mg (granules) once daily for patients less than 17 kg, 200 mg/50 mg (granules/tablets) once daily for patients 17-30 kg, and 400 mg/100 mg (granules/tablets) once daily for patients at least 30 kg. Two 200 mg/50 mg tablets may be used for patients who cannot swallow 400 mg/100 mg tablets.

3. Combined medication:

(1), adult useThe recommended dose of sofosbuvir and velpatasvir combined with ribavirin is based on body weight(Administered with food): 1000 mg daily for patients weighing less than 75 kg and 1200 mg daily for patients weighing at least 75 kg, given in two divided doses. The starting and therapeutic doses of ribavirin may be reduced based on hemoglobin and creatinine clearance. For ribavirin dose adjustments, please refer to the ribavirin prescribing information.

(2) Pediatric patients 3 years of age and older The recommended dose of combined ribavirin and empacirol is based on body weight, patients weighing less than 47kg 15mg per kilogram per day (split doses morning and afternoon), 47-49k 600 mg per day for patients who weigh 50 kg (One tablet in the morning200 mg and two tablets of 200 mg in the afternoon), and 800 mg per day for patients who weigh 50-65 kg (Morning2 tablets of 200mg, 2 tablets of 200mg in the afternoon), patients 66-80kg take 1000mg daily (morning2 tablets of 200mg in the morning, 3 tablets of 200mg in the afternoon), Patients greater than80kg take 1200mg per day (3 tablets of 200mg in the morning and 3 tablets of 200mg in the afternoon), usually with food.

4. Recommended treatment plan and duration:

For patients with hepatitis C virus/HIV-1 co-infection, untreated and treated patients without cirrhosis and patients with compensated cirrhosis, treatment with sofosbuvir and velpatasvir is recommended for 12 weeks12 weeks, untreated and treated patients with decompensation Patients with chronic liver cirrhosis should be treated with sofosbuvir, velpatasvir and ribavirin for 12 weeks. For treatment-naïve and treatment-experienced liver transplant recipients without cirrhosis or compensated cirrhosis, it is recommended to use sofosbuvir, velpatasvir and ribavirin for 12 weeks.

4. Adverse reactions:

All-grade adverse reactions observed in greater than or equal to 5% of subjects treated with sofosbuvir and velpatasvir included headache (22%), fatigue (15%), nausea (9%), asthenia (5%), and insomnia (5%). In subjects receiving sofosbuvir, velpatasvir and ribavirin for the treatment of fever, the most common adverse reactions with a frequency of 10% or greater (all grades) were fatigue (32%), anemia (26%), nausea (15%), headache (11%), insomnia (11%), and diarrhea (10%).

5. Storage:

Sofosbuvir and velpatasvir are available as tablets or pills for oral administration and are usually storedBelow 30°C (86°F), aliquot in original containers. Do not use if carton tamper-evident seal or packaging has been opened or damaged.

6. Taboo:

For patients in whom ribavirin is contraindicated, the combination of sofosbuvir, velpatasvir and ribavirin is contraindicated. Sofosbuvir and velpatasvir are contraindicated in combination with strong inducers of liver enzymes CYP2B6, CYP2C8, or CYP3A4, or P-glycoprotein, as these substances may reduce the effectiveness of the drug.

7. Mechanism of action:

Sofosbuvir is an inhibitor of HCV NS5B RNA-dependent RNA polymerase, which is required for viral replication. Sofosbuvir is a nucleotide prodrug that undergoes intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), which can be incorporated into HCV RNA through NS5B polymerase and serves as a chain terminator. In biochemical assays, GS-461203 inhibited the polymerase activity of recombinant NS5B from HCV genotypes 1b, 2a, 3a, and 4a with IC50 values u200bu200branging from 0.36 to 3.3 micromolar. GS-461203 is neither an inhibitor of human DNA and RNA polymerase nor an inhibitor of mitochondrial RNA polymerase.

Velpatasvir is an inhibitor of the HCV NS5A protein, which is required for viral replication. Resistance selection and cross-resistance studies in cell culture indicate that velpatasvir uses NS5A as its mode of action.

The original drug of sofosbuvir and velpatasvir has been launched in China and has entered the scope of Class B medical insurance. The domestic trade name is protonsa, and the specification is (400mg+100mg) * 28 tablets. The price per box is about RMB 4,000. The original drug of sofosbuvir and velpatasvir has also been launched overseas. There are also generic drugs of sofosbuvir and velpatasvir produced in other countries. The specifications of the Bangladesh Everest Pharmaceutical Factory are (400mg + 100mg) * 28 tablets per box, and the price is around RMB 850 (the price may fluctuate due to the exchange rate). The generic drugs produced abroad are basically the same as the original drugs at home and abroad.