Question

What are the symptoms of rash with efavirenz used in PEP?

16 September 2011. Related: All topics, Side effects.

What are the typical efavirenz-induced rash characteristics ?

Under PEP, suffered vast diffuse (75% body surface) macular rash mostly at the back and extremities, erythematous, warm, very itchy, relieved by topical corticosteroid cream, lasted only for 5-6 days, with no other typical acute HIV seroconversion symptoms.

Would you please kindly describe what is the typical characteristics of ARS rash ? Thank you very much.

Answer

Answer: Simon Collins

Hi

Rash symptoms related to efavirenz can range from very mild to severe. Approximately 15-20% of people experience some form of rash, usually mild and manageable, with less than 5% of people needing to stop treatment.

The following information below is from the summary information from the European licensing information.

I am more concerned that you were prescribed efavirenz as part of a PEP combination.

UK guidelines for PEP, do not recommend NNRTIs (such as efavirenz) because of the low but potentially serious risk of side effects. This may be higher in people who are HIV-negative.

This is also because drug-related rash might be confused with symptoms of seroconversion.

PEP combinations in the UK use a protease inhibitor (PI) boosted by ritonavir plus two nucleoside analogues (nukes). See: UK Department of Health Guidelines for PEP (2008).

Information about efavirenz-related rash from the Summary of Product Characteristics.

From Section 4.4 (page 4)

Rash: mild-to-moderate rash has been reported in clinical studies with efavirenz and usually resolves with continued therapy. Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. Severe rash associated with blistering, moist desquamation or ulceration has been reported in less than 1% of patients treated with efavirenz. The incidence of erythema multiforme or Stevens-Johnson syndrome was approximately 0.1%. Efavirenz must be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement or fever. If therapy with efavirenz is discontinued, consideration should also be given to interrupting therapy with other antiretroviral agents to avoid development of resistant virus (see section 4.8).

From section 4.8c (page 19)

Rash: in clinical studies, 26% of patients treated with 600 mg of efavirenz experienced skin rash compared with 17% of patients treated in control groups. Skin rash was considered treatment related in 18% of patients treated with efavirenz. Severe rash occurred in less than 1% of patients treated with efavirenz, and 1.7% discontinued therapy because of rash. The incidence of erythema multiforme or Stevens-Johnson syndrome was approximately 0.1%.

Rashes are usually mild-to-moderate maculopapular skin eruptions that occur within the first two weeks of initiating therapy with efavirenz. In most patients rash resolves with continuing therapy with efavirenz within one month. Efavirenz can be reinitiated in patients interrupting therapy because of rash. Use of appropriate antihistamines and/or corticosteroids is recommended when efavirenz is restarted.

Experience with efavirenz in patients who discontinued other antiretroviral agents of the NNRTI class is limited. Reported rates of recurrent rash following a switch from nevirapine to efavirenz therapy, primarily based on retrospective cohort data from published literature, range from 13 to 18%, comparable to the rate observed in patients treated with efavirenz in clinical studies. (See section 4.4.)