Etravirine - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Severe, potentially life threatening and fatal skin reactions have been reported.

This includes cases of Stevens-Johnson syndrome, hypersensitivity reaction, toxic epidermal necrolysis and erythema multiforme.

Immediately discontinue treatment if severe hypersensitivity, severe rash or rash with systemic symptoms or liver transaminase elevations develops and monitor clinical status, including liver transaminases closely.

Monitor for immune reconstitution syndrome and fat redistribution. ( 5.3, 5.4 ) 5.1 Severe Skin and Hypersensitivity Reactions Severe, potentially life-threatening and fatal skin reactions have been reported.

In clinical trials, these include cases of Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme.

Hypersensitivity reactions including Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) 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 etravirine compared to 0.2% of placebo subjects.

A total of 2.2% of HIV-1-infected subjects receiving etravirine discontinued from Phase 3 trials due to rash [see Adverse Reactions ] .

Rash occurred most commonly during the first 6 weeks of therapy.

The incidence of rash was higher in females [see Adverse Reactions ] .

Stevens-Johnson syndrome was reported in 1.1% (2/177) of pediatric patients less than 18 years of age receiving etravirine in combination with other HIV-1 antiretroviral agents in an observational study.

Discontinue etravirine 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, angioedema).

Clinical status including liver transaminases should be monitored and appropriate therapy initiated.

Delay in stopping etravirine treatment after the onset of severe rash may result in a life-threatening reaction.

5.2 Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions The concomitant use of etravirine and other drugs may result in potentially significant drug interactions, some of which may lead to [see Drug Interactions ]: Loss of therapeutic effect of concomitant drug or etravirine and possible development of resistance.

Possible clinically significant adverse reactions from greater exposures of etravirine or other concomitant drugs.

See Table 4 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations.

Consider the potential for drug interactions prior to and during etravirine therapy and review concomitant medications during etravirine therapy.

5.3 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including etravirine.

During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia (PCP) or tuberculosis), which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves' disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.

5.4 Fat Redistribution Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy.

The mechanism and long-term consequences of these events are currently unknown.

A causal relationship has not been established.