Lyophilizate for the preparation of a solution for infusions in the form of a solid mass from white to almost white.
1 f.
caspofungin acetate 60.6 mg,
which corresponds to the content of caspofungin (in the form of anhydrous base) 54.6 mg *
Excipients: sucrose 39 mg, mannitol 26 mg, acetic acid ice 2 mg, sodium hydroxide qs up to pH 6.
Vials of colorless glass with a capacity of 10 ml (1) - packs of cardboard.
* including excess to ensure the appropriate dosage of the active substance (50 and 70 mg, respectively).
Lyophilizate for the preparation of a solution for infusions in the form of a solid mass from white to almost white.
1 f.
caspofungin acetate 83.9 mg,
which corresponds to the content of caspofungin (in the form of anhydrous base) 75.6 mg *
Excipients: sucrose - 54 mg, mannitol - 36 mg, acetic acid ice - 2.7 mg, sodium hydroxide - qs to pH 6.
Vials of colorless glass with a capacity of 10 ml (1) - packs of cardboard.
* including excess to ensure the appropriate dosage of the active substance (50 and 70 mg, respectively).
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2010.
PHARMACHOLOGIC EFFECT
Antifungal drug for systemic use. It is a semisynthetic lipopeptide compound (echinocandin) synthesized from the fermentation product Glarea lozoyensis.Caspofungin inhibits the synthesis of? - (1,3) -D-glucan - the most important component of the cell wall of many rifomycetes and yeast.
In vitro, caspofungin is active against various pathogenic fungi of the genus Aspergillus (including Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus nidulans, Aspergillus terreus and Aspergillus candidus) and Candida (including Candida albicans, Candida dubliniensis, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lipolytica, Candida lusitaniae, Candida parapsilosis, Candida rugosa and Candida tropicalis).
In vivo, caspofungin activity was detected in parenteral administration to animals with normal and reduced immunity infected with Aspergillus and Candida. The use of caspofungin in these cases promotes an increase in the lifespan of infected animals (Aspergillus and Candida) and the eradication of pathogenic fungi (Candida) in the affected organs. Also, caspofungin is active in animals with immunodeficiency, infected with Candida glabrata, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, in which eradication of pathogenic fungi (Candida) is achieved in the affected organs. Caspofungin is highly active in the prevention and treatment of pulmonary aspergillosis, which is revealed in studies on models of lethal lung infections in vivo.
Caspofungin is active against strains of Candida fungi resistant to fluconazole, amphotericin B or flucytosine, which have a different mechanism of action.
Some patients in the process of treatment with the drug are allocated species of Candida fungi with reduced sensitivity to caspofungin. The determination of the minimum inhibitory concentration (MPC) for caspofungin is not carried out, because there is no correlation between the MIC and the clinical efficacy of the drug.Drug resistance to the drug in patients with invasive aspergillosis is not noted.
Standardized methods for determining the sensitivity to the synthesis of? - (1,3) -D-glucan have not been established, and the results of in vitro sensitivity studies may not correlate with clinical data.
PHARMACOKINETICS
Distribution
After a single intravenous infusion for 1 hour, the concentration of caspofungin in the plasma decreases in a multiphase manner. Immediately after the infusion, a short? -phase follows, followed by a? -phase with T 1/2 from 9 to 11 hours, which is the main characteristic of the profile and has a distinct log-linear relationship between 6 and 48 hours after infusion. During this period, the concentration of the drug in the plasma is significantly reduced. There is also an additional? Phase with T 1/2 from 40 to 50 hours. The prevailing mechanism that influences plasma clearance is distribution rather than excretion or biotransformation. Caspofungin binds intensely to proteins (approximately 97%) with minimal penetration into erythrocytes. About 92% of the 3 H-label is found in the tissues 36-48 hours after the administration of a single dose of 70 mg of labeled 3 H caspofungin acetate. During the first 30 hours after administration, excretion and biotransformation of caspofungin are insignificant.
Metabolism
Caspofungin is slowly metabolized by hydrolysis and N-acetylation and subjected to spontaneous chemical destruction before the peptide compound with an open ring. At a later date (5 or more days after the administration of a single dose of labeled 3 H caspofungin acetate), a low level (less than 7 pmol / mg protein or 1.3% or less of the administered dose) of the covalent binding of the radioactive label is observed in the plasma, which may be due to formation of two reactive intermediates of chemical destruction of caspofungin. Additional metabolism involves hydrolysis to constituent amino acids and their derivatives, including dihydroxyhomotyrosine and N-acetyl-dihydroxyhomotyrosine. These two tyrosine derivatives are found only in the urine, which indicates their rapid renal clearance.
