

Relistor (Wyeth)
vials containing 12 mg/0.6 mL solution
Approved indication: opioid-induced constipation
Australian Medicines Handbook section 12.4.4

Constipation is one of the common adverse effects of opioid analgesics. This constipation is caused by several mechanisms such as altered smooth muscle tone in the gut.

Methylnaltrexone is related to the opioid antagonist naltrexone. Whereas naltrexone is particularly used to block the effects of opioids on the central nervous system, methylnaltrexone is more selective for peripheral opioid receptors. This is because adding a methyl group reduces lipid solubility which limits the molecule's ability to cross the blood-brain barrier. Blocking opioid receptors in the gut should relieve constipation without counteracting the analgesic effects of opioids.

While naltrexone is taken by mouth, methylnaltrexone has to be given by subcutaneous injection. It has a half-life of approximately eight hours and most of the dose is excreted unchanged, mainly in the urine. The dose is adjusted according to the patient's weight and is usually given on alternate days as needed.

A dose-ranging study was carried out in 33 patients receiving opioids for palliative care. For patients receiving a minimum dose of at least 5 mg the median time until a bowel movement was 1.26 hours. Almost half of these patients responded within four hours. Higher doses did not improve the response.1

A double-blind placebo-controlled trial was carried out in 133 terminally ill patients taking opioids and laxatives. They were given injections every other day for two weeks. A bowel motion occurred within four hours of the first injection in 48% of the methylnaltrexone group and in 15% of the placebo group. The median time between the injection and a bowel movement was 6.3 hours with methylnaltrexone, but more than 48 hours with placebo. After two weeks the response rate was 38% with methylnaltrexone and 8% with placebo. Pain scores were largely unchanged during the study.2

Patients given methylnaltrexone are more likely than those given placebo to complain of nausea, dizziness, flatulence, abdominal pain and increased temperature.2 Diarrhoea can occur and if it is persistent, treatment should be discontinued. The drug should not be used if the patient is suspected of having an obstruction of the bowel.

The longer-term efficacy of methylnaltrexone is uncertain because the patients in the trials had a limited life expectancy. At present methylnaltrexone is reserved for palliative care patients with opioid-induced constipation whose response to laxatives has been insufficient.

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Notes on references

