Html code will be here
Coronavir
Antiviral drug for the treatment of COVID-19
Coronavir (MNN: favipiravir), 200 mg, film-coated tablets, shelf-life:1,5 years, manufactured by R-Pharm, JSC (marketing authorization No. LP-006323 dated 06.07.2020). Use by medical prescription, before starting please see the Full Prescribing Information.
Coronavir is the only drug containing favipiravir approved in the Russian Federation, the efficacy of Coronavir was proven in outpatient subjects in the clinical study.
Using Coronavir at an early stage of coronavirus infection, including out-patient treatment regimen, helps to minimize the risk of the development of life-threatening complications requiring hospitalization.
Coronavir can be prescribed for out-patient use, and it is particularly important for self-isolated patients with mild and moderate symptoms of the disease, who do not require hospitalization at this moment.
Out-patient treatment regimen will potentially reduce the load of the hospital stock of specialized medical centers and help healthcare system to function in a more cost-efficient way.
Summary of product characteristics: Coronavir
Indications for use
Novel Coronovirus (COVID-19) treatment.
Treatment regimen
The drug is administered orally, 30 minutes before a meal.
Recommended dosage regimen to treat coronavirus infection (COVID-19), caused by virus SARS-CoV-2 is provided below:
The drug should be prescribed after laboratory confirmation of the diagnosis and/or in the presence of typical clinical symptoms.
Novel Coronovirus (COVID-19) treatment.
Treatment regimen
The drug is administered orally, 30 minutes before a meal.
Recommended dosage regimen to treat coronavirus infection (COVID-19), caused by virus SARS-CoV-2 is provided below:
- For patients with body weight <75 kg: 1600 mg (8 tablets) twice daily on Day 1, then 600 mg (3 tablets) twice daily on Days 2-10; the entire treatment course requires 70 tablets;
- For patients with body weight ≥75 kg: 1800 mg (9 tablets) twice daily on Day 1, then 800 mg (4 tablets) twice daily on Days 2-10; the entire treatment course requires 90 tablets.
The drug should be prescribed after laboratory confirmation of the diagnosis and/or in the presence of typical clinical symptoms.
- Coronavir is manufactured in accordance with the highest quality standards at the Yaroslavl plant of finished dosage forms and biotechnological substances (R-Pharm, JSC). It is a modern enterprise with a GMP certificate that provides contract manufacturing services not only to domestic, but also to leading foreign pharmaceutical companies.
- Coronavir is manufactured using an ultra-pure pharmaceutical substance with an extremely low content of impurities.
- The list of excipients of Coronavir is similar to the one of Avigan (reference favipiravir-containing drug). Comparative studies have shown that the dissolution profile of Coronavir is completely equivalent to the dissolution profile of Avigan.
- Toxicity (acute, chronic, and genotoxicity) and pharmacokinetic studies on various animal species (mice, rats, and rabbits) have shown that the toxicity and pharmacokinetic profile of Coronavir correspond to the profile of the reference drug.
- Coronavir's packages are labeled with Data Matrix codes, which provides additional protection against counterfeiting and makes it possible to verify information about the drug, including the data on the manufacturer and shelf-life, using the "Honest Sign" mobile app in the pharmacy.
Clinical studies of Coronavir
Efficacy, safety, and pharmacokinetics of Coronavir were studied in Phase III, Open-Label, Multicenter, Randomized Clinical Study in Patients with Mild and Moderate Course of Coronavirus Infection (COVID-19).
The name of study: Open-label, Multicenter, Randomized, Parallel Group Clinical Study to Assess Efficacy and Safety of TL-FVP-t in Comparison with Standard of Care Treatment in Patients with Mild and Moderate Course Coronavirus Infection (SARS-CoV-2/COVID-19); protocol number TL-FVP-t-01, permission of the Ministry of Health of the Russian Federation № 201 of May 20, 2020.
Reference to the State Register of Clinical Trials
Reference to the State Register of Clinical Trials
Study Design
Study population:
168 patients with a mild and moderate COVID-19 (127 out-patient and 41 in-patients with a 3:1 ratio) were enrolled in the study.
Study groups:
Details: The study was performed with the support of the central laboratory for PCR-diagnostics. Verification of CT data was performed by Central Committee.