Excretion
About 75% of the drug is excreted from the body (pharmacokinetic study with radiolabeled caspofungin): 41% with urine and 34% with feces. Concentrations in plasma label and caspofungin during the first 24-48 hours after the dose are not different, after which the level of the drug decreases more rapidly, with a decrease in its concentration below the level of quantitation detected 6-8 days after the dose, and radioactive label - after 22.3 of the week. A small amount of caspofungin is excreted unchanged in the urine (approximately 1.4% of the dose). The kidney clearance of the initial drug is low and is approximately 0.15 ml / min.
Pharmacokinetics in special clinical cases
Concentration of caspofungin in plasma in healthy men and women on the 1st day after the administration of a single dose of 70 mg is the same. After 13 daily administrations of 50 mg, the concentration of caspofungin in plasma in some women is approximately 20% higher than in men.
The content of caspofungin in plasma in healthy men and women of advanced age (65 years and older), compared with healthy young men, slightly increased by 28% (AUC). In elderly patients with invasive candidiasis or during empirical therapy, the same moderate changes in the plasma concentration of the drug were observed, as in the healthy elderly group in relation to healthy young patients. Correction of the dosing regimen for the elderly (65 years and older) patients is not required.
The concentration of caspofungin in the plasma of patients with mild hepatic insufficiency (5-6 points on the Child-Pugh scale) after administration of a single dose of 70 mg increases by approximately 55% (AUC), compared to healthy volunteers. Administration of the drug to these patients for 14 days (70 mg on day 1 followed by daily administration of 50 mg) is accompanied by a moderate increase in its plasma concentration and is 19-25% (AUC) on the 7th and 14th day, compared with healthy volunteers.
Five long-term clinical trials were conducted with the study of Candidas В® in patients under 18 years of age, including drug pharmacokinetics studies (initially in adolescents (12-17 years) and children (2-11 years), then in young children (3-23 years) months), and in newborns and children of the first three months of life).
In adolescents (12-17 years) who received caspofungin at a dose of 50 mg / m 2 (maximum daily dose of 70 mg), the concentration in the blood plasma (AUC 0-24 h ) generally corresponded to the concentration in adults taking caspofungin at a dose of 50 mg / day. All adolescents received caspofungin at a dose above 50 mg, and 6 out of 8 patients received a maximum daily dose of 70 mg. The concentration of caspofungin in blood plasma in these patients was lower compared to the concentration in adults receiving the drug at a daily dose of 70 mg, exactly the dose that was most often prescribed to adolescents.
In children aged 2-11 years who received caspofungin at a dose of 50 mg / m 2 per day (maximum daily dose of 70 mg), its concentration in blood plasma (AUC 0-24) was comparable to that in adult patients who received caspofungin in a dose of 50 mg / day. On the first day of application, the concentration of the drug in blood plasma (AUC 0-24 ) was slightly higher in children than in adults (by 37% at comparable doses of 50 mg / m 2 and 50 mg 1 time / day). However, it must be emphasized that the concentration in blood plasma (AUC 0-24 ) in children on the first day was still lower than in adults with prolonged treatment.
In children aged 3-23 months, who received caspofungin at a daily dose of 50 mg / m 2 (maximum dose of 70 mg), the concentration of caspofungin in blood plasma for prolonged use was comparable to the concentration in adults who received a dose of 50 mg / day. As with older children, in children of this age group who received caspofungin at a dose of 50 mg / m 2 , the concentration of the drug in the blood plasma was higher on the first day of treatment compared with adults receiving a standard dose of caspofungin 50 mg. The pharmacokinetic parameters of caspofungin at a dose of 50 mg / m 2 in children of the younger age group (3-23 months) and in the older group (2-11 years) with comparable dosing regimens were comparable.
