The daily dose of KANSIDAS® is administered to adults (> 18 years) by slow intravenous infusion (> 1 hour) once a day.
Empirical Therapy
On the first day, a single loading dose of 70 mg is given, on the second and subsequent days of treatment, the daily dose is 50 mg per day. The duration of treatment depends on the clinical and microbiological effectiveness of the drug. Empirical therapy should be carried out until neutropenia is completely resolved. When confirming a fungal infection, patients should receive the drug for at least 14 days; therapy with KANSIDAS® should be continued for at least 7 days after the disappearance of clinical manifestations of both fungal infection and neutropenia. The daily dose of the drug KANSIDAS® can be increased to 70 mg if the daily dose of 50 mg is well tolerated by the patient, but does not give the expected clinical effect. Despite the fact that an increase in the daily dose to 70 mg did not demonstrate an increase in efficacy, the safety data suggest that taking the drug at the above dose is well tolerated.
Invasive Candidiasis
On the first day, a single loading dose of 70 mg is given, on the second and subsequent days of treatment, the daily dose is 50 mg per day. The duration of treatment of invasive candidiasis is determined by the clinical effect and microbiological efficacy. The general rule is the continuation of antifungal therapy for at least 14 days after the last receipt of blood culture. Patients with persistent neutropenia may require longer treatment prior to resolution of neutropenia.
The safety and efficacy of repeated use of daily doses up to 150 mg (range: 1 to 51 days, mean: 14 days) were studied in 100 adult patients with invasive candidiasis. A high dose of the drug KANSIDAS ® was generally well tolerated by patients, however, the effectiveness of the drug at a high dose was generally similar to the efficacy of the drug in patients taking the drug at a daily dose of 50 mg.
Invasive aspergillosis
On the first day, a single loading dose of 70 mg is given, on the second and subsequent days of treatment, the daily dose is 50 mg per day.
The duration of treatment depends on the severity of the underlying disease, the degree of recovery of the patient from immunosuppression and the clinical effect. Information on the efficacy of administering a daily dose of 70 mg to patients in whom a daily dose of 50 mg does not lead to the expected clinical response is absent. Safety data indicates good tolerability with an increase in the daily dose of up to 70 mg. The efficacy of doses above 70 mg in patients with invasive aspergillosis is not well understood.
Esophageal and oropharyngeal candidiasis
The daily dose is 50 mg per day, therapy should be continued at least 7-14 days after the disappearance of symptoms. Information on the effectiveness of loading dose 70 mg is not available.
Elderly patients
Elderly patients (65 years and older) do not need dose adjustment.
Decreased kidney function, sexual and racial differences
Do not require dose adjustment.
Patients with hepatic insufficiency
Adults with mild hepatic insufficiency (5-6 points on the Child-Pugh scale) do not need dose adjustment.For liver failure of moderate degree (from 7 to 9 on the Child-Pugh scale), the maintenance daily dose of the drug KANSIDAS® decreases to 35 mg per day (based on pharmacokinetic data), but the loading dose of 70 mg on the first day of treatment is preserved if there are appropriate indications.
Clinical experience in the use of the drug in adult patients with severe hepatic insufficiency (more than 9 on the Child-Pugh scale) does not.
With the simultaneous use of the drug CANDIDAS® from inducers of clearance of drugs (rifampicin, efavirenz, nevirapine, phenytoin, dexamethasone or carbamazepine) should consider the possibility of increasing the daily dose of KANSIDAS ® to 70 mg / m2 for this group of patients (but not exceeding the permissible dose of 70 mg).
Children
The daily dose of KANSIDAS® is administered to children (from 3 months to 18 years) by slow intravenous infusion (> 1 hour) once a day.
The dose of the drug is calculated taking into account the body surface area of the patient according to the Mosteller formula (see "Preparation of KANSIDAS® Solution for Intravenous Infusions for Children").
For all indications on the first day, a single loading dose of 70 mg / m2 (should not exceed the permissible dose of 70 mg), in the following days - 50 mg / m2 per day (should not exceed the permissible dose of 70 mg). The duration of therapy is determined individually and depends on the indication to the appointment (see general recommendations for use in adult patients in this section).
