New option for management of HIV-1 infection in treatment-naive patients: once-daily, fixed-dose combination of rilpivirine-emtricitabine-tenofovir

Figures & data

Table 1 Administration and place in therapy^17,71

Dosage and administration	One tablet by mouth once daily Administer with a meal
Dosage form	Tablets (purplish-pink, capsule-shaped, film-coated)
Strengths	Each tablet contains: 25 mg of rilpivirine 300 mg of TDF 200 mg FTC
Dosage adjustments	Renal impairment: Do not use in patients with moderate to severe renal impairment (creatinine clearance <50 mL per minute). Separate agents to accommodate dosage adjustments necessary for TDF and FTC Hepatic impairment: No adjustment required for patients with mild or moderate hepatic impairment (Child-Pugh Classes A and B) Not been studied in patients with severe hepatic impairment (Child-Pugh Class C)
Important adverse effect concerns that may require monitoring	Rash, renal dysfunction, losses in bone mineral density, depressive disorders
Recommended place in therapy per antiretroviral treatment guidelines	Alternative therapy option for NNRTI-based antiretroviral therapy Caution recommended in patients with baseline viral load >100,000 copies/mL

Abbreviations: NNRTI, non-nucleoside reverse transcriptase inhibitor; FTC, emtricitabine; TDF, tenofovir disoproxil fumarate.

Table 2 Pharmacokinetic characteristics

Pharmacokinetic parameter	Rilpivirine	Tenofovir	Emtricitabine
Oral bioavailability	Unknown	25%	93%
Protein binding	99.7%	<0.7%	<4%
Elimination pathway	Hepatic	Renal	Renal
Elimination half-life	Approximately 48 hours	Approximately 17 hours	Approximately 10 hours
Predominant elimination pathway	Hepatic (CYP 3A)	Renal	Renal

Abbreviation: CYP, cytochrome P450.

Table 3 Abbreviated drug interactions associated with rilpivirine

Concomitant medication	Comments
Medications that should not be coadministered with rilpivirine
Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin	Strong CYP enzymatic induction may result in significant decreases in rilpivirine plasma concentrations
Antimycobacterials: rifampin and rifabutin	Strong CYP enzymatic induction may result in significant decreases in rilpivirine plasma concentrations. Rilpivirine AUC, Cmin and Cmax decreased by 46%, 49%, and 35%, respectively, when used concomitantly with rifabutin. Rilpivirine AUC, Cmin and Cmax decreased by 80%, 89%, and 69%, respectively, when used concomitantly with rifampin
Proton pump inhibitors	Changes in gastric pH leading to subsequent decreases in rilpivirine exposure. Rilpivirine AUC and Cmin decrease by 40% and 33%, respectively, when omeprazole coadministered
Efavirenz	AUC of rilpivirine decreased by 70% in presence of efavirenz. Important pharmacokinetic implications when switching from efavirenz to rilpivirine. May extend to other NNRTI agents with persistent inductive effects on CYP system
Macrolide antibiotics: clarithromycin, erythromycin	May result in increased exposure to rilpivirine through inhibition of CYP 3A. Consider use of azithromycin, where possible
Medications requiring adjustment or added monitoring when coadministered with rilpivirine
Ketoconazole	Inhibition of CYP 3A isoenzymes may result in increased rilpivirine plasma concentrations (Cmax and Cmin increased by 30% and 76%, respectively) and decreased concentrations of ketoconazole (Cmax and Cmin decreased by 15% and 65%, respectively). Monitor for breakthrough fungal infections. Other antifungal agents may be evaluated for usage
H2 receptor antagonists	Use with caution because H2 receptor antagonists increase the gastric pH. H2 receptor antagonists and rilpivirine should be spaced out. H2 receptor antagonists should be administered 12 hours before rilpivirine or 4 hours after rilpivirine ingestion
Antacids	Antacids change gastric pH. Administer antacids 2 hours before or 4 hours after rilpivirine dose.
Methadone	AUC of R- and S-methadone decreased by 16% in the presence of rilpivirine. Cmin of both R- and S-methadone decreased by about 21%. Monitor for signs of methadone withdrawal. May need to adjust dose
Antiarrhythmics	Potential for decreased concentrations of rilpivirine
Medications known to prolong QT interval	Potential pharmacodynamic interaction with other QT prolonging medications
Tenofovir	Rilpivirine pharmacokinetics virtually unchanged in presence of tenofovir. Tenofovir pharmacokinetics slightly elevated (Cmin 24% higher) in presence of rilpivirine. Consider monitoring serum creatinine
Medications requiring no dosage adjustment or intervention
Didanosine	Coadminister on an empty stomach
Darunavir/ritonavir	No dosage adjustment recommended. However, rilpivirine AUC is 130% higher with darunavir/ritonavir coadministration
Lopinavir/ritonavir	No dosage adjustment recommended. However, rilpivirine AUC is 52% higher with lopinavir/ritonavir coadministration
Atorvastatin	No dosage adjustment recommended
Acetaminophen	No dosage adjustment recommended
Ethinyl estradiol	Subtle increases in AUC, Cmin and Cmax of ethinyl estradiol. No dosage adjustment necessary
Sildenafil	No dosage adjustment recommended

Abbreviations: AUC, area under the concentration-time curve; C_max, peak plasma concentration; C_min, trough plasma concentration; CYP, cytochrome P450; NNRTI, non-nucleoside reverse transcriptase inhibitor.

Complera^® (package insert)Foster City, CAGilead Sciences2011

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Panel on Antiretroviral Guidelines for Adults and AdolescentsGuidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescentsDepartment of Health and Human ServicesNovember 172011 Available from: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdfAccessed March 8, 2012

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