Emtricitabine / Tenofovir Disoproxil Fumarate

Pronunciation: (EM-trye-SYE-ta-been/ten-OF-oh-vir DYE-soe-PROX-il FUE-ma-rate)
Class: Nucleoside analog reverse transcriptase inhibitor combination

Trade Names

Truvada
- Tablets emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg

Pharmacology

Emtricitabine

Inhibits activity of HIV-1 reverse transcriptase by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA, resulting in chain termination.

Tenofovir disoproxil fumarate

Tenofovir disoproxil fumarate is a prodrug of tenofovir, which inhibits the activity of HIV-1 reverse transcriptase by competing with deoxyadenosine 5'-triphosphate and by DNA chain termination, after incorporation into DNA.

Indications and Usage

Treatment of HIV-1 infection in combination with other antiretroviral agents.

Contraindications

None well documented.

Dosage and Administration

Adults

PO Emtricitabine 200 mg/tenofovir 300 mg once daily.

Renal Function Impairment
Adults

PO

CrCl 50 mL/min or more

Give dose every 24 h.

CrCl 30 to 49 mL/min

Give dose every 48 h.

CrCl less than 30 mL/min

Do not administer.

General Advice

Administer without regard to meals. Administer with food if GI upset occurs.
If coadministering with didanosine enteric-coated tablets, administer with a light meal or under fasted conditions. If coadministering with didanosine buffered tablet, administer under fasted conditions.

Storage/Stability

Store at 59° to 86°F. Dispense only in the original container.

Drug Interactions

Adefovir

May increase serum concentrations of emtricitabine or tenofovir and/or other renally eliminated drugs. Do not administer emtricitabine/tenofovir with adefovir.

Atazanavir

Concurrent use may increase tenofovir AUC and C _max . Coadministration of tenofovir and atazanavir may decrease atazanavir AUC and C _max . Do not coadminister without the addition of ritonavir.

Didanosine

AUC and C _max of didanosine may be elevated, increasing the risk of adverse reactions (eg, neuropathy, pancreatitis). Monitor patients closely and administer under fasting conditions or with a light meal (ie, less than 400 kcal [20% fat]).

Drugs that reduce renal function or compete for active tubular secretion (eg, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir)

May increase serum concentrations of emtricitabine or tenofovir and/or other renally eliminated drugs. Closely monitor the patient and adjust treatment as needed.

Food

Administration of emtricitabine/tenofovir following a high-fat meal (784 kcal; 49 g of fat) or light meal (373 kcal; 8 g of fat) may delay the time of tenofovir C _max . Administration with a high-fat meal or light meal may increase tenofovir AUC and C _max compared with administration in the fasted state. However, emtricitabine/tenofovir may be taken without regard to food.

Lamivudine

Because of similarities between emtricitabine and lamivudine, do not coadminister drugs containing lamivudine.

Lopinavir/ritonavir

Tenofovir concentrations may be elevated, increasing the risk of adverse reactions. Monitor closely for emtricitabine/tenofovir-associated adverse reactions. Discontinue in patients who develop adverse reactions.

Nephrotoxic agents

The risk of nephrotoxicity may be increased. Avoid emtricitabine/tenofovir with concurrent or recent use of a nephrotoxic agent.

Adverse Reactions

Incidences of the following adverse reactions were reported with combined use of emtricitabine/tenofovir plus efavirenz.

CNS

Depression, fatigue (9%); dizziness (8%); headache (6%); insomnia (5%); asthenia (postmarketing).

Dermatologic

Rash (7%).

EENT

Nasopharyngitis (5%).

GI

Diarrhea, nausea (9%); vomiting (2%); abdominal pain, increased amylase, pancreatitis (postmarketing).

Genitourinary

Acute renal failure, acute tubular necrosis, Fanconi syndrome, increased creatinine, interstitial nephritis, nephrogenic diabetes insipidus, polyuria, proteinuria, proximal renal tubulopathy, renal failure, renal insufficiency (postmarketing).

Hepatic

Hepatic steatosis, hepatitis, increased liver enzymes (postmarketing).

