emtricitabine/rilpivirine/tenofovir disoproxil fumarate

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: Mostly metabolized by the liver (CYP3A enzyme system); 25% excreted in feces unchanged, <1% excreted unchanged in urine

Half-Life: 50 hr

tenofovir disoproxil fumarate

Absorption: Tenofovir disoproxil fumarate is a prodrug, which is split into tenofovir, the active component

Distribution: Absorption is enhanced by food

Metabolism/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.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Drugs that may significantly ↓ rilpivirine levels (may ↓ virologic response, ↑ risk 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;
CCr <50 mL/min;
Lactation: HIV-infected patients should not breast feed.

Use Cautiously in:

History of suicidal ideation or depression;
HIV-1 RNA >100,000 copies/mL (↑ risk of virologic failure);
History of pathologic fractures/osteoporosis/bone loss;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk (monitor viral load closely);
Pedi: Children <12 yr (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

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

Endo: Graves' disease

F and E: hypophosphatemia

GI: diarrhea, nausea, autoimmune hepatitis, HEPATOTOXICITY, LACTIC ACIDOSIS/HEPATOMEGALY WITH STEATOSIS, POST-TREATMENT ACUTE EXACERBATION OF HEPATITIS B

GU: ACUTE RENAL FAILURE/FANCONI SYNDROME

MS: ↓bone mineral density, bone pain, muscle pain, osteomalacia, polymyositis

Neuro: abnormal dreams, depression, dizziness, fatigue, headache, insomnia, Guillain-Barré syndrome, SUICIDAL THOUGHTS

Misc: immune reconstitution syndrome

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inducers, including carbamazepine, oxcarbazepine, phenobarbital, phenytoin, dexamethasone (more than a single dose), rifabutin, rifampin, and rifapentine may ↓ levels and effectiveness; concurrent use contraindicated.
Proton pump inhibitors including esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole↑ gastric pH and may ↓ blood levels and effectiveness; concurrent use contraindicated.
Antacids including aluminum hydroxide, magnesium hydroxide, and calcium carbonate↑ gastric pH and may ↓ blood levels; administer at least 2 hr before or 4 hr after.
Blood levels and effectiveness may be ↓ by H₂-receptor antagonists including cimetidine, famotidine, and nizatidine; administer 12 hr after or 4 hr before.
Nephrotoxic agents, including NSAIDs↑ risk of nephrotoxicity; avoid concurrent use.
Concurrent use of other drugs that risk of torsades de pointes may ↑ risk of serious arrhythmias.
May alter requirements for methadone maintenance.
Blood levels and risk of adverse effects may be ↑ by clarithromycin, and erythromycin; consider azithromycin as an alternative.
Ledipasvir/sofosbuvir , sofosbuvir/velpatasvir, and sofosbuvir/velpatasvir/voxilaprevirmay ↑ tenofovir levels.

Drug-Natural Products:

St. John's wort may ↓ 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

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.
Monitor bone mineral density in patients who have a history of pathologic bone fracture or are at risk for osteoporosis or bone loss. Calcium and vitamin D supplementation may be beneficial for all patients.
Monitor for signs or symptoms of severe skin or hypersensitivity reactions (severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis or eosinophilia). Discontinue Complera immediately if signs develop.

Lab Test Considerations:

Monitor viral load and CD4 cell count regularly during therapy.
- Assess for hepatitis B virus (HBV). Complera 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 co-infected 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, LDL, 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.
- Calculate creatinine clearance (CCr), serum creatinine, urine glucose, and urine protein prior to therapy. CCr should be >70 mL/min before starting therapy. Monitor CCr, urine glucose, and urine protein in all patients periodically during therapy and serum phosphorous in patients with chronic kidney disease. Assess patients with persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness for proximal renal tubulopathy; evaluate renal function promptly.

Implementation ⬆ ⬇

PO: Administer once daily with food

Patient/Family Teaching ⬆ ⬇

Emphasize the importance of taking Complera as directed, at the same time each day. Do not take more than prescribed amount and do not stop taking without consulting health care professional. Take missed doses with a meal if remembered <12 hr from the time it is usually taken, then return to regular schedule. If more than 12 hr from time dose is usually taken, omit dose and resume dosing schedule; do not double doses. Advise patient to read Patient Information prior to starting therapy and with each Rx refill in case of changes.
Advise patient to take antacids 2 hr before or 4 hr after and H₂-antagonists 12 hr before or 4 hr after Complera.
Instruct patient that Complera should not be shared with others.
Inform patient that Complera does not cure AIDS or prevent associated or opportunistic infections. Complera may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and to avoid sharing needles or donating blood to prevent spreading the AIDS virus to others. Advise patient that the long-term effects of Complera are unknown at this time.
Advise patient to notify health care professional immediately if signs and 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.
May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
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 patients to notify health care professional if pregnancy is planned or suspected. Advise patient to avoid breastfeeding during Complera therapy. Encourage women who become pregnant during Complera therapy to join the Antiviral Pregnancy Registry that monitors pregnancy outcomes in women exposed to Complera during pregnancy. Enroll patient by calling 1-800-258-4263.
Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