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

Is active against strains Mycobacterium tuberculosis, detectable in humans. Anti-tuberculosis drug of the II series (according to the classification of the World Health Organization).

Tests for sensitivity. Sensitivity of strains M. tuberculosis to capreomycin in vitro varies depending on the environment and the technique used. Typically, the minimum inhibitory concentration for M. tuberculosis is the lowest in a liquid medium that does not contain the egg protein (7H10 or Dubos), and is from 1 to 5 mg / l when using an indirect method. Comparable inhibitory concentrations are obtained by applying 7H10 agar in a direct sensitivity test. When carrying out an indirect sensitivity test on standard test tubes with chopped 7H10 agar, sensitive strains are inhibited by the concentration of capreomycin from 10 to 25 mg / ml. Environments containing egg white, Lowenstein-Jensen or ATS, are required to inhibit sensitive strains with a concentration of 25 to 50 mg / l.

Cross-resistance. When monotherapy rapidly causes the emergence of resistant strains, has a full cross-resistance with biomycin and partial - with aminoglycosides.

There is no cross-resistance between capreomycin and isoniazid, aminosalicylic acid, cycloserine, streptomycin, ethionamide, ethambutol.

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

Pharmacokinetics:

Capreomycin It is not absorbed in sufficient quantity from the gastrointestinal tract and therefore must be administered parenterally. Time to reach the maximum concentration in the blood plasma (TC_mOh) - 1-2 hours after intramuscular (IM) administration of 1000 mg and its value is 20-47 mg / l; after 10h - 4 mg / l. After 24 hours, low concentrations of the drug remained in the serum. Daily administration of 1000 mg capreomycin for 30 days or more does not lead to any significant accumulation in most patients with normal and reduced renal function. When intramuscular injection of 1000mg capreomycin to healthy volunteers, 52% of it was excreted in the urine within 12 hours.

After intravenous (IV) infusion for 1 hour at a dose of 1000 mg, the maximum concentration in the blood plasma (C_mOh) is 30-50 mg / l. Bioavailability for iv and / m administration is the same. It does not pass through the blood-brain barrier, it penetrates the placental barrier. In the body it is not metabolized. It is excreted mainly by the kidneys (within 12 hours - 50-60% dose) by glomerular filtration in unchanged form, in small amounts - with bile.

Do not cumulate with a daily dose of 1000 mg for 30 days with normal kidney function. When the renal function is impaired, the half-life period (T_1/2) increases and there is a tendency to accumulation.

Indications:Tuberculosis of the lungs (if first-line drugs (isoniazid, rifampicin and streptomycin) have been ineffective or can not be used due to toxic effects or the presence of resistant strains Mycobacterium tuberculosis) in combination with other anti-TB drugs. Before using the drug should determine the sensitivity to capreomycin isolated strain Mycobacterium tuberculosis.

Contraindications:

Hypersensitivity to capreomycin, pregnancy, the period of breastfeeding, children under 18 years of age (safety and efficacy have not been established).

Carefully:

Renal failure, hearing impairment, dehydration, myasthenia gravis gravis, parkinsonism, old age, simultaneous use of capreomycin with drugs that have ototoxic and nephrotoxic effect (see the sections "Interaction with other drugs," Special Notice ").

Pregnancy and lactation:

Use during pregnancy is contraindicated.

If you need to use the drug during lactation at the time of treatment should stop breastfeeding.

Dosing and Administration:

Capreomycin for injection can be used intramuscularly or intravenously.

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 for patients with normal renal function is 1000 mg / day, but not more than 20 mg / kg / day.

Enter intramuscularly (deep) or intravenously (by drip, by infusion for 60 minutes) once a day for 60-120 days, then 1000 mg 2 or 3 times a week for 12-24 months in combination with other antituberculous drugs.

Patients with impaired renal function should reduce the dose in accordance with the clearance of creatinine (CC).

Calculation of the dose to achieve an average equilibrium concentration of capreomycin in serum 10 mg / ml (based on creatinine clearance):

Clearance creatinine (ml / min)	Clearance of capreomycin (l / kg / hr.10²)	Period half-life (h)	*Dose (mg / kg) for the following intervals between administrations**
Clearance creatinine (ml / min)	Clearance of capreomycin (l / kg / hr.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**

* for patients with reduced renal function, the calculation of the initial maintenance dose is given for optional doses of capreomycin; it is expected that increasing the intervals between doses will lead to an increase in the maximum and decrease in the minimum concentration of capreomycin in the serum as compared to shorter intervals;

** The usual dose for patients with normal renal function, 1000 mg / day and not exceeding 20 mg / kg / day, is administered for 60-120 days, and then 1000 mg is administered 2 or 3 times a week.

For the / m introduction the contents of the vial (500 mg, 750 mg, 1000 mg) are dissolved in 1 ml, 1.5 ml, 2 ml of a 0.9% solution of sodium chloride or water for injection, respectively. You should wait 2-3 minutes until the content is completely dissolved. Enter by deep intravenous injection, as a superficial injection can cause increased pain and the development of aseptic abscesses.

