Edurant

• Generic Name: rilpivirine tablets
• Brand Name: Edurant
• Drug Class: HIV, NNRTIs

Edurant (Rilpivirine Tablets) side effects drug center

• Related Drugs
  Agenerase Biaxin Cabenuva Combivir Crixivan Epivir Epzicom Foscavir Isentress Kaletra Capsules Kaletra Tablets Kivexa Lexiva Megace Mepron Mycobutin Odefsey Optivar Prezista Rescriptor Retrovir Reyataz Selzentry Symtuza Valtrex Videx Viracept Viread Vistide Zerit

 

PROFESSIONAL

CONSUMER

SIDE EFFECTS

• Overview
• Consumer Information
• Professional Information

 

Edurant Side Effects Center

What Is Edurant?

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-naïve adult patients.

What Are Side Effects of Edurant?

Common side effects of Edurant include:

• nausea,
• vomiting,
• stomach pain,
• diarrhea,
• fatigue,
• tiredness,
• headache,
• dizziness,
• skin rash,
• depressive disorders,
• sleep problems (insomnia),
• unusual dreams,
• changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist), and
• wasting

Tell your doctor if you have serious side effects of Edurant including:

• mood changes,
• anxiety,
• severe depression,
• feeling hopeless,
• thoughts about suicide or hurting yourself,
• fever,
• chills,
• cough with yellow or green mucus,
• stabbing chest pain,
• wheezing,
• feeling short of breath,
• itching,
• loss of appetite,
• dark urine,
• clay-colored stools,
• yellowing of the skin or eyes (jaundice),
• severe pain in your upper stomach spreading to your shoulder or back,
• stomach bloating,
• sweating, or
• chills

Dosage for Edurant

The recommended dose of Edurant is one 25 mg tablet once daily taken orally with a meal.

What Drugs, Substances, or Supplements Interact with Edurant?

Edurant should be used with caution when coadministered with a drug with a known risk of Torsade de Pointes.

Edurant During Pregnancy and Breastfeeding

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.

Additional Information

Our Edurant (rilpivirine) provides a comprehensive view of available drug information as well as related drugs, user reviews, supplements, and diseases and conditions.

 

Edurant Consumer Information

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).

Seek medical treatment if you have a serious drug reaction that can affect many parts of your body. Symptoms may include: skin rash, fever, swollen glands, flu-like symptoms, muscle aches, severe weakness, unusual bruising, or yellowing of your skin or eyes.

Call your doctor at once if you have:

• mood changes, anxiety, feeling sad or hopeless, thoughts about suicide or hurting yourself;
• liver problems--right-sided upper stomach pain, dark urine, jaundice (yellowing of the skin or eyes); or
• symptoms of depression--mood changes, feelings of low self-worth, loss of interest in things you once enjoyed, new sleep problems, thoughts about hurting yourself.

Rilpivirine affects your immune system, which may cause certain side effects (even weeks or months after you've taken this medicine). Tell your doctor if you have:

• signs of a new infection--fever, night sweats, swollen glands, cold sores, cough, wheezing, diarrhea, weight loss;
• trouble speaking or swallowing, problems with balance or eye movement, weakness or prickly feeling; or
• swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence.

Common side effects may include:

• sleep problems (insomnia);
• depression;
• skin rash;
• headache; or
• changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

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.

Read the entire detailed patient monograph for Edurant (Rilpivirine Tablets)

 

Edurant Professional Information

SIDE EFFECTS

The following adverse reactions are discussed below and in other sections of the labeling:

• Skin and Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
• Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
• Depressive Disorders [see WARNINGS AND PRECAUTIONS]

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.

Clinical Trials Experience In Adults

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-Naive 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 2. Selected laboratory abnormalities are included in Table 3.

