Sprice - instructions for use, analogs, reviews and release forms (tablets 20 mg, 50 mg, 70 mg, 80 mg, 100 mg and 140 mg) of the drug for the treatment of chronic myelogenous leukemia and acute lymphocytic leukemia in adults, children and in pregnancy

In this article, you can read the instructions for using the drug Spruce. There are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors specialists on the use of Sprice in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Sprisel in the presence of existing structural analogs. Use for the treatment of chronic myelogenous leukemia and acute lymphoblastic leukemia in adults, children, as well as during pregnancy and lactation.

Spruce antitumor agent, protein tyrosine kinase inhibitor.

Dasatinib (active ingredient in the Spriceil preparation) inhibits the BCR-ABL tyrosine kinase and SRC family tyrosine kinases, as well as many other oncogenic kinases, including c-KIT, the EHR receptor kinase and the PDGFβ receptor. Dasatinib binds to the active and inactive forms of the enzyme BCR-ABL and inhibits it at subnanomolar concentrations (0.6-0.8 nmol / ml).

In vitro, dasatinib exhibits activity on cellular models of leukemia, both in susceptible and resistant to imatinib cells. Dasatinib overcomes the resistance to imatinib associated with the overexpression of the BCR-ABL enzyme, the BCR-ABL kinase domain mutations, the activation of alternative mechanisms inducing kinases of the SRC family (LYN, ICS), and also the overexpression of the multiple drug resistance gene.

Composition

Dasatinib + excipients.

Pharmacokinetics

When ingested, Spricel is rapidly absorbed from the gastrointestinal tract. The maximum concentration in the blood is observed after 0.5-3 hours. Eating does not have a significant effect on absorption.Binding to plasma proteins - 96%. Isozyme CYP3A4 is the main enzyme responsible for the metabolism of dasatinib. Metabolites do not play a big role in the pharmacological action of Sprysel. The drug is excreted mainly by the intestines, mainly in the form of metabolites. Unchanged dasatinib accounts for 0.1% and 19% of the dose excreted by the kidneys and intestines, respectively, the rest of the dose is metabolites.

Pharmacokinetics in special clinical cases

The pharmacokinetics of dasatinib was evaluated in 8 patients with moderate hepatic impairment (after a single dose of the drug at a dose of 50 mg) and 5 patients with severe hepatic impairment (after a single dose of the drug in a dose of 20 mg) compared to the pharmacokinetics in healthy volunteers ( after taking a drug at a dose of 70 mg). In patients with moderate hepatic impairment, a decrease values ​​of pharmacokinetic parameters (maximum blood concentration dasatinib and AUC - area under the concentration-time curve) compared to their values ​​in healthy volunteers. In patients with severe impairment of liver function - an even more pronounced decrease in thesepharmacokinetic parameters.

In patients with impaired renal function, the pharmacokinetics of dasatinib does not change.

Indications

• chronic myelogenous leukemia in the chronic phase, the phase of acceleration or in the phase of the lymphoid or myeloid blast crisis with resistance or intolerance to previous therapy, including imatinib;
• acute lymphoblastic leukemia with a positive Philadelphia chromosome with resistance or intolerance to previous therapy.

Forms of release

Tablets coated with 20 mg, 50 mg, 70 mg, 80 mg, 100 mg and 140 mg.

Instructions for use and dosing regimen

The drug is taken regardless of food intake. Tablets should be swallowed whole.

In the chronic phase of chronic myelogenous leukemia, the recommended initial dose is 100 mg once a day in the morning or evening.

AT the remaining cases - 140 mg once a day in the morning or evening.

A dose change is possible in view of the clinical response and tolerability of the drug by the patient.

In the absence of a hematologic or cytogenetic response, it is possible to increase the dose of the drug in the chronic phase of chronic myelogenous leukemia up to 140 mg once a day,with far-reaching chronic myelogenous leukemia (the phase of acceleration or blast crisis) and acute limboflastnom leukemia with a positive Philadelphia chromosome - up to 180 mg once a day.