For IV injection the capreomycin solution prepared in the same way is diluted with 100 ml of 0.9% sodium chloride solution and injected for 60 minutes.

Side effects:

From the urinary system: nephrotoxicity (increased urea nitrogen concentration in blood plasma, decreased phenol sulfonphthalein excretion and the appearance of abnormal urinary sediment (cylinders, erythrocytes, leukocytes)), toxic nephritis, electrolyte imbalances reminiscent of Barter's syndrome.

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

From the central 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 accompanied by a sometimes febrile reaction.

If you notice any other side effects not listed in the instructions for use, tell your doctor.

Overdose:

Symptoms: dizziness, tinnitus, vertigo (damage to the auditory and vestibular departments of the VIII pair of cranial nerves), a decrease in the general muscle 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 in the volume of 3-5 ml / h / kg; control of water balance, concentration of electrolytes and QC; for the removal of neuromuscular blockade - the introduction of cholinesterase inhibitors, calcium preparations; with pronounced impaired renal function - hemodialysis, symptomatic therapy aimed at maintaining respiration and circulation.

Interaction:

The miorelaksiruyuschy effect is enhanced by ether diethyl, reduced - neostigmine methyl sulfate.

In combination with other anti-tuberculosis drugs (streptomycin, biomycin); from polymyxins, colistin, amikacin, gentamicin, tobramycin, vancomycin, kanamycin and neomycin, the ototoxic and nephrotoxic effect is mutually reinforced.

Special instructions:

Research of kidney function should be carried out before treatment and once a week during treatment. It is recommended to monitor the concentration of capreomycin in the blood.

Before the start of treatment should be audiometry and assessment of vestibular function and once a week during treatment.

During treatment, hematologic parameters and liver function are monitored. Since hypokalemia may develop during treatment, the serum potassium content should be determined monthly.

With caution should be used for kidney failure, hearing impairment, dehydration, old age. If it is necessary to prescribe the drug in such cases, one should compare the ratio of the expected benefit of therapy and the risk of impairment of the function of the VIII pair of cranial nerves and damage to the kidneys.

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

Nephrotoxic effect is associated with the concentration of capreomycin in the blood serum. Damage to the kidneys with tubular necrosis, an increase in the concentration of urea nitrogen in the blood (AMK) or serum creatinine and the appearance of an abnormal urinary sediment were noted.Very frequent cases of a slight increase in AMC and serum creatinine were observed in patients undergoing long-term treatment. For elderly patients, patients with impaired renal function or dehydration and patients receiving other nephrotoxic drugs, the risk of developing acute tubal necrosis is significantly higher. In a large percentage of these cases, the appearance in the urine of cylinders, erythrocytes and leukocytes. An increase in the concentration of AMC more than 30 mg / 100 ml, as well as any other signs of a decrease in renal function with an increase in the concentration of AMC or without it requires careful examination of the patient, reduce the dose or completely discontinue the drug. The clinically significant occurrence of an abnormal urinary sediment and a significant increase in the concentration of AMK (or serum creatinine) under the influence of capreomycin has not been established.

The risk of damage to the spinal cord and vestibule nerves (branches of the VIII pair of cranial nerves) is higher 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.

Always prescribed in combination with other anti-TB drugs.

Because of the risk of mutual enhancement of the nephro- and ototoxic effect, simultaneous administration with streptomycin and biomycin Not recommended; with polymyxin, colistin, amikacin, gentamicin, tobramycin, vancomycin, kanamycin should be used with caution. In elderly patients with normal renal function, dose adjustment is not required, in the case of impaired renal function, the dose is reduced depending on the QC (see section "Dosing and Administration").

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

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

If there is no improvement in the condition for 2-3 weeks or when new symptoms appear, consult a specialist.

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 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 administration, 500 mg, 750 mg or 1000 mg.

Packaging:

For 500 mg, 750 mg or 1000 mg capreomycin in vials, hermetically sealed with rubber stoppers, crimped with aluminum caps.

1 bottle together with the instruction for use is placed in a pack of cardboard.

5 bottles of the drug are placed in a contour mesh package made of a polyvinyl chloride film.

5 bottles of the drug are placed in a contour mesh package made of a polyvinylchloride film and a flexible package based on aluminum foil or a packaging material combined on a paper basis.

1 or 2 contoured cell packs with vials together with instructions for use are placed in a pack of cardboard.

Packing for hospitals

10 contour mesh packages with vials together with an equal number of instructions for use are placed in a cardboard box.

Storage conditions:

AT dry, protected from light, 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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003655

Date of registration:30.05.2016 / 02.05.2017

Expiration Date:30.05.2021

The owner of the registration certificate:BRYNTSALOV-A, CJSC BRYNTSALOV-A, CJSC Russia

Manufacturer: & nbsp

BRYNTSALOV-A, CJSC Russia

Representation: & nbspBRYNTSALOV-A, CJSCBRYNTSALOV-A, CJSC

Information update date: & nbsp05.12.2017

Illustrated instructions

Instructions

Capreomycin-Ferein® (Capreomycin-Ferein®)