Capremabol - instructions for use, dose, side effects, contraindications

Anti-tuberculosis drug. The polypeptide antibiotic produced Streptomyces capreolus (the minimum suppressing concentration (MIC) is 1.25-2.5 mg / L when determined in a liquid medium). Suppresses the synthesis of protein in a bacterial cell, has a bacteriostatic effect.

Effective only in relation to Mycobacterium tuberculosis.

When monotherapy rapidly causes the emergence of resistant strains, has a full cross-resistance with viomycin and partial - with aminoglycosides.

Pharmacokinetics:

Capreomycin is practically not absorbed in the gastrointestinal tract (GIT) (less than 1%). Time to reach the maximum concentration in the blood plasma (TC_max) -1-2 hours after intramuscular injection of 1.0 g and its value is 20-47 mg / l; after 10 hours - 4 mg / l. After IV infusion in a dose of 1.0 g, the maximum concentration in the blood plasma (C_max) is 30-50 mg / l. Bioavailability for intravenous and intramuscular injection is the same. It does not pass through the blood-brain barrier (BBB), it penetrates the placental barrier. It is not metabolized.It is excreted mainly by the kidneys (within 12 hours - 50-60% of the dose) by glomerular filtration in unchanged form, in small amounts - with bile.

Do not cumulate with a daily dose of 1.0 g for 30 days. When the renal function is impaired, the elimination half-life (T_1/2) increases and there is a tendency to accumulation.

Indications:

Capreomycin is used for pulmonary tuberculosis, if first-line drugs (isoniazid, rifampicin, aminosalicylic acid and streptomycin) were ineffective or could not be used due to toxic effects or the presence of resistant tubercle bacilli.

To confirm the presence of a susceptible to capreomycin strain M. tuberculosis sensitivity should be determined.

Contraindications:

Hypersensitivity to the drug, pregnancy, lactation period, children's age (up to 12 years - safety and efficacy of the application are not established).

Carefully:

Renal failure, hearing impairment, dehydration, myasthenia gravis gravis, parkinsonism, old age.

It is necessary to compare the risk of additional impairment of the function of the VIII pair of cranial nerves and damage to the kidneys with a positive effect of treatment. Since other anti-tuberculosis drugs (streptomycin, biomycin) also have a similar and sometimes irreversible toxic effect, especially on the VIII pair of cranial nerves and kidney function, concomitant administration of these drugs with Capremabol® for injections is not recommended. Use Capremabol® with polymyxin B, colistin, amikacin, gentamicin, tobramycin, vancomycin, kanamycin and neomycin, which may have ototoxic and nephrotoxic effects, should be taken with great care.

Pregnancy and lactation:

Capreomycin is contraindicated in pregnancy. If you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Intramuscularly (deep) and intravenously. Capreomycin is applied intramuscularly with the following dilution: the contents of the vial (1 g) are dissolved in 2 ml of 0.9% sodium chloride for injection or sterile water for injection. It should wait 2-3 minutes until the contents of the bottle finally dissolve.

Diluted capreomycin is administered by deep intramuscular injection, as a superficial injection can cause increased soreness and development of aseptic abscesses.

To introduce a dose of 1 g, you must use the entire contents of the vial. For a dose of less than 1 g, the following dilution table can be used.

Table of dilutions

The amount of solvent added to a 10 ml vial containing a dose of 1 g	Volume of a solution of capreomycin	Concentration of solution (approx.)
2.15 ml	2.85 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.

The solution may become pale straw color and eventually darken, but this is not accompanied by loss of activity or the appearance of toxicity. After dilution, all solutions of capreomycin can be stored in the refrigerator for no more than 24 hours.

Capreomycin is always prescribed in combination with at least one antituberculous drug, to which the strain of tubercle bacilli that is present in the patient is sensitive.

The usual dose is 1 g per day (do not exceed 20 mg / kg / day.).

It is administered intramuscularly and intravenously for 60-120 days, and then 1 g 2-3 times a week.

Treatment of tuberculosis should be continued for 12-24 months. Patients with reduced renal function should reduce the dose based on creatinine clearance in accordance with the instructions given in Table. 1.

These dosages are chosen so as to achieve an average equilibrium level of capreomycin of 10 mg / l.

Table 1. Calculation of dosages to achieve an average equilibrium concentration of capreomycin in the serum 10 mg / l (based on creatinine clearance)

Clearance creatinine (ml / min)	Clearance capreomycin (l / kg / h x 10²)	Period half-life (clock)	Dose (mg / kg) for the following dosage intervals
Clearance creatinine (ml / min)	Clearance capreomycin (l / kg / h x 10²)	Period half-life (clock)	24 hours	48 hours	72 hours
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 intravenous administration, the contents of the vial (1 g) are dissolved in 100 ml of a 0.9% sodium chloride solution (NaCl) and injected for 60 minutes (IV drip).

Side effects:

From the urinary system: nephrotoxicity (oliguria, impaired renal function).

