Rilpivirine (4 brand names, 2 dosage forms, 2 routes)
Available dosage forms: TABLET, SUSPENSION, EXTENDED RELEASE.
Routes of administration: ORAL, INTRAMUSCULAR.
Brand Names
- CABENUVA KIT
- DOLUTEGRAVIR; RILPIVIRINE
- EMTRICITABINE; RILPIVIRINE; TENOFOVIR ALAFENAMIDE
- RILPIVIRINE
Boxed Warning
Severe acute exacerbations of hepatitis B virus (HBV) have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), two of the components of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets . Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets. If appropriate, initiation of anti-hepatitis B therapy may be warranted [see Warnings and Precautions (5.1)].
Indications and Usage
Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg: • as initial therapy in those with no antiretroviral treatment history with HIV-1 RNA less than or equal to 100,000 copies/mL at the start of therapy or • to replace a stable antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies/mL) on a stable antiretroviral regimen for at least 6 months with no treatment failure and no known substitutions associated with resistance to the individual components of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets [see Microbiology (12.4) and Clinical Studies (14)]. Limitations of Use: • More rilpivirine-treated subjects with HIV-1 RNA greater than 100,000 copies/mL at the start of therapy experienced virologic failure (HIV-1 RNA ≥50 copies/mL) compared to rilpivirine-treated subjects with HIV-1 RNA less than or equal to 100,000 copies/mL [see Clinical Studies (14)].
Contraindications
Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are contraindicated when coadministered with the following drugs; coadministration may result in loss of virologic response and possible resistance to emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets or to the class of NNRTIs [see Warnings and Precautions (5.7), Drug Interactions (7), and Clinical Pharmacology (12.3)]: • Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin • Antimycobacterials: rifampin, rifapentine • Glucocorticoid (systemic): dexamethasone (more than a single-dose) • Herbal Products: St John’s wort (Hypericum perforatum) • Proton Pump Inhibitors: e.g., dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole
Adverse Reactions
The following adverse reactions are discussed in other sections of the labeling: • Severe Acute Exacerbations of Hepatitis B in Patients Coinfected with HIV-1 and HBV [see Warnings and Precautions (5.1)]. • Skin and Hypersensitivity Reactions [see Warnings and Precautions (5.2)]. • Hepatotoxicity [see Warnings and Precautions (5.3)]. • Depressive Disorders [see Warnings and Precautions (5.4)]. • New Onset or Worsening Renal Impairment [see Warnings and Precautions (5.5)]. • Bone Loss and Mineralization Defects [see Warnings and Precautions (5.6)]. • Lactic Acidosis/Severe Hepatomegaly with Steatosis [see Warnings and Precautions (5.8)]. • Immune Reconstitution Syndrome [see Warnings and Precautions (5.9)].
Mechanism of Action
Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are a fixed-dose combination of the antiretroviral drugs FTC, RPV, and TDF [see Microbiology (12.4)].
Overdosage
If overdose occurs the patient must be monitored for evidence of toxicity. Treatment of overdose with emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets consists of general supportive measures, including monitoring of vital signs and ECG (QT interval) as well as observation of the clinical status of the patient. Emtricitabine: Hemodialysis treatment removes approximately 30% of the FTC dose over a 3-hour dialysis period starting within 1.5 hours of FTC dosing (blood flow rate of 400 mL per minute and a dialysate flow rate of 600 mL per minute). It is not known whether FTC can be removed by peritoneal dialysis. Rilpivirine: There is no specific antidote for overdose with RPV. Human experience of overdose with RPV is limited. Since RPV is highly bound to plasma protein, dialysis is unlikely to result in significant removal of RPV. Tenofovir DF: Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%. Following a single 300 mg dose of TDF, a 4-hour hemodialysis session removed approximately 10% of the administered tenofovir dose.