Jakawi
Instructions for use:
- 1. Release form and composition
- 2. Indications for use
- 3. Contraindications
- 4. Method of application and dosage
- 5. Side effects
- 6. Special instructions
- 7. Drug interactions
- 8. Analogs
- 9. Terms and conditions of storage
- 10. Terms of dispensing from pharmacies
Jakavi is a protein tyrosine kinase inhibitor, an antineoplastic agent.
Release form and composition
Dosage form of the drug - tablets:
- 5 mg: round, almost white or white, with NVR engraved on one side and L5 on the other, without bevel;
- 15 mg: oval, biconvex, almost white or white, engraved with "NVR" on one side and "L15" on the other, without bevel;
- 20 mg: oblong, biconvex, almost white or white, engraved with "NVR" on one side and "L20" on the other, without chamfer.
Packing of tablets: 14 pcs. in blisters, in a cardboard box 4 blisters; 60 pcs. in banks, in a cardboard box 1 can.
Active ingredient: ruxolitinib (in the form of phosphate), in 1 tablet - 5, 15 or 20 mg.
Excipients: hydroxypropyl cellulose, sodium starch glycolate (type A), microcrystalline cellulose, povidone, magnesium stearate, lactose monohydrate, colloidal silicon dioxide.
Indications for use
Jakavi is a remedy for the treatment of myelofibrosis, including primary and secondary, which developed as a result of essential thrombocythemia and polycythemia vera.
Contraindications
- age under 18;
- period of pregnancy and lactation;
- hypersensitivity to any of the components that make up Jakavi.
Carefully:
- severe infectious diseases in the acute phase;
- severe renal failure and hemodialysis;
- liver failure;
- anemia;
- thrombocytopenia;
- neutropenia;
- lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
- simultaneous use of powerful CYP3A4 isoenzymes.
Method of administration and dosage
The drug is indicated for oral administration. Eating does not affect effectiveness.
Initial doses for patients, depending on the number of platelets:
- 50-100 × 10 9 / l - 5 mg 2 times a day;
- 100-200 × 10 9 / l - 15 mg 2 times a day;
- > 200 × 10 9 / l - 20 mg 2 times a day.
In the initial dose, treatment is carried out for 4 weeks. The further dose is selected individually, taking into account the tolerance and effectiveness of Jakavi.
In the case of a decrease in the number of platelets less than 50 × 10 9 / l or a decrease in the absolute number of neutrophils less than 0.5 × 10 9 / l, treatment is suspended. The therapy is resumed at a dose of 5 mg 2 times a day after an increase in the number of platelets / neutrophils above the indicated indicators. Further, the dose, if necessary, is gradually increased, carefully controlling the number of blood cells.
If the platelet count is less than 100 × 10 9 / L, it is recommended to reduce the dose of Jakavi in order to avoid interruption in treatment due to the developed thrombocytopenia.
If necessary, and provided that the number of platelets and neutrophils is sufficient, the dose of the drug can be increased by a maximum of 5 mg 2 times a day no more than once every 2 weeks.
The maximum permissible daily dose is 50 mg: 25 mg 2 times a day.
If you miss a dose, do not take an additional dose. The patient should take the next dose at the usual time.
Treatment with the drug is continued as long as its therapeutic effect persists.
Special patient groups
In patients with severe renal failure (with creatinine clearance <30 ml / minute) and liver failure, it is recommended to reduce the initial dose by 50%. Patients should be closely monitored. To avoid the development of side effects, the dose is reduced if necessary.
In patients with end-stage renal disease on hemodialysis, data on the use of ruxolitinib are limited. The initial dose for such patients is 15 or 20 mg 1 time per day, depending on the number of platelets. After assessing the balance of benefits and risks, an additional dose may be prescribed after the hemodialysis procedure.
Elderly patients over 65 years of age do not need dose adjustment.
The safety and effectiveness of ruxolitinib in children and adolescents under 18 years of age have not been established.
Patients who simultaneously receive potent inhibitors of the CYP3A4 isoenzyme (nelfinavir, itraconazole, saquinavir, indinavir, voriconazole, ketoconazole, telithromycin, lopinavir, ritonavir, clarithromycin, grapefruit juice), when taking the drug, reduce the daily dose by about 50% or per day, or reducing the frequency of admission to 1 time per day, if such a regimen is possible). Patients should be carefully monitored for hematological parameters, as well as clinical signs for the development of side effects of Jakavi.
Side effects
The most common adverse events reported in clinical trials are anemia and thrombocytopenia.
Hematological adverse events: anemia (81.7%), thrombocytopenia (67.4%), neutropenia (15.3%). These reactions are dose-dependent.
The most common non-hematological laboratory disorders include increased activity of alanine aminotransferase (ALT) (26.2%) and asparaginine aminotransferase (AST) (18.6%), hypercholesterolemia (16.6%).
The most common non-hematological adverse reactions are subcutaneous hematomas (18.6%), dizziness (14%), headache (12.6%).
In the III phase of clinical trials, the cancellation of Jakavi due to the development of side effects (regardless of the cause-and-effect relationship) was required in 9.6% of patients.
