bictegravir/emtricitabine/tenofovir DF

Action and Spectrum

Actions and Spectrum:  

bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a fixed-dose combination antiretroviral therapy used for the treatment of human immunodeficiency virus-1 (HIV-1) infection in adults. 

bictegravir is an HIV-1 integrase strand transfer inhibitor that blocks the integration of viral DNA into the host genome, preventing the replication of the virus. emtricitabine and tenofovir alafenamide are nucleoside reverse transcriptase inhibitors that inhibit the activity of reverse transcriptase, an enzyme necessary for the replication of HIV-1. 

The combination of bictegravir, emtricitabine, and tenofovir alafenamide provides a comprehensive antiretroviral regimen that targets multiple stages of the HIV-1 life cycle. This combination therapy has demonstrated potent antiviral activity and high genetic barriers to resistance, making it an effective treatment option for both treatment-naive and treatment-experienced HIV-1 infected individuals. 

The spectrum is primarily limited to the treatment of HIV-1 infection. It is not effective against other viral infections or other types of retroviruses. B/F/TAF is indicated for use in combination with other antiretroviral agents and should only be prescribed by qualified healthcare professionals experienced in  treating HIV-1 infection. 

Drug Interaction

Adverse Reaction

Frequency defined 

Adults  

1-10% 

Fatigue (2-3%) 

Dizziness (2%) 

Insomnia (2%) 

Diarrhea (3-6%) 

Nausea (3-5%) 

Headache (4-5%) 

ALT >5x ULN (1-2%) 

AST >5x ULN (1-2%) 

Creatine kinase ≥10x ULN (4%) 

Abnormal dreams (<3%) 

Neutrophil <750 mm³ (2%) 

Amylase >2x ULN (2%)  

Frequency Not Defined 

children 

Abdominal pain 

Black Box Warning

Black Box Warning:  

It is recommended that all HIV-1 positive patients undergo testing for Hepatitis B (HBV) prior to commencing antiretroviral therapy, as co-infection with HBV can lead to severe acute exacerbations of Hepatitis B, particularly in those who have stopped taking emtricitabine or tenofovir disoproxil fumarate, both of which are present in BIC/FTC/TAF.

Patients who are co-infected with HIV-1 and HBV and have discontinued BIC/FTC/TAF should receive close clinical and laboratory monitoring of their hepatic function for a minimum of several months.

Contraindication / Caution

Contraindication/Caution:  

bictegravir/emtricitabine/tenofovir alafenamide is a prescription medication indicated for the treatment of HIV-1 infection in adults. As with any medication, certain contraindications should be considered before prescribing this drug. 

bictegravir/emtricitabine/tenofovir alafenamide is contraindicated in patients with a known hypersensitivity to any of the components of the medication. This includes patients who have previously experienced an allergic reaction to bictegravir, emtricitabine, tenofovir alafenamide, or any other ingredients present in the formulation. 

Additionally, bictegravir/emtricitabine/tenofovir alafenamide is contraindicated in patients with severe renal impairment (estimated creatinine clearance < 30 mL/min) or end-stage renal disease requiring hemodialysis. 

Finally, bictegravir/emtricitabine/tenofovir alafenamide should not be co-administered with certain medications due to the potential for significant drug interactions. These medications include dofetilide, rifampin, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, and St. John’s wort. 

It is important to carefully evaluate the patient’s medical history and current medications to identify any contraindications before prescribing bictegravir/emtricitabine/tenofovir alafenamide. Failure to do so may lead to adverse drug reactions or treatment failure. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology: 

bictegravir functions as an integrase strand transfer inhibitor (INSTI), which hinders the incorporation of HIV-1 DNA into the genetic material of the host cell.emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) that inhibits reverse transcriptase, a viral enzyme that is essential for the replication of HIV-1.  

