Indications
Management of HIV infection in treatment-naı¨ve patients
with HIV-1 RNA 100,000 copies/mL at the start
of therapy (for use as a complete regimen). Management
of HIV infection in patients on a stable antiretroviral
regimen with HIV-1 RNA 50 copies/mL (to replace
their current antiretroviral regimen).
Action
Emtricitabine—Phosphorylated intracellularly where
it inhibits HIV reverse transcriptase, resulting in viral
DNA chain termination. Rilpivirine—Inhibits HIVreplication
by noncompetitively inhibiting HIV reverse
transcriptase. Tenofovir—Phosphorylated intracellularly
where it inhibits HIV reverse transcriptase resulting
in disruption of DNA synthesis. Therapeutic Effects:
Slowed progression of HIV infection and
decreased occurrence of sequelae.
Pharmacokinetics
emtricitabine
Absorption: Rapidly and extensively absorbed; 93%
bioavailable.
Distribution: Unknown.
Metabolism and Excretion: Some metabolism,
86% renally excreted, 14% fecal excretion.
Half-life: 10 hr.
rilpivirine
Absorption: Well absorbed following oral administration.
Distribution: Unknown.
Protein Binding: 99.7%.
Metabolism and Excretion: Mostly metabolized
by the liver (CYP3A enzyme system); 25% excreted in
feces unchanged, 1% excreted unchanged in urine.
Half-life: 50 hr.
tenofovir
Absorption: Tenofovir disoproxil fumarate is a
prodrug, which is split into tenofovir, the active component.
Distribution: Absorption is enhanced by food.
Metabolism and Excretion: 70–80% excreted
unchanged in urine by glomerular filtration and active
tubular secretion.
Half-life: Unknown.
TIME/ACTION PROFILE (blood levels)
ROUTE ONSET PEAK DURATION
emtricitabine
PO
rapid 1–2 hr 24 hr
rilpivirine PO unknown 4–5 hr 24 hr
tenofovir PO unknown 2 hr* 24 hr
* When taken with food.
Contraindications/Precautions
Contraindicated in: Drugs that may significantlyp
rilpivirine levels (maypvirologic response,qrisk of
resistance and cross-resistance); Concurrent use of
other antiretrovirals; Concurrent use of carbamazepine,
oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine,
proton pump inhibitors, dexamethasone (1
dose), or St. John’s wort; Concurrent use of other products
containing emtricitabine, rilpivirine (unless dose
adjustment needed with rifabutin), tenofovir, lamivudine,
or adefovir; CCr 50 mL/min; Lactation: HIV-infected
patients should not breast feed.
Use Cautiously in: History of suicidal ideation or
depression; History of pathologic fractures/osteoporosis/
bone loss; OB: Use during pregnancy only if potential
benefit justifies potential fetal risk; Pedi: Children
12 yr (safety and effectiveness not established).
Adverse Reactions/Side Effects
Combination.
GI: HEPATOTOXICITY. GU: renal impairment. MS:p
bone density. Derm: DRUG REACTION WITH EOSINOPHILIA
AND SYSTEMIC SYMPTOMS (DRESS). Misc: POSTTREATMENT
ACUTE EXACERBATION OF HEPATITIS B, immune
reconstitution syndrome.
rilpivirine
CNS: SUICIDAL THOUGHTS, depression, insomnia, headache.
emtricitabine/tenofovir
CNS: abnormal dreams, depression, dizziness, fatigue,
headache, insomnia. F and E: hypophosphatemia.
GI: LACTIC ACIDOSIS/HEPATOMEGALY WITH STEATOSIS, diarrhea,
nausea. Derm: rash. GU: ACUTE RENAL FAILURE/
FANCONI SYNDROME. MS: bone pain,pbone mineral
density, muscle pain, osteomalacia.
Interactions
Drug-Drug: Mayqrisk of nephrotoxicity with other
nephrotoxic drugs; avoid if possible. Strong CYP3A4
inducers, including carbamazepine, oxcarbazepine,
phenobarbital, phenytoin, dexamethasone
(more than a single dose), rifabutin, rifampin, and
rifapentine mayplevels and effectiveness; concurrent
use contraindicated. Proton pump inhibitors including
esomeprazole, lansoprazole, omeprazole,
pantoprazole, and rabeprazoleqgastric pH and
maypblood levels and effectiveness; concurrent use
contraindicated. Antacids including aluminum hydroxide,
magnesium hydroxide, and calcium carbonateqgastric
pH and maypblood levels; administer
at least 2 hr before or 4 hr after. Blood levels and
effectiveness may bepby H2-receptor antagonists including
cimetidine, famotidine, nizatidine, and
ranitidine; administer 12 hr after or 4 hr before. Nephrotoxic
agents, including NSAIDsqrisk of nephrotoxicity;
avoid concurrent use. Concurrent use of other
drugs thatqrisk of torsade de pointes mayqrisk
of serious arrhythmias. May alter requirements for
methadone maintenance. Blood levels and risk of adverse
effects may beqby clarithromycin, and erythromycin;
consider azithromycin as an alternative. Ledipasvir/
sofosbuvir and sofosbuvir/velpatasvir
mayqtenofovir levels.
Drug-Natural Products: St. John’s wort mayp
blood levels and effectiveness; concurrent use contraindicated.
Route/Dosage
PO (Adults and Children 12 yr and 35 kg): 1
tablet once daily. Concurrent rifabutin therapy—
Give an additional 25 mg of rilpivirine once daily.
Availability
Tablets: emtricitabine 200 mg/rilpivirine 25 mg/ tenofovir
disoproxil fumarate 300 mg.
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