EMTRICITABINE AND TENOFOVIRDISOPROXILFUMARATE TABLETS 200 MG/300 MG

Indications

• HIV infection in combination with other antiretroviral drugs
• Chronic hepatitis B infection with compensated liver disease
• Chronic hepatitis B infection with decompensated liver disease

Dosage

Children: For children weighing up to 30 kg: 1 mg/kg twice daily. For children weighing 30-59 kg: 30 mg twice daily.

Adults: 245 mg once daily by mouth.

Mechanism of action

Tenofovir disoproxil is converted intracellularly to tenofovir diphosphate, which competes with natural deoxyadenosine triphosphate for incorporation into viral DNA. This incorporation causes chain termination and inhibits viral replication. The drug targets the reverse transcriptase enzyme, which is crucial for the replication of HIV and hepatitis B virus.

Pharmacodynamics

As an NRTI, tenofovir disoproxil exhibits a dose-dependent effect on viral replication. It effectively reduces viral load in patients with HIV and chronic hepatitis B. The drug's efficacy is enhanced when used in combination with other antiretroviral agents, leading to improved outcomes in managing these viral infections.

Pharmacokinetics

Tenofovir disoproxil is well absorbed in the gastrointestinal tract, with peak plasma concentrations occurring approximately 1-2 hours after oral administration. It has a half-life of about 12-18 hours, allowing for once-daily dosing. The drug is primarily eliminated via renal excretion, and dosage adjustments are recommended for patients with renal impairment.

Contra-indications

• Hypersensitivity to peanut or soya products
• Renal impairment with creatinine clearance less than 50 mL/minute

Adverse effects

• Abdominal distension
• Proximal renal tubulopathy
• Fatigue
• Dizziness
• Somnolence

Interactions

• Ciclosporin - unknown effect on exposure
• Eltrombopag - unknown effect on exposure
• Ledipasvir with sofosbuvir - unknown effect on exposure
• Leflunomide - unknown effect on exposure
• Teriflunomide - unknown effect on exposure
• Velpatasvir - unknown effect on exposure
• Voxilaprevir with sofosbuvir and velpatasvir - potentially increases concentration

Precautions

• Caution in elderly patients due to limited information
• Monitor renal function and serum phosphate before treatment and periodically thereafter
• Counsel patients regarding the impact on driving and skilled tasks due to potential dizziness and fatigue

Pregnancy

Manufacturer advises avoidance during pregnancy due to limited safety data.

Breast-feeding

Manufacturer advises caution; consult relevant guidelines.

Storage

Store below 30°C, in a dry place, away from direct light.

Formulations

• Tablets: 245 mg
• Granules: 132 mg (approx. equivalent to 245 mg when reconstituted)

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

Indications

• HIV-1 infection
• Chronic hepatitis B virus infection

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing recommendations.

Adults: Refer to the relevant clinical guidelines or the BNF for specific dosing recommendations.

Mechanism of action

Tenofovir disoproxil fumarate is converted to its active form, tenofovir, which competes with natural deoxynucleotides for incorporation into viral DNA by reverse transcriptase. This incorporation results in chain termination, preventing further viral replication. It also has a similar mechanism against HBV, inhibiting viral replication.

Pharmacodynamics

Tenofovir exhibits a dose-dependent inhibition of HIV-1 and HBV replication. The drug is effective against a broad range of HIV-1 subtypes and has been shown to have a high barrier to resistance. Its antiviral activity is measured by its ability to reduce viral load in patients, leading to improved immune function as indicated by increases in CD4+ T-cell counts.

Pharmacokinetics

After oral administration, tenofovir disoproxil fumarate is rapidly absorbed and converted to tenofovir. It has a bioavailability of approximately 25% when taken with food. The drug is primarily eliminated by the kidneys, with a half-life of about 17 hours. Steady-state concentrations are achieved within 2 days of dosing. Renal function should be monitored as tenofovir can cause nephrotoxicity.

Adverse effects

• Nausea
• Diarrhea
• Headache
• Fatigue
• Rash
• Renal impairment
• Bone mineral density loss
• Lactic acidosis

Interactions

• Didanosine
• Acyclovir
• Cidofovir
• Rifampicin
• St. John's Wort

Precautions

• Monitor renal function regularly
• Assess for signs of lactic acidosis
• Evaluate bone mineral density in long-term use
• Use with caution in patients with pre-existing renal impairment

Pregnancy

Tenofovir disoproxil fumarate is classified as category B. Animal studies have not shown teratogenic effects, but clinical data in pregnant women are limited. Use only if clearly needed.

Breast-feeding

Tenofovir is excreted in human milk. The decision to continue breastfeeding or discontinue the drug should consider the benefits of breastfeeding against the mother's need for the drug.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets: 300 mg

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.