Composition, form of production and packaging
Powder for the preparation of solution for iv and in / m introduction of white or almost white color.
1 f.
capreomycin (in the form of sulfate) 1 g
Vials (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Polypeptide antibiotic produced by Streptommyces capreolus. It has a bacteriostatic effect only on various strains of Mycobacterium tuberculosis (the minimum inhibitory concentration is 1.25-2.5 mg / L on average in the determination in a liquid medium). The mechanism of action of capreomycin is associated with the suppression of protein synthesis in a bacterial cell. Anti-tuberculosis drug of the II series (according to the classification of the World Health Organization).
With monotherapy, capreomycin rapidly causes the emergence of resistant strains of mycobacteria. Capreomycin has a full cross-resistance with viomycin, partial cross-resistance with some antibiotics-aminoglycosides (including with kanamycin and neomycin). There is no cross-resistance between capreomycin and isoniazid, aminosalicylic acid, cycloserine, streptomycin, ethionamide, ethambutol.
Capreomycip should be used only as part of complex therapy, as an anti-tuberculosis drug of the II series, incl. with ineffectiveness and intolerance of anti-tuberculosis drugs of the 1st row (isoniazid, rifampicin, pyrazinamide, streptomycin, ethambutol) and in the presence of sensitivity of the patient's mycobacteria to capreomycin and simultaneously used other anti-tuberculosis drugs.
Capreomycin has a teratogenic effect (anomalies in the development of the skeleton in experiments on rats).
PHARMACOKINETICS
Capreomycin is practically not absorbed in the gastrointestinal tract (less than 1%), therefore it is introduced into the body only parenterally. C max in the blood plasma is achieved 1-2 hours after the / m administration of 1g capreomycin and is 20-47 mg / l; after 10 hours the concentration is 4 mg / l. After IV infusion of capreomycin for 1 hour in a dose of 1 g of C max is 30-50 mg / l.
AUC for iv and in / m administration is the same.
Capreomycin does not penetrate the blood-brain barrier, but penetrates the placental barrier.
In the body, capreomycin is not metabolized.
It is excreted mainly in the night (during 12 hours - 50-60% of the dose) by glomerular filtration in unchanged form, in small amounts - with bile.
Capreomycin does not cumulate with a daily dose of 1 g for 30 days with normal kidney function. If the kidney function T 1/2 is impaired, the tendency to accumulation appears.
INDICATIONS
As part of complex therapy - pulmonary tuberculosis, with ineffectiveness or intolerance of anti-tuberculosis drugs of the I series, as well as in resistance to them.
DOSING MODE
Before the beginning of therapy it is necessary to confirm the presence of a patient sensitive to capreomycin strain of Mycobacterium tuberculosis.
The average dose of capreomycin is 1 g / day. not more than 20 mg / kg / day.
Capreomycin is given in / m (deep) or IV (drip by infusion with a duration of 60 min) 1 time per day. for 60-120 days, and then for 1 g 2 or 3 times a week for 12-24 months in combination with other anti-tuberculosis drugs.
Patients with impaired function of the night should reduce the dose in accordance with the creatinine clearance according to the following table:
(Mg / kg) for the following dosage intervals:
24 h 48 h 72 h
0 0.54 55.5 1.29 2.58 3.87
10 1.01 29.4 2.43 4.87 7.30
20 1.49 20.0 3.58 7.16 10.7
30 1.97 15.1 4.72 9.45 14.2
40 2.45 12.2 5.87 11.7
50 2.92 10.2 7.01 14.0
60 3.40 8.8 8.16
80 4.35 6.8 10.4
100 5.31 5.6 12.7
110 5.78 5.2 13.9
For IV introduction, the contents of the vial (1 g) are dissolved in 100 ml of a 0.9% solution of sodium chloride (NaCl) and injected for 60 minutes (IV drip). For the / m introduction of the contents of the vial. 1 g dissolved in 1 ml, 1.5 ml, 2 ml 0.9% solution of sodium chloride or sterile water for injection, respectively (wait 2-3 minutes until the powder is completely dissolved).
With the / m injection capreomycin is injected deep into the muscle, as a superficial injection can cause increased soreness and development of aseptic abscesses.
For IV injection, the capreomycin solution prepared in the same way is dissolved in 100 ml of 0.9% sodium chloride solution and injected for 60 minutes.
To introduce a dose of 1 g, you must use the entire contents of the vial containing 1 g of the drug. To introduce a dose of less than 1 g of this vial, the following dilution table is recommended:
DIVISION TABLE
The amount of the solvent added to a 10 ml vial containing a dose of 1 g. The volume of the capreomycin solution for injection. The concentration of the solution (approx.)
2.5 ml 2.83 ml 370 mg * / ml
2.63 ml 3.33 ml 315 mg * / ml
3.3 ml 4 ml 260 mg * / 'ml
4.3 ml 5 ml 210 mg * / ml
* Equivalent activity of capreomycin.
A solution of capreomycin may acquire a pale straw color and eventually darken, this is not accompanied by a loss of activity or the appearance of toxicity. After dilution, the solution can be stored in the refrigerator for no more than 24 hours.
SIDE EFFECT
On the part of the urinary system: nephrotoxicity (an increase in the urea nitrogen level in the blood of more than 20 mg / 100 ml, a decrease in the phenol sulfonphthalein release and the appearance of an abnormal urinary sediment, electrolyte imbalance reminiscent of the Barter syndrome and the development of toxic nephritis).
