Tenofovir alafenamide

Tenofovir alafenamide Uses, Dosage, Side Effects, Food Interaction and all others data.

Tenofovir alafenamide is a phosphonamidate prodrug of tenofovir (2'-deoxyadenosine monophosphate analog). Tenofovir alafenamide as a lipophilic cell-permeant compound enters primary hepatocytes by passive diffusion and by the hepatic uptake transporters OATP1B1 and OATP1B3. Tenofovir alafenamide is then converted to tenofovir through hydrolysis primarily by carboxylesterase 1 (CES1) in primary hepatocytes. Intracellular tenofovir is subsequently phosphorylated by cellular kinases to the pharmacologically active metabolite tenofovir diphosphate.

Tenofovir diphosphate inhibits HBV replication through incorporation into viral DNA by the HBV reverse transcriptase, which results in DNA chain-termination.Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases that include mitochondrial DNA polymerase γ and there is no evidence of toxicity to mitochondria in cell culture.

Tenofovir alafenamide has been shown to be a potent inhibitor of hepatitis B viral replication.

Tenofovir alafenamide presents a better renal tolerance when compared with the counterpart tenofovir disoproxil. This improved safety profile seems to be related to a lower plasma concentration of tenofovir.

In clinical trials, tenofovir alafenamide was shown to present 5-fold more potent antiviral activity against HIV-1 when compared to tenofovir disoproxil.

Trade Name Tenofovir alafenamide
Generic Tenofovir Alafenamide
Tenofovir Alafenamide Other Names Tenofovir alafenamide
Type Oral
Formula C21H29N6O5P
Weight Average: 476.474
Monoisotopic: 476.193705056
Protein binding

Tenofovir alafenamide is reported to bind to plasma proteins and ex vivo studies have registered that approximately 80% of the administered dose of this drug is presented in a bound state.

Groups Approved
Therapeutic Class Hepatic viral infections (Hepatitis B)
Manufacturer
Available Country United States
Last Updated: September 19, 2023 at 7:00 am
Tenofovir alafenamide
Tenofovir alafenamide

Uses

Tenofovir alafenamide is a hepatitis B virus (HBV) nucleoside analog reverse transcriptase inhibitor and is used for the treatment of chronic hepatitis B virus infection in adults with compensated liver disease.

Tenofovir alafenamide is also used to associated treatment for these conditions: Hepatitis B Chronic Infection, Human Immunodeficiency Virus Type 1 (HIV-1), Human Immunodeficiency Virus Type 1 (HIV-1) Infection

How Tenofovir alafenamide works

Tenofovir alafenamide presents 91% lower plasma concentration with an intracellular presence of about 20-fold higher when compared to tenofovir disoproxil. This is due to its prolonged systemic exposure and its higher intracellular accumulation of the active metabolite tenofovir diphosphate.

Tenofovir alafenamide accumulates more in peripheral blood mononuclear cells compared to red blood cells.

Once activated, tenofovir acts with different mechanisms including the inhibition of viral polymerase, causing chain termination and the inhibition of viral synthesis. To know more about the specific mechanism of action of the active form, please visit the drug entry of tenofovir.

Dosage

Tenofovir alafenamide dosage

Testing Prior To Initiation Of Tenofovir alafenamide: Prior to initiation of Tenofovir alafenamide, patients should be tested forHIV-1 infection. Tenofovir alafenamide alone should not be used in patients with HIV infection

It is recommended that serum creatinine, serum phosphorous, estimated creatinine clearance, urine glucose, and urine protein be assessed before initiating Tenofovir alafenamide and during therapy in all patients as clinically appropriate

Recommended Dosage In Adults: The recommended dosage of Tenofovir alafenamide is 25 mg (one tablet) taken orally once daily with food

Side Effects

The following adverse reactions are discussed in other sections of the labeling:

  • Lactic Acidosis/Severe Hepatomegaly with Steatosis
  • Severe Acute Exacerbation of Hepatitis B
  • New Onset or Worsening of Renal Impairment

The most common side effects are headache, stomach pain, tiredness, cough, nausea, back pain

Toxicity

The LD50 of tenofovir alafenamide has not been reported. In cases of overdose, continuous monitoring of vital signs is required as the adverse effects in high doses has not been evaluated. However, in case of overdose, tenofovir is efficiently removed by hemodialysis with an extraction coefficient of 54%.

Carcinogenic reports have only been performed with tenofovir disoproxil and it is important to consider that tenofovir alafenamide does not present a high systemic exposure. However, long-term exposure with 10-fold dosages of tenofovir disoproxil was reported to produce liver adenomas in females. Tenofovir alafenamide was not reported to present mutagenic potential and it did not present effects on fertility.

Interaction

Tenofovir is a substrate of P-glycoprotein (P-gp) and BCRP. Drugs that strongly affect P-gp and BCRP activity may lead to changes in Tenofovir absorption. Consult the full prescribing information prior to and during treatment for potential drug drug interactions.

Food Interaction

  • Take at the same time every day.
  • Take with or without food. Recommendations vary from product to product - consult individual product monographs for additional information.

Volume of Distribution

In clinical trials, the reported volume of distribution of tenofovir alafenamide was higher than 100 L.

Elimination Route

As compared to the parent molecule, tenofovir, tenofovir alafenamide presents a lipophilic group that masks the negative charge of the parent moiety which improves its oral bioavailability.

