Edurant (rilpivirine HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Rilpivirine, an antiretroviral agent, is a human immunodeficiency virus (HIV) nonnucleoside reverse transcriptase inhibitor (NNRTI).
Rilpivirine, a diarylpyrimidine human immunodeficiency virus (HIV) nonnucleoside reverse transcriptase inhibitor (NNRTI), inhibits replication of HIV type 1 (HIV-1) by interfering with viral RNA- and DNA-directed polymerase activities of reverse transcriptase. Diarylpyrimidine NNRTIs (e.g., rilpivirine, etravirine) are capable of adapting to mutations in HIV-1 reverse transcriptase because of structural flexibility that allows for binding to the allosteric NNRTI binding pocket in a variety of conformations. Unlike other currently available NNRTIs, rilpivirine contains a cyanovinyl group that contributes to potency and maintains the drug's binding ability, despite the emergence of some resistance mutations.
In vitro, rilpivirine is highly active against wild-type HIV-1, but has limited activity against HIV type 2 (HIV-2). Rilpivirine has been active against some clinical HIV-1 isolates resistant to other commercially available NNRTIs (efavirenz, nevirapine). However rilpivirine-resistant strains have been selected in cell culture and have emerged during clinical use.
Cross-resistance can occur between rilpivirine and other commercially available NNRTIs, and is expected in patients who have virologic failure while receiving a regimen that contains rilpivirine. Considerable cross-resistance occurs between rilpivirine and etravirine; up to 90% of rilpivirine-resistant isolates that developed in patients receiving rilpivirine in phase 3 clinical studies also were resistant to etravirine. In addition, patients experiencing virologic failure while receiving a rilpivirine regimen in phase 3 clinical studies were more likely to have developed NNRTI-class resistance and treatment-emergent resistance to nucleoside and HIV nucleotide reverse transcriptase inhibitors (NRTIs) than patients experiencing virologic failure while receiving an efavirenz regimen.
After oral administration, peak rilpivirine plasma concentrations are generally attained within 4-5 hours. Rilpivirine is primarily metabolized in the liver by cytochrome (CYP) P-450 isoenzyme 3A. After a single oral dose, an average of 85% of the dose is eliminated in feces (75% as metabolites) and 6% is eliminated in urine (only trace amounts as unchanged rilpivirine).
The terminal elimination half-life of rilpivirine is approximately 50 hours. In individuals with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment receiving multiple doses of rilpivirine, exposure to the drug was 47 or 5% higher, respectively, compared to healthy individuals. Coinfection with HIV and hepatitis B virus (HBV) and/or hepatitis C virus (HCV) does not appear to have a clinically important effect on exposure to the drug.
Mild renal impairment does not have a clinically important effect on rilpivirine pharmacokinetics. Only limited data are available regarding pharmacokinetics of the drug in patients with moderate or severe renal impairment or end-stage renal disease, but rilpivirine concentrations may be increased as a result of altered absorption, distribution, or elimination. In vitro studies indicate that rilpivirine is approximately 99.7% bound to plasma proteins, primarily albumin.
Because rilpivirine is highly bound to plasma proteins, peritoneal dialysis and hemodialysis are unlikely to result in clinically important removal of the drug. Total exposure to rilpivirine dosage of 25 mg once daily is 30-40% lower during pregnancy when compared to the postpartum period; however, based on the exposure-response relationship of rilpivirine, this is not considered clinically relevant in patients who are virologically suppressed (viral load <50 copies/mL). Protein binding of rilpivirine is approximately 99% during the second and third trimesters, and the postpartum period.
Clinically relevant differences in pharmacokinetics based on sex, race, or hepatitis B and/or C coinfection have not been observed. Pharmacokinetics in treatment-naive HIV-1-infected pediatric patients 2 to less than 18 years of age and weighing >=16 kg receiving the recommended weight-based dosing regimen of rilpivirine tablets and tablets for oral suspension are similar or slightly higher than those observed in treatment-naive adult patients. In clinical trials, body weight in pediatric patients (ranging from 33-93 kg) did not have a clinically important effect on rilpivirine pharmacokinetics.
