emtricitabine/rilpivirine/tenofovir alafenamide

REMS

HIV infection in treatment-naive patients with HIV-1 RNA <100,000 copies/mL at the start of therapy (for use as a complete regimen).
HIV infection in patients on a stable antiretroviral regimen with HIV-1 RNA <50 copies/mL for ≥6 mo and have no history of treatment failure or no known substitutions associated with resistance to the individual components of the medication (to replace their current antiretroviral regimen).

Action ⬆ ⬇

Emtricitabine: Phosphorylated intracellularly, where it inhibits HIV reverse transcriptase, resulting in viral DNA chain termination.
Rilpivirine: Inhibits HIV-replication 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: 93% absorbed following oral administration.

Distribution: Unknown.

Metabolism/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/Excretion: Primarily metabolized by the liver via the CYP3A isoenzyme; 25% excreted in feces unchanged; <1% excreted unchanged in urine.

Half-Life: 50 hr.

Tenofovir Alafenamide

Absorption: Tenofovir alafenamide is a prodrug, which is hydrolyzed into tenofovir, the active component; absorption enhanced by high-fat meals.

Distribution: Unknown.

Metabolism/Excretion: Tenofovir is phosphorylated to tenofovir diphosphate (active metabolite); 32% excreted in feces; <1% in urine.

Half-Life: 0.51 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
Emtricitabine PO	rapid	1–2 hr	24 hr
Rilpivirine PO	unknown	4–5 hr	24 hr
Tenofovir PO	unknown	1 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Concurrent use of carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, proton pump inhibitors, dexamethasone (>1 dose), or St. John's wort;
Severe renal impairment or end-stage renal disease not receiving hemodialysis;
Lactation: Breastfeeding is not recommended in patients with HIV.

Use Cautiously in:

Chronic hepatitis B virus (HBV) infection (may exacerbate following discontinuation)
;
History of suicidal ideation or depression;
HIV-1 RNA >100,000 copies/mL (↑ risk of virologic failure);
Renal impairment or receiving nephrotoxic medications (↑ risk of renal impairment);
Severe hepatic impairment;
OB: Monitor viral load closely when used during pregnancy;
Pedi: Children <25 kg (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

CV: QT interval prolongation

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS)

Endo: Graves disease

GI: ACUTE EXACERBATION OF HBV, autoimmune hepatitis, HEPATOTOXICITY, LACTIC ACIDOSIS/HEPATOMEGALY WITH STEATOSIS

GU: ACUTE RENAL FAILURE/FANCONI SYNDROME

Metab: hyperlipidemia

MS: polymyositis

Neuro: depression, Guillain-Barré syndrome, headache, sleep disturbances, SUICIDAL ATTEMPTS/THOUGHTS

Misc: immune reconstitution syndrome

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inducers, including carbamazepine, oxcarbazepine, phenobarbital, phenytoin, dexamethasone (more than a single dose), rifampin, and rifapentine, may ↓ levels and effectiveness of rilpivirine; concurrent use contraindicated.
Proton pump inhibitors, including esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole, ↑ gastric pH and may ↓ levels and effectiveness of rilpivirine; concurrent use contraindicated.
QT interval prolonging medications may ↑ risk of torsades de pointes.
Medications that compete for active tubular secretion, including acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, or aminoglycosides, may ↑ levels and risk of toxicity of emtricitabine and tenofovir; avoid concurrent use.
Antacids including aluminum hydroxide, magnesium hydroxide, and calcium carbonate↑ gastric pH and may ↓ levels and effectiveness of rilpivirine; administer antacid ≥2 hr before or ≥4 hr after.
H2-antagonists, including cimetidine, famotidine, and nizatidine, ↑ gastric pH and may ↓ levels and effectiveness of rilpivirine; administer ≥12 hr before or ≥4 hr after rilpivirine.
Nephrotoxic agents, including NSAIDs, may ↑ risk of nephrotoxicity; avoid concurrent use.
Rifabutin may ↓ levels and effectiveness of rilpivirine and tenofovir; concurrent use not recommended.
Fluconazole, itraconazole, ketoconazole, posaconazole, and voriconazole may ↑ levels and risk of toxicity of rilpivirine and tenofovir.
May ↓ levels and effectiveness of ketoconazole.
May alter requirements for methadone maintenance.
Clarithromycin or erythromycin may ↑ levels and risk of toxicity of rilpivirine; consider azithromycin as an alternative.
Ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, and sofosbuvir/velpatasvir/voxilaprevir may ↑ levels and risk of toxicity of tenofovir.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness of rilpivirine; concurrent use contraindicated.

