Lamivodine / Tenofovir Misproxil Fomarate 300mg /300mg ( each film coated tablets contains Lamivodine / Tenofovir 300mg /300mg)

Indications

• Human Immunodeficiency Virus (HIV) infection
• Chronic Hepatitis B infection

Dosage

Children: Refer to the BNF for Children for specific dosing information based on the child's age and weight.

Adults: Refer to the relevant clinical guidelines or BNF for specific dosing information based on the condition being treated.

Mechanism of action

Lamivudine is phosphorylated by cellular enzymes to its active triphosphate form. This active metabolite competes with the natural substrate, deoxycytidine triphosphate, for incorporation into viral DNA by reverse transcriptase. Once incorporated, lamivudine causes chain termination, thereby inhibiting further viral DNA synthesis.

Pharmacodynamics

Lamivudine exhibits antiviral activity by selectively inhibiting the reverse transcriptase enzyme of HIV and hepatitis B virus. It has a favorable safety profile with a low incidence of side effects. The drug is effective against HIV strains that are resistant to other NRTIs, making it a valuable option in antiretroviral therapy.

Pharmacokinetics

Lamivudine is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It has a bioavailability of approximately 86% and is primarily eliminated via renal excretion. The half-life of lamivudine is about 5 to 7 hours in individuals with normal renal function, which may be prolonged in patients with renal impairment. Its pharmacokinetic profile allows for once-daily dosing in many cases.

Contra-indications

• Hypersensitivity to lamivudine or any of its components
• Severe hepatic impairment

Adverse effects

• Nausea
• Diarrhea
• Headache
• Fatigue
• Insomnia
• Lactic acidosis
• Hepatomegaly with steatosis
• Pancreatitis

Interactions

• Zidovudine may increase the risk of hematologic toxicity when used with lamivudine
• Concurrent use with other antiretroviral agents should be approached with caution

Precautions

• Monitor for signs of lactic acidosis
• Assess liver function regularly
• Proper counseling regarding adherence to therapy
• Consider resistance testing before initiation in treatment-experienced patients

Pregnancy

Lamivudine is classified as Category C. Use only if the benefits outweigh the risks.

Breast-feeding

Lamivudine is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Oral solution
• Tablets

Indications

• HIV infection
• Chronic hepatitis B

Dosage

Children: Refer to BNF for Children for specific pediatric dosing information.

Adults: Refer to BNF for specific dosing information.

Mechanism of action

Once tenofovir is activated by bi-phosphorylation, it functions as an antiviral acyclic nucleoside phosphonate. It inhibits viral reverse transcriptase, exhibiting an inhibitory constant of approximately 0.022 micromolar. Tenofovir competes with deoxyadenosine 5'-triphosphate to generate new viral DNA, leading to chain termination and inhibition of viral replication. Its safety profile is maintained due to its low affinity for cellular DNA polymerases, including mitochondrial DNA polymerase gamma.

Pharmacodynamics

Tenofovir has demonstrated high efficacy in treatment-naive HIV patients, showing comparable effectiveness to efavirenz while exhibiting lower toxicity than some other antiretrovirals, such as stavudine. In patients with hepatitis B, tenofovir treatment has been associated with undetectable viral DNA levels after one year.

Pharmacokinetics

Tenofovir is absorbed after oral administration and is primarily eliminated by the kidneys. It has a half-life that allows for once-daily dosing and achieves therapeutic concentrations in plasma and tissues. The metabolism of tenofovir involves conversion to its active form, which is then incorporated into viral DNA, leading to its antiviral effects.

Contra-indications

• Hypersensitivity to tenofovir or any excipients in the formulation
• Severe renal impairment (CrCl < 30 mL/min) without appropriate dosage adjustment

Adverse effects

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

Interactions

• Antiepileptics (carbamazepine, fosphenytoin, oxcarbazepine, phenobarbital, phenytoin, primidone) with tenofovir alafenamide: Severe (decreases exposure)
• Tipranavir with tenofovir alafenamide: Severe (decreases exposure)
• Rifamycins with tenofovir alafenamide: Severe (decreases exposure)
• St John’s Wort with tenofovir alafenamide: Severe (decreases exposure)
• Fostemsavir with tenofovir disoproxil: Moderate (increases exposure)
• Fostemsavir with tenofovir alafenamide: Moderate (increases exposure)
• Ciclosporin with tenofovir alafenamide: Unknown (increases exposure)
• Ciclosporin with tenofovir disoproxil: Unknown (increases exposure)
• Eltrombopag with tenofovir alafenamide: Unknown (increases exposure)
• Eltrombopag with tenofovir disoproxil: Unknown (increases exposure)

Precautions

• Monitor renal function regularly during treatment
• Use with caution in patients with a history of renal disease
• Consider bone density monitoring in patients on long-term therapy

Pregnancy

Tenofovir is categorized as a pregnancy category B drug. Animal studies have not shown any harm, but human data is limited. Weigh risks and benefits when prescribing during pregnancy.

Breast-feeding

Tenofovir is excreted in breast milk, but the amount is considered low. The benefits of breastfeeding should be considered against the potential risk of HIV transmission.

Storage

Store at room temperature (20-25°C) in a tightly closed container. Keep away from light and moisture.

Mechanism of action

Once tenofovir is activated by a bi-phosphorylation it acts as an antiviral acyclic nucleoside phosphonate. It is a potent inhibitor of the viral reverse transcriptase with an inhibitory constant of approximately 0.022 micromolar. Once activated, tenofovir acts with different mechanisms including the inhibition of viral polymerase causing chain termination and the inhibition of viral synthesis. All these activities are attained by its competition with deoxyadenosine 5'-triphosphate in the generation of new viral DNA. Once tenofovir is incorporated in the chain, it induces a chain termination which in order inhibits viral replication. The safety of tenofovir relies on its low affinity towards the cellular DNA polymerase including the mitochondrial DNA polymerase gamma.

Pharmacodynamics

Tenofovir has been shown to be highly effective in patients that have never had an antiretroviral therapy and it seemed to have lower toxicity than other antivirals such as [stavudine]. In phase 3 clinical trials, tenofovir presented a similar efficacy than [efavirenz] in treatment-naive HIV patients. In hepatitis B infected patients, after one year of tenofovir treatment, the viral DNA levels were undetectable.