Sofosbuvir/velpatasvir

What is Sofosbuvir/velpatasvir?

• Sofosbuvir:

1. It is a nucleotide analog HCV NS5B polymerase inhibitor.
2. It is a white to off-white crystalline solid with a solubility of at least 2 mg/mL across the pH range of 2–7.7 at 37 °C and is slightly soluble in water.
3. Chemical name: (S)-isopropyl 2-((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)-(phenoxy)phosphorylamino)propanoate
4. Molecular formula: C22H29FN3O9P
5. Molecular weight: 529.45

• velpatasvir:

1. It is an NS5A inhibitor.
2. It is practically insoluble (less than 0.1 mg/mL) above pH 5, slightly soluble (3.6 mg/mL) at pH 2, and soluble (greater than 36 mg/mL) at pH 1.2.
3. Chemical name: Methyl {(1R)-2-[(2S,4S)-2-(5-{2-[(2S,5S)-1-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}-5-methylpyrrolidin-2-yl]-1,11-dihydro[2]benzopyrano[4',3':6,7]naphtho[1,2-d]imidazol-9-yl}-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl]-2-oxo-1-phenylethyl}carbamate
4. Molecular formula: C49H54N8O8
5. Molecular weight: 883.0

What are the uses of this medicine?

It is indicated for the treatment of adults and pediatric patients 3 years of age and older with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection and:

• without cirrhosis or with compensated cirrhosis
• with decompensated cirrhosis for use in combination with ribavirin.

How does this medicine work?

Sofosbuvir is an inhibitor of the 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 by the NS5B polymerase and acts as a chain terminator. In a biochemical assay, GS-461203 inhibited the polymerase activity of the recombinant NS5B from HCV genotype 1b, 2a, 3a, and 4a with an IC50 value ranging from 0.36 to 3.3 micromolar. GS-461203 is neither an inhibitor of human DNA and RNA polymerases nor an inhibitor of mitochondrial RNA polymerase.

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

Who Should Not Use this medicine?

Sofosbuvir/velpatasvir and ribavirin combination regimen is contraindicated in patients for whom ribavirin is contraindicated.

What are the brand names and dosage forms of this medicine?

• Brand name: Epclusa; NDC codes: 61958-2201-1, 61958-2203-1, 61958-2204-1, 61958-2205-1.
• EPCLUSA is available as tablets or pellets for oral use. Each dosage form is available in two dose strengths:

1. 400 mg/100 mg Tablets: pink, diamond-shaped, film-coated tablet debossed with "GSI" on one side and "7916" on the other side. Each tablet contains 400 mg of sofosbuvir and 100 mg of velpatasvir.
2. 200 mg/50 mg Tablets: pink, oval-shaped, film-coated tablet debossed with "GSI" on one side and "S/V" on the other side. Each tablet contains 200 mg of sofosbuvir and 50 mg of velpatasvir.
3. 200 mg/50 mg Oral Pellets: white to off-white, film-coated pellets in unit-dose packets. Each packet contains 200 mg of sofosbuvir and 50 mg of velpatasvir.
4. 150 mg/37.5 mg Oral Pellets: white to off-white, film-coated pellets in unit-dose packets. Each packet contains 150 mg of sofosbuvir and 37.5 mg of velpatasvir.

Is this medicine FDA approved?

It is approved by US FDA on June 28, 2016.

What are the active and inactive ingredients in Sofosbuvir/velpatasvir?

• Active ingredients:

1. Velpatasvir
2. Sofosbuvir

• Inactive ingredient:

1. Alcohol
2. Copovidone K25-31
3. Microcrystalline Cellulose
4. Croscarmellose Sodium
5. Magnesium Stearate
6. Water
7. Titanium Dioxide
8. Polyethylene Glycol 3350
9. Talc
10. Ferric Oxide Red
11. Polyvinyl Alcohol, Unspecified

How should this medicine be used?

• Take EPCLUSA exactly as your healthcare provider tells you to take it. Do not change your dose unless your healthcare provider tells you to.
• Do not stop taking EPCLUSA without first talking with your healthcare provider.
• Take EPCLUSA oral pellets or tablets by mouth, with or without food.
• For adults the usual dose of EPCLUSA is one 400/100 mg tablet each day.
• For children 3 years of age and older your healthcare provider will prescribe the right dose of EPCLUSA oral pellets or tablets based on your child's body weight.
• Do not miss a dose of EPCLUSA. Missing a dose lowers the amount of medicine in your blood. Refill your EPCLUSA prescription before you run out of medicine.

What side effects can this medication cause?

• Hepatitis B virus reactivation
• Slow heart rate (bradycardia)
• fainting or near-fainting
• dizziness or lightheadedness
• weakness
• extreme tiredness
• shortness of breath
• chest pains
• confusion
• memory problems

What to do in case of emergency/overdose?

No specific antidote is available for overdose with EPCLUSA. If overdose occurs the patient must be monitored for evidence of toxicity. Treatment of overdose with EPCLUSA consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient. Hemodialysis can efficiently remove the predominant circulating metabolite of sofosbuvir, GS-331007, with an extraction ratio of 53%. Hemodialysis is unlikely to result in significant removal of velpatasvir since velpatasvir is highly bound to plasma protein.

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• If EPCLUSA is administered with ribavirin, the combination regimen is contraindicated in pregnant women and in men whose female partners are pregnant.
• No adequate human data are available to establish whether or not EPCLUSA poses a risk to pregnancy outcomes.

Can this medicine be used in children?

• The safety and effectiveness in pediatric subjects were comparable to those observed in adults.
• The safety and effectiveness of EPCLUSA have not been established in pediatric patients less than 3 years of age.

What should I know about storage and disposal of this medication?

• Store EPCLUSA tablets or oral pellets below 86°F (30°C).
• Keep EPCLUSA tablets in the original container.
• Do not use EPCLUSA oral pellets if the carton tamper-evident seal or the packet has been opened or damaged.

• Dailymed label info on Sofosbuvir/velpatasvir
• FDA Sofosbuvir/velpatasvir

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