Preventive efficacy of recombinant interferon alpha-2b in the context of the COVID-19 pandemic

Summary. The COVID-19 pandemic has caused a global health crisis and continues to cause enormous economic damage. The number of infected people has already exceeded 48 million people, and more than 1 million deaths have been registered. Currently, there is a steady increase in new cases of COVID-19 in the Russian Federation. The new coronavirus infection caused by the SARS-CoV-2 virus has some clinical and immunopathogenetic features. SARS-CoV-2 is a single-stranded RNA virus belonging to the family Coronaviridae, genus Betacoronavirus. COVID-19 can be asymptomatic; the most common clinical manifestation is viral pneumonia; the development of acute respiratory distress syndrome is noted in no more than 5% of cases. The entry gates of the pathogen are the epithelium of the upper respiratory tract and epithelial cells of the gastrointestinal tract. When the virus enters the human respiratory tract, suppression of mucociliary clearance activity and death of epithelial cells is observed, which allows the virus to penetrate the peripheral blood with subsequent damage to target organs (lungs, digestive tract, heart, kidneys). An excessive response of the immune system with massive release of cytokines, which causes acute respiratory distress syndrome, plays an important pathogenetic role during SARS-CoV-2 infection, especially in severe cases of the disease. Clinical and experimental studies have shown that SARS-CoV-2 may be significantly more sensitive to type I interferons (IFN-I) than other types of coronaviruses. IFN-I deficiency is thought to play a key role in the pathogenesis of COVID-19, and several studies have shown that delayed IFN-I signaling is associated with sustained viral replication and serious complications. The use of drugs in this group (IFN-I) for the treatment and prevention of COVID-19 seems relevant for study. Numerous studies have noted the successful use of recombinant interferon α-2b for the prevention of acute viral infections. In order to determine the preventive effectiveness of interferon α-2b with an antioxidant complex in medical workers who have direct contact with those infected with the SARS-CoV-2 virus, a study was conducted. 109 medical workers in contact with COVID-19 patients were observed for a month. For preventive purposes, 75 medical workers took interferon α-2b with an antioxidant complex (vitamins E and C) in various regimens for 10 days, and the comparison group consisted of 34 medical workers without a preventive course. Among medical workers who received preventive therapy with interferon α-2b, only 5.3% of employees were infected with the SARS-CoV-2 virus during the observation period, while in the comparison group without a preventive course, the proportion of those infected with the COVID-19 coronavirus infection was 32. 4% of health workers. The data obtained indicate the high preventive activity of this drug against the new coronavirus infection.

An acute respiratory infection caused by SARS-CoV-2 appeared in China in 2022 and quickly spread throughout the world, presenting global health with the most difficult problem of combating a new infectious agent.

According to statistics, the total number of people infected in the world is more than 52 million, with more than 1.2 million deaths recorded. In some countries, the situation with the number of new cases of infection is declining, while in other countries the epidemic is still gaining momentum. On the territory of the Russian Federation, the number of cases of COVID-19 is growing and currently exceeds 1.8 million people, and the mortality rate is more than 32 thousand people [1].

The new coronavirus SARS-CoV-2 is a single-stranded RNA virus of the Betacoronavirus genus, whose genome has 79% homology with the causative agent of severe acute respiratory syndrome, the coronavirus SARS-CoV-2, discovered in 2003-2004. The high infectivity of the SARS-CoV-2 virus is partly due to new mutations in the receptor-binding domain, namely at the S1/S2 subunit boundary of the S protein [2].

Transmission of infection occurs through airborne droplets (coughing, sneezing, talking). The contact and household route is realized through objects contaminated with the pathogen. A fecal-oral mechanism is possible (the pathogen was found in fecal samples from patients infected with SARS-CoV-2).

Isolation of the virus from a patient begins 48 hours before the manifestation of clinical symptoms and reaches a maximum in the first 1-3 days from the onset of the disease. As a little-studied virus, SARS-CoV-2, in accordance with the current sanitary legislation of the Russian Federation, was previously classified as pathogenicity group II.

