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 capreolus (the minimum inhibitory concentration of MPC is 1.25-2.5 mg / L when determined in a liquid medium). Mechanism The action of capreomycin is associated with the suppression of protein synthesis in a bacterial cell. Anti-TB drug II number (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 kanamycin and neomycin). There is no cross-resistance between capreomycin and isoniazid, aminosalicylic acid, cycloserine, streptomycin, ethionamide and ethambutol. Has a teratogenic effect.

Capreomycin should be used only as part of complex therapy, as an antituberculous drug II series, incl. with inefficiency and intolerance of anti-TB drugs I 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.

Pharmacokinetics:

Virtually not absorbed in the gastrointestinal tract (less than 1%). The maximum concentration in blood plasma C_max 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 C_max is 30-50 mg / l. The area under the "concentration-time" curve for intravenous and intramuscular injection is the same.

Capreomycin does not pass through the blood-brain barrier, it penetrates the placental 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.

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

Contraindications:Hypersensitivity, pregnancy, the period of breastfeeding, children's age.

Carefully:

Caution should be applied capreomycin in patients with renal insufficiency and already existing hearing impairments. If it is necessary to prescribe the drug in such cases, it is necessary to compare the relationship between the expected benefit of therapy and the risk of additional impairment of the function of the VIII pair of cranial nerves and kidney damage.

With caution appoint capreomycin (as well as other antibiotics) to patients with any form of allergy, including drug.

During and after surgery, use with caution on the background of medicines,causing neuromuscular blockade (especially with a high probability of incomplete termination in the postoperative period).

Dehydration, myasthenia gravis gravis, parkinsonism, old age.

Pregnancy and lactation:Use during pregnancy is contraindicated. During the use of the drug should be excluded from breastfeeding.

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:

Clearance toreatinin (ml / min)	Clearance capreomycin (l / kg / hr 10²)	Period half-life (clock)	Dose (mg / kg) for the following dosage intervals
Clearance toreatinin (ml / min)	Clearance capreomycin (l / kg / hr 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).

For intramuscular injection, the contents of the 1 g bottle are dissolved in 2 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 is injected deep into the muscle, 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 containing 1 g of the drug. To introduce a dose of less than 1 g of this vial, the following dilution table is recommended:

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

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 (an increase in the level of urea nitrogen in the blood of more than 20 mg / 100 ml, a decrease in the excretion of phenolsulfonphthalein and the appearance of an abnormal urinary sediment, electrolyte imbalance reminiscent of Barter's syndrome and the development of toxic nephritis).

From the central nervous system: neurotoxicity, neuromuscular blockade.

From the sense organs: ototoxicity (subclinical hearing loss, tinnitus and dizziness).

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.

From the hematopoietic system: eosinophilia, leukocytosis, leukopenia, thrombocytopenia, hyperuricuria (more than 20 mg / 100ml) cylindruria, hematuria, leukocyturia.

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

Overdose:

SymptomsDizziness, tinnitus, vertigo (vestibular and auditory failure divisions VII cranial nerves), reducing the overall tone, neuro-muscular blockade (respiratory paralysis), hypokalemia, hypocalcemia, hypomagnesemia, and electrolyte disturbances, 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:

Muscle relaxant effect increases with diethyl ether, aminoglycosides, polymyxins, preservatives citrate blood decreases - neostigmine.

In combination with other anti-tuberculosis drugs (streptomycin, viomycin), as well as in combination with polymyxin, sodium kolistimetatom, amikacin, gentamicin, tobramycin, vancomycin, kanamycin, neomycin, furosemide, ethacrynic acid or methoxyflurane ototoxic and nephrotoxic effect is synergistic.

Special instructions:

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.

Simultaneous reception with streptomycin and viomycin 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 solution for intravenous and intramuscular injection 1 g.

Packaging:

1 g of active substance in a bottle of colorless tubular glass, type I, with a capacity of 10 ml, closed with a stopper with a notch from bromobutyl rubber, with an aluminum snap-in lid.

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

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

2. One vial of the preparation and one ampoule of solvent together with the instruction for use are 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:PL-000502

Date of registration:01.03.2011 / 18.01.2016

Expiration Date:01.03.2016

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

Manufacturer: & nbsp

BELCO PHARMA India

Representation: & nbspROUTEC LIMITEDROUTEC LIMITEDUnited Kingdom

Information update date: & nbsp28.04.2015

Illustrated instructions

Instructions

Capreomycin (Capreomycin)