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

The polypeptide antibiotic produced Streptomyces capreolus (the minimum inhibitory concentration of MPC is 1.25-2.5 mg / L when determined in a liquid medium). Inhibits the synthesis of protein in a bacterial cell, has a bacteriostatic effect.

Effective only in relation to Mycobacterium tuberculosis. With monotherapy, it quickly causes the emergence of resistant strains, has full cross-resistance with viomycin and partial-with aminoglycosides.

Has a teratogenic effect (skeletal abnormalities in experiments on rats).

Pharmacokinetics:

Virtually not absorbed in the gastrointestinal tract (less than 1%). Time to reach the maximum concentration (Cmax) in plasma - 1 to 2 hours after intramuscular injection of 1 g and the maximum concentration (Cmah) is 20-47 mg / l; after 10 hours - 4 mg / l. After intravenous one-hour infusion at a dose of 1 g, the maximum concentration (Cmah) is 30-50 mg / l. The area under the concentration-time curve (AUC) for intravenous and intramuscular administration is the same. It does not pass through the blood-brain barrier, 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.

Not cumulated with normal kidney function. When the renal function is impaired, the half-life period (T_1/2) is increasing.

Indications:

Tuberculosis of the lungs (including with ineffectiveness and intolerance of drugs of the 1st series). Capreomycin should be given in combination with other anti-TB drugs.

Contraindications:

Capreomycin is contraindicated in children (under 18 years of age - safety and efficacy not established), patients with hypersensitivity to capreomycin, pregnant and lactating mothers. It is not recommended simultaneous use with other antituberculous drugs for parenteral use (streptomycin, viomycin, kanamycin, amikacin).

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 renal damage with a positive effect of treatment.

Use capreomycin with polymyxin, gentamicin, tobramycin, vancomycin, 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:

Capreomycin for injection can be used intramuscularly or intravenously at a dose of 15-16 mg / kg body weight with the following dilution: the contents of the vial (1 g) are dissolved in 2 ml of a 0.9% solution of sodium chloride for injection or sterile water for injection. It should wait 2-3 minutes, until the contents of the bottle finally dissolve.

Intravenously. For intravenous drip infusion dissolved capreomycin for injections should be diluted in 100 ml of 0.9% sodium chloride solution for injection and injected for 60 minutes.

Intramuscularly. Diluted capreomycin for injections are administered by deep intramuscular injection, since surface 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.

After dilution, all solutions of capreomycin for injection can be stored in the refrigerator for no more than 24 hours.

Capreomycin is always prescribed in combination with another at least one anti-tuberculosis 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 or intravenously for 60-120 days, and then 1 g in either of the two ways 2-3 times a week.

(Note: Treatment of tuberculosis should be continued for 12-24 months.If it is not possible to inject drugs for injection, then when they are discharged from the hospital, they should be replaced with oral medications).

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

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

Creatinine clearance (ml / min)	Clearance of capreomycin (l / kg / hx 10²)	Half-life (h)	Dose (mg / kg) for the following intervals between administrations
Creatinine clearance (ml / min)	Clearance of capreomycin (l / kg / hx 10²)	Half-life (h)	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	20,0	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	3,4	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

Side effects:

From the urinary system: nephrotoxicity (increased urea nitrogen in the blood plasma, reduced excretion of phenolsulfonphthalein), toxic nephritis.

Laboratory indicators: thrombocytopenia, leukocytosis, leukopenia, increased uric acid (more than 20 mg / 100 ml), cylindruria, hematuria, leukocyturia, hypokalemia, hypomagnesemia, hypocalcemia.

From the nervous system: neurotoxicity, neuromuscular blockade.

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

From the digestive system: violation of liver function (when used in combination with other hepatotoxic anti-TB drugs).

Local Reactions: pain and compaction at the injection site, aseptic abscess.

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

Other: bleeding.

Overdose:

Signs and Symptoms:

Nephrotoxic effect, observed with parenteral administration of capreomycin, 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 developing acute necrosis of renal tubules 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.

With the onset of toxic effects of capreomycin, hypokalemia, hypocalcemia, hypomagnesemia and electrolyte imbalance resembling Barter's syndrome were observed in patients.

Treatment: in the treatment of overdose it is necessary to carry out measures aimed at maintaining breathing and circulation, as well as careful monitoring of the concentration of gases in the blood, serum electrolytes, etc.

To excrete capreomycin in patients with severe kidney disease, hemodialysis can be used.

