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 |
| Molecular Weight | 605.7 |
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 | Avoid. Potential embryofetal toxicity and teratogenicity based on animal studies. No adequate human data. |
| 2nd trimester | Avoid. May cause fetal harm. Use only if maternal benefit justifies risk. |
| 3rd trimester | Avoid. May cause fetal harm, including low birth weight and neonatal cytopenias. |
Clinical note
Strong CYP3A4 inhibitors may increase levels and inducers may decrease levels Can cause QT prolongation and sudden death.
| FDA category | Contraindicated |
| Placental transfer | Crosses placenta in animals; likely in humans due to molecular weight and lipophilicity. |
| Breastfeeding | Present in animal milk; no human data. Discontinue breastfeeding or drug due to potential serious adverse reactions in nursing infants. |
■ 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 |
HypokalemiaHypomagnesemiaLong QT syndromeConcomitant use with strong 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. |
| Food/Dietary | Avoid grapefruit, grapefruit juice, and Seville oranges as they inhibit CYP3A4 and can increase nilotinib levels. Administer nilotinib on an empty stomach: no food for at least 2 hours before and 1 hour after dose. High-fat meals significantly increase absorption and risk of toxicity. |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| 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. |
| 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. |
| Clinical Pearls | Nilotinib is a BCR-ABL tyrosine kinase inhibitor indicated for Philadelphia chromosome-positive chronic myeloid leukemia (CML). It has a black box warning for QT interval prolongation and sudden death. Correct hypokalemia and hypomagnesemia before initiation. Monitor ECG at baseline, day 7, and periodically. Avoid use with strong CYP3A4 inhibitors or inducers. Administer on empty stomach (1 hour before or 2 hours after a meal). Nilotinib can cause pancreatitis, so monitor lipase. It also increases risk of peripheral arterial occlusive disease. Dose reduction needed for hepatic impairment (Child-Pugh A, B, C). |
| Patient Advice | Take nilotinib on an empty stomach, at least 1 hour before or 2 hours after a meal. · Swallow capsules whole with water; do not open or crush. · Avoid grapefruit, grapefruit juice, and Seville oranges during treatment. · Report symptoms of pancreatitis (severe abdominal pain) or peripheral arterial disease (leg pain, wounds) immediately. · You will need regular blood tests to monitor heart function (ECG), blood counts, and pancreatic enzymes. · Do not take any new medications, including over-the-counter or herbal products, without consulting your doctor. · Contact your doctor if you experience fainting, palpitations, or irregular heartbeat. · Use effective contraception during treatment and for at least 14 days after stopping. |