Sofosbuvir, velpatasvir and voxilaprevir

What is Sofosbuvir, velpatasvir and voxilaprevir?

• Sofosbuvir:

1. It is a nucleotide analog HCV NS5B polymerase inhibitor.
2. 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
3. Molecular formula: C22H29FN3O9P
4. Molecular weight: 529.45

• Velpatasvir:

1. It is an NS5A inhibitor.
2. 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
3. Molecular formula: C49H54N8O8
4. Molecular weight: 883.0

• Voxilaprevir:

1. It is an NS3/4A protease inhibitor.
2. Chemical name: (1aR,5S,8S,9S,10R,22aR)-5-tert-butyl-N-{(1R,2R)-2-(difluoromethyl)-1-[(1-methylcyclopropanesulfonyl) carbamoyl]cyclopropyl}-9-ethyl-18,18-difluoro-14-methoxy-3,6-dioxo-1,1a,3,4,5,6,9,10,18,19,20,21,22,22a-tetradecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoxaline-8-carboxamide
3. Molecular formula: C40H52F4N6O9S
4. Molecular weight: 868.9

What are the uses of this medicine?

It is indicated for the treatment of adult patients with chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis who have:

• genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV regimen containing an NS5A inhibitor.
• genotype 1a or 3 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor.

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 µM. 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.

Voxilaprevir is a noncovalent, reversible inhibitor of the NS3/4A protease, which is necessary for the proteolytic cleavage of the HCV encoded polyprotein (into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins) and is essential for viral replication. In a biochemical inhibition assay, voxilaprevir inhibited the proteolytic activity of recombinant NS3/4A enzymes from clinical isolates of HCV genotypes 1b and 3a with Ki values of 38 and 66 pM, respectively.

Who Should Not Use this medicine?

It is contraindicated with rifampin.

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

• Brand names: Vosevi; NDC codes: 61958-2401-1.
• Each VOSEVI tablet contains 400 mg of sofosbuvir, 100 mg of velpatasvir, and 100 mg of voxilaprevir.

Is this medicine FDA approved?

It is approved by US FDA on July 18, 2017.

What are the active and inactive ingredients in Sofosbuvir, velpatasvir and voxilaprevir?

• Active ingredients:

1. Sofosbuvir
2. Velpatasvir
3. Voxilaprevir

• Inactive ingredients:

1. Alcohol
2. Copovidone K25-31
3. Microcrystalline Cellulose
4. Croscarmellose Sodium
5. Magnesium Stearate
6. Acetone
7. Lactose Monohydrate
8. Water
9. Titanium Dioxide
10. Polyethylene Glycol 3350
11. Talc
12. Ferric Oxide Red
13. Ferric Oxide Yellow
14. Ferrosoferric Oxide
15. Silicon Dioxide
16. Polyvinyl Alcohol, Unspecified

How should this medicine be used?

The recommended dosage of VOSEVI is one tablet, taken orally, once daily with food. One tablet of VOSEVI contains 400 mg of sofosbuvir, 100 mg of velpatasvir, and 100 mg of voxilaprevir.

What side effects can this medication cause?

• Serious Symptomatic Bradycardia When Coadministered with Amiodarone.
• Hepatobiliary Disorders
• Cardiac Disorders
• Skin and Subcutaneous Tissue Disorders

What to do in case of emergency/overdose?

No specific antidote is available for overdose with VOSEVI. If overdose occurs the patient must be monitored for evidence of toxicity. Treatment of overdose with VOSEVI 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 or voxilaprevir since velpatasvir and voxilaprevir are 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?

No adequate human data are available to establish whether or not VOSEVI poses a risk to pregnancy outcomes. In animal reproduction studies, no evidence of adverse developmental outcomes was observed with the components of VOSEVI (sofosbuvir, velpatasvir, or voxilaprevir) at exposures greater than those in humans at the recommended human dose (RHD).

Can this medicine be used in children?

Safety and effectiveness of VOSEVI have not been established in pediatric patients.

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

Store below 30 °C (86 °F). Dispense only in original container.

• Dailymed label info on Sofosbuvir, velpatasvir and voxilaprevir
• FDA Sofosbuvir, velpatasvir and voxilaprevir

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