TM

[ F a v i p i r a v i r ]
Tablets 200mg
Favipiravir is a viral RNA polymerase inhibitor that has demonstrated Inhibitory concentration (IC50) of Favipiravir RTP on human RNA
efficacy against a broad spectrum of RNA viruses. It has also polymerase II was 905 μmol/L.
demonstrated promising clinical evidence, with positive results in mild to
moderate COVID-19 cases. Pharmacokinetics
Favipiravir can be used for coronavirus patients with co-morbid Absorption
conditions such as diabetes and heart disease. It offers rapid reduction in The following table shows pharmacokinetic parameters of Favipiravir
viral load and provides faster symptomatic and radiological improvement. after an oral administration in adults at 1600mg twice daily for 1 day, then
Favipiravir provides a substitute for compassionate use in COVID-19 600mg twice daily for 4 days followed by 600mg once daily for 1 day
based on its mechanism of action inhibiting virus RNA-dependent RNA (1600mg / 600mg BID).
polymerase (RdRp) and safety data in clinical studies. Its definite dosage
and duration of therapy for COVID-19 is still under clinical investigation. Pharmacokinetic parameters of Favipiravir
Dosage studied for COVID-19 infection in published clinical trials is:
Cmax AUC Tmax T1/2
Day 2 to min Dosage (μg/mL) (μg.hr/mL) (hr) (hr)
Day 1 Day 7(a) or max 64.56 446.09 1.5
Day 14(b) Day 1 (17.2) (28.1) (0.75, 4) 4.8±1.1
1600mg /
Total Daily Dose 1600mg BID 600mg BID 600mg BID 64.69 553.98 1.5
Day 6 (24.1) (31.2) (0.75, 2) 5.6±2.3

Morning 8 Tablets (1600mg) 3 Tablets (600mg) Distribution

When Favipiravir was orally administered to adult male subjects at
Evening 8 Tablets (1600mg) 3 Tablets (600mg) 1200mg twice daily for 1 day followed by 800mg twice daily for 4 days
(1200mg / 800mg BID), the geometric mean concentration of the drug in
semen was 18.341μg/mL on Day 3, and 0.053μg/mL on the second day
Further, the dose of Favipiravir Tablets for the treatment of COVID-19 as after the treatment. The semen levels became below the limit of
approved by DCGI is: quantification (0.02μg/mL) in all subjects in 7 days after the end of the
treatment. The mean ratio of the drug concentration in semen to that in
Day 2 to max
Day 1 plasma was 0.53 on Day 3 and 0.45 on the second day after the
Day 14
treatment.
Total Daily Dose 1800mg BID 800mg BID
Metabolism
Favipiravir was not metabolized by cytochrome P-450 (CYP), mostly
Morning 9 Tablets (1800mg) 4 Tablets (800mg) metabolized by aldehyde oxidase (AO), and partly metabolized to a
hydroxylated form by xanthine oxidase (XO). A glucuronate conjugate
Evening 9 Tablets (1800mg) 4 Tablets (800mg) was observed in human plasma and urine as a metabolite other than the
hydroxylated form.
At higher doses proposed for COVID-19, QT interval monitoring, LFT
monitoring and plasma level monitoring of the drug may be needed. Excretion
(a) Chen, C., Huang, J., Cheng, Z., Wu, J., Chen, S., Zhang, Y., ... & Yin, P. (2020). Favipiravir was mainly excreted as a hydroxylated form into the urine,
Favipiravir versus arbidol for COVID-19: a randomized clinical trial. MedRxiv. and little amount unchanged drug was observed. In an oral 7 day multiple
(b) Cai, Q., Yang, M., Liu, D., Chen, J., Shu, D., Xia, J., ... & Yang, Y. Experimental
treatment with favipiravir for COVID-19: an open-label control study. Engineering dose study with healthy adults, cumulative urinary excretion ratio of the
2020. S2095809920300631, doi, 10. unchanged drug and the hydroxylated form was 0.8% and 53.1%,
respectively, during 48 hours after the last administration.
DESCRIPTION
Piravir contains Favipiravir which is a new antiviral drug that selectively Special population
and potently inhibits the RNA-dependent RNA polymerase (RdRp) of Patients with hepatic impairment
RNA viruses. Chemically, Favipiravir is When Favipiravir was orally administered to subjects with mild and
6-Fluoro-3-hydroxypyrazine-2-carboxamide. Its molecular formula is moderate liver function impairment (Child-Pugh classification A and B) at
C5H4FN3O2 and the structural formula is: 1200mg twice daily for 1 day followed by 800mg twice daily for 4 days
(1200mg / 800mg BID), compared to healthy adult subjects, Cmax and
O AUC at day 5 were approximately 1.6 fold and 1.7 fold, respectively in
subjects with mild liver function impairment, and 1.4 fold and 1.8 fold,
F N respectively in subjects with moderate liver function impairment.
NH2
When Favipiravir was orally administered to subjects with severe liver
function impairment (Child-Pugh classification C) at 800mg twice daily for
1 day followed by 400mg twice daily for 2 days (800mg / 400mg BID),
N OH
compared to healthy adult subjects, Cmax and AUC at day 3 were
Favipiravir approximately 2.1 fold and 6.3 fold, respectively.