The new coronavirus infection associated with COVID-19 can be asymptomatic; viral pneumonia is a common clinical manifestation, and in 5% of cases the development of acute respiratory distress syndrome is recorded. The entry gates of the pathogen are the epithelium of the upper respiratory tract and epithelial cells of the gastrointestinal tract. It has been established that angiotensin-converting enzyme 2 (ACE2) receptors, which are expressed on the surface of the epithelium of the upper respiratory tract, enterocytes of the small intestine, vascular endothelium, macrophages, brain neurons and glia, are of particular importance in the process of virus penetration into target cells.

Today it is already known that the development of lung damage as the main clinical manifestation of infection is determined primarily by damage to type II alveolar cells [3, 4]. When the virus enters the human respiratory tract, suppression of mucociliary clearance activity is observed due to inhibition of the motility of epithelial cilia, which is accompanied by the death of epithelial cells. Next, the virus penetrates through the mucous membrane of the respiratory tract into the peripheral blood with subsequent damage to target organs (lungs, digestive tract, heart, kidneys).

An important pathogenetic significance during SARS-CoV-2 infection, especially in severe cases of the disease, is played by an excessive response of the immune system with massive release of cytokines - a “cytokine storm”, which causes acute respiratory distress syndrome [5, 6]. Cytokine storm is characterized by excessive activation of cytotoxic lymphocytes and macrophages with the induction of proinflammatory cytokines and inflammatory markers C-reactive protein and serum ferritin, which leads to a hyperinflammatory response [6]. Another significant aspect of the immune response in COVID-19 is the suppression of the production of interferons (IFN) types I and III. By probing coronaviruses with various pathogen recognition receptors (TLRs), nuclear transcription factors (factor-κΒ) and interferon regulatory factors 3 and 7 (IRF3, IRF7), the ability of the SARS-CoV-2 virus to stimulate the synthesis of pro-inflammatory cytokines and multidirectional effects on the synthesis were demonstrated interferons type I and III [7]. It has been established that the initial viral load determines the induction of type I IFN at the early stage of COVID-19 infection: a high viral load can suppress the interferon response, and with a low viral load and a normal immune response, effective elimination of the infection occurs. The same study showed that interferon induction is more often impaired in older people [7]. Other authors have found that the SARS-CoV-2 virus inhibits the production of its own interferon, which reduces antiviral activity, activation of regulatory cells, triggers hyperactivation of macrophages with hyperproduction of cytokines and causes an imbalance in the immune system [8]. IFN-I deficiency is believed to play a key role in the pathogenesis of SARS-CoV-2. Delayed IFN-I signaling has been shown to be associated with sustained viral replication and serious complications.

According to some authors, in vitro studies suggest that SARS-CoV-2 may be significantly more sensitive to type I IFN than other respiratory viruses and coronaviruses. Prophylactic intranasal administration or inhalation of recombinant interferons may limit viral replication in the upper respiratory tract, and supplemental type I IFN may also be useful for pulmonary involvement.

To date, specific prevention of COVID-19 has been developed - two vaccines have been registered in the Russian Federation - “Gam-COVID-Vac” and “EpiVac-Corona”. Large-scale production of these vaccines is just gaining momentum, and mass vaccination will not begin soon. At the beginning of the pandemic, then in the absence of specific prevention and with an increase in the number of infections among medical workers, it seemed very relevant to use long-standing and successfully used drugs for the prevention and treatment of acute viral respiratory infections. Viferon - recombinant interferon α-2b - is one of the well-studied drugs with proven clinical and immunological effectiveness. The combined use of nasal and rectal forms of interferon α-2b with antioxidants in previous studies revealed a strong tendency to accelerate the regression of fever and intoxication, and also more effectively prevented repeated hospitalizations for acute respiratory infections during a 3-month follow-up [9, 10]. The use of a combination of rectal and topical forms of interferon α-2b (Viferon) for the prevention of a new coronavirus infection during the COVID-19 pandemic is quite justified, and studying the effectiveness of such a preventive course was the purpose of this study.

