Universal reference book for medicines
Name of the preparation: TASIGNA ® (TASIGNA ® )

Active substance: nilotinib

Type: Antitumor drug.
Protein tyrosine kinase inhibitor
Manufacturer: NOVARTIS PHARMA (Switzerland) manufactured by NOVARTIS PHARMA STEIN (Switzerland), which manufactures NOVARTIS PHARMA STEIN (Switzerland)
Composition, form of production and packaging
Hard
gelatin capsules, size 1, opaque, reddish brown, with "NVR" and "BCR" axial markings in black ink;
contents of capsules - powder from white to yellowish-white color.
1 caps.

nilotinib hydrochloride monohydrate 165.45 mg,

which corresponds to the content of nilotinib 150 mg

[PRING] lactose monohydrate - 117.08 mg, crospovidone - 11.93 mg, poloxamer 188 - 2.39 mg, silicon dioxide colloid - 1.58 mg, magnesium stearate - 1.58 mg.

The composition of the capsule shell: gelatin - 74.54 mg, titanium dioxide (E171) - 760 μg, iron oxide oxide yellow (E172) - 340 μg, iron oxide red oxide (E172) - 360 μg.

Ink composition: shellac (E904), ethanol denatured (methylated alcohol), iron dye oxide black (E172), butanol, water, macrogol, isopropanol.

4 things.
- blisters (7) - packs of cardboard.
4 things.
- blisters (7) - packs cardboard (4) - cardboard boxes.
8 pcs.
- blisters (5) - packs of cardboard.
8 pcs.
- blisters (5) - packs cardboard (3) - cardboard boxes.
Capsules hard gelatinous, size №0, opaque, light yellow color, with axial marking "NVR" and "TKI" of red color;
the contents of the capsules are white or almost white powder.
1 caps.

nilotinib hydrochloride monohydrate 220.6 mg,

which corresponds to the content of nilotinib 200 mg

[PRING] lactose monohydrate - 156.11 mg, crospovidone - 15.91 mg, poloxamer 188 - 3.18 mg, silicon dioxide colloid - 2.1 mg, magnesium stearate - 2.1 mg.

The composition of the capsule shell: gelatin - 98.82%, titanium dioxide (E171) - 1%, iron-oxide oxide yellow (E172) - 0.18%.

Ink composition: shellac (E904), propylene glycol, iron dye red oxide (E172), potassium hydroxide, water.

4 things.
- blisters (7) - packs of cardboard.
4 things.
- blisters (7) - packs cardboard (4) - cardboard boxes.
8 pcs.
- blisters (5) - packs of cardboard.
8 pcs.
- blisters (5) - packs cardboard (3) - cardboard boxes.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2013.

PHARMACHOLOGIC EFFECT

An antineoplastic agent, a protein tyrosine kinase inhibitor.
Nilotinib effectively inhibits the tyrosine kinase activity of the Bcr-Abl oncoprotein cell lines and the primarily positive for the Philadelphia chromosome (Ph-positive) leukemia cells.
The drug has a high affinity for binding sites to ATP and thus has a marked inhibitory effect on the wild-type Bcr-Abl oncoprotein, and also shows activity against imatinib-resistant 32 and 33 mutant forms of Bcr-Abl tyrosine kinase, with the exception of the T315I mutation .
Nilotinib selectively inhibits proliferation and induces apoptosis of cell lines and Ph-positive leukemia cells in patients with chronic myelogenous leukemia (CML).
Nilotinib has little or no effect on other known protein kinases (including kinase of Src family proteins), except for kinases that have receptors for platelet growth factors (PDGRF), Kit-, CSF-1, DDR receptors and ephrine receptors.
Inhibition of protein kinases of this type occurs at drug concentrations within the range of therapeutic doses recommended for the treatment of CML for oral administration.
Against the backdrop of therapy with nilotinib 400 mg twice per day in adult patients with Ph + CML in the chronic phase with intolerance or ineffectiveness of previous therapy, including imatinib, the frequency of achieving a large cytogenetic response was 52%, and this response was achieved fairly quickly - during the first 3 months of therapy (median - 2.8 months) - and persisted against the background of continued use of the drug (within 24 months) in 77% of patients.
The overall survival of patients after 24 months of therapy was 87%.
Using nilotinib 400 mg twice daily in adult patients with Ph + CML in the accelerated phase with intolerance or resistance to prior therapy, including imatinib, the hematological response rate was 55%, and this response was achieved fairly quickly - during the first month of therapy (median -1 month) - and persisted amid continued use of the drug (within 24 months) in 49% of patients.
The rate of achievement of a large cytogenetic response was 32%, and this response was preserved in 66% of patients with continued use of the drug (within 24 months).
PHARMACOKINETICS

