Tenofovir + Emtricitabine

Oral
HIV-1 infection

Patient on haemodialysis: Not recommended.

CrCl (mL/min)	Dosage
<30	Not recommended.
30-49	1 tablet every 48 hr.

May be taken with or without food. Take consistently either always w/ or always w/o food.

Lactation. Not to be used for treatment of chronic hepatitis B virus (HBV) infection.

Liver impairment. Renal impairment; avoid in CrCl <30ml/min and in patients on dialysis. Pregnancy. Not to be used with other emtricitabine, tenofovir disoproxil fumarate or other cytidine analogues (e.g. lamivudine and zalcitabine) preparations. Avoid use in antiretroviral-experienced patients with K65R mutation; in treatment experienced patients, use of combination drug to be guided by laboratory testing and treatment history. Increased risk for severe and potentially fatal hepatic adverse reactions in patients with HIV and hepatitis B or C virus co-infection treated with antiretroviral agents. If combination drug is discontinued in patients co-infected with HIV and HBV, monitor hepatic function for several months for acute exacerbation of hepatitis. Discontinue therapy if there is a rapid rise in aminotransferase concentrations, progressive hepatomegaly or steatosis, metabolic or lactic acidosis of unknown cause. Test for presence of chronic HBV before initiating therapy. Check CrCl before initiation of therapy and monitor renal function (CrCl and serum phosphate) every 4 wkly during the 1st year and then every 3 mthly (more frequently in patients at risk for renal impairment). Bone monitoring needed for patient with history of pathologic bone fracture or at risk of osteopenia. Monitor child exposed in utero to combination drug for possible mitochondrial dysfunction.

Nausea, vomiting, diarrhoea, abdominal pain, dyspepsia, flatulence, pain, hypersensitivity, increased pigmentation, asthenia, osteonecrosis, osteomalacia, metabolic abnormalities (e.g. hyperglycaemia, insulin resistance, hypercholesterolaemia, hypertriglyceridaemia, hyperlactataemia), lipodystrophy, elevated lipase, amylase, creatine kinase or transaminases levels, hyperbilirubinaemia, insomnia, abnormal dreams. Neutropenia, anaemia, Immune Reactivation Syndrome. Renal impairment, acute renal failure, Fanconi syndrome.
Potentially Fatal: Lactic acidosis and severe hepatomegaly with steatosis.

PO: B

Treatment is supportive and monitor for signs of toxicity. Haemodialysis may be helpful as it can remove up to 30% of the emtricitabine dose and 10% of the tenofovir dose. Unknown if peritoneal dialysis is useful.

Decreased atazanavir concentration with tenofovir unless also co-administered with ritonavir. Increased serum concentration of both tenofovir and emtricitabine or co-administered drug if taken with drugs that are eliminated by active tubular secretion.
Potentially Fatal: Increased risk of renal impairment with recent or concurrent use of nephrotoxic agents (e.g. aminoglycosides, amphotericin B, foscarnet, ganciclovir, pentamidine, vancomycin, cidofovir or interleukin-2); monitor renal function wkly if unavoidable. Increased didanosine levels and thereby increasing risk of pancreatitis and peripheral neuropathy, with a high treatment failure rate with concurrent use; avoid concurrent use. Do not use emtricitabine with lamivudine due to similar resistance profile. Increased risk of lactic acidosis with α-interferon.

Description:
Mechanism of Action: Tenofovir disoproxil fumarate, a diester prodrug of tenofovir, is rapidly converted to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analogue of adenosine 5'-monophosphate while emtricitabine is a synthetic nucleoside analogue of cytidine. Both emtricitabine and tenofovir inhibit HIV-1 reverse transcriptase, resulting in DNA chain termination.
Pharmacokinetics:
Absorption: Tenofovir: Rapidly absorbed; converted to tenofovir after oral doses; oral bioavailability: approx 25% after fasting, increased when taken with a high fat meal; peak plasma concentrations reached in 1 hr (fasting) to 2 hr (with food). Emtricitabine: Rapidly and well absorbed from GI tract; peak plasma concentrations achieved in 1-2 hours; bioavailability: 93% (capsules); 75% (oral solution).
Distribution: Tenofovir: Widely distributed into most tissues, especially kidneys, liver and intestinal contents; protein binding: <0.7% to plasma proteins, 7% to serum protein. Emtricitabine: Protein binding: <4%, independent of concentration.
Metabolism: Emtricitabine: Limited metabolism.
Excretion: Tenofovir: Excreted renally by glomerular filtration and active tubular secretion; terminal elimination half life: 12-18 hr. Emtricitabine: Excreted largely unchanged in the urine and to a lesser extent in the faeces; plasma elimination half-life: 10 hr.

Store between 15-30°C (59-86°F).

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