Nexataf 25 mg Tablet

Uses

Nexataf 25 mg Tablet 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.

Nexataf 25 mg Tablet 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 Nexataf 25 mg Tablet 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

Nexataf 25 mg Tablet dosage

Testing Prior To Initiation Of Nexataf 25 mg Tablet: Prior to initiation of Nexataf 25 mg Tablet, patients should be tested forHIV-1 infection. Nexataf 25 mg Tablet 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 Nexataf 25 mg Tablet and during therapy in all patients as clinically appropriate

Recommended Dosage In Adults: The recommended dosage of Nexataf 25 mg Tablet 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 Nexataf 25 mg Tablet, 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 Nexataf 25 mg Tablet will harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with Nexataf 25 mg Tablet.

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 Nexataf 25 mg Tablet in pediatric patients less than 18 years of age have not been established.

Geriatric Use: Clinical trials of Nexataf 25 mg Tablet 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 Nexataf 25 mg Tablet is required in patients with mild, moderate, or severe renal impairment. Nexataf 25 mg Tablet is not recommended in patients with end stage renal disease (estimated creatinine clearance below 15 mL per minute)

Hepatic Impairment: No dosage adjustment of Nexataf 25 mg Tablet is required in patients with mild hepatic impairment (Child-Pugh A). The safety and efficacy of Nexataf 25 mg Tablet in patients with decompensated cirrhosis (Child-Pugh B or C) have not been established; therefore Nexataf 25 mg Tablet 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 Nexataf 25 mg Tablet 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

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