Suction

After ingestion, the absorption of nilotinib is about 30%.
The average T max of the drug in blood plasma is about 3 hours. In healthy volunteers, while taking the drug with food C max and AUC, nilotinib increased by 112% and 82%, respectively, compared with fasting nylotinib. When taking the drug 30 minutes or 2 hours after eating, the bioavailability of nilotinib is increased by 29% and 15%, respectively. In patients undergoing total or partial gastrectomy, the absorption of nilotinib (relative bioavailability) decreases by approximately 48% and 22%, respectively.
A single application of nilotinib 400 mg in the form of apple sauce dissolved in a teaspoon of the contents of two 200 mg capsules is bioequivalent to the use of 2 intact 200 mg capsules.

Distribution

The ratio of concentrations of nilotinib in the blood and plasma is 0.71.
The binding to plasma proteins in vitro is about 98%.
In the equilibrium state, the systemic exposure of nilotinib was dose-dependent.
However, when applying
drug in a dose exceeding 400 mg 1 time / day, an increase in the exposure of nilotinib, depending on the increase in the dose of the drug, was less pronounced.

The daily C ss of nilotinib in plasma was 35% higher when administered at a dose of 400 mg 2 times / day than when applied at a dose of 800 mg 1 time / day.
AUC of nilotinib administered 400 mg twice a day was approximately 13.4% higher than when administered at a dose of 300 mg 2 times / day. When taking the drug for 12 months inside at a dose of 400 mg 2 times / day C min and C max of nilotinib by 15.7% and 14.8% were higher than those with the drug at a dose of 300 mg 2 times / day, respectively. There was no significant increase in C ss of nilotinib with an increase in the dose from 400 mg 2 times / day to 600 mg 2 times / day. Plasma exposure of nilotinib in the period between the application of the first dose and the achievement of C ss increases approximately 2-fold with the administration of the drug 1 time / day and 3.8 times with the reception 2 times / day. C ss was reached by the 8th day.
Metabolism

In healthy volunteers, the main ways of metabolizing nilotinib are oxidation and hydroxylation.
In the blood plasma, nilotinib circulates mainly unchanged. All metabolites of nilotinib have little pharmacological activity.
Excretion

After a single application of nilotinib in healthy volunteers, more than 90% of the dose is excreted within 7 days, mostly with feces.
69% of the drug is excreted unchanged. T 1/2 with a repeated application of the daily dose was approximately 17 hours.
When nilotinib was used in patients with impaired liver function, there was no significant

changes in pharmacokinetic parameters of nilotinib.
A single dose of the drug showed a decrease in AOL of nilotinib by 35%, 35% and 19% in patients with mild, moderate and severe impairment of liver function (compared to patients without hepatic impairment). With max, the nilotinba in the equilibrium state increased by 29%, 18% and 22%, respectively.
Individual differences in pharmacokinetics among patients were moderate to severe.

INDICATIONS

- newly diagnosed Ph + XML in the chronic phase in adults;

- Ph + XML in the chronic phase and the phase of acceleration in adult patients with intolerance or resistance to prior therapy, including imatinib.

