Tasigna

Antitumor antineoplastic agent Tasigna based on the protein kinase inhibitor nilotinib.

Indications Tasigna

Tasigna is used in the following cases:

• for the treatment of newly diagnosed chronic myeloid leukemia in adults with a characteristic chromosomal translocation;
• for the treatment of newly diagnosed chronic and accelerated myeloid leukemia in adults with a characteristic chromosomal translocation, as well as in cases of addiction or hypersensitivity to the previous therapeutic regimen (this includes treatment with imatinib).

Release form

Tasigna is produced in capsule form:

• dense capsules 150 mg - these are reddish forms with the inscription NVR and BCR in black;
• 200 mg dense capsules are yellowish forms with the inscription NVR and TKI in red.

The capsules contain a powdery substance of a whitish-yellowish hue.

A blister plate contains four capsules of 150 mg, or four or fourteen capsules of 200 mg. A cardboard pack contains 2-7 blister plates.

The active ingredient in Tasigna is nilotinib hydrochloride monohydrate.

Pharmacodynamics

Tasigna is a potent inhibitor of the Abl tyrosine kinase activity of the Bcr-Abl oncoprotein, which acts in successive generations of cell structures and primary Philadelphia chromosome-positive leukemia cells.

Tasigna forms a tight binding site at the ATP binding site, creating the strongest inhibitor of Bcr-Abl, and remains active against 32 imatinib-resistant mutants of Bcr-Abl.

As a result of its biological and chemical activity, Tasigna selectively inhibits proliferative changes and induces apoptotic processes in successive cell generations and in primary positive leukemia-affected cells isolated from patients with chronic myeloid leukemia.

Tasigna has little or no effect on the vast majority of protein kinases, including serine protein kinase. The exceptions are platelet kinase protein kinase, receptor tyrosine kinase activity, and ephrin receptor kinases: Tasigna inhibits them at levels observed after oral administration of a therapeutic dose of the drug.

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Pharmacokinetics

The maximum blood level of Tasign is observed within 3 hours after oral administration of capsules. Absorption may be about 30%. When Tasign is taken with food, the maximum blood level of the drug increases. When Tasign is taken half an hour or 2 hours after a meal, the bioavailability of the drug increases by 29 or 15%, respectively. Absorption of Tasign may be impaired in patients who have undergone gastrectomy or partial gastric resection.

Plasma protein binding may be approximately 98%.

The main metabolic pathways of Tasign are oxidation and hydrooxidation processes, with nilotinib being the main ingredient in the serum.

After a single dose, more than 90% of the drug is excreted within a week, mainly in the feces.

The estimated half-life calculated to determine the kinetic properties of multiple doses of Tasigna was 17 hours.

Exposure to the active ingredient of Tasigna at steady state is considered dose-dependent. Steady state is generally achieved by day 8. The increase in serum exposure to nilotinib between the initial dose and steady state was 2-fold with once-daily dosing and 3.8-fold with twice-daily dosing of Tasigna.

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Dosing and administration

The encapsulated medicine Tasigna is recommended for taking twice a day (once every 12 hours), 2 hours after eating. After taking the capsules, you cannot eat for another sixty minutes.

Tasigna is taken with water, without crushing or emptying the capsules. The exception is patients who have problems swallowing food: they are allowed to dilute the powder from the capsules in 1 teaspoon of apple puree.

If the patient accidentally misses a dose of Tasigna, there is no need to take an additional capsule: the next prescribed dose of Tasigna is taken.

Before starting therapy, the patient must undergo an ECG and determine the quantitative content of potassium and magnesium in the bloodstream.

The standard dose of Tasign is 300 mg of the drug twice a day - 2 capsules of 150 mg. If the doctor prescribed 400 mg twice a day, then capsules of 200 mg are used.

The duration of Tasigna administration is determined by the presence of a clinical effect from the drug.

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Use Tasigna during pregnancy

Studies have shown reproductive toxicity of Tasigna, so this drug cannot be used for treatment during pregnancy: there is a high risk of complications for the fetus.

Patients of childbearing potential should use reliable contraception during treatment with Tasigna. This should be continued for two weeks after the end of therapy.

Animal studies have shown that Tasigna passes into breast milk. For this reason, you should not use this medication during the entire period of breastfeeding.

Contraindications

Experts do not recommend prescribing Tasigna:

• during pregnancy;
• during breastfeeding;
• in pediatrics (children under 18 years of age);
• in case of lactase deficiency, in case of impaired glucose-galactose absorption, in case of galactose hypersensitivity;
• if you are prone to allergies to Tasigna.

Relative contraindications are:

• decompensated and severe heart disease;
• complicated liver pathologies;
• pancreatitis.

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Side effects Tasigna

Tasigna therapy may be accompanied by some side effects:

• infectious complications in the form of folliculitis, pharyngitis, pneumonia, herpes, thrush, gastroenteritis;
• skin papilloma;
• thrombocytopenia, anemia, neutropenia;
• thyroid dysfunction;
• weight loss, electrolyte imbalances, diabetes mellitus, loss of appetite;
• headaches, dizziness, neuropathy, tremors in the limbs, migraine;
• sleep disorders, anxiety, depressive states;
• retinal hemorrhages, conjunctivitis, deterioration of visual function;
• vertigo;
• heart rhythm disturbances, angina pectoris, tachycardia, high blood pressure, blood clotting disorders;
• shortness of breath, nosebleeds, chest pain, pulmonary edema;
• nausea, bowel disorders, pain in the stomach, thirst, jaundice;
• hyperhidrosis, redness and rashes on the skin, disruption of pigment formation, the appearance of blisters and cysts on the skin;
• muscle and joint pain, pain in the arms and legs;
• urinary disorders;
• chest pain, erectile dysfunction, breast enlargement;
• feeling of fatigue, swelling, fever, hot flashes.

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Overdose

There are several cases of intentional overdose of Tasign, as well as cases of combining the drug with alcoholic beverages or other drugs. In these situations, symptoms such as neutropenia, vomiting attacks, and loss of strength were noted. The condition of the liver and heart was not monitored. No deaths were observed after episodes of overdose.

If there is a suspicion that the patient has taken an excessive amount of Tasign, it is recommended to conduct a thorough diagnostic of the body's functionality, after which symptomatic and supportive therapy is prescribed.

Interactions with other drugs

• Medicinal substances that can increase the concentration of Tasign in the blood serum:
  • imatinib;
  • ketoconazole, voriconazole, ritonavir, itraconazole, telithromycin, clarithromycin.
• Medicinal substances that reduce the concentration of Tasign in the blood serum:
  • CYP3A4 isoenzyme inducers (phenytoin, phenobarbital, rifampicin, carbamazepine, St. John's wort).
• Tasigna may be administered in combination with warfarin, the anticoagulant properties of which are not affected. The use of Tasigna with midazolam leads to a slight increase in the concentration of the latter, but the degree of metabolism of midazolam did not change.
• Tasigna is not prescribed in combination with antiarrhythmic drugs, which include amiodarone, sotalol, quinidine, procainamide, as well as with drugs that affect the quality of the QT interval (pimozide, methadone, chloroquine, clarithromycin, etc.).
• Taking Tasigna with food is not recommended as it increases serum concentrations of nilotinib.
• It is not recommended to take Tasigna with grapefruit juice and medications that inhibit the CYP3A4 isoenzyme.

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Storage conditions

Store Tasigna in its original packaging, away from direct sunlight and moisture, at temperatures between +18 and +30°C. Keep medicines, including Tasigna, out of the reach of children.

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Shelf life

Tasigna capsules in their original packaging can be stored for up to three years.