emtricitabine/rilpivirine/tenofovir alafenamide

REMS

Management of 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).
Management of 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: Rapidly and extensively absorbed; 93% bioavailable.

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 women with HIV.

Use Cautiously in:

History of suicidal ideation or depression;
HIV-1 RNA >100,000 copies/mL (↑ risk of virologic failure);
Hepatitis B virus (HBV) or hepatitis C infection or hepatic impairment;
Renal impairment or receiving nephrotoxic medications (↑ risk of renal impairment);
Severe hepatic impairment;
OB: Monitor viral load closely when used during pregnancy;
Pedi: Children 12 yr or 35 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 ↓ rilpivirine levels and its effectiveness; concurrent use contraindicated.
Proton pump inhibitors including esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole↑ gastric pH and may ↓ rilpivirine levels and its effectiveness; concurrent use contraindicated.
Concurrent use of 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 ↑ emtricitabine and tenofovir levels and toxicity; avoid if possible.
Antacids including aluminum hydroxide, magnesium hydroxide, and calcium carbonate↑ gastric pH and may ↓ rilpivirine levels; administer antacid ≥2 hr before or ≥4 hr after.
H2-antagonists, including cimetidine, famotidine, and nizatidine, ↑ gastric pH and may ↓ rilpivirine levels; administer H₂-antagonist ≥12 hr before or ≥4 hr after rilpivirine.
Nephrotoxic agents, including NSAIDs, ↑ risk of nephrotoxicity; avoid concurrent use.
Rifabutin may ↓ rilpivirine and tenofovir alafenamide levels and their effectiveness; concurrent use not recommended.
Fluconazole, itraconazole, ketoconazole, posaconazole, and voriconazole may ↑ rilpivirine and tenofovir alafenamide levels and risk of toxicity.
May ↓ ketoconazole levels.
May alter requirements for methadone maintenance.
Clarithromycin or erythromycin may ↑ rilpivirine levels and risk of toxicity; consider azithromycin as an alternative.
Ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, and sofosbuvir/velpatasvir/voxilaprevir may ↑ tenofovir levels and risk of toxicity.

Drug-Natural Products:

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

Route/Dosage ⬆ ⬇

PO (Adults and Children ≥12 yr and ≥35 kg): 1 tablet once daily.

Renal Impairment

PO (Adults and Children ≥12 yr and ≥35 kg): End-stage renal disease (CCr <15 mL/min) AND receiving hemodialysis: 1 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 with fever, blisters, mucosal involvement, eye inflammation [conjunctivitis]); lymphadenopathy, and/or facial swelling, associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.
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. Odefsey is not approved for administration in patients with HIV and HBV. If therapy is discontinued, may cause severe exacerbation of hepatitis B. Monitor liver function in coinfected patients for several mo after stopping therapy.
- Monitor liver function tests before and periodically during therapy, especially in patients with underlying liver disease or marked ↑ transaminase. May cause ↑ serum creatinine, AST, ALT, total bilirubin, total cholesterol, low-density lipoprotein cholesterol, and triglycerides. May cause lactic acidosis and severe hepatomegaly with steatosis. These events are more likely to occur if patients are female, obese, or receiving nucleoside analogue medications for extended periods of time. Monitor patient for signs (increased serum lactate levels, elevated liver enzymes, liver enlargement on palpation). Therapy should be suspended if clinical or laboratory signs occur.
- Assess serum creatinine, creatinine clearance, urine glucose, and urine protein before starting and periodically during therapy. Also assess serum phosphorous in patients with chronic kidney disease. Patients taking nephrotoxic agents, including NSAIDs, are at increased risk for renal impairment.

Implementation ⬆ ⬇

PO: Administer once daily with a meal.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed. Avoid missing doses, may result in development of resistance. Do not stop taking Odefsey without consulting health care professional. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
Instruct patient that Odefsey should not be shared with others.
Inform patient that Odefsey does not cure AIDS and may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and avoid sharing needles or donating blood to prevent spreading HIV to others.
Advise patient to notify health care professional immediately if symptoms of lactic acidosis (nausea, vomiting, unusual or unexpected stomach discomfort, and weakness), hypersensitivity (swelling of face, eyes, lips, mouth, tongue or throat; difficulty swallowing; shortness of breath), severe liver problems (yellow skin or white part of eyes, dark "tea-colored" urine, light-colored stools, loss of appetite, nausea, stomach-area pain), or DRESS occur.
Inform patients and families of risk of suicidal thoughts and behavior and advise that behavioral changes, emergency or worsening signs and symptoms of depression, unusual changes in mood, or emergence of suicidal thoughts, behavior, or thoughts of self-harm should be reported to health care professional immediately.
Immune reconstitution syndrome may trigger opportunistic infections or autoimmune disorders. Notify health care professional if symptoms (signs and symptoms of an infection or inflammation) occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
Rep: Advise patient to notify health care professional if pregnancy is planned or suspected. Advise patient to avoid breastfeeding during Odefsey therapy. Monitor viral load closely during pregnancy. Encourage women who become pregnant during Odefsey therapy to join the Antiviral Pregnancy Registry that monitors pregnancy outcomes in women exposed to Odefsey during pregnancy. Enroll patient by calling 1-800-258-4263.

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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 ⬆