The purpose of this study was to evaluate the preventive effectiveness of recombinant interferon α-2b (Viferon) in the context of the COVID-19 pandemic in healthcare workers.

Material and research methods

Under observation were 109 medical workers of Clinical Hospital No. 2, in contact with patients with COVID-19, aged from 25 to 60 years (average age - 39.2 ± 4.9 years), 26 men and 83 women. Of these, 75 were medical workers who, for preventive purposes, were prescribed a course of taking interferon α-2b (Viferon) for 10 days in various combination regimens of rectal and topical forms. The subjects were divided into three groups depending on the preventive course regimens chosen by the medical workers themselves: 15 people (20%) agreed to take only Viferon gel for topical use - intranasally 2 times a day, 45 (60%) medical workers agreed to a combination of interferon α-2b in the form of a gel 2 times a day intranasally and suppositories 1 million IU rectally 1 time a day on weekdays, 15 (20%) health workers received Viferon intranasally in the form of a gel 2 times and rectally in suppositories 1 million IU 1 time a day daily, and on the day of duty, a suppository of 3 million IU rectally once a day. The comparison group consisted of 34 medical workers who refused the preventive course (Fig.).

Observation lasted for 1 month. All healthcare workers underwent a weekly nasopharyngeal and oropharyngeal swab test to detect SARS-CoV-2 RNA by polymerase chain reaction (PCR) using the AmpliSens® Cov-Bat-FL reagent kit.

The examination of infected medical workers was carried out in accordance with the temporary methodological recommendations “Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)”. Verification of the diagnosis was carried out by PCR using nucleic acid amplification, and AT-SARS-CoV-2 IgM, IgG was also determined using the ELISA method. Instrumental diagnostics included pulse oximetry to assess the severity of hypoxemia, as well as chest computed tomography (CT) in all sick health workers.

Results and discussion

In the group with a prophylactic course of interferon α-2b, there were 17 (22.7%) men and 58 (77.3%) women aged 25 to 60 years, the average age was 38.9 ± 4.2 years. In the group without a prophylactic course there were 9 (26.5%) men and 25 (73.5%) women, the average age was 40.4 ± 3.9 years.

In the group with a preventive course of interferon α-2b, 4 (5.3%) medical workers infected with SARS-CoV-2 were identified (1 man and 3 women). At the same time, three sick health workers used only Viferon gel locally intranasally 2 times a day and 1 health worker used a combination of rectal (suppositories 1 million IU) and topical forms. SARS-CoV-2 virus RNA was detected in 2 women in the first week, 1 woman in the second week, and 1 man in the fourth week (table). All infected health workers report a violation of the Viferon prophylactic course regimen (multiplicities and combinations). In the group of health workers without a preventive course of interferon α-2b, the proportion of cases of COVID-19 was 32.4% (11 out of 34 health workers) (Fig.). The number of patients and the timing of detection of SARS-CoV-2 virus RNA in healthcare workers are presented in the table.

When assessing the severity of COVID-19 in 4 sick medical workers who received a preventive course, asymptomatic infection was found in three and degree 1 lung damage was found in one according to computed tomography (Fig.). In the group of medical workers without prophylaxis, all 11 medical workers with COVID-19 developed bilateral pneumonia of varying severity according to CT data: 5 patients had CT-1, 3 had CT-2 lesions, 2 health workers had CT-3 and CT- 4 – in one patient (Fig.). No asymptomatic disease was observed in this group. The results of the study in the comparison groups of medical workers in an infectious diseases hospital are presented in Fig.

A pronounced preventive effectiveness of the use of interferon α-2b was revealed in various schemes, both for local use in the form of a gel (3 out of 15 fell ill), and in a combination of rectal and topical forms of interferon α-2b (1 out of 60) compared with a group of medical workers without preventive therapy (11 out of 34).

Such results are expected and coincide with our previously obtained data on the effectiveness of interferon α-2b in ARVI [9, 10] and with the opinion of other researchers. Thus, experimental studies conducted in in vitro format suggest that SARS-CoV-2 may be significantly more sensitive to type I IFN than other respiratory viruses and coronaviruses. It is assumed that prophylactic intranasal administration or inhalation of recombinant interferons can limit viral replication in the upper respiratory tract.

