Nilotinib

BRAND NAME:

Tasigna – It contains the active ingredient of Nilotinib. It is available in capsules with strengths of 50mg,150mg, and 200mg.

MECHANISM OF ACTION:

Nilotinib is a kinase inhibition that works by blocking the action of abnormal proteins that signal cancer cells to multiply. It does this by binding to the ATP-binding site of the inactive conformation of the BCR-ABL protein, which stabilizes the inactive conformation. Nilotinib is structurally similar to imatinib but binds to the BCR-ABL protein with higher affinity which can help overcome resistance caused by mutations. 

PHARMACOKINETICS:

Absorption: Peak plasma concentrations are attained 3 hours following oral administration. Food increases oral bioavailability. When administered 30 minutes after a high-fat meal, AUC increased by 82% relative to administration in the fasted state.

Distribution: Nilotinib has a steady-state volume of distribution of 0.55 to 3.9 L/kg.

Metabolism: Nilotinib is metabolized in the liver, principally by CYP3A4 to primarily inactive metabolites, it undergoes oxidation.

Excretion: After oral administration, nilotinib is eliminated through feces mainly as an unchanged drug.

PHARMACODYNAMICS:

Nilotinib is a transduction inhibitor that may treat several leukemias, including chronic myeloid leukemia, by targeting BCR-ABL, c-kit, and PDGF. 

DOSAGE AND ADMINISTRATION:

Nilotinib is available as an oral capsule. Usually, it is taken twice a day without food. Nilotinib needs to be taken empty-handed, at least two hours before or one hour after a meal. Take nilotinib daily at around the same time. 

Nilotinib is available in capsules with the strength of 150mg and 200mg.

DRUG INTERACTIONS:

Drug interaction with nilotinib may include

• Anti-arrhythmic drugs – disopyramide, quinidine, amiodarone, sotalol and procainamide

• Antibiotics – clarithromycin, moxifloxacin

• Anti-malarial drugs – chloroquine

• Anti-psychotics – haloperidol, pimozide

• Opioid analgesics – methadone, fentanyl, alfentanil

• Anti-convulsants - phenytoin, carbamazepine, phenobarbital

• Blood-thinner – warfarin

• Anti-HIV drugs – rifampin 

• Anti-fungal – itraconaole and ketoconazole

• Immunosuppressants – cyclosporine, tacrolimus and sirolimus

CONTRAINDICATIONS:

Nilotinib should not be used with people with long QT syndrome, hypokalemia, and hypomagnesemia.

SIDE EFFECTS:

Side effects of nilotinib can vary from person to person. They also depend on the treatment of patients. Side effects of nilotinib may include

• Rash

• Itching

• Nausea

• Vomiting

• Diarrhea

• Constipation

• Heartburn

• Headache

• Dizziness

• Loss of appetite

• Headache

• Dizziness

• Tiredness

• Night sweats

• Muscle cramps

• Hair loss

• Dry skin

Some side effects can be serious

• Unusual bleeding or bruising

• Blood in urine

• Bloody or black

• Sudden headache

• Chest pain

• Numbness

• Nausea

• Fever

• Pale skin

• Weight gain

• Swelling of hands

• Dark urine

OVERDOSE:

The patient took more doses than the prescribed dose which led to an overdose. Symptoms of overdose may include

• Fever

• Vomiting

• Sore throat

• Signs of infection

• Drowsiness

TOXICITY:

Taking excessive doses than the prescribed dose leads to toxicity. Nilotinib is metabolized in the liver largely by the cytochrome p450 system and liver injury may be due to the accumulation of a toxic intermediate or from a drug-drug interaction with other medications.