Oncology drugs where CYP3A4 and P‑gp are important pharmacokinetic (PK) considerations
Reference table for oncology drugs with clinically relevant CYP3A4 and P-glycoprotein pharmacokinetic considerations.
This sheet summarises oncology drugs where CYP3A4 and P‑gp are important pharmacokinetic considerations.
What's on the table:
Drug name
The generic name and, in brackets, a common brand name.
Class
The therapeutic class or mechanism category. Examples include CDK4/6 inhibitor, EGFR TKI, PARP inhibitor, VEGFR TKI, SERM, and aromatase inhibitor.
Key metabolic pathways
The main bio-transformation and clearance routes. These include dominant CYP isoenzymes, UGTs, non-CYP mechanisms, and renal or fecal elimination.
They highlight where CYP3A4/P-gp-active compounds may change exposure.
Tmax
Approximate time to maximum plasma concentration after an oral dose. For depot drugs, it is measured after injection. It indicates how quickly a drug peaks and when overlapping exposures may matter most.
Half-life
Approximate terminal elimination half-life. It indicates persistence and accumulation. Longer half-lives mean greater sensitivity to sustained CYP3A4 inhibition or induction.
Dose-limiting / key toxicity
The adverse effects that constrain dosing in practice. This is a clinical red-flag column.
PK-driven exposure changes can have tangible safety consequences.
How to use this sheet
Feel free to copy information above about your medicines into personal notes or a treatment journal.
If your drug is not listed, you might ask an AI assistant:
For [enter your drug name], can you tell me the:
drug class;
key metabolic pathways, especially CYP3A4 and transporters;
typical Tmax; (initial supplement overlap period of concern)
usual half-life; (broader preiod for supplement overlap concern)
main dose-limiting or key toxicities?
Not every drug listed is a “pure” CYP3A4 substrate. Some have mixed or minimal CYP3A4 metabolism.
Evidence type for all drugs on this table is Clinical PK and drug label.
Drug name | Drug Class | Key metabolic pathways | Evidence type | Tmax | Half-life | Dose-limiting / key toxicity |
|---|---|---|---|---|---|---|
Palbociclib (Ibrance) | CDK4/6 inhibitor | Mostly metabolized by CYP3A4, with additional metabolism via SULT2A1; minimal renal clearance. | Clinical PK and FDA label; in vitro metabolism characterization. | ≈ 6 h (range ≈ 3–12 h; food-dependent) | ≈ 29 h (mean ≈ 29 ± 5 h) | Neutropenia is the main dose-limiting toxicity; leukopenia, anemia, fatigue and GI effects also common. |
Ribociclib (Kisqali) | CDK4/6 inhibitor | Hepatic metabolism predominantly via CYP3A4; limited renal clearance. | Clinical PK and label; in vitro CYP profiling. | ≈ 1–5 h | ≈ 32–36 h | Neutropenia and other hematologic toxicity; QTc prolongation and hepatotoxicity are major safety signals requiring ECG/LFT monitoring. |
Abemaciclib (Verzenio) | CDK4/6 inhibitor | Metabolized via CYP3A4; more lipophilic with broader tissue distribution; minimal renal clearance. | Clinical PK and label; in vitro metabolism. | ≈ 8 h | ≈ 18–38 h (mean ≈ 18 h) | GI toxicity (diarrhea) and fatigue are dose-limiting; neutropenia occurs but is less frequent/severe than palbociclib/ribociclib. |
Erlotinib (Tarceva) | EGFR TKI | Primarily metabolized by CYP3A4, with contributions from CYP1A2 and CYP2C8; biliary/fecal excretion. | Clinical PK and label; DDI/safety reviews. | ≈ 4 h | > 36 h | Skin rash and diarrhea are characteristic and can be dose-limiting; hepatotoxicity relevant. |
Gefitinib (Iressa) | EGFR TKI | Metabolized mainly by CYP3A4 and CYP2D6; fecal excretion. | Clinical PK and label. | ≈ 3–7 h | ≈ 41 h | Diarrhea and acneiform rash common; hepatotoxicity can be dose-limiting. |
Osimertinib (Tagrisso) | EGFR TKI (3rd-gen) | Mostly metabolized by CYP3A4/5; active metabolites contribute; mainly fecal elimination. | Clinical PK and label; comparative EGFR-TKI analyses. | ≈ 6 h | ≈ 48–60 h | Diarrhea, rash, ILD/pneumonitis, QTc prolongation, cardiomyopathy. |
Ibrutinib (Imbruvica) | BTK inhibitor (covalent) | Mostly metabolized by CYP3A4; metabolites excreted mainly in feces. | Clinical PK and label; BTK inhibitor reviews. | ≈ 1–2 h | ≈ 4–6 h | Bleeding, atrial fibrillation, hypertension, diarrhea. |
