The drug Giacavi® take inside, regardless of time food intake.
If you need to use the drug in doses other than 10 mg, you should use the drug Giacavi® in the form of tablets 5 mg, 15 mg, 20 mg.
Initial dose
The recommended initial dose of Jakavi ® in the treatment of patients with myelofibrosis is 15 mg 2 times a day for patients with a platelet count of 100-200 x 109/ l; and 20 mg twice daily for patients with platelet count> 200 x 109/ l.
The maximum recommended initial dose in patients with platelet counts 50-100 x 109/ l is 5 mg 2 once a day inside, followed by correction dose that is performed with caution (see Table 1).
Table 1. The recommended initial dose of the drug Jakavi® in the treatment of patients with myelofibrosis
| Number of platelets | Initial dose |
| >200 x 109 | 20 mg 2 times a day |
| 100-200 x 109 | 15 mg 2 times a day |
| 50 - less than 100 x 109 | 5 mg 2 times a day |
The recommended initial dose of Jakavi® in the treatment of patients with true polycythemia is 10 mg 2 times a day inside.
Dose selection
Dose of Jakavi® is adjusted based on the safety and effectiveness of the treatment. Treatment of patients with myelofibrosis should be suspended if a platelet count is less than 50 x 109/ l or with a decrease in the absolute number of neutrophils less than 0,5 x 109/ l.
After the restoration of the platelet count and neutrophils above these values, the use of the Giacavi® preparation can be resumed at a dose of 5 mg twice a day, a further gradual increase in the dose with a careful control of the amount shaped blood elements (see Table 2).
Table 2. Myelofibrosis: the maximum dose of the drug Giacavi® with the resumption of therapy after suspension of its use due to thrombocytopenia (for patients with a platelet count of 100 x 109/ l and more to the beginning of therapy)
| Number of platelets | The maximum dose of the drug Giacavi® with the resumption of therapy |
| 125 x 109/ l and more | 20 mg 2 times a day |
| 100 - less than 125 х 109/ l | 15 mg 2 times a day |
| 75 - less than 100 х 109/ l | 10 mg 2 times a day for 2 weeks minimum; further, with the preservation of the number of platelets, it is possible to increase to 15 mg 2 times a day |
| 50 - less than 75 x 109/ l | 5 mg 2 times a day for 2 weeks minimum; further, if the number of platelets is maintained, it is possible to increase to 10 mg 2 times a day |
| less than 50 x 109/ l | Suspension of use |
* When resuming the use of the drug, Giacavi® should be started with a dose of at least 5 mg twice a day below that used before the suspension of its use.
It is recommended to reduce the dose of the drug with a decrease in the number of platelets less than 100 x 109/ l, in order to avoid the suspension of therapy due to developed thrombocytopenia (see Table 3).
Table 3. Myelofibrosis: the recommended dose of the drug Giacavi® (for patients with a platelet count of 100 x 109/ l and more to the beginning of therapy)
| | Dose, used before the decrease in the number of platelets |
| amount platelets
| 25 mg 2 times a day | 20 mg 2 times a day | 15 mg 2 times in day
| 10 mg 2 times in day
| 5 mg 2 times a day |
| Reduced dose
| Reduced dose
| Reduced dose
| Reduced dose
| Reduced dose
|
| 100 - less than 125 x 109/ l
| 20 mg 2 times a day | 15 mg 2 times a day | Without changes
| Without changes
| Without changes
|
| 75 - less 100 x 109/ l
| 10 mg 2 times a day | 10 mg 2 times a day | 10 mg 2 times in day
| Without changes
| Without changes
|
| 50 - less than 75 x 109/ l
| 5 mg 2 times a day | 5 mg 2 times a day | 5 mg 2 times in a day
| 5 mg 2 times in a day
| Without changes
|
| less 50 x 109/ l | Suspension applications | Suspension applications | Suspension applications | Suspension applications | Suspension applications |
Consideration should be given to reducing the dose with a decrease in hemoglobin concentration in the blood of <120 g / l in patients with true polycythemia, with a decrease in hemoglobin concentration in the blood <100 g / l - a dose reduction is recommended.
Treatment should be suspended with a decrease in hemoglobin concentration in the blood <80 g / l in patients with true polycythemia (see Table 4).
Table 4. Dose reduction in patients with true polycythemia
| The concentration of hemoglobin and / or the number of platelets | Recommended dose |
| The concentration of hemoglobin ≥ 120 g / l and the number of platelets ≥ 100 x 109/ l | Dose correction is not required |
| The concentration of hemoglobin 100 - <120 g / l and the number of platelets 75 <100 x 109/ l | Consider the possibility of reducing the dose of the drug, in order to avoid the suspension of therapy due to developing anemia and thrombocytopenia. |
| Concentration of hemoglobin 80 - <100 g / l OR number of platelets 50 - <75 х 109/ l | Reduction of the dose by 5 mg 2 times a day. Have of patients taking 5 mg twice daily, a dose reduction of up to 5 mg once daily is recommended. |
| Concentration of hemoglobin <80 g / l OR number of platelets <50 x 109/ l | Suspension applications |
In case of therapeutic necessity, and if the number of platelets and neutrophils in patients with myelofibrosis or hemoglobin concentration in patients with true polycythemia is sufficient, the dose of the drug Giacavi® can be increased as much as 5 mg 2 times a day, up to a maximum dose of 25 mg 2 times a day.