QUALITATIVE AND QUANTITATIVE COMPOSITION Elderly

Piravir (Favipiravir) Tablets are available for oral administration as: Since the elderly often have reduced physiological functions, Favipiravir
should be administered with care to them by monitoring their general
Piravir Tablets 200mg conditions.
Each film-coated tablet contains:
Favipiravir…200mg THERAPEUTIC INDICATIONS
Piravir (Favipiravir) is indicated for treatment of novel or re-emerging
CLINICAL PHARMACOLOGY pandemic influenza virus infections (Limited to cases in which other
Mechanism of Action influenza antiviral drugs are ineffective or not sufficiently effective).
It is considered that Favipiravir is metabolized in cells to a ribosyl
triphosphate form (Favipiravir RTP) and that Favipiravir RTP selectively DOSAGE AND ADMINISTRATION
inhibits RNA polymerase involved in influenza viral replication. With The usual adult dosage for treatment of influenza virus infection is
regards to the activity against human DNA polymerases α, β and γ, 1600mg of Favipiravir administered orally twice daily on Day 1, followed
Favipiravir RTP (1000 μmol/L) showed no inhibitory effect on α, by 600mg orally twice daily from Day 2 to Day 5. The total treatment
9.1-13.5% inhibitory effect on β and 11.7-41.2% inhibitory effect on γ. duration should be 5 days.
CONTRAINDICATIONS Pregnancy
Favipiravir is contraindicated in: Early embryonic deaths and teratogenicity have been observed in animal
• Patients with known hypersensitivity to Favipiravir or to any excipient studies with exposure levels similar to or lower than the clinical exposure.
of the product. Do not administer Favipiravir to women known or suspected to be
• Women known and suspected to be pregnant. pregnant.