USES: Rilpivirine is used with other HIV medications to help control HIV infection. It helps to decrease the amount of HIV in your body so your immune system can work better. This lowers your chance of getting HIV complications (such as new infections, cancer) and improves your quality of life.
Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). It blocks the virus from growing and infecting more cells. Rilpivirine is not a cure for HIV infection.
To decrease your risk of spreading HIV disease to others, continue to take all HIV medications exactly as prescribed by your doctor. Use an effective barrier method (latex or polyurethane condoms/dental dams) during sexual activity as directed by your doctor. Do not share personal items (such as needles/syringes, toothbrushes, and razors) that may have contacted blood or other body fluids.
Consult your doctor or pharmacist for more details.
Generic name: rilpivirine HCl
Pronunciation: (RIL-pi-VIR-een)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Edurant
Indications
The following indications are listed for Edurant:
- Hiv Infection
Also known as: Human Immunodeficiency Virus Disease, Human Immunodeficiency Virus Infection.
Dosing
Rilpivirine is commercially available as rilpivirine hydrochloride; dosage is expressed in terms of rilpivirine.
If rilpivirine (Edurant(R)) is coadministered with rifabutin, the rilpivirine dosage should be increased to 50 mg once daily. If rifabutin coadministration is halted, the rilpivirine dosage should be decreased to 25 mg once daily.
Rilpivirine hydrochloride is available as oral tablets (Edurant(R)) and tablets for oral suspension (Edurant PED(R)); both formulations are administered once daily with a meal. Rilpivirine tablets should be administered to adults and pediatric patients weighing >=25 kg. Rilpivirine tablets for oral suspension should be administered only to pediatric patients weighing >=14 kg to <25 kg.
Rilpivirine oral tablets and tablets for oral suspension have differing pharmacokinetic profiles; therefore, the tablets and tablets for oral suspension should not be substituted on a milligram-per-milligram basis.
Rilpivirine tablets for oral suspension must be dispersed in drinking water and immediately consumed with a meal. If not consumed immediately, the suspension should be discarded and a new dose prepared. Rilpivirine tablets for oral suspension should not be crushed, chewed, or swallowed whole.
In order to properly prepare the tablets for oral suspension for administration, an appropriate number of tablets should be placed in a cup and 5 mL of room temperature drinking water should be added. The cup should be swirled carefully for 1--2 minutes; the oral suspension should begin to have a cloudy appearance. After swirling the cup for 1--2 minutes, the oral suspension may be consumed immediately or the suspension can be further diluted with 5 mL of drinking water, orange juice, or applesauce to assist in administration. All the medicine within the cup should be consumed immediately; a spoon may be used if needed. If medicine is still present in the cup, another 5 mL of drinking water (or alternative beverage or soft food) may be added to the cup, swirled, and consumed immediately.
Food enhances rilpivirine bioavailability. Systemic exposure is approximately 40 or 50% lower if rilpivirine tablets are administered under fasting conditions or with only a protein-rich nutritional drink, respectively, compared with following a standard meal (533 kcal) or high-caloric meal (928 kcal). Systemic exposure is 31 or 28% lower if rilpivirine tablets for oral suspension are dispersed in drinking water in fasted conditions or after yogurt consumption, respectively, compared with following a meal in adults containing 533 kcal.
If a dose of rilpivirine is missed within 12 hours of the time it is usually taken, take the missed dose as soon as possible with a meal. If a dose of rilpivirine is missed by more than 12 hours, then skip the missed dose and resume the normal dosing schedule.
Rilpivirine must be used in conjunction with other antiretrovirals. Single-entity rilpivirine should not be used concomitantly with emtricitabine/rilpivirine/tenofovir alafenamide or cabotegravir/rilpivirine injeciton. Single-entity rilpivirine should not be used concomitantly with emtricitabine/rilpivirine/tenofovir DF, unless needed for adjustment of rilpivirine dosage (e.g., when the fixed combination is used concomitantly with rifabutin).