In newborns and children up to 3 months, who received caspofungin at a dose of 25 mg / m 2 , the peak concentration of caspofungin (C 1h ) and its threshold concentration (C 24h ) after repeated injections corresponded to those in adults who received the drug at a dose of 50 mg / day. On the first day, the peak concentration of C 1h was comparable to that of adults, and the threshold concentration C 24h was moderately increased in newborns and infants compared to the corresponding values ​​in adults. Determination of the concentration of the drug in the blood plasma (AUC 0-24 ) was not performed in this study due to the difficulties in sampling. It should be noted that the study of efficacy and safety during prospective adequate clinical trials of the drug Kansidas ® in newborns and children under 3 months was not carried out.
INDICATIONS
- empirical therapy in patients with febrile neutropenia in case of suspected fungal infection;
- Invasive candidiasis (including candidemia) in patients with neutropenia and without it;
- Invasive aspergillosis (in patients refractory to other therapy or not tolerating it);
- esophageal candidiasis;
- oropharyngeal candidiasis.
DOSING MODE
The daily dose of Cancidas is administered by slow intravenous infusion (1 hour) 1 time / day.
With empirical therapy , a single loading dose of 70 mg is administered on the first day, the daily dose at the second and subsequent days of treatment is 50 mg / 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 should be continued by Cancidas at least 7 days after the disappearance of clinical manifestations of both fungal infection and neutropenia. Existing data on safety and tolerability of Cancidas can increase the daily dose to 70 mg if the daily dose of 50 mg is well tolerated by the patient, but does not give the expected clinical effect.
In case of invasive candidiasis, a single loading dose of 70 mg is administered on the first day of therapy, on the second and subsequent days of treatment, the daily dose is 50 mg / 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.
In case of invasive aspergillosis, a single loading dose of 70 mg is administered on day 1, on a second and subsequent days of treatment, the daily dose is 50 mg / day.The duration of treatment depends on the severity of the underlying disease, the degree of recovery of the patient from immunosuppression, the clinical and microbiological effect of the therapy.
Existing data on safety and tolerability of Cancidas can increase the daily dose to 70 mg if the daily dose of 50 mg is well tolerated by the patient, but does not give the expected clinical effect.
With esophageal and oropharyngeal candidiasis, the daily dose is 50 mg / day on all days of treatment.
Patients older (65 years and older) dose adjustment is not required.
It is not necessary to correct the dosage regimen when prescribing the drug to patients with impaired renal function , and also for sexual and racial differences.
Patients with mild hepatic insufficiency (5-6 points on the Child-Pugh scale) do not need dose adjustment. With moderate hepatic insufficiency (from 7 to 9 points on the Child-Pugh scale) the maintenance daily dose of Candidasa decreases to 35 mg / day, but with appropriate indications a loading dose of 70 mg remains in the first day of therapy. The clinical experience of the drug in patients with severe hepatic insufficiency (more than 9 points on the Child-Pugh scale) is not present.
The daily dose of the drug Kansidas В® is administered to children (from 3 months to 17 years) by slow intravenous infusion (1 hour) 1 time / day.
The dose of the drug is calculated taking into account the body surface area of ​​the patient according to the Mosteller formula.
For all indications on the first day, a single loading dose of 70 mg / m 2 (not exceeding the permissible dose of 70 mg) is introduced, in the following days 50 mg / m2 per day (should not exceed the admissible dose of 70 mg). The duration of therapy is determined individually and depends on the indication to the destination.
The daily dose of Candidas В® can be increased to 70 mg / m 2 if the daily dose of 50 mg / m 2 is well tolerated by the patient, but does not give the expected clinical effect (should not exceed the admissible dose of 70 mg).
With simultaneous administration of Candidas В® with drug clearance inducers (rifampicin, efavirenz, nevirapine, phenytoin, dexamethasone or carbamazepine), the possibility of increasing the daily dose of Candidas В® to 70 mg / m 2 for this group of patients should be considered (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.
Preparation of the drug Kansidas В® for intravenous infusions for adults
Do not use solutions containing dextrose (AD-glucose), because in infusion solutions containing dextrose, Kansidas В® is unstable.
Cancidas В® is not mixed and not administered concomitantly with any other medicines, as there is no evidence of its compatibility with other drugs for IV administration.
Examine the finished infusion solution to make sure there are no suspended particles or discoloration.
Step 1. Preparation of the primary solution in the vial
Before dilution, the cold vial of powder should be brought to room temperature and, under aseptic conditions, add 10.5 ml of sterile water for injection (bacteriostatic water for injection, methylparaben, propylparaben or bacteriostatic water for injection with benzyl alcohol). The concentration of the drug in the primary solution will be 7 mg / ml (flask 70 mg) or 5 mg / ml (50 mg bottle).