From the central nervous system: neurotoxicity, neuromuscular blockade.
From the sense organs: ototoxicity (subclinical hearing loss, tinnitus and dizziness).
On the part of the liver: a violation of liver function tests with simultaneous treatment with capreomycin and other antituberculous drugs that cause changes in liver function.
Allergic reactions: with simultaneous treatment with capreomycin and other antituberculosis drugs, urticaria and skin rashes in the form of spots and nodules, sometimes accompanied by a febrile reaction.
From the hematopoietic system: eosinophilia, leukocytosis, leukopenia, thrombocytopenia, hyperuricuria (more than 20 mg / 100 ml), cylindruria, hematuria, leukocyturia.
Local reactions: pain and tightness and increased bleeding at the injection site, aseptic abscesses.
If you notice any other side effects not listed in the instructions, tell your doctor.
CONTRAINDICATIONS
Hypersensitivity, pregnancy, the period of breastfeeding, children's age.
Carefully. Caution should be used capreomycin in patients with renal insufficiency and already existing hearing impairment. If it is necessary to prescribe the drug in such cases, it is necessary to compare the relationship between the expected benefit of therapy and the risk of additional impairment of the function of the VIII pair of cranial nerves and kidney damage.
With caution appoint kapreomptsip (like other antibiotics) to patients with any form of allergy, including drug.
During and after surgery, use with caution on the background of drugs that cause neuromuscular blockade (especially with a high probability of incomplete termination in the postoperative period).
Dehydration, myasthenia gravis, parkinsonism, advanced age.
PREGNANCY AND LACTATION
Use during pregnancy is contraindicated.
During the use of the drug should be excluded from breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Caution should be used capreomycin in patients with renal insufficiency. If it is necessary to prescribe the drug, then the ratio of the expected benefit of therapy and the risk of additional damage to the kidneys
APPLICATION FOR CHILDREN
Contraindicated in childhood.
APPLICATION IN ELDERLY PATIENTS
Use with caution in old age.
SPECIAL INSTRUCTIONS
Prior to treatment with capreomycin and regularly during treatment (1-2 times per week), audiometry and vestibular function evaluation should be performed.
The study of kidney function should be performed before treatment and once a week during treatment. It is recommended to monitor the concentration of the drug in the blood. During treatment, hematologic parameters and liver function are also monitored.
Damage to the kidneys, which can occur with capreomycin, is accompanied by tubular necrosis, an increase in the level of urea nitrogen in the blood or serum creatinine, the appearance of a pathological sediment in the urine. For elderly patients, patients with impaired renal function or dehydration and patients receiving other nephrotoxic drugs, the risk of developing acute tubal necrosis is significantly higher.
A slight increase in urea nitrogen and serum creatinine was observed in the majority of patients who received long-term therapy. Many of them noted the appearance in the urine of cylinders, erythrocytes and leukocytes. If the urea nitrogen level increases more than 30 mg / 100 ml, as well as any other signs of a decrease in renal function with an increase in the level of urea nitrogen or without it, and if a kidney function is suspected, a thorough examination of the patient, a dose reduction based on creatinine clearance or complete cancellation of the drug.
Damage to the auditory and vestibular divisions of the VIII pair of cranial nerves occurs in patients with renal dysfunction or dehydration, as well as in the treatment with ototoxic agents. Such patients often experience dizziness and noise in the ears.
After rapid intravenous injection of capreomycin, neuromuscular blockade or respiratory paralysis is possible.
Since hypokalemia may develop during treatment, the serum potassium content should be determined on a monthly basis.
During treatment, it is necessary to constantly monitor the regimen and dosage regimens, the correctness and regularity of the appointments. In the case of missed injections, administer as soon as possible, only if the time of the next dose is not reached; Doses do not double.
Simultaneous reception with streptomycin and biomycin is not recommended.
Influence on the ability to drive vehicles, mechanisms. During the use of the drug, care should be taken when driving vehicles, mechanisms and other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
OVERDOSE
Symptoms: dizziness, tinnitus, vertigo (defeat of the auditory and vestibular divisions of the VII pair of cranial nerves), decrease in general tone, neuromuscular blockade (respiratory paralysis), hypokalemia, hypocalcemia, hypomagnesemia and electrolyte imbalance, acute necrosis of renal tubules .
Treatment: with normal kidney function - hydration with maintenance of urine at a level of 3-5 ml / h / kg; control of water balance, electrolyte level and creatinine clearance; for the removal of neuromuscular blockade - the introduction of anticholinesterase drugs, calcium preparations; with severe renal dysfunction - hemodialysis.
DRUG INTERACTION
The miorelaxing effect is enhanced by diethyl ether, aminoglycosides, polymyxins, nitrate blood preservatives, reduced - neostigmine methylsulfate.
In combination with other anti-tuberculosis drugs (streptomycin, viomycin), as well as when combined with polymyxin, colistin, amikacin, gentamicin, tobramycin, vancomycin, kanamycin, nemycin, furosemide, ethacrynic acid or methoxyfluorane, the ototoxic and nephrotoxic effect is mutually reinforced.
Simultaneous reception with streptomycin and viomycin is not recommended.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
In a dry place, at a temperature of no higher than 25 В° C. Keep out of the reach of children.
Shelf life - 2 years. Do not use after the expiration date printed on the package.
