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

Polypeptide antibiotic produced by Streptomyces capreolus (the minimum inhibitory concentration of MPC 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 only in relation to Mycobacterium tuberculosis capreolus.

Anti-TB drug II number (according to the classification of the World Health Organization). With monotherapy, it quickly causes the emergence of resistant strains, has full cross-resistance with viomycin and partial-with aminoglycosides. There is no cross-resistance between capreomycin and isoniazid, aminosalicylic acid, cycloserine, streptomycin, ethionamide and ethambutol. Has a teratogenic effect (skeletal abnormalities in experiments on rats).

Pharmacokinetics:

Time to reach the maximum concentration (TCmax) in plasma - 1 to 2 hours after intramuscular injection of 1.0 g and its value is 20-47 mg / l; after 10 hours - 4 mg / l.After intravenous (IV) infusion for an hour at a dose of 1 g, the maximum concentration (Cmax) is 30-50 mg / l. Bioavailability for intravenous and intramuscular injection 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% of the dose) by glomerular filtration in unchanged form, in small amounts - with bile.

Do not cumulate with a daily dose of 1.0 g 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:As part of complex therapy for pulmonary tuberculosis, incl. with ineffectiveness and intolerance of anti-tuberculosis drugs of the first series.

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

Carefully:

With caution should be used for kidney failure, hearing impairment, dehydration, myasthenia gravis, parkinsonism, 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.

Pregnancy and lactation:When pregnancy is contraindicated. If you need to use the drug during lactation at the time of treatment should stop breastfeeding.

Dosing and Administration:

Before the beginning of therapy it is necessary to confirm the presence of a patient sensitive to capreomycin strain of Mycobacterium tuberculosis. The average dose is 1 g / day, not more than 20 mg / kg / day.

Enter in / m deep, or IV, (dropwise, by infusion of 60 minutes) 1 time per day for 60-120 days, then 1 g 2 or 3 times a week for 12-24 months, in combination with other anti-TB drugs. Patients with impaired renal function should reduce the dose in accordance with the clearance of creatinine (CC).

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

Creatinine clearance (ml / min)	Clearance of capreomycin (l / kg / hr x10²)	The elimination half-life T_1/2(h)	Dose^a (mg / kg) for the following intervals between administrations
Creatinine clearance (ml / min)	Clearance of capreomycin (l / kg / hr x10²)	The elimination half-life T_1/2(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	3.40	8.8	8.16
80	4.35	6.8	10.4^b
100	5.31	5.6	12.7^b
110	5.78	5.2	13.9 ^b

^a- for patients with reduced renal function, the calculation of the initial maintenance dose is given for optional doses of capreomycin; 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.

^b- The usual dosage for patients with normal kidney function, 1 g / day and not exceeding 20 mg / kg / day, is administered for 60-120 days, and then administered 1 g 2 or 3 times a week.

For the / m introduction, the contents of the vial (0.5 g, 0.75 g) are dissolved in 2 ml of a 0.9% solution of sodium chloride or water for injection. 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, 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 capreomycin solution can be stored in the refrigerator for no more than 24 hours.

Side effects:

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

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

From the central nervous system: neurotoxicity, neuromuscular blockade. From the senses: ototoxicity (subclinical hearing loss, including irreversible, tinnitus, dizziness).

From the side of the liver: violation of liver function indicators (when used in combination with other anti-TB drugs that cause changes in liver function).

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

Allergic reactions: urticaria, skin rashes in the form of spots and nodules, accompanied by a sometimes febrile reaction.

Overdose:

Symptoms: dizziness, tinnitus,(defeat of the cochlear and vestibular nerves (branches of the VIII pair of cranial nerves)), a 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 maintaining urine at a rate 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 severe renal dysfunction - hemodialysis.

Interaction:The miorelaxing effect is enhanced by ether diethyl, other aminoglycosides, polymyxins, citrated blood preservatives, reduced - neostigmine methyl sulfate. In combination with other anti-tuberculosis drugs (streptomycin, viomycin), as well as in combination with polymyxins, incl. colistin, amikacin, gentamicin, tobramycin, vancomycin, kanamycin, neomycin, furosemide, ethacrynic acid or methoxyflurane, ototoxic and nephrotoxic effects are mutually reinforced.

Special instructions:

Research of kidney function should be carried out before treatment and I once a week during treatment. Before the start of treatment should be audiometry and evaluation of the vestibular function. It is recommended to monitor the concentration of capreomycin in the blood. During treatment, hematologic parameters and liver function are monitored. Since hypokalemia may develop during treatment, the serum potassium content should be determined on a monthly basis.

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.Increasing the concentration of AMC more than 30 mg / 100 ml, as well as any other signs of a decrease in renal function, with or without an increase in AMC concentration, requires a thorough examination of the patient, reducing the dose or completely discontinuing 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 defeat of the cochlear and vestibular nerves (branches of the VIII pair of cranial nerves) occurs in patients with impaired renal function or dehydration, as well as in those who receive drugs that have ototoxic effect. Often such patients experience dizziness and noise in the ears.

Always prescribed in combination with other anti-TB drugs. Simultaneous reception with streptomycin and biomycin is not recommended.

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).

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

If there is no improvement in the condition within 2-3 weeks or when new symptoms appear, specialist consultation is necessary.

Actions when skipping the introduction of one or more doses of the drug.

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 infusion and intramuscular injection of 0.5 g, 0.75 g of active substance in bottles with a capacity of 10 ml.

Packaging:

1 bottle with instructions for use in a pack of cardboard.

10 bottles with instructions for use in a cardboard box.

For hospitals:

- 50 bottles and 5 instructions for use in a cardboard box;

- from 1 to 50 bottles with an equal number of instructions for use in a cardboard box.

Complete with a solvent. Water for injection 5 ml in an ampoule.

1 vial and 1 ampoule in a contoured cell package (KNU) with instructions for use in a pack of cardboard.

5 bottles and 5 ampoules in separate KNU with instructions for use in a pack of cardboard.

In the pack put a knife to open the ampoules or a scarifier ampoule.

When using ampoules with notches, rings or break points, the ampoule opener opener or ampoule scarifier is allowed not to be inserted.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

After the expiry date of the drug, unused vials should be carefully opened, the contents dissolved in a large amount of water and drained into the drain.

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000100

Date of registration:22.12.2010

The owner of the registration certificate:KRASFARMA, JSC KRASFARMA, JSC Russia

Manufacturer: & nbsp

KRASFARMA, JSC Russia

Information update date: & nbsp12.02.2015

Illustrated instructions

Instructions

Capreomycin (Capreomycin)