OPIOID-INDUCED CONSTIPATION MANAGEMENT GUIDELINES
The management of opioid-induced constipation is based on recommendations from the American Gastroenterological Association (AGA). The guideline only focuses on medical management (both prescription and over-the-counter products) and does not address the role of psychological therapy, alternative medicine approaches, surgery, or devices.
ROME IV DIAGNOSTIC CRITERIA
Opioid-induced constipation (OIC): new or worsening symptoms of constipation when initiating, changing, or increasing opioid therapy that must include ≥2 of the following (>25% of defecations):

• Straining

• Lumpy or hard stools

• Sensation of incomplete evacuation

• Sensation of anorectal obstruction or blockage

• Manual maneuvers to facilitate defecations (eg, digital evacuation, support of the pelvic floor)

• Fewer than 3 spontaneous bowel movements per week

PATIENT EVALUATION
General approach to patients with suspected OIC:

• Ensure that the indication for opioid therapy is appropriate and that the patient is taking the minimum necessary opioid dose.

• Obtain a careful history to evaluate defecation and dietary patterns, stool consistency, symptoms of dyssynergic defecation (eg, sensation of incomplete evacuation), or alarm symptoms (eg, blood in stool or accompanying weight loss).

• Obtain a medical history to assess comorbid illnesses and regular medication use.

• Explore or exclude other potential causes of constipation, such as pelvic outlet dysfunction, mechanical obstruction, metabolic abnormalities, and contributions of other diseases or medications.

MANAGEMENT OF OIC
AGA recommendations:

1. Lifestyle modifications (eg, increasing fluid intake, regular moderate exercise, and toileting as soon as possible) are an appropriate first step for all patients with constipation.

2. Changing to an equianalgesic dose of an alternative, less-constipating opioid (“opioid switching”) may be beneficial.

3. Once OIC is confirmed and other causes of constipation excluded, the use of laxatives as first-line agents is recommended.

4. For laxative-refractory1 OIC, it is recommended to use PAMORAs such as naldemedine or naloxegol, and suggested to use methylnaltrexone, over no treatment.

5. No recommendations were made on the use of intestinal secretagogues (lubiprostone) and selective 5-HT agonists (prucalopride) in OIC.

PHARMACOLOGICAL TREATMENT FOR OIC
Generic Brand Strength Form Adult Dose
LAXATIVES
Osmotic
lactulose 10g/15mL oral soln 15–30mL once daily; max 60mL/day.
Kristalose 10g, 20g crystals for reconstitution Dissolve 10–20g in 4oz water once daily; max 40g/day.
magnesium citrate 1.745g/30mL oral soln Take with a full 8oz glass of liquid. ≥12yrs: 6.5–10oz (192–296mL) once daily or in divided doses. Max 10oz/24hrs.
magnesium hydroxide 400mg/5mL liquid Take with a full 8oz glass of liquid. ≥12yrs: 30–60mL once daily or in divided doses.
polyethylene glycol (PEG) Glycolax 17g pwd for oral soln Dissolve 17g in 8oz water and drink once daily for max 14 days.
Miralax 17g pwd for oral soln ≥17yrs: Dissolve 17g in 4–8oz liquid and drink once daily
for max 7 days.
Stimulant
bisacodyl Dulcolax 5mg e-c tabs 1–3 tabs daily. Results usually within 6–12hrs; reevaluate if ineffective.
100mg softgel 1–3 softgels daily. Results usually within 12–72hrs; reevaluate if ineffective.
10mg supp 1 supp rectally once daily. Retain for 15–20mins. Results usually within 15–60mins; reevaluate if ineffective.
Fleet 5mg tabs 1–3 tabs daily. Results usually within 6–12hrs; reevaluate if ineffective.
10mg supp 1 supp rectally daily. Retain for 15–20mins. Results usually within 15–60mins; reevaluate if ineffective.
10mg/30mL enema 1 enema rectally daily. Results usually within 5–20mins; reevaluate if ineffective.
senna Senokot 8.6mg tabs 2 tabs once daily; max 4 tabs twice daily.
Senokot Xtra 17.2mg tabs 1 tab once daily; max 2 tabs twice daily.
Detergent/surfactant stool softeners
docusate sodium Colace 50mg, 100mg caps 50–300mg daily.
10mg/mL liquid Mix in 6–8oz of milk or juice. 50–150mg once or twice daily.
60mg/15mL syrup Mix in 6–8oz of milk or juice. 60–360mg daily.
Lubricant
mineral oil Fleet Mineral Oil Enema 100% enema 1 enema rectally daily. Results usually within 2–15mins; reevaluate if ineffective.
PERIPHERALLY ACTING μ-OPIOID RECEPTOR ANTAGONISTS (PAMORAs)2
methylnaltrexone Relistor3,4 150mg tabs Take on an empty stomach with water ≥30mins before first meal of day. 450mg once daily in the AM. CrCl<60mL/min or hepatic impairment (Child-Pugh B or C): 150mg once daily.
8mg/0.4mL, 12mg/0.6mL soln for SC inj 12mg SC once daily. Advanced illness: give once every other day as needed (max 1 dose/24hrs). <38kg or >114kg: 0.15mg/kg. 38–<62kg: 8mg. 62–114kg: 12mg. Renal (CrCl<60mL/min) or severe hepatic impairment: reduce dose by ½ (see full labeling).
naldemedine Symproic4 0.2mg tabs 0.2mg once daily.
naloxegol Movantik3,4 12.5mg, 25mg tabs Take on an empty stomach. 25mg once daily in the AM; may reduce to 12.5mg once daily if not tolerated. Renal impairment (CrCl<60mL/min): 12.5mg once daily; may increase to 25mg once daily if tolerated.
NOTES
Key:e-c = enteric coated; pwd = powder; soln = solution; supp = suppository.

1 Laxative-refractory OIC is defined as moderate or severe symptoms of constipation despite the use of laxatives from ≥1 laxative classes for a minimum of 4 days within a 2-week period. AGA recommends using a combination of ≥2 types of laxatives before escalating therapy, and that scheduled use of laxatives (vs “as needed” basis) is required before considering alternative treatment.

2 Avoid in conditions that compromise the blood-brain barrier due to potential for serious withdrawal or reversal of anesthesia.

3 Discontinue all laxative therapy prior to initiation; may use as needed if suboptimal response after 3 days.

4 Discontinue if opioid pain therapy is also discontinued.

Not an inclusive list of medications and/or official indications. Please see drug monograph at www.eMPR.com and/or contact company for full drug labeling.

REFERENCES
Adapted from Crockett SD, Greer KB, Heidelbaugh JJ, et al. American Gastroenterological Association Institute Guideline on the Medical Management of Opioid-Induced Constipation. Gastroenterology. 2018 Oct 16. pii: S0016-5085(18)34782-6. doi: 10.1053/j.gastro.2018.07.016.

Created 12/2018