Mavyret
Mavyret
Generic Name
Mavyret
Mechanism
- Asunavir → inhibits the viral NS3/4A serine protease, blocking cleavage of the HCV polyprotein and preventing replication.
- Daclatasvir → targets the NS5A protein, disrupting viral replication and assembly.
- Dual inhibition results in a synergistic antiviral effect, reducing the risk of resistance development.
Pharmacokinetics
| Parameter | Approximate Value |
| Absorption | Rapid oral absorption; peak plasma concentrations in 1–3 h. |
| Bioavailability | ~25–30 % (affected by food intake). |
| Distribution | High protein binding (~96 %). |
| Metabolism | Primarily cytochrome P450 3A4 (CYP3A4). |
| Elimination | Hepatic biliary excretion; 50–60 % fecal, 30–40 % renal. |
| Half‑life (asunavir) | ~27 h; (daclatasvir) ~12 h. |
| Drug‑Drug Interactions | Strong CYP3A4 inducers (e.g., rifampin, carbamazepine) markedly reduce efficacy; inhibitors increase plasma levels.
Indications
- Chronic HCV infection, genotypes 1–6, in adults (≥18 years).
- Treatment–naïve or previously untreated patients.
- Duration: 12 weeks for genotype 2 non‑cirrhotic; 12 weeks for genotypes 1–6 in non‑cirrhotic patients; 12–24 weeks for cirrhotic patients (Child‑Pugh A or B) or treatment‑experienced cases.
- Not FDA‑approved for hepatitis B co‑infection or HIV/HCV co‑infection.
Contraindications
| Category | Key Points | |
| Contraindications | Known hypersensitivity to asunavir or daclatasvir; pregnant or breastfeeding women (category X). | |
| Warnings | Cirrhosis: Dosage adjustment and extended monitoring. | |
| Drug interactions: Strong CYP3A4/5 inhibitors (e.g., ketoconazole, itraconazole) may increase toxicity; strong inducers (e.g., rifampin) may negate efficacy. | ||
| Renal impairment: Not established; avoid in creatinine clearance <30 mL/min. | ||
| Hepatitis B reactivation: Screen at baseline; monitor ALT/AST; avoid in co‑infection unless carefully monitored. |
Dosing
| Population | Dose | Frequency | Notes |
| Adults ≥18 y (genotypes 1–6, non‑cirrhotic) | Asunavir 75 mg + Daclatasvir 150 mg | Once daily | Take with or without food. |
| Cirrhotic (Child‑Pugh A/B) or treatment‑experienced | Same formulation | 12–24 weeks | Extend duration to 24 weeks if cirrhosis or prior treatment failure. |
| Genotype 2, non‑cirrhotic | Same | 12 weeks | No additional dosing intervals. |
• Missed dose: Take as soon as remembered; skip if more than 12 h elapsed; do not double dose.
• Discontinuation: Stop immediately if severe hepatotoxicity or hypersensitivity occurs; consult hepatology.
Adverse Effects
| Class | Examples |
| Common (≥5 %) | Headache, fatigue, nausea, myalgia, mild rash, mild transaminase elevation. |
| Serious (≤1 %) | Hepatotoxicity (ALT/AST >5× ULN), severe drug‑interaction‑related toxicity, sudden onset hepatitis B flare, severe allergic reaction (anaphylaxis). |
| Pregnancy | Teratogenic potential – contraindicated. |
Monitoring
- Baseline: CBC, CMP (ALT/AST, bilirubin, albumin), hepatitis B surface antigen, HIV serology if indicated, creatinine clearance.
- During therapy: ALT/AST every 4 weeks; CBC monthly; monitor for jaundice or signs of hepatic decompensation.
- End‑of‑treatment (EOT): ALT/AST, HCV RNA at 12 weeks post‑treatment for SVR assessment.
- Drug interactions: Re‑evaluate prescriptions at each visit; consider therapeutic drug monitoring for drugs with narrow therapeutic indices.
Clinical Pearls
- Simplify: Once‑daily dosing improves adherence compared to other DAA combos; counsel patients on the importance of daily intake regardless of meals.
- Avoid in severe liver disease: In Child‑Pugh C, data are lacking; consider alternative regimens or defer initiation.
- Interaction vigilance: Concomitant use of ketoconazole, clarithromycin, or fluconazole can raise asunavir levels; adjust or replace these agents.
- Hepatitis B screening: Always screen for hepatitis B surface antigen; a positive result mandates evaluation for potential reactivation before initiating Mavyret.
- Weight‑based patient: No weight adjustment required; but caution in bariatric surgery patients—absorption may be altered.
- Rescue strategy: If early viral breakthrough occurs, switch to a protease‑inhibitor‑free DAA regimen (e.g., sofosbuvir‑velpatasvir) after genotypic resistance testing.
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• Keywords: Mavyret, hepatitis C treatment, direct‑acting antiviral, asunavir, daclatasvir, NS3/4A protease inhibitor, NS5A inhibitor, genotype 1–6, HCV, liver function monitoring, CYP3A4 interactions.