NILOTINIB D-TARTRATE
Clinical safety rating: avoid
Strong CYP3A4 inhibitors may increase levels and inducers may decrease levels Can cause QT prolongation and sudden death.
BCR-ABL tyrosine kinase inhibitor; binds to and inhibits the ATP-binding site of BCR-ABL, thereby inhibiting tyrosine kinase activity and downstream signaling pathways, leading to apoptosis in CML cells.
| Metabolism | Primarily metabolized by CYP3A4; also a substrate for CYP2C8 and P-glycoprotein. |
| Excretion | Fecal (93%), renal (4%) |
| Half-life | 17 hours (terminal elimination half-life); supports once-daily dosing |
| Protein binding | 98% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 2.5 L/kg (large Vd, extensive tissue distribution) |
| Bioavailability | 30% (oral); increased by 20% with high-fat meal (avoid) |
| Onset of Action | Not applicable (oral administration); clinical response observed within 2–4 weeks |
| Duration of Action | 24 hours (dosing interval); continuous BCR-ABL inhibition maintained |
400 mg orally twice daily, approximately 12 hours apart, with food.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), use with caution and monitor closely; no specific dose recommendations available. |
| Liver impairment | Child-Pugh A: 400 mg twice daily. Child-Pugh B: Reduce to 200 mg twice daily. Child-Pugh C: Reduce to 200 mg once daily. |
| Pediatric use | For pediatric patients (≥1 year): 230 mg/m² orally twice daily (maximum 400 mg per dose) rounded to the nearest 50 mg increment. |
| Geriatric use | No specific dose adjustment recommended; monitor for adverse effects and renal function, as elderly patients may have increased sensitivity and higher risk of electrolyte abnormalities and fluid retention. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inhibitors may increase levels and inducers may decrease levels Can cause QT prolongation and sudden death.
| FDA category | Contraindicated |
| Breastfeeding | No data on human milk excretion. M/P ratio unknown. Due to potential serious adverse reactions in nursing infants, breastfeeding is contraindicated during nilotinib therapy and for at least 2 weeks after the last dose. |
| Teratogenic Risk | Nilotinib D-tartrate is embryotoxic and fetotoxic in animal studies. In human pregnancy, there is a potential for fetal harm. First trimester exposure carries risk of structural anomalies; second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and fetal distress due to placental insufficiency. |
■ FDA Black Box Warning
QT interval prolongation and sudden death: Nilotinib causes concentration-dependent QT prolongation; do not use in patients with hypokalemia, hypomagnesemia, or long QT syndrome; monitor ECG and electrolytes.
| Common Effects | Myelosuppression |
| Serious Effects |
Hypokalemia, hypomagnesemia, long QT syndrome, and concomitant use of drugs known to prolong QT interval or potent CYP3A4 inhibitors.
| Precautions | QT prolongation, sudden cardiac death, myelosuppression, pancreatitis, hepatotoxicity, tumor lysis syndrome, hemorrhage (including gastrointestinal and intracranial), fetal harm (Pregnancy Category D), fluid retention (pleural effusion, pericardial effusion, ascites), and electrolyte abnormalities. |
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| Fetal Monitoring | Monitor complete blood counts, hepatic function, pancreatic enzymes, serum electrolytes, and electrocardiogram (QTc interval) regularly throughout pregnancy. Serial fetal ultrasound assessments for growth and anatomy are recommended. Monitor for signs of fetal distress. |
| Fertility Effects | Nilotinib may impair male and female fertility based on animal studies. In males, it caused reduced spermatogenesis and testicular toxicity; in females, it disrupted estrous cycles and reduced fertility. Reversibility in humans is unknown. |