tenofovir disoproxil fumarate or tenofovir DF

Action and Spectrum

Actions and Spectrum: 

Actions: 

tenofovir DF is a analog of adenosine monophosphate which is a nucleoside reverse transcriptase inhibitor which is converted to tenofovir with the help of initial diester hydrolysis for its conversion and intracellular phosphorylation by different associated cell enzymes where it is transformed to tenofovir diphosphate where it shows the action of termination on the chain. This converted tenofovir inhibits the action of HIV-1 reverse transcriptase and also HBV reverse transcriptase with combined action of triphosphate into DNA by incorporation and also by chain termination. 

Spectrum: 

tenofovir DF is a nRTI’s which is a fumarate salt that is used in the treatment of HIV-1 in combination with other drugs and in treatment of HBV infection by inhibiting the activity of reverse transcriptase of both HIV-1 and HBV by competitively acting with triphosphate and incorporation into DNA which results in chain termination. The spectrum of tenofovir DF is mostly with other drugs that are useful in the treatment of infections mentioned above. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Rash (18%) 

Headache (14%) 

Pain (13%) 

Diarrhea (11%) 

Depression (11%) 

1-10% 

Back pain (9%) 

Nausea (8%) 

Fever (8%) 

Abdominal Pain (7%) 

Asthenia (6%) 

Anxiety (6%) 

Vomiting (5%) 

Insomnia (5%) 

Arthralgia (5%) 

Pneumonia (5%) 

Dyspepsia (4%) 

Dizziness (3%) 

Myalgia (3%) 

Lipodystrophy (1%) 

Peripheral Neuropathy (1%) 

Black Box Warning

Black Box Warning: 

After discontinuation of treatment with this drug it is recommended to closely monitor patients’ health by assessing all the lab tests and reports before starting the treatment again. Exacerbations of hepatitis B is very severe and acute in patients who discontinued treatment for hepatitis B.

Contraindication / Caution

Contraindication/Caution: 

Contraindications 

• None 

Cautions 

• Coinfection of HIV-1 and HBV 
• Immune reconstitution syndrome 
• Bone loss and mineralization defects 
• Hepatomegaly with steatosis 
• Renal impairment 
• Hepatic impairment 
• Drug interactions 
• Breastfeeding 

Pregnancy / Lactation

Pregnancy consideration:  

No data is available regarding the administration of the drug during pregnancy. 

Breastfeeding warnings:  

Limited data that shows instructions not to breast fed their babies who has HIV-1 infection when undergoing treatment with tenofovir DF. 

Pregnancy category: 

Category A: well-controlled and satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

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: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

tenofovir DF is a analog of adenosine monophosphate which is a nucleoside reverse transcriptase inhibitor which is converted to tenofovir with the help of initial diester hydrolysis for its conversion and intracellular phosphorylation by different associated cell enzymes where it is transformed to tenofovir diphosphate where it shows the action of termination on the chain. This converted tenofovir inhibits the action of HIV-1 reverse transcriptase and HBV reverse transcriptase with combined action of triphosphate into DNA by incorporation and also by chain termination. 

Pharmacodynamics: 

tenofovir DF is a nRTI’s class of drug that inhibits certain enzymes that are necessary for chain growth and ultimately avoid replication of HIV-1 and HBV infections. It undergoes reactions to form tenofovir which is the main product that inhibits the action of HIV-1 and HBV reverse transcriptase enzyme with competitive action of triphosphate and after incorporation inti DNA and thereby termination of chain. 

Pharmacokinetics: 

Absorption 

tenofovir DF administration after having heavy meal raises the bioavailability of the drug which is 40% and also increase in Cmax that is 1 hour (14%) and viceversa with light meal. 

Distribution 

tenofovir to humn plasma protein binding is less than 0.7% and with serum protein is less than 7.2%. when IV of tenofovir DF 1.0 mg/kg and 3.0 mg/kg is given Vd at steady state is 1.3 L/kg and 1.2 L/kg. 

Metabolism 

tenofovir DF which is a fumarate salt is converted to tenofovir which is a monophosphate and is again converted to tenofovir diphosphate which is a chain terminator that shows the action of inhibition. 

Elimination and Excretion 

Unchanged drug in the urine after IV administration of tenofovir DF is 75% in 3 days. Elimination is by glomerular filtration and active tubular secretion and have competitive mechanism with other drugs that are eliminated by kidneys. After oral dose, half-life of tenofovir DF is 17 hours. Total clearance is highly dependent on renal function which is estimated to be 230 mL/h/kg. average renal clearance is approx. 160 mL/h/kg which is more than GFR. So Active tubular secretion is most needed for the elimination of tenofovir. 

Adminstartion

Administration: 

tenofovir DF can be taken with or without food and monitor closely when combining with didanosine drug. Time of 2 hors before didanosine or 1 hour after taking it should be kept in recommendation.

Patient Information Leaflet

Patient information leaflet 

Generic Name: tenofovir disoproxil fumerate 

Pronounced: ten-of-oh-vir dye-soe-prox-il fue-ma-rate 

Why do we use tenofovir DF? 

tenofovir DF is used with other antiretroviral agents to help reduce the viral load of HIV in the body which can help reduce infections further and ultimately gives the quality in our lives. tenofovir DF is a nucleoside reverse transcriptase inhibitor that is used in the treatment of chronic hepatitis B infection and for HIV infection with other medications to treat this condition.