[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Other antivirals](https://durgical.com/en/pharmacology/classes/other-antivirals/) › Nirmatrelvir + ritonavir

[Pharmacology](https://durgical.com/en/pharmacology/) · [Other antivirals](https://durgical.com/en/pharmacology/classes/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

- Class: [Other antivirals](https://durgical.com/en/pharmacology/classes/other-antivirals/)
- Enzyme: SARS-CoV-2 main protease (Mpro, 3CL protease)
- ATC code: J05AE30

✂**SARS-CoV-2 main protease (Mpro, 3CL protease)**Nirmatrelvir + ritonavir

ⓘ The figure shows nirmatrelvir bound to the active site of the SARS-CoV-2 main protease (Mpro).

**Target in 3D:** SARS-CoV-2 main protease (Mpro, 3CL protease). PDB structure 8DZ2 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/8DZ2) · Drag to rotate · pinch to zoom

## 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 →](https://durgical.com/en/conditions/covid-19/)

## Adverse effects

### Common

- Altered taste (dysgeusia)
- Diarrhoea
- Nausea, vomiting and headache
- Muscle aches

### Serious (rare, important)

- Life-threatening reactions from drug interactions
- Hypersensitivity, including anaphylaxis and severe skin reactions
- Liver injury (raised transaminases, hepatitis, jaundice)
- HIV resistance in people with uncontrolled or undiagnosed HIV

## 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.

## Memory aid

Nirmatrelvir does the work, ritonavir «rides along» to block CYP3A: check every other medicine.

## 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).

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/nirmatrelvir-ritonavir/)

## Related drugs

- [Remdesivir](https://durgical.com/en/pharmacology/remdesivir/)

## Related conditions

- [COVID-19](https://durgical.com/en/conditions/covid-19/)

[← Back to the class: Other antivirals](https://durgical.com/en/pharmacology/classes/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](https://medlineplus.gov/druginfo/meds/a622005.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=J05AE30) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/pharmacology/nirmatrelvir-ritonavir/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/nirmatrelvir-ritonavir/