White or almost white precipitate will completely dissolve. Gently mix the contents of the vial until a clear solution is obtained. Inspect the primary solution to ensure 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 below 25 В° C.
Step 2. Preparation of the final infusion solution
Solution for infusion is prepared in conditions of compliance with asepsis. The solvents used are sterile saline for infusion or Ringer's solution with lactate. To prepare the final infusion solution to be administered to the patient, in a plastic infusion bag or vial with an infusion solvent (sterile saline for infusions or Ringer's lactate solution) of 250 ml capacity, add the appropriate amount of the initial Cancidas solution prepared in step 1 (as shown in the table 1). If a daily dose of 50 mg or 35 mg is administered, the infusion volume can be reduced to 100 ml.
Do not use a cloudy or precipitated solution.
The finished final infusion solution should be used within 24 hours if it is stored at room temperature (below 25 В° C); for 48 hours when stored in a refrigerator (2-8 В° C).
Cancidas В® is administered by slow (? 1 h) IV infusion.
Table 1. Preparation of the final infusion solution of Candidas В®
Dose * of the drug The volume of the primary solution for addition to the tank with a solvent for intravenous infusion Standard dilution (250 ml of solvent);concentration of the final infusion solution dilution in a reduced volume (100 ml of solvent); concentration of the final infusion solution
70 mg 10 ml 0.27 mg / ml not recommended
70 mg (from 2 fl-50 mg) ** 14 ml 0.27 mg / ml is not recommended
50 mg 10 ml 0.19 mg / ml 0.45 mg / ml
35 mg (from 1 vial of 70 mg) under moderate hepatic impairment 5 ml of 0.14 mg / ml 0.33 mg / ml
35 mg (from 1 vial of 50 mg) under moderate hepatic impairment 7 ml 0.14 mg / ml 0.33 mg / ml
* - vial powder Cancidas always added 10.5 mL of a solvent regardless of the dose (50 mg or 70 mg).
** - In the absence of a vial 70 mg dose may be prepared from two vials of 50 mg.
Preparation of drug solution Cancidas В® for / in infusion children
cooking process drug solution Cancidas В® for / in children similar to the preparation of infusion solution for infusion adults. It includes the above two steps - the preparation of the primary and the final solution.
The main difference consists in determining the dose which is calculated according to the formula below, and takes into account the value of patient surface area.
Definition (TIC) of body surface area for dose calculation in children
Before preparing the infusion solution is necessary to calculate body surface area (BSA) of the child by the following formula (Mosteller formula):
BSA (m 2 ) = square root of: Height (cm)? Body weight (kg) / 3600
Preparation of the drug for use in children older than 3 months (using a vial of 70 mg)
Identify necessary for the child loading dose using PPT (calculated as described above) and the following equation:
BSA (m 2 )? 70 mg / m 2Loading dose =
Maximum loading dose on the first day of treatment should not exceed 70 mg, independently of the calculated dose to the patient.
Selection of the vial is determined by the dose quantity, in mg, which is scheduled to enter the child. To ensure the accuracy of dosing in children who require a dose not exceeding 50 mg is recommended to use vial containing 50 mg of the drug (caspofungin concentration 5.2 mg / ml). Vials containing 70 mg of caspofungin is recommended to stay for children who require a dose exceeding 50 mg.
Preparation of the solution for infusion in 2 phases - see Preparation solution. Drug Cancidas В® for / in infusion adults
Take from vial of the drug equal to the calculated loading dose. Aseptically transfer this amount (ml) of reconstituted drug Cancidas in the tank / in infusion containing 250 ml of 0.9%, 0.45% or 0.225% sodium chloride for injection, or lactated Ringer's solution for injection. If necessary, the final solution volume can be reduced so that the final drug concentration did not exceed 0.5 mg / ml.
Ready infusion solution should be used within 24 hours when stored at a temperature not higher than 25 В° C or within 48 hours when stored in a refrigerator at 2-8 В° C. If determined by the formula above, the value of the loading dose is less than 50 mg, then it is possible to prepare the infusion solution from the vial 50 mg (cm. Below partition Preparation preparation for administration to children over the age of 3 months (using flacon 50 mg). When using a vial 50 mg of the drug concentration in the initial solution will be 5.2 mg / ml.
