DASATINIB
Clinical safety rating: avoid
Contraindicated (not allowed)
Dasatinib is a tyrosine kinase inhibitor that targets BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. It inhibits BCR-ABL autophosphorylation and downstream signaling, leading to apoptosis in Philadelphia chromosome-positive (Ph+) leukemia cells.
| Metabolism | Primarily metabolized by CYP3A4; also a substrate of CYP3A4 and CYP2C8. |
| Excretion | Approximately 85% of the dose is eliminated via feces (mainly as metabolites), and about 4% via urine (parent drug and metabolites). Less than 1% is excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is 3-5 hours. This short half-life supports twice-daily dosing, but active metabolite (N-desmethyl dasatinib) has a similar half-life and contributes to PD activity. |
| Protein binding | Approximately 96% bound to plasma proteins, primarily to albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | Vd is 2505 L (approximately 35.8 L/kg for a 70 kg adult), indicating extensive tissue distribution. This large Vd contributes to long tissue retention despite short plasma half-life. |
| Bioavailability | Oral bioavailability is approximately 14-34% (mean ~30%). A high-fat meal reduces AUC by 15-20% (not clinically significant, but label advises caution with grapefruit juice). |
| Onset of Action | Oral: Onset of BCR-ABL inhibition occurs within 1-2 hours post-dose; maximal inhibition correlates with peak plasma concentrations (Cmax at 0.5-6 hours). |
| Duration of Action | Duration of target inhibition persists for 6-12 hours, supporting BID dosing. Continuous suppression of BCR-ABL requires repeated dosing due to short half-life. |
| Molecular Weight | 488.01 |
140 mg orally once daily; reduce to 100 mg once daily if no cytogenetic response after 3 months or 140 mg once daily with dose escalation to 200 mg once daily as tolerated.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), reduce initial dose to 140 mg once daily; consider further dose reduction based on tolerability. |
| Liver impairment | Child-Pugh A: 140 mg once daily. Child-Pugh B: 100 mg once daily. Child-Pugh C: 100 mg once daily with close monitoring or consider alternative therapy. |
| Pediatric use | Weight-based dosing: 10-20 kg: 40 mg once daily; 20-30 kg: 60 mg once daily; 30-45 kg: 80 mg once daily; >45 kg: 100 mg once daily. For children ≥1 year with chronic phase CML or Ph+ ALL. |
| Geriatric use | No specific dose adjustment recommended; monitor renal function (CrCl) and adjust accordingly. Elderly patients may have increased risk of pleural effusion and fluid retention; use lowest effective dose and monitor closely. |
| 1st trimester | Human data limited; animal studies show embryotoxicity and teratogenicity. Avoid use unless benefit outweighs risk. |
| 2nd trimester | Potential fetal harm; may cause fetal hypotension, anemia, or growth restriction. Use only if absolutely necessary. |
| 3rd trimester | Potential fetal harm similar to t2; risk of neonatal cytopenias and bleeding. Monitor neonate for adverse effects. |
Clinical note
Antacids and H2 blockers decrease absorption May cause severe myelosuppression and fluid retention.
| Placental transfer | Dasatinib crosses the placenta in humans (documented by measurable concentrations in fetal circulation). Low molecular weight and high protein binding suggest transfer. |
| Breastfeeding | Dasatinib is excreted into human milk in low levels. Based on its high potency and potential for serious adverse reactions in infants (e.g., myelosuppression, fluid retention), breastfeeding is not recommended during treatment and for at least 7 days after last dose. |
■ FDA Black Box Warning
Dasatinib can cause pulmonary arterial hypertension (PAH) which may develop at any time during treatment, including after prolonged therapy. PAH may be reversible upon discontinuation. Evaluate patients for signs and symptoms of cardiopulmonary disease before and during treatment.
| Common Effects | Myelosuppression |
| Serious Effects |
Hypersensitivity to dasatinib or any excipients
| Precautions | Pulmonary arterial hypertension, Pleural effusions, pericardial effusions, and other fluid retention events, QT prolongation, Myelosuppression (thrombocytopenia, neutropenia, anemia), Bleeding-related events (including severe CNS and GI hemorrhages), Use with potent CYP3A4 inducers or inhibitors requires dose adjustment, Fetal harm if used during pregnancy |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L4 (Hazardous) |
| Teratogenic Risk | Dasatinib is embryotoxic and fetotoxic in animal studies. In humans, it is contraindicated in pregnancy due to risk of fetal harm. First trimester exposure may cause major congenital malformations. Second and third trimester exposure may lead to fetal growth restriction, oligohydramnios, and fetal demise. Adequate contraception is required during treatment. |
| Fetal Monitoring | Monitor complete blood count (CBC) with differential, liver function tests (LFTs), serum electrolytes, and renal function at baseline and periodically. Monitor for signs of fluid retention, pleural effusion, pulmonary arterial hypertension, and cardiac dysfunction. Perform fetal ultrasound to assess growth and amniotic fluid volume if used inadvertently during pregnancy. |
| Fertility Effects | Dasatinib may impair male and female fertility. In animal studies, testicular degeneration and reduced spermatogenesis were observed. Reversible menstrual irregularities and ovarian failure may occur in females. Use effective contraception during treatment and for at least 30 days after the last dose. |
| Avoid grapefruit and grapefruit juice. High-fat meals may decrease absorption; administer at the same time each day to maintain consistent exposure. |
| Clinical Pearls | Monitor for pleural effusions; consider dose reduction or interruption if effusion develops. Check liver function tests monthly for first 2 months, then periodically. Avoid concurrent use with CYP3A4 strong inhibitors unless dose reduction is possible. QT interval prolongation risk; correct hypokalemia/hypomagnesemia before initiation. May cause pulmonary arterial hypertension; evaluate dyspnea promptly. |
| Patient Advice | Take your medication exactly as prescribed, usually once daily with or without food. · Report any new or worsening shortness of breath, chest pain, or cough immediately. · Avoid grapefruit and grapefruit juice during treatment. · Use effective contraception during treatment and for 30 days after the last dose. · Do not take any new medications, including over-the-counter drugs and supplements, without consulting your doctor. |