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

The polypeptide antibiotic produced Streptomyces capreolus. It has a bacteriostatic effect only on various strains Mycobacterium tuberculosis (the minimum inhibitory concentration is 1.25-2.5 mg / l on average when determined in a liquid medium). The mechanism of action of capreomycin is associated with the suppression of protein synthesis in a bacterial cell. Anti-tuberculosis drug of the II series (according to the classification of the World Health Organization).

With monotherapy capreomycin quickly causes the emergence of resistant strains of mycobacteria. Capreomycin has complete cross-resistance with viomycin, partial cross-resistance - with some antibiotics-aminoglycosides (including with kanamycin and neomycin). There is no cross-resistance between capreomycin and isoniazid, aminosalicylic acid, cycloserine, streptomycin, ethionamide, ethambutol.

Capreomycin should be used only as part of complex therapy, as an anti-tuberculosis drug of the II series, incl. with inefficiency and intolerance of anti-tuberculosis drugs of the 1st series (isoniazid, rifampicin, pyrazinamide, streptomycin, ethambutol) and in the presence of sensitivity of the patient's mycobacteria to capreomycin and to simultaneously used other antituberculous drugs.

Capreomycin has a teratogenic effect (anomalies in the development of the skeleton in experiments on rats).

Pharmacokinetics:

Capreomycin is practically not absorbed in the gastrointestinal tract (less than 1%), therefore it is introduced into the body only parenterally. The maximum concentration in the blood plasma (Cmax) is achieved 1-2 hours after intramuscular injection of 1 g capreomycin and is 20-47 mg / l; after 10 hours the concentration is 4 mg / l. After intravenous infusion of capreomycin for 1 hour at a dose of 1 g of Cmah is 30-50 mg / l. The area under the "concentration-time" curve for intravenous and intramuscular injection is the same.

Capreomycin does not penetrate the blood-brain barrier, but penetrates the placental barrier.

In organism capreomycin 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. Within 6 hours after the administration of 1 g of the drug, the concentration of capreomycin in urine is 1.68 mg / ml in the average urine volume of 228 ml.

Capreomycin does not cumulate with a daily dose of 1 g for 30 days with normal kidney function. If the kidney function is impaired, the elimination half-life increases and a tendency to accumulation appears.

Indications:

As part of complex therapy - pulmonary tuberculosis, with ineffectiveness or intolerance of anti-tuberculosis drugs of the I series, as well as in resistance to them.

Contraindications:

Hypersensitivity to capreomycin, simultaneous use with streptomycin and iniomycin, pregnancy, the period of breastfeeding, the age of 18 years.

Carefully:

Chronic renal failure, hearing impairment, 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); dehydration, myasthenia gravis, parkinsonism,elderly age; simultaneous use with polymyxin, sodium colistimetate, amikacin, gentamicin, tobramycin, vancomycin, kanamycin, neomycin, furosemide, ethacrynic acid.

Pregnancy and lactation:

Use during pregnancy is contraindicated.

If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

Before the start of therapy, it is necessary to confirm the presence of a patient sensitive to capreomycin strain Mycobacterium tuberculosis.

The average dose of capreomycin is 1 g / day, not more than 20 mg / kg / day.

Capreomycin is administered intramuscularly (deep) or intravenously (by dropwise infusion with a duration of 60 minutes) once a day for 60-120 days, and then - 1 g 2 or 3 times a week for 12-24 months in combination with other antituberculous preparations.

Patients with impaired renal function should reduce the dose in accordance with the creatinine clearance according to the following table:

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

For intramuscular injection, the contents of the vial: 500 mg or 750 mg are dissolved respectively in 1 ml or 1.5 ml of a 0.9% solution of sodium chloride or sterile water for injection (wait 2-3 minutes until the powder is completely dissolved). With intramuscular injection capreomycin are injected deep into the relatively large muscle, since a superficial injection can cause increased soreness and development of aseptic abscesses.

For intravenous drip injection, the capreomycin solution prepared in the same way is dissolved in 100 ml of 0.9% sodium chloride solution and injected for 60 minutes.

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

Side effects:

From the urinary system: nephrotoxicity (increased nitrogen urea in the blood more than 20 mg / 100 ml, decrease in excretion of phenolsulfonphthalein and the appearance of abnormal urinary sediment, cylinduria, hematuria, leukocyturia, electrolyte imbalance resembling Barter's syndrome, oliguria, development of toxic nephritis, acute renal tubular necrosis).

From the central nervous system: neurotoxicity, neuromuscular blockade.

From the sense organs: ototoxicity (decrease, loss of hearing, tinnitus and dizziness), vertigo.

From the side of the liver: violation of liver function tests with simultaneous treatment with capreomycin and other anti-tuberculosis drugs that cause changes in liver function.

Allergic reactions: with the simultaneous use of capreomycin and other anti-tuberculosis drugs - hives and skin eruptions in the form of spots and nodules, accompanied by a sometimes febrile reaction.

