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Home , Cathartic, Laxative, Macrogol, Rectal pain

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Opioid-induced Inside 1 How cause constipation – a preventable problem 1 Impact of -induced constipation One of the most common adverse effects of chronic opioid 2 Managing opioid-induced constipation 3 Prevention and treatment of opioid- 1-4 therapy is constipation. Up to 95% of patients prescribed an induced constipation 4-6 opioid report constipation as a side effect, which can occur 4 Other factors affecting constipation soon after taking the first dose.6 4 Ongoing patient management

Older adults tend to be at higher risk of constipation because of immobility, poor diet, poor fluid intake and concurrent use of constipating medicines.7 Older adults Key points from chronic are likely to be less active, treated with opioid and therefore, are at considerable risk of developing constipation. Constipation is a debilitating adverse effect of opioid To prevent opioid-induced constipation, Australian guidelines recommend prescribing analgesics. suitable concurrently with opioid analgesics.1,7,8 An analysis of the DVA When initiating an opioid dataset found that of the 42,000 members in the veteran community dispensed an , consider a 9 opioid analgesic, over 70% were not concurrently dispensed a . combined laxative Other medicines, particularly those that are highly , can also cause with a stool softener. constipation, which may further compound the problem.10 Osmotic laxatives may be This therapeutic brief outlines how to prevent and treat opioid-induced constipation, appropriate for patients in palliative care or for those with including the most appropriate laxatives to use, and highlights commonly used non-responsive constipation. medicines that may also contribute to constipation. Review use of bulking agents. Review other medicines that How opioids cause Impact of opioid- may further contribute to constipation induced constipation constipation. Opioids cause constipation by Opioid-induced constipation can be so Opioid-induced constipation has an impact binding to specific receptors in the intolerable that it causes significant on quality of life that is comparable to and central nervous social and psychological trauma for other common chronic conditions.6,12,14 system, resulting in reduced bowel patients. It has been reported to be Some patients would rather endure motility through direct and indirect the most bothersome side effect of than suffer from the severe (anticholinergic) mechanisms. The opioid analgesics.5 Unmanaged chronic constipation that can arise with long- delayed colonic transit time discourages constipation may cause rectal pain term opioid therapy.3 One study found , and causes excessive water and bleeding, abdominal pain and that approximately one-third of patients and re-absorption from distension, urinary incontinence, faecal missed, decreased or stopped using faeces, which further dehydrates stool.4,5 impaction, rectal tearing, and, in very opioids in order to make it easier to have a bowel motion; the majority (86%) of these Most patients develop some degree of severe cases, and 6,7,12 patients experienced increased pain as a constipation after opioid initiation. Even colonic perforation. In a study of result, which reduced their quality of life.5,6 though tolerance develops to some patients who had and were Reducing the opioid dose is not considered opioid adverse effects, constipation living in a nursing home, physical useful, as analgesia may be compromised often persists unless remedial measures aggression was shown to be associated 13 and constipation may not resolve.3,4 are taken.2,4,5,11 with constipation.

Veterans’ Medicines Advice and Therapeutics Education Services Therapeutic Brief 27 – Opioid-induced constipation - a preventable problem. June 2011. Veterans’MATES

Managing opioid-induced constipation The aim is to prevent opioid-induced In established cases of constipation, a of laxative may also be influenced constipation. If a patient develops this rectal examination is usually necessary as by patients’ preferences, routes of adverse effect, the goal is to return it can reveal the presence of soft or dry administration, side effects and the bowel function to an acceptable level for faeces, or faecal impaction, which may required onset of action. Osmotic that patient. influence the laxative choice. Sometimes, laxatives may be appropriate for patients a plain abdominal x-ray is also performed, in palliative care, those with malignant Assessment although there is a poor correlation neoplasia or for those with non- There is no objective definition of between symptoms and the extent of responsive constipation (see table 1). constipation because of the great 7,15 faecal loading shown on x-ray. Generally, bulking agents are not individual variation in normal bowel habits, recommended for patients with opioid- and because patients and healthcare Pharmacological management induced constipation as they increase professionals can vary significantly in Before starting opioid therapy, discuss the risk of bowel obstruction, especially their definition of constipation.4, 7,10 In the associated risk of constipation and if the patient has poor fluid intake or broad terms, constipation is described as the possible need for taking laxatives is immobile.7 infrequent defecation (generally fewer than with the patient.3,4 These recommendations also 3 times per week), often with straining and In conjunction with lifestyle measures 1 apply to palliative care patients taking passage of hard, uncomfortable stools. (page 4), consider a combined stimulant opioid analgesics. laxative with a stool softener when initiating opioids.1,7,8 The use and choice Table 1 includes a list of laxatives by class that are appropriate for managing opioid-induced constipation. Table 1: Laxatives used for opioid-induced constipation1,7,8,15,16 Oral laxatives

