Fabidac

Uses

Treatment of novel or re-emerging pandemic influenza virus infections (limited to cases in which other influenza antiviral drugs are ineffective or not sufficiently effective).
This drug is only approved as an experimental drug and still a lot of studies is needed about it’s efficacy and also toxic reactions and use in children.

Fabidac is also used to associated treatment for these conditions: Treatment resistant Novel Influenza, Treatment resistant Reemerging Influenza

How Fabidac works

The mechanism of action of favipiravir is novel compared to existing influenza antivirals that primarily prevent entry and exit of the virus from cells. The active favipiravir-RTP selectively inhibits RNA polymerase and prevents replication of the viral genome. There are several hypotheses as to how favipiravir-RTP interacts with RNA dependent RNA polymerase (RdRp). Some studies have shown that when favipiravir-RTP is incorporated into a nascent RNA strand, it prevents RNA strand elongation and viral proliferation. Studies have also found that the presence of purine analogs can reduce favipiravir’s antiviral activity, suggesting competition between favipiravir-RTP and purine nucleosides for RdRp binding.

Although favipiravir was originally developed to treat influenza, the RdRp catalytic domain (favipiravir's primary target), is expected to be similar for other RNA viruses. This conserved RdRp catalytic domain contributes to favipiravir's broad-spectrum coverage.

Dosage

Fabidac dosage

The usual adult dosage is 1600 mg of Fabidac administered orally twice daily on Day 1, followed by 600 mg orally twice daily from Day 2 to Day 5 or as directed by physicians. The total treatment duration should be 5 days.

Side Effects

Most common side effects are Diarrhea and increase of blood uric acid levels.

Toxicity

Based on single-dose toxicity studies, the lethal dose for oral and intravenous favipiravir in mice is estimated to be >2000 mg/kg. In rats, the lethal dose for oral administration is >2000 mg/kg, while the lethal dose in dogs and monkeys is >1000 mg/kg. Symptoms of overdose appear to include but are not limited to reduced body weight, vomiting, and decreased locomotor activity.

In repeat-dose toxicity studies involving dogs, rats, and monkeys, notable findings after administration of oral favipiravir included: adverse effects on hematopoietic tissues such as decreased red blood cell (RBC) production, and increases in liver function parameters such as aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and total bilirubin, and increased vacuolization in hepatocytes. Testis toxicity was also noted.

Fabidac is known to be teratogenic; therefore, administration of favipiravir should be avoided in women if pregnancy is confirmed or suspected.

Toxicity information regarding favipiravir in humans is not readily available.

Precaution

Fabidac should not be given in pregnant women, requirement of the confirmation of non-pregnancy in women of childbearing potential before use, thorough contraception measures from the start of the treatment to 7 days after the end of the treatment. Caution should be taken for Hepatic and renal impaired patient or use Fabidac as per the direction of registered Physician

Interaction

In animal studies, decreased RBC production,and increases in liver function parameters such as AST, ALP, ALT and total bilirubin, and increased vacuolization in hepatocytes. Toxicity information regarding Fabidac in humans is not readily available.

Food Interaction

Volume of Distribution

The apparent volume of distribution of favipiravir is 15 - 20 L.

Elimination Route

The bioavailability of favipiravir is almost complete at 97.6%. The mean Cmax for the recommended dosing schedule of favipiravir is 51.5 ug/mL.

Studies comparing the pharmacokinetic effects of multiple doses of favipiravir in healthy American and Japanese subjects are below:

Japanese subjects First Dose: Cmax = 36.24 ug/mL tmax = 0.5 hr AUC = 91.40 ugxhr/mL

American subjects First Dose: Cmax = 22.01 ug/mL tmax = 0.5 hr AUC = 44.11 ugxhr/mL

Japanese Subjects Final Dose: Cmax = 36.23 ug/mL Tmax = 0.5 hr AUC = 215.05 ugxhr/mL

American Subjects Final Dose: Cmax = 23.94 ug/mL Tmax = 0.6 hr AUC = 73.27 ugxhr/mL

When favipiravir was given as a single dose of 400 mg with food, the Cmax decreased. It appears that when favipiravir is given at a higher dose or in multiple doses, irreversible inhibition of aldehyde oxidase (AO) occurs and the effect of food on the Cmax is lessened.

Half Life

The elimination half-life of favipiravir is estimated to range from 2 to 5.5 hours.

Clearance

The recommended oral dosing regimen for favipiravir is as follows: Day 1: 1600 mg twice daily; Days 2-5: 600 mg twice daily.

The reported CL/F for favipiravir 1600 mg dosed once daily is 2.98 L/hr ±0.30 and the CL/F values for favipiravir 600 mg dosed twice daily on days 1-2 and once daily on days 3-7 were 6.72 L/hr ±1.68 on Day 1, and 2.89 L/hr ±0.91 on Day 7. There is currently no reported clearance data for favipiravir 1600 mg dosed twice daily.

Elimination Route

Fabidac's metabolites are predominantly renally cleared.

Pregnancy & Breastfeeding use

Fabidac may cause delayed development or death of embryos during the early stage of pregnancy. Should not be given during pregnancy.

Contraindication

Fabidac is contraindicated for pregnant women and women who may possibly be pregnant.

Acute Overdose

In animal studies, decreased RBC production,and increases in liver function parameters such as AST, ALP, ALT and total bilirubin, and increased vacuolization in hepatocytes. Toxicity information regarding Fabidac in humans is not readily available.

Storage Condition

Keep below 30°C temperature, protected from light & moisture. Keep out of the reach of children.

Innovators Monograph

You find simplified version here Fabidac