Recommendations for correcting the dose of the drug due to side effects

When myelosuppression should reduce the dose, interrupt therapy or cancel it. If necessary, transfusions of platelet or erythrocyte mass should be performed. With stable myelosuppression, it is possible to use hematopoietic growth factors.

Patients with a chronic phase of chronic myelogenous leukemia (the initial dose of 100 mg once a day) with an absolute number of neutrophils less than 0.5 × 10⁹/ l or the number of platelets less than 50 × 10⁹/ l it is necessary to cancel the preparation of Spriceil to achieve an absolute number of neutrophils more than 1 × 10⁹/ l and the number of platelets more than 50 × 10⁹/ l. And then resume therapy at the previous dose. The same patients with a platelet count of less than 25 × 10⁹/ l or an absolute number of neutrophils less than 0.5 × 10⁹/ l (for 7 or more days), you should take a break in treatment before reaching the baseline. Therapy should be resumed in a reduced dose (80 mg once a day), if this is the second episode, or stop treatment if this is the third episode.

In patients with chronic myelogenous leukemia (in the phase of acceleration or blast crisis) and acute limboflastnym leukemia with a positive Philadelphia chromosome (initial dose of 140 mg once a day) with an absolute number of neutrophils less than 0.5 × 10⁹/ l or the number of platelets less than 10 × 10⁹/ l must be established, what causes cytopenia. If cytopenia is not associated with leukemia, treatment should be discontinued until an absolute number of neutrophils is greater than 1 × 10⁹/ l and the number of platelets more than 20 × 10⁹/ l and resume therapy at the previous dose. In case of recurrence of cytopenia, one should again be convinced of its nature and resume therapy in a reduced dose of 100 mg once a day, if this is the second episode, or 80 mg once a day, if this is the third episode.

If the resulting cytopenia is associated with leukemia, consider increasing the dose to 180 mg once a day.

With the development of severe non-hematologic side effects, treatment is suspended until the symptom of the side effect disappears or until the patient's condition improves. Treatment can be resumed in a reduced dose.

The renal clearance of dasatinib and its metabolites is less than 4%, so dose adjustments for impaired renal function not required.

Dasatinib is metabolized mainly by the liver, so the drug should be used with caution in patients with moderate and severe liver dysfunction.

Clinically significant differences in pharmacokinetics in elderly patients have not been identified, so dose adjustment is not required.

Side effect

• headache, dizziness;
• infectious complications (pneumonia, upper respiratory tract infections, herpetic infections, enterocolitis, sepsis), including bacterial, viral, fungal infections;
• fever;
• febrile neutropenia, pancytopenia, erythroblastopenia;
• hypersensitivity reactions, including erythema nodosum;
• insomnia, depression, drowsiness;
• fatigue;
• perversion of taste;
• anxiety, emotional lability;
• psychosis;
• decreased libido (sexual desire);
• cerebral hemorrhages;
• tremor (fast, rhythmic movements of limbs or trunk);
• fainting;
• amnesia (loss of memory);
• convulsions;
• cerebrovascular accident (stroke);
• impaired vision;
• dry eyes, conjunctivitis;
• noise in ears;
• bleeding;
• tides;
• increased blood pressure;
• arrhythmia (cardiac rhythm disturbance);
• congestive heart failure, myocardial dysfunction;
• cardiopalmus;
• angina pectoris;
• thrombophlebitis (vein thrombosis with inflammation of its wall);
• pericarditis (inflammatory lesion of the serosa of the heart);
• myocardial infarction;
• Pleural effusion (accumulation of fluid in the pleural cavity);
• shortness of breath, cough;
• pulmonary infiltrates;
• pulmonary edema;
• pneumonitis (inflammation of the vascular wall of the alveoli);
• pulmonary hypertension;
• bronchial asthma, bronchospasm;
• diarrhea;
• nausea, vomiting;
• abdominal pain;
• a violation of appetite;
• inflammation of the mucous membranes;
• gastrointestinal bleeding;
• dyspepsia, bloating, constipation;
• gastritis (inflammation of the gastric mucosa);
• colitis (inflammation of the mucous membrane of the large intestine);
• anorexia (a neuropsychic disorder manifested by an obsessive desire to lose weight, fear of obesity);
• dysphagia (difficulty swallowing);
• ascites (fluid in the abdominal cavity);
• anal fissures;
• pancreatitis (inflammation of the pancreas);
• esophagitis (inflammation of the mucosa of the esophagus);
• Cholestasis (decreased bile flow into the duodenum);
• cholecystitis (inflammation of the gallbladder);
• hepatitis (inflammation of the liver);
• skin rash, itching;
• acne;
• alopecia (baldness);
• dry skin;
• hyperhidrosis (profuse sweating);
• hives;
• dermatitis, including eczema;
• skin ulcers;
• bullous dermatosis;
• disorders of pigmentation;
• defeat of nails;
• musculoskeletal pain;
• myalgia (pain in the muscle), arthralgia (pain in the joint);
• myositis (inflammatory process in skeletal muscles), muscle weakness;
• musculoskeletal stiffness;
• increased activity of creatine phosphokinase in the blood;
• rhabdomyolysis (extreme degree of myopathy);
• kidney failure;
• frequent urination;
• proteinuria (protein in the urine);
• gynecomastia (enlargement of the breast with hypertrophy of glands and adipose tissue);
• menstrual cycle disorders;
• fluid retention, localized edema of subcutaneous tissue of various locations, edema of the tongue, edema of the lips, edema of the conjunctiva;
• chest pain;
• chills;
• Hyperuricemia (increased uric acid in the blood).

