Abbreviations/Key
b.i.dChoice of Laxatives
Constipation and Advanced Illness
- •reducing bowel transit time (exercise, stimulant laxatives, osmotic laxatives)
- •increasing fecal water (osmotic laxatives, stimulant laxatives)
- •increasing the ability of the feces to retain water (fiber, docusate, osmotic laxatives).
Mode of Action and Classification
- •liquid paraffin and magnesium hydroxide oral emulsion BP
- •magnesium hydroxide suspension (Milk of Magnesia®)
- •magnesium sulfate (Epsom Salts)
Characteristics of Stimulant Laxatives
Onset of action
Evidence Base
- •senna vs. lactulose35
- •senna vs. misrakasneham (an Ayurvedic herbal remedy)36
- •senna and lactulose vs. co-danthramer (dantron and poloxamer)37
- •senna and lactulose vs. magnesium hydroxide and liquid paraffin.38
Sykes N. A clinical comparison of lactulose and senna with magnesium hydroxide and liquid paraffin emulsion in a palliative care population. Unpublished data, 1991. [Cited in Candy B, Jones L, Goodman ML, Drake R, Tookman A. Laxatives or methylnaltrexone for the management of constipation in palliative care patients. Cochrane Database Syst Rev 2011;1:CD003448.]
Cautions
Committee on Safety of Medicines and Medicines Control Agency. Danthron restricted to constipation in the terminally ill. Current Problems in Pharmacovigilance 2000;26:4. Available from http://www.mhra.gov.uk/home/groups/plp/documents/websiteresources/ con007462.pdf.
Undesirable Effects
Dose and Use
Bisacodyl
- •start with 10–20 mg PO at bedtime
- •if necessary, increase by stages to 20 mg PO t.i.d.
- •by suppository: 10–20 mg PR once daily.
Senna
- •start with 17.2 mg at bedtime or, if taking opioids, 17.2 mg b.i.d.
- •if necessary, increase progressively to 17.2 mg→25.8 mg→34.4 mgt.i.d.
Sodium picosulfate (UK)
- •start with 5–10 mg at bedtime; 10 mg if taking regular opioids
- •if necessary, increase daily by 5 mg until a satisfactory result is achieved
- •median satisfactory dose=15 mg at bedtime
- •typical maximum dose=30 mg.34
Supply
- 1.Ask about the patient’s past and present bowel habit and use of laxatives; record the date of last bowel action.
- 2.Palpate for fecal masses in the line of the colon; examine the rectum digitally if the bowels have not been open for ≥3 days or if the patient reports rectal discomfort or has diarrhea suggestive of fecal impaction with overflow.
- 3.For inpatients, keep a daily record of bowel actions.
- 4.Encourage fluids generally, and fruit juice and fruit specifically.
- 5.When an opioid is prescribed, prescribe senna (Box A) and titrate the dose according to response.Box ADose schedule for senna
- •if not constipated:
- generally start with 17.2 mg at bedtime
- if no response after 24–48 h, increase to 17.2 mg at bedtime and each morning
- •if already constipated
- generally start with 17.2 mg at bedtime and each morning
- if no response after 24–48 h, increase to 25.8 mg at bedtime and each morning
- •if no response after a further 24–48 h, consider adding a third daytime dose
- •if necessary, consider increasing to 34.4 mgt.i.d., occasionally higher.
- •
- 6.During dose titration and subsequently: if ≥3 days since last bowel action, give suppositories, e.g., bisacodyl 10 mg and glycerol 4 g, or a micro-enema. If these are ineffective, administer a phosphate enema and possibly repeat the next day.
- 7.If the maximum tolerated dose of senna is ineffective (Box A), halve the dose and add an osmotic laxative, then titrate as necessary, e.g.:
- •lactulose 15 mL once daily–b.i.d. or
- •polyethylene glycol (macrogol) 1 sachet each morning
- •
- 8.Alternatively, prescribe SC methylnaltrexone (Box B).Box BMethylnaltrexone for opioid-related constipation
- Methylnaltrexone is relatively expensive ($55 per 12 mg vial) and should be considered only when the optimum use of laxatives is ineffective. Because constipation in advanced disease is generally multifactorial in origin, methylnaltrexone does not replace the need for other laxatives. Most patients who respond do so after 1–2 doses.
- •marketed as a SC injection for use in patients with “advanced illness” and opioid-related constipation despite treatment with laxatives
- •about 1/3–1/2 of patients given methylnaltrexone have a bowel movement within 4 h, without loss of analgesia or the development of opioid withdrawal symptoms
- •dose recommendations (from USA PI):
- for patients weighing 38–62 kg, start with 8 mg on alternate days
- for patients weighing 62–114 kg, start with 12 mg on alternate days
- outside this range, give 150 microgram/kg on alternate days
- in severe renal impairment (creatinine clearance <30 mL/min), the dose should be halved
- the interval between administrations can be varied, either extended or reduced, but not more than once daily
- •methylnaltrexone is contraindicated in cases of known or suspected bowel obstruction. It should be used with caution in patients with conditions which may predispose to perforation. Common undesirable effects include abdominal pain/colic, diarrhea, flatulence, and nausea; these generally resolve after a bowel movement; postural hypotension also can occur.
- 9.If the stimulant laxative causes intestinal colic, divide the total daily dose into smaller more frequent doses. Alternatively, change to an osmotic laxative (see above), then titrate as necessary.
- 10.An osmotic laxative may be preferable in patients with a history of colic with senna or other stimulant laxative, e.g., bisacodyl.
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Footnotes
Series Co-Editors: Andrew Wilcock, DM, FRCP, and Robert Twycross, DM, FRCP