General

Pronunciation:
em-tri-sye-ti-been/te-noe-fo-veer dye-soe-prox-il fue-ma-rate

Trade Name(s)

• Truvada

Ther. Class.

antiretrovirals

Pharm. Class.

nucleoside reverse transcriptase inhibitors

Indications

• HIV infection (in combination with other antiretroviral agents).
• Pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in at-risk individuals.

Action

Emtricitabine and tenofovir disoproxil fumarate:  Phosphorylated intracellularly where it inhibits HIV reverse transcriptase, resulting in inhibition of viral replication.

Therapeutic Effect(s):

• Slowed progression of HIV infection and decreased occurrence of sequelae.
• Reduction in risk of sexually acquired HIV infection in at-risk individuals.

Pharmacokinetics

Emtricitabine

Absorption: Rapidly and extensively absorbed (93% bioavailable).

Distribution: Unknown

Metabolism and Excretion: Undergoes some metabolism with 86% renally excreted and 14% excreted in feces as metabolites.

Half-life: 10 hr

Tenofovir Disoproxil Fumarate

Absorption: Tenofovir disoproxil fumarate is a prodrug and undergoes hydrolysis to be converted to tenofovir, the active component

Distribution: Unknown.

Metabolism and Excretion: 70–80% excreted unchanged in urine by glomerular filtration and active tubular secretion.

Half-life: 17 hr.

TIME/ACTION PROFILE (plasma concentrations)

Contraindication/Precautions

Contraindicated in:

• Unknown or positive HIV status (for PrEP);
• Severe renal impairment (HIV treatment) (CCr <30 mL/min);
• Moderate or severe renal impairment (PrEP) (CCr <60 mL/min);
• Lactation:  Breastfeeding should be avoided in mothers infected with HIV.

Use Cautiously in:

• Hepatitis B virus (HBV) (may lead to acute exacerbation of HBV upon discontinuation);
• Moderate renal impairment (CCr 30–49 mL/min) (adjust dosing interval);
• History of pathologic fractures/osteoporosis/bone loss;
• OB:  Use during pregnancy only if potential maternal benefit justifies potential fetal risk (in women with HIV, monitor viral load closely);
• Pedi:  Safety and effectiveness not established in children who weigh <17 kg (HIV treatment) or <35 kg (PrEP).

Adverse Reactions/Side Effects

Endo: Graves' disease

F and E: hypophosphatemia

GI: ↑ liver enzymes, abdominal pain, autoimmune hepatitis, LACTIC ACIDOSIS/HEPATOMEGALY WITH STEATOSIS, POST-TREATMENT ACUTE EXACERBATION OF HEPATITIS B

GU: ACUTE RENAL FAILURE/FANCONI SYNDROME, renal impairment

Metabolic: ↓ weight

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

Neuro: Guillain-Barré syndrome, headache

Misc: immune reconstitution syndrome

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• Nephrotoxic agents, including  NSAIDs, ↑ risk of nephrotoxicity; avoid concurrent use.
• Other drugs eliminated by active tubular secretion, including  acyclovir,  adefovir,  aminoglycosides,  cidofovir,  ganciclovir,  valacyclovir, and  valganciclovir, may ↑ levels.
• May ↓  atazanavir  levels and effectiveness; administer atazanavir with ritonavir when used with emtricitabine/tenofovir disoproxil fumarate.
•  Lopinavir/ritonavir,  atazanavir/ritonavir, or  darunavir/ritonavir  may ↑ tenofovir levels and risk of toxicity; closely monitor.
•  Sofosbuvir/velpatasvir,  sofosbuvir/velpatasvir/voxilaprevir, or  ledipasvir/sofosbuvir  may ↑ tenofovir levels and risk of toxicity; closely monitor.

Route/Dosage

HIV-1 Infection

PO (Adults and Children ≥35 kg): One tablet (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) once daily.

PO (Children 28–<35 kg): One tablet (emtricitabine 167 mg/tenofovir disoproxil fumarate 250 mg) once daily.

PO (Children 22–<28 kg): One tablet (emtricitabine 133 mg/tenofovir disoproxil fumarate 200 mg) once daily.

PO (Children 17–<22 kg): One tablet (emtricitabine 100 mg/tenofovir disoproxil fumarate 150 mg) once daily.