Preparation of the drug to be administered to children at the age of 3 months (using 50 mg vial)
Determine necessary for the child daily maintenance dose, using BSA (calc tannuyu as described above) and the following equation:
BSA (m2 ) x 50 mg / m 2 = daily maintenance dose
daily maintenance dose should not exceed 70 mg, independently of the calculated dose to the patient.
Preparation of the solution for infusion in 2 phases - see Preparation drug solution Cancidas. В® for / in infusion adults.
Take from vial of the drug equal to the calculated daily maintenance dose. Aseptically transfer this amount (ml) of reconstituted drug Cancidas В®a tank / in infusion containing 250 ml of 0.9%, 0.45% or 0.225% sodium chloride for injection, or lactated Ringer's solution for injection. If necessary, the final solution volume can be reduced so that the final drug concentration did not exceed 0.5 mg / ml.
Ready infusion solution should be used within 24 hours when stored at a temperature not higher than 25 В° C or within 48 hours when stored in a refrigerator at 2-8 В° C.
If the calculated daily maintenance dose of 50 mg, is possible to use a 70 mg vial, as described above, wherein the concentration of the reconstituted solution will be 7.2 mg / ml.
SIDE EFFECT
Identified adverse reactions associated with the use of the drug, typically had mild course and rarely require discontinuation of the drug in both adults and children.
Common side effects: (? 1/100 but <1/10) very often (? 1/10), common and uncommon (1/1000, but <1/100?).
In adults:
the part of the body as a whole: often - fever, headache, feeling chills.
From the digestive system: often - nausea, diarrhea, vomiting, abdominal pain, blood serum increased activity of ACT, ALT, alkaline phosphatase, direct and total bilirubin.
From hemopoiesis system: often - anemia.
Cardio-vascular system:often - tachycardia, phlebitis / thrombophlebitis, peripheral edema, venous postinfuzionnye complications tides.
On the part of the respiratory system: often - shortness of breath.
Skin and subcutaneous tissue: rash, pruritus (including injection site), increased sweating.
From the laboratory parameters: often - hypoalbuminemia, hypoproteinemia, hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia, leukopenia, neutropenia, thrombocytopenia, eosinophilia, decreased hemoglobin and hematocrit, increased partial thromboplastin and prothrombin time, proteinuria, leucocyturia, microscopic hematuria, increase in serum concentrations of blood creatinine; rarely - hypercalcemia.
There are anecdotal reports of rare cases of liver dysfunction and allergic reactions - rash, facial swelling, itching, burning sensation, or bronchoconstriction, and anaphylaxis. The post-marketing period revealed rare cases of liver dysfunction as well as peripheral edema and hypercalcemia. In patients with invasive aspergillosis - pulmonary edema, respiratory distress syndrome in adults, infiltrates on chest radiograph.
Children:
From the body as a whole: very often - fever, often - headache, a feeling of chills, gistaminoposredovannye reaction (eg allergic and anaphylactic reactions).
Cardio-vascular system: often - tachycardia, decreased blood pressure, flushing, peripheral edema.
From the digestive system: often - abnormal liver function, serum increased activity of ACT, ALT.
Skin and subcutaneous tissue: often - a rash, itching (including injection site).
From the laboratory parameters: often - hypokalemia, hypomagnesemia, hypercalcemia, eosinophilia, elevated serum concentrations of glucose and phosphorus, reducing the phosphorus concentration in the serum.
Local reactions: often - pain at the site of catheter insertion, gistaminoposredovannye reaction at the injection site - swelling.
CONTRAINDICATIONS
- Children up to age 3 months;
- Hypersensitivity to the components of the drug.
With caution prescribed drug in the concomitant use of cyclosporin, as well as in patients with moderate hepatic failure patients (from 7 to 9 points on the Child-Pugh).
PREGNANCY AND LACTATION
Clinical experience in use of the drug during pregnancy and lactation (breast feeding) not. Animals caspofungin crosses the placental barrier. Caspofungin should not be given to women during pregnancy, except in cases where use of the drug is essential.
Since there is no data on the allocation of caspofungin in breast milk, breast-feeding should be discontinued, if necessary, the appointment during lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
No correction is required dosing regime when administering the drug to patients with reduced kidney function .
