Recommended Topic Related To:

Edurant

"A new analysis of data from 20 major U.S. cities reveals continued signs of sexual risk among gay and bisexual men, but shows dramatically lower sexual risk among those who accurately know their HIV status. The findings were published today in CD"...

Edurant

Edurant Side Effects Center

Medical Editor: Charles Patrick Davis, MD, PhD

Edurant (rilpivirine) is a reverse transcriptase inhibitor used in combination with other antiretroviral agents and is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-na´ve adult patients. There is no generic available in the US. Some common side effects associated with Edurant are nausea, abdominal pain, fatigue, headache, dizziness depressive disorders, abnormal dreams, fat redistribution, and wasting.

Endurant (rilpivirine) is available as a tablet in the strength of 27.5 mg of rilpivirine hydrochloride that is equal to and labeled as 25 mg of rilpivirine. The recommended dose of Edurant is one 25 mg tablet once daily taken orally with a meal. Edurant should be used with caution when coadministered with a drug with a known risk of Torsade de Pointes. No human data on the effect of rilpivirine on fertility are available. No adequate and well-controlled studies of Edurant use in pregnant women have been conducted. To monitor maternal-fetal outcomes of pregnant women exposed to Edurant, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263. The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. It is not known whether rilpivirine is secreted in human milk. Because of both the potential for HIV transmission and the potential for adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving Edurant. Safety and effectiveness of Edurant in pediatric aged patients has not been established.

Our Edurant (rilpivirine) provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Edurant FDA Prescribing Information: Side Effects
(Adverse Reactions)

SIDE EFFECTS

The following adverse drug reactions (ADRs) are discussed in greater detail in other sections of the package insert:

Clinical Trials Experience

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 another drug and may not reflect the rates observed in clinical practice.

The safety assessment is based on the Week 96 pooled data from 1368 patients in the Phase 3 controlled trials TMC278-C209 (ECHO) and TMC278-C215 (THRIVE) in antiretroviral treatment-na´ve HIV-1 infected adult patients, 686 of whom received EDURANT (25 mg once daily) [see Clinical Studies]. The median duration of exposure for patients in the EDURANT arm and efavirenz arm was 104.3 and 104.1 weeks, respectively. Most ADRs occurred in the first 48 weeks of treatment. The proportion of subjects who discontinued treatment with EDURANT or efavirenz due to ADR, regardless of severity, was 2% and 4%, respectively. The most common ADRs leading to discontinuation were psychiatric disorders: 10 (1%) subjects in the EDURANT arm and 11 (2%) subjects in the efavirenz arm. Rash led to discontinuation in 1 (0.1%) subject in the EDURANT arm and 10 (1.5%) subjects in the efavirenz arm.

Common Adverse Drug Reactions

ADRs of at least moderate intensity ( ≥ Grade 2) reported in at least 2% of adult subjects are presented in Table 1. Selected treatment-emergent laboratory abnormalities are included in Table 2.

Table 1: Selected Treatment-Emergent Adverse Drug Reactions of at least Moderate Intensity* (Grades 2-4) Occurring in at Least 2% of Antiretroviral Treatment-Na´ve HIV-1 Infected Adult Subjects (Week 96 Analysis)

System Organ Class, Preferred Term, % Pooled Data from the Phase 3 TMC278-C209 and TMC278-C215 Trials
EDURANT + BR
N=686
Efavirenz + BR
N=682
Gastrointestinal Disorders
  Abdominal pain 2% 2%
  Nausea 1% 3%
  Vomiting 1% 2%
General Disorders and Administration Site Conditions
  Fatigue 2% 2%
Nervous System Disorders
  Headache 3% 4%
  Dizziness 1% 7%
Psychiatric Disorders
  Depressive disorders† 5% 4%
  Insomnia 3% 4%
  Abnormal dreams 2% 4%
Skin and Subcutaneous Tissue Disorders
  Rash 3% 11%
N = total number of subjects per treatment group; BR = background regimen
* Intensities are defined as follows: Moderate (discomfort enough to cause interference with usual activity); Severe (incapacitating with inability to work or do usual activity).
† Includes adverse drug reactions reported as depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicide ideation.