Table 2: Selected Adverse Drug Reactions of at least Moderate Intensity* (Grades 2-4) Occurring in at Least 2% of Antiretroviral Treatment-Naive 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

ADRs of at least moderate intensity (≥ Grade 2) occurring in less than 2% of antiretroviral treatment-Naive 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-Naive Subjects

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

Table 3: Selected Changes in Laboratory Parameters (Grades 1 to 4) Observed in Antiretroviral Treatment-Naive 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 -0.69 (-1.12, 0.27) micrograms/dL in the EDURANT group and of -0.02 (-0.48, 0.44) micrograms/dL in the efavirenz group.

In the EDURANT group, 43/588 (7.3%) of subjects with a normal 250 micrograms ACTH stimulation test at baseline developed an abnormal 250 micrograms ACTH stimulation test (peak cortisol level < 18.1 micrograms/dL) during the trial compared to 18/561 (3.2%) in the efavirenz group. Of the subjects who developed an abnormal 250 micrograms ACTH stimulation test during the trial, fourteen subjects in the EDURANT group and nine subjects in the efavirenz group had an abnormal 250 micrograms ACTH stimulation test at Week 96. Overall, there were no serious adverse events, deaths, or treatment discontinuations that could clearly be attributed to adrenal insufficiency. The clinical significance of the higher abnormal rate of 250 micrograms ACTH stimulation tests in the EDURANT group is not known.

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 4. The clinical benefit of these findings has not been demonstrated.

Table 4: Lipid Values, Mean Change from Baseline*

Mean (95% CI)	Pooled Data from the Week 96 Analysis of the Phase 3 TMC278-C209 and TMC278-C215 Trials
	EDURANT+BR				Efavirenz + BR
	N	Baseline	Week 96		N	Baseline	Week 96
		Mean (mg/dL)	Mean (mg/dL)	Mean Change† (mg/dL)		Mean (mg/dL)	Mean (mg/dL)	Mean Change† (mg/dL)
Total Cholesterol (fasted)	546	161	166	5	507	160	187	28
HDL-cholesterol (fasted)	545	41	46	4	505	40	51	11
LDL-cholesterol (fasted)	543	96	98	1	503	95	109	14
Triglycerides (fasted)	546	122	116	-6	507	130	141	11
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.

Clinical Trials Experience In Pediatric Patients

The safety assessment is based on the Week 48 analysis of the single-arm, open-label, Phase 2 trial, TMC278-C213, in which 36 antiretroviral treatment-Naive HIV-1 infected patients 12 to less than 18 years of age and weighing at least 32 kg received EDURANT (25 mg once daily) in combination with other antiretroviral agents [see Clinical Studies]. The median duration of exposure was 63.5 weeks. There were no patients who discontinued treatment due to ADRs. No new ADRs were identified compared to those seen in adults.

ADRs were reported in nineteen pediatric subjects (52.8%). Most ADRs were Grade 1 or 2. The most common ADRs reported in at least 2 subjects (regardless of severity) include headache (19.4%), depression (19.4%), somnolence (13.9%), nausea (11.1%), dizziness (8.3%), abdominal pain (8.3), vomiting (5.6%) and rash (5.6%).

Observed laboratory abnormalities were comparable to those in adults.

Adrenal Function

In trial TMC278 C213, at Week 48, the overall mean change from baseline in basal cortisol showed an increase of 1.59 (0.24, 2.93) micrograms/dL.

Six of 30 (20%) subjects with a normal 250 micrograms ACTH stimulation test at baseline developed an abnormal 250 micrograms ACTH stimulation test (peak cortisol level < 18.1 micrograms/dL) during the trial. Three of these subjects had an abnormal 250 micrograms ACTH stimulation test at Week 48. Overall, there were no serious adverse events, deaths, or treatment discontinuations that could clearly be attributed to adrenal insufficiency. The clinical significance of the abnormal 250 micrograms ACTH stimulation tests is not known.

Postmarketing Experience

Adverse reactions have been identified during postmarketing experience 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

Skin and Subcutaneous Tissue Disorders: Severe skin and hypersensitivity reactions including DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)

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

&Copy; Edurant Patient Information is supplied by Cerner Multum, Inc. and Edurant Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.