The daily dose of KANSIDAS® can be increased to 70 mg / m2 In the event that the daily dose of 50 mg / m2 well tolerated by the patient, but does not give the expected clinical effect (should not exceed the allowable dose of 70 mg). Despite the fact that an increase in the daily dose to 70 mg /m2 did not demonstrate an increase in efficacy, safety data suggest that taking the drug at the above dose has good tolerability.
When KANSIDAS® is used simultaneously with drug clearance inducers (rifampicin, efavirenz, nevirapine, phenytoin, dexamethasone or carbamazepine), the possibility of increasing the daily dose of KANSIDAS® to 70 mg / m2 for children (but not exceeding the permissible dose of 70 mg).
The clinical experience of the drug in children with any degree of liver failure is not.
Use in children
The efficacy and safety of the use of KANSIDAS® in children from 3 months to 18 years correlates with a sufficient evidence base for clinical trials in adult patients, pharmacokinetics in children and additional prospective studies data, on the basis of which the drug is successfully used in children for the same indications as and in adult patients (see section "Indications for use").
There is no data on the safety and efficacy of KANSIDAS® in newborn infants and children less than 3 months of age.
Instructions for preparing a solution
Do not use solvents containing dextrose (α-D- glucose), because in infusion solutions containing dextrose, KANSIDAS® is unstable.
KANSIDAS® is not mixed and not administered concomitantly with any other medications, since there is no evidence of its compatibility with other drugs for intravenous administration.
A ready-made infusion solution should be inspected to ensure that there are no suspended particles or discoloration.
Preparation of KANSIDAS® solution for intravenous infusions for adults
Step 1. Preparation of the primary solution in the vial
Before dilution, a cold vial of KANSIDAS® should be brought to room temperature and, under aseptic conditions, add 10.8 ml of one of the following solvents: sterile water for injection, 0.9% solution of sodium chloride for infusions, bacteriostatic water for injection with methylparaben, propylparaben or bacteriostatic water for injections with 0.9% gasoline alcohol. The concentration of the drug in the solution is 7.0 mg / ml (bottle 70 mg) or 5.0 mg / ml (50 mg bottle).
The white or almost white powder of the drug KANSIDAS® should completely dissolve. Gently stir the contents of the vial until a clear solution is obtained. Inspect the primary solution to ensure that there is no suspended sediment or discoloration. Prepared in this way, the primary solution can be stored in a vial for up to 24 hours at a temperature of no higher than 25 ° C.
Step 2. Preparation of the final infusion solution of the drug KANSIDAS®
Solution for infusion is prepared in conditions of compliance with asepsis.As solvents used 0.9% solution of sodium chloride for infusion or Ringer's solution with lactate. To prepare a final infusion solution for administration to a patient, into a plastic infusion bag or vial containing 250 ml of an infusion solvent (sterile 0.9% sodium chloride solution for infusion or Ringer's lactate solution), an appropriate amount of the primary solution prepared in step 1 of the drug KANSIDAS® (as shown in Table 2 below). When a daily dose of 50 mg or 35 mg is administered, the volume of the added solvent can be reduced to 100 ml.
Do not use a cloudy or precipitated solution.
The final final infusion solution must be used:
- for 24 hours when stored at room temperature (not above 25 ° C);
- for 48 hours when stored in a refrigerator (2-8 ° C).
CANCIDAC® is administered by slow intravenous infusion (> 1 hour).
