Note: This document contains side effect information about rilpivirine. Some dosage forms listed on this page may not apply to the brand name Edurant.

Summary

More frequent side effects include: attempted suicide, suicidal ideation, depressed mood, depression, dysphoria, major depressive disorder, and mood changes. Continue reading for a comprehensive list of adverse effects.

Applies to rilpivirine: oral tablet.

Serious side effects of Edurant

Along with its needed effects, rilpivirine (the active ingredient contained in Edurant) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking rilpivirine:

Less common

• Changes in behavior
• cloudy or bloody urine
• discouragement
• feeling sad or empty
• gaseous stomach pain
• indigestion
• irritability
• lack of appetite
• loss of interest or pleasure
• recurrent fever
• severe nausea or vomiting
• stomach fullness
• swelling of the face, feet, or lower legs
• thoughts of killing oneself
• tiredness
• trouble concentrating
• trouble sleeping
• yellow eyes or skin

Incidence not known

• Blurred vision
• chest tightness
• chills
• cough
• dizziness
• fever
• headache
• hives, itching, skin rash
• hoarseness
• irritation
• joint pain, stiffness, or swelling
• nervousness
• pounding in the ears
• redness of the skin
• slow or fast heartbeat
• sore throat
• swollen, painful, or tender lymph glands in the neck, armpit, or groin
• trouble breathing or swallowing

Other side effects of Edurant

Some side effects of rilpivirine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

• Abnormal dreams
• diarrhea
• fear
• nausea
• sleepiness or unusual drowsiness
• stomach discomfort
• unusual tiredness or weakness
• vomiting

For Healthcare Professionals

Applies to rilpivirine: oral tablet.

General

The most common side effects reported from monthly and every 2 month IM dosing studies were injection site reactions, headache, and pyrexia.

Most side effects occurred in the first 48 weeks of oral therapy. The most common side effects (at least moderate severity) were depression, headache, insomnia, increased transaminases, and rash. This drug was discontinued due to side effects in 2% of patients.

Safety findings from phase 3 trials were similar when this drug was used in combination with cabotegravir tablets or other antiretroviral agents. The manufacturer product information for cabotegravir tablets and cabotegravir-rilpivirine (the active ingredient contained in Edurant) IM should be consulted for additional information.^[Ref]

Dermatologic

Common (1% to 10%): Rash (included rash, erythematous rash, generalized rash, macular rash, maculopapular rash, morbilliform rash, papular rash, pruritic rash)

Frequency not reported: Lipodystrophy

Postmarketing reports: Severe skin and hypersensitivity reactions (including drug reaction with eosinophilia and systemic symptoms [DRESS])^[Ref]

During phase 3 trials, 3% of patients using this drug reported at least grade 2 therapy-related rashes; most rashes were grade 1 or 2 and developed in the first 4 to 6 weeks of therapy.^[Ref]

Endocrine

In the pooled phase 3 trials, at week 96, there was an overall mean change from baseline in basal cortisol of -19.1 nmol/L (-0.69 mcg/dL) in the rilpivirine (the active ingredient contained in Edurant) group, and of -0.6 nmol/L (-0.02 mcg/dL) in the efavirenz group. At week 96, the mean change from baseline in ACTH-stimulated cortisol levels was lower in the rilpivirine group (+18.4 nmol/L) than in the efavirenz group (+54.1 nmol/L). Mean values for both basal and ACTH-stimulated cortisol values at week 96 were within the normal range.

In the rilpivirine group, 43 of 588 patients with normal 250 mcg ACTH stimulation test at baseline developed abnormal 250 mcg ACTH stimulation test (peak cortisol level less than 18.1 mcg/dL) during the trial versus 18 of 561 patients in the efavirenz group. Abnormal 250 mcg ACTH stimulation test at week 96 was seen in 14 of the 43 rilpivirine patients and 9 of the 18 efavirenz patients. Clinical significance of abnormal 250 mcg ACTH stimulation tests (or the higher rate in the rilpivirine group) has not been established.

Overall, there were no serious side effects, deaths, or treatment discontinuations that could clearly be attributed to adrenal insufficiency.^[Ref]

Frequency not reported: Decreased basal cortisol, decreased adrenocorticotropic hormone (ACTH)-stimulated cortisol levels, adrenal insufficiency, abnormal 250 mcg ACTH stimulation test^[Ref]

Gastrointestinal

During clinical studies, elevated lipases were observed with this drug plus cabotegravir; grade 3 and 4 lipase increases occurred at a higher incidence with this drug plus cabotegravir compared with current antiretroviral therapy. These elevations were generally asymptomatic and did not lead to discontinuation of therapy. A case of fatal pancreatitis with grade 4 lipase and confounding factors (including history of pancreatitis) was reported in 1 study; causality to the injection regimen could not be ruled out.^[Ref]

Very common (10% or more): Nausea, increased pancreatic amylase

Common (1% to 10%): Abdominal pain (included abdominal pain, upper abdominal pain), vomiting, abdominal discomfort, increased lipase, dry mouth, flatulence, diarrhea

Frequency not reported: Pancreatitis^[Ref]

Hematologic

Common (1% to 10%): Decreased white blood cell count, decreased hemoglobin, decreased platelet count^[Ref]

Hepatic

Very common (10% or more): Increased ALT (up to 18%), increased AST (up to 16%), increased transaminases

Common (1% to 10%): Increased total bilirubin

Uncommon (0.1% to 1%): Hepatotoxicity, blood bilirubin increased

Frequency not reported: Cholecystitis, cholelithiasis, drug-induced acute allergic hepatitis^[Ref]

Increased ALT (grade 1: 18%; grade 2: 5%; grade 3: 1%; grade 4: 1%), AST (grade 1: 16%; grade 2: 4%; grade 3: 2%; grade 4: 1%), and total bilirubin (grade 1: 5%; grade 2: 3%; grade 3: 1%) have been reported.

