Favipravir Prescribing Guide

FAVIPRAVIR 200 mg TABLET (HAIFUKANG®)
WARNINGS FOR PRESCRIBER (following product leaflet)	PRIOR to the TREATMENT, EXPLAIN THOROUGHLY the efficacy and risks (including risk of exposure to fetus) IN WRITING to patients or their family members and OBTAIN their WRITTEN CONSENT. Kindly refer to the information below – especially on pregnancy, women of child-bearing potential and men.
Pregnancy	Contraindicated - Teratogenic & embryotoxic in animal studies
Women of Child-bearing Potential	Confirm a negative pregnancy test result before starting favipravir. Explain risks fully, advise for effective contraception during & for 7 days after end of treatment. If pregnancy suspected during the treatment, discontinue favipravir immediately and consult a doctor.
Lactation	·          Major metabolite of favipravir was found to be distributed in breast milk. ·          STOP LACTATION when administering favipravir to lactating women.
Men	Favipravir is distributed in the sperms. Explain risks fully, advise for effective contraception during & for 7 days after end of treatment. Avoid sexual intercourse with pregnanct women.
Therapeutic indications	For the treatment of novel or re-emerging influenza (only used when other anti-influenza virus agents are insufficiently effective) – licensed in Japan & China
Dosage	Influenza Started prompty after the onset of influenza-like symptoms. Total for 5 days. 1600 mg BD x 1/7 , then 600 mg BD COVID-19 [OFF-LABEL] 1.     Dosing for COVID-19 in adults [based on latest slide available from ID Team, HQE @ 28.08.2020]: 1800 mg BD x 1/7 , then 800 mg BD [Total duration = 5-10 days] *Teratogenic effect: contraindicated for women of childbearing potential and men whose partner is of childbearing potential. Avoid if GFR < 30 mL/min 2.     Dosing for COVID-19 in adults [based on most available literature]: 1600 mg BD x 1/7 , then 600 mg BD [Total duration = 7-14 days] 3.     Because high favipiravir concentrations are required for in vitro activity against SARS-CoV-2, it has been suggested that high favipiravir dosages, like those used in the treatment of Ebola virus disease, should be considered for the treatment of COVID-19. One such favipiravir regimen used in the treatment of Ebola virus disease includes: *Day 1: 2400 mg at 0 hr, 2400 mg at 8 hr, 1200 mg at 16 hr, then *Day 2-10: 1200 mg BD
Administration	Take on empty stomach
Adverse reactions (based on physical product leaflet)	Adverse Reaction ≥ 1% 0.5-1 % < 0.5% Hypersensitivity ·    Rash ·    Eczema, pruritus Hepatic ·   AST increased ·   ALT increased ·   γ-GTP increased ·   ALP increased ·   Blood bilirublin increased Gastrointestinal ·   Diarrhoea (4.8%) ·   Nausea ·   Vomitting ·   Abdominal pain ·   Abdominal discomfort ·   Duodenal ulcer ·   Haematochezia ·   Gastritis Haematologic ·   Neutrophil ↓ ·   White blood cell ↓ ·   White blood cell ↑ ·   Monocyte ↑ ·   Reticulocyte ↓ Metabolic disorder ·   Uric acid ↑ ·   Triglycerides ↑ ·   Glucosuria ·   Blood potassium ↓ Respiratory ·   Asthma ·   Oropharyngeal pain ·   Rhinitis ·   Nasopharyngitis Others ·   Blood CK ↑ ·   Haematuria ·   Tonsil polyp ·   Pigmentation ·   Dysgeusia (taste distortion) ·   Bruise ·   Blurred vision ·   Eye pain ·   Vertigo ·   Supraventricular extrasystoles
Contraindications	·         Women known or suspected to be pregnant ·         Hypersensitvity to any ingredient of the drug
Special Population	·       Paediatric: Safety and efficacy have NOT been established. Psychoneurotic symptoms such as abnormal behaviour have been reported following following administration of anti-influenza virus agents. Patient/Family should be informed on this and arrangement made so that children/minors are not left alone (for at least 2 days when they are treated at home).   ·       Elderly: Limited clinical data. Carefully evaluate for benefits risks, or as directed by a physician. ·       Renal impairment: Plasma concentration of metabolites of favipravir may increase. Adequate information is NOT available on safety in patients with renal dysfunction. ·       Liver impairment: Plasma concentration of favipravir may increase.
Potential Drug interactions	·       Favipravir is mostly metabolised by aldehyde oxidase (AO). ·       It is partly metabolised to a hydroxylated form by xanthine oxidase (XO). ·       It inhibits CYP2C8 in a dose dependant manner. ·       May enhance uric acid level when co-administered with pyrazinamide. ·       May increase blood level of repaglinide and paracetamol. ·       May reduce blood level of famciclovir and sulindac. ·       Co-administration with theophylline / aminophylline may increase favipravir plasma level. ·       Other potential drug-drug interaction with favipravir: §  Pioglitazone §  Moxonidine §  Treprostinil §  Most hormonal contraception / HRT (additional action such as dose adj may not be required) For most updated interaction resources, kindly refer to: https://www.covid19-druginteractions.org/checker or https://www.covid19-druginteractions.org/prescribing-resources

