Key points from the evidence

Key points from the evidence

The content of this evidence summary was up-to-date in January 2014. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.

Summary

Colistimethate sodium (Colobreathe, Colomycin injection and Promixin) is licensed for treating pulmonary infections caused by Pseudomonas aeruginosa in people with cystic fibrosis but not in non-cystic fibrosis bronchiectasis. Four small case series (total n=148) provide weak evidence for the effectiveness of nebulised colistimethate sodium (Colomycin injection and Promixin) in people with non-cystic fibrosis bronchiectasis and P. aeruginosa. Nebulised or inhaled colistimethate sodium is very commonly associated with adverse respiratory effects, including cough, dyspnoea, bronchospasm and sore throat.

Regulatory status: off-label. The manufacturer of Promixin, Profile Pharma, has indicated that it plans to apply for a UK marketing authorisation for nebulised colistimethate sodium for treating chronic P. aeruginosa infection within 2–3 years.

The topic was prioritised because there was a high volume of requests from the NHS for information on this topic and there is uncertainty about the balance of risks and benefits when colistimethate sodium is used for non-cystic fibrosis bronchiectasis.

Effectiveness

  • Out of 3 similar case series, 2 found that nebulised colistimethate sodium statistically significantly reduced the mean number of exacerbations. The third did not look at this outcome.

  • Out of the 3 case series, 1 found that treatment statistically significantly reduced the mean number of hospital admissions. The 2 others found no significant difference.

  • All 3 case series found that treatment had no significant effect on forced expiratory volume in 1 second (FEV1). However, 1 of the 3 case series found that treatment statistically significantly reduced the annual decline in FEV1 and forced vital capacity (FVC).

  • A fourth study found no significant differences in the mean number of hospital admissions, duration of hospital stay, or duration of antibiotic use between nebulised colistimethate sodium and nebulised tobramycin.

Safety

  • Out of 3 similar case series, 2 did not report on adverse events. The third study reported that there were no adverse events.

  • A fourth study reported that there was no significant difference between nebulised colistimethate sodium and nebulised tobramycin in drug-related adverse events or withdrawals because of adverse events.

  • The summary of product characteristics for Promixin states that acquired resistance to colistimethate sodium by P. aeruginosa has been reported during clinical use.

Patient factors

  • The most common adverse effects of nebulised or inhaled colistimethate sodium are cough, dyspnoea, bronchospasm and sore throat (affecting at least 1 in 10 people).

  • In 1 study, 3 out of 30 patients did not receive nebulised colistimethate sodium because of intolerance.

  • Some people may find it difficult or inconvenient to use a nebuliser.

  • Some people may prefer to use an inhaler. However, all of the case series used nebulised colistimethate sodium. No case series used the colistimethate sodium dry powder inhaler (Colobreathe).

Resource implications

  • Colobreathe costs £968.80 for 56 capsules (containing 1.6625 million units) and a Turbospin inhaler.

  • Colomycin injection costs £18.00 for 10 vials containing 1 million units of colistimethate sodium and £32.00 for 10 vials containing 2 million units of colistimethate sodium.

  • Promixin costs £138.00 for 30 vials containing 1 million units of colistimethate sodium. The price includes the cost of the nebuliser, training, support service and all related consumables.

Key points

This evidence summary outlines the evidence for nebulised or inhaled colistimethate sodium for treating non-cystic fibrosis bronchiectasis.

Colistimethate sodium is a polymyxin antibiotic with activity against gram negative bacteria including P. aeruginosa. Colistimethate sodium powder for nebuliser solution (Colomycin injection, 1 or 2 million international units or Promixin, 1 million international units) is licensed for treating pulmonary infections caused by P. aeruginosa in people with cystic fibrosis. A dry powder inhaler (Colobreathe, 1.6625 million international units) is also licensed for the treatment of chronic pulmonary infections caused by P. aeruginosa in those aged 6 years and over with cystic fibrosis. Use of nebulised or inhaled colistimethate sodium for treating non-cystic fibrosis bronchiectasis is off-label.