DOSING MODE

The preparation Taxosa ® should be taken 2 times / day (every 12 hours), 2 hours after eating.
After taking the drug, you can take food no earlier than 1 hour later.
Capsules should be swallowed whole, washed down with water.
For patients with difficulty swallowing, the contents of the capsules may be dissolved in 1 teaspoon of apple puree immediately before taking. To dissolve the contents of capsules, use only apple puree. The contents of capsules should not be dissolved in more than one teaspoon of apple puree.
In case of missed intake of the next dose, do not take additional medication, it is necessary to take the next prescribed dose of Tasignon ® .

Treatment with the drug is carried out as long as the clinical effect remains.

Before the beginning, 7 days after the beginning and during the treatment with the drug it is recommended to conduct an ECG study.

Before the appointment of the drug, if necessary, should be corrected hypomagnesemia and hypokalemia.
In the process of treatment, it is recommended to monitor the level of potassium and magnesium in the blood serum, especially in patients at risk of developing metabolic disorders.
Due to the risk of development of tumor lysis syndrome, the clinically significant dehydration and increased uric acid concentration in patients should be corrected, if necessary.

For the treatment of Ph + CML in the chronic phase and the acceleration phase in adults
patients with intolerance or resistance to prior therapy, including imatinib, the recommended dose of Tasignon ® is 400 mg 2 times / day.
Treatment with the drug is carried out as long as the clinical effect remains.

In patients with impaired hepatic function in the appointment of nilotinib, there was no significant change in the pharmacokinetic parameters of the drug; therefore, a correction of the Tasigna dosage regimen is not required for this category of patients.
Nevertheless, these patients should be used with caution.
Data on the use of Tasigne ® in patients with impaired renal function (creatinine content in the blood serum 1.5 times> VGN) is not available.
Since the kidneys do not play a significant role in the excretion of nilotinib and its metabolites, there is no expectation of a decrease in overall clearance with the use of Tacine ® in this category of patients.
Patients with cardiovascular disorders: because clinical data on the use of Tacine® in patients with severe heart disease (including unstable angina, uncontrolled chronic heart failure, severe bradycardia, or recent myocardial infarction) use caution in such cases.

In clinical trials, patients aged> 65 years with Ph + XML in the chronic phase and accelerated phase with intolerance or resistance to prior therapy, including imatinib, accounted for 30% of the total number of patients, respectively.
Significant differences in the efficacy and safety of the use of Tasigne ® in this category of patients, compared with patients aged 18 to 65 years, was not revealed.
Correction of the dosing regimen in the development of neutropenia and thrombocytopenia

Ph + CML in the chronic phase - 400 mg 2 times / day Reduction of the absolute number of neutrophils <1 × 10 9 / l and / or platelet count <50 × 10 9 / l 1. Cancellation of Tasigne ® and regular clinical blood tests;
2. Renewal within 2 weeks of treatment with Tasigne ® at a dose that was used before the interruption of therapy if the absolute number of neutrophils is> 10 9 / L and / or the platelet count is> 50 × 10 9 / L; 3. With the preservation of cytopenia, a dose reduction of Tasigne ® may be reduced to 400 mg once / day.
Ph + XML in the acceleration phase - 400 mg 2 times / day Reduction of the absolute number of neutrophils <0.5 × 10 9 / l and / or platelet count <10 × 10 9 / l 1. Cancellation of Tasigne ® and regular clinical blood tests;
2. Renewal within 2 weeks of treatment with Tasigne ® at a dose that was used before the interruption of therapy, if the absolute number of neutrophils is> 10 5 / L and / or the platelet count is> 20 × 10 9 / L; 3. With the preservation of cytopenia, a dose reduction of Tasigne ® may be reduced to 400 mg once / day.
Correction of the dosing regimen with the development of serious non-hematological side effects

With the development of moderately severe or severe non-hematologic side effects associated with taking the drug, therapy with Taciox® should be discontinued.