Renal Impairment 
PO (Adults ≥35 kg): CCr 30–49 mL/min:  One tablet (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) every 48 hr.  CCr <30 mL/min (including hemodialysis):  Not recommended.

HIV-1 PrEP

PO (Adults and Children ≥35 kg): One tablet (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) once daily.

Availability (generic available)

Tablets: emtricitabine 100 mg/tenofovir disoproxil fumarate 150 mg, emtricitabine 133 mg/tenofovir disoproxil fumarate 200 mg, emtricitabine 167 mg/tenofovir disoproxil fumarate 250 mg, emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg

Assessment

• Assess for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
• Monitor weight periodically during therapy; may require dose modification.
• 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.

Lab Test Considerations:

Screen patients for HIV-1 infection immediately before starting therapy for  HIV-1 PrEP  and at least every 3 mo during therapy, and upon diagnosis of any sexually transmitted infections. If recent (<1 mo) exposures to HIV-1 are suspected (condomless sex or condom breaking during sex with a partner of unknown HIV-1 status, unknown viremic status, or a recent sexually transmitted infection) or clinical symptoms consistent with acute HIV-1 infection occur, use a test approved by the FDA as an aid in the diagnosis of acute or primary HIV-1 infection. If HIV-1 test indicates possible HIV-1 infection, or symptoms consistent with acute HIV-1 infection develop following a potential exposure event, convert  HIV-1 PrEP  regimen to HIV treatment regimen until negative infection status is confirmed.

Monitor viral load and CD4 cell count regularly during therapy.

• Assess for HBV.  Truvada  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 months after stopping therapy. May use anti-hepatitis therapy. Offer vaccination to patients uninfected with HIV.
• 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.
• Monitor 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 without regard to food.

Patient/Family Teaching

• Emphasize the importance of taking  Truvada  as directed. Do not take more than prescribed amount and do not stop taking without consulting health care professional. Uninfected individuals who miss doses are at greater risk of acquiring HIV-1. Advise patient to read  Medication Guide  prior to starting therapy and with each Rx refill in case of changes.
• Advise patients taking  Truvada  for  HIV-1 PrEP  to only take  Truvada  if confirmed HIV-1 negative. Some HIV-1 tests can miss HIV-1 infection in patients recently infected. Notify health care professional if flu-like symptoms (tiredness, fever, joint or muscle aches, headache, sore throat, vomiting or diarrhea, rash, night sweats, enlarged lymph nodes in the neck or groin) occur. Advise patient to use condoms consistently and correctly to lower chances of sexual contact with any body fluids (semen, vaginal secretions, blood), the importance of knowing their HIV-1 status and the HIV-1 status of their partner(s), the need to get tested at least every 3 mo or more frequently for HIV-1 and other sexually transmitted infections (syphilis, chlamydia, gonorrhea), and to ask their partner to get tested. Advise patient if they become HIV-1 positive, more antiretroviral medication than  Truvada  is needed to treat HIV-1.
• Advise patients taking  Truvada  to  treat HIV-1 infection  that  Truvada  alone is not a complete treatment for HIV-1; other antiretroviral medications are required.
• Instruct patient that  Truvada  should not be shared with others.
• Inform patient that  Truvada  does not cure AIDS or prevent other sexually transmitted infections, associated or opportunistic infections.  Truvada  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 HIV to others.
• Advise patient to notify health care professional immediately if signs and symptoms of lactic acidosis (nausea, vomiting, unusual or unexpected stomach discomfort, and weakness) or severe liver problems (yellow skin or white part of eyes, dark "tea-colored" urine, light-colored stools, loss of appetite, nausea, stomach-area pain) occur.
• Immune reconstitution syndrome may trigger opportunistic infections or autoimmune disorders (Graves' disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis). 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.
• Rep:  Advise patient to notify health care professional if pregnancy is planned or suspected. Advise patient to avoid breastfeeding during  Truvada  therapy. Encourage women who become pregnant during  Truvada  therapy to join the Antiretroviral Pregnancy Registry that monitors pregnancy outcomes in women exposed to  Truvada  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.

Evaluation/Desired Outcomes

• Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
• Decrease in viral load and increase in CD4 cell counts.
• Reduced risk of sexually acquired HIV-1 infection in at-risk individuals.