Table 2. Preparation of the final infusion solution KANSIDAS®
| Dose* The drug KANSIDAS® | Volume of the primary solution of the preparation KANSIDAS® for addition in a container with a solvent for intravenous infusion | Standard Intelligence (the primary solution of the preparation KANSIDAS® + 250ml solvent), the concentration of the final infusion solution | Reduced volume dilution (the primary solution of the preparation KANSIDAS® +100 ml solvent), the concentration of the final infusion solution |
| 70 mg | 10 ml | 0.27 mg / ml | Not recommended |
| 70 mg (from 2 flus to 50 mg) ** | 14 ml | 0.27 mg / ml | Not recommended |
| 50 mg | 10 ml | 0.19 mg / ml | 0.45 mg / ml |
| 35 mg (from 1 vial of 70 mg) with moderate hepatic insufficiency | 5 ml | 0.14 mg / ml | 0.33 mg / ml |
| 35 mg (from 1 vial of 50 mg) with moderate hepatic insufficiency | 7 ml | 0.14 mg / ml | 0.33 mg / ml |
* 10.8 ml of the solvent is always added to the bottle of KANSIDAS ® regardless of its dose (50 mg or 70 mg)
** in the absence of a 70 mg dose, a dose can be prepared from 2 50 mg bottles
Preparation of KANSIDAS® solution for intravenous infusions for children
Determination of body surface area (PPT) for dose calculation in children
Before preparing the infusion solution, it is necessary to calculate the body surface area (PPT) of the child according to the following formula (Mosteller formula):
PPT (m2) = The square root of [Height (cm) х Weight (kg) / 3600]
Preparing the drug for administration to children over the age of 3 months (using a 70 mg bottle)
1.Determine the required loading dose for the child using the PPT (calculated as described above) and the following equation:
Load dose = PPT (m2) x 70 mg / m2
The maximum loading dose on the first day of treatment should not exceed 70 mg, regardless of the estimated dose for this patient.
2. Before dilution, a cold vial of KANSIDAS® should be brought to room temperature.
3. Under aseptic conditions, add 10.5 ml of one of the following solvents: sterile water for injection, 0.9% solution of sodium chloride for infusions, bacteriostatic water for injection with methylparaben, propylparaben or bacteriostatic water for injections with 0.9% benzyl alcohol. Prepared in this way, the primary solution can be stored in a vial for up to 24 hours at room temperature not higher than 25 ° C. The concentration of the drug in the solution is 7.2 mg / ml.
4. A volume of the drug equal to the calculated loading dose is extracted from the vial (item 1). In aseptic conditions, transfer this volume (ml) of the reconstituted KANSIDAS® preparation into an IV infusion tank containing 250 ml of 0.9%, 0.45% or 0.225% solution of sodium chloride for injection, or Ringer's lactate for injection solution.If necessary, the volume of the added solvent can be reduced so that the final concentration of the drug does not exceed 0.5 mg / ml.
The ready-made infusion solution should be used within 24 hours when stored at a temperature of no higher than 25 ° C or for 48 hours when stored in a refrigerator at 2-8 ° C.
5. If the loading dose value, determined by the above formula, is less than 50 mg, then you can prepare the infusion solution from the 50 mg bottle (see paragraphs 2-4 of the section "Preparation of the drug for administration to children over the age of 3 months (using bottle 50 mg) "). When using a 50 mg bottle, the concentration of the drug in the primary solution is 5.2 mg / ml.
Preparation of the drug for administration to children over the age of 3 months (using a 50 mg bottle)
1. Determine the daily support dose necessary for the child using the PPT (calculated as described above) and the following equation:
Daily maintenance dose = PPT (m2) х 50 mg / m2
The daily maintenance dose should not exceed 70 mg, regardless of the estimated dose for this patient.
2. Before dilution, a cold vial of KANSIDAS® should be brought to room temperature.
3. Under aseptic conditions, add 10.5 ml of one of the following solvents: sterile water for injection, 0.9% solution of sodium chloride for infusions, bacteriostatic water for injection with methylparaben, propylparaben or bacteriostatic water for injections with 0.9% benzyl alcohol. Prepared in this way, the primary solution can be stored in a vial for up to 24 hours at room temperature not higher than 25 ° C. The concentration of the drug in the solution is 5.2 mg / ml.
4. A volume of the drug equal to the calculated loading dose is extracted from the vial (item 1). In aseptic conditions, transfer this volume (ml) of the reconstituted KANSIDAS® preparation into an IV infusion tank containing 250 ml of 0.9%, 0.45% or 0.225% solution of sodium chloride for injection, or Ringer's lactate for injection solution. If necessary, the volume of the added solvent can be reduced so that the final concentration of the drug does not exceed 0.5 mg / ml.
The ready-made infusion solution should be used within 24 hours when stored at a temperature of no higher than 25 ° C or for 48 hours when stored in a refrigerator at 2-8 ° C.
5. If the calculated daily maintenance dose is more than 50 mg, then a 70 mg vial can be used (see Fig.above items 2 ^ 1 of the section "Preparing the preparation for administration to children over the age of 3 months (using the 70 mg bottle)"), the concentration of the drug in the primary solution being 7.2 mg / ml.