PROMIXIN Powder for nebuliser solution Ref.[27635] Active ingredients: Colistimethate

Bronchospasm

Nebulisation of colistimethate sodium may induce coughing or bronchospasm. It is advisable to administer the first dose under medical supervision. Pre-dosing with a bronchodilator is recommended and should be routine, especially if this is part of the patient’s current therapeutic regimen. FEV1 should be evaluated pre and post dosing. If there is evidence of colistimethate sodium induced bronchial hyperreactivity in a patient not receiving pre-treatment bronchodilators the test should be repeated on a separate occasion using a bronchodilator. Evidence of bronchial hyperreactivity in the presence of a bronchodilator may indicate an allergic response and Promixin should be discontinued. Bronchospasm that occurs should be treated as medically indicated.

Bronchial hyperreactivity in response to colistimethate sodium may develop with continued use over time and it is recommended that pre and post treatment FEV1s are evaluated at regular clinic visits.

Renal impairment

Colistimethate sodium is renally excreted and is nephrotoxic if high serum concentrations are achieved. Whilst this is unlikely during inhalation therapy, serum concentration estimations are recommended especially in patients with renal impairment.

Nephrotoxicity

Impairment of renal function has been reported, usually following use of higher than recommended intravenous or intramuscular doses in patients with normal renal function, or failure to reduce the intravenous or intramuscular dosage in patients with renal impairment or when used concomitantly with other nephrotoxic drugs. The effect is usually reversible on discontinuation of therapy.

Neurotoxicity

High serum concentrations of colistimethate sodium after intravenous or intramuscular administration may be associated with overdosage or failure to reduce the dosage in patients with renal impairment, and this may lead to neurotoxicity. Concomitant use with either non-depolarising muscle relaxants or antibiotics with similar neurotoxic effects can also lead to neurotoxicity. Dose reduction of colistimethate sodium may relieve symptoms. Neurotoxic effects that have been reported include: vertigo, transient facial paraesthesia, slurred speech, vasomotor instability, visual disturbances, confusion, psychosis and apnoea. (see also Section 4.5)

Porphyria

Use with extreme caution in patients with porphyria.

Microbial Resistance

Colistimethate sodium acquired resistance in mucoid Pseudomonas aeruginosa during clinical use has been reported. Susceptibility testing should be performed on patients who are treated on a long term basis, at regular clinic visits, and whenever a patient experiences an exacerbation (see Section 5.1).

Due to the effects of colistimethate sodium on the release of acetylcholine, non-depolarising muscle relaxants should be used with extreme caution in patients receiving Promixin as their effects could be prolonged (see Section 4.4).

Concomitant use of inhaled colistimethate sodium with other medications that are nephrotoxic or neurotoxic (e.g. cephalothin sodium, aminoglycosides, non-depolarising muscle relaxants) including those which are administered by the i.v. or i.m. routes should only be undertaken with the greatest caution (see Section 4.4).

Safety in human pregnancy has not been established. Animal studies do not indicate a teratogenic potential. However there is evidence that colistimethate sodium crosses the placenta and consequently there is potential for foetal toxicity if administered during pregnancy. Promixin should only be given during pregnancy if the benefits outweigh any potential risk.

Colistimethate sodium is excreted in breast milk; breast feeding is not recommended during therapy.

Neurotoxicity, characterised by dizziness, confusion or visual disturbances have been reported following parenteral administration of colistimethate sodium. If these effects occur patients should be warned against driving or operating machinery.

The commonest undesirable effects following nebulisation of colistimethate sodium are coughing and bronchospasm (indicated by chest tightness which may be detected by a decrease in FEV1) in approximately 10% of patients. (See also Section 4.4)

Adverse reactions are tabulated below by system organ class and frequency. Frequencies are defined as Very common (≥1/10): common (≥1/100 to <1/10): uncommon (≥1/1,000 to <1/100): rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000), not known (cannot be estimated from the available data)

Should hypersensitivity reactions such as skin rash occur treatment with colistimethate sodium should be withdrawn.

Cases of sore throat or sore mouth may be due to hypersensitivity or superinfection with Candida species.

Reporting of suspected adverse reactions

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

The addition of other antibiotics to solutions of Promixin may lead to precipitation. This medicinal product should not be mixed with other medicinal products except those mentioned in section 6.6.