What are the potential side effects of guaifenesin (expectorant)?

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Last updated: December 24, 2025View editorial policy

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Side Effects of Guaifenesin

Guaifenesin has a well-established and favorable safety profile with predominantly mild gastrointestinal side effects, and serious adverse events are exceedingly rare. 1, 2

Common Side Effects

The most frequently reported adverse effects are gastrointestinal in nature and generally mild 2:

  • Nausea, vomiting, and gastrointestinal upset are the primary side effects, occurring in a minority of patients 3, 2
  • Headache has been reported as a minor adverse effect 3
  • Drowsiness may occur but is uncommon 3
  • Dizziness has been documented in some patients 2

In a post-marketing surveillance study of 552 adults taking extended-release guaifenesin 1200 mg every 12 hours for 7 days, only 28 patients (5%) experienced treatment-emergent adverse events, with gastrointestinal effects (n=11) and nervous system effects (n=8) being most common 2. All adverse events were mild in severity, with no serious adverse events or deaths 2.

Rare but Serious Considerations

While extremely uncommon, one case report documented central nervous system depression and asystole following a massive intentional overdose of guaifenesin (blood concentration 25.0 μg/mL, far exceeding therapeutic levels) 4. This represents the only reported human fatality attributed to guaifenesin and occurred in the context of suicide with co-ingestion of other substances 4.

Laboratory Interference

Guaifenesin can produce color interference with certain clinical laboratory tests, specifically:

  • 5-hydroxyindoleacetic acid (5-HIAA) determinations 5
  • Vanillylmandelic acid (VMA) determinations 5

This is important to consider when evaluating patients for carcinoid syndrome or pheochromocytoma.

Clinical Context and Safety Profile

Multiple clinical guidelines acknowledge guaifenesin's low incidence of adverse effects 3. The American College of Physicians and CDC note that over-the-counter symptomatic relief medications, including guaifenesin, have a low incidence of minor adverse effects 3.

The safety profile is consistent across formulations, with extended-release preparations showing similar tolerability to immediate-release forms 6, 1. In comparative studies, guaifenesin demonstrates fewer adverse effects than many alternative therapies, particularly opioid-based antitussives 7.

Important Caveats

  • Guaifenesin is not detected by primary screening methods employed by some toxicology laboratories and may be missed unless specifically suspected 4
  • The medication has no anticholinergic properties, meaning it does not cause dry mouth, urinary retention, or cognitive impairment that are common with antihistamines 8
  • Efficacy remains controversial in some clinical contexts, with recent high-quality studies showing no effect on sputum volume or properties in acute respiratory tract infections 9, though this relates to effectiveness rather than safety

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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