Which of the following medications, Omeprazole, Calcium + Vitamin D, or Prednisone, is most likely to cause an acute adverse drug reaction to the skin?

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Last updated: January 9, 2026 • View editorial policy

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Acute Cutaneous Adverse Drug Reactions: Medication Comparison

Among omeprazole, calcium + vitamin D, and prednisone, prednisone is the medication most likely to cause acute adverse skin reactions, while calcium + vitamin D has no documented acute cutaneous adverse reactions. 1

Prednisone and Corticosteroid-Related Skin Reactions

Prednisone causes well-documented acute and chronic dermatological adverse reactions that are explicitly listed in FDA labeling and clinical guidelines. 2

Acute Dermatologic Reactions from Prednisone

The FDA drug label for prednisone lists extensive dermatologic adverse reactions including: 2

  • Acne and acneiform eruptions
  • Allergic dermatitis
  • Rash
  • Urticaria (which may be associated with arthralgias, dizziness, life-threatening hypotension, nausea, and severe weakness)
  • Angioedema and angioneurotic edema
  • Erythema
  • Facial edema
  • Perineal irritation

Chronic Skin Changes from Corticosteroids

Beyond acute reactions, cosmetic skin changes occur in 80% of patients after 2 years of corticosteroid treatment, demonstrating the high frequency of cutaneous effects. 1 Clinical trials have documented that skin rash is more common in prednisolone-treated patients compared to other anti-inflammatory agents. 1

Calcium + Vitamin D: No Acute Cutaneous Reactions

No significant acute cutaneous adverse reactions are documented in the clinical literature for calcium and vitamin D supplementation. 1 This makes calcium + vitamin D the safest option among the three medications regarding acute skin reactions.

Omeprazole: Not Addressed in Available Evidence

The provided evidence does not specifically address omeprazole's cutaneous adverse reaction profile. However, based on general medical knowledge, proton pump inhibitors like omeprazole can rarely cause cutaneous adverse reactions, but these are significantly less common than with corticosteroids.

Clinical Context: Drug-Induced Skin Reactions

When evaluating any new rash in patients on multiple medications, systematic evaluation of all potential culprits is required, with particular attention to recently initiated drugs. 1 The most commonly implicated drug classes in severe cutaneous adverse reactions are: 3, 4

  • Antibiotics (88.1% of severe cases, most commonly cephalosporins at 23.7%)
  • NSAIDs (22.4% of cases)
  • Anticonvulsants (13.8% of cases)

Important Clinical Pitfall

Any confirmed drug-induced rash should be documented as a drug allergy to prevent future exposure. 1 When prednisone causes a rash, mild-to-moderate reactions can be managed with topical therapies and antihistamines, though this creates a paradoxical situation since systemic steroids are often used to treat severe drug-induced rashes from other medications. 1

Management Considerations

Patients who develop rash on one medication may not experience recurrence with structurally different alternatives, allowing for therapeutic substitution when necessary. 1 When using topical steroids to manage drug-induced rashes, avoid high-potency topical steroids in intertriginous areas due to increased risk of skin atrophy. 1

References

1
Guideline

Cutaneous Adverse Reactions to Medications

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

3
Research

Drug-induced severe cutaneous adverse reactions: Determine the cause and prevention.

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 2019

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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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