Do not increase the initial dose of the drug in during the first 4 weeks of treatment, and then no more often than 1 time in 2 weeks.
The maximum dose of the drug Giacavi® is 25 mg 2 times a day inside.
In case of missed intake of the next dose of the drug, the patient should not take an additional dose, the next dose should be taken at the usual prescribed time.
Treatment with the drug is continued as long as the therapeutic effect remains.
Monitoring Recommendations
Counting blood cells: Before calculating the Giacavi® preparation, the number of blood cells should be counted.
Absolute number of blood elements should be monitored every 2-4 weeks during the selection of the dose of rutzolitinib and further on the clinical indications.
Correction of the dose while using powerful inhibitors of the isoenzyme CYP3A4 or fluconazole
In the case of simultaneous application with potent inhibitors of the isoenzyme CYP3A4 (clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir / ritonavir, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice) or with double moderate inhibitors of CYP2C9 and CYP3A4 isoenzymes (for example, fluconazole), the total daily dose of the Giacavi® preparation should be reduced by approximately 50%, by decreasing the daily dose divided into 2 doses, or by appropriately reducing the frequency of administration to 1 time per day (in the case that such a regimen is possible). It should avoid simultaneous use of the drug with fluconazole at a dose of more than 200 mg per day. More frequent monitoring of hematological parameters and clinical signs and symptoms associated with adverse reactions to the Giacavi® preparation is recommended at the beginning of simultaneous use of potent inhibitors of the CYP3A4 isoenzyme or double moderate inhibitors of the CYP2C9 and CYP3A4 isoenzymes (see Table 5).
Table 5. Correction of the dose while using powerful inhibitors of the isoenzyme CYP3A4 or double moderate inhibitors of isoenzymes CYP2C9 and CYP3A4
| The use of the drug Giacavi® simultaneously with powerful inhibitors CYP3A4 | Recommended dose adjustment |
| Initial dose in patients with myelofibrosis and platelet count |
| 100 x 109/l and more | 10 mg 2 times a day |
| 50 - less than 100 х 109/l | 5 mg once a day |
| Initial dose in patients with true polycythemia | 5 mg 2 times a day |
| Patients taking the drug at a dose established on the basis of safety and effectiveness of the treatment: | |
| ≥10 mg 2 times a day | Dose reduction by 50% |
| 5 mg 2 times a day | 5 mg once a day |
| 5 mg once a day | It is necessary to stop the use of powerful inhibitors CYP3A4 or the preparation Giacavi® for the period of application of powerful inhibitors CYP3A4 |
Special patient groups
Impaired renal function
In patients with myelofibrosis Mr. a violation of the function of heavy-colored nights (QC less than 30 ml / min) the recommended initial dose based on the number of platelets, should be reduced by approximately 50%. The recommended initial dose for treatment of patients with true polycythemia and impaired renal function of severe degree is 5 mg 2 times a day inwards.
Patients with impaired renal function of severe degree receiving the preparation of Giacavi ® should be carefully observed, if necessary, the dose of the drug should be reduced in order to avoid the development of unwanted drug reactions.
There are limited data on the use of rutzolithinib in patients with terminal stage of renal failure on hemodialysis. In this category of patients with myelofibrosis, treatment should start with a single dose of 15 mg or 20 mg (based on the number of platelets) followed by single doses only after each hemodialysis and with a thorough assessment of the benefit / risk ratio.
In patients with true polycythemia and terminal stage of renal failure on hemodialysis treatment should start with a single dose of 10 mg after hemodialysis procedures only on the day of its conduct with careful monitoring of the condition and evaluation of the benefit / risk ratio (see Table 6).
Table 6. The recommended dose of Jakavi® in patients with impaired renal function
| Degree of severity of renal dysfunction | amount platelets
| Recommended initial dose |
| Patients with myelofibrosis: Average (QC 30-59 ml / min) or Heavy (SC 15-29 ml / min) | More 150 x 109/ l | Dose correction is not required |
| 100x109/ l - 150 x 109/ l | 10 mg 2 times a day |
| 50 - less than 100 х 109/ l | 5 mg once a day |
| Less 50x109/ l | Suspension of use |
| Patients with true polycythemia: Average (QC 30-59 ml / min) or Heavy (SC 15-29 ml / min) | Any | 5 mg 2 times a day |
Impaired liver function
In patients with impaired hepatic function, the recommended initial dose, based on the number of platelets, should be reduced by approximately 50%. Patients with diagnosed severe liver dysfunction who receive Giacavi ® should be carefully observed, if necessary, the dose of the drug should be reduced to avoid the development of unwanted drug reactions (see Table 7).
Table 7. Recommended dose of Giacavi® in patients with impaired hepatic function
| Degree of severity of liver dysfunction | Number of platelets | Recommended initial dose |
| Patients with myelofibrosis: mild, moderate or severe (class A, B or C for Child-Pugh classification)
| More 150 x 109/ l | Dose correction is not required |
| 100 х109/ l - 150 x 109/ l | 10 mg 2 times a day |
| 50 - less than 100 x109/ l | 5 mg once a day |
| Less 50 x 109/ l | Suspension of use |
| Patients with true polycythemia: mild, moderate or severe (class A, B or C by Child-Pugh classification)
| Any | 5 mg 2 times a day |
Patients aged ≤ 18 years
The safety and efficacy of Giacavi® in patients <18 years of age have not been established.
Patients ≥65 years of age
TOdosage adjustment is not required.