Nilotinib

Nilotinib is a prescription medicine used for the treatment of chronic myeloid leukemia.

• Nilotinib is available under the following different brand names: Tasigna

Adult and pediatric dosage

Capsule

• 50mg
• 150mg
• 200mg

Chronic Myeloid Leukemia

Adult dosage

• Newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML)
  • 300 mg orally every 12 hours
• Resistant or intolerant
  • 400 mg orally every 12 hours

Pediatric dosage

• 230 mg/m2 orally twice daily, round to the nearest 50-mg dose; not to exceed 400 mg/dose
• Dosing based on body surface area (BSA)
  • Less than 0.32 m2: 50 mg per dose; total daily dose (TDD): 100 mg
  • 0.33–0.54 m2: 100 mg per dose; TDD: 200 mg
  • 0.55–0.76 m2: 150 mg per dose; TDD: 300 mg
  • 0.77–0.97 m2: 200 mg per dose; TDD: 400 mg
  • 0.98–1.19 m2: 250 mg per dose; TDD: 500 mg
  • 1.2–1.41 m2: 300 mg per dose; TDD: 600 mg
  • 1.42–1.63 m2: 350 mg per dose; TDD: 700 mg
  • Above 1.64 m2: 400 mg per dose; TDD: 800 mg

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of the Nilotinib include:

• nausea,
• vomiting,
• diarrhea,
• constipation,
• rash,
• temporary hair loss,
• night sweats,
• pain in the bones, spine, joints, or muscles,
• headache,
• tiredness,
• runny or stuffy nose,
• sneezing,
• cough, and
• sore throat.

Serious side effects of the Nilotinib include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• fast or pounding heartbeats,
• sudden dizziness,
• lightheadedness,
• bruising,
• blood in the urine or stools,
• swelling,
• rapid weight gain,
• shortness of breath,
• sudden headache,
• confusion,
• vision problems,
• upper stomach pain (that may spread to the back),
• nausea,
• vomiting,
• dark urine,
• yellowing of the skin or eyes (jaundice),
• fever,
• chills,
• night sweats,
• mouth sores,
• pale skin,
• unusual weakness,
• leg pain,
• cold feeling,
• chest pain,
• numbness,
• trouble walking,
• speech problems,
• muscle cramps,
• fast or slow heart rate,
• decreased urination, and
• tingling in the hands and feet or around the mouth

Rare side effects of the Nilotinib include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Nilotinib has severe interactions with the following drugs:
  • arsenic trioxide
  • disopyramide
  • goserelin
  • ibutilide
  • indapamide
  • leuprolide
  • pentamidine
  • pimozide
  • procainamide
  • quinidine
  • sotalol
  • toremifene
• Nilotinib has serious interactions with at least 138 other drugs.
• Nilotinib has moderate interactions with at least 287 other drugs.
• Nilotinib has minor interactions with at least 78 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Long QT syndrome, hypokalemia, hypomagnesemia

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Nilotinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Nilotinib?”