The number of centers: 16 (10 active centers — 4 out-patient; 6 — in-patient).
Regions: Moscow and the Moscow Region, St. Petersburg and the Leningrad Region, Voronezh.
168 patients with a mild and moderate COVID-19 (127 out-patient and 41 in-patients with a 3:1 ratio) were enrolled in the study.
Study groups:
- Coronavir 1800 mg (9 tablets) twice daily on the first day, then 800 mg (tablets) twice daily (days 2-10).
- Standard therapy (control) group (umefenovir + intranasal interferon alfa; or chloroquine).
Details: The study was performed with the support of the central laboratory for PCR-diagnostics. Verification of CT data was performed by Central Committee.
The number of centers: 16 (10 active centers — 4 out-patient; 6 — in-patient).
Regions: Moscow and the Moscow Region, St. Petersburg and the Leningrad Region, Voronezh.
Main criteria of patients' inclusion / exclusion in the study
- Mild to moderate COVID-19.
- The presence of SARS-CoV-2, confirmed by a positive result of a PCR test from the oropharynx/nasopharynx.
- The duration of the disease in patients (from the appearance of the first symptoms or the delivery of biomaterial for PCR no more than 6 days before randomization).
- Patients should not have received etiotropic therapy for COVID-19.
- Age from 18 to 60 years old.
- Absence of significant somatic pathology.
End points
Primary points
- Time to improvement in clinical status (defined as a decrease in the WHO Clinical Improvement Ordinal Scale score by at least 1 category).
- Time to the elimination of the virus (defined as the absence of SARS-CoV-2 based on the results of 2 consecutive PCR tests with an interval of at least 24 hours).
- The proportion of patients (%) with an improvement in clinical status at selected time points from the beginning of therapy.
- The proportion of patients (%) with established elimination of the virus at separate time points from the beginning of therapy.
- Percentage of patients (%) with a resolution of lung changes on CT on day 14 (from initiation of therapy).
- Time until the temperature returns to normal.
Results of the final analysis
Results of the final analysis are published in the journal "INFECTIOUS DISEASE: news, opinions, education.": T.A. Ruzhentsova, P. V. Chukhlyaev, D. A. Khavkina et al. Efficacy and safety of using favipiravir in complex therapy of mild and moderate COVID-19. Efficacy and safety of using favipiravir in complex therapy of mild and moderate COVID-19 low and moderate severity. // Infectious disease: news, opinions, education. 2020. V. 9, № 4. С. 00–00. (in Russ.) The full publication is available here.
Results of interim analysis
The clinical trial interim analysis results were published in the journal "Medical opponent": T.A. Ruzhentseva, P.V. Chukhlyaev, D.A. Khavkina et al. Etiotropic therapy options for treatment of coronavirus infection caused by SARS-CoV-2 in outpatient patients. Medical opponent, 2020;1 (9): 48-58. (in Russ.) The full publication is available here.
Characteristics of the patients
included in the study:
Full analysis set: 60 patients
Study groups:
included in the study:
Full analysis set: 60 patients
Study groups:
- Coronavir group - 40
- Control group - 20
Cohorts: all patients were included
in the outpatient cohort
The severity of the disease:
in the outpatient cohort
The severity of the disease:
- mild severity - 45% of patients
- moderate severity - 55% of patient
Efficacy
Primary endpoints
In comparison with the standard therapy (control) group, the patients treated with Coronavir show more rapid resolution of COVID-19 symptoms:
Primary endpoints
In comparison with the standard therapy (control) group, the patients treated with Coronavir show more rapid resolution of COVID-19 symptoms:
- clinical improvement was achieved 3 days earlier than in the control group (the difference is statistically significant)
- elimination of the virus was achieved on average 1 day earlier.
Note: the mean values (±SD) are presented;
*the statistical analysis was performed using a log-rank test;
**to the WHO scale;
***the difference is statistically significant
*the statistical analysis was performed using a log-rank test;
**to the WHO scale;
***the difference is statistically significant
Time to clinical status improvement according to WHO scale,
Kaplan-Mayer curves (n = 60):
Kaplan-Mayer curves (n = 60):
Primary, secondary, and exploratory endpoints:
- Percentage of patients with clinical status improvement in different time points: there was a considerable difference between the rate of clinical improvement in Coronavir group on the 7th and 14th day in comparison with the control group.
