EMFANEF

Indications

• HIV infection

Dosage

Children: Child 4 months–17 years (body-weight up to 33 kg): 6 mg/kg once daily. Child 4 months–17 years (body-weight 33 kg and above): 240 mg once daily.

Adults: 200 mg once daily by mouth using capsules or 240 mg once daily by mouth using oral solution.

Mechanism of action

Emtricitabine is a cytidine analog that, when phosphorylated to emtricitabine 5'-triphosphate, competes with deoxycytidine 5'-triphosphate for HIV-1 reverse transcriptase. It incorporates itself into the viral DNA during replication, leading to chain termination. This prevents the incorporation of additional nucleotides and inhibits the transcription of viral RNA into DNA, thereby preventing viral replication.

Pharmacodynamics

Emtricitabine acts by competing with natural substrates of HIV-1 reverse transcriptase, leading to the termination of viral DNA synthesis. It has a long duration of action, allowing for once-daily dosing. Clinicians should monitor for potential side effects, including lactic acidosis and hepatomegaly with steatosis, which can occur with nucleoside analogs.

Pharmacokinetics

Emtricitabine is absorbed well following oral administration, with peak plasma concentrations occurring approximately 1 to 2 hours post-dose. It has a long half-life, allowing for its once-daily administration. Emtricitabine is primarily excreted through the kidneys, and dosage adjustments may be necessary in patients with renal impairment. It is metabolized minimally by the liver.

Contra-indications

• Severe hepatic impairment
• Severe renal impairment (creatinine clearance <30 mL/min)

Adverse effects

• Decreased appetite
• Asthenia
• Constipation
• Diarrhoea
• Dizziness
• Electrolyte imbalance
• Flatulence
• Gastrointestinal discomfort
• Headache
• Abnormal dreams
• Dyspepsia
• Hyperbilirubinaemia
• Hyperglycaemia
• Hypersensitivity reactions
• Hypertriglyceridaemia
• Neutropenia
• Pain
• Rash
• Pustular skin reactions
• Sleep disorders
• Angioedema (uncommon)

Interactions

• Cobicistat and elvitegravir may impact emtricitabine efficacy
• Potential for increased risk of treatment failure in pregnancy when used with elvitegravir
• Monitor for changes in drug levels when co-administered with other antiretrovirals

Precautions

• Caution in patients with hepatic impairment due to increased risk of side effects
• Monitor renal function regularly, particularly in those with existing renal impairment
• Patients should be advised on the risks of lactic acidosis and hepatomegaly with steatosis

Pregnancy

Not recommended for initiation during pregnancy due to risk of treatment failure and maternal-to-child transmission of HIV-1. Women who become pregnant during therapy should be switched to an alternative regimen.

Breast-feeding

Emtricitabine is excreted in human breast milk, caution is advised when administering to breastfeeding mothers.

Storage

Store in the original container, protected from moisture, and keep out of reach of children.

Formulations

• 200 mg capsules
• 240 mg oral solution

Mechanism of action

Emtricitabine is a cytidine analog which, when phosphorylated to emtricitabine 5'-triphosphate, competes with deoxycytidine 5'-triphosphate for HIV-1 reverse transcriptase. As HIV-1 reverse transcriptase incorporates emtricitabine into forming DNA strands, new nucleotides are unable to be incorporated, leading to viral DNA chain termination. Inhibition of reverse transcriptase prevents transcription of viral RNA into DNA, therefore the virus is unable to incorporate its DNA into host DNA and replicate using host cell machinery. This reduces viral load. Emtricitabine, a synthetic nucleoside analog of cytosine, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate. Emtricitabine 5'-triphosphate inhibits the activity of the HIV-1 reverse transcriptase by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA which results in chain termination. Emtricitabine 5'-triphosphate is a weak inhibitor of mammalian DNA polymerase alpha, beta, epsilon and mitochondrial DNA polymerase gamma.

Pharmacodynamics

Emtricitabine is a cytidine analog that competes with the natural substrate of HIV-1 reverse transcriptase to be incorporated into newly formed DNA, terminating its transcription. It is administered once daily so it has a long duration of action. Patients should be counselled regarding the risk of lactic acidosis and hepatomegaly with steatosis.