Pharmacodynamics: 

bictegravir blocks the integration of HIV-1 DNA into the host cell genome by inhibiting the activity of integrase, an enzyme that is essential for the replication of HIV-1. emtricitabine and tenofovir inhibit the reverse transcriptase enzyme, which is essential for the replication of HIV-1. The combination of these drugs reduces the viral load and increases CD4+ T-cell count, resulting in the suppression of HIV-1 replication and the prevention of the progression of the disease. 

MOA:  

The mechanism of action of involves the inhibition of the viral replication cycle. Specifically, bictegravir prevents the integration of viral DNA into the host cell genome by binding to the active site of integrase and inhibiting its activity. emtricitabine and tenofovir alafenamide, on the other hand, work by inhibiting reverse transcriptase, an enzyme that converts viral RNA into DNA during the replication cycle.  

Pharmacokinetics: 

Absorption 

B/F/TAF is orally administered and undergoes dissolution in the gastrointestinal tract. bictegravir, emtricitabine, and tenofovir alafenamide are all absorbed through the gastrointestinal tract. bictegravir is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), while emtricitabine and tenofovir alafenamide are not. 

Distribution 

bictegravir, emtricitabine, and tenofovir alafenamide are widely distributed in the body. The plasma protein binding of bictegravir, emtricitabine, and tenofovir alafenamide is approximately 98%, 86%, and 80%, respectively. The volume of distribution of bictegravir, emtricitabine, and tenofovir alafenamide is 42.3 L, 1.3 L/kg, and 0.57 L/kg, respectively. 

Metabolism 

bictegravir undergoes biotransformation by cytochrome P450 (CYP) 3A4 and uridine diphosphate-glucuronosyltransferase (UGT) 1A1, while emtricitabine and tenofovir alafenamide do not undergo significant metabolism. tenofovir alafenamide is converted to tenofovir in the plasma and tissues, and bictegravir and emtricitabine are excreted unchanged. 

Elimination and Excretion 

bictegravir, emtricitabine, and tenofovir alafenamide are primarily excreted through the kidneys. The elimination half-life of bictegravir, emtricitabine, and tenofovir alafenamide is approximately 18 hours, 10 hours, and 0.51 hours, respectively. tenofovir is excreted both in the urine and feces, while bictegravir and emtricitabine are primarily excreted in the urine. 

Adminstartion

Administration:  

bictegravir/emtricitabine/tenofovir alafenamide is a fixed-dose combination medication used in the management of human immunodeficiency virus (HIV) infection. The administration of bictegravir/emtricitabine/tenofovir AF is oral and the recommended dosage is one tablet once daily taken with or without food. 

It is advised that the tablet should be swallowed whole and not crushed, broken or chewed, as it may lead to a reduction in the medication’s efficacy. Patients with renal or hepatic impairment may require dose adjustments to minimize the risk of adverse events. 

bictegravir/emtricitabine/tenofovir AF should be used in conjunction with other antiretroviral medications to provide comprehensive management of HIV infection. It is crucial to adhere to the medication regimen and follow up with routine medical appointments to monitor treatment efficacy and manage any potential side effects. 

Patient Information Leaflet

Patient information leaflet 

Generic name:
bictegravir/emtricitabine/tenofovir AF  

Why do we use bictegravir/emtricitabine/tenofovir AF?  

bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a fixed-dose combination medication that is indicated for the treatment of human immunodeficiency virus-1 (HIV-1) infection in adults. This medication is used as a complete regimen and should not be coadministered with other antiretroviral medications. 

bictegravir is an integrase strand transfer inhibitor that blocks the HIV integrase enzyme, thereby preventing the virus from integrating its genetic material into the host DNA.  

The medication is effective in suppressing HIV viral load to undetectable levels and improving CD4+ cell counts. Additionally, B/F/TAF has demonstrated non-inferior efficacy and better tolerability when compared to other antiretroviral regimens. 

It is important to note that B/F/TAF should not be used in patients with severe renal impairment or end-stage renal disease, as tenofovir alafenamide can cause renal impairment.