Rilpivirine - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Skin and Hypersensitivity Reactions: Severe skin and hypersensitivity reactions have been reported during postmarketing experience, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), with rilpivirine-containing regimens.

Immediately discontinue treatment if hypersensitivity or rash with systemic symptoms or elevations in hepatic serum biochemistries develop and closely monitor clinical status, including hepatic serum biochemistries.

Hepatotoxicity: Hepatic adverse events have been reported in patients with underlying liver disease, including hepatitis B or C virus co-infection, or in patients with elevated baseline transaminases.

A few cases of hepatotoxicity have occurred in patients with no pre-existing hepatic disease.

Monitor liver function tests before and during treatment with EDURANT or EDURANT PED in patients with underlying hepatic disease, such as hepatitis B or C virus co-infection, or marked elevations in transaminase.

Also consider monitoring liver functions tests in patients without pre-existing hepatic dysfunction or other risk factors.

Depressive Disorders: Severe depressive disorders have been reported.

Immediate medical evaluation is recommended for severe depressive disorders.

Patients may develop immune reconstitution syndrome.

5.1 Skin and Hypersensitivity Reactions Severe skin and hypersensitivity reactions have been reported during the postmarketing experience, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), with rilpivirine-containing regimens.

While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunctions, including elevations in hepatic serum biochemistries.

During the Phase 3 clinical trials, treatment-related rashes with at least Grade 2 severity were reported in 3% of subjects receiving EDURANT.

No Grade 4 rash was reported.

Overall, most rashes were Grade 1 or 2 and occurred in the first four to six weeks of therapy [see Adverse Reactions (6.1 and 6.2) ] .

Discontinue EDURANT or EDURANT PED immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, including but not limited to, severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis or eosinophilia.

Clinical status including laboratory parameters should be monitored and appropriate therapy should be initiated.

5.2 Hepatotoxicity Hepatic adverse events have been reported in patients receiving a rilpivirine-containing regimen.

Patients with underlying hepatitis B or C virus infection, or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations with use of EDURANT or EDURANT PED.

A few cases of hepatic toxicity have been reported in adult patients receiving a rilpivirine-containing regimen who had no pre-existing hepatic disease or other identifiable risk factors.

Appropriate laboratory testing prior to initiating therapy and monitoring for hepatotoxicity during therapy with EDURANT or EDURANT PED is recommended in patients with underlying hepatic disease such as hepatitis B or C virus infection, or in patients with marked elevations in transaminases prior to treatment initiation.

Liver enzyme monitoring should also be considered for patients without pre-existing hepatic dysfunction or other risk factors.

5.3 Depressive Disorders The adverse reaction depressive disorders (depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicidal ideation) has been reported with EDURANT.

Patients with severe depressive symptoms should seek immediate medical evaluation to assess the possibility that the symptoms are related to EDURANT or EDURANT PED, and if so, to determine whether the risks of continued therapy outweigh the benefits.

During the Phase 3 trials in adults (N=1368) through 96 weeks, the incidence of depressive disorders (regardless of causality, severity) reported among EDURANT (n=686) or efavirenz (n=682) was 9% and 8%, respectively.

Most events were mild or moderate in severity.