imatinib
Brand: Gleevec, Glivec
ISMP High Alert Prototype Drug
Drug Class: BCR-ABL tyrosine kinase inhibitor
Drug Family: antineoplastic
Subclass: first-generation targeted tyrosine kinase inhibitor
Organ Systems: hematology-oncology
Mechanism of Action
Competitive inhibitor of the ATP-binding site of BCR-ABL tyrosine kinase (product of the Philadelphia chromosome t(9;22) translocation); blocks BCR-ABL from phosphorylating substrates that drive leukemic cell proliferation; also inhibits c-KIT and PDGFR.
BCR-ABL tyrosine kinasec-KITPDGFR
Indications
- chronic myeloid leukemia (CML) — standard first-line for Ph+ CML
- acute lymphoblastic leukemia (Ph+ ALL)
- gastrointestinal stromal tumor (GIST) — c-KIT driven
Contraindications
- imatinib hypersensitivity
Adverse Effects
Common
- nausea/vomiting
- fluid retention/edema (periorbital edema characteristic)
- muscle cramps
- fatigue
- skin rash
Serious
- severe fluid retention (pleural effusion, pulmonary edema, cardiac tamponade)
- myelosuppression (usually early in therapy)
- hepatotoxicity
- cardiac dysfunction/QTc prolongation
- growth retardation in children
Pharmacokinetics (ADME)
| Absorption | 98% oral bioavailability; administer with food to reduce GI upset |
| Distribution | widely distributed; 95% protein-bound |
| Metabolism | hepatic CYP3A4 (primary), CYP2C9, CYP2D6; active metabolite N-desmethyl imatinib |
| Excretion | fecal (68%) and renal (13%) |
| Half-life | 18 hours (parent); 40 hours (N-desmethyl metabolite) |
| Onset | 2–4 hours |
| Peak | 2–4 hours |
| Duration | once-daily |
| Protein Binding | 95% |
| Vd | moderate |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| CYP3A4 inducers (rifampin, carbamazepine) | reduce imatinib levels substantially; may require dose doubling | major |
| warfarin | imatinib inhibits CYP2C9; INR elevations — use LMWH instead of warfarin where possible | major |
| simvastatin/lovastatin | CYP3A4 inhibition increases statin levels; use pravastatin or rosuvastatin instead | major |
Nursing Considerations
- Administer with a large glass of water and food to minimize GI adverse effects.
- Monitor for fluid retention — daily weights and assessment for edema; imatinib-induced fluid retention is common and can range from mild edema to life-threatening fluid accumulation.
- Monitor CBC weekly during the first month, biweekly during the second month, then periodically; imatinib causes early myelosuppression.
- Conduct therapeutic response monitoring via BCR-ABL PCR — major molecular response (MR3.0 — ≥3 log reduction) should be achieved by 12 months.
Clinical Pearls
- Imatinib transformed CML from a disease with median survival of 4–5 years (with prior therapies) to one where patients now have near-normal life expectancy when treated, representing the paradigm shift in targeted cancer therapy.
- BCR-ABL mutations (particularly T315I — the 'gatekeeper' mutation) confer resistance to imatinib; ponatinib is the only TKI active against T315I mutant CML.
Safety Profile
Pregnancy contraindicated
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.