Tibotec Therapeutics, in cooperation with FDA ( Food and Drug Administration ), has informed healthcare professionals of an important safety update to the Severe Skin Reactions Warnings and Precautions section of the Intelence ( Etravirine ) tablets prescribing information.
Specifically, the existing Warning and Precaution regarding Severe Skin Reactions has been strengthened to reflect that there have been postmarketing reports of:

• fatality due to toxic epidermal necrolysis

• hypersensitivity reactions, sometimes accompanied by hepatic failure.

Additionally, Guidance has been added that Intelence should be immediately discontinued when signs and symptoms of severe skin or hypersensitivity reactions develop.
Given the clinical relevance of these adverse reactions, the following information regarding severe skin and hypersensitivity reactions has been included in the Intelence Prescribing Information:

Warnings and Precautions

Severe Skin and Hypersensitivity Reactions - Severe, potentially life-threatening, and fatal skin reactions have been reported. These include cases of Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme.
Hypersensitivity reactions have also been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure.
In Phase 3 clinical trials, Grade 3 and 4 rashes were reported in 1.3% of subjects receiving Intelence compared to 0.2% of placebo subjects. A total of 2% of HIV-1-infected subjects receiving Intelence discontinued from Phase 3 trials due to rash.
Rash occurred most commonly during the first 6 weeks of therapy.

Discontinue Intelence immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions develop ( including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, hepatitis, eosinophilia ).
Clinical status including liver transaminases should be monitored and appropriate therapy initiated.
Delay in stopping Intelence treatment after the onset of severe rash may result in a life-threatening reaction.

Patient Package Insert

The What are the possible side effects of Intelence ? section of the Patient Package Insert has also been updated.
In Phase 3 studies, the most frequently reported adverse drug reaction of at least Grade 2 in severity was rash ( 9.0% ).
Stevens-Johnson syndrome, hypersensitivity reaction, and erythema multiforme were reported in less than 0.1% of subjects during clinical development with Intelence.
In general, in clinical trials, rash was mild to moderate, occurred primarily in the second week of therapy, and was infrequent after week 4.
Rash generally resolved within 1-2 weeks on continued therapy.
A total of 2% of HIV-1 infected subjects in Phase 3 trials receiving Intelence discontinued due to rash.

Source: FDA, 2009

XagenaMedicine2009


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