Many researchers are actively studying the effectiveness of interferons and the possibility of using IFN in treatment regimens for COVID-19. Annsea Park and Akiko Iwasaki [7] in their study noted the effect of the combination of lopinavir/ritonavir and interferon α-2b in the form of inhaled IFN. A number of authors show the potential of using IFN λ for the treatment of coronavirus infection SARS-CoV-2 both in patients with mild disease and in patients with varying degrees of severity of pneumonia [11]. Other authors show the potential of using IFN λ for the treatment of coronavirus infection caused by SARS-CoV-2 in patients with both mild disease and varying degrees of severity of pneumonia [11].

In China, recommendations from various authors have been published for the treatment of COVID-19 by administering 5 million units of recombinant interferon α by steam inhalation twice a day in combination with ribavirin [12, 13]. Administration of IFN drugs by various routes (vapor inhalation, intravenous and subcutaneous routes) has varying effectiveness. The interferon drugs themselves are well described and have already proven their safety in several clinical trials [14]. E. Mantlo et al. their study assessed the antiviral activity of type I IFN against infection caused by SARS-CoV-2. Interferon α and interferon β at a concentration of 50 IU have been shown to reduce viral titers by 3.4 log and more than 4 log, respectively. These data demonstrate the effectiveness of human type I IFN in suppressing SARS-CoV-2 infection, which may provide the basis for future treatment options for COVID-19 [15].

According to the results of our observations, a 10-day preventive course of combined use of interferon α-2b with antioxidants was more effective than a course with only intranasal administration of interferon α-2b in gel form in preventing infection with the SARS-CoV-2 virus during a pandemic, the proportion of those infected in these groups was 1.6% and 20%, respectively. Combined regimens of recombinant interferon α-2b (Viferon) have shown their high preventive effectiveness among medical workers during a pandemic in the absence of specific prevention. The data obtained convincingly indicate the advisability of using the drug Viferon for the prevention of COVID-19 in a pandemic, and in combination with nasal (gel/ointment) and rectal forms of interferon α-2b with antioxidants (suppository) they are more effective for emergency post-exposure prevention of COVID-19.

Thus, the use of recombinant interferon for the prevention of COVID-19 during a pandemic is a promising area for further research.

