Cobicistat
PIs
HIV protease inhibitors (PIs)
A booster with no anti-HIV activity: it blocks the liver enzyme CYP3A4 so that atazanavir or darunavir reach higher, longer-lasting levels.
Quick facts
- Group
- HIV protease inhibitors (PIs)
- Target
- Cytochrome P450 3A4 (CYP3A4)
- Used for
- Boosting atazanavir or darunavir
- Key effects
- Nausea · Small
- Monitor
- Serum creatinine and urine tests · HIV viral load
- ATC
- V03AX03
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows cobicistat bound in the active site of human CYP3A4.
Cobicistat is a ritonavir analogue designed only as a pharmacokinetic enhancer. It is a potent, selective inhibitor of CYP3A4, so it slows the first-pass and systemic breakdown of protease inhibitors and some integrase inhibitors that are CYP3A substrates. Unlike ritonavir it has no antiviral activity and does not induce CYP enzymes. It also blocks the tubular secretion of creatinine, which raises serum creatinine slightly without a real fall in kidney filtration.
- Cobicistat inhibits liver and gut CYP3A4
- Atazanavir or darunavir are broken down more slowly
- Their levels stay higher and last longer
- It also blocks tubular creatinine secretion
Indications
- Boosting atazanavir or darunavir in HIV-1 infection, alone or in fixed-dose combinations (also with elvitegravir) HIV infection and AIDS →
Adverse effects
Common
- Nausea
- Small, reversible rise in serum creatinine
Contraindications
- Hypersensitivity to cobicistat
- Drugs whose high levels are dangerous and depend on CYP3A for clearance (checked against the label)
- Strong CYP3A inducers such as St John's wort
Key interactions
- CYP3A substrates (many drugs)
- Their levels rise; every medicine is checked before starting
- St John's wort
- Lowers cobicistat and the boosted drug; loss of HIV control
- Hormonal contraceptives
- May be less effective; another method is used
- Antacids, H2 blockers and proton pump inhibitors (with atazanavir)
- Lower atazanavir absorption; timing is separated
What is monitored
- Serum creatinine and urine tests (an early small rise is expected)
- Liver tests and bilirubin
- HIV viral load
Administration and safety
- Oral, with food, at the same time as atazanavir or darunavir
- Not interchangeable with ritonavir without checking the regimen
Pregnancy and breastfeeding
Human data are limited; the HIV team chooses the regimen in pregnancy.
Nursing care
- Make a full medicine list, including herbal products, before starting
- Explain that a slight creatinine rise can be expected and is checked
- Teach to report yellow skin or eyes, rash or less urine
- Advise a non-hormonal contraceptive method when needed
Pharmacokinetics
- Absorption
- Oral, taken with food together with the boosted drug
- Metabolism
- A strong, selective CYP3A4 inhibitor and not an enzyme inducer; it also inhibits some drug transporters
Test yourself
Think of the answer, then tap the question to see it.
Does cobicistat have activity against HIV?
No. It is only a booster that inhibits CYP3A4.
Why can serum creatinine rise with cobicistat without kidney damage?
It blocks the tubular secretion of creatinine, not glomerular filtration.
What are two differences between cobicistat and ritonavir?
Cobicistat has no antiviral activity and does not induce CYP enzymes; it is also more selective for CYP3A4.
Connections
← Back to the class: HIV protease inhibitors (PIs)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Cobicistat: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Human CYP3A4 bound to an inhibitor (RCSB Protein Data Bank, 2024).
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.