CAPREOMYCIN Powder for solution for injection Ref.[6531] Active ingredients: Capreomycin

Warnings

The use of capreomycin 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.

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

Precautions

As capreomycin 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 capreomycin therapy, serum potassium levels should be determined frequently.

A partial neuromuscular block can occur after large doses of capreomycin.

Capreomycin should be administered cautiously to patients with a history of allergy, particularly to drugs.

Simultaneous administration of other antituberculous drugs which also have ototoxic and nephrotoxic potential (e.g. streptomycin, viomycin) is not recommended. Also, use with other drugs that are not given for the treatment of tuberculosis but have ototoxic or nephrotoxic potential (e.g. polymyxin, colistin sulphate, amikacin, gentamicin, tobramycin, vancomycin, kanamycin and neomycin) should also be undertaken only with great caution.

Pregnancy

The safety of capreomycin for use during pregnancy has not been established. Capreomycin has been shown to be teratogenic in rats when given at 3.5 times the human dose. There are no adequate and well controlled studies in pregnant women. Capreomycin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Fertility

Studies have not been performed to determine potential for carcinogenicity, mutagenicity, or impairment of fertility.

Breast-feeding

It is not known whether capreomycin is excreted in human milk. Caution should be exercised when administering to a nursing woman.

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 capreomycin (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 capreomycin 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 capreomycin have had eosinophilia exceeding 5%, but this has subsided with the reduction of capreomycin dosage to two or three times weekly.

Hypersensitivity: Urticaria and maculopapular rashes associated in some cases with febrile reactions have been reported when capreomycin 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 capreomycin. 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.

Not applicable.