Capreomycin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT KAPREOMYCIN (CAPREOMYCIN)

Composition:

Active substance: capreomycin;

1 vial contains 1 g of sterile capreomycin sulfate, calculated as capreomycin.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: amorphous powder, white or almost white.

Pharmacotherapeutic group.
Antituberculosis agents. Antibiotics. ATC code: J04AB30.

Pharmacological properties.

Pharmacodynamics.

Inhibits protein synthesis in bacterial cells, exerting a bacteriostatic effect. Selectively active against intracellular and extracellular Mycobacterium tuberculosis. When used as monotherapy, rapidly induces the emergence of resistant strains; cross-resistance with kanamycin is observed. Cross-resistance between capreomycin and biomycin, kanamycin, and neomycin may occur.

Pharmacokinetics.

Poorly absorbed (<1%) from the gastrointestinal tract. After intramuscular administration of a 1 g dose, the maximum plasma concentration (Cmax) of 20–47 mg/L is achieved within 1–2 hours. After a one-hour intravenous infusion of a 1 g dose, Cmax reaches 30 mg/L. Does not cross the blood-brain barrier, but crosses the placental barrier. Not metabolized; excreted unchanged and in active form via glomerular filtration in the kidneys (52% of the dose within 12 hours), at high concentrations (small amounts excreted with bile). Urine concentrations average 1.68 mg/mL within 6 hours after administration of a 1 g dose. Elimination half-life (T1/2) is 3–6 hours. Does not accumulate with daily administration of 1 g for 30 days in patients with normal renal function. In renal impairment, T1/2 is prolonged and accumulation tendency is observed.

Clinical characteristics.

Indications.

Combination therapy of pulmonary tuberculosis caused by capreomycin-susceptible mycobacteria, when drugs of the first line are ineffective or not tolerated.

Contraindications.
Hypersensitivity to capreomycin.

Interaction with other medicinal products and other forms of interaction.

Capreomycin should be administered with great caution simultaneously with polymyxin sulfate A, colistin, amikacin, gentamicin, tobramycin, vancomycin, kanamycin, and neomycin due to possible additive nephro- and ototoxic effects. Concurrent use with solutions containing B-complex vitamins is not recommended. Concomitant administration with antidiarrheal agents increases the risk of developing pseudomembranous colitis.

Incompatible with erythromycin, ampicillin, diphenylhydantoin, barbiturates, aminophylline, calcium gluconate, and magnesium sulfate. Capreomycin should not be administered simultaneously with other injectable antituberculosis agents (streptomycin, biomicin) due to possible enhancement of toxic effects, particularly on the VIII cranial nerve and renal function.

Incompatible with agents exerting ototoxic (aminoglycosides, polymyxins, furosemide, ethacrynic acid) and nephrotoxic (aminoglycosides, polymyxins, methoxyflurane) effects, and with agents causing neuromuscular blockade (aminoglycosides, polymyxins, diethyl ether and halogenated hydrocarbons for inhalational anesthesia, citrate blood anticoagulants). Neuromuscular blockade is reversed by neostigmine.

Special precautions for use

The medicinal product should be administered with caution to patients prone to allergic reactions, particularly those with drug allergies.

Hearing should be monitored periodically (1–2 times weekly) before and during treatment by audiometry to detect hearing impairment at high frequencies, and vestibular, renal (weekly), and liver function as well as serum potassium levels (monthly) should be assessed. Dosage adjustment is required in renal impairment depending on creatinine clearance.

The drug should be used with caution during and after surgery in combination with agents causing neuromuscular blockade (especially when there is a high likelihood of incomplete reversal of neuromuscular blockade in the postoperative period).

During treatment, dosage regimens and administration schedules should be continuously monitored for accuracy and regularity. If a dose is missed, the drug should be administered as soon as possible, provided that the time for the next scheduled dose has not yet arrived; the dose should not be doubled. Capreomycin may be prescribed only after determining strain susceptibility.

Limited use is recommended in patients with involvement of the VIII cranial nerve pair, myasthenia gravis, parkinsonism, dehydration, or impaired renal function, including elderly patients.

Use during pregnancy or breastfeeding. Use during pregnancy or breastfeeding is contraindicated. If it is necessary to use the drug, breastfeeding should be discontinued.

Ability to affect the reaction rate when driving or operating machinery. Given the possibility of adverse effects, it is recommended to refrain from driving or operating machinery.

Administration and Dosage

Administer intramuscularly, deeply. The usual adult dose is 1 g once daily (but not exceeding 20 mg/kg/day) for 60–120 days. Then continue treatment with 1 g of the drug administered 2 or 3 times per week. The total duration of treatment is 12 to 24 months.

To prepare the solution, dissolve the contents of the vial in 2 mL of 0.9% sodium chloride solution or in water for injections. Wait 2–3 minutes for complete dissolution.

Dosage in elderly patients. No dose adjustment is necessary.

Dosage in patients with impaired renal function. Dose adjustment should be based on creatinine clearance (see table):

Children.

Capreomycin is contraindicated in children.

Overdose.

Symptoms: renal function impairment, up to acute tubular necrosis (risk is increased in elderly patients, those with pre-existing renal dysfunction or dehydration), damage to the auditory and vestibular portions of the eighth cranial nerve, neuromuscular blockade leading to respiratory arrest (especially with rapid intravenous administration), electrolyte imbalance (hypokalemia, hypocalcemia, hypomagnesemia), electrolyte disturbances resembling Bartter syndrome or exacerbation of other adverse reactions.

Treatment: Symptomatic therapy: respiratory and circulatory support, hydration to maintain urine output at 3–5 mL/kg/hour (with normal kidney function); to counteract neuromuscular blockade, including respiratory depression and apnea – administration of anticholinesterase agents, calcium preparations, and hemodialysis (especially in patients with severe renal impairment); monitoring of fluid and electrolyte balance and creatinine clearance is required.

Side effects.

Renal and urinary system: nephrotoxicity – toxic nephritis, kidney damage with tubular necrosis, dysuria (increased or decreased frequency of urination or urine volume), renal failure, elevated blood urea nitrogen and serum creatinine levels, presence of abnormal sediment or formed blood elements in urine.

Nervous system and sensory organs: unusual fatigue, weakness, drowsiness; ototoxicity – hearing loss, including irreversible, tinnitus, ringing, buzzing, or sensation of "fullness" in the ears; vestibulotoxicity – impaired motor coordination, unsteady gait, dizziness; neuromuscular blockade.

Gastrointestinal tract: nausea, vomiting, anorexia, thirst.

Hepatobiliary disorders: hepatotoxicity with impaired liver function parameters (especially in patients with a history of liver disease), elevated liver enzymes and bilirubin levels, decreased bromsulphthalein excretion without changes in serum enzymes.

Allergic reactions: hypersensitivity reactions, including skin rashes, urticaria, maculopapular eruptions, pruritus, skin redness, edema.

Cardiovascular system: cardiac arrhythmias.

Blood system: leukocytosis, leukopenia, eosinophilia, thrombocytopenia.

Electrolyte imbalance: hypokalemia, hypomagnesemia, hypocalcemia.

Local reactions: pain, infiltration at the injection site, development of sterile abscesses or increased bleeding at the injection site.

Other: myalgia, respiratory difficulty (due to decreased respiratory muscle tone); increased body temperature (observed during combination therapy).

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

After reconstitution, use immediately.

Packaging.

1 g in a vial.

Prescription status. Prescription only.

Manufacturer. JSC "Kyivmedpreparat".

Manufacturer's address and location of business activity.

139 Saksaganskogo Street, Kyiv, 01032, Ukraine.