Interaction:

The miorelaxing effect is enhanced when combined with diethyl ether, aminoglycosides, polymyxins, nitrate blood preservatives, and decreases with the simultaneous administration of neostigmine methyl sulfate.

In combination with other antituberculosis drugs (streptomycin, viomycin), as well as when combined with polymyxins (including colistin), amikacin, gentamicin, tobramycin, vancomycin, kanamycin, neomycin, furosemide, ethacrynic acid or methoxyfluorane, the ototoxic and nephrotoxic effect is mutually reinforced.

Special instructions:

Before the treatment with capreomycin and regularly (1-2 times a week) during the treatment should be audiometry and evaluation of the vestibular function.

Renal function testing should be performed both before the treatment with capreomycin for injections and weekly during treatment.Kidney damage was observed with renal tubular necrosis, increased levels of blood urea nitrogen (BUN) or serum creatinine and occurrence of abnormal urinary sediment. A slight increase in BUN or serum creatinine were observed in a substantial portion of patients who were 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.

Clinically significant abnormal urinary sediment appearance and significant increase in BUN levels (creatinine or serum) under capreomycin not established. Since hypokalemia may develop during treatment, the serum potassium concentration should be determined monthly.

During treatment, hematologic parameters and liver function are monitored. When administering capreomycin, the entire contents of the vial should be used. Capreomycin is always prescribed in combination with other anti-TB drugs.

During and after surgery capreomycin with caution used against 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 case of missed injection, the missed dose is administered as soon as possible, only if the time of the next dose has not come; 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:

The effect of capreomycin on the ability to drive vehicles and mechanisms has not been studied.

Form release / dosage:

Powder for solution for intravenous and intramuscular injection, 1.0 g.

Packaging:

Primary packaging of medicinal product

By 1.0 g of active substance in a vial of clear glass, sealed with a stopper of chlorobutyl rubber, crimped with an aluminum cap. The bottle is fitted with a polymer cap FLIP OFF.

Secondary packaging of medicinal product

1 bottle with instructions for use in a cardboard pack.

Packing "In Balk".

Primary packaging of medicinal product

By 1.0 g of active substance in a vial of clear glass, sealed with a stopper of chlorobutyl rubber, crimped with an aluminum cap. The bottle is fitted with a polymer cap FLIP OFF.

Secondary packaging of medicinal product

For 100, 500 bottles in a cardboard box. The label is labeled with label paper or self-adhesive on the box.

When packaging the kit (drug with a solvent) at the enterprise OAO "Pharmasintez" (Russia):

Primary packaging of medicinal product

By 1.0 g of active substance in a vial of clear glass, sealed with a stopper of chlorobutyl rubber, crimped with an aluminum cap. The bottle is fitted with a polymer cap FLIP OFF.

2 ml and 5 ml of solvent in a polyethylene ampoule. The label is attached to the ampoule from paper label, or written, or from polymer materials self-adhesive.

Secondary packaging of medicinal product

1 bottle with the drug (1.0 g active substance) complete with 1 ampoule solvent "Sodium chloride solution for injection 0.9%" 2 ml / or 1 bottle with the drug (1,0 g of active substance) complete with 1 ampoule of solvent "Sodium Chloride Solution for Injection 0.9%" of 5 ml is placed in a contour mesh box made of a polyvinylchloride film and aluminum foil printed lacquered.

On 1 contour acheikova packing together with the instruction on application place in a pack from a cardboard for consumer tare of subgroups chrome or chrome-ersatz. The packets are placed in a group package.

Storage conditions:

If the product is packaged without a solvent:

At a temperature of 15 to 30 ° C. The prepared solution should not be stored in the refrigerator for more than 24 hours.

In the case of packaging the preparation with a solvent:

At a temperature of 15 to 25 ° C. The prepared solution should not be stored in the refrigerator for more than 24 hours.

Shelf life:

2 years. Do not use after the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001086

Date of registration:15.08.2011 / 07.08.2014

Expiration Date:Unlimited

The owner of the registration certificate:Lock-Beta Pharmaceuticals (I) Pvt.LtdLock-Beta Pharmaceuticals (I) Pvt.Ltd India

Manufacturer: & nbsp

LOK-BETA PHARMACEUTICALS (I), Pvt. Ltd. India

Representation: & nbspLock-Beta Pharmaceuticals (I) Pvt.LtdLock-Beta Pharmaceuticals (I) Pvt.Ltd

Information update date: & nbsp04.12.2017

Illustrated instructions

Instructions

Capreomycin (Capreomycin)