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:

• Black Box:  Unknown or positive HIV status (for PrEP);
• Severe renal impairment (HIV treatment);
• Moderate or severe renal impairment (PrEP);
• Lactation:  Breastfeeding should be avoided in patients infected with HIV.

Use Cautiously in:

• Black Box:  Chronic hepatitis B virus (HBV) infection (may exacerbate following discontinuation);
• Moderate renal impairment (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

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 and risk of toxicity.
• May ↓  atazanavir  levels and effectiveness; administer atazanavir with ritonavir when used with emtricitabine/tenofovir disoproxil fumarate.
•  Lopinavir/ritonavir,  atazanavir/ritonavir, or  darunavir/ritonavir  may ↑ levels and risk of toxicity of tenofovir; monitor closely.
•  Sofosbuvir/velpatasvir,  sofosbuvir/velpatasvir/voxilaprevir, or  ledipasvir/sofosbuvir  may ↑ levels and risk of toxicity of tenofovir; monitor closely.

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:

Black Box:  Screen patients for HIV-1 infection immediately before starting therapy for  HIV-1 PrEP , 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 HBV. Monitor liver function in coinfected patients for several months after stopping therapy.
• Black Box:  Monitor liver function tests prior to, during, and following therapy.
• May ↑ 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 (↑ serum lactate levels, ↑ 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. 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.
• Black Box:  Do not stop taking without consulting health care provider. Discontinuing therapy may lead to severe exacerbations. Inform patient of importance of HBV testing before starting antiretroviral therapy.
• Black Box:  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 provider 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 HIV or prevent other sexually transmitted infections or 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 provider immediately if signs and symptoms of lactic acidosis (nausea, vomiting, unusual or unexpected stomach discomfort, 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 provider if symptoms (signs and symptoms of an 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.
• Rep:  Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding during 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 HIV 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.