Capreomycin-DEKO - instructions for use, dose, side effects, contraindications

The polypeptide antibiotic produced Streptomyces capreolus. The minimum suppressive concentration 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 in relation to Mycobacterium tuberculosis. When monotherapy rapidly causes the emergence of resistant strains, has a full cross-resistance with biomycin and partial - with aminoglycosides. Cross resistance is not observed between capreomycin and isoniazid, aminosalicylic acid, cycloserine, streptomycin, ethionamide and ethambutol. Has a teratogenic effect.

Pharmacokinetics:

Virtually not absorbed in the gastrointestinal tract (less than 1%). The maximum concentration in the blood plasma after intramuscular injection of 1 g in 1-2 hours is 20-47 mg / l; after 10 hours is 4 mg / l. After intravenous infusion of 1 h in a dose of 1 g, the maximum concentration in the blood plasma is 30-50 mg / l. AUC (area under the pharmacokinetic curve "concentration-time") for intravenous and intramuscular administration 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 g with normal kidney function for 30 days. If the kidney function is impaired, the elimination half-life increases and a tendency to accumulation appears.

Indications:Tuberculosis of the lungs (if first-line drugs (isoniazid, rifampicin, aminosalicylic acid, streptomycin) have been ineffective or can not be used due to toxic effects or the presence of resistant strains Mycobacterium tuberculosis), in combination with other anti-TB drugs.

Contraindications:

Hypersensitivity to capreomycin, pregnancy, the period of breastfeeding, children under 18 years of age (safety and efficacy have not been established), simultaneous use with viomycin and streptomycin.

Carefully:

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

Pregnancy and lactation:

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

Dosing and Administration:

It is used intramuscularly or intravenously, 1.0 g once a day (not more than 20 mg / kg / day) attraction 60-120 days, then 1.0 g intramuscularly or intravenously 2-3 times a week. Treatment of tuberculosis should be continued for 12-24 months. Capreomycin-Deco is always prescribed in combination with at least one other antituberculous drug, to which the strain is sensitive Mycobacterium tuberculosis, which is available for this patient.

Patients with impaired renal function should reduce the dose in accordance with the clearance of creatinine (CC). These doses are chosen to achieve an average equilibrium concentration of capreomycin in the serum of 10 mg / l (Table 1).

Table 1. Calculation of doses to achieve an average equilibrium concentration of capreomycin

in the serum of blood 10 mg / l (based on creatinine clearance)

Creatinine clearance, ml / min	Dose for the following intervals between administrations, mg / kg
Creatinine clearance, ml / min	24 h	48 h	72 h
0	1,29	2,58	3,87
10	2,43	4,87	7,30
20	3,58	7,16	10,7
30	4,72	9,45	14,2
40	5,87	11,7	-
50	7,01	14	-
60	8,16	-	-
80	10,4	-	-
100	12,7	-	-
110	13,9	-	-

Preparation of solutions

Capreomycin-Deco can be used intramuscularly or intravenously with the following dilution: the contents of the vial (1 g) are dissolved in 2 ml of a 0.9% solution of sodium chloride or water for injection. You should wait 2-3 minutes for the final dissolution of the contents of the vial.

Intravenously. For intravenous infusion, dissolved capreomycin diluted in 100 ml of 0.9% sodium chloride solution, injected for 60 minutes.

Intramuscularly. With intramuscular injection, diluted capreomycin injected deeply into the muscle.

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.

Side effects:The frequency of side effects listed below, was determined by the following grading respectively: very often (> 1/10), often (> 1/100, ≤1 / 10) infrequently (> 1/1000, ≤1 / 100), rare (> 1/10000, ≤1 / 1000), very rarely (≤1 / 10000).

From the urinary system: Nephrotoxicity (increase of urea nitrogen in blood plasma, reduction of excretion fenolsulfonftaleina and occurrence of abnormal urinary sediment (cylinders, erythrocytes, leucocytes)), oliguria, toxic nephritis.

