Does the combination of iron supplements and naproxen (nonsteroidal anti-inflammatory drug (NSAID)) increase the incidence of constipation in adult or elderly patients?

Does Iron and Naproxen Increase Incidence of Constipation?

Yes, both iron supplements and naproxen independently cause constipation, and using them together would be expected to have an additive effect on constipation risk, though no studies directly examine this specific combination.

Iron Supplements and Constipation

Iron supplements are well-established causes of constipation:

• Constipation rates range from 4-29% in iron-supplemented patients versus 1.6-28% in control groups 1
• Iron is specifically listed among medications that commonly cause constipation in cancer patients, alongside opioids, antiemetics, and other agents 2
• In critical care patients, those taking iron supplements experienced constipation at a rate of 75%, making iron one of the medications most strongly associated with constipation 3
• Iron can cause severe gastrointestinal complications including ileus secondary to bowel obstruction from constipation, even in patients without predisposing surgical history 4

The mechanism involves unabsorbed iron (the majority of oral iron passes unabsorbed into the colon) altering gut microbiota and directly affecting bowel motility 5.

NSAIDs and Constipation

While NSAIDs like naproxen are primarily known for causing upper gastrointestinal complications (ulcers, bleeding), constipation is not a prominently reported side effect of naproxen or other NSAIDs in the guideline literature 2. The major gastrointestinal concerns with NSAIDs focus on:

• Increased risk of gastrointestinal bleeding and ulceration (2.5-5-fold increase) 2
• Nausea, dyspepsia, and abdominal pain 2
• Diarrhea rather than constipation 2

However, NSAIDs are mentioned among drugs that can contribute to constipation in advanced cancer patients 2, suggesting they may play a contributory role in certain clinical contexts.

Combined Risk Assessment

When prescribing iron and naproxen together, anticipate constipation primarily from the iron component:

• Start prophylactic laxatives when initiating iron supplementation, particularly in elderly patients or those with other constipation risk factors 2
• Osmotic laxatives (polyethylene glycol 17g/day, lactulose) or stimulant laxatives (senna, bisacodyl) are preferred first-line options 2
• Limit elemental iron to no more than 100 mg per day and use once-daily dosing to minimize gastrointestinal side effects 1, 5

Strategies to Minimize Constipation Risk

For iron supplementation:

• Use alternate-day dosing (every other day) which may reduce gastrointestinal symptoms while maintaining efficacy 1
• Consider ferric maltol if traditional ferrous salts cause intolerable symptoms, as it demonstrates gastrointestinal side effects comparable to placebo 1
• Take with vitamin C (250-500 mg) to enhance absorption, potentially allowing lower iron doses 1

For the combination:

• Ensure adequate hydration and dietary fiber intake 2
• Monitor bowel movements closely, particularly in elderly patients who are 5 times more prone to constipation 2
• In elderly patients, polyethylene glycol (17g/day) offers efficacy with a good safety profile 2

Important Caveats

• Age is a critical risk factor: Patients over 65 years taking NSAIDs have 2-3.5-fold increased risk of gastrointestinal complications 2, and elderly patients are particularly susceptible to constipation from any cause 2
• The combination of iron and naproxen creates dual gastrointestinal risks: constipation from iron and upper GI bleeding/ulceration from naproxen 2, 1
• Consider gastroprotection with a proton pump inhibitor for the naproxen component, especially in patients over 60 years, as this reduces bleeding ulcer risk by 75-85% 2
• If constipation becomes severe despite laxatives, consider switching to intravenous iron rather than continuing oral supplementation 1