Tenofovir

287.21

287.21

1308068-626-2

W4HFE001U5

DTXSID9040132

J05AR03

29339900

136

-1.6

Solid

1.79±0.1 g/cm3(Predicted)

276-280°C

616°C

326.4±34.3 °C

1.740

H2O: 13.4 mg/mL (25 ºC)

Store at -20°C

D +21° (c = 1 in 0.1M HCl)

3.8and 6.7

3.8 and 6.7

III

8

UN 3261 8/PG 2

3

R34:Causes burns.

S22-S26-S27-S36/37/39-S45

SZ6563600

C

P280, P305+P351+P338, P310

H318

|Danger|H318 (100%): Causes serious eye damage [Danger Serious eye damage/eye irritation]|P280, P305+P351+P338, and P310|Aggregated GHS information provided by 2 companies from 1 notifications to the ECHA C&L Inventory.

There haven't been reports regarding the LD50 of the parent compound nor the effects of an overdose. However, based on the reports with the derivative that most rapidly transforms into tenofovir, tenofovir disoproxil, it is recommended to monitor overdose patients. As well, it is widely known that tenofovir is efficiently removed by hemodialysis. Administration of high doses of tenofovir has been reported to produce bone toxicity reported as osteomalacia and reduced bone mineral density and to produce some degree of renal toxicity. To know more about the carcinogenicity and mutagenic potential of tenofovir, as well as the effect on fertility, please visit the drug entries for the derivatives [tenofovir disoproxil] and [tenofovir alafenamide].

Like all nucleoside analogues used as therapy of hepatitis B, tenofovir can cause transient increases in serum aminotransferases during or after therapy. These abnormalities appear to be due to an exacerbation or flare of the underlying hepatitis B. Three types of flares due to nucleoside analogue therapy have been described: transient flares during initiation of therapy (treatment flares), flares occurring in association with development of antiviral resistance (breakthrough flares) and flares occurring in the few months after stopping therapy (withdrawal flares). Treatment flares generally arise during the first few months of starting therapy, are usually mild, asymptomatic and self-limited and do not require dose modification or interruption of therapy. Breakthrough flares generally follow the development of antiviral resistance and subsequent rise in HBV DNA levels during nucleoside analogue therapy. Breakthrough flares can be symptomatic and severe. Because tenofovir is associated with a very low rate of antiviral resistance (

Tenofovir is minimally bound to plasma proteins and only about 7.2% of the administered dose is found in the bound state.

Tenofovir has been shown to be effective against HIV, herpes simplex virus-2, and hepatitis B virus. To know more about the specific product indications, please visit the information in the orally available forms of tenofovir, [tenofovir alafenamide] and [tenofovir disoproxil].|Treatment of HIV-1 infection:Truvada is indicated in antiretroviral combination therapy for the treatment of HIV-1 infected adults.Truvada is also indicated for the treatment of HIV-1 infected adolescents, with NRTI resistance or toxicities precluding the use of first line agents, aged 12 to < 18 years.Pre-exposure prophylaxis (PrEP):Truvada is indicated in combination with safer sex practices for pre-exposure prophylaxis to reduce the risk of sexually acquired HIV-1 infection in adults at high risk.

Tenofovir is an acyclic nucleotide analogue of adenosine used in combination with other agents in the therapy of the human immunodeficiency virus (HIV) and as single agent in hepatitis B virus (HBV) infection. Tenofovir does not appear to be a significant cause of drug induced liver injury.

Antiviral Agents

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.

Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS. (See all compounds classified as Anti-HIV Agents.)|Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. (See all compounds classified as Antiviral Agents.)|Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. (See all compounds classified as Reverse Transcriptase Inhibitors.)

Tenofovir as the active moiety presents a very low bioavailability when orally administered. Hence, the administration of this active agent is required to be under its two prodrug forms, [tenofovir disoproxil] and [tenofovir alafenamide]. This reduced absorption is suggested to be related to the presence of two negative charges among its structure. This negative charge limits its cellular penetration, and its passive diffusion across cellular membranes and intestinal mucosa hindering its availability for oral administration. Intravenous tenofovir has been shown to produce a maximum plasma concentration of 2500 ng/ml with an AUC of 4800 ng.h/ml.|Tenofovir is eliminated in the urine by tubular secretion and glomerular filtration. The elimination of this compound is driven by the activity of the human organic anion transporters 1 and 3 and its secretion is mainly ruled by the activity of the multidrug resistance-associated protein 4.|Accumulation of tenofovir in plasma is related to the presence of nephrotoxic effects. It is reported that tenofovir presents a volume of distribution of 0.813 L/kg.|The clearance of tenofovir is highly dependent on the patient renal stage and hence the clearance rate in patients with renal impairment is reported to be of 134 ml/min while in patients with normal function the clearance rate can be of 210 ml/min.

Tenofovir activation is performed by a bi-phosphorylation which in order forms the biologically active compound, tenofovir biphosphate. This metabolic activation has been shown to be performed in hepG2 cells and human hepatocytes. After activation, it does present minimal metabolic processing by the cytochrome enzyme isoenzyme CYP3A.

The reported half-life of tenofovir is of 32 hours.

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.

(R)-9-(2-phosphonylmethoxypropyl)adenine

Human drugs -> Truvada -> EMA Drug Category|Antivirals for systemic use -> Human pharmacotherapeutic group|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients