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

It is recommended that colistimethate sodium (CMS) should be administered under the supervision of physicians with appropriate experience in its use.

Posology

The dosage can be adjusted depending on the severity of the condition and clinical response.

Recommended dose range

Administration via inhalation

Adults, adolescents and children ≥2 years:

1-2 MIU two to three times per day (max 6 MIU/day).

Children <2 years:

0.5-1 MIU twice daily (max 2 MIU/ day).

Relevant clinical guidance on treatment regimens, including duration of treatment, periodicity and co-administration of other antibacterial agents should be adhered to.

Older people:

Dose adjustment is not considered necessary.

Renal impairment:

Dose adjustment is not considered necessary, however caution is advised in patients with renal impairment (see sections 4.4 and 5.2).

Hepatic impairment:

Dose adjustment is not considered necessary.

Method of administration

Promixin for nebulisation is intended for administration by nebulisation using a suitable nebuliser.

Drug delivery characteristics from in vitro studies with different nebuliser systems are detailed below;

^# Measured using a simulated inhalation: exhalation (I:E) ratio of 1:1, a tidal volume of 500mL and 15 breathes per minute.

• All Promixin reconstituted with a 50:50 mixture of WFI and 0.9% saline to the recommended volume for each nebuliser system.
• Pari Boy SX operated at 1.6 bar pressure, 5.1L/min flow rate.
• (d) is calculated from (b) / 100 x ©
• (f) = (d) / (e)

^# Measured using a simulated inhalation: exhalation (I:E) ratio of 1:1, a tidal volume of 500mL and 15 breathes per minute.

• All Promixin reconstituted with a 50:50 mixture of WFI and 0.9% saline to the recommended volume for each nebuliser system.
• Pari Boy SX operated at 1.6 bar pressure, 5.1L/min flow rate.
• (d) is calculated from (b) / 100 x ©
• (f) = (d) / (e)

Colistimethate sodium undergoes hydrolysis to the active substance colistin in aqueous solution.

For special precautions for disposal and handling of reconstituted solutions, see Section 6.6

If other treatments are being taken, they should be taken in the order recommended by the physician.

Dose conversion table

In the EU, the dose of colistimethate sodium (CMS) must be prescribed and administered only as International Units (IU). The product label states the number of IU per vial.

Confusion and medication errors have occurred because of the different expressions of dose in terms of potency. The dose is expressed in the US, and other parts of the world, as milligrams of colistin base activity (mg CBA).

The following conversion table is prepared for information and the values must be considered nominal and approximate only.

CMS conversion table:

^* Nominal potency of the drug substance = 12.500 IU/mg

Overdosage may cause apnoea, muscle weakness, vertigo, transient facial paraesthesia, slurred speech, vasomotor instability, visual disturbances, confusion, psychosis and renal insufficiency.

No antidote is available. Management of overdose is by means of supportive treatment and measures designed to increase clearance of colistimethate sodium such as inducing an osmotic diuresis with mannitol, peritoneal dialysis or prolonged haemodialysis.

Unopened: 3 years.

After reconstitution:

Chemical and physical in-use stability of solution reconstituted in the original vial has been demonstrated for up to 24 hours at 2 to 8°C. Patients self-treating with nebulised antibiotic should be advised to use solutions immediately after preparation. If this is not possible, solutions should not be stored for longer than 24hrs in a refrigerator.

Promixin may be reconstituted to produce a clear colourless to pale yellow solution,with either Water for Injections (WFI) to produce a hypotonic solution, a 50:50 mixture of WFI and 0.9% sodium chloride to produce an isotonic solution, or with 0.9% sodium chloride to produce a hypertonic solution. The volume used for reconstitution should be in accordance with the instructions for use provided with the nebuliser device, and is normally not more than 4ml. During reconstitution swirl gently to avoid frothing. When reconstituted, Promixin may be used with any conventional nebuliser suitable for delivery of antibiotic solutions.

Solutions should be used immediately after reconstitution, however if this is not possible solutions must be used within 24 hours and stored in a refrigerator. Any unused solution remaining in the nebuliser must be discarded following treatment. For instructions on the use of Promixin with the I-neb AAD System, please refer to detailed instructions provided with the device.

Conventional nebulisers operate on a continuous flow basis and it is likely that some nebulised drug will be released into the local environment. When used with a conventional nebuliser, Promixin should be administered in a well-ventilated room, particularly in hospitals where several patients may be using nebulisers at the same time. Tubing or filters may be used to prevent waste aerosol from entering the environment.