The incidence of side effects: very often - ≥ 1/10, often - from ≥ 1/100 to <1/10, infrequently - ≥ 1/1000 to <1/100, rarely - from ≥ 1/10 000 to <1 / 1000, very rarely - <1/10 000.
Possible adverse reactions:
- from the hematopoietic system: very often - neutropenia of 1 and 2 degrees of severity, thrombocytopenia of 1 and 2 degrees of severity, anemia, including 3 degrees of severity (> 80-65 g / l), bleeding (including purpura, petechiae, subcutaneous hemorrhage, intracranial hemorrhage and gastrointestinal bleeding); often - thrombocytopenia of 3 degrees of severity (50-25 × 10 9 / L) and 4 degrees of severity (<25 × 10 9 / L), neutropenia of 3 degrees of severity (<1-0.5 × 10 9 / L) and 4 degrees severity (<0.5 × 10 9 / l), grade 4 anemia (<65 g / l);
- from the liver and biliary tract: very often - an increase in the activity of ACT 1, 2 degrees, an increase in the activity of ALT 1 degree; often - an increase in ALT activity 5–20 times higher than normal;
- from the side of metabolism: very often - hypercholesterolemia 3 and 4 degrees; often - increased body weight;
- from the digestive system: often - flatulence;
- from the nervous system: very often - headache, dizziness; often - imbalance; infrequently - Meniere's disease;
- infectious and parasitic diseases: very often - urinary tract infections (cystitis, pyuria, urosepsis), kidney infections; often - herpes zoster, tuberculosis.
Classification of the severity of side effects:
- 1 - mild;
- 2 - moderate degree;
- 3 - severe degree;
- 4 - extremely severe, life-threatening.
special instructions
Before the appointment of Jakavi, it is necessary to carry out a general blood test with the counting of blood cells. The absolute number of blood cells should be monitored every 2–4 weeks during the titration period of the drug dose and further on clinical indications.
With the development of anemia, it may be necessary to transfuse the erythrocyte mass into the patient and adjust the dose of the drug.
At 8–12 weeks of treatment, the hemoglobin index reaches the lowest possible level (15–20 g / l lower than the initial value). In the future, it gradually increases and remains at a level 10 g / l below the initial (before the start of therapy). This trend is observed in patients regardless of whether they receive blood transfusion during treatment.
Severe neutropenia (stages 3 and 4), if it develops, is usually noted by 12 weeks of taking Jakavi. In general, it is reversible and corrected by temporary discontinuation of the drug.
Before prescribing therapy, it is recommended to conduct an examination for the presence and risk of developing severe fungal, bacterial, viral and mycobacterial infections. There are isolated cases of tuberculosis in patients receiving ruxolitinib. Jakavi should not be prescribed until an active, severe infectious process is resolved. Patients should be closely monitored for symptoms of infection so that appropriate treatment is promptly provided if necessary.
The drug can cause the development of herpes zoster. The doctor must teach the patient to timely identify early signs of this disease in order to start treatment on time.
A separate case of the development of progressive multifocal leukoencephalopathy (PML) in a patient taking Jakavi is known. As a result, clinicians should be wary of the occurrence of neuropsychiatric symptoms that may indicate PML.
After stopping treatment, symptoms of myelofibrosis (fatigue, night sweats, fever, bone pain, itching, weight loss, symptomatic splenomegaly) may return. In clinical studies, the general scale of signs of myelofibrosis gradually returned to baseline values within 7 days after discontinuation of the drug.
Women of fertile age are advised to use reliable contraceptive methods during the period of Jakavi use. In the event of pregnancy during treatment, the balance of benefits and risks should be carefully evaluated, taking into account data on the embryotoxicity of the drug.
No studies have been conducted on the effect of ruxolitinib on reaction rate and ability to concentrate. However, given the likelihood of dizziness, patients are advised to exercise caution when driving or performing any work requiring attention.
Drug interactions
Potent inhibitors of the isoenzyme CYP3A4 increase the concentration of ruxolitinib and lengthen its half-life. With their simultaneous use, the dose of Jakavi should be reduced by about 50%, patients should be closely monitored for a decrease in the number of blood cells and, if necessary, the dose should be adjusted.
With the simultaneous use of mild and moderate inhibitors of the CYP3A4 isoenzyme (for example, erythromycin), the total concentration of ruxolitinib increases slightly, but dose adjustment of Jakavi is not required, only careful observation of patients and an assessment of the number of blood cells is recommended.
In the case of the combined use of inducers of the isoenzyme CYP3A4 at the beginning of treatment, dose adjustment of ruxolitinib is not required, however, if the effectiveness of Jakavi decreases, a gradual increase in its dose may be required.
In healthy volunteers who received a powerful inducer of the CYP3A4 isoenzyme rifampicin in a daily dose of 600 mg (in 1 dose) for 10 days, the total dose of ruxolitinib with its single dose per day decreased by 71%, and the half-life decreased to 1.7 hours (from 3, 3 h). The relative amount of active metabolites increased in relation to the starting substance.
With the simultaneous appointment of P-glycoprotein or other transporters, dose adjustment is not recommended.
Analogs
There is no information about Jakavi analogues.
Terms and conditions of storage
Keep out of the reach of children. Do not exceed a storage temperature of 30 ° C.
Shelf life of tablets in blisters - 1 year, tablets in jars - 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
