The drug Vaidaz is injected subcutaneously into the area of the shoulder, hip, or abdomen. Place of injection should alternate. Place for the next injection should be more than 2.5 cm from the previous one. Vaidase should not be injected into damaged, hyperemic, dense or painful skin areas (including areas of skin with hemorrhages).
Before the introduction of the drug Vaidas recommended to appoint antiemetics.
The recommended initial dose of Vaidas preparation for the first cycle of therapy for all patients, regardless of the values of the initial hematological parameters, is 75 mg / m2 surface of the body. The drug is administered daily for 7 days followed by a break of 21 days (28-day therapeutic cycle).
At least 6 therapeutic cycles should be performed. Treatment is continued as long as its effectiveness remains or until symptoms of disease progression appear.
During the observation of patients, the response from the blood counts and possible manifestations of toxicity,in particular from the blood and kidneys, which may require the postponement of the next course of treatment or a change in the dose of the drug. Below are presented the possibilities of changing the dose of Vaidaz preparation for the development of various types of toxicity.
Dose change in detecting symptoms of hematologic toxicity
Hematologic toxicity is considered to be the maximum reduction in cell number during a given cycle of treatment (nadir), if the platelet count is reduced to 50.0 x 109 l and below and / or the absolute number of neutrophils (AFN) decreases to 1 x 109/ l and below.
Reduction considered increasing the number of cells in the cell line (s) (s) on at least half of the difference between the initial number of cells and the nadir (i.e., the number of cells in the recovery ≥ nadir + (0.5 x [original number - nadir]).
Patients with the initial (before the start of therapy with the drug Vaidaz) indicators of the number of leukocytes ≥3.0 x 109/ l, the absolute number of neutrophils ≥1.5 x 109/ l, the number of platelets ≥75.0 x 109/ l
If Vaydaza background of treatment in these patients develop symptoms of hematological toxicity, the next cycle of drug treatment delayed until recovery platelet counts and absolute neutrophil count to the initial values.If the duration of the recovery period does not exceed 14 days, a change in the dose of the drug is not required. If the amount of blood cells has not increased to the desired value within 14 days, the dose should be reduced according to the guidelines outlined below. When using an altered dose, the duration of the therapy cycle should be restored to 28 days.
| Number of blood cells | % from the initial dose for the next cycle, if recovery * of the number of blood cells took more than 14 days |
| Absolute number of neutrophils | Number of platelets |
| ≤ 1.0 x 109/ l | ≤ 50,0 х 109/ l | 50% |
| > 1.0 x 109/ l | > 50.0 x 109/ l | 100% |
* Recovery = Number (number) ≥ min # of + (0.5 x [k-in Initial - a minimum quantity])
Patients with baseline (before the start of therapy with Vaidaz) with white blood cell count <3.0 x 109/ l, the absolute number of neutrophils <1.5 x 109/ l, the number of platelets <75.0 x 109/ l
If before another course of treatment Vaydaza a decrease in the number of leukocytes, or an absolute number of neutrophils or platelets less than or equal to 50% of their original values, or more than 50%, but with evidence of improved differentiation of any cell germ administration Vaydaza preparation circuit and dose not must change.
