Usage
- Favipiravir is an antiviral medication primarily used for the treatment of influenza in Japan. It is indicated for novel influenza strains (those causing more severe disease) that are unresponsive to standard antiviral therapies. It has also been investigated for its potential use against other viral infections, including COVID-19.
- Pharmacological classification: Antiviral agent, specifically a pyrazinecarboxamide derivative.
- Mechanism of action: Favipiravir is a prodrug that is metabolized to its active form, favipiravir-ribofuranosyl-5’-triphosphate (favipiravir-RTP). Favipiravir-RTP acts as a selective inhibitor of viral RNA-dependent RNA polymerase (RdRp), the enzyme responsible for viral RNA replication. By inhibiting RdRp, Favipiravir prevents viral replication within infected cells.
Alternate Names
- International/Regional Variations: T-705
- Brand Names: Avigan, Favikast, Favicovid, Fabihenz, Favtris, Favibest.
How It Works
- Pharmacodynamics: Favipiravir’s primary effect is the inhibition of viral RNA replication. It achieves this through the selective inhibition of viral RdRp. It mimics both guanosine and adenosine, interfering with viral primer extension.
- Pharmacokinetics: Favipiravir is administered orally and is rapidly and almost completely absorbed (bioavailability approximately 97.6%). It is metabolized to its active form, favipiravir-RTP, intracellularly. It is primarily cleared renally, with an elimination half-life of 2 to 5.5 hours.
- Mode of Action: Favipiravir-RTP acts as a purine nucleoside analogue. It inhibits viral RdRp. It mimics both guanosine and adenosine for the viral RdRp, leading to the prevention of RNA strand elongation and halting viral proliferation.
- Elimination Pathways: Primarily renal excretion. Minimal hepatic metabolism via aldehyde oxidase and uridine 5’-diphospho-glucuronosyltransferase (UGT), not CYP enzymes.
Dosage
Standard Dosage
Adults:
- The recommended dosage for influenza is 1600 mg twice daily on Day 1, followed by 600 mg twice daily on Days 2-5.
- For COVID-19, dosage regimens vary and may involve higher doses and longer durations (up to 14 days), typically 1800 mg twice on day one, then 800 mg twice daily.
- Administration is oral, preferably on an empty stomach. However, it may be taken with food to reduce gastrointestinal side effects.
Children:
- Use in children is not recommended due to limited safety and efficacy data.
Special Cases:
- Elderly Patients: Careful administration is advised. Dosage adjustments may be necessary based on renal function.
- Patients with Renal Impairment: Dose adjustment may be needed based on creatinine clearance.
- Patients with Hepatic Dysfunction: Increase in plasma levels has been reported. Careful monitoring and possible dosage adjustment are recommended.
- Patients with Comorbid Conditions: Use with caution in patients with gout, hyperuricemia, or other metabolic disorders. For patients with diabetes or taking anticoagulants such as warfarin, interactions must be considered.
Clinical Use Cases
Favipiravir is not typically used in clinical settings involving intubation, surgical procedures, mechanical ventilation, or ICU use. Emergency use is primarily for influenza pandemics or severe viral infections when other options are unavailable. For COVID-19 use is limited to mild to moderate cases.
Dosage Adjustments
Dose modifications may be required for patients with renal or hepatic dysfunction, gout, or other metabolic disorders. Consider drug interactions, especially with pyrazinamide, repaglinide, theophylline, famciclovir, acyclovir, and sulindac.
Side Effects
Common Side Effects
- Diarrhea
- Hyperuricemia (elevated uric acid levels)
- Nausea
- Vomiting
- Abdominal pain
- Decreased neutrophil count
Rare but Serious Side Effects
- Liver dysfunction (elevated liver enzymes)
- Severe allergic reactions (e.g., hives, skin rash, itching/swelling, severe dizziness, difficulty breathing)
- Thrombocytopenia (low platelet count)
- Psychiatric symptoms (e.g., abnormal behavior, delirium, hallucinations)
Long-Term Effects
Data on long-term effects are limited.
Adverse Drug Reactions (ADR)
- Stevens-Johnson syndrome
- Jaundice
- Pneumonia
- Shock
Contraindications
- Pregnancy (known or suspected) – Favipiravir is teratogenic in animals and is contraindicated in pregnancy.