Class Generic name (Brand name) Administration & Safety considerations

Combined sodium + stimulant laxative (e.g. Coloxyl with Senna®) RPBS with stool softener Can be used long-term in patients taking opioids. There is no convincing evidence to suggest that chronic Senna standardised (e.g. Senokot®) RPBS use of stimulant laxatives causes colon or Stimulant laxatives colonic injury. (e.g. Bisalax®, Dulcolax®) PBS Restricted a,b,c

Often combined with a stimulant laxative for opioid- Stool softeners Docusate sodium (e.g. Coloxyl®) RPBS induced constipation. There is limited evidence to show effectiveness of stool softeners when used alone.

Macrogol () laxative Fluid and electrolyte disturbances may occur – use with (e.g. Movicol®, Osmolax®) PBS Restricted b,c,d caution in cardiovascular disease (e.g. heart failure) and renal impairment (less of a risk with laxatives). Saline laxatives containing Laxatives containing sodium phosphate are not (e.g. Epsom Salts) Not PBS listed recommended for the elderly (e.g. Fleet®). Osmotic laxatives syrup (e.g. Actilax®, Duphalac®) Contraindicated in intestinal obstruction. PBS Restricted b,c is a common adverse effect. Avoid lactulose if fluid intake is poor. liquid (e.g. Sorbilax®) Not PBS listed Lactulose contains galactose and lactose. Rectal laxatives

Sodium citrate + sodium lauryl sulfoacetate + sorbitol – also known as saline laxatives (e.g. Rectal laxatives may be used for faecal impaction or if Osmotic laxatives Microlax®) RPBS there is insufficient response to oral laxatives. Avoid embedding in faecal matter, as it suppositories RPBS delays the laxative effect. ® Bisacodyl enemas (e.g. Bisalax ) and suppositories ® Stimulant laxatives Avoid sodium phosphate enemas (e.g. Fleet ). (e.g. Bisalax®, Dulcolax®) PBS Restricted a,b,c a Patient in residential aged care facility. b Palliative care. c Malignant neoplasia. d Non-responsive constipation or faecal impaction. See PBS Schedule for complete list of restricted benefits.

Veterans’ Medicines Advice and Therapeutics Education Services Therapeutic Brief 27 – Opioid-induced constipation - a preventable problem. June 2011. Veterans’MATES

Prevention and treatment of opioid-induced constipation*1,7,8,15

Scenario Recommendation Considerations

Prevention

Opioid initiation Consider the use of a combined stimulant laxative Since opioids reduce , with a stool softener, such as docusate sodium causing hard faeces to form, the most + senna (e.g. Coloxyl with Senna®). An osmotic useful laxatives are those that increase laxative may also be appropriate, such as macrogol peristalsis and soften the stool. (e.g. Movicol®, Osmolax®) or lactulose Bulking agents are not recommended. (e.g. Actilax®).

Treatment

Established If not initiated with opioid therapy, consider use of constipation a combined stimulant laxative with a stool softener – such as docusate sodium + senna (e.g. Coloxyl with Senna®). If initial management is ineffective: • for hard faeces consider adding an oral osmotic laxative, such as macrogol (e.g. Movicol®, Osmolax®) or lactulose (e.g. Actilax®). • for soft faeces consider adding another oral stimulating agent, such as bisacodyl (e.g. Bisalax®).

Non-responsive If the regular laxative regimen is unsuccessful, For palliative care patients, (refractory) constipation consider the following management options: may be added when • glycerol conventional laxatives are unsuccessful. • small volume (e.g. Bisalax®, Microlax®) • macrogol (polyethylene glycol) laxative (e.g. Movicol®, Osmolax®) • saline** laxative.