Store rilpivirine tablets and tablets for oral suspension at 20--25oC; (excursions permitted between 15-30oC). Store tablets in original bottle to protect from light and tablets for oral suspension in original package to protect from moisture.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Most rilpivirine drug interaction studies reported to date used rilpivirine dosages of 75 or 150 mg once daily; these dosages are considerably higher than the usually recommended rilpivirine dosage (25 mg once daily). Rilpivirine is primarily metabolized by cytochrome P-450 isoenzyme 3A (CYP3A).
The following drug interactions are based on studies using single-entity rilpivirine. When rilpivirine fixed combinations are used, interactions associated with each drug in the fixed combination should be considered.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Concomitant use of rilpivirine with drugs that induce cytochrome P-450 isoenzyme 3A (CYP3A) or drugs that elevate gastric pH is contraindicated since substantially decreased plasma rilpivirine concentrations may occur and may result in loss of virologic response and development of resistance to rilpivirine and/or class resistance to HIV NNRTIs.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects of at least moderate to severe intensity reported in 2% or more of patients in clinical trials include depressive disorders, insomnia, headache, and rash.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of rilpivirine tablets (Edurant(R)) and tablets for oral suspension (Edurant PED(R)) have been established for the treatment of HIV-1 infection in treatment-naive pediatric patients >=2 years of age and weighing >=14 kg.
The use of rilpivirine in this patient population is supported by the results of 3 trials (i.e., Trial TMC278-C213, Trial TMC278HTX2002, MOCHA trial). The single arm, open-label, phase 2, TMC278-C213 trial involved 2 cohorts of treatment-naive HIV-1 infected pediatric patients. Cohort 1 assessed the efficacy, safety, and pharmacokinetics of rilpivirine tablets in 36 pediatric patients (12 to <18 years of age and weighing >=32 kg). Cohort 2 assessed the safety, tolerability, antiviral activity, and pharmacokinetics of rilpivirine tablets and tablets for oral suspension weight-adjusted doses in 18 pediatric patients (6 to <12 years of age and weighing >=17 kg). The single-arm, open-label, phase 2, TMC278HTX2002 trial assessed the safety, tolerability, antiviral activity, and pharmacokinetics of rilpivirine tablets and tablets for oral suspension weight-adjusted doses in 26 pediatric patients (2 to <12 years of age and weighing >=16 kg). In the ongoing MOCHA trial, the safety, tolerability, and pharmacokinetics of oral/injectable cabotegravir and oral/injectable rilpivirine are being evaluated.
Rilpivirine tablets for oral suspension (Edurant PED(R)) are not recommended for use in pediatric patients <2 years of age or weighing <14 kg.
The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to rilpivirine during pregnancy. Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting https://www.apregistry.com/.
The overall risk of birth defects with first-trimester exposure for rilpivirine was not markedly different compared to the background rate for major birth defects of 2.7% in the United States reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). Limitations of using an external comparator (the MACDP) includes differences in populations and methodology, and confounding due to the underlying disease. The rate of miscarriage is not reported in the APR.
In a small study of 19 HIV-1 infected women on a rilpivirine-based regimen, protein binding was similar during the second and third trimesters and the postpartum period; however, total exposure of rilpivirine was approximately 30-40% lower during pregnancy when compared to the postpartum period. Of the 12 virologically suppressed patients at baseline (<50 copies/mL), virologic suppression with a rilpivirine-based regimen was maintained through the third trimester in 10 patients, and was well-tolerated. Among 10 infants born to HIV-1 infected women, all were HIV-1 negative at delivery and for 16 weeks post-partum. All infants received prophylactic zidovudine treatment at delivery.
Animal data have shown no increases in embryo-fetal toxicity at rilpivirine exposures 15-70 times the equivalent human exposure.
Monitor viral load closely in pregnant women; lower rilpivirine exposures have been observed in pregnant individuals.
Based on limited data, rilpivirine is present in human milk; however, there are no data on the effects of rilpivirine on the breast-fed infant or on milk production.
The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding. The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.
The manufacturer makes no specific dosage recommendations for geriatric patients.
Consult the product labeling of commercially available fixed-combination products containing rilpivirine for specific dosage adjustments of each component in geriatric patients.
Experience in those 65 years of age and older is insufficient to determine whether they respond differently to rilpivirine than younger adults. Dosage should be selected with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.
ICD codes
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Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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