Kapreomitsin

General characteristics. Structure:

Active ingredient: a kapreomitsina sulfate in terms of капреомицин 500 mg, 750 mg, 1000 mg.

Pharmacological properties:

The polypeptide antibiotic produced by Streptomyces capreolus. Okazyvayoet bacteriostatic action only on various strains of Mycobacterium tuberculosis (the minimum overwhelming concentration is on average equal to 1,25 - 2,5 mg/l when determining in fluid medium). The mechanism of action of a kapreomitsin is connected with suppression of synthesis of protein in a bacterial cell. Antitubercular пре­парат the II row (according to classification of World Health Organization). At monotherapy капреомицин quickly causes emergence resistant, strains of mycobacteria. Kapreomitsin has full cross stability with Viomycinum, partial cross stability - with some antibiotics aminoglycosides (including with Kanamycinum and Neomycinum). Pereyokrestny stability between kapreomitsiny and an isoniazid, aminosalicylic acid, Cycloserinum, streptomycin, Etioniamidum, Ethambutolum is not noted. Kapreomitsin has to be applied only as a part of complex therapy as antitubercular drug II of a row, including at inefficiency and a neperenosiyomost of antitubercular medicines I of a row (an isoniazid, to reeves - picene, Pyrazinamidum, streptomycin, Ethambutolum) and with sensitivity of mycobacteria of the patient to a kapreomitsin and to at the same time used other antitubercular drugs. Kapreomitsin has teratogenic effect (anomalies of a skeletogeny in experiments on rats). 

Pharmacokinetics. Kapreomitsin is practically not soaked up in digestive tract (meyony 1%) therefore it is entered into an organism only parenterally. The maximum konyotsentration in a blood plasma Sshakh is reached in 1-2 hours after intramuscular introduction of 1 g of a kapreomitsin and makes 20-47 mg/l; in 10 hours concentration is equal to 4 mg/l. After intravenous infusion of a kapreomitsin within 1 hour in a dose of 1 g Stakh makes 30-50 mg/l. The area under a curve "concentration time" at intravenous and intramuscular administration is identical. Kapreomitsin does not get through a blood-brain barrier, but gets through a placental barrier. In an organism капреомицин it is not metabolized. It is removed generally by kidneys (during 12ch-50-60% of a dose) by glomerular filtering in not changed look, in small amounts - with bile. Kapreomitsin does not kumulirut at daily introduction in a dose 1 g within 30 days at normal function of kidneys. At a renal failure the period of a poyoluvyvedeniye increases and the tendency to cumulation / appears

Indications to use:

As a part of complex therapy - a pulmonary tuberculosis, at inefficiency or intolerance of antitubercular drugs I of a row, and also at resistance to them.

Route of administration and doses:

Before therapy it is necessary to confirm existence at the patient of Mycobacterium tuberculosis strain, chuvstviyotelny to a kapreomitsin.  
The average dose of a kapreomitsin makes 1 g/days, no more than 20 mg/kg/days. 
Kapreomitsin enter intramusculary (deeply) or intravenously (kapelno puyoty infusions lasting 60 minutes) 1 time a day within 60-120 days, and then - on 1 g 2 or 3 times a week within 12-24 months into combinations with other proyotivotuberkulezny drugs. 
Patients with renal failures should reduce a dose in a sootvetstyoviya with clearance of creatinine according to the following table:

Clearance           Clearance               Period                    Dose (mg/kg)     
creatinine      of a kapreomitsin    of semi-removal      for the following
(ml/min.)           (l/kg/h * 102)        (h)                           intervals between
                                                                                           introductions
                                                                                       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 7,3
                             20 1,49                                        20 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 
                                                 60 3,4 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 intramuscular introduction contents of a bottle of 0,5 g, 0,75 g, 1 g are rastvoyoryat respectively in 1 ml, 1,5 ml, 2 ml of 0,9% of solution of sodium of chloride or steyorilny water for injections (it is necessary to wait 2-3 min. before full dissolution of powder). 
At an intramuscular injection капреомицин enter deeply into a muscle, a poyoskolka the superficial injection can cause the increased morbidity and razyovity aseptic abscesses. 
For intravenous drop administration the solution of a kapreomitsin prepared in the same way dissolve 0,9% of solution of sodium of chloride in 100 ml and enter within 60 minutes. 
For introduction of a dose of 1 g it is necessary to use all contents of the bottle containing 1 g of drug. For introduction of a dose less than 1 g from such bottle rekomenyodutsya to use the following table of cultivations:

Amount of solvent,    Volume of solution of a kapreomitsin       Concentration of a kapreomitsin in
added to a bottle           for injections                                   the received solution (approximately)
with a capacity of 10 ml,
1 g containing a dose 
          2,15                                                                                      ml 2,85 ml 350 mg/ml
          2,63                                                                                      ml 3,33 ml 300 mg/ml
            3,3                                                                                            ml 4 ml 250 mg/ml
            4,3                                                                                            ml 5 ml 200 mg/ml

Solution of a kapreomitsin can get pale straw coloring and over time darken, but it is not followed by loss of activity or emergence of toxicity. After cultivation it is possible to store solution in the refrigerator no more than 24 hours.