No published randomised controlled trials (RCTs) have investigated nebulised or inhaled colistimethate sodium for non-cystic fibrosis bronchiectasis. Four small case series were identified that reported outcomes in a total of 148 people with non-cystic fibrosis bronchiectasis and P. aeruginosa colonisation who received nebulised colistimethate sodium.

Three of the case series (White et al. 2012, n=30; Dhar et al. 2010, n=19; and Steinfort and Steinfort 2007, n=18) used historical self-controls to compare outcomes before and after treatment with nebulised colistimethate sodium. Two of these case series found that treatment statistically significantly reduced the mean number of exacerbations (from 3.93 to 2.09 per year [p<0.002] in White et al. 2012 and from 7.8 to 2.7 per year [p<0.001] in Dhar et al. 2010). The third case series did not report exacerbations. White et al. 2012 and Steinfort and Steinfort 2007 found that treatment had no significant effect on hospital admissions, but Dhar et al. 2010 found that treatment statistically significantly reduced the mean number of hospital admissions (from 3.0 to 0.95 per year, p=0.002).

Two of the case series (White et al. 2012 and Dhar et al. 2010) found that treatment had no significant effect on FEV1. The third case series (Steinfort and Steinfort 2007) also found that treatment had no significant effect on FEV1 or FVC. However, it found that treatment statistically significantly reduced the annual decline in FEV1 (from 104 ml per year before treatment to 44 ml after treatment, p=0.035) and FVC (from 110 ml per year before treatment to 48 ml after treatment, p=0.033).

The fourth case series (Berlana et al. 2011, n=81) compared post-treatment outcomes in people who had received nebulised colistimethate sodium alone, tobramycin alone or both. There were no significant differences in the mean number of hospital admissions, duration of hospital stay, or duration of antibiotic use between colistimethate sodium and tobramycin. Combination treatment significantly reduced these outcomes compared with tobramycin alone.

White et al. (2012) and Dhar et al. (2010) did not report adverse events, and Steinfort and Steinfort (2007) reported that there were no adverse events. In Berlana et al. (2011), drug-related adverse events were reported by 58% of people who took colistimethate sodium, most commonly dyspnoea (shortness of breath), bronchospasm and cough (each affecting 12% of patients), wheezing (10%) and dry mouth (6%). There was no significant difference between colistimethate sodium and tobramycin in drug-related adverse events or withdrawals because of adverse events.

According to the summaries of product characteristics, colistimethate sodium is very commonly associated with adverse respiratory effects (affecting at least 1 in 10 people) including cough, dyspnoea, bronchospasm and sore throat. The summary of product characteristics for Promixin states that there have been reports of P. aeruginosa acquiring resistance to colistimethate sodium during clinical use.

The 4 case series provide weak evidence for the safety and effectiveness of nebulised colistimethate sodium for treating non-cystic fibrosis bronchiectasis and colonisation with P. aeruginosa. One unpublished RCT, Inhaled Promixin in the treatment of non-cystic fibrosis bronchiectasis, has now been completed and, once fully published and peer-reviewed, may provide higher level evidence about the safety and efficacy of nebulised colistimethate sodium for treating non-cystic fibrosis bronchiectasis.

About this evidence summary

'Evidence summaries: unlicensed or off-label medicines' summarise the published evidence for selected unlicensed or off-label medicines that are considered to be of significance to the NHS, where there are no clinically appropriate licensed alternatives. The summaries provide information for clinicians and patients to inform their decision-making and support the construction and updating of local formularies.

The summaries support decision-making on the use of an unlicensed or off-label medicine for an individual patient, where there are good clinical reasons for its use, usually when there is no licensed medicine for the condition requiring treatment, or the licensed medicine is not appropriate for that individual.

The strengths and weaknesses of the relevant evidence are critically reviewed within this summary, but this summary is not NICE guidance.