What are the side effects of Guaiatussin AC (Guaifenesin and Codeine)?

Side Effects of Guaiatussin AC (Codeine 10mg/5mL + Guaifenesin 100mg/5mL)

The most important side effects to anticipate are constipation (which should always be prophylactically managed), nausea, vomiting, and sedation from the codeine component, while guaifenesin itself has minimal side effects. 1

Codeine-Related Side Effects (Primary Concern)

Common and Expected Side Effects

• Constipation is universal and should always be anticipated with prophylactic measures implemented 1
• Nausea and vomiting are frequent, particularly during initial dosing 1
• Sedation and dizziness may occur, especially in opioid-naive patients 1

Serious Safety Concerns with Codeine

• Respiratory depression can occur, particularly in patients with liver cirrhosis where codeine metabolites accumulate 2
• Variable efficacy and toxicity based on CYP2D6 metabolism:
  • Poor metabolizers: essentially ineffective (no conversion to morphine) 1, 2
  • Ultrarapid metabolizers: potentially toxic due to excessive morphine production 1, 2
• Drug interactions with CYP2D6 inhibitors reduce therapeutic effects 2

Additional Opioid-Related Effects

• Anorexia and asthenia (weakness) 1
• Vertigo 1
• Potential for dependence with prolonged use (typical opioid concern)

Guaifenesin-Related Side Effects (Minimal)

Generally Well-Tolerated Profile

• Guaifenesin does NOT cause anticholinergic side effects such as dry mouth, urinary retention, or cognitive impairment 2, 3
• Side effects are generally mild when they occur 4, 5

Rare but Documented Concerns

• Central nervous system depression and cardiovascular collapse have been reported in massive overdose (one case report at 25 μg/mL blood concentration) 4
• This represents an extreme toxicity scenario unlikely at therapeutic doses 4

Clinical Pitfalls to Avoid

Patient Selection Issues

• Avoid in liver cirrhosis patients due to codeine metabolite accumulation and respiratory depression risk 2
• Screen for CYP2D6 status if known, as poor metabolizers will have no benefit and ultrarapid metabolizers face toxicity risk 1, 2
• Check for concurrent CYP2D6 inhibitors that will reduce codeine effectiveness 2
• Avoid with MAO inhibitors 2

Monitoring Considerations

• Always implement constipation prophylaxis at treatment initiation—this is not optional 1
• Monitor for excessive sedation, particularly in elderly patients
• Reassess need for continued opioid therapy frequently 1

Acetaminophen Interaction Warning

• Many patients may be taking other acetaminophen-containing products; total daily acetaminophen should not exceed 3-4g to prevent hepatotoxicity 1
• This formulation does not contain acetaminophen, but patients often use multiple cough/cold products simultaneously

Comparative Context

Codeine shows no clear superiority over other step 2 opioids (tramadol, dihydrocodeine) for cough suppression, and all have similar side effect profiles with nausea, vomiting, and constipation 1. The combination with guaifenesin is rational for productive cough requiring both suppression and mucus clearance 2, though clinical trial data comparing this specific combination to alternatives remains limited 6.