What are alternative pharmacologic options for chronic idiopathic constipation when Trulance (plecanatide) cannot be used?

Alternatives to Trulance (Plecanatide) for Chronic Idiopathic Constipation

For patients who cannot use Trulance, start with polyethylene glycol (PEG) 17g daily as the first-line alternative, and if over-the-counter agents fail, advance to linaclotide 72-145 μg daily or prucalopride 1-2 mg daily as prescription alternatives. 1

First-Line Over-the-Counter Alternatives

Polyethylene glycol (PEG) is the strongest first-line alternative, with a strong recommendation from the 2023 AGA-ACG guidelines, costing only $10-45/month compared to Trulance's $526/month. 1

• Start with PEG 17g daily and titrate based on symptom response 1
• PEG has demonstrated durable response over 6 months with moderate certainty of evidence 1
• Common side effects include bloating, abdominal discomfort, and cramping, but these are generally manageable 1

Magnesium oxide 400-500 mg daily is another cost-effective option (<$50/month) with conditional recommendation 1

• Use with caution in patients with renal insufficiency 1
• Prior studies used higher doses of 1,000-1,500 mg daily 1

Lactulose 15g daily (<$50/month) is particularly useful if the patient is pregnant, as it is the only osmotic agent studied in pregnancy 1

Short-Term or Rescue Therapy Options

Bisacodyl 5-10 mg daily or sodium picosulfate 10 mg daily are strongly recommended for short-term use (4 weeks or less) or as rescue therapy 1

• These stimulant laxatives ranked first at 4 weeks in network meta-analysis 2
• Can be combined with other agents for breakthrough symptoms 1
• Abdominal cramping may limit tolerability at higher doses 1

Senna 8.6-17.2 mg daily (<$50/month) is conditionally recommended, though long-term safety data are limited 1

Prescription Alternatives When OTC Agents Fail

Linaclotide (Strong Recommendation)

Linaclotide 72-145 μg daily (maximum 290 μg daily) is strongly recommended with moderate certainty of evidence, costing $523/month 1

• This is a guanylate cyclase-C agonist, the same mechanism as Trulance, but with different pharmacokinetics 3, 4
• May provide additional benefit for abdominal pain beyond improving bowel frequency 1
• Diarrhea may occur in a subset of patients, leading to discontinuation 1
• Treatment duration in trials was 12 weeks, but the drug label does not provide a limit 1

Prucalopride (Strong Recommendation)

Prucalopride 1-2 mg daily is strongly recommended with moderate certainty of evidence, costing $563/month 1, 5

• This is a serotonin type 4 (5-HT4) receptor agonist that enhances colonic motility 1, 5
• Ranked first at 12 weeks in network meta-analysis, particularly effective in patients who previously failed laxatives 2
• May provide additional benefit for abdominal pain 1, 5
• Side effects include headache, abdominal pain, nausea, and diarrhea 1
• Start at 1-2 mg daily and titrate to 2 mg daily based on response 5

Lubiprostone (Conditional Recommendation)

Lubiprostone 24 μg twice daily is conditionally recommended with low certainty of evidence, but is the most cost-effective prescription secretagogue at $374/month 1, 6

• Acts on chloride channel type 2 in the gut to increase intestinal secretion 1, 6
• May have benefit for abdominal pain 1
• Nausea is the most common side effect but is dose-dependent and reduced when taken with food and water 1, 6
• Effects manifest within 2 days among responders 6

Treatment Algorithm

1. Start with PEG 17g daily, titrate up based on response 1, 6

2. If inadequate response, add or switch to magnesium oxide 400-500 mg daily (if no renal insufficiency) 1, 6

3. Add bisacodyl 5-10 mg as needed for short-term relief or rescue therapy 1, 6

4. If OTC agents fail after adequate trial, advance to prescription therapy:

   • Linaclotide 72-145 μg daily or prucalopride 1-2 mg daily are first-choice prescription alternatives with strong recommendations 1
   • Lubiprostone 24 μg twice daily is the most cost-effective prescription option if cost is a primary concern 6

5. Combination therapy is reasonable: OTC agents can be combined with prescription secretagogues or prokinetics 6, 7

Important Clinical Caveats

• Fiber supplementation can be added at any stage (14g/1,000 kcal intake per day), but ensure adequate hydration as fiber intake increases to avoid worsening symptoms 1, 6

• Linaclotide has higher certainty of evidence (moderate) compared to lubiprostone (low), making it a stronger choice when cost is not prohibitive 6

• Prucalopride is particularly effective in patients who have failed laxatives, based on the patient populations studied in clinical trials 2

• Active monitoring is essential: patients need to be actively managed and monitored to maximize clinical outcomes, with consideration for retrying past treatments if not adequately trialed initially 7

• Avoid prolonged use of stimulant laxatives (bisacodyl, senna) as monotherapy due to unknown long-term safety, though short-term or intermittent use is appropriate 1