Laxative use and altered drug absorption

To the Editor

A 57-year-old woman with chronic schizophrenia presented with intermittent upper limb tremor, leg and neck stiffness, and the sensation of her eyes rolling upwards. She had previously been stable for several years taking chlorpromazine 25–50 mg per night, olanzapine 17.5 mg per night and benztropine 2 mg twice daily. The benztropine had been prescribed to reduce the tremor she had developed whilst using antipsychotic medication. She had also experienced years of chronic constipation and used Dulcolax (bisacodyl) tablets. Despite an increasing dose, the effect of Dulcolax diminished over several years. One month prior to admission, her constipation medication was changed to three sachets of Movicol per day, with improvement in constipation but also the development of her current symptoms. Her GP then replaced Movicol with Actilax, but the symptoms persisted until Actilax was ceased during admission. Her constipation responded well to magnesium pellegrino, the extrapyramidal symptoms resolved, and she was able to be discharged on her usual medications.

Laxatives are a commonly prescribed over-the-counter medication. They are classified as bulk-forming laxatives, surfactant agents, osmotic agents, or stimulants. This patient experienced extrapyramidal symptoms whilst using Movicol and Actilax, both of which are osmotic agents. Movicol contains polyethylene glycol (PEG), a large osmotically active polymer which is not absorbed, causing intestinal water retention. It is also iso-osmolar with intestinal contents, promoting intestinal water secretion and thereby increasing stool frequency (Selby and Corte, 2010). Actilax differs from Movicol in that it contains lactulose, a synthetic disaccharide. It is not metabolised by enzymes within the intestine. As an undigested sugar within the intestinal lumen, it draws water to itself to maintain an iso-osmotic state, resulting in a laxative effect (Selby and Corte, 2010).

Evidence is sparse regarding the effect of laxatives on the absorption of other medications (Ramkumar and Rao, 2005). A study comparing absorption of amoxicillin co-administered with PEG versus placebo found a very small reduction in the duration and rate of absorption amongst the PEG group (Padoin et al., 1995). There are reports in the literature of subtherapeutic levels of levothyroxine in two hypothyroid patients associated with antacid and osmotic laxative use (Mersebach et al., 1999).

There is no evidence regarding the effect of laxatives on the intestinal absorption of orally administered benztropine, chlorpromazine, or olanzapine. The symptoms in this case were most likely due to one of two scenarios: either the laxatives reduced benztropine absorption, or they increased the concentration of one or both antipsychotics. Given the reports of laxatives causing reduced drug concentrations, a laxative-associated reduction in benztropine bioavailability, leading to the development of antipsychotic-induced extrapyramidal side effects, is the most likely explanation.

This case illustrates a rare but significant interaction between laxatives and benztropine used to control the extrapyramidal side effects of antipsychotic medication. Given the prevalence of laxative use, clinicians should be aware of the possibility that laxatives alter the absorption of other medications.