Cautions

• Grade 3/4 thrombocytopenia, neutropenia, and anemia may occur; perform complete blood cell counts (CBC) every 2 weeks for the first 2 months and then monthly thereafter, or as clinically indicated; myelosuppression was generally reversible and usually managed by withholding drug temporarily or dose reduction
• Sudden deaths were reported; ventricular repolarization abnormalities may have contributed to their occurrence; evaluate the cardiovascular status and monitor/manage cardiovascular risk factors during therapy
• QT interval reported; significant prolongation of the QT interval may occur when the drug is inappropriately taken with food; avoid taking with food; prolongation of the QT interval can result in torsade de pointes, which may result in syncope, seizure, and/or death
• May cause hypophosphatemia, hypokalemia, hyperkalemia, hypocalcemia, and hyponatremia; correct hypokalemia or hypomagnesemia before administration; monitor periodically during therapy
• Cardiovascular events (eg, ischemic heart disease, peripheral arterial occlusive disease, ischemic cerebrovascular events) reported in patients with newly diagnosed Ph+ CML; evaluate cardiovascular status, monitor cardiovascular risk factors, and manage during therapy
• Use caution in history of pancreatitis; monitor serum lipase monthly or as clinically indicated; in case lipase elevations are accompanied by abdominal symptoms, interrupt doses and consider appropriate diagnostics to exclude pancreatitis
• Use caution in hepatic impairment; monitor hepatic function tests (HFTs) monthly or as clinically indicated; reduce the dose and monitor QT interval
• May result in elevations in bilirubin, AST/ALT, and alkaline phosphatase; Grade 3-4 elevations of bilirubin, AST, and ALT were reported at higher frequency in pediatric than in adult patients; monitor HFTs monthly or as clinically indicated
• Tumor lysis syndrome cases were reported in patients with resistant or intolerant CML; maintain adequate hydration and correct uric acid levels before initiating therapy
• Total gastrectomy may reduce nilotinib systemic exposure; perform more frequent follow-up of these patients; if necessary, consider dose increase or alternative therapy
• Hemorrhages from any site may occur; advise patients to report signs and symptoms of bleeding and medically manage as needed
• Monitor for signs of severe fluid retention (eg, unexpected rapid weight gain, swelling) and symptoms of respiratory or cardiac compromise (eg, shortness of breath) during treatment; evaluate etiology and treat patients accordingly
• May cause fetal harm
• Growth retardation reported in pediatric patients with Ph+ CML-CP; growth deceleration was more pronounced in children aged <12 years at baseline; monitor growth and development in pediatric patients
• Monitoring BCR-ABL transcript levels
  • Monitoring transcript levels in patients who discontinued therapy
  • Monitor BCR-ABL transcript levels in patients eligible for treatment discontinuation using an FDA authorized test validated to measure MR levels with a sensitivity of at least MR4.5 (BCR-ABL/ABL ≤ 0.0032% IS)
  • In patients who discontinue therapy, assess BCR-ABL transcript levels monthly for 1 year, then every 6 weeks for the second year, and every 12 weeks thereafter during treatment discontinuation
  • For patients who fail to achieve MMR after 3 months of treatment reinitiation, perform BCR-ABL kinase domain mutation testing
  • Monitoring of BCR-ABL transcript levels in patients who have reinitiated therapy after the loss of molecular response
  • Monitor CBC and BCR-ABL transcripts in patients who reinitiate treatment with Tasigna due to loss of MR quantitation every 4 weeks until a major molecular response is re-established, then every 12 weeks
• Drug interaction overview
  • Substrate of CYP3A4
    • Clinical significance unknown: Competitive inhibitor of CYP2C8, CYP2D6, and is an inducer of CYP2B6 and CYP2C8; inhibitor of UGT1A1 and P-gp
  • Strong CYP3A4 inhibitors
    • Avoid coadministration; if unable to avoid it, decrease dose and monitor for QT prolongation
    • Strong CYP3A4 inhibitors may increase concentrations and adverse reactions of nilotinib
  • Strong CYP3A4 inducers
    • Avoid coadministration
    • Strong CYP3A4 inducers may decrease concentrations and adverse reactions of nilotinib
  • Proton pump inhibitors (PPIs)
    • Avoid coadministration
    • PPIs decrease nilotinib concentrations and efficacy
    • As an alternative, use H2-blockers ~10 hr before or ~2 hr after nilotinib or use antacids ~2 hr before or ~2 hr after nilotinib
  • Drugs that prolong QT interval
    • Avoid coadministration
    • Coadministration with drugs that prolong QT interval may potentiate the QT-prolonging effects of nilotinib

Pregnancy and Lactation

• No available data on pregnant women to inform the drug-associated risk; in animal reproduction studies, administration of nilotinib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes including embryo-fetal lethality, fetal effects, and fetal variations in rats and rabbits at maternal exposures (AUC) approximately 2 and 0.5 times, respectively, exposures in patients at recommended dose; advise pregnant women of the potential risk to the fetus
• Pregnancy test
  • Females of reproductive potential should have a pregnancy test before starting treatment
• Contraception
  • Based on animal studies, the drug can cause fetal harm when administered to a pregnant woman; advise females of reproductive potential to use effective contraception during treatment with the drug and for at least 14 days after the last dose
• Infertility
  • The risk of infertility in females or males of reproductive potential has not been studied in humans; in studies in rats and rabbits, the fertility in males and females was not affected
• Lactation
  • No data are available regarding the presence of nilotinib or its metabolites in human milk or its effects on a breastfed child or milk production
  • However, nilotinib is present in the milk of lactating rats
  • Owing to the potential for serious adverse reactions in a nursing child, advise lactating women not to breastfeed during treatment and for at least 14 days after the last dose