Laikocin - 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 full cross-resistance with biomycin, 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 mycobacteria patient 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 blood plasma CmAch 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 pharmacokinetic curve "concentration-time" 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.

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, pregnancy, the period of breastfeeding, children's age, simultaneous use with streptomycin, viomycin.

Carefully:

Chronic renal failure, hearing impairment, allergic diseases, including drug allergy; during and after surgical interventions, with the use of drugs that cause neuromuscular blockade (especially with a high probability of incomplete termination in the postoperative period); dehydration; myasthenia gravis 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 you need to use the drug during lactation, you should stop 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 drip, by infusion 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 anti-tuberculosis drugs.

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

Clearance creatinine (ml / min)	Clearance capreomycin (l / kg / h x 10²)	Period half-life (hours)	Dose (mg / kg) for the following dosage intervals
Clearance creatinine (ml / min)	Clearance capreomycin (l / kg / h x 10²)	Period half-life (hours)	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

Method of preparation of solutions

For intramuscular injection, the contents of the vial (1 g) are dissolved in 2 ml of 0.9% sodium chloride solution 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 an aseptic abscess.

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.

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:

DIVISION TABLE

The amount of solvent added to a 10 ml vial containing 1 g	Volume of capreomycin solution for injection	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.

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 reminiscent of Barter's syndrome, development of toxic nephritis and acute necrosis of renal tubules).

From the central nervous system: neurotoxicity, neuromuscular blockade.

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

From the side of the liver: a violation of liver function tests with simultaneous treatment with capreomycin and other antituberculous 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 / 100 ml).

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

Other: hypokalemia, hypomagnesemia, hypocalcemia.

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 at a level of 3-5 ml / h / kg; control of water balance, electrolyte level and creatinine clearance; for the elimination of neuromuscular blockade - the introduction of anticholinesterase drugs, calcium preparations; with severe renal dysfunction - hemodialysis.

Interaction:

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

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

Special instructions:

If it is necessary to apply the drug to patients with chronic renal insufficiency and 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, increased 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 a large proportion of patients,who received long-term therapy. Many of them noted the appearance in the urine of cylinders, erythrocytes and leukocytes. If the urea nitrogen level increases 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, and if a kidney function is suspected, a thorough examination of the patient, a dose reduction based on creatinine clearance or complete cancellation of the drug.

Damage to the auditory and vestibular divisions of the VIII pair of cranial nerves occurs in patients with renal dysfunction or dehydration, as well as in the treatment with ototoxic agents. Such patients often experience dizziness and noise in the ears.

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 missed injections, administer as soon as possible, only if the time of the next dose is not reached; Doses do not double.

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

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

Form release / dosage:

Powder for solution for intravenous and intramuscular injection 1 g.

Packaging:

Vials of colorless transparent glass with a capacity of 10 ml, containing 1.0 g of the preparation.

Each vial is packaged in a cardboard box with instructions for use.

Solvent: water for injection (RU No. LP-002377 dated February 18, 2014) to 5.0 or 10.0 ml in a vial of colorless neutral glass or from low-density polyethylene with a fault line.

1 bottle with a drug and 1 ampoule 10.0 ml or 2 ampoules of 5.0 ml with a solvent or 1 bottle with a preparation without a solvent together with instructions for use in a cardboard pack.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LS-000889

Date of registration:11.11.2005 / 09.02.2016

Expiration Date:Unlimited

The owner of the registration certificate:FARMGID CJSCFARMGID CJSC Russia

Manufacturer: & nbsp

Laika Labs Limited India

Representation: & nbspLAYKA LES LIMITED LAYKA LES LIMITED India

Information update date: & nbsp09.02.2018

Illustrated instructions

Instructions

Laikocin (Lycocin)