Capreomycin - 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. With monotherapy, it quickly causes the emergence of resistant strains, has full cross-resistance with viomycin 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:

Treatment of pulmonary forms of tuberculosis caused by susceptible strains of M. tuberculosis, in the event that the antituberculous drugs of the 1st row (isoniazid, rifampicin, aminosalicylic acid and streptomycin) were ineffective (presence of resistant tubercle bacilli) or can not be used due to toxic effects, in combination with other antituberculosis 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; elderly age; simultaneous application with polymyxin, colistin, amikacin, gentamycin, tobramycin, vancomycin, kanamycin, neomycin, furosemide, ethacrynic acid, methoxyflurane; allergic diseases, including drug allergy; during and after surgery with the use of drugs that cause neuromuscular blockade (especially with a high probability of incomplete termination in the postoperative period).

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 is applied only parenterally: intramuscularly (preferably) or intravenously.

Capreomycin is always prescribed in combination with at least one other antituberculous drug, to which the strain M. tuberculosis, which is available for this patient.

The average dose for patients with normal renal function is 1 g / day, but not more than 20 mg / kg / day.for 60-120 days (intramuscular or intravenously), and then 1 g intramuscularly or intravenously 2-3 times a week. Treatment of tuberculosis should be continued for 12-24 months.

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

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

Clearance creatinine (ml / min)	Clearance of capreomycin (l / kg / h x 10²)	Period half-life (h)	Dose (mg / kg) for the following intervals between administrations
Clearance creatinine (ml / min)	Clearance of capreomycin (l / kg / h x 10²)	Period 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	7,30
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	-	-

Preparation of solutions

For intramuscular or intravenous administration, 0.5 g of the drug is dissolved in 1 ml, 0.75 g of the drug is dissolved in 1.5 ml of a 0.9% solution of sodium chloride for injection or sterile water for injection. To finally dissolve the contents of the bottle, you should wait 2-3 minutes.

Intravenously. With intravenous infusion, dissolved capreomycin should be diluted in 100 ml of 0.9% solution of sodium chloride for injection and injected within 60 minutes. Intramuscularly. With intramuscular injection, dissolved capreomycin are injected deep into the relatively large muscle, since a superficial injection can cause increased soreness and development of aseptic abscesses.

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 incidence of side effects listed below was determined accordingly by the following gradation: very often (> 1/10), often (> 1/100, ≤1 / 10), infrequently (> 1/1000, ≤1 / 100), rarely (> 1/10000, ≤1 / 1000), very rarely (≤1 / 10000).

Co the side of the urinary system: nephrotoxicity (increased nitrogen urea in the blood plasma, reduced excretion of phenolsulfonphthalein and the appearance of abnormal urinary sediment (cylinders, erythrocytes, leukocytes)), 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: ototoxicity - deafness (subclinical and clinically pronounced, including irreversible), tinnitus, dizziness.

From the digestive system: rarely - a violation of the liver (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:

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.

After rapid intravenous administration, neuromuscular blockade or respiratory paralysis may develop.

When the toxic effect of capreomycin in patients was observed hypokalemia, hypocalcemia, hypomagnesemia and electrolyte imbalance reminiscent of Barter's syndrome.

Treatment: with normal kidney function - hydration with maintenance of urine in the 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 miorelaxing effect (partial neuromuscular blockade) is intensified against the background of general anesthesia using diethyl ether, and also with the simultaneous use of capreomycin with aminoglycosides, polymyxins, nitrate blood preservatives; decreases - neostigmine methylsulfate.

In combination with other anti-tuberculosis drugs (streptomycin, viomycin), as well as when combined 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.

Possible damage to the kidneys with necrosis of the renal tubules, increased urea nitrogen in the blood (further 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 AMC of more than 30 mg / 100 ml, as well as any other signs of a decrease in renal function with or without AMC, requires a 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 content of AMC (or serum creatinine) under the influence of capreomycin has not been established.

The concentration of electrolytes in the blood serum should be determined on a monthly basis. during treatment can develop hypokalemia, hypomagnesemia, hypocalcemia.

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.

Care should be taken when prescribing antibiotics, including capreomycin, for patients with any form of allergy, especially drug.

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:

It is not recommended to drive during therapy with the drug. It should be refrained from other activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Powder for solution for intravenous and intramuscular injection 0.5 g, 0.75 g.

Packaging:

In the manufacture of the drug at the Sanjivani Paranteral Limited, India:

By 0.5 g or 0.75 g of active substance into the bottles of colorless transparent glass type I (Eur. Ph.), Sealed with rubber stoppers, crimped aluminum caps with plastic caps "Flip off". One bottle together with the instruction for use is placed in a cardboard box.

When the product is packaged at the enterprise, PharmConcept LLC, Russia:

One bottle together with instructions for use in a pack of cardboard.

In the production of the drug at the enterprise OOO PharmConcept, Russia:

By 0.5 g or 0.75 g of active substance into the bottle of colorless transparent glass of the 1 st hydrolytic class, hermetically sealed with a rubber stopper, crimped with an aluminum cap. A label from label or writing paper, or a self-adhesive label, is applied to the vial.

One bottle together with instructions for use in a pack of cardboard.

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:

2 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002762

Date of registration:15.12.2014 / 31.03.2017

Expiration Date:15.12.2019

The owner of the registration certificate:Sanjivani Parantaral Co., Ltd.Sanjivani Parantaral Co., Ltd. India

Manufacturer: & nbsp

SANJIVANI PARANTERAL, Limited India

FarmKoncept, OOO Russia

Representation: & nbspSP.INKOMED LLCSP.INKOMED LLC

Information update date: & nbsp03.12.2017

Illustrated instructions

Instructions

Capreomycin (Capreomycin)