DrugindexOnline^{2nd edition}

Pronouncation: (em-try-SIGH-tah-bean/teh-NOE-fo-veer DIE-so-prox-ill FYU-mah-rate)
Class: Nonnucleoside analog reverse transcriptase inhibitor combination

Trade Names:
Truvada
- Tablets 200 mg emtricitabine/300 mg tenofovir disoproxil fumarate (equiv. to 245 mg tenofovir disoproxil)

Mechanism of Action

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

Standard considerations.

Dosage and Administration

Adults

PO 200 mg emtricitabine/300 mg tenofovir disoproxil fumarate once daily.

Renal Function Impairment
Adults

PO Ccr 50 mL/min or more give dose every 24 h. Ccr 30 to 49 mL/min give dose every 48 h. Ccr 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 tablets at controlled room temperature (59° to 86°F).

Drug Interactions

Atazanavir, lopinavir/ritonavir

Tenofovir concentrations may be elevated, increasing the risk of adverse effects. The AUC and C _min of atazanavir may be decreased.

Didanosine

AUC and C _max of didanosine may be elevated, increasing the risk of adverse effects (eg, pancreatitis, neuropathy).

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

May increase serum concentrations of emtricitabine or tenofovir.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Emtricitabine

Asthenia, headache, dizziness (more than 5%); abnormal dreams, depressive disorder, insomnia, neuropathy, peripheral neuritis, paresthesia.

Tenofovir

Headache, depression (more than 5%); asthenia, dizziness, insomnia, abnormal dreams, paresthesia, peripheral neuropathy.

Dermatologic

Emtricitabine

Rash including pruritus, maculopapular, urticaria, vesiculobullous, pustular (more than 5%).

Tenofovir

Rash including pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash, sweating.

EENT

Emtricitabine

Rhinitis.

GI

Emtricitabine

Abdominal pain, diarrhea, nausea, vomiting (more than 5%); dyspepsia.

Tenofovir

Nausea, vomiting, diarrhea, vomiting (more than 5%); abdominal pain, flatulence, anorexia, dyspepsia; pancreatitis (postmarketing).

Genitourinary

Tenofovir

Renal function impairment, renal failure, acute renal failure, Fanconi syndrome, proximal tubulopathy, proteinuria, increased creatinine, acute tubular necrosis (postmarketing).

Hypersensitivity

Tenofovir

Allergy (postmarketing).

Lab Tests

Emtricitabine

Elevated ALT, AST, bilirubin, creatine kinase, decreased neutrophils, pancreatic amylase, serum amylase, serum glucose, serum lipase, triglycerides.

Metabolic-Nutritional

Tenofovir

Weight loss, hypophosphatemia, lactic acidosis (postmarketing).

Musculoskeletal

Emtricitabine

Arthralgia, myalgia.

Tenofovir

Back pain, arthralgia, myalgia.

Respiratory

Emtricitabine

Cough.

Tenofovir

Pneumonia, dyspnea (postmarketing).

Miscellaneous

Tenofovir

Pain, chest pain, fever.

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. Truvada is not indicated for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy have not been established in patients co-infected with HBV and HIV.

Monitor Lactic acidosis Monitor patient for signs of lactic acidosis. Withhold drug and notify health care provider immediately of any of the following: profound weakness or tiredness; unexpected stomach discomfort; fatty diarrhea; feeling cold, dizzy, or lightheaded; slow or irregular heartbeat.

Pregnancy

Category B .

Lactation

Undetermined. HIV-infected mothers should not 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 concomitant diseases or other drug therapy.

Bone effects

Decreases from baseline bone mineral density at the lumbar spine and hip have been seen. Ensure that bone density monitoring is performed in HIV-infected patient with history of pathologic bone fracture or at substantial risk for osteopenia. 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.

Hepatitis B

Exacerbations of hepatitis B have been reported after discontinuation of emtricitabine. It is recommended that all patients with HIV be tested for chronic hepatitis B virus (HBV) before initiating antiretroviral therapy. Patients co-infected with HIV and HBV should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment.

Renal function impairment

Dosage adjustment is recommended.

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 if a dose is missed to take it as soon as possible and then 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 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 combined with other antiviral agents.
• Instruct patient to report the following symptoms immediately to health care provider: abdominal swelling or enlargement; fatty diarrhea; profound weakness or tiredness; unexpected stomach discomfort; feeling cold, dizzy, or lightheaded; slow or irregular heartbeat.
• Inform patient that 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 should remain under a physician'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 breastfeeding. Advise HIV-infected mothers not to breast-feed to prevent infecting infants with HIV.