QT time prolongation
Adverse drug events
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Explanations of the substances for patients
We have no additional warnings for the combination of abarelix and rilpivirine. Please also consult the relevant specialist information.
The reported changes in exposure correspond to the changes in the plasma concentration-time curve [ AUC ]. We do not expect any change in exposure for abarelix, when combined with rilpivirine (100%). We do not expect any change in exposure for rilpivirine, when combined with abarelix (100%).
The pharmacokinetic parameters of the average population are used as the starting point for calculating the individual changes in exposure due to the interactions.
The bioavailability of abarelix is unknown. The terminal half-life [ t12 ] is rather long at 316.8 hours and constant plasma levels [ Css ] are only reached after more than 1267.2 hours. The protein binding [ Pb ] is 97.5% strong. The metabolism via cytochromes is currently still being worked on.
Rilpivirine has a low oral bioavailability [ F ] of 24%, which is why the maximum plasma level [Cmax] tends to change strongly with an interaction. The terminal half-life [ t12 ] is rather long at 38 hours and constant plasma levels [ Css ] are only reached after more than 152 hours. The protein binding [ Pb ] is very strong at 99.7% and the volume of distribution [ Vd ] is very large at 96 liters, Since the substance has a low hepatic extraction rate of 0.05, displacement from protein binding [Pb] in the context of an interaction can lead to increased exposure. The metabolism mainly takes place via CYP3A4.
|Serotonergic Effects a||0||Ø||Ø|
Rating: According to our knowledge, neither abarelix nor rilpivirine increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, neither abarelix nor rilpivirine increase anticholinergic activity.
QT time prolongation
Rating: In combination, abarelix and rilpivirine can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||aba||ril|
|Elevated ALT||1.0 %||n.a.||+|
|Elevated AST||1.0 %||n.a.||+|
Hypersensitivity reaction: rilpivirine
Based on your answers and scientific information, we assess the individual risk of undesirable side effects. These recommendations are intended to advise professionals and are not a substitute for consultation with a doctor. In the restricted test version (alpha), the risk of all substances has not yet been conclusively assessed.
Abstract: Rilpivirine is a potent nonnucleoside reverse transcriptase inhibitor (NNRTI) with high efficacy in the treatment of HIV infection in treatment-naïve patients. This drug is active against both wild-type HIV-1 and a wide variety of first-generation NNRTI. Rilpivirine has a highly favorable pharmacokinetics profile, but, because its absorption depends on gastric pH, it should be administered with food to ensure correct absorption. Rilpivirine is metabolized by cytochrome P450 (CYP) 3A and consequently potential interactions should be considered when it is administered with P450 (CYP) 3A inducers or inhibitors. Although higher doses can behave as enzyme inducers, at a dose of 25mg/day, rilpivirine is unlikely to alter the concentrations of other drugs metabolized through this pathway. Because of its prolonged half-life, rilpivirine can be administered orally once daily.
Abstract: Rilpivirine (RPV), the latest nonnucleoside reverse transcriptase inhibitor active against HIV-1, is prescribed in a standard dosage of 25 mg once a day in combination with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF). The aim of this observational study was to characterize the RPV pharmacokinetic profile, to quantify interpatient variability, and to identify potential factors that could influence drug exposure. RPV concentration data were collected from HIV-infected patients as part of routine therapeutic drug monitoring performed in our center (Laboratory of Clinical Pharmacology). A population pharmacokinetic analysis was performed with NONMEM by comparing various structural models. The influence of demographic and clinical covariates, as well as frequent genetic polymorphisms in 5 genes (CYP3A4*22, CYP3A5*3, CYP2C19*2, CYP2C19*17, UGT1A1*28, and UGT1A4*2), on RPV elimination was explored. A total of 325 plasma concentration measurements were obtained from 249 HIV-positive patients. Plasma concentrations ranged from 12 to 255 ng/ml. A one-compartment model with zero-order absorption best characterized RPV pharmacokinetics. The average RPV clearance (CL) was 11.7 liters/h, the average volume of distribution was 401 liters, and the mean absorption time was 4 h. The interinterindividual variability (IIV) for CL was estimated to be 33%. None of the available demographic or genetic covariates showed any influence on RPV pharmacokinetics, but 29% of the patients were predicted to present minimal concentrations below the recently identified target cutoff value of 50 ng/ml. The variability in RPV pharmacokinetics appears to be lower than that for most other antiretroviral drugs. However, under the standard regimen of 25 mg daily, a significant number of patients might be underdosed. It remains to be investigated whether the underexposure has an impact on the development of resistance while patients are on maintenance therapy.
Abstract: PURPOSE: Rilpivirine, prescribed for the treatment of HIV infection, presents an important inter-individual pharmacokinetic variability. We aimed to determine population pharmacokinetic parameters of rilpivirine in adult HIV-infected patients and quantify their inter-individual variability. METHODS: We conducted a multicenter, retrospective, and observational study in patients treated with the once-daily rilpivirine/tenofovir disoproxil fumarate/emtricitabine regimen. As part of routine therapeutic drug monitoring, rilpivirine concentrations were measured by UPLC-MS/MS. Population pharmacokinetic analysis was performed using NONMEM software. Once the compartmental and random effects models were selected, covariates were tested to explain the inter-individual variability in pharmacokinetic parameters. The final model qualification was performed by both statistical and graphical methods. RESULTS: We included 379 patients, resulting in the analysis of 779 rilpivirine plasma concentrations. Of the observed trough individual plasma concentrations, 24.4% were below the 50 ng/ml minimal effective concentration. A one-compartment model with first-order absorption best described the data. The estimated fixed effect for plasma apparent clearance and distribution volume were 9 L/h and 321 L, respectively, resulting in a half-life of 25.2 h. The common inter-individual variability for both parameters was 34.1% at both the first and the second occasions. The inter-individual variability of clearance was 30.3%. CONCLUSIONS: Our results showed a terminal half-life lower than reported and a high proportion of patients with suboptimal rilpivirine concentrations, which highlights the interest of using therapeutic drug monitoring in clinical practice. The population analysis performed with data from "real-life" conditions resulted in reliable post hoc estimates of pharmacokinetic parameters, suitable for individualization of dosing regimen.