ADVERSE REACTIONS Nursing Mothers

The following clinically significant adverse reactions have been reported The major metabolite of Favipiravir, a hydroxylated form, was found to be
with other anti-influenza virus agents. Patients should be carefully distributed in breast milk. When administering Favipiravir to lactating
monitored, and if any abnormality is observed, the treatment should be women, instruct to stop lactation.
discontinued and appropriate measures should be taken.
Shock, anaphylaxis, pneumonia, hepatitis fulminant, hepatic dysfunction, DRUG INTERACTIONS
jaundice, toxic epidermal necrolysis (TEN), oculomucocutaneous In vitro: Favipiravir inhibited irreversibly AO in a dose and time dependent
syndrome (Stevens-Johnson Syndrome), acute kidney injury, white manner, and inhibited CYP2C8 in a dose dependent manner. There were
blood cell count decreased, neutrophil count decreased, platelet count no inhibitory activity to XO, and weak inhibitory activity to CYP1A2, 2C9,
decreased, neurological and psychiatric symptoms (consciousness 2C19, 2D6, 2E1 and 3A4. The hydroxylated metabolite showed weak
disturbed, abnormal behavior, deliria, hallucination, delusion, convulsion, inhibitory activity to CYP1A2, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4.
etc.) and colitis hemorrhagic. Favipiravir should be administered with care when co-administered with
the following drugs:
If the following adverse reactions occur, appropriate measures should be
taken according to the symptoms: Mechanism &
Drugs Signs
AST (GOT) increased, ALT (GPT) increased, γ-GTP increased, diarrhea, Risk Factors
neutrophil count decreased, white blood cell count decreased, blood uric
Pyrazinamide Blood uric acid level Reabsorption of uric
acid increased, blood triglycerides increased, rash, nausea, vomiting,
increases. When acid in the renal tubule
abdominal pain, glucose urine present, eczema, pruritus, blood ALP
pyrazinamide 1.5g once is additively enhanced.
increased, blood bilirubin increased, abdominal discomfort, duodenal
daily and Favipiravir
ulcer, haematochezia, gastritis, white blood cell count increased,
1200mg / 400mg BID were
reticulocyte count decreased, monocyte increased, blood potassium
administered, the blood
decreased, asthma, oropharyngeal pain, rhinitis, nasopharyngitis, blood
uric acid level was 11.6
CK (CPK) increased, blood urine present, tonsil polyp, pigmentation,
mg/dL when pyrazinamide
dysgeusia, bruise, vision blurred, eye pain, vertigo and supraventricular
was administered alone,
extrasystoles.
and 13.9mg/dL in
combination with
“To report SUSPECTED ADVERSE REACTIONS to Getz Pharma’s
Favipiravir.
Pharmacovigilance Section, please contact at
[email protected] or +92-21-38636363” Repaglinide Blood level of repaglinide Inhibition of CYP2C8
may increase, and adverse increases blood level of
WARNINGS reactions to repaglinide repaglinide.
• Since early embryonic deaths and teratogenicity have been observed may occur.
in animal studies for Favipiravir, do not administer the drug to women
Theophylline Blood level of Favipiravir Interaction with XO may
known or suspected to be pregnant.
may increase, and adverse increase blood level of
• When administering Favipiravir to women of child-bearing potential,
reactions to Favipiravir may Favipiravir.
confirm a negative pregnancy test result before starting the treatment.
occur.
Explain fully the risks and instruct thoroughly to use most effective
contraceptive methods with her partner during and for 7 days after the Efficacy of these drugs may Inhibition of AO by
Famciclovir
end of the treatment. If pregnancy is suspected during the treatment, be reduced. Favipiravir may
Sulindac
instruct to discontinue the treatment immediately and to consult a decrease blood level of
doctor. active forms of these
• Favipiravir is distributed in sperm. When administering the drug to drugs.
male patients, explain fully the risks and instruct thoroughly to use
most effective contraceptive methods in sexual intercourse during STORAGE
and for 7 days after the end of the treatment (men must wear a Do not store above 30°C.
condom). In addition, instruct not to have sexual intercourse with Protect from sunlight and moisture.
pregnant women.
• Prior to the treatment, explain thoroughly the efficacy and risk The expiration date refers to the product correctly stored at the required
(including the risk of exposure to fetus) to patients or their family conditions.
members.
• Examine carefully the necessity of Favipiravir before use. HOW SUPPLIED
Piravir (Favipiravir) Tablets 200mg are available in blister pack of 20’s.
PRECAUTIONS
• Favipiravir is a drug, the use of which is considered only when there Keep out of reach of children.
is an outbreak of novel or re-emerging influenza virus infections in
which other anti-influenza virus agents are not effective or To be sold on prescription of a registered medical practitioner only.
insufficiently effective.
• Favipiravir is not effective against bacterial infections.
• Favipiravir is not recommended for use in children. Please read the contents carefully before use.
• Favipiravir should be administered with care in patients with gout or a This package insert is continually updated from time to time.
history of gout, and patients with hyperuricaemia (Blood uric acid level
may increase, and symptoms may be aggravated).
• Increase plasma level of Favipiravir has been reported in patients with
liver function impairment.
• Psychoneurotic symptoms such as abnormal behavior after
administration of Favipiravir have been reported. Patients / their
family should be instructed that after the start of treatment abnormal
behavior may be developed, and patients are not left alone for at least
2 days when they are treated at home. Since similar symptoms
associated with influenza encephalopathy have been reported, the Manufactured by:
same instruction as above should be given.
• Influenza virus infection may be complicated with bacterial infections
or may be confused with influenza-like symptoms. In case of bacterial
infection or suspected to be bacterial infection, appropriate measures
L-200012569
should be taken, such as administration of anti-bacterial agents.