Tenofovir alafenamide is highly stable in plasma and, after administration of this prodrug, there is a low concentration of tenofovir in plasma. After oral administration, tenofovir alafenamide is rapidly absorbed by the gut. When a single dose is administered, a peak concentration of 16 ng/ml of the parent compound, corresponding to about 73% of the dose, is observed after 2 hours with an AUC of 270 ng*h/mL. Once inside the body, tenofovir alafenamide enters hepatocytes by passive diffusion regulated by the organic anion transporters 1B1 and 1B3 for its activation.

Administration of tenofovir alafenamide concomitantly with a high-fat meal results in an increase of about 65% in its internal exposure.

Half Life

The reported half-life for tenofovir alafenamide is of 0.51 hours.

Clearance

The reported clearance rate of tenofovir alafenamide is 117 L/h. In patients with severe renal impairment, this value can be decreased by 50%, reporting a rate of 61.7 L/h.

Elimination Route

Tenofovir alafenamide has been registered to present a bile elimination that corresponds to 47% of the administered dose and a renal elimination the represents about 36%. From the recovered dose in urine, about 75% is represented as unchanged tenofovir followed by uric acid and a small dose of tenofovir alafenamide. On the other hand, in feces, 99% of the recovered dose corresponds to tenofovir.

Pregnancy & Breastfeeding use

Before you take Tenofovir alafenamide, tell your healthcare provider about all of your medical conditions, including if you are pregnant or plan to become pregnant. It is not known if Tenofovir alafenamide will harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with Tenofovir alafenamide.

Pregnancy Registry: There is a pregnancy registry for women who take antiviral medicines during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk with your healthcare provider about how you can take part in this registry.

Contraindication

None

Special Warning

Pediatric Use: Safety and effectiveness of Tenofovir alafenamide in pediatric patients less than 18 years of age have not been established.

Geriatric Use: Clinical trials of Tenofovir alafenamide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Renal Impairment: No dosage adjustment of Tenofovir alafenamide is required in patients with mild, moderate, or severe renal impairment. Tenofovir alafenamide is not recommended in patients with end stage renal disease (estimated creatinine clearance below 15 mL per minute)

Hepatic Impairment: No dosage adjustment of Tenofovir alafenamide is required in patients with mild hepatic impairment (Child-Pugh A). The safety and efficacy of Tenofovir alafenamide in patients with decompensated cirrhosis (Child-Pugh B or C) have not been established; therefore Tenofovir alafenamide is not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment

Acute Overdose

If overdose occurs, monitor patient for evidence of toxicity. Treatment of overdosage with Tenofovir alafenamide consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient. Tenofovir is efficiently removed by hemodialysiswith an extraction coefficient of approximately 54%

Storage Condition

Store below 86°F (30°C). Keep in its original container. Keep the container tightly closed.

Innovators Monograph

You find simplified version here Tenofovir alafenamide

Tenofovir alafenamide contains Tenofovir Alafenamide see full prescribing information from innovator Tenofovir alafenamide Monograph, Tenofovir alafenamide MSDS, Tenofovir alafenamide FDA label

FAQ

What is Tenofovir alafenamide used for?

Tenofovir alafenamide is used to treat chronic hepatitis B virus (HBV) infection in adults with compensated liver disease.

When should I take Tenofovir alafenamide?

Take this medication by mouth with food as directed by your doctor, usually once daily. If you are on dialysis, on your dialysis days, take your daily dose of this medication following dialysis.

What are the common side effects of Tenofovir alafenamide?

The common side effects of Tenofovir alafenamide are include:

  • Abdominal or stomach discomfort
  • bloody urine
  • dark urine
  • decreased appetite
  • decreased frequency or amount of urine
  • diarrhea
  • fast, shallow breathing
  • general feeling of discomfort
  • increased blood pressure
  • increased thirst
  • light-colored stools
  • loss of appetite
  • lower back or side pain
  • muscle pain or cramping
  • nausea and vomiting
  • right upper abdominal or stomach pain and fullness
  • sleepiness
  • swelling of the face, fingers, or lower legs
  • troubled breathing
  • unusual tiredness or weakness
  • weight gain
  • yellow eyes and skin

Is Tenofovir alafenamidee safe in pregnancy?

Tenofovir alafenamide containing fixed-dose drug combinations (FDCs) are increasingly being used in managing pregnant women living with HIV. However,Tenofovir alafenamide is not currently recommended during pregnancy due to limited pharmacokinetic and safety data.

Is Tenofovir alafenamide safe during breastfeeding?

Breastfeeding is not recommended during use of this drug.

Can I drink alcohol with Tenofovir alafenamide?

Avoid drinking alcohol. It may increase your risk of liver damage. Using this medicine will not prevent your disease from spreading.

When is the best time to take Tenofovir alafenamide?

For the best effect, take this medication at evenly spaced times. To help you remember, take this medication at the same time every day.

How is Tenofovir alafenamide eliminated?

Tenofovir alafenamide is minimally eliminated in urine. The pharmacokinetics of TAF and TFV in HIV-uninfected subjects with severe renal impairment and matched healthy controls were evaluated.

Will Tenofovir alafenamide affect my contraception?

Tenofovir alafenamide is unlikely to affect the pharmacokinetics of hormonal oral contraceptives.

Can Tenofovir alafenamide be crushed?

Tenofovir alafenamide should not be chewed, crushed, or split. Crushing of tablets is not recommended in the product information.

*** Taking medicines without doctor's advice can cause long-term problems.
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