Impaction – confirmed Enemas and suppositories are generally Manual removal of impacted faeces by symptoms (faecal recommended to clear the before starting may be required before laxatives can soiling or overflow a program. be effective. diarrhoea***) and rectal Management options include: Start regular laxative regime once examination • glycerol suppository impaction has been alleviated to prevent further opioid-induced constipation. • daily saline** enema (e.g. Microlax®) if softening is effective but peristalsis is ineffective. If rectal treatment is contraindicated, macrogol can be used (e.g. Movicol®, Osmolax®)

*RPBS availability and PBS restricted benefits are outlined in table 1. **Laxatives containing sodium phosphate are not recommended (e.g. Fleet®). *** agents are not recommended to stop overflow diarrhoea.

Veterans’ Medicines Advice and Therapeutics Education Services Therapeutic Brief 27 – Opioid-induced constipation - a preventable problem. June 2011. Veterans’Mates

New developments Lifestyle measures4,7,8 not suppress the urge to defecate; Tapentadol (Palexia IR®), a centrally In addition to pharmacological for example, when out, they should acting opioid analgesic that also management, and where appropriate, use public toilets instead of waiting inhibits noradrenaline re-uptake, and patients should be advised to: to get home. the combined preparation oxycodone/ where possible, drink adequate (Targin®) have been recently . go to the toilet regularly, preferably amounts of fluids, and eat optimal approved by the Therapeutic Goods at the same time each day, and take levels of fibre-rich foods (e.g. or Administration (TGA). In clinical advantage of the pear juice) if current intake is deficient. that occurs after eating or drinking studies, constipation has been reported increase general activity and hot drinks. as a common side effect for both exercise within their capabilities, 17,18 preparations; therefore the advice ensure comfort and privacy to facilitate as movement can be difficult when provided on page 3 is also applicable. unhurried, complete defecation. chronic pain is involved.

Other factors affecting constipation Ongoing patient Multiple factors can contribute to For patients taking medicines that are management constipation in older adults suffering likely to cause constipation, if appropriate, from chronic pain, including adverse consider reducing the dose or using a When reviewing patients taking opioids, effects of other medicines, neurological different medicine where possible. ask about their bowel function. Any 10 disorders and mechanical obstructions. Pre-existing constipation improvements or decline in their condition Questioning the patient and conducting may require stopping the laxative, adjusting A discussion with your patient can a thorough assessment can help to the dose or adding another agent. reveal any pre-existing constipation and identify the cause(s). laxatives the patient is taking to treat it, When monitoring patients, also consider Other medicines particularly over-the-counter medicines. recent lifestyle and environmental factors Besides opioid analgesics, there This will help to develop a treatment that can affect their bowel function, such are some other medicines that can plan to ensure that the constipation is as any newly added medicine(s) and/or commonly cause constipation:7,8,19,20 managed and does not worsen with diagnosed medical condition(s), changes opioid treatment. For example, if the to diet or mobility levels, and weather Aluminium- and/or patient is taking a bulking agent, consider conditions; for example, a heat wave calcium-containing changing to a combined stimulant can cause significant and laxative with a stool softener if suitable.4 electrolyte loss. Agents with anticholinergic effects – e.g. tricyclic , oxybutynin, antihistamines, Further information

Antipsychotics – e.g. chlorpromazine, To establish effective Palliative Care Therapeutic pericyazine, prochlorperazine, , management options, a Guidelines 2010 (Gastrointestinal olanzapine, risperidone, quetiapine Home Medicines Review symptoms) Gabapentin and pregabalin (HMR) may help to identify Continence Foundation of Australia Iron supplements other causative medicines. www.continence.org.au Calcium supplements Ensure this concern is Verapamil (the most likely of all mentioned when you calcium channel blockers to make the referral. Full reference list available at: cause constipation) www.veteransmates.net.au

Veterans’MATES Provided by: University of South Australia Quality Use of Medicines and Pharmacy Research Centre In association with: Discipline of General Practice, The University of Adelaide Discipline of Public Health, The University of Adelaide Repatriation General Hospital, Daw Park NPS – Better choices, Better health Australian Medicines Handbook and Therapeutics Information Service