Acalabrutinib (Calquence) | BTK inhibitor | Metabolized by CYP3A4; greater BTK selectivity. | Clinical PK and label; comparative BTK reviews. | ≈ 0.5–2 h | ≈ 1–2 h | Headache, diarrhea, infections, cytopenias; bleeding and CV AEs less frequent than with ibrutinib. |
Zanubrutinib (Brukinsa) | BTK inhibitor | Metabolized by CYP3A4; optimized BTK selectivity. | Clinical PK and label. | ≈ 2 h | ≈ 2–4 h | Neutropenia, infections, hypertension; bleeding and cytopenias. |
Imatinib (Gleevec) | BCR-ABL / KIT / PDGFR TKI | Metabolized mainly by CYP3A4; active metabolite contributes. | Clinical PK and label; targeted-therapy reviews. | ≈ 2–4 h | ≈ 18 h | Myelosuppression, edema, GI symptoms, hepatotoxicity. |
Sunitinib (Sutent) | VEGFR/MET/PDGFR TKI | Metabolized primarily by CYP3A4 to active metabolite; fecal elimination. | Clinical PK and label; VEGF-pathway inhibitor reviews. | ≈ 6–12 h | ≈ 40–60 h | Hypertension, fatigue, hand-foot syndrome, hypothyroidism, hepatotoxicity, cardiac events. |
Sorafenib (Nexavar) | RAF/VEGFR/PDGFR TKI | Metabolized mainly by CYP3A4 and UGT1A9; excreted in feces. | Clinical PK and label. | ≈ 3 h | ≈ 25–48 h | Hand-foot skin reaction, diarrhea, hypertension, fatigue, rash, hepatotoxicity, cardiac ischemia. |
Dasatinib (Sprycel) | BCR-ABL / SRC TKI | Metabolized predominantly by CYP3A4. | Clinical PK and label. | ≈ 0.5–3 h | ≈ 3–5 h | Myelosuppression, pleural effusions, bleeding, QTc prolongation. |
Tamoxifen (Nolvadex) | SERM | Metabolized by CYP3A4, CYP2D6 and others to active metabolites (endoxifen). | Clinical PK and label; in vitro CYP studies. | ≈ 4–7 h | ≈ 5–7 days (parent) | Endometrial cancer risk, venous thromboembolism, hot flushes. |
Anastrozole (Arimidex) | Aromatase inhibitor | Metabolized via hepatic phase I/II pathways with minor CYP involvement. | Clinical PK and label. | ≈ 2 h | ≈ 40–50 h | Arthralgia, bone density loss/fracture risk, hot flushes. |
Letrozole (Femara) | Aromatase inhibitor | Hepatic metabolism mainly via CYP3A4 and CYP2A6; excreted in urine and feces. | Clinical PK and label. | ≈ 1–2 h | ≈ 48 h | Arthralgia, bone loss, hypercholesterolemia, hot flushes. |
Fulvestrant (Faslodex) | SERD (IM) | Extensive hepatic metabolism mainly via CYP3A4 to inactive metabolites. | Clinical PK and label. | Tmax ≈ 7 days (IM) | ≈ 40–50 days | Injection-site reactions, hepatotoxicity, GI effects. |
Exemestane (Aromasin) | Steroidal aromatase inhibitor | Metabolized by CYP3A4 and reduction; metabolites excreted via urine and feces. | Clinical PK and label. | ≈ 1–2 h | ≈ 24 h | Hot flushes, arthralgia, fatigue, bone loss. |
Olaparib (Lynparza) | PARP inhibitor | Metabolized mostly via CYP3A4; eliminated via urine and feces. | Clinical PK and label; PARP-inhibitor reviews. | ≈ 1.5–3 h | ≈ 12–15 h | Anemia, neutropenia, thrombocytopenia, nausea, fatigue; rare MDS/AML. |
Niraparib (Zejula) | PARP inhibitor | Metabolized via non-CYP pathways (e.g. carboxylesterases); minor CYP involvement; renal/fecal elimination. | Clinical PK and label; PARP-inhibitor reviews. | ≈ 3–4 h | ≈ 36–48 h | Thrombocytopenia, anemia, neutropenia, hypertension, fatigue. |
Talazoparib (Talzenna) | PARP inhibitor | Limited metabolism; excreted primarily unchanged; minor CYP involvement. | Clinical PK and label; PARP-inhibitor reviews. | ≈ 2 h | ≈ 90 h | Anemia, other cytopenias, fatigue, nausea. |
Rucaparib (Rubraca) | PARP inhibitor | Metabolized by CYP2D6 and CYP1A2 with contributions from CYP3A4; renal/fecal excretion. | Clinical PK and label; PARP-inhibitor reviews. | ≈ 1.5–3 h | ≈ 17–20 h | Nausea, fatigue, elevated liver enzymes, cytopenias. |
Bevacizumab (Avastin) | Anti-VEGF mAb | Proteolytic catabolism; not CYP-metabolized; IV administration. | Clinical PK and label; VEGF-targeted therapy reviews. | Peak at end of infusion | ≈ 20 days | Hypertension, proteinuria, bleeding, GI perforation, impaired wound healing, thromboembolism. |
Axitinib (Inlyta) | VEGFR TKI | Metabolized primarily by CYP3A4/5, with contributions from CYP1A2, CYP2C19, UGT1A1. | Clinical PK and label; VEGF-inhibitor reviews. | ≈ 2.5–4 h | ≈ 2.5–6 h | Hypertension, diarrhea, fatigue, hand-foot syndrome; hypertensive crises/thromboembolism. |
Pazopanib (Votrient) | VEGFR/PDGFR TKI | Metabolized mainly by CYP3A4 with minor CYP1A2/CYP2C8 involvement. | Clinical PK and label; VEGF-pathway reviews. | ≈ 2–4 h | ≈ 30 h | Hepatotoxicity, hypertension, diarrhea, hair color changes. |