After the disappearance of side effects, treatment with the drug can be resumed at a dose of 400 mg 1 time / day.
If necessary, it is possible to increase the dose to 400 mg 2 times / day.
With an increase in lipase activity in the blood 2 times higher than IGN, bilirubin concentration 3 times higher than IGN or hepatic transaminases 5 times higher than IGN, the dose of Tasignon ® should be reduced to 400 mg 1 time / day or temporarily interrupted therapy.

SIDE EFFECT

The most common non-hematological side effects associated with the use of the drug: rash, itchy skin, nausea, headache, fatigue, constipation, diarrhea, vomiting, myalgia.
Most side effects were moderately expressed. Less often (<10% and? 5%): mild alopecia, muscle spasms, anorexia, joint pain, bone pain, abdominal pain, peripheral edema and asthenia.
Side effects are listed below for organs and systems with the frequency of occurrence: very often (? 1/10), often (? 1/100, <1/10) infrequently (? 1/1000, <1/100), separately presented by-products effects with unknown frequency.

The incidence of adverse events observed in more than 5% of cases is presented in parentheses.

Infections: often - folliculitis, infrequently - infections of the upper respiratory tract (including, pharyngitis, nasopharyngitis, rhinitis), pneumonia, bronchitis, urinary tract infections, herpetic infection, candidiasis (including oral candidiasis) gastroenteritis;
frequency unknown - sepsis, subcutaneous abscess, perianal abscess, furuncle, mycosis of smooth skin of the feet.
Benign and malignant neoplasms: often - papilloma of the skin;
frequency unknown - papilloma of the oral mucosa.
From the hemopoietic system: very often thrombocytopenia (31%), neutropenia (17%), anemia (14%);
often - febrile neutropenia, pancytopenia, lymphopenia;frequency unknown - thrombocythemia, leukocytosis, eosinophilia.
From the immune system: the frequency is unknown - hypersensitivity.

