Subsidised use of methylnaltrexone in Australia for palliative care

To the Editor: Methylnaltrexone is a peripheral opioid antagonist registered for the treatment of opioid-induced constipation (OIC) on the basis of quality Phase III studies.1 Monitoring uptake of a new medication such as methylnaltrexone after it has been listed on the Pharmaceutical Benefits Scheme (PBS) is crucial to understanding how such medications can be best used in routine clinical practice.

Compared with the whole population, higher numbers of palliative care patients receive laxatives. Many factors contribute to this, with opioid use remaining the most cited reason.2 Australian epidemiological data estimate that more than 5000 people annually experience resistant OIC at the end of life.3 In 2004, a palliative care section was added to the PBS for people with “active, progressive, far-advanced disease for whom the prognosis is limited and the focus of care is the quality of life”.4 The subsidised medications available under this section have increased from an initially modest number, and now include methylnaltrexone, listed in March 2010 for OIC that is unresponsive to other laxatives.

Following PBS listing of a drug, its use is monitored by the Drug Utilisation Sub-Committee (DUSC) of the Pharmaceutical Benefits Advisory Committee.5 The DUSC conducted a review of all de-identified pharmacy claims for PBS-subsidised methylnaltrexone prescriptions from 1 March 2010 to 28 February 2011 (Methylnaltrexone 12 mg/0.6 mL [Relistor] utilisation report. Item 7.1, October 2011 agenda; unpublished report, available from DUSC@health.gov.au). Assuming that all initial prescriptions supplied corresponded to new patients, 261 patients were treated. Only 93 prescriptions for continuing medication were supplied. Uptake was far less than expected, with fewer initial and continuing prescriptions per patient contributing to this.

The review raises a number of issues. We cannot presently conclude whether these results represent:

• a multifactorial aetiology of constipation in this patient population, to which opioid use contributes relatively little;

• greater than expected effectiveness of other laxatives for treating OIC;

• patient preference; or

• differences between the efficacy of methylnaltrexone shown in clinical trials and its effectiveness in day-to-day clinical practice.

This illustrates that monitoring the actual uptake and continued use of new medications after their introduction is crucial, even when high-quality Phase III trials support their use.