Капреомицин-ДЕКО

Actions: Капреомицин-ДЕКО is active against human strains of Mycobacterium tuberculosis.

Frequent cross-resistance occurs between Капреомицин-ДЕКО and viomycin. Varying degrees of cross-resistance between Капреомицин-ДЕКО and kanamycin and neomycin have been reported. No cross-resistance has been observed between Капреомицин-ДЕКО and isoniazid, aminosalicylic acid, cycloserine, streptomycin, ethionamide or ethambutol.

Indications: Капреомицин-ДЕКО should be used concomitantly with other appropriate antituberculous agents for the treatment of pulmonary infections caused by Капреомицин-ДЕКО-susceptible strains of Mycobacterium tuberculosis when the primary agents (isoniazid, rifampicin, streptomycin and ethambutol) have been ineffective or cannot be used because of toxicity or the presence of resistant tubercle bacilli.

The usual dose is 1g daily (but 20mg/kg/day should not be exceeded) given by deep intramuscular injection only for 60 to 120 days, followed by 1g intramuscularly two or three times a week. Капреомицин-ДЕКО is always administered in combination with at least one other antituberculous agent to which the patient's strain of tubercle bacillus is susceptible.

Капреомицин-ДЕКО should be dissolved in 2ml of 0.9% Sodium Chloride Intravenous Infusion BP or Water for Injections PhEur. Two to three minutes should be allowed for complete solution.

For administration of a 1g dose, the entire contents of the vial should be given. For dosages of less than 1g the following dilution table may be used:

The elderly: As for adults. Reduce dosage if renal function is impaired.

Patients with reduced renal function: A reduced dosage should be given based on creatinine clearance using the guidance given in the following table. These dosages are designed to achieve a mean steady-state Капреомицин-ДЕКО level of 10 micrograms/ml, at various levels of renal function:

Paediatric population

Not for paediatric use since the safety of Капреомицин-ДЕКО for use in infants and children has not been established. No data are available.

Hypersensitivity to the active substance.

Warnings

The use of Капреомицин-ДЕКО in patients with renal insufficiency or pre-existing auditory impairment must be undertaken with great caution, and the risk of additional eighth cranial nerve impairment or renal injury should be weighed against the benefits to be derived from treatment.

Капреомицин-ДЕКО must be used only in conjunction with adequate doses of other antituberculous drugs. The use of Капреомицин-ДЕКО alone allows the rapid development of strains resistant to it.

Precautions

As Капреомицин-ДЕКО is potentially ototoxic, audiometry and assessment of vestibular function should be performed before starting treatment and at regular intervals during treatment.

Regular tests of renal function should be made throughout the period of treatment, and reduced dosage should be used in patients known, or suspected, renal impairment (see “Dosage and Administration”).

Since hypokalaemia may occur during Капреомицин-ДЕКО therapy, serum potassium levels should be determined frequently.

A partial neuromuscular block can occur after large doses of Капреомицин-ДЕКО.

Капреомицин-ДЕКО should be administered cautiously to patients with a history of allergy, particularly to drugs.

Not relevant

Renal: Elevation of serum creatinine or blood urea and abnormal urine sediment have been observed. Toxic nephritis was reported in one patient with tuberculosis and portal cirrhosis who was treated with Капреомицин-ДЕКО (1g) and aminosalicylic acid daily for one month. This patient developed renal insufficiency and oliguria and died. The post-mortem showed subsiding acute tubular necrosis.

Electrolyte disturbances resembling Bartter's syndrome have been reported in one patient.

Hepatic: A decrease in bromsulphthalein excretion without change in serum enzymes has been noted in the presence of pre-existing liver disease. Abnormal results in liver function tests have occurred in many patients receiving Капреомицин-ДЕКО in combination with other antituberculous agents which are also known to cause changes in hepatic function. Periodic determinations of liver function are recommended.

Haematological: Leucocytosis and leucopenia have been observed. Rare cases of thrombocytopenia have been reported. Most patients receiving daily Капреомицин-ДЕКО have had eosinophilia exceeding 5%, but this has subsided with the reduction of Капреомицин-ДЕКО dosage to two or three times weekly.

Hypersensitivity: Urticaria and maculopapular rashes associated in some cases with febrile reactions have been reported when Капреомицин-ДЕКО and other antituberculous drugs were given concomitantly.

Otic: Clinical and subclinical auditory loss has been noted. Some audiometric changes have proved reversible and others, with permanent loss have not been progressive following withdrawal of Капреомицин-ДЕКО. Tinnitus and vertigo have occurred.

Injection site reactions: Pain and induration at injection sites have been observed. Excessive bleeding and sterile abscesses have also been reported at these sites.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continues monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard.

Signs and symptoms: Hypokalaemia, hypocalcaemia, hypomagnesaemia and an electrolyte disturbance resembling Bartter's syndrome have been reported to occur in patients with Капреомицин-ДЕКО toxicity. Nephrotoxicity, including acute tubular necrosis; and ototoxicity, including dizziness, tinnitus, vertigo and loss of high-tone acuity (see 'Warnings' and 'Precautions'). Neuromuscular blockage or respiratory paralysis may occur following rapid intravenous administration.

If Капреомицин-ДЕКО is ingested, toxicity is unlikely because less than 1% is absorbed from an intact gastro-intestinal system.

Treatment: Symptomatic and supportive therapy is recommended. Activated charcoal may be more effective than emesis or lavage in reducing absorption.

Patients who have received an overdose of Капреомицин-ДЕКО and have normal renal function should be hydrated to maintain a urine output of 3-5ml/kg/hr. Fluid balance electrolytes and creatinine clearance should be monitored.

Haemodialysis is effective in patients with significant renal disease.

Pharmacotherapeutic group: Antimycobacterials, ATC code: J04AB30

Капреомицин-ДЕКО is active against human strains of Mycobacterium tuberculosis.

Капреомицин-ДЕКО sulphate is not significantly absorbed from the gastrointestinal tract, and must be administered parenterally.

Following intramuscular injection of 1g of Капреомицин-ДЕКО in human subjects, peak serum concentrations in the range of 20-50µg/ml are achieved after 1-2 hours. Serum concentrations are low at 24 hours and daily injections of 1g for 30 days produced no significant accumulation in subjects with normal renal function.

Капреомицин-ДЕКО is excreted in the urine, essentially unaltered, and approximately 50% of a 1g intramuscular dose is excreted within 12 hours.

There are no preclinical data of relevance to the prescriber in addition to those summarised in other sections of the Summary of Product Characteristics.

Not applicable.

The solution may acquire a pale straw colour and darken with time, but this is not associated with loss of potency or the development of toxicity.

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.