References

1.        Product leaflet: Favipravir 200 mg Tablet - Haifukang 海复康

2.        UpToDate [online]: Drug information: Favipravir

3.        Assessment of Evidence for COVID-19-Related Treatments: Updated 8 May 2020

4.        Interactions with Experimental COVID-19 Therapies. Liverpool Drug Interaction Group, University of Liverpool. Updated on 5 May 2020.  

General resources for COVID-19: https://www.covid19-druginteractions.org/prescribing-resources

All info accessed on 10 May 2020

Prepared by J. Ho [10 May 2020]

Tocilizumab Administration Guide

TOCILIZUMAB 400 MG  / 20 ML (20 MG/ML) ACTEMRA®			FRIDGE item NOT in HKGU Formulary
ROUTE	DILUTION	INFUSION RATE
INTRAVENOUS	Dilute to final volume of 100 ml NS 2,3	Infused over 1 hr 2,3 (using a dedicated IV line) 3
	Allow diluted solution for infusion to reach room temperature prior to administration 3
DILUENT	NS 1
STABILITY	·       For vials: Store at 2-8ºC. DO NOT freeze. Keep container in outer carton to protect from light 1 ·       For prepared infusion solution: Physically and chemically stable in 0.9% NaCl at 30ºC for 24 hrs (provided aseptic techniques applied). 1 ·       Only solutions which are clear to opalescent, colourless to pale yellow and free of visible particles must be infused. 1,3
DOSING	·       Limited data available; dosing used in clinical trials includes the following: 3 §  4-8 mg/kg (usual dose: 400 mg/dose; max: 800 mg/dose) as a single dose; may repeat dose in ≥12 hours in patients who remain febrile within 24 hours of initial dose (NIH 2020c). §  8 mg/kg (max: 800 mg/dose) as a single dose; may repeat dose in 8-12 hours if signs/symptoms worsen or do not improve (Genentech 2020). §  8 mg/kg (max: 800 mg/dose) every 12 hours for 2 doses (NIH 2020a). §  8 mg/kg as a single dose (NIH 2020b; NIH 2020e). HOWEVER, LATEST SLIDE available from ID Team, HQE @ 28.08.2020: Dose recommended: 8 mg/kg single dose (MAX: 800 mg/dose). ·       Tocilizumab may reduce the serum concentration of chloroquine and ritonavir (component of Kaletra). 4 ·       The renal dosing recommendations are based upon the best available evidence and clinical expertise: 3 CrCl (mL/min) Suggested Renal Adjustment ≥30 No dosage adjustment necessary. <30 There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, based on tocilizumab's molecular weight (148 kDa), it is unlikely to be significantly renally eliminated (expert opinion).
ADVERSE REACTIONS	>10% 1-10% o Increased serum cholesterol (20%) o Increased ALT (≤36%) o Increased AST (≤22%) o Infusion-related reaction (4-20%) o Hypertension (6%) o Peripheral edema (<2%) o Skin rash (2%) o Leukopenia (<2%) o Thrombocytopenia (1%) o Increased serum bilirubin (<2%) o Herpes simplex infection (<2%) o  Headache (7%) o  Nasopharyngitis (7%) o  URTI (7%) o  Conjunctivitis (<2%) o Hypothyroidism (<2%) o Increased LDL (9%) o Nephrolithiasis (<2%) o Gastric ulcer (<2%) o Oral mucosa ulcer (2%) o Stomatitis (<2%) o Upper abdominal pain (2%) o Weight gain (<2%) o Bronchitis (3%) o Cough (<2%) o Dyspnea (<2%)
REFERENCES	1.     Product Leaflet (Actemra - Roche). 2.     COVID-19 treatment and drug doses [Sarawak General Hospital, updated 23.03.2020] 3.     UptoDate: Tocilizumab: Drug information [Accessed online on 8 May 2020] 4.     UptoDate: Drug Interaction Checker [Accessed online on 8 May 2020]
Prepared by J. Ho [8 May 2020]