Features of use:

Prior to treatment kapreomitsiny and regularly in the course of treatment (1-2 times a week) it is necessary to carry out an audiometriya and assessment of vestibular function.
The research of function of kidneys should be conducted before treatment and once in неде­лю during treatment. Control of concentration of drug in blood is recommended. During treatment control also hematologic indicators and function of a pecheyona.
Injury of kidneys which can be observed against the background of use of a kapreoyomitsin is followed by a necrosis of tubules, increase in level of an urea nitrogen in blood or serumal creatinine, emergence of a pathological deposit in urine. For patients of advanced age, patients with renal failures or dehydration and the patients receiving other nephrotoxic drugs, the risk of development of an acute necrosis of tubules is much higher.
Slight increase of an urea nitrogen and serumal creatinine nayoblyudatsya at the most part of the patients receiving long therapy. At many of them emergence in urine of cylinders, erythrocytes and leukocytes was noted. At a poyovysheniya of level of an urea nitrogen of more than 30 mg / 100 the ml, and also at any other signs of decrease in renal function with increase in level of an urea nitrogen or without it, and also at suspicion on a renal failure is required tshchatelyyony inspection of the patient, a dose decline on the basis of clearance of creatinine or full drug withdrawal.
Damage of acoustical and vestibular departments of the VIII couple of cranial nerves happens at patients to a renal failure or dehydration, and also at treatment by the drugs having ototoksichesky effect. Such patients often test dizziness and a sonitus.
After bystry intravenous administration of a kapreomitsin neuromuscular blockade or respiratory paralysis are possible.
As during treatment the hypopotassemia can develop, it is ezhemeyosyachno necessary to carry out determination of content of potassium in serum.
During treatment it is necessary to control constantly the mode and schemes a dozirovayoniya, correctness and a regularity of performance of appointments. In case of the admission of an injyoektion enter as soon as possible, only if there did not come time of introduction of a sleduyuyoshchy dose; doses do not double.
The concomitant use with streptomycin and Viomycinum is not recommended.
During administration of drug it is necessary to be careful at control of vehicles, mechanisms and when performing other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From an urinary system: nephrotoxicity (increase уров­ня an urea nitrogen in blood of more than 20 mg / 100 ml, reduction of allocation of a fenolsulfonftalein and emergence of an abnormal uric deposit, disturbances of elektroyolitny balance reminding a syndrome of Barter and development of a toxic nefriyot).
From the central nervous system: neurotoxicity, neuromuscular blockade.
From sense bodys: ototoxicity (subclinical hearing loss, sonitus and dizziness).
From a liver: disturbance of indicators of function of a liver at odnovremenyony treatment kapreomitsiny and other antitubercular drugs, koyotory is caused by changes of function of a liver.
Allergic reactions: at simultaneous treatment kapreomitsiny and drugiyom antitubercular drugs - the urticaria and skin rashes in the form of spots and small knots which are followed sometimes by feverish reaction.
From the hemopoietic system: eosinophilia, leukocytosis, leukopenia, thrombocytopenia, hyperuricuria (more than 20 mg / 100 ml), cylindruria, hamaturia, leukocyturia.
Local reactions: pain and consolidation and the strengthened bleeding in the place of an injyoektion, aseptic abscesses.
If you noticed any other side effects which are not specified in an instrukyotion, report about it to the doctor.

Contraindications:

Hypersensitivity, pregnancy, breastfeeding period, children's age. 
Use at pregnancy Use at pregnancy is contraindicated. During use of drug it is necessary to exclude breastfeeding.

Overdose:

Symptoms: dizziness, sonitus, вертиго (defeat of acoustical and vesyotibulyarny departments of the VII couple of cranial nerves), decrease in the general tone, neuromuscular blockade (respiratory paralysis), hypopotassemia, hypocalcemia, hypomagnesiemia and disturbances of electrolytic balance, acute necrosis of renal kayonalets.
Treatment: at normal function of kidneys - hydration with maintenance to urine - educations at the level of 3-5 ml/h/kg; control of a water balance, level of electrolytes and clearance of creatinine; for elimination of neuromuscular blockade - administration of antikholinesterazny medicines, calcium drugs; at the expressed nayorusheniye of function of kidneys - a hemodialysis. 
Use with other medicines Myorelaxation effect amplifies diethyl ether, aminoglycosides, polymyxins, citrate preservatives of blood, decreases - a neostigmina methyl sulfate. In a combination with other antitubercular medicines (streptomycin, Viomycinum), and also at a combination to polymyxin, colistin. amikacin, gentamycin, Tobramycinum, Vancomycinum, Kanamycinum, Neomycinum, furosemide, Acidum etacrynicum or a metoksiflurany ototoksichesko and nephrotoxic action mutually amplifies.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the places unavailable to children. 
Period of validity 3 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Powder for preparation of injection solution for intravenous and intramuscular administration. On 1 g of active agent in the bottle of transparent glass corked by a stopper from the chlorbutyl rubber which is pressed out by an aluminum cap. The polymeric cap of Flip off is put on a bottle. On 1 фл. in a cardboard pack.