- Percentage of patients with complete elimination of the virus: the difference between groups in virus elimination rate was observed on the 3rd and 5th day of the therapy, but it was not significant (due to the small sample size).
Note: The statistical analysis was performed using Fisher exact test; *the difference is statistically significant.
Percentage of patients (%) demonstrating improvement or deterioration of coronavirus pneumonia on CT scans on Day 5
There was clinically significant difference between Coronavir and control group in terms of the convalescence rate detected by CT scans to Day 5
Full Prescribing Information of Coronavir
SAFETY
Coronavir is characterized by a favorable safety and tolerability profile, corresponding to the historical data for favipiravir. According to the results of the studies, Coronavir is generally well-tolerated by the patients
Safety data in clinical trials of Coronavir
- In a clinical study of the 3rd phase of the drug Koronavir, adverse reactions were observed in 70 out of 108 (63.9%) patients, including: hyperuricemia (43 patients (39.8%)), increased ALT (36 patients (33.33 %)), increased AST (24 patients (22.2%)), diarrhea (16 patients (14.8%)), increased creatine kinase (15 patients (13.9%)), hyperglycemia (11 patients (10.2%)), sinus bradycardia (10 patients (9.3%)), nausea (9 patients (8.3%)), abdominal pain (8 patients (7.4%)), pain in the upper abdomen (7 patients (6.5%)), increased LDH (6 patients (5.6%)), headache (4 patients (3.7%)), skin rash (4 patients (3.7%)), hyperbilirubinemia (4 patients (3.7%)), sinus tachycardia (3 patients (2.8%)), hematuria (2 patients (1.9%)), hyperhidrosis (1 patient (0.9%)), chilliness of the feet (1 patient (0.9%)), muscle weakness (1 patient (0.9%)), eye pain (1 patient (0, 9%)), dizziness (1 patient (0.9%)), vomiting (1 patient (0.9%)), increased blood pressure (1 patient (0.9%)), increased ferritin levels (1 patient (0.9%)), hypercreatininemia (1 patient (0.9%) )), leukocyturia (1 patient (0.9%)), the presence of bilirubin in the urine (1 patient (0.9%)), an increase in the level of urobilinogen in the urine (1 patient (0.9%)), proteinuria (1 patient (0.9%)), glucosuria (1 patient (0.9%)), thrombocytosis (1 patient (0.9%)), casts in urine (1 patient (0.9%) )).
- During the therapy with favipiravir, the most common side effect is a transient increase in blood uric acid levels.
Literature data on adverse reactions while using favipiravir
The following adverse reactions were observed in clinical studies of other favipiravir drugs in patients with influenza infection (data from a pooled population analysis pooled to assess safety). Estimation of the incidence of unwanted adverse reactions is based on the WHO classification: very often (≥1 / 10); often (≥1 / 100 to <1/10); infrequently (≥1 / 1000 to <1/100); rarely (≥1 / 10,000 to <1/1000); very rare (<1/10 000); the frequency is unknown (it is not possible to establish the frequency from the available data).
Blood disorders of the lymphatic system:
Often: neutropenia, leukopenia;
Rarely: leukocytosis, monocytosis, reticulocytopenia.
Metabolic and nutritional disorders:
Often: hyperuricemia, hypertriglyceridemia;
Uncommon: glucosuria;
Rare: hypokalemia.
Immune system disorders:
Uncommon: rash;
Rarely: eczema, itching.
Respiratory, chest, and mediastinal disorders:
Rarely: bronchial asthma, sore throat, rhinitis, nasopharyngitis
Gastrointestinal disorders:
Often: diarrhea;
Uncommon: nausea, vomiting, abdominal pain;
Rarely: abdominal discomfort, duodenal ulcer, bloody stools, gastritis.
Hepatic biliary tract disorders:
Often: increased ALT activity, increased AST activity, increased glutamyl transferase (GGT) activity;
Rarely: an increase in the activity of alkaline phosphatase (ALP), an increase in the concentration of bilirubin in the blood.
Others:
Rarely: abnormal behavior, increased activity of creatine phosphokinase (CPK), hematuria, laryngeal polyp, hyperpigmentation, impaired taste sensitivity, hematoma, blurred vision, eye pain, vertigo, supraventricular extrasystoles, chest pain.