Literature/References

Online map of the spread of coronavirus. URL: https://coronavirus-monitor.ru/. [Onlayn-karta rasprostraneniya korona-virusa URL: https://coronavirus-monitor.ru/.]
Lu R., Xiang Zhao, Juan Li et al. Genomic characterization and epidemiology of 2022 novel coronavirus: implications for virus origins and receptor binding // Lancet. 2020; 395(10224):565–574. DOI: 10.1016/S0140-6736(20)30251-8.
Walls AC, Park YJ, Tortorici MA et al. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein // Cell. 2020; 181(2):281-292. DOI: 10.1016/j.cell.2020.02.058.
Omarova Kh. G., Makashova V. V., Ponezheva Zh. B. et al. Current issues of the pathogenesis of COVID-19 and possible measures to prevent severe forms of the disease // Attending Physician. 2020; 8: 77-82. DOI: 10.26295/OS.2020.77.18.013. The Lechaschy Physician Journal. 2020; 8: 77-82. DOI: 10.26295/OS.2020.77.18.013.]
Qing Ye, Bili Wang, Jianhua Mao. The pathogenesis and treatment of the `Cytokine Storm' in COVID-19 // J Infect. 2020; 80 (6): 607-613. DOI: 10.1016/j.jinf.2020.03.037.
Mehmet Soy, Gökhan Keser et al. Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment // Clin Rheumatol. 2020; 39 (7): 2085-2094. DOI: 10.1007/s10067-020-05190-5.
Annsea Park, Akiko Iwasaki. Type I and Type III Interferons – Induction, Signaling, Evasion, and Application to Combat COVID-19 // Cell Host Microbe. 2020; 27 (6): 870-878. DOI: 10.1016/j.chom.2020.05.008.
Margarida Sa Ribero, Nolwenn Jouvenet et al. Interplay between SARS-CoV-2 and the type I interferon response // PLoS Pathog. 2020; 16(7):e1008737. DOI: 10.1371/journal.ppat.1008737.
Akimkin V. G., Korotchenko S. I. et al. Epidemiological and immunological effectiveness of using the drug “VIFERON-gel” for the prevention of influenza and other acute respiratory infections in organized military groups // Epidemiology and infectious diseases. Current issues. 2011; 1:28-36. Epidemiologiya i infektsionnyye bolezni. Aktual'nyye voprosy. 2011; 1:28-36.]
Kalyuzhin O. V., Ponezheva Zh. B., Kupchenko A. N. et al. Clinical and interferon-modulating effectiveness of a combination of rectal and topical forms of interferon-α2b in acute respiratory infections // Therapeutic archive 2018; 11: 48. Terapevticheskiy arkhiv 2018; 11:48.]
Evangelos Andreakos, Sotirios Tsiodras. COVID-19: lambda interferon against viral load and hyperinflammation // EMBO Mol Med. 2020; 12(6):e12465. DOI: 10.15252/emmm.202012465.
Dong L., Hu S., Gao J. Discovering drugs to treat coronavirus disease 2022 (COVID-19) // Drug Discov. Ther. 2020; 14:58-60. https://doi.org/10.5582/ddt.2020.01012.
Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV) // Bioscience Trends. 2022. https://doi.org/10.5582/bst.2020.01020.
Mager DE, Jusko WJ Receptor-mediated pharmacokinetic/pharmacodynamic model of interferon-β1a in humans // Pharm. Res. 2002; 19 (10): 1537-1543. https://doi.org/10.1023/A:1020468902694.
Mantlo E., Bukreyeva N. et al. Antiviral activities of type I interferons to SARS-CoV-2 infection //Antiviral Res. 2020; 179: 104811. DOI: 10.1016/j.antiviral.2020.104811.

Zh. B. Ponezheva*, 1, Doctor of Medical Sciences A. A. Grishaeva* I. V. Mannanova* A. N. Kupchenko* S. B. Yatsyshina*, Candidate of Biological Sciences S. V. Krasnova**, Candidate of Medical Sciences Sciences V. V. Malinovskaya***, Doctor of Biological Sciences, Professor V. G. Akimkin*, Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences

* FBUN TsNIIE Rospotrebnadzor RF, Moscow, Russia ** GBUZ IKB No. 2 DZM, Moscow, Russia *** FGBU NICEM im. N. F. Gamaleyi Ministry of Health of Russia, Moscow, Russia

1Contact information

Preventive efficacy of recombinant interferon α-2b in the context of the COVID-19 pandemic / Zh. B. Ponezheva, A. A. Grishaeva, I. V. Mannanova, A. N. Kupchenko, S. B. Yatsyshina, S. V. Krasnova, V. V. Malinovskaya, V. G. Akimkin For citation: Ponezheva Zh. B., Grishaeva A. A., Mannanova I. V., Kupchenko A. N., Yatsyshina S. B., Krasnova S. V., Malinovskaya V.V., Akimkin V.G. Preventive effectiveness of recombinant interferon α-2b in the context of the COVID-19 pandemic // Treating Doctor. 2020; 12 (23): 56-60. DOI: 10.26295/OS.2020.29.66.011 Tags: coronavirus infection, prevention, immunity

Content

Characteristics of altevir (interferon alpha 2-b) (amp. 3 million IU/ml 1 ml No. 5)

Composition: Interferon alpha-2b human recombinant.

Pharmacological action: Pharmacological action - antiviral, immunomodulatory, antitumor, antiproliferative.

Prevents viral infection of cells, changes the properties of the cell membrane, prevents adhesion and penetration of the virus into the cell.

Initiates the synthesis of a number of specific enzymes, disrupts the synthesis of viral RNA and viral proteins in the cell.

Changes the cytoskeleton of the cell membrane, metabolism, preventing the proliferation of tumor (especially) cells.

It has a