 Contraindications

• pregnancy;
• lactation period (breastfeeding);
• children and adolescents under 18;
• increased sensitivity to dasatinib or other components of the drug.

Application in pregnancy and lactation

Patients during treatment and at least 3 months afterwards must use reliable contraceptive methods. If the pregnancy occurred during treatment with the drug Spriceil, and also if it became known that the drug was used in pregnancy, should immediately inform the patient about the possible risk to the fetus.

It is not known whether dasatinib passes into breast milk. Breastfeeding should be stopped for the duration of treatment with the Spricele preparation.

Use in children

The drug is contraindicated in childhood and adolescence (up to 18 years).

Application in elderly patients

Clinically significant differences in pharmacokinetics in elderly patients have not been identified, so dose adjustment is not required.

special instructions

When treated with Spriceil, serious (grade 3 and 4 NCI CTC) thrombocytopenia, anemia and neutropenia are possible. More often, these reactions are recorded in patients with a far-advanced phase of chronic myelogenous leukemia or acute lymphoblastic leukemia with a positive Philadelphia chromosome than in patients with a chronic phase of chronic myelogenous leukemia.A complete clinical blood test should be performed weekly for the first 2 months of treatment, and then monthly or more often, according to clinical indications. Oppression of bone marrow hemopoiesis is usually reversible and occurs with the temporary cancellation or reduction of the dose of Sprice.

Most cases of bleeding in the background of the use of the drug were associated with severe thrombocytopenia. Severe cerebral hemorrhages, including fatal ones, have been reported in less than 1% of patients receiving Sprysel. Severe gastrointestinal bleeding was noted in 4% of patients. Usually, a temporary withdrawal of the drug and the appointment of blood transfusions were required. Other severe bleeding was reported in 2% of patients.

When taking Sprisel, fluid retention may occur. Fluid retention was severe in 10% of patients, including pronounced pleural and pericardial effusion in 7% and 1% of patients, respectively. Pronounced ascites and generalized edema developed in less than 1% of patients. 1% of patients reported severe pulmonary edema. When there is shortness of breath or a dry cough, an X-ray examination of the chest organs is necessary.Fluid retention is usually stopped with maintenance therapy with the inclusion of diuretics or a short course of glucocorticosteroids (GCS). When expressed pleural effusion, oxygen therapy and thoracocentesis were required.

Dasatinib should be used with caution in patients with an extended QT interval or at a risk of prolonging it (with hypokalemia, hypomagnesemia, congenital syndrome of the extended QT interval, with antiarrhythmic therapy and other drugs that can prolong the QT interval, with prior therapy with high doses of anthracyclines). Before the appointment of Sprysel, correction of hypokalemia and hypomagnesemia should be performed.