Blood disorders of the lymphatic system:
Often: neutropenia, leukopenia;
Rarely: leukocytosis, monocytosis, reticulocytopenia.
Metabolic and nutritional disorders:
Often: hyperuricemia, hypertriglyceridemia;
Uncommon: glucosuria;
Rare: hypokalemia.
Immune system disorders:
Uncommon: rash;
Rarely: eczema, itching.
Respiratory, chest, and mediastinal disorders:
Rarely: bronchial asthma, sore throat, rhinitis, nasopharyngitis
Gastrointestinal disorders:
Often: diarrhea;
Uncommon: nausea, vomiting, abdominal pain;
Rarely: abdominal discomfort, duodenal ulcer, bloody stools, gastritis.
Hepatic biliary tract disorders:
Often: increased ALT activity, increased AST activity, increased glutamyl transferase (GGT) activity;
Rarely: an increase in the activity of alkaline phosphatase (ALP), an increase in the concentration of bilirubin in the blood.
Others:
Rarely: abnormal behavior, increased activity of creatine phosphokinase (CPK), hematuria, laryngeal polyp, hyperpigmentation, impaired taste sensitivity, hematoma, blurred vision, eye pain, vertigo, supraventricular extrasystoles, chest pain.
Teratogenicity risk of favipivir
- Pregnancy, planning of pregnancy and the period of breastfeeding are strict contraindications to the use of favipiravir due to the risk of teratogenic effect observed in preclinical studies.
- It is necessary to use effective methods of contraception (condom with spermicide) during and after taking the drug: within 1 month for women and within 3 months for men.
- When prescribing favipiravir to women with preserved reproductive potential, a negative pregnancy test should be obtained before starting treatment.
- If pregnancy is suspected during therapy with favipiravir, you should immediately stop using the drug and consult with a doctor.
- Male patients are strongly advised not to have sex with pregnant women.
- While the allocation in the human body, favipiravir passes into breast milk. When prescribing the drug to lactating women, breastfeeding should be stopped while taking the drug and within 7 days after the therapy stops.
Recommendations for a doctor
- Before prescribing the drug, it is recommended to re-examine the approved instructions for medical use of the drug Koronavir (INN: favipiravir), film-coated tablets, 200 mg.
- It is necessary to inform patients about the drug, the expected effectiveness of the proposed therapy, the safety of the drug, and the need for contraception.
- It is recommended to provide patients with the Informed Consent Form for study and signing, in duplicate, one of which is handed over to the patient or his legal representative, and the second is kept in the patient's medical records.
- Please answer the questions if the patient (s) or his (her) guardian / legal representative had them before signing the document.
- In order to minimize the risk of adverse reactions from the liver and biliary tract, we recommend that patients be prescribed a biochemical blood test during and after the course of treatment to monitor liver function indicators wellness.
Pharmacovigilance / Information for healthcare professional
- Submission of messages concerning the suspected adverse reactions is significant after the marketing authorization for the medicinal product is received. This allows continuous monitoring of the benefit-risk ratio for this medicinal product.
- If you were informed of the development of an adverse reaction to the drug Koronavir (INN: favipiravir), film-coated tablets, 200 mg., You should report this to the Medicines Technology LLC company. Please contact the pharmacovigilance department by e-mail Safety@drugsformulation.ru or by phone: +7 (495) 225-62-00 (ext. 6212).
- You can also inform the Federal Service for Surveillance in Healthcare: by e-mail: pharm@roszdravnadzor.ru or at the address: 109074, Russia, Moscow, Slavyanskaya square, 4, building 1.
Supplementary materials for healthcare professionals
You can get the answer to any question about Coronavir by e-mail: covid-19@rpharm.ru
Information about adverse reactions to Coronavir should be sent by e-mail: safety@rpharm.ru
Information about adverse reactions to Coronavir should be sent by e-mail: safety@rpharm.ru
© R-Pharm, 2002-2021
info@rpharm.ru | +7 (495) 956 79 37; +7 (495) 956 79 38 |
119421, 111B, Leninsky Prospect, Moscow
Reprinting or any other use of materials is only possible with a reference to the website