No new ADR terms were identified in adult subjects in the Phase 3 TMC278-C209 and TMC278-C215 trials between 48 weeks and 96 weeks nor in the Phase 2b TMC278-C204 trial through 240 weeks. The incidence of adverse events in the Phase 2b TMC278-C204 trial was similar to the Phase 3 trials through 96 weeks.

Less Common Adverse Drug Reactions

Treatment-emergent ADRs of at least moderate intensity ( ≥ Grade 2) occurring in less than 2% of antiretroviral treatment-na´ve subjects receiving EDURANT are listed below by System Organ Class. Some adverse events have been included because of investigator's assessment of potential causal relationship and were considered serious or have been reported in more than 1 subject treated with EDURANT.

Gastrointestinal Disorders: diarrhea, abdominal discomfort

Hepatobiliary Disorders: cholecystitis, cholelithiasis

Metabolism and Nutrition Disorders: decreased appetite

Nervous System Disorders: somnolence

Psychiatric Disorders: sleep disorders, anxiety

Renal and Urinary Disorders: glomerulonephritis membranous, glomerulonephritis mesangioproliferative, nephrolithiasis

Laboratory Abnormalities in Treatment-Na´ve Subjects

The percentage of subjects treated with EDURANT or efavirenz in the Phase 3 trials with selected treatment-emergent clinical laboratory abnormalities (Grades 1 to 4), representing worst Grade toxicity are shown in Table 2.

Table 2: Selected Treatment-Emergent Changes in Laboratory Parameters (Grades 1 to 4) Observed in Antiretroviral Treatment-Na´ve HIV-1-Infected Adult Subjects (Week 96 Analysis)

Laboratory Parameter Abnormality, (%) DAIDS Toxicity Range Pooled Data from the Phase 3 TMC278-C209 and TMC278-C215 Trials
EDURANT + BR
N=686
Efavirenz + BR
N=682
BIOCHEMISTRY      
Increased Creatinine
  Grade 1 ≥ 1.1 ≤ 1.3 x ULN 6% 1%
  Grade 2 > 1.3 ≤ 1.8 x ULN 1% 1%
  Grade 3 > 1.8 ≤ 3.4 x ULN < 1% 0
  Grade 4 > 3.4 x ULN 0 < 1%
Increased AST
  Grade 1 ≥ 1.25 ≤ 2.5 x ULN 16% 19%
  Grade 2 > 2.5 ≤ 5.0 x ULN 4% 7%
  Grade 3 > 5.0 ≤ 10.0 x ULN 2% 2%
  Grade 4 > 10.0 x ULN 1% 1%
Increased ALT
  Grade 1 ≥ 1.25 ≤ 2.5 x ULN 18% 20%
  Grade 2 > 2.5- ≤ 5.0 x ULN 5% 7%
  Grade 3 > 5.0 ≤ 10.0 x ULN 1% 2%
  Grade 4 > 10.0 x ULN 1% 1%
Increased Total Bilirubin
  Grade 1 ≥ 1.1- ≤ 1.5 x ULN 5% < 1%
  Grade 2 > 1.5- ≤ 2.5 x ULN 3% 1%
  Grade 3 > 2.5- ≤ 5.0 x ULN 1% < 1%
  Grade 4 > 5.0 x ULN 0 0
Increased Total Cholesterol (fasted)
  Grade 1 5.18-6.19 mmol/L 200-239 mg/dL 17% 31%
  Grade 2 6.20-7.77 mmol/L 240-300 mg/dL 7% 19%
  Grade 3 > 7.77 mmol/L > 300 mg/dL < 1% 3%
 