- Breastfeeding – Excretion in breast milk and potential effects on infant are not fully characterized.
- Hypersensitivity to favipiravir or any component of the formulation.
Drug Interactions
- Pyrazinamide (increased risk of hyperuricemia)
- Repaglinide (risk of hypoglycemia)
- Theophylline (potential for altered levels)
- Famciclovir and acyclovir (potential interaction)
- Sulindac (potential interaction)
- Warfarin (potential interaction, careful INR monitoring required)
- Alcohol (interaction unknown, caution advised)
- Ritonavir (may decrease Favipiravir levels)
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Contraindicated. Favipiravir is known to be teratogenic in animal studies. It should not be used during pregnancy.
- Breastfeeding: Favipiravir is excreted in breast milk. Breastfeeding is contraindicated during favipiravir treatment.
- Safer alternative options should be considered for both pregnant and breastfeeding women.
Drug Profile Summary
- Mechanism of Action: Inhibits viral RNA polymerase (RdRp), preventing viral replication.
- Side Effects: Diarrhea, hyperuricemia, nausea, vomiting, liver dysfunction, allergic reactions.
- Contraindications: Pregnancy, breastfeeding, hypersensitivity.
- Drug Interactions: Pyrazinamide, repaglinide, theophylline, famciclovir, acyclovir, sulindac, warfarin.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: 1600 mg BID (Day 1), then 600 mg BID (Days 2-5) for influenza.
- Monitoring Parameters: Liver function tests, complete blood count (CBC), uric acid levels.
Popular Combinations
- Favipiravir is usually used as monotherapy. However, it may be used in combination with other antivirals in certain cases, but data on combinations is limited.
Precautions
- General Precautions: Evaluate renal and hepatic function, uric acid levels, and screen for gout before starting treatment. Monitor for adverse reactions throughout therapy.
- Specific Populations:
- Pregnant Women: Contraindicated.
- Breastfeeding Mothers: Contraindicated.
- Children & Elderly: Not recommended for children. Use with caution in elderly, adjusting dose for renal function.
- Lifestyle Considerations: Caution with alcohol, avoid if possible. Limited information is available on the impact on driving.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Favipiravir?
A: For influenza in adults, the recommended dosage is 1600 mg twice daily on Day 1, followed by 600 mg twice daily on Days 2-5. For COVID-19, dosage and duration may vary; a common regime is 1800 mg twice on day one, then 800mg twice daily for up to 14 days.
Q2: What is the mechanism of action of Favipiravir?
A: Favipiravir inhibits viral RNA-dependent RNA polymerase (RdRp), thus blocking viral replication.
Q3: What are the common side effects of Favipiravir?
A: Common side effects include diarrhea, hyperuricemia, nausea, vomiting, and decreased neutrophil count.
Q4: Is Favipiravir safe to use during pregnancy or breastfeeding?
A: No. Favipiravir is contraindicated in pregnancy and breastfeeding due to potential teratogenic and embryotoxic effects.
Q5: What are the significant drug interactions with Favipiravir?
A: Notable drug interactions include those with pyrazinamide, repaglinide, theophylline, famciclovir, acyclovir, sulindac, and warfarin. Ritonavir may decrease favipiravir levels.
Q6: How should Favipiravir be administered?
A: Favipiravir is administered orally, preferably on an empty stomach. However, taking it with food might reduce gastrointestinal upset.
Q7: What should be monitored in patients receiving Favipiravir?
A: Monitor liver function tests (LFTs), complete blood count (CBC), and uric acid levels regularly.
Q8: Can Favipiravir be used in children?
A: Use in children is not recommended due to insufficient safety and efficacy data.
Q9: Is Favipiravir effective against COVID-19?
A: It has shown some efficacy in treating mild to moderate COVID-19 but its use is not universal and depends on local guidelines and drug availability.
Q10: What precautions should men take when on Favipiravir?
A: Favipiravir is present in semen. Men should use effective contraception during treatment and for 7 days after the last dose to avoid potential fetal exposure. They should also avoid intercourse with pregnant women.
