Drug Action
Elbasvir is an HCV NS5A inhibitor and grazoprevir is an HCV NS3/4A protease inhibitor; they reduce viral load by inhibiting hepatitis C virus RNA replication.
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Drug reference
Elbasvir is an HCV NS5A inhibitor and grazoprevir is an HCV NS3/4A protease inhibitor; they reduce viral load by inhibiting hepatitis C virus RNA replication.
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Chronic hepatitis C infection of genotypes 1 or 4 (with or without ribavirin) (initiated by a specialist) ▶BY MOUTH ▶Adult: 50/100 mg once daily for 12 weeks (may extend to 16 weeks in some circumstances—consult product literature) DOSE EQUIVALENCE AND CONVERSION ▶Dose expressed as x/y mg elbasvir/grazoprevir.
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Hepatitis B co-infection. re-treatment following previous exposure to elbasvir with grazoprevir, or to drugs of the same classes (NS5A inhibitors or NS3/4A inhibitors other than telaprevir, simeprevir, boceprevir)— efficacy not demonstrated
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NICE decisions ▶Elbasvir–grazoprevir for treating chronic hepatitis C (October 2016) NICE TA413 Elbasvir with grazoprevir is recommended, within its marketing authorisation, as an option for treating genotype 1 or 4 chronic hepatitis C infection: . of genotype 1a—12 weeks’ treatment (consider use in combination with ribavirin for 16 weeks in patients with a baseline hepatitis C virus RNA level of more than 800 000 IU/mL or specific NS5A polymorphisms causing at least a 5-fold reduction in activity of elbasvir); . of genotype 1b—12 weeks’ treatment; . of genotype 4—12 weeks’ treatment (consider use in combination with ribavirin for 16 weeks in patients with a baseline hepatitis C virus RNA level of more than 800 000 IU/mL). This is contingent on the manufacturer providing the drug at the same price or lower than that agreed with the Commercial Medicines Unit. www.nice.org.uk/guidance/ta413 Scottish Medicines Consortium (SMC) decisions SMC No. 1203/17 The Scottish Medicines Consortium advises (January 2017) that Zepatier ® (elbasvir with grazoprevir) is accepted for use within NHS Scotland for the treatment of chronic hepatitis C in adults with genotype 1a, 1b or 4; this advice is contingent upon the continuing availability of the Patient Access Scheme in NHS Scotland or a list price that Infection is equivalent or lower.
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MHRA/CHM ADVICE: DIRECT-ACTING ANTIVIRALS TO TREAT CHRONIC HEPATITIS C: RISK OF INTERACTION WITH VITAMIN K ANTAGONISTS AND CHANGES IN INR (JANUARY 2017) An EU-wide review has identified that changes in liver function, secondary to hepatitis C treatment with direct- acting antivirals, may affect the efficacy of vitamin K antagonists; the MHRA has advised that INR should be monitored closely in patients receiving concomitant treatment. MHRA/CHM ADVICE: DIRECT-ACTING ANTIVIRAL INTERFERON- FREE REGIMENS TO TREAT CHRONIC HEPATITIS C: RISK OF HEPATITIS B REACTIVATION (JANUARY 2017) An EU-wide review has concluded that direct-acting antiviral interferon-free regimens for chronic hepatitis C can cause hepatitis B reactivation in patients co-infected with hepatitis B and C viruses; the MHRA recommends to screen patients for hepatitis B before starting treatment—patients infected with both hepatitis B and C viruses must be monitored and managed according to current clinical guidelines. MHRA/CHM ADVICE: DIRECT-ACTING ANTIVIRALS FOR CHRONIC HEPATITIS C: RISK OF HYPOGLYCAEMIA IN PATIENTS WITH DIABETES (DECEMBER 2018) Rapid reduction in hepatitis C viral load during direct- acting antiviral therapy for hepatitis C may improve glucose metabolism in patients with diabetes and result in symptomatic hypoglycaemia if diabetic treatment is continued at the same dose. The MHRA advises healthcare professionals: . to monitor glucose levels closely in patients with diabetes during direct-acting antiviral therapy for hepatitis C, especially within the first 3 months of treatment and modify diabetic medication or doses when necessary; . to be vigilant for changes in glucose tolerance and advise patients of the risk of hypoglycaemia; . to inform the healthcare professional in charge of the diabetic care of the patient when direct-acting antiviral therapy is initiated. Infection
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→Appendix 1: elbasvir. grazoprevir
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▶Common or very common Alopecia. anxiety. appetite decreased. arthralgia. asthenia. constipation. depression . diarrhoea. dizziness. dry mouth. gastrointestinal discomfort. headache. insomnia. irritability. myalgia. nausea. pruritus. vomiting ▶Uncommon Anaemia. transient ischaemic attack
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Manufacturer advises use only if potential benefit outweighs risk.
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Manufacturer advises avoid—present in milk in animal studies.
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Manufacturer advises avoid in moderate to severe impairment.
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Manufacturer advises monitor liver function before treatment, at week 8 in all patients, at week 12 in patients receiving 16 weeks of treatment, and then as clinically indicated—consider discontinuing treatment if alanine aminotransferase (ALT) is greater than 10 times the upper limit of normal; discontinue treatment if ALT elevation is accompanied by signs or symptoms of hepatic impairment or inflammation.
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There can be variation in the licensing of different medicines containing the same drug. Tablet CAUTIONARY AND ADVISORY LABELS 3 ELECTROLYTES: May contain Sodium ▶Zepatier (Merck Sharp & Dohme Ltd) A Elbasvir 50 mg, Grazoprevir 100 mg Zepatier 50mg/100mg tablets | 28 tablet P £12,166.67 ANTIVIRALS › NON-STRUCTURAL PROTEIN 5A INHIBITORS
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Hepatic effects Manufacturer advises that patients and their carers should consult a healthcare professional if signs and symptoms of hepatic dysfunction occur (including fatigue, weakness, lack of appetite, nausea and vomiting, jaundice or discoloured faeces). Vomiting Manufacturer advises if vomiting occurs within 4 hours of a dose, an additional dose should be taken. Missed doses Manufacturer advises if a dose is more than 16 hours late, the missed dose should not be taken and the next dose should be taken at the normal time.
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50/100 mg once daily for 12 weeks (may extend
First-line fragment. Read the complete Indications and Dose section above.
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