On the part of the organs of hematopoiesis: eosinophilia (passing with a decrease in dose to 2-3 g per day), leukocytosis, leukopenia, rarely - thrombocytopenia.

Laboratory indicators: Hypokalemia, hypomagnesemia, hypocalcemia, electrolyte imbalance.

From the nervous system: neurotoxicity, neuromuscular blockade.

From the sense organs: Ototoksichnosg - deafness (subclinical and clinically expressed, including irreversible), tinnitus, dizziness.

From the digestive system: rarely - a violation of liver function (when used in combination with other hepatotoxic anti-tuberculosis drugs), the relationship of which with the use of capreomycin is not clear.Local reactions: rarely - pain and compaction at the injection site, aseptic abscess, increased bleeding at the injection site.

Allergic reactions: rarely - hives, maculopapular rash, fever.

Overdose:

Symptoms: dizziness, tinnitus, vertigo (defeat of the auditory and vestibular divisions of the VIII 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 in a volume of 3-5 ml / h / kg; control of water balance, electrolyte concentration and creatinine clearance; for the removal of neuromuscular blockade - the introduction of cholinesterase inhibitors, calcium preparations; with severe renal dysfunction - hemodialysis.

Interaction:

The muscle relaxant effect is enhanced by diethyl ether, other aminoglycosides, polymyxins, citrated blood preservatives; decreases - neostigmine methylsulfate.

In combination with other anti-tuberculosis drugs (streptomycin, viomycin), as well as in combination with polymyxins, including colistin; amikacin, gentamycin, tobramycin, vancomycin, kanamycin, neomycin, furosemide, ethacrynic acid, or methoxyflurane, the ototoxic and nephrotoxic effect is mutually reinforced.

Special instructions:

When using the drug, the kidney function should be examined before treatment and once a week during treatment.

Before the start of treatment and regularly (1-2 times a week) during the treatment should be audiometry and evaluation of the vestibular function. During treatment, hematologic parameters and liver function are monitored.

To confirm the presence of a capreomycin-sensitive strain Mycobacterium tuberculosis a sensitivity test should be carried out.

An increase in urea nitrogen in the blood plasma of more than 30 mg / 100 ml, as well as any other signs of renal dysfunction with an increase in urea nitrogen in the blood plasma or without it, requires a careful examination of the patient, reducing the dose or completely discontinuing the drug.

When the drug is administered, the entire contents of the vial should be used.The concentration of electrolytes in the blood serum should be determined on a monthly basis. during treatment, hypokalemia, hypomagnesemia, hypocalcemia may develop.

Capreomycin is always prescribed in combination with other anti-tuberculosis drugs.

During and after surgery, it is used 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.

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 solution for intravenous and intramuscular injection, 1 g.

Packaging:

For 1 g of active substance (capreomycin) in a glass bottle with a capacity of 10 ml of glass grade HC-1, HC-3 or hydrolytic class 1, hermetically sealed with a rubber stopper, crimped with an aluminum or combined cap.

1 or 10 bottles together with instructions for use in a pack of cardboard.

50 bottles with the appropriate number of instructions for use in a box of cardboard (for hospitals).

When the product is packaged with a solvent:

2 or 5 ml of solvent into neutral glass ampoules of grade НС-1 or НС-3.

1 bottle with the drug and 1 ampoule with solvent Water for injection, solvent for the preparation of dosage forms for injection (RU No. LS-000512 dated June 25, 2010), together with the instruction for use and the scarifier or knife ampoule into the outline packing of the film PVC.

1 package per pack of cardboard.

When packing ampoules with a ring or break point, the scarifier or ampoule knife is not inserted.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 of the year.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-002107

Date of registration:18.06.2013 / 29.07.2016

Expiration Date:18.06.2018

The owner of the registration certificate:COLORIT-PHARMA, LLC COLORIT-PHARMA, LLC Russia

Manufacturer: & nbsp

COLORIT-PHARMA, LLC Russia

Information update date: & nbsp05.12.2017

Illustrated instructions

Instructions

Capreomycin-DECO (CAPREOMYCIN-DEKO)