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Rilpivirine

Medically reviewed by Drugs.com. Last updated on Sep 26, 2020.

Pronunciation

(ril pi VIR een)

Index Terms

  • Rilpivirine HCl
  • TMC278

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Edurant: 25 mg

Brand Names: U.S.

  • Edurant

Pharmacologic Category

  • Antiretroviral, Reverse Transcriptase Inhibitor, Non-nucleoside (Anti-HIV)

Pharmacology

As a non-nucleoside reverse transcriptase inhibitor, rilpivirine has activity against HIV-1 by binding to reverse transcriptase. It consequently blocks the RNA-dependent and DNA-dependent DNA polymerase activities, including HIV-1 replication. It does not require intracellular phosphorylation for antiviral activity.

Absorption

Increased 40% with a meal (normal-to-high calorie)

Metabolism

Hepatic, primarily by CYP3A4

Excretion

Feces (85%, ~25% as unchanged drug); urine (~6%; <1% as unchanged drug)

Time to Peak

Plasma: 4 to 5 hours

Half-Life Elimination

~50 hours

Protein Binding

99.7% (primarily albumin)

Special Populations: Renal Function Impairment

Exposure was similar in HIV-1-infected subjects with mild renal impairment relative to HIV-1–infected subjects with healthy renal function; no dose adjustment is required. There is limited information regarding the pharmacokinetics in patients with moderate or severe renal impairment or in patients with ESRD. Concentrations may be increased because of alteration of drug absorption, distribution, and metabolism secondary to renal dysfunction. The potential impact is not expected to be of clinical relevance for subjects with moderate renal impairment; no dose adjustment is required.

Special Populations: Hepatic Function Impairment

The multiple-dose exposure was 47% higher in subjects with mild hepatic impairment and 5% higher in subjects with moderate hepatic impairment; no dose adjustment is required. Rilpivirine has not been studied in subjects with severe hepatic impairment.

Use: Labeled Indications

HIV-1 infection: Treatment of HIV-1 infections in antiretroviral treatment-naive patients ≥12 years of age and weighing ≥35 kg, with HIV-1 RNA ≤100,000 copies/mL at the start of therapy in combination with other antiretroviral agents

Contraindications

Coadministration with anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin), antimycobacterials (rifampin, rifapentine), proton pump inhibitors (esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole), systemic dexamethasone (more than a single dose), or St John's wort.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to rilpivirine or any component of the formulation

Dosing: Adult

HIV-1 infection, treatment: Patients ≥35 kg: Oral: 25 mg once daily.

Note: Do not use rilpivirine-based regimens in patients with pre-antiretroviral therapy CD4 count <200 cells/mm3 and/or HIV RNA >100,000 copies/mL (HHS [adult] 2019).

Pregnancy: 25 mg once daily in patients on stable regimen prior to pregnancy and who are virologically suppressed

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Pediatric

HIV-1 infection, treatment: Use in combination with other antiretroviral agents.

Infants and Children <12 years or <35 kg: Not recommended for use; no dosing recommendations available.

Children and Adolescents ≥12 years and ≥35 kg: Oral: 25 mg once daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Administration

Swallow tablet whole with water. Administer with a normal- to high-calorie meal. Taking with a protein supplement drink alone does not increase absorption.

Dietary Considerations

Take with a normal- to high-calorie meal. Taking with a protein supplement drink alone does not increase absorption.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Keep in original container; protect from light.

Drug Interactions

Antacids: May decrease the serum concentration of Rilpivirine. Management: Administer antacids at least 2 hours before or 4 hours after rilpivirine when used with most rilpivirine products. However, administer antacids at least 6 hours before or 4 hours after the rilpivirine/dolutegravir combination product. Consider therapy modification

Antihepaciviral Combination Products: May increase the serum concentration of Rilpivirine. Avoid combination

CarBAMazepine: May decrease the serum concentration of Rilpivirine. Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Rilpivirine. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to concomitant therapy when possible. If concomitant therapy cannot be avoided, monitor for reduced clinical effects of the CYP3A4 substrate. Consider therapy modification

Darunavir: May increase the serum concentration of Rilpivirine. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

DexAMETHasone (Systemic): May decrease the serum concentration of Rilpivirine. Avoid combination

Didanosine: Rilpivirine may decrease the absorption of Didanosine. More specifically, simultaneous coadministration of these drugs creates a conflict between recommendations to administer with (rilpivirine) and without (didanosine) food. Didanosine may decrease the absorption of Rilpivirine. More specifically, simultaneous coadministration of these drugs creates a conflict between recommendations to administer with (rilpivirine) and without (didanosine) food. Management: Administer didanosine on an empty stomach at least 2 hours before or 4 hours after rilpivirine, due to the requirement that rilpivirine be administered with food. Consider therapy modification

Efavirenz: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Efavirenz. Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Efavirenz. Avoid combination

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Ergonovine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Ergonovine. Specifically, this would be most likely with delavrdine, while other Non-Nucleoside Reverse Transcriptase Inhibitors may be more likely to decrease the concentration of Ergonovine. Avoid combination

Etravirine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Etravirine. This has been observed with the NNRTIs efavirenz and nevirapine. Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Etravirine. This has been observed with delavirdine. Avoid combination

Fosphenytoin: May decrease the serum concentration of Rilpivirine. Avoid combination

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

Histamine H2 Receptor Antagonists: May decrease the serum concentration of Rilpivirine. Management: Administer histamine H2 receptor antagonists at least 12 hours before or 4 hours after rilpivirine. Consider therapy modification

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Ketoconazole (Systemic): May increase the serum concentration of Rilpivirine. Rilpivirine may decrease the serum concentration of Ketoconazole (Systemic). Monitor therapy

Levomethadone: Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Levomethadone. Management: Levomethadone dosage adjustments will likely be required with efavirenz and nevirapine, and may be necessary with rilpivirine as well. Monitor therapy

Lopinavir: May increase the serum concentration of Rilpivirine. Monitor therapy

Macrolide Antibiotics: May increase the serum concentration of Rilpivirine. Management: Consider the use of azithromycin or another non-macrolide alternative when appropriate to avoid this potential interaction. Consider therapy modification

Methadone: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the metabolism of Methadone. Management: Methadone dosage adjustments will likely be required with efavirenz and nevirapine, and may be necessary with rilpivirine as well. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy

OXcarbazepine: May decrease the serum concentration of Rilpivirine. Avoid combination

PHENobarbital: May decrease the serum concentration of Rilpivirine. Avoid combination

Phenytoin: May decrease the serum concentration of Rilpivirine. Avoid combination

Primidone: May decrease the serum concentration of Rilpivirine. Avoid combination

Proton Pump Inhibitors: May decrease the serum concentration of Rilpivirine. Avoid combination

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Reverse Transcriptase Inhibitors (Non-Nucleoside): May increase the serum concentration of Rilpivirine. This mechanism applies to coadministration of delavirdine. Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Rilpivirine. This mechanism applies to coadministration of efavirenz, etravirine, and nevirapine. Avoid combination

Rifabutin: May decrease the serum concentration of Rilpivirine. Management: Increase the rilpivirine dose to 50 mg/day during rifabutin treatment. Decrease back to 25 mg/day following rifabutin discontinuation. Use of rifabutin with the emtricitabine/rilpivirine/tenofovir alafenamide combination product is not recommended. Consider therapy modification

Rifamycin Derivatives: May decrease the serum concentration of Rilpivirine. Avoid combination

Saquinavir: May enhance the arrhythmogenic effect of Rilpivirine. Saquinavir may increase the serum concentration of Rilpivirine. Avoid combination

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

St John's Wort: May decrease the serum concentration of Reverse Transcriptase Inhibitors (Non-Nucleoside). Specifically, St. Johns Wort may increase the metabolism of Reverse Transcriptase Inhibitors (Non-Nucleoside). Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Central nervous system: Depression (5% to 9%; children and adolescents: 19%), headache (3%; children and adolescents: 19%), drowsiness (children and adolescents: 14%)

Endocrine & metabolic: Decreased plasma cortisol (7%; children and adolescents: 20%; decrease from baseline via ACTH stimulation test; clinical significance is unknown), increased serum cholesterol (7% to 17%), increased LDL cholesterol (5% to 14%)

Gastrointestinal: Nausea (1%; children and adolescents: 11%)

Hepatic: Increased serum ALT (1% to 18%), increased serum AST (1% to 16%)

1% to 10%:

Central nervous system: Dizziness (1%; children and adolescents: 8%), insomnia (3%), abnormal dreams (2%), fatigue (2%)

Dermatologic: Skin rash (3% to 6%)

Endocrine & metabolic: Increased serum triglycerides (2%)

Gastrointestinal: Abdominal pain (2%; children and adolescents: 8%), vomiting (1%; children and adolescents: 6%)

Hepatic: Increased serum bilirubin (1% to 5%)

Renal: Increased serum creatinine (1% to 6%)

<1%, postmarketing, and/or case reports (Limited to important or life-threatening): Angioedema, conjunctivitis, DRESS syndrome, facial edema, fever, hepatitis, hypersensitivity reaction, localized vesiculation, nephrotic syndrome, suicidal ideation

Warnings/Precautions

Concerns related to adverse effects:

• Depressive disorders: May cause depression, depressed mood, dysphoria, mood changes, negative thoughts, suicide attempts, or suicidal ideation; if changes are noted, seek professional intervention immediately; reevaluate risk versus benefit of continued rilpivirine therapy.

• Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance).

• Hepatotoxicity: Has been reported during use. Patients with significant transaminase elevations or hepatitis B or C prior to treatment may be at greater risk for hepatic adverse events. Hepatotoxicity has occurred in a few adult patients with no prior hepatic disease or risk factors. Baseline and periodic laboratory LFT evaluation during therapy is recommended for patients with pre-existing risk factors; also consider LFT monitoring in patients without identifiable hepatic disease risk.

• Hypersensitivity: Hypersensitivity and severe skin reactions have been reported, including severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis or eosinophilia, or drug reaction with eosinophilia and systemic symptoms (DRESS) with rilpivirine-containing regimens. Some skin reactions were accompanied by constitutional symptoms (eg, fever); other skin reactions were associated with organ dysfunction (eg, hepatic serum biochemistry elevations). In clinical trials, treatment-related rashes ≥ Grade 2 were reported in 3% of patients. Most rashes were Grade 1 or 2 and occurred within the first 4 to 6 weeks of therapy. No Grade 4 rashes were reported. Monitor laboratory parameters and clinical status; discontinue if any hypersensitivity or skin rash develop.

• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.

Concurrent drug therapy issues:

• QTc prolongation: Doses >25 mg daily have been associated with QTc prolongation; use caution when coadministering with a drug with a known risk of torsades de pointes (HHS [adult] 2019).

Monitoring Parameters

Cholesterol, triglycerides, hepatic transaminases; signs of skin rash, fever, and/or hypersensitivity reactions, signs and symptoms of infection

Reproductive Considerations

The Health and Human Services perinatal HIV guidelines consider rilpivirine an alternative component of antiretroviral therapy for females living with HIV who are not yet pregnant but are trying to conceive.

For males and females living with HIV and planning a pregnancy, maximum viral suppression below the limits of detection with antiretroviral therapy (ART), modification of therapy (if needed), optimization of the woman’s health, and a discussion of the potential risks and benefits of ART therapy during pregnancy is recommended prior to conception (HHS [perinatal] 2019).

Pregnancy Considerations

Rilpivirine has moderate to high placental transfer.

No increased risk of overall birth defects has been observed following first trimester exposure according to data collected by the antiretroviral pregnancy registry. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm delivery, stillbirth, low birth weight, and small for gestational age infants. Actual risks may be influenced by maternal factors, such as disease severity, gestational age at initiation of therapy, and specific ART regimen; therefore, close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children without HIV but who were exposed to ART in utero and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction. Hypersensitivity reactions (including hepatic toxicity and rash) are more common in women on nonneucleoside reverse transcriptase inhibitor therapy; it is not known if pregnancy increases this risk.

The Health and Human Services (HHS) perinatal HIV guidelines consider rilpivirine an alternative ART for pregnant females living with HIV who are antiretroviral naive, who have had ART therapy in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). Females who become pregnant while taking rilpivirine may continue if viral suppression is effective and the regimen is well tolerated. The pharmacokinetics are highly variable in pregnancy; data are insufficient to recommend pregnancy-specific dosing; however, viral loads should be monitored more frequently when standard doses are used in pregnant females.

The HHS perinatal HIV guidelines recommend rilpivirine as a component in alternative regimens for initial use in antiretroviral-naive pregnant females with a pretreatment HIV RNA ≤100,000 copies/mL and CD4 cell count ≥200 cells/mm3.

In general, ART is recommended for all pregnant females living with HIV to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Monitoring of pregnant females is more frequent than in nonpregnant adults. ART should be continued postpartum for all females living with HIV and can be modified after delivery.

Health care providers are encouraged to enroll pregnant females exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or http://www.APRegistry.com). Health care providers caring for pregnant females living with HIV and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2019).

Patient Education

What is this drug used for?

• It is used to treat HIV infection.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Vomiting

• Dizziness

• Abdominal pain

• Fatigue

• Headache

• Trouble sleeping

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Behavioral changes

• Mood changes

• Infection

• Depression like thoughts of suicide, anxiety, emotional instability, or confusion

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Abnormal heartbeat

• Change in body fat

• Severe skin problems like red, blistered, or swollen skin; peeling skin; itchy or painful skin

• Eye irritation

• Eye redness

• Trouble swallowing

• Severe abdominal pain

• Sores in mouth, throat, nose, or eyes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Frequently Asked Questions