PROCRIT - Severe Cutaneous Adverse Reactions

SUMMARY  

• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice.¹
• Blistering and skin exfoliation reactions including erythema multiforme (EM) and Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with erythropoiesis-stimulating agents (ESAs; including PROCRIT) in the post-marketing setting. Discontinue PROCRIT therapy immediately if a severe cutaneous reaction, such as SJS/TEN, is suspected.¹
• A case report of a fatal EM post epoetin alfa was identified, but a causal relationship could not be made.²
• A case report of drug reaction with eosinophilia and systemic symptoms (DRESS) occurred in a patient after starting epoetin alfa 8 days prior to arriving at an emergency department. Upon admission, epoetin alfa was discontinued. The patient improved with methylprednisolone intravenous (IV) therapy for 2 days, however, rash, eosinophils, and creatinine worsened post methylprednisolone IV discontinuation. Patient was restarted on methylprednisolone with improvement and discharged on a steroid taper.³

PRODUCT LABELING

Please refer to the following sections of the full Prescribing Information¹ which are relevant to your inquiry: WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS.

BACKGROUND

SJS and TEN are rare and severe cutaneous disorders that are extremely serious and potentially fatal. They are characterized by epidermal loss and multi-site mucositis, accompanied by systemic disturbance. Fever, malaise, and upper respiratory tract symptoms generally precede cutaneous eruptions by several days. Cutaneous pain, which is a prominent early feature, may signal initial stages of epidermal necrolysis. The earliest lesions may involve circular epidermal discolorations and/or purpuric macules. Initial sites of involvement are commonly the upper torso, proximal limbs, and face. Thereafter, lesions spread to involve the rest of the trunk and distal limbs.⁴

Severe cutaneous adverse reactions (SCAR) in general have been associated with exposures to certain drugs, particularly anti-infective medications. Clear evidence of associations with any genetic predisposition are lacking.⁵

In regard to SJS/TEN:⁵

• SJS/TEN have been associated with chemical exposures, mycoplasma pneumonia, human immuno-deficiency virus (HIV), tuberculosis and viral infections.  
• SJS/TEN have also been associated with cancer and radiotherapy.
• Drugs most commonly associated with TEN include anticonvulsants, sulfa preparations, allopurinol, corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs).

In regard to EM:⁶

• EM can occur in patients of all ages.
• The herpes simplex virus is the most commonly identified etiology, accounting for more than 50% of cases.
• Mycoplasma pneumoniae and fungal infections are also identified as common etiologies.
• Medications most often associated with EM are barbiturates, hydantoins, NSAIDs, penicillins, phenothiazines, and sulfonamides.
• EM has also been associated with a variety of vaccines and other medications.
• SCAR occur in approximately 1 in every 1000 hospitalized patients. SJS/TEN occurs with varying incidence between 2 and 7 cases/million/year in hospitalized patients.⁷ Prevalence/incidence ranges from 1% (SJS/TEN) to 48% (urticaria and/or angioedema).⁸

clinical DATA

POSTMARKETING DATA

Cases of severe cutaneous reactions of blistering and skin exfoliation, including EM and SJS/ TEN, have been reported in patients treated with ESAs (including PROCRIT) in the post-marketing setting.⁹

Since epoetin alfa (including PROCRIT) was first commercially available in June 1989, it is estimated there is over 10 million patient-years of exposure to epoetin alfa (including PROCRIT). During this time, there have been a small number of cases reported, which indicates that severe cutaneous reactions including SJS/TEN occurred rarely in the post-marketing setting.⁹

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 23 July 2025.