Route/Dosage ⬆ ⬇

PO (Adults and Children ≥25 kg): One tablet once daily.

Renal Impairment

PO (Adults and Children ≥25 kg): End-stage renal disease (CCr <15 mL/min) AND receiving hemodialysis: One tablet once daily (to be given after hemodialysis).

Availability ⬆ ⬇

Tablets: emtricitabine 200 mg/rilpivirine 25 mg/tenofovir alafenamide 25 mg

Assessment ⬆ ⬇

Assess for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
Monitor for signs and symptoms of DRESS (fever, rash, blisters, mucosal lesions, conjunctivitis), lymphadenopathy, or facial swelling associated with involvement of other organs (hepatitis, nephritis, blood dyscrasias, myocarditis, myositis) during therapy. If symptoms occur, discontinue Odefsey.
Assess mental status (orientation, mood, behavior) before and periodically during therapy. Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.

Lab Test Considerations:

Monitor viral load and CD4 cell count regularly during therapy.
- Assess for HBV. Odefseyis not approved for use in patients with HIV and HBV. If therapy is discontinued in HBV-positive patient, may cause severe exacerbation of HBV. Monitor liver function in coinfected patients for several months after stopping therapy.
- Monitor liver function tests prior to, during, and following therapy.
- May ↑ total cholesterol, LDL-C, and triglycerides. May cause lactic acidosis and severe hepatomegaly with steatosis. These events are more likely to occur if patient is female, obese, or receiving nucleoside analogue medications for extended periods. If clinical or laboratory signs of lactic acidosis occur, discontinue therapy.
- Assess serum creatinine, CCr, urine glucose, and urine protein before starting and periodically during therapy. Monitor serum phosphorous in patients with chronic kidney disease.

Implementation ⬆ ⬇

PO: Administer once daily with food.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Caution patient that missing doses may result in development of resistance.
Do not stop taking without consulting health care provider. Discontinuing therapy may lead to severe exacerbation. Inform patient of importance of HBV testing before starting antiretroviral therapy.
Instruct patient that Odefsey should not be shared with others.
Inform patient that Odefsey does not cure HIV but may ↓ risk of transmission. Caution patient to use a condom and avoid sharing needles or donating blood to prevent spreading HIV.
Advise patient to notify health care provider immediately if symptoms of lactic acidosis (nausea, vomiting, unusual or unexpected stomach discomfort, weakness), hypersensitivity (swelling of face, eyes, lips, mouth, tongue, or throat; difficulty breathing), liver disease (yellow skin or conjunctiva, dark urine, light-colored stool, loss of appetite, nausea, abdominal pain), or DRESS occur.
Inform patient of risk of suicidal thoughts and behavior and advise that behavioral changes, worsening signs of depression, mood changes, or suicidal thoughts or behavior should be reported to health care provider immediately.
Immune reconstitution syndrome may trigger opportunistic infections or autoimmune disorders. Notify health care provider if symptoms (infection or inflammation) occur.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications, especially St. John's wort.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Monitor viral load closely during pregnancy. Encourage women who become pregnant during therapy to join the Antiviral Pregnancy Registry that monitors outcomes. Enroll patient by calling 1-800-258-4263.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