Increased LDL Cholesterol (fasted)
  Grade 1 3.37-4.12 mmol/L 130-159 mg/dL 14% 26%
  Grade 2 4.13-4.90 mmol/L 160-190 mg/dL 5% 13%
  Grade 3 ≥ 4.91 mmol/L ≥ 191 mg/dL 1% 5%
Increased Triglycerides (fasted)
  Grade 2 5.65-8.48 mmol/L 500-750 mg/dL 2% 2%
  Grade 3 8.49-13.56 mmol/L 751-1,200 mg/dL 1% 3%
  Grade 4 > 13.56 mmol/L > 1,200 mg/dL 0 1%
BR = background regimen; ULN = upper limit of normal
N = number of subjects per treatment group
Note: Percentages were calculated versus the number of subjects in ITT.

Adrenal Function

In the pooled Phase 3 trials, at Week 96, there was an overall mean change from baseline in basal cortisol of 19.1 (-30.87; -7.39) nmol/L in the EDURANT group and of +0.1 (-12.63; 12.80) nmol/L in the efavirenz group. At Week 96, the mean change from baseline in ACTH-stimulated cortisol levels was lower in the EDURANT group (+18.4 ± 8.36 nmol/L) than in the efavirenz group (+54.1 ± 7.24 nmol/L). Mean values for both basal and ACTH-stimulated cortisol values at Week 96 were within the normal range. Overall, there were no serious adverse events, deaths, or treatment discontinuations that could clearly be attributed to adrenal insufficiency.

Serum Creatinine

In the pooled Phase 3 trials, an increase in serum creatinine was observed over the 96 weeks of treatment with EDURANT. Most of this increase occurred within the first four weeks of treatment, with a mean change of 0.1 mg/dL (range: -0.3 mg/dL to 0.6 mg/dL) observed after 96 weeks of treatment. In subjects who entered the trial with mild or moderate renal impairment, the serum creatinine increase observed was similar to that seen in subjects with normal renal function. These changes are not considered to be clinically relevant and no subject discontinued treatment due to increases in serum creatinine. Serum creatinine increases occurred regardless of the background N(t)RTI regimen.

Serum Lipids

Changes from baseline in total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides are presented in Table 3. The clinical benefit of these findings has not been demonstrated.

Table 3: Lipid Values, Mean Change from Baseline*

Pooled Data from the Week 96 Analysis of the Phase 3 TMC278-C209 and TMC278-C215 Trials
Mean (95% CI) EDURANT + BR Efavirenz + BR
N Baseline Mean (mg/dL) Week 96 N Baseline Mean (mg/dL) Week 96
Mean (mg/dL) Mean Change† (mg/dL) Mean (mg/dL) Mean Change† (mg/dL)
Total Cholesterol (fasted) 584 161 167 5 549 161 190 28
HDL-cholesterol (fasted) 582 41 46 4 548 40 51 11
LDL-cholesterol (fasted) 580 96 98 1 547 96 110 14
Triglycerides (fasted) 584 124 117 -7 549 133 148 12
N = number of subjects per treatment group; BR = background regimen
* Excludes subjects who received lipid lowering agents during the treatment period
† The change from baseline is the mean of within-patient changes from baseline for patients with both baseline and Week 96 values

Subjects co-infected with hepatitis B and/or hepatitis C virus

In subjects co-infected with hepatitis B or C virus receiving EDURANT, the incidence of hepatic enzyme elevation was higher than in subjects receiving EDURANT who were not co-infected. This observation was the same in the efavirenz arm. The pharmacokinetic exposure of rilpivirine in co-infected subjects was comparable to that in subjects without co-infection.

Postmarketing Experience

Adverse reactions have been identified during post-marketing in patients receiving a rilpivirine containing regimen. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Renal and Genitourinary Disorders: nephrotic syndrome

Read the entire FDA prescribing information for Edurant (Rilpivirine Tablets) »

A A A

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


WebMD Daily

Get breaking medical news.