Pharmacology · Other antivirals
Nirmatrelvir + ritonavir !
An oral COVID-19 treatment for people at high risk, started within 5 days of symptoms. Ritonavir boosts it and causes many interactions.
Updated 2026-11-01
The figure shows nirmatrelvir bound to the active site of the SARS-CoV-2 main protease (Mpro).
Mechanism of action
Nirmatrelvir is a peptidomimetic inhibitor of the SARS-CoV-2 main protease (Mpro, also called 3CL protease). It binds the active site, so the viral polyproteins are not cut into the proteins the virus needs to replicate. Ritonavir, an HIV protease inhibitor, is added only to inhibit CYP3A and slow the breakdown of nirmatrelvir.
- Ritonavir inhibits CYP3A and raises nirmatrelvir levels
- Nirmatrelvir binds the active site of the main protease
- The viral polyprotein is not cut
- SARS-CoV-2 replication falls
Pharmacokinetics
- Absorption
- Oral
- Metabolism
- Nirmatrelvir by CYP3A, which ritonavir blocks
- Elimination
- Boosted nirmatrelvir mainly by the kidneys; exposure rises in kidney disease
Indications
- Mild to moderate COVID-19 in adults at high risk of progression to severe disease, started as soon as possible and within 5 days of symptom onset COVID-19 →
Adverse effects
Common
- Altered taste (dysgeusia)
- Diarrhoea
- Nausea, vomiting and headache
- Muscle aches
Contraindications
- History of serious hypersensitivity to nirmatrelvir or ritonavir
- Drugs highly dependent on CYP3A whose high levels are dangerous (e.g. amiodarone, simvastatin, lovastatin, sildenafil for pulmonary hypertension)
- Strong CYP3A inducers (rifampicin, carbamazepine, phenytoin, St John's wort)
Key interactions
- Tacrolimus, ciclosporin (calcineurin inhibitors)
- Large rises in levels with toxicity; among the most frequent serious interactions
- Amiodarone, simvastatin, lovastatin, sildenafil (pulmonary hypertension)
- Contraindicated: their levels rise and can cause serious reactions
- Rifampicin, carbamazepine, phenytoin, St John's wort
- Contraindicated: lower nirmatrelvir levels, treatment failure and resistance
- Combined hormonal contraceptives
- Less effective: an additional method is used
What is monitored
- Complete medicine review before prescribing
- Kidney function (doses depend on it)
- Signs of toxicity of interacting drugs; drug levels for calcineurin inhibitors
- Liver tests if symptoms appear
Administration and safety
- Oral; tablets swallowed whole
- Started as early as possible after diagnosis
- The full course is completed even if symptoms improve
Nursing care
- List every prescription, over-the-counter and herbal product and share it with the pharmacist
- Teach that taste changes are common and harmless
- Teach a backup contraceptive method
- Teach to report jaundice, dark urine, rash or swelling
Pregnancy and breastfeeding
Human data are limited; ritonavir registry data have not shown more birth defects.
Test yourself
Think of the answer, then tap the question to see it.
Which viral enzyme does nirmatrelvir inhibit?
The SARS-CoV-2 main protease (Mpro, 3CL protease).
Why is ritonavir combined with nirmatrelvir?
To inhibit CYP3A and raise nirmatrelvir levels.
Within how many days of symptom onset is nirmatrelvir-ritonavir started?
Within 5 days.
Which transplant drug's levels rise dangerously with nirmatrelvir-ritonavir?
Tacrolimus (or ciclosporin).
Related drugs
Related conditions
← Back to the class: Other antivirals
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Nirmatrelvir and Ritonavir: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.