Can Vonoprazan (proton pump inhibitor), Cinitapride (dopamine D2 receptor agonist), Mebeverine (antispasmodic) and Chlordiazepoxide (benzodiazepine) cause pedal edema in an adult patient with gastrointestinal issues and anxiety or insomnia?

Pedal Edema and Current Medications

None of the four medications you listed (Vonoprazan, Cinitapride, Mebeverine, or Chlordiazepoxide) are established causes of pedal edema based on available evidence, and you should investigate other etiologies including cardiac, renal, hepatic, venous insufficiency, or other medications not mentioned.

Medication-Specific Analysis

Vonoprazan (Proton Pump Inhibitor)

• Vonoprazan is a potassium-competitive acid blocker with a well-characterized safety profile showing no association with pedal edema 1, 2
• In systematic reviews of 77 studies, the most common adverse events were gastrointestinal (abdominal pain, constipation, diarrhea, nausea, dyspepsia) with no mention of edema 1, 2
• Long-term safety data up to 5 years show no edema as a reported adverse effect 3, 1

Cinitapride (Prokinetic Agent)

• No evidence in the provided literature links cinitapride to pedal edema
• This dopamine D2 receptor antagonist (not agonist as stated in the expanded question) is not among the medication classes known to cause edema 4, 5

Mebeverine (Antispasmodic)

• No evidence associates mebeverine with pedal edema
• Antispasmodics are not listed among the common medication culprits for drug-induced edema 4, 5

Chlordiazepoxide (Benzodiazepine)

• Benzodiazepines are not recognized causes of pedal edema 6
• The primary adverse effects include drowsiness, dizziness, paradoxical agitation, and increased fall risk—not fluid retention 6

Actual Medication Culprits to Consider

The American Heart Association and American College of Cardiology identify these as the primary medication causes of pedal edema: 4, 5

• Calcium channel blockers (especially dihydropyridines like amlodipine) through increased capillary permeability 4, 5
• NSAIDs through sodium/water retention, increased capillary permeability, and renal dysfunction 4, 5
• Thiazolidinediones (diabetes medications) causing 3-5% incidence through plasma volume expansion 4
• Corticosteroids through sodium retention and increased capillary permeability 4
• Insulin through increased plasma volume and sodium/water retention 4
• Vasodilators (hydralazine, minoxidil) causing sodium and water retention 4
• Hormone therapy (estrogen-containing medications) increasing fluid retention 4

Recommended Diagnostic Approach

Before attributing edema to any medication, systematically exclude these conditions: 4, 5

1. Cardiac causes: Examine for orthopnea, paroxysmal nocturnal dyspnea, jugular venous distention, S3 gallop, or pulmonary rales 4, 5
2. Renal dysfunction: Check serum creatinine, urinalysis for proteinuria (nephrotic syndrome) 4
3. Hepatic disease: Assess for ascites, jaundice, spider angiomata 5
4. Venous insufficiency: Look for varicose veins, skin changes, unilateral vs bilateral distribution 6, 5
5. Lymphedema: Consider if there is a predisposition or relevant history 6
6. Review ALL medications the patient is taking beyond those listed, particularly over-the-counter NSAIDs 4, 5

Critical Management Pitfall

Do not empirically prescribe diuretics without determining the underlying cause, as this can lead to severe electrolyte imbalances, volume depletion, and falls, particularly if the edema is medication-induced rather than from heart failure. 5