The drug Spricel contains lactose: in a daily dose of 100 mg - 135 mg of lactose and in a daily dose of 140 mg - 189 mg of lactose.

Impact on the ability to drive vehicles and manage mechanisms

If a patient observes treatment-related symptoms, such as dizziness and visual impairment that affect his ability to concentrate and respond quickly, it is recommended that you stop driving and performing potentially dangerous activities that require increased attention and speed of psychomotor reactions.

Drug Interactions

Dasatinib is a substrate for the isoenzyme CYP3A4. Inhibitors of the isoenzyme CYP3A4 (eg, ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, atazanavir, indinavir, nelfinavir, saquinavir, telithromycin, grapefruit juice) can increase the concentration of dasatinib in the blood plasma, therefore, their use with dasatinib should be avoided. Patients who can not avoid systemic administration of a potent inhibitor of the CYP3A4 isoenzyme should be closely monitored for the timely detection of signs of toxicity.

Inductors of the isoenzyme CYP3A4 can reduce the concentration of dasatinib in plasma. It is necessary to avoid the joint use of powerful inductors of the isoenzyme CYP3A4 with Spriceil. Patients taking inductors of the isoenzyme CYP3A4 (eg, dexamethasone, phenytoin, carbamazepine, rifampicin, Phenobarbital or preparations of St. John's wort) should be given drugs that do not (or have a minimal degree of) ability to induce this isoenzyme.

Antacids (preparations containing aluminum hydroxide and / or magnesium hydroxide) should be taken at least 2 hours before or 2 hours after taking dasatinib.

Prolonged inhibition of gastric acid secretion by histamine H2 receptor blockers and proton pump inhibitors (eg, Famotidine and omeprazole) can lead to a decrease in dasatinib concentration. The combined use of these drugs and dasatinib is not recommended. As their alternative, you can use antacids.

Dasatinib is an inhibitor of the isoenzyme CYP3A4, so its combined use with substrates of the CYP3A4 isoenzyme can enhance the action of this substrate. Substrates of the CYP3A4 isoenzyme with a narrow therapeutic range, such as alfentanil, astemizole, terfenadine, cisapride, ciclosporin, fentanyl, pimozide, quinidine, sirolimus, tacrolimus and ergot alkaloids (ergotamine, dihydroergotamine) should be used with caution in patients receiving dasatinib.

Analogues of the drug Spriceil

Structural analogs for the active substance:

• Dasatinib.

Analogues of the drug Spraysel on the pharmacological group (antineoplastic agents - inhibitors of protein kinases):

• Albitinib;
• The Athlete;
• Bosulif;
• Vargatef;
• Votrient;
• Genfatinib;
• Gefitinib;
• Histamel;
• Gleihib;
• Glivec;
• Dasatinib;
• Djakavi;
• Zelborough;
• Ibrans;
• Iglib;
• Imagliv;
• Imatib;
• Imatinib;
• Imbruvik;
• Imvek;
• Inlita;
• Iressa;
• Capresa;
• Cotellus;
• Xalqori;
• Lenwima;
• Mechinist;
• Nexavar;
• Neopax;
• Nilotinib;
• Ninlaro;
• Sorafenib;
• Steiverg;
• Sunitinib;
• Sutent;
• Tagrisso;
• Tayverb;
• Tarlenib;
• Tarceva;
• Taxis;
• Tafinlar;
• Thorizel;
• Filachromine;
• Everolimus;
• Erlotinib.

Review of a hematologist

I have experience of treatment with Spriceil drug of patients with chronic myelogenous leukemia. At the initial dose of 100 mg once a day, almost all after some time, there were signs of myelosuppression, so you had to take a break in treatment and wait for the return of blood values ​​to the baseline level. But after the resumption of therapy in the same dose, almost all had a second and third episode of myelosuppression, so the treatment had to be stopped. In addition, in patients receiving Sprysel, there have always been multiple side effects.

Similar medicines:

Other medicines: