Side Effects of Iron Supplements
Iron supplements commonly cause gastrointestinal side effects including constipation (12%), nausea (11%), diarrhea (8%), abdominal pain, heartburn, and black stools, with these effects occurring more frequently than placebo. 1, 2
Common Gastrointestinal Side Effects
Most Frequent Adverse Effects
- Constipation occurs in approximately 12% of patients taking oral iron 1
- Nausea affects approximately 11% of patients 1
- Diarrhea develops in about 8% of patients 1
- Heartburn and abdominal pain are discriminating symptoms that reliably distinguish iron supplementation from placebo 2
- Black stools are a common and expected side effect that helps differentiate iron therapy from placebo 2
Timing and Duration of Side Effects
- Gastrointestinal side effects typically have rapid onset after starting iron supplementation 2
- Symptoms may persist even after discontinuation, with 67% of patients reporting symptoms during a one-week washout period after stopping iron 2
- Side effects can continue throughout the treatment period 2
Less Common but Serious Adverse Effects
Severe Gastrointestinal Complications
- Iron pill gastritis with mucosal injury, erythema, and ulceration can occur, potentially causing life-threatening gastrointestinal bleeding and worsening anemia 3
- Bowel obstruction and ileus from iron-induced constipation have been reported, though rarely 4
- Vomiting occurs more frequently with higher or weekly dosing regimens (21% with weekly dosing vs 11% with daily dosing) 5
Intravenous Iron-Specific Reactions
- Hypersensitivity reactions can occur with IV iron formulations, though they are very infrequent (<1:250,000 administrations with recent formulations) but may be life-threatening 1
- Hypotension can develop during IV iron infusion 6
- Headache (6%), dizziness (4%), pyrexia (4%), and hypertension (2%) have been reported in pediatric patients receiving IV iron 6
Factors That Influence Side Effect Severity
Dose-Related Effects
- Higher doses increase side effects without improving absorption due to hepcidin elevation blocking further iron uptake 1, 7
- Low-dose regimens (30 mg iron/day) are as effective as higher dose regimens (60-120 mg iron/day) but produce fewer side effects 1
- Taking iron more than once daily increases side effects without benefit because hepcidin remains elevated for up to 48 hours 1, 7
Formulation Differences
- No substantial evidence demonstrates that any one oral iron formulation is better tolerated than another, despite common perceptions 1
- Ferric maltol demonstrates gastrointestinal side effects comparable to placebo in clinical trials 8
- Iron polysaccharide offers no advantage over ionic iron salts in tolerability and may be less effective 8
Critical Pitfalls to Avoid
Drug Interactions
- Do not take iron within 2 hours of tetracycline antibiotics as iron interferes with tetracycline absorption 9
- Avoid taking iron with aluminum-based antacids or phosphate binders, which reduce iron absorption 7
- Do not consume tea or coffee within one hour of iron administration, as these are powerful inhibitors of absorption 7, 8
Dosing Errors
- Avoid multiple daily doses, as this increases side effects without improving absorption 7
- Do not assume all gastrointestinal symptoms are due to iron; persistent symptoms warrant evaluation for other causes including iron-induced gastric injury 1, 3
Special Populations
- Pregnant women experience uncomfortable side effects (constipation, nausea, vomiting) that contribute to poor compliance 1
- In inflammatory bowel disease, unabsorbed oral iron can worsen disease activity through generation of reactive oxygen species 8
When Side Effects Indicate Need for Alternative Therapy
- Consider switching to intravenous iron if oral iron causes intolerable gastrointestinal symptoms despite formulation changes and dosing adjustments 1, 8
- IV iron should be considered if blood counts or iron stores fail to improve with oral supplementation despite adherence 1
- In patients with clinically active inflammatory bowel disease or previous intolerance to oral iron, IV iron may be appropriate as first-line treatment 8