Capreomycin

Capreomycin is an anti-tuberculosis agent.

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Indications Capreomycin

It is used for pulmonary tuberculosis, which develops due to drug-sensitive strains of mycobacteria (Koch's bacillus is a microorganism that causes tuberculosis), in situations where type 1 anti-tuberculosis drugs do not have the required effect or cannot be used due to toxic effects or the presence of resistant tuberculosis bacilli.

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Release form

The drug is released in the form of powder for intramuscular injections.

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Pharmacodynamics

An antibiotic extracted from the Streptomyces capreolus element. The drug demonstrates activity against various strains of Koch's bacillus.

No cross-resistance is observed between capreomycin and cycloserine, isoniazid, PAS, streptomycin, ethionamide, and ethambutol. However, cross-resistance is detected when the substance is combined with kanamycin, florimycin, or neomycin.

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Pharmacokinetics

The drug is almost not absorbed inside the gastrointestinal tract (less than 1%). After intramuscular administration in a 1000 mg portion, the plasma Cmax value (equal to 20-47 mg/l) is noted after 1-2 hours. When using a 60-minute intravenous infusion of 1000 mg of the drug, the Cmax values are equal to 30-50 mg/l. The AUC level after intramuscular and intravenous administration is the same. The drug passes through the placenta, but not through the BBB.

It is not subject to exchange processes, excretion is carried out unchanged, mainly through the kidneys (over 12 hours - approximately 50-60% of the portion), by means of glomerular filtration. A small part of the element is excreted together with bile. In urine, the substance indicators over 6 hours from the moment of administration of the drug in a 1 g portion are on average equal to 1.68 mg / ml. The half-life is in the range of 3-6 hours.

In individuals with healthy renal function, the substance does not accumulate when used daily in a dose of 1000 mg (over a 30-day period). If a disorder in renal function is present, the half-life increases and a tendency for accumulation of the drug develops.

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Dosing and administration

Before use, it is recommended to determine the patient's sensitivity to the drug of the microflora that provoked the disease. The drug should be administered deeply, intramuscularly. It is used with caution in people with any form of allergy (especially drug-induced).

Often, 1000 mg of the drug is administered daily (maximum 20 mg/kg of the substance per day) over a 60-120-day period, and later 2-3 times per week in the same dose. Therapy should continue for 1-2 years.

People with kidney problems need to adjust the dosage and the duration of the interval between injections (taking into account the CC values). The more severe the renal dysfunction, the longer the intervals between injections should be.

The medicinal powder is first dissolved in physiological injection fluid or sterile injection water (2 ml). It takes 2-3 minutes for the substance to completely dissolve.

Renal function must be constantly monitored throughout the entire treatment period (once a week), and in addition, audiometry must be performed (assess hearing acuity) and the functioning of the vestibular apparatus must be checked.

Because the use of Capreomycin may provoke the development of hypokalemia, it is necessary to constantly monitor plasma potassium levels.

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Use Capreomycin during pregnancy

There is no information regarding the safety of using Capreomycin during breastfeeding or pregnancy, which is why it can only be prescribed after assessing all possible risks and benefits.

Contraindications

Main contraindications:

• severe intolerance associated with the use of drugs;
• combined administration with other parenteral anti-tuberculosis agents that have oto- and nephrotoxic effects (for example, florimycin or streptomycin);
• The use of the drug together with amikacin, tobramycin, and also polymyxin sulfate or vancomycin, neomycin or colimycin, kanamycin or gentamicin should be done with extreme caution, because this may result in a combination of oto- and nephrotoxic activity.

Side effects Capreomycin

The use of the drug may cause some side effects:

• an increase in plasma levels of creatinine and urea, and in addition the appearance of erythrocytes and leukocytes in the urine;
• there are isolated data on the development of electrolyte disorders and toxic nephritis;
• the appearance of ototoxicity (damage to the functionality of the auditory organs);
• changes in liver function tests have been observed in many people using the drug in combination anti-tuberculosis treatment;
• eosinophilia, leukopenia or leukocytosis. Thrombocytopenia is rarely observed;
• allergy symptoms in the form of maculopapular rashes, urticaria and increased temperature (observed with combination treatment);
• compaction and pain in the injection area;
• There is information about the appearance of severe bleeding and “cold” type abscesses (abscesses or abscesses of a tuberculous nature, with a weak inflammatory expression) at the site of drug administration.

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Overdose

In case of poisoning, kidney function is impaired, which can develop into acute tubular necrosis (increased risks in this case are in elderly people and people with dehydration or an existing problem with kidney function). Also, damage to the vestibular and auditory zones of the 8th pair of cranial neurons is noted. Blocking of the neuromuscular system activity is possible, sometimes reaching the point of stopping the respiratory processes (often due to rapid administration of drugs) and electrolyte imbalance (hypokalemia, -magnesemia or -calcemia).

Symptomatic measures are taken: support of blood flow and respiratory function, and in addition, hydration, allowing to bring the urine outflow to the value of 3-5 ml/kg/hour (normal kidney function), which will prevent blocking of neuromuscular activity. To prevent apnea and respiratory depression, anticholinesterase agents or calcium drugs are used, and hemodialysis is also performed (especially in people with severe forms of renal disorders). It is also necessary to monitor the values of EBV and CC.

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Interactions with other drugs

Cisplatin with vancomycin increases the risk of nephrotoxic or ototoxic manifestations.

There is no compatibility with medications that have ototoxic (furosemide with aminoglycosides, as well as ethacrynic acid with polymyxins) and nephrotoxic (aminoglycosides with methoxyflurane and polymyxins) effects, as well as with substances that provoke a blockade of neuromuscular activity (polymyxins with aminoglycosides, halogenated hydrocarbon elements for inhalation anesthesia, diethyl ether, as well as citrate blood preservatives).

The muscle relaxant effect is reduced by the use of neostigmine methyl sulfate.

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Storage conditions

Capreomycin should be stored in a place inaccessible to small children. Temperature values are maximum 25°C.

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Shelf life

Capreomycin can be used for a period of 2 years from the date of manufacture of the pharmaceutical substance.

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Application for children

There is no data regarding the safety of using the drug in pediatrics.

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Analogues

Analogues of the drug are Benemicin, Rifampicin, Cycloserine with Kapocin, Mdserin with Rifabutin, and also Coxerin, Rifapentine, Makox with R-cinex and R-butin with Rifacin. The list also includes Mikobutin, R-cin and Rifapex.

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