Elbasvir + Grazoprevir


Thông tin thuốc gốc
Chỉ định và Liều dùng
Oral
Chronic hepatitis C
Adult: Available preparation:
Elbasvir 50 mg and grazoprevir 100 mg

As monotherapy or in combination with ribavirin in patients with genotypes 1 or 4 infection: 1 tablet once daily for 12-16 weeks depending on HCV genotype, associated polymorphism and response to previous treatment (refer to detailed product guideline).
Hepatic Impairment
Moderate to severe (Child-Pugh B or C): Contraindicated.
Chống chỉ định
Hypersensitivity. Moderate to severe hepatic impairment. Concomitant use with organic anion transporting polypeptide 1B (OATP1B) inhibitors or strong inducers of CYP3A or P-glycoprotein (P-gp).
Thận trọng
Patient with hepatitis B virus (HBV)/HCV co-infection, who completed HCV treatment, and not receiving HBV antiviral therapy or receiving immunosuppressants; diabetes. Pregnancy and lactation.
Phản ứng phụ
Significant: ALT elevations, symptomatic hypoglycaemia in diabetic patients.
Gastrointestinal disorders: Nausea, diarrhoea, constipation, abdominal pain, dry mouth, vomiting.
General disorders and admin site conditions: Fatigue, asthenia, irritability.
Immune system disorders: Angioedema.
Investigations: Elevated bilirubin, decreased haemoglobin.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia.
Nervous system disorders: Headache, dizziness.
Psychiatric disorders: Insomnia, anxiety, depression.
Skin and subcutaneous tissue disorders: Pruritus, alopecia.
Potentially Fatal: HBV reactivation (in HBV/HCV co-infected patients).
Monitoring Parameters
Perform test in patients with genotype 1a for presence of virus with NS5A resistance-associated polymorphisms prior to initiation of treatment. Monitor LFT at baseline, then week 8 and 12 of treatment and as clinically indicated. Monitor HCV-RNA at baseline, then at week 4, 8, 12 during treatment follow-up and as clinically indicated. Perform Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti HBc) screening prior to therapy, if tested positive, monitor signs of hepatitis flare or HBV reactivation during treatment and post-treatment follow-up. Monitor blood glucose, and signs and symptoms of hypoglycaemia in diabetic patients.
Tương tác
Decreased serum concentrations and efficacy with inducers of CYP3A or P-gp (e.g. efavirenz, phenytoin, carbamazepine, bosentan, etravirine, modafinil, rifampicin, nafcillin). May increase the serum concentrations of tacrolimus, sunitinib and HMG-CoA reductase inhibitors (e.g. atorvastatin, rosuvastatin, fluvastatin, lovastatin, simvastatin). Increased concentration with cobicistat-containing agents and CYP3A inhibitors (e.g. ketoconazole).

Grazoprevir: Increased serum concentration with OATP1B (e.g. atazanavir, ciclosporin, rifampicin).
Food Interaction
Decreased serum concentrations with St. John’s wort.
Tác dụng
Description: Elbasvir and grazoprevir both reduce viral load of hepatitis C virus (HCV) via distinct mechanisms of action at multiple steps in the viral lifecycle.
Elbasvir inhibits HCV nonstructural protein 5A (NS5A), which is essential for viral RNA replication and virion assembly.
Grazoprevir inhibits HCV NS3/4A protease, thereby preventing the proteolytic cleavage of HCV encoded polyprotein into mature forms, and viral replication.
Pharmacokinetics:
Absorption: Elbasvir: Bioavailability: 32%. Time to peak plasma concentration: 3 hours (range: 3-6 hours).
Grazoprevir: Bioavailability: 27%. Time to peak plasma concentration: 2 hours (range: 30 minutes to 3 hours).
Distribution: Elbasvir: Distributed into most tissues including the liver. Volume of distribution: Approx 680 L. Plasma protein binding: >99.9% to albumin and α-1 acid glycoprotein.
Grazoprevir: Distributed predominantly to the liver. Volume of distribution: Approx 1,250 L. Plasma protein binding: 98.8% to albumin and α-1 acid glycoprotein.
Metabolism: Metabolised in the liver by CYP3A via partial oxidative metabolism.
Excretion: Via faeces (>90%); urine (<1%).
Elbasvir: Elimination half-life: Approx 24 hours.
Grazoprevir: Elimination half-life: Approx 31 hours.
Đặc tính

Chemical Structure Image
Elbasvir

Source: National Center for Biotechnology Information. PubChem Database. Elbasvir, CID=71661251, https://pubchem.ncbi.nlm.nih.gov/compound/Elbasvir (accessed on Jan. 22, 2020)


Chemical Structure Image
Grazoprevir

Source: National Center for Biotechnology Information. PubChem Database. Grazoprevir, CID=44603531, https://pubchem.ncbi.nlm.nih.gov/compound/Grazoprevir (accessed on Jan. 22, 2020)

Bảo quản
Store below 30°C.
Phân loại MIMS
Phân loại ATC
J05AP54 - elbasvir and grazoprevir ; Belongs to the class of antivirals for treatment of HCV infections. Used in the treatment of hepatitis C viral infections.
References
Anon. Elbasvir and Grazoprevir. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 16/08/2019.

Buckingham R (ed). Elbasvir. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/08/2019.

Buckingham R (ed). Grazoprevir. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/08/2019.

Joint Formulary Committee. Elbasvir with Grazoprevir. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/08/2019.

Zepatier Tablets (Merck Sharp & Dohme Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 16/08/2019.

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