Reyvow
Reyvow
Generic Name
Reyvow
Mechanism
- Nirmatrelvir: a reversible, SARS‑CoV‑2 main protease (Mpro) inhibitor that blocks viral polyprotein cleavage, halting viral replication.
- Ritonavir: a CYP3A4 inhibitor that boosts nirmatrelvir levels by reducing its metabolism, allowing lower doses and shorter treatment duration.
Pharmacokinetics
| Parameter | Typical Values (IV‑free regimen) |
| Absorption | Rapid; Cmax at ~2 h post‑dose. |
| Bioavailability | ~75 % with ritonavir co‑administration. |
| Protein binding | ~75 % (nirmatrelvir) and ~48 % (ritonavir) |
| Distribution | Extensively distributed; trough concentrations maintained above EC90 for ~48 h. |
| Metabolism | Primarily CYP3A4 (nirmatrelvir). Ritonavir is a strong CYP3A4 inhibitor. |
| Elimination | Renal (≈80 %) and hepatic. Half‑life ~6 h (adjusted to ~12 h with ritonavir). |
| Drug‑Drug Interactions | ↑Risk with CYP3A4 substrates or inhibitors; avoid potent CYP3A4 inducers (e.g., rifampin). |
Indications
- Oral treatment of mild-to‑moderate COVID‑19 in adults and adolescents (≥12 y, ≥40 kg) within 5 days of symptom onset.
- Used in patients with ≥1 high‑risk factor for progression (e.g., age >60, obesity, diabetes, chronic kidney disease, immunosuppression).
- Not indicated for post‑exposure prophylaxis.
Contraindications
- Contraindications
- Hypersensitivity to nirmatrelvir, ritonavir, or other study components.
- Use of strong CYP3A4 inducers (e.g., rifampin).
- Warnings
- Severe hepatic impairment: avoid due to potential accumulation.
- Renal impairment: dose adjustment required; avoid in eGFR <30 mL/min/1.73 m².
- Drug interactions: caution with QT‑prolonging agents, warfarin, digoxin, statins, and other CYP3A4 substrates.
- Pregnancy: limited data; use only if benefits outweigh risks.
Dosing
- Standard dose: *300 mg nirmatrelvir with 100 mg ritonavir* twice daily for 5 days.
- Renal adjustment:
- *eGFR 30–49 mL/min*: same 5‑day course (no dose change).
- *eGFR <30 mL/min*: Not recommended – no data support use.
- Administration details
- Take with or without food (no food effect).
- Encourage adequate oral fluid intake to mitigate dysgeusia.
- If a dose is missed, take as soon as remembered unless ≥12 h since last dose → skip.
Adverse Effects
- Common
- Dysgeusia (taste alteration) – ~7 %
- Diarrhea, nausea, vomiting – ~4–5 %
- Headache, fatigue – <4 %
- Serious
- Hypersensitivity reactions (rash, angioedema).
- Transient liver enzyme elevations (↑ALT/AST).
- QTc prolongation (especially with concomitant QT‑prolonging drugs).
- No increased risk of cardiotoxicity noted in clinical trials.
Monitoring
- Baseline: liver function tests (ALT, AST, bilirubin), serum creatinine/eGFR, electrolytes.
- During therapy:
- LFTs at day 3 and day 5 (if abnormal, consider discontinuation).
- ECG if taking other QT‑prolonging medications.
- Monitor for signs of hypersensitivity or hepatic dysfunction.
- Post‑treatment: assess resolution of symptoms and consider repeat LFTs if clinically indicated.
Clinical Pearls
- Early treatment is key – efficacy markedly diminishes >5 days after symptom onset.
- Dose adjustment is unnecessary for mild‑moderate renal impairment but is contraindicated in severe CKD; consult alternative antivirals.
- Ritonavir’s CYP3A4 inhibition creates a drug‑interaction "black hole": review the patient’s medication list for major inhibitors/inducers before initiation.
- Use in pregnancy: limited data; if necessary, weigh risks carefully; consider supportive care as first line.
- High‑risk patients benefit most: elderly, immunocompromised (e.g., transplant recipients), and those with obesity or diabetes.
- Not for post‑exposure prophylaxis – do not use in asymptomatic or fully vaccinated contacts.
- Adherence: the two‑tablet daily regimen is shorter than many other antivirals, improving patient compliance.
> *Reyvow* is a cornerstone oral antiviral in the COVID‑19 therapeutic armamentarium, providing a rapid, targeted intervention to prevent disease progression in vulnerable populations.