Amitiza: new treatment option for chronic idiopathic constipation

PHARMACOLOGY

Lubiprostone is a prostone that selectively activates chloride channels to increase intestinal fluid secretion without altering serum electrolyte concentrations. This increases intestinal motility and the passage of stool whilst alleviating symptoms associated with chronic idiopathic constipation.¹

CLINICAL STUDIES

Three double-blind, placebo-controlled studies evaluated the safety and efficacy of lubiprostone 24 microgram twice daily in patients with chronic idiopathic constipation, defined as less than three spontaneous bowel movements (SBMs) per week in the absence of enema or suppository use.^1–3 

The primary outcome measure was the mean number of SBMs at the end of week 1 for the first and second studies and the change from baseline in SBM frequency at week 1 for the third study.^1–3

Bowel movements increased

In the first study (n=242), the mean number of SBMs at the end of week 1 was significantly greater in the lubiprostone-treated group than in the placebo group (5.69 vs 3.46, p=0.0001). Of the 120 patients given lubiprostone, 56.7% reported an SBM within 24 hours of the first dose compared with 36.9% of the 122 who received placebo (p=0.0024).² 

Similar results were seen in the second study involving 237 patients (mean number of SBMs 5.89 with lubiprostone vs 3.99 with placebo, p=0.0001), with a greater percentage of patients treated with lubiprostone having an SBM within the first 24 hours (61.3% vs 31.4%, p<0.0001).³

In the third study (n=124), the change from baseline in SBM frequency at week 1 was significantly greater for lubiprostone than placebo: 3.66 versus 1.26 (p<0.001).¹

Lubiprostone maintained this superiority to placebo through weeks 2–4 of therapy in all studies. Patients who were given lubiprostone reported significant improvements in stool consistency, straining and severity of constipation at all timepoints.^2,3

Well tolerated

Lubiprostone was generally well tolerated in all three studies, with nausea, diarrhoea and headache the most commonly observed adverse effects.¹ 

To reduce the risk of nausea, patients should be advised to take lubiprostone with food. In addition, patients should be advised to inform the prescriber if severe diarrhoea, dyspnoea or chest discomfort occurs.^1–3

Long-term safety

The long-term safety and tolerability of lubiprostone were assessed in three open-label studies involving 784 patients with chronic idiopathic constipation receiving 24 microgram twice daily for 12 months. Results from these studies showed a decrease in constipation severity, abdominal bloating and discomfort over the treatment period. Lubiprostone remained well tolerated.¹

Dose changes

Lubiprostone requires no change in dosage for the elderly or patients with renal impairment; however, patients with moderate to severe hepatic impairment should take a reduced dose of one capsule once daily.¹

References:

1. Amitiza Summary of Product Characteristics, October 2012.
2. Johanson JE et al. Am J Gastroenterol 2008; 103: 170–7.
3. Barish CF et al. Dig Dis Sci 2010; 55: 1090–7.

View Amitiza drug record

Further information: Sucampo

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