From the endocrine system: infrequently - hyperthyroidism, hypothyroidism;
frequency is unknown - secondary hyperparathyroidism, thyroiditis.
On the part of metabolism: often - anorexia (7%), electrolyte disorders (hypomagnesemia, hyperkalemia, hypokalemia, hyponatremia, hypocalcemia, hypophosphatemia, hypercalcemia, hyperphosphataemia), hyperglycemia, diabetes mellitus, hypercholesterolemia, hyperlipidemia, decreased appetite;
infrequently - dehydration, increased appetite; the frequency is unknown - hyperuricemia, gout, hypoglycemia, dyslipidemia.
From the nervous system: very often - headache (15%);
often - dizziness, peripheral neuropathy, paresthesia, hypoesthesia, a violation of taste sensations; infrequently - intracranial hemorrhage, migraine, loss of consciousness, tremor, impaired concentration, hyperesthesia; frequency is unknown - cerebral edema, optic neuritis, inhibition, dysesthesia, restless legs syndrome.
Mental disorders: often - depression, insomnia, anxiety;
frequency is unknown - disorientation, confusion, amnesia, dysphoria.
From the side of the organ of vision: often - intraocular hemorrhage, periorbital edema, conjunctivitis, itching in the eyes, dry eye syndrome;
infrequent - vision impairment, blurred vision, decreased visual acuity, eyelid edema, photopsy, flushing (sclera, conjunctiva, eyeball), eye irritation; frequency unknown - edema of the optic disc, diplopia, photophobia, eyelid swelling, blepharitis, eye pain, chorioretinopathy, conjunctival hemorrhage, allergic conjunctivitis, diseases of the eye mucosa.
From the side of the hearing organ and labyrinthine disturbances: often - vertigo;
frequency unknown - decreased hearing acuity, pain in the ears, tinnitus.
From the cardiovascular system: often - angina pectoris, arrhythmias (including AV blockade, atrial flutter, extrasystole, tachycardia, atrial fibrillation, bradycardia), palpitations, prolongation of the QT interval on the ECG, blood rushes, increased blood pressure;
infrequently - heart failure, pericardial effusion, IHD, cyanosis, the appearance of heart murmurs, hypertensive crisis, occlusion of peripheral arteries, formation of hematomas; the frequency is unknown - myocardial infarction, ventricular dysfunction, pericarditis, ejection fraction reduction, hemorrhagic shock, lowering of blood pressure, thrombosis.
On the part of the respiratory system: often - dyspnea at rest and with physical exertion, epistaxis, cough, dysphonia;
infrequent - pulmonary edema, pleural effusion, interstitial lung diseases, chest pain, pleural pain, pleurisy, pain in the pharynx and / or larynx, irritation of the pharyngeal mucosa; frequency unknown - pulmonary hypertension, wheezing.
On the part of the digestive system: very often - nausea (20%), constipation (12%), diarrhea (11%), vomiting (10%);
often - abdominal pain (including epigastric pain) (6%), abdominal discomfort, bloating, dyspepsia, flatulence, pancreatitis, impaired liver function; infrequently - gastrointestinal bleeding, melena, ulceration of the oral mucosa, gastroesophageal reflux, stomatitis, dry mouth, pain in the esophagus, hepatitis, jaundice, toxic liver damage; frequency is unknown - perforation of gastrointestinal ulcers, retroperitoneal haemorrhage, vomiting blood, stomach ulcer, ulcerative esophagitis, partial bowel obstruction, gastritis, enterocolitis, hemorrhoids, hiatal hernia, rectal bleeding, increased sensitivity of tooth enamel, gingivitis, cholestasis, hepatomegaly .
Dermatological reactions:very often - rash (28%), pruritus (24%); often - increased sweating at night, eczema, hives, erythema, rash, dermatitis (allergic and akneformny), dry skin, bruising, acne; infrequently - Exfoliative rash, swelling of the face, drug eruption, skin pain, ecchymosis; frequency is unknown - erythema multiforme, erythema nodosum, skin ulcer, plantar-palmar syndrome eritrodizestezii, petechiae, increased photosensitivity, blisters, skin cysts, sebaceous gland hyperplasia, skin atrophy, skin discoloration, skin peeling, skin hyperpigmentation, skin hypertrophy.
On the part of the musculoskeletal system:very often - myalgia (10%); often - arthralgia (7%), muscle spasms (8%), bone pain (6%), limb pain, pain in the iliac fossa, musculoskeletal chest pain, musculoskeletal pain, pain in the side; infrequently - stiffness, muscle weakness, swelling of the joints; frequency is unknown - arthritis.
From the urinary system: often - pollakiuria; rarely - dysuria, urgency to urinate, nocturia; frequency is unknown - kidney failure, hematuria, urinary incontinence, chromaturia.
On the part of the reproductive system: rarely - pain in the breast, gynecomastia, erectile dysfunction; the frequency is unknown - the seal of the mammary glands, menorrhagia, nipple swelling.
General reactions: Very often - fatigue (17%); often - asthenia (6%), fluid retention and swelling (5%), fever, chest pain (including non-cardiac pain), pain in the neck and back pain, chest discomfort, malaise; infrequently - facial edema, peripheral edema, flu syndrome, chills, body temperature change sensation (striping "hot flashes" and "feeling cold"); frequency is unknown - localized swelling.
From the laboratory parameters:often - reduced hemoglobin in the blood plasma increased activity of amylase, GGT, CPK, alkaline phosphatase, decrease or increase in body weight; rarely - increase LDH activity in blood plasma, increasing concentrations of urea in blood plasma; frequency is unknown - blood plasma increased concentration of troponin content of unconjugated bilirubin concentrations of insulin, elevated levels of VLDL and HDL, elevated levels of parathyroid hormone in the blood plasma.
Previous clinical use
In therapy drug Tasigna ® were observed following side effects without indications causal relationship with nilotinib (frequency not installed): Cases of tumor lysis syndrome.
CONTRAINDICATIONS

- Pregnancy;

- the period of lactation (breastfeeding);

- child and adolescence to 18 years (there is no data on the use);
- hereditary galactose intolerance, lactase deficiency or malabsorption of glucose-galactose;
- Hypersensitivity to the components of the drug.