Patients in whom the number of blood cells did not exceed 50% of the threshold from the baseline in the absence of signs of improvement in differentiation of cell sprouts, the next course of treatment with Vaidaz should be delayed until the absolute number of neutrophils and platelets is restored. If the recovery process took no more than 14 days, a change in the dose of Vaidaz is not required. If the number of blood cells did not reach the desired level within 14 days, it is necessary to determine the cellular saturation of the bone marrow. With a cell saturation index> 50%, no change in the dose of the drug is required. If the cellular saturation of the bone marrow is ≤50%, the administration of Vaidaz should be delayed and the dose reduced according to the recommendations given in the table:
| Cellular saturation of bone marrow | % of the initial dose for the next cycle, if recovery * the number of blood cells took more than 14 days |
| | Recovery * ≤21 days | Recovery * > 21 days |
| 15-50% | 100% | 50% |
| <15 | 100% | 33% |
* Recovery = amount (number) ≥ minimum quantity + (0.5 x [Source code - the minimum number])
After the dose change, the cycle time must be restored to 28 days.An example of calculating an individual dose of azacitidine is shown in the table below:
| m2 body surface | 100% of the recommended initial dose (75 mg / m2) | 50% of the recommended initial dose (37.5 mg / m2) | 33% of the recommended initial dose (25 mg / m2) |
| | Daily dose | Volume of solution | Daily dose | Volume of solution | Daily dose | Volume of solution |
| 1,4 | 105 mg | 4.2 ml ** | 52.5 mg | 2.1 ml | 35 mg | 1.4 ml * |
| 1,5 | 112.5 mg | 4.5 ml ** | 56.25 mg | 2.25 ml * | 37.5 mg | 1.5 ml * |
| 1,6 | 120 mg | 4.8 ml ** | 60 mg | 2.4 ml * | 40 mg | 1.6 ml * |
| 1,7 | 127.5 mg | 5.1 ml ** | 63.75 mg | 2.55 ml * | 42.5 mg | 1.7 ml * |
| 1,8 | 135 mg | 5.4 ml ** | 67.5 mg | 2.7 ml * | 45 mg | 1.8 ml * |
| 1,9 | 142.5 mg | 5.7 ml ** | 71.25 mg | 2.85 ml * | 47.5 mg | 1.9 ml * |
* 1 bottle containing 100 mg of azacitidine
** 2 vials containing 100 mg of azacitidine
Application featuresI in certain groups of patients
Use in patients with impaired renal function
Do not change the starting dose of azacitidine in patients with impaired renal function (see section "Pharmacokinetics"). With an unexplained decrease in serum bicarbonate concentration of less than 20 mmol / L, the dose for the next cycle of therapy should be reduced by 50%. If there is an unexplained increase in serum creatinine concentration or a concentration of urea nitrogen in the blood 2 or more times from baseline values or above the upper limit of the norm, another cycle of therapy should be postponed until these parameters are restored tonormal or initial values, and the dose of the drug in the next cycle should be reduced by 50%.
Use in patients with impaired liver function
Special studies in patients with impaired liver function were not performed. The condition of patients with severe hepatic insufficiency should be carefully monitored in order to detect undesirable events in a timely manner. This category of patients does not need to change the initial dose of the drug. The subsequent dose change will depend on the results of the blood test.
Elderly patients
Elderly patients do not need a special dosing regimen.
Since elderly patients are more likely to have impaired renal function, it is recommended that kidney function be monitored during treatment.
Children and teens
Vaidaz is not recommended for children under the age of 18 due to lack of clinical experience.
RECOMMENDATIONS FOR PREPARATION OF SOLUTION AND INJECTION
The contents of the vial with the drug are dissolved in 4 water for injection to a concentration of 25 mg / 1 ml. After adding water to the injection bottle, it must be shaken vigorously until a homogeneous white suspension is obtained.If the required dose exceeds 100 mg, use 2 bottles of the drug.
Immediately prior to administration, it is necessary to re-translate the contents of the syringe into the suspension state. To do this, vigorously roll the syringe between the palms until a homogeneous white suspension is obtained. The temperature of the suspension during the injection should be 20-25 ° C. Do not use if it contains large particles.
For subcutaneous injection, a 25 gauge needle is recommended, with the needle inserted under the skin of the shoulder, hip or abdomen at an angle of 45-90 °. No more than 4 ml of the dissolved preparation is injected into one area. Doses greater than 4 ml should be administered in 2 different areas.
A suspension of Vaidase preparation should be prepared immediately before use.
The ready-made suspension should be stored at a temperature of no more than 25 ° C for 45 minutes or at a temperature of 2 ° C to 8 ° C not more than 8 hours. Before administration, allow the syringe to reach a temperature of 20-25 ° C (but not more than 30 minutes). If these time limits are exceeded, the prepared suspension must be destroyed accordingly, a new suspension must be prepared in return for it.