On the part of the organs of hematopoiesis: eosinophilia, leukocytosis, leukopenia, thrombocytopenia.

Local Reactions: pain and densification and increased bleeding at the injection site, aseptic abscess.

Other: hypokalemia, hypomagnesemia, hypocalcemia, hyperuricuria.

Overdose:

Symptoms: dizziness, noise in the ears, vertigo (defeat of the auditory and vestibular departments of the VII pair of cranial nerves), a decrease in the general tone, neuromuscular blockade (respiratory paralysis), hypokalemia, hypocalcemia, hypomagnesemia and electrolyte imbalance, acute renal tubular necrosis.

Treatment: with normal kidney function - hydration with maintenance of urine at a level of 3-5 ml / h / kg; control of water balance, electrolyte level 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 is enhanced by diethyl ether, aminoglycosides, polymyxins, citrated blood preservatives, reduced - neostigmine methylsulfate.

In combination with other anti-tuberculosis drugs (streptomycin, biomycin), and when combined with polymyxin, sodium colistimetate, amikacin, gentamicin, tobramycin, vancomycin, kanamycin, neomycin, furosemide, ethacrynic acid or methoxyfluorane, the ototoxic and nephrotoxic effect is mutually reinforced.

Special instructions:

If it is necessary to administer the drug to patients with chronic renal failure, hearing impairment, the ratio of expected benefit to therapy and the risk of additional impairment of the function of the VIII pair of cranial nerves and renal damage should be compared.

Prior to treatment with capreomycin and regularly during treatment (1-2 times per week), audiometry and vestibular function evaluation should be performed.

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. During treatment, hematologic parameters and liver function are also monitored.

Damage to the kidneys, which can occur with the use of capreomycin, is accompanied by necrosis of the renal tubules, an increase in the level of urea nitrogen in the blood or serum creatinine, the appearance of a pathological sediment in the urine.

For elderly patients, patients with impaired renal function or dehydration and patients receiving other nephrotoxic drugs, the risk of developing acute necrosis of the renal tubules is much higher.

A slight increase in urea nitrogen and serum creatinine was observed in the majority of patients who received long-term therapy. Many of them noted the appearance in the urine of cylinders, erythrocytes and leukocytes. With an increase in the urea nitrogen level of more than 30 mg / 100 ml,as well as any other signs of a decrease in renal function with an increase in the level of urea nitrogen or without it, as well as in case of suspected renal dysfunction, a thorough examination of the patient, a dose reduction based on creatinine clearance or complete withdrawal of the drug is required.

Auditory and vestibular damage VIII pairs of cranial nerves occur more often in patients with impaired renal function or dehydration, as well as with the simultaneous use of drugs that have ototoxic effect. Such patients often experience dizziness and tinnitus.

After rapid intravenous injection of capreomycin, neuromuscular blockade or respiratory paralysis is possible.

Since hypokalemia may develop during treatment, the serum potassium content should be determined on a monthly basis.

During treatment, it is necessary to constantly monitor the regimen and dosage regimens, the correctness and regularity of the appointments. In the case of a miss, the injection is administered as soon as possible, only if the time of administration of the next dose has not come; Doses do not double.

In the absence of improvement in the state for 2-3 weeks.or when new symptoms appear, specialist advice is needed.

Simultaneous use with streptomycin and biomycin Not recommended.

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

During the use of the drug, care should be taken when driving vehicles, mechanisms and other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Powder for the preparation of solution for intravenous and intramuscular injection 500 mg, 750 mg.

Packaging:

500 mg of active substance into a tube of colorless tubular glass, type I, 5 ml in volume, closed with a stopper with a notch from bromobutyl rubber, with an aluminum snap closure or 750 mg of active substance into a bottle of colorless tubular glass, type I, with a capacity of 10 ml, closed by a stopper with a notch from brombutyl rubber, with an aluminum snap closure,

Solvent - "Water for Injection", 2 ml or 5 ml manufactured by OJSC "Pharmasynthesis", Russia (RU No.LP-001844) or sodium chloride, 2 ml or 5 ml manufactured by OJSC "Pharmasintez", Russia (RU No.LP-001960) .

1.One bottle with the drug with instructions for use in a cardboard pack,

2. One bottle with the drug and one ampoule with a solvent, together with the instruction for use, is placed in a pack of cardboard.

Storage conditions:

In a dry place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-002289

Date of registration:31.10.2013 / 18.01.2016

Expiration Date:31.10.2018

The owner of the registration certificate:Rowecq LimitedRowecq Limited United Kingdom

Manufacturer: & nbsp

BELCO PHARMA India

Representation: & nbspROUTEC LIMITEDROUTEC LIMITEDUnited Kingdom

Information update date: & nbsp04.12.2017

Illustrated instructions

Instructions

Capreomycin (Capreomycin)