Hypersensitivity

Allergic reactions, angioedema (postmarketing).

Lab Tests

Increased fasting cholesterol (22%); increased creatine kinase (9%); increased serum amylase (8%); elevated fasting triglycerides (4%); decreased neutrophils, hematuria, increased AST (3%); hyperglycemia, increased ALT (2%); increased alkaline phosphatase (1%).

Metabolic-Nutritional

Hypokalemia, hypophosphatemia, lactic acidosis (postmarketing).

Musculoskeletal

Muscular weakness, myopathy, osteomalacia, rhabdomyolysis (postmarketing).

Respiratory

Sinusitis, upper respiratory tract infections (8%); dyspnea (postmarketing).

Precautions

Warnings

Lactic acidosis and hepatomegaly with steatosis (including fatal cases) have been reported with use of nucleoside analogues alone and in combination with other antiretroviral agents. Emtricitabine/tenofovir is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy have not been established in patients coinfected with HBV and HIV. Severe, acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued emtricitabine/tenofovir. Closely monitor hepatic function with clinical and laboratory follow-up for at least several months in patients who discontinue emtricitabine/tenofovir and are coinfected with HIV-1 and HBV. If appropriate, initiation of anti–hepatitis B therapy may be warranted.

Monitor

Monitor patient for signs of lactic acidosis. For at least several months, closely monitor hepatic function with clinical and laboratory follow-up in patients who discontinue emtricitabine/tenofovir and are coinfected with HIV and HBV. Consider bone mineral density monitoring for HIV-1–infected patients who have a history of pathologic bone fracture or who are at risk for osteopenia. It is recommended that CrCl be calculated in all patients prior to initiating therapy and as clinically appropriate during therapy with emtricitabine/tenofovir. Routinely monitor calculated CrCl and serum phosphorus in patients at risk for renal impairment.

Pregnancy

Category B .

Lactation

Undetermined. Advise HIV-infected women not to breast-feed infants.

Children

Safety and efficacy not established.

Elderly

Use with caution because of greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Renal Function

Dosage adjustments are recommended. Do not administer to patients with CrCl less than 30 mL/min or to patients with ESRD requiring dialysis.

Bone effects

Decreases from baseline bone mineral density at the lumbar spine and hip have been seen. Ensure that supplementation with calcium and vitamin D has been considered in patients with HIV-associated osteopenia or osteoporosis.

Fat redistribution

Redistribution and accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance, may occur.

Immune reconstitution syndrome

During initial phase of treatment, patients may develop an inflammatory response to indolent or residual opportunistic infections.

Renal effects

Renal impairment, including acute renal failure and Fanconi syndrome, can occur.

Overdosage

Symptoms

Limited clinical experience is available.

Patient Information

Advise patient or caregiver to review the patient information leaflet before starting therapy and with each refill.
Advise patient to take 1 tablet once daily without regard to meals, but to take with food if stomach upset occurs.
Instruct patient that if a dose is missed, to take it as soon as possible and then to take the next dose at the regularly scheduled time. If it is almost time for the next dose, advise patient not to take the missed dose, and to wait and take the next dose as scheduled. Caution patient not to double the next dose to catch up.
Warn patient that this drug is not to be used by itself, but is to be combined with other antiviral agents.
Instruct patient to report the following symptoms immediately to health care provider: abdominal swelling or enlargement; fatty diarrhea; feeling cold, dizzy, or light-headed; profound weakness or tiredness; slow or irregular heartbeat; unexpected stomach discomfort.
Inform patient that the drug does not completely eliminate HIV virus and, therefore, does not reduce risk of transmitting HIV to others. Appropriate precautions must still be followed.
Advise patient that drug is not a cure for HIV infection and that they may continue to acquire illnesses associated with HIV infection (including opportunistic infections) and to remain under a health care provider's care.
Advise patient with HIV-associated osteopenia or osteoporosis to discuss need for supplementation with calcium and vitamin D with health care provider
Advise women to notify health care provider if pregnant, planning to become pregnant, or breast-feeding. Advise HIV-infected women not to breast-feed to prevent infecting infants with HIV.