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CYP3A4 inhibitors, inducers and substrates

CYP3A4 is the most abundant CYP enzyme in the liver, and it also works in the wall of the small intestine. It clears more medicines than any other CYP enzyme, including midazolam and simvastatin. Because it acts in the gut wall, it changes how much of a swallowed medicine reaches the blood, which is why grapefruit juice can matter. Clarithromycin, itraconazole and ritonavir are strong inhibitors; rifampin and St. John's wort are strong inducers.

This is the desk's mapped set for CYP3A4, taken from the same catalog the desk uses to grade pairs. It is not a complete list. A drug that isn't listed here hasn't been cleared as safe; it just isn't on this list.

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What inhibition and induction mean

Inhibition. An inhibitor slows CYP3A4. Drugs that depend on CYP3A4 can build up, so their levels and effects can rise. Reversible inhibition starts as the inhibitor builds up and fades as it clears. Some inhibitors destroy the enzyme, and the effect lasts until the body makes more.

Induction. An inducer makes the body produce more CYP3A4. Levels of drugs that depend on CYP3A4 can fall, and so can their effect. Induction builds over days to weeks and takes about as long to fade after the inducer stops.

Substrates marked activation pathway are ones CYP3A4 turns into an active or reactive product. For these, inhibition can mean less of that product, and induction can mean more.

Strong, moderate and weak are the desk's grades for how much a perpetrator changes a sensitive substrate's exposure, in FDA's fold-change bins. FDA table of substrates, inhibitors and inducers.

Names with a solid underline open that drug's page of label-sourced pairs. Names with a dotted underline open the desk with that drug.

CYP3A4 inhibitors (87)

Strong inhibitors (25)

≥5-fold ↑ AUC of a sensitive index substrate

Moderate inhibitors (31)

≥2 to <5-fold ↑ AUC

Weak inhibitors (31)

≥1.25 to <2-fold ↑ AUC

CYP3A4 inducers (48)

Strong inducers (12)

≥80% ↓ AUC of a sensitive index substrate

Moderate inducers (19)

≥50 to <80% ↓ AUC

Weak inducers (17)

≥20 to <50% ↓ AUC

CYP3A4 substrates (355)

Sensitive substrates (41)

Exposure rises the most when CYP3A4 is blocked.

Major-pathway substrates (273)

CYP3A4 is one of the main routes for these.

Minor-pathway substrates (41)

CYP3A4 is a smaller route for these; other routes carry most of the load.

Pair pages that run through CYP3A4 (271)

Label-sourced pair pages where the desk's top finding is a CYP3A4 interaction, grouped by the desk's grade.

Avoid together (262)

Serious concern (9)

Educational reference only. Not FDA-cleared. The Prescribing Information governs.