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Patients with mild hepatic insufficiency (5-6 points on a scale Child-Pugh) dose adjustment is required. At moderate hepatic impairment (from 7 to 9 points on the Child-Pugh) supporting Cancidas daily dose is reduced to 35 mg / day, but when indicated persists loading dose of 70 mg on the first day of therapy. Clinical experience with the drug in a severe hepatic insufficiency (more than 9 points on a scale Child-Pugh) do not.
APPLICATION FOR CHILDREN
Contraindications: Children under the age of 3 months.
The daily dose of the drug Cancidas В® is administered to children (from 3 months to 17 years) by slow i / v infusion (? 1 h), 1 time / day.
APPLICATION IN ELDERLY PATIENTS
Elderly patients (65 years and older) dose adjustment is required.
SPECIAL INSTRUCTIONS
Use in Pediatrics
Efficacy and safety of the drug Cancidas В® in children from 3 months to 17 years is confirmed by a sufficient number of clinical studies on the basis of which the drug has been used successfully in these patients for the same indications as in adults.
There are no data on the safety and efficacy of the drug Cancidas В® in infants and children under the age of 3 months.
OVERDOSE
No data on drug overdose. In clinical studies, it was well tolerated, the highest dose tested - one-time single dose of 210 mg (6 healthy volunteers).
Also good tolerability was shown when administered in a daily dose of 100 mg during 21 days (15 healthy volunteers).
In case of overdose of caspofungin dialysis is not carried out.
DRUG INTERACTION
Caspofungin acetate is not an inhibitor of an enzyme system cytochrome P450 (CYP), and is not an inducer of CYP3A4-mediated metabolism of other drugs. Caspofungin is not a substrate for P-glycoprotein enzyme and is a weak substrate for cytochrome P450.
On the pharmacokinetics of Cancidas not affect itraconazole, amphotericin B, mycophenolate, nelfinavir, or tacrolimus.
In turn, Cancidas В® does not affect the pharmacokinetic parameters of itraconazole, amphotericin B, rifampin, or active metabolite of mycophenolate.
Cancidas В®reduced the 12-hour concentration of tacrolimus in the blood of 26%. Patients receiving both drugs, recommended standard monitoring of tacrolimus blood concentrations and, if necessary, its correction dosing regimen.
With simultaneous use of cyclosporin and may Cancidas transient (tested after drug withdrawal) increased activity of AST and ALT (not more than 3 times, compared with the upper limit of normal) and caspofungin increase AUC by about 35% without changing the concentration of cyclosporine. When co-administration of these agents (for up to 290 days) were no serious adverse events noted by the liver. The simultaneous appointment of Cancidas and cyclosporine may be justified where the potential benefits of such a purpose greater than the possible risk.
Rifampin can either accelerate or retard the distribution of caspofungin. With the simultaneous co-administration with rifampin for 14 days noted transient increase in the plasma concentration of caspofungin on the first day (increased AUC by about 60%). At the same time, this inhibiting effect was not observed when the assignment caspofungin occurred against conducted within 14 days of monotherapy rifampin, thus on the background of stable inductor effect of rifampin noted a slight decrease AUC and concentration caspofungin the end of infusion, and a threshold concentration - about 30 %.
The simultaneous use of inductors Cancidas clearance of drugs (efavirenz, nevirapine, phenytoin, carbamazepine or dexamethasone) may lead to a clinically significant reduction in the concentration of caspofungin. Available data indicate that these drugs induced decrease in caspofungin concentrations occur sooner by accelerating the elimination rather than metabolism. Therefore, the combined use Cancidas with efavirenz, nelfinavir, nevirapine, rifampin, dexamethasone, phenytoin or carbamazepine should consider the possibility of increasing the daily dosage to 70 mg Cancidas after applying normal loading dose of 70 mg.
In children, the combined use of dexamethasone and caspofungin may be accompanied by a clinically significant reduction in the threshold concentration of caspofungin.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be kept out of reach of children at a temperature of from 2 В° to 8 В° C. Shelf life - 2 years.
The mixed solution in the vial primary Cancidas В® can be stored at a temperature below 25 В° C for 24 hours before the preparation of an infusion solution intended for administration to the patient.
The prepared final infusion solution Cancidas В® in a plastic infusion bag or bottle for in / infusions can be stored at a temperature below 25 В° C for 24 hours or in a refrigerator at a temperature of from 2 В° to 8 В° C for 48 hours.
The information is provided for your information, do not self-medicate, it is dangerous for your health.