Laboratory indicators: thrombocytopenia, leukopenia, leukocytosis, hyperuricuria (more than 20 mg / 100 ml), cylindruria, hematuria, leukocyturia. From the nervous system: neurotoxicity, neuromuscular blockade.

From the sense organs: ototoxicity, vestibular disorders. Local reactions: pain and compaction at the injection site, aseptic necrosis.

Allergic reactions: urticaria, maculopapular rash, hyperthermia, eosinophilia.

Other: bleeding.

Overdose:

Signs and Symptoms: The nephrotoxic effect observed with the parenteral administration of Capremabol® is associated with the concentration of the drug in the blood serum.

For elderly patients, patients with impaired renal function or dehydration and patients receiving other nephrotoxic drugs, the risk of acute tubular necrosis is much higher. Damage to the auditory and vestibular divisions of the VIII pair of cranial nerves occurs in patients with impaired renal function or dehydration, as well as in those receiving ototoxic agents. Often such patients experience dizziness and noise in the ears.

When the toxic effect of Capremabol® appeared in patients, hypokalemia, hypocalcemia, hypomagnesemia and electrolyte balance disturbances resembling Barter's syndrome were observed.

Treatment: in the treatment of overdose it is necessary to carry out measures aimed at maintaining breathing and blood circulation, as well as careful monitoring of the concentration of blood gases, serum electrolytes, etc. Hypodialysis can be used to excrete Capremobola® in patients with severe kidney disease.

Interaction:

Are common: Prior to treatment with capremabol ® and regularly during the treatment should be audiometry and evaluation of the vestibular function.

Renal damage was noted with tubular necrosis, an increase in the level of urea nitrogen in the blood (AMK) or serum creatinine and the appearance of an abnormal urinary sediment. A slight increase in AMK and serum creatinine was observed in a significant proportion of patients undergoing long-term treatment. In a large percentage of these cases, the appearance in the urine of cylinders, erythrocytes and leukocytes. An increase in the AMC level of more than 30 mg / 100 ml, as well as any other signs of a decrease in renal function, with or without an increase in the level of AMC, requires careful examination of the patient, a reduction in the dose or complete withdrawal of the drug.

The clinically significant occurrence of an abnormal urinary sediment and a significant increase in the level of DMC (or serum creatinine), under the influence of Capremabol®, has not been established.

Care should be taken when prescribing antibiotics, including Capremabol®, to patients with any form of allergy, especially drug.

The muscle relaxant effect is enhanced by ether for anesthesia, aminoglycosides, polymyxins, nitrate preservatives of blood, reduced by neostigmine. In combination with other anti-tuberculosis drugs (streptomycin, viomycin), as well as when combined with polymyxin B, colistin, amikacin, gentamicin, tobramycin, vancomycin, kanamycin, neomycin, furosemide, ethacrynic acid or methoxyfluorane, the ototoxic and nephrotoxic effect is mutually enhanced.

Special instructions:

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. Before the start of treatment should be audiometry and evaluation of the vestibular function. During treatment, hematologic parameters and liver function are monitored.

When you enter, you must use the entire contents of the vial.

Always prescribed in combination with other anti-TB drugs.

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).

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.

If there is no improvement in the condition for 2-3 weeks or when new symptoms appear, consult a specialist.

Lab tests: a regular check of kidney function should be performed throughout the treatment period, and in patients with a known or suspected decrease in renal function, the dose should be reduced.

Research of renal function should be performed both before the beginning of treatment with Capremabol®, and weekly during treatment. Since hypokalemia may develop during treatment, frequent serum potassium levels should be performed.

Effect on the ability to drive transp. cf. and fur:

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Powder for the preparation of solution for intravenous and intramuscular injection.

Packaging:

1.0 g of active substance in glass bottles with a capacity of 10 ml.

Each label is labeled with a label or a self-adhesive label, a RFID sensor, or without a sensor.

The solvent - "Water for injection" in glass ampoules of 5 ml.

1. 1 bottle of the drug and instructions for use are placed in a pack of cardboard.

2. 1 bottle of preparation and 1 ampoule with solvent are packed in a contour mesh box made of polyvinylchloride film and foil of aluminum lacquered or without foil. One contour mesh package and instructions for use are put in a cardboard pack.

3. 5 bottles of the drug are packed in contoured cell packs made of polyvinyl chloride film and foil of aluminum lacquered or without foil. One outline package and instructions for use are put in a pack of cardboard.

4. 5 bottles with the preparation complete with 5 ampoules of the solvent are packed in contoured cell packs made of polyvinylchloride film and foil of aluminum lacquered or without foil.One contour mesh package with the preparation, one contour mesh package with a solvent and instruction for use is put in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-003738/09

Date of registration:15.05.2009 / 12.09.2014

Expiration Date:Unlimited

The owner of the registration certificate:PREBAND PFC, LLCPREBAND PFC, LLC Russia

Manufacturer: & nbsp

PREBAND PFC LLC Russia

Information update date: & nbsp03.12.2017

Illustrated instructions

Instructions

Capremabol® (Capremabol®)