Rilpivirina

Uses

Rilpivirina is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in combination with other antiretrovirals to specifically treat human immunodeficiency virus type 1 (HIV-1).

Rilpivirina, in combination with other agents, is indicated for the treatment of HIV-1 infections in antiretroviral treatment-naive patients with HIV-1 RNA ≤100,000 copies/mL and CD4+ cell count >200 cells/mm³. The FDA combination therapy approval of rilpivirine and dolutegravir is indicated for adults with HIV-1 infections whose virus is currently suppressed (< 50 copies/ml) on a stable regimen for at least six months, without history of treatment failure and no known substitutions associated to resistance to any of the two components of the therapy.

Rilpivirina is also used to associated treatment for these conditions: Human Immunodeficiency Virus Type 1 (HIV-1) Infection

How Rilpivirina works

Rilpivirina is a non-competitive NNRTI that binds to reverse transcriptase. Its binding results in the blockage of RNA and DNA- dependent DNA polymerase activities, like HIV-1 replication. It does not present activity against human DNA polymerases α, β and γ. Rilpivirina's flexible structure around the aromatic rings allows the adaptation to changes in the non-nucleoside RT binding pocket, reducing the likelihood of viral mutations conferring resistance.

Toxicity

In the event of an overdose, contact a poison control centre. Patients should be treated with symptomatic and supportive measures, including monitoring of the QT interval. Dialysis is not expected to remove significant amounts of the drug from plasma as it is highly bound to albumin.

Food Interaction

• Avoid St. John's Wort. St.John's Wort will decrease levels of this medication.
• Take with food. Absorption is increased by 40% if taken with food.

[Moderate] GENERALLY AVOID: Coadministration with grapefruit or grapefruit juice may increase the plasma concentrations of rilpivirine.

The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit.

In 15 study subjects given rilpivirine (150 mg once daily) with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily), mean rilpivirine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) were increased by 30%, 49% and 76%, respectively.

In 16 study subjects given a single 500 mg dose of a less potent CYP450 3A4 inhibitor chlorzoxazone two hours after rilpivirine (150 mg once daily), mean rilpivirine Cmax, AUC, and Cmin were increased by 17%, 25%, and 18%, respectively.

Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability).

In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands.

Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

ADJUST DOSING INTERVAL: The administration of rilpivirine in a fasting state may decrease its oral absorption.

Under fasted conditions, the systemic exposure to rilpivirine was 40% lower compared to normal or high-fat caloric meals (533 to 928 Kcal).

The systemic exposure was 50% lower when rilpivirine was taken with a protein-rich nutritional beverage.

MANAGEMENT: Coadministration of grapefruit or grapefruit juice with rilpivirine should preferably be avoided.

For optimal absorption, it is recommended to take rilpivirine on a regular schedule with a meal.

Rilpivirina Drug Interaction

Major: efavirenz / emtricitabine / tenofovir, sotalolMinor: sulfamethoxazole / trimethoprimUnknown: aspirin, charcoal, charcoal, amphetamine / dextroamphetamine, anastrozole, aspirin, bictegravir / emtricitabine / tenofovir alafenamide, exenatide, tadalafil, ubiquinone, copper gluconate, heparin, acetaminophen, vitamin a topical, bioflavonoids, emtricitabine / tenofovir, cholecalciferol

Rilpivirina Disease Interaction

Moderate: depression, liver impairment, renal impairment

Volume of Distribution

In HIV-1 patients, the apparent volume of distribution in the central compartment was 152-173 L.

Elimination Route

Rilpivirina has a T_max of 3-4 hours and has a mean AUC of 2235 ± 851 ng*h/mL. A 25mg dose reaches a C_max of 247 ng/mL in healthy subjects and 138.6 ng/mL in patients with HIV-1.

Half Life

Rilpivirina has a terminal half-life of 34-55 hours.

Clearance

In HIV-1 patients, the apparent total clearance is estimated to be 6.89-8.66 L/h.

Elimination Route

Rilpivirina is 85% eliminated in the feces and 6.1% eliminated in the urine. 25% of a dose is recovered in the feces as the unchanged parent drug, while 9

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