What is the cause of an erythematous rash in patients treated with Gemcitabine (gemcitabine)?

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Last updated: March 28, 2025View editorial policy

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From the Guidelines

Gemcitabine can cause an erythematous rash as a cutaneous side effect in patients, with the rash being a common adverse event associated with the combination of gemcitabine and erlotinib, as seen in the NCIC CTG PA.3 trial 1. The rash typically appears as a maculopapular, pruritic eruption on the trunk, extremities, and sometimes the face, usually developing within the first two treatment cycles.

  • Management includes:
    • Topical corticosteroids (such as hydrocortisone 1% or triamcinolone 0.1%) for symptomatic relief
    • Oral antihistamines like cetirizine 10mg daily or diphenhydramine 25-50mg every 6 hours for itching
    • Emollients to maintain skin hydration
  • For severe cases, temporary dose reduction or brief treatment interruption may be necessary, with gradual reintroduction once symptoms improve.
  • Prophylactic antihistamines before gemcitabine administration can help prevent recurrence. The mechanism involves direct drug toxicity and hypersensitivity reactions affecting keratinocytes and dermal blood vessels, as suggested by the increased incidence of rash in patients receiving erlotinib plus gemcitabine compared to gemcitabine alone 1. Most rashes are mild to moderate and resolve without permanent sequelae, though severe reactions require prompt dermatological consultation, and patients should be educated to report skin changes promptly to allow for early intervention. It is worth noting that the occurrence of grade 2 or higher skin rash is associated with better response and overall survival of patients receiving erlotinib, as shown in the NCIC CTG PA.3 trial 1. However, the evidence from the 2023 study 1 suggests that gemcitabine alone may have a lower incidence of skin rash compared to combination therapy, but this study did not specifically address the cause of the rash. Therefore, the most recent and highest quality evidence suggests that gemcitabine can cause an erythematous rash, and management should focus on symptomatic relief and prevention of recurrence 1.

From the FDA Drug Label

The most common (≥20%) adverse reactions of single-agent gemcitabine are nausea/vomiting, anemia, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), neutropenia, increased alkaline phosphatase, proteinuria, fever, hematuria, rash, thrombocytopenia, dyspnea, and edema Rash 30 <1 0 Rash/desquamation (0. 6% versus 0)

The cause of an erythematous rash in patients treated with Gemcitabine is not explicitly stated in the label, but rash is listed as a common adverse reaction.

  • Rash is reported in 30% of patients, with <1% being Grade 3 or 4.
  • Additionally, rash/desquamation is reported in 0.6% of patients in the gemcitabine with carboplatin arm. However, the label does not provide information on the cause of the rash. 2 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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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