The incidence of hepatic enzyme elevation was greater in patients coinfected with hepatitis B and/or C virus compared with uninfected patients.

During clinical studies, elevated transaminases (ALT/AST) were observed with this drug plus cabotegravir; these elevations were primarily attributed to acute viral hepatitis. A few patients on oral therapy (rilpivirine plus cabotegravir) had transaminase elevations attributed to suspected drug-related hepatotoxicity; these changes were reversible when therapy was stopped.

Small, nonprogressive increases in total bilirubin (without clinical jaundice) were observed with this drug plus cabotegravir; these changes were not considered clinically relevant as they likely reflected competition between cabotegravir and unconjugated bilirubin for a common clearance pathway (UGT1A1).^[Ref]

Hypersensitivity

Postmarketing reports: Severe skin and hypersensitivity reactions (including DRESS)

Immunologic

Uncommon (0.1% to 1%): Immune reconstitution/reactivation syndrome

Frequency not reported: Autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome, autoimmune hepatitis)^[Ref]

Local

Injection site reactions (ISRs) were the most common side effects associated with the IM administration of this drug; up to 1% of patients discontinued treatment with rilpivirine (the active ingredient contained in Edurant) and cabotegravir injections due to ISRs. ISRs were generally of mild (grade 1: up to 75%) or moderate (grade 2: up to 36%) severity; up to 4% of patients had severe (grade 3) ISRs. The median duration of overall ISR events was 3 days. The percentage of patients reporting ISRs decreased over time.^[Ref]

Very common (10% or more): Injection site reactions (up to 84%), injection site pain and discomfort, injection site nodule, injection site induration

Common (1% to 10%): Injection site swelling, injection site erythema, injection site pruritus, injection site bruising, injection site warmth, injection site hematoma

Uncommon (0.1% to 1%): Injection site abscess, injection site cellulitis, injection site anesthesia, injection site hemorrhage, injection site discoloration^[Ref]

Metabolic

Common (1% to 10%): Decreased appetite

Frequency not reported: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance")^[Ref]

Musculoskeletal

Common (1% to 10%): Myalgia^[Ref]

Nervous system

Very common (10% or more): Headache, dizziness

Common (1% to 10%): Somnolence

Uncommon (0.1% to 1%): Vasovagal reactions (in response to injections)^[Ref]

Other

Very common (10% or more): Increased fasted total cholesterol (up to 17%), increased fasted low-density lipoprotein (LDL) cholesterol (up to 14%), pyrexia (included pyrexia, feeling hot, body temperature increased)

Common (1% to 10%): Increased fasted triglycerides, fatigue, asthenia, malaise, increased weight^[Ref]

Increased fasted total cholesterol (grade 1: 17%; grade 2: 7%; grade 3: less than 1%), fasted LDL cholesterol (grade 1: 14%; grade 2: 5%; grade 3: 1%), and fasted triglycerides (grade 2: 2%; grade 3: 1%) have been reported.

At 48 weeks in 2 studies, patients who received this drug plus cabotegravir gained 1.5 kg (median) in weight, while patients who continued their current antiretroviral therapy gained 1 kg (median) in weight (pooled analysis). In the individual studies, the median weight gains in the arms with this drug plus cabotegravir were 1.3 and 1.8 kg, respectively, compared to 1.5 and 0.3 kg in the arms with current antiretroviral therapy. In another study, the median weight gain at 48 weeks was 1 kg in both the monthly and 2-monthly rilpivirine plus cabotegravir dosing arms.^[Ref]

Psychiatric

Very common (10% or more): Insomnia

Common (1% to 10%): Depression, depressed mood, depressive disorders (reported as depressed mood, depression, dysphoria, major depression, altered mood, negative thoughts, suicide attempt, suicidal ideation), abnormal dreams, sleep disorders, anxiety^[Ref]

Psychiatric disorders were the most common side effects leading to treatment discontinuation. In the phase 3 clinical trials, ten patients (1%), discontinued this drug due to psychiatric disorders.

During phase 3 trials through 96 weeks, depressive disorders (regardless of causality, severity) were reported in 9% of patients.^[Ref]

Renal

Common (1% to 10%): Increased creatinine

Frequency not reported: Membranous glomerulonephritis, mesangioproliferative glomerulonephritis, nephrolithiasis

Postmarketing reports: Nephrotic syndrome^[Ref]

Grade 1, 2, and 3 increases in creatinine have been reported in 6%, 1%, and less than 1% of patients, respectively.

During phase 3 trials, an increase in serum creatinine was seen over 96 weeks of therapy. Most of this increase occurred within the first 4 weeks of therapy, with a mean change of 0.1 mg/dL (range: -0.3 to 0.6 mg/dL) observed after 96 weeks of therapy. In subjects with mild or moderate baseline renal dysfunction, the serum creatinine increase observed was similar to that seen in subjects with normal renal function. These changes were not considered clinically relevant and no subject discontinued therapy due to increases in serum creatinine.^[Ref]