With caution should be used drug in patients with risk factors for lengthening QT interval on the ECG (congenital lengthening QT interval, with drug by uncontrolled or severe cardiac disease, including recent myocardial infarction, chronic heart failure, unstable angina or clinically significant bradycardia) violations liver function, pancreatitis (including history).
It should not be administered with drugs that are potent inhibitors of isoenzyme CYP3F4 or prolong the QT interval, especially in patients with hypokalemia and hypomagnesemia (perhaps more pronounced elongation of the QT interval).
simultaneous application of the drug should be avoided with grapefruit juice, and other products that are known inhibitors of CYP3A4.
PREGNANCY AND LACTATION

The drug is contraindicated during pregnancy and lactation (breastfeeding).
During therapy with Tasigna ® patients, especially women of childbearing age should use reliable methods of contraception.
APPLICATION FOR FUNCTIONS OF THE LIVER

Because the kidneys do not play a significant role in the excretion of nilotinib and its metabolites are not expected to reduce the total clearance in the application of Tasigna in patients with renal insufficiency.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Precautions should be used when the drug hepatic insufficiency.
APPLICATION FOR CHILDREN

Contraindications: childhood and adolescence to 18 years (no data on the use).
APPLICATION IN ELDERLY PATIENTS

Elderly patients do not need medication dosing regimen correction.
SPECIAL INSTRUCTIONS

Treatment should be carried out by specialists with experience in the treatment of CML.
Since use of the drug Tasigna ® may develop thrombocytopenia, neutropenia, and anemia (most common in patients with CML in accelerated phase) should be carried out clinical analysis of blood every two weeks during the first 2 months of drug therapy, and then - monthly or in case of clinical necessity . Myelosuppression, occurring during therapy, is generally reversible and manageable. Normalization of platelet and neutrophil usually able to reach after temporary cessation or reduction therapy Tasigna dose.
In applying the drug Tasigna ®in clinical trials, uncommon (0.1-1%) were cases of sudden death in patients with heart disease or a high risk of cardiovascular complications. These patients often have comorbid conditions and received concomitant therapy. Violations of ventricular repolarization may be an additional risk factor. According to postmarketing studies estimated the frequency of spontaneous reports of sudden death was 0.02% as of 1 patient per year.
With an increase in the activity of lipase in the blood plasma, accompanied by abdominal symptoms, the drug should be discontinued, conducted appropriate examination of the patient in order to exclude pancreatitis.
In applying Tasigna recommended monthly monitoring of liver function (transaminase, bilirubin).
Since patients who have undergone total gastrectomy, the bioavailability of nilotinib might be reduced, careful monitoring of these patients.
Impact on the ability to drive vehicles and manage mechanisms

Some side effects of the drug, including dizziness or visual disturbances, may adversely affect the ability to drive vehicles and potentially hazardous activities that require high concentration and psychomotor speed reactions. Therefore, during the treatment period, patients should use caution when driving and other potentially hazardous activities.
OVERDOSE

Symptoms reported isolated cases of overdose in which the co-administration of an unknown number of capsules with alcohol and other drugs. It noted the development of neutropenia, vomiting and drowsiness. ECG changes and signs of liver toxicity was observed.
Treatment: observation of the patient, symptomatic therapy.
DRUG INTERACTION

Drugs that are capable of increasing the concentration of nilotinib plasma
Nilotinib is metabolized primarily in the liver, and is also a substrate for the removal systems of many drugs - P-glycoprotein. The absorption and the subsequent elimination of nilotinib may affect drugs acting on isozyme CYP3A4 and / or P-glycoprotein. In clinical studies, the application of nilotinib with imatinib (substratum and moderator isoenzyme CYP3A4 and P-glycoprotein), both drugs inhibited slightly isoenzyme CYP3A4 and P-glycoprotein, wherein the AUC for imatinib increased 18-39%, a nilotinib AUC - to 18- 40%.
Nilotinib bioavailability in healthy volunteers increased 3 times while applying a strong inhibitor of CYP3A4 isoenzyme ketoconazole. Avoid the simultaneous application nilotinib with drugs that are potent inhibitors of isoenzyme CYP3A4 (including ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin and telithromycin), and to consider alternative therapy drugs, without inhibiting or significantly inhibiting the isozyme CYP3A4. If necessary, treatment with drugs, which are potent inhibitors of isoenzyme CYP3A4, treatment with Tasigna ®It must be on, suspended opportunity. If necessary, concomitant use Tasigna with drugs that are potent inhibitors of isoenzyme CYP3A4, necessary to carefully control the individual to detect possible elongation QTcF interval.
Drugs that are able to reduce the concentration of nilotinib plasma
Inducers of CYP3A4 isoenzyme may enhance metabolism of nilotinib and reduce its concentration in the blood plasma. When simultaneous administration with drugs, which are inducers isoenzyme CYP3A4 (including phenytoin, rifampin, carbamazepine, phenobarbital and St. John's wort) may decrease the concentration of nilotinib. If necessary, therapy drugs that are inducers of CYP3A4 isoenzyme, should consider the use of other means of providing lower-inducing effect on the isoenzyme CYP3A4.
When assigning healthy volunteers with nilotinib isoenzyme CYP3A4 inducer rifampicin (600 mg / day for 12 days) there was a decrease nilotinib systemic exposure (AUC) is approximately 80%.
Solubility nilotinib is pH-dependent, thus, with an increase in pH (acidity decrease) the solubility of the drug decreases. In healthy individuals with a strong increase in pH on background esomeprazole (40mg 1 time / day for 5 days) reduction in suction nilotinib was moderate (AUC and Cmax decrease by 27% and 34% respectively). If necessary, the drug Tasigna ® can be used simultaneously with esomeprazole or other proton pump inhibitors.
Effect nilotinib concentration in plasma preparations used as concomitant therapy
Nilotinib is a competitive inhibitor of isozymes CYP3A4, CYP2C8, CP2C9, CYP2D6 and UGT1A1 in vitro, while the lowest value of the inhibition constant (Ki) was 0.13 .mu.M for CYP2C9. In healthy individuals the use of nilotinib with warfarin (a substrate of CYP2C9) had no clinically significant effect on farmakokinstiku or pharmacodynamics of warfarin. When neobhYodimosti drug Tasigna ® can be
used in conjunction with warfarin without increasing the anticoagulant effect of the latter. For a single application of the drug Tasigna ® with midazolam in healthy volunteers showed an increase midazolam concentration to 30%, but the level of midazolam metabolism to its main metabolite, 1-gidroksimidazolama not changed.
Antiarrhythmic drugs and other drugs which cause lengthening of the interval QT
should not assign nilotinib with antiarrhythmics (e.g., amiodarone, disopyramide, procainamide, hinidiiom and sotalol) and other drugs that cause lengthening of the interval QT (e.g., chloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin, bepridilom and pimozide).
Other types of interactions that may affect the concentration of serum nilotinib
When concomitantly with meals there is an increase of absorption nilotinib, leading to increase of its plasma concentrations.
Avoid the simultaneous application of the drug Tasigna ®with grapefruit juice, and other products that are known inhibitors of isoenzyme CYP3A4.
If necessary, possible to use Tasigna with stimulators of hematopoiesis, such as erythropoietin, G-CSF, as well as hydroxycarbamide and anagrelide.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

TERMS AND CONDITIONS OF STORAGE

The drug should be kept out of reach of children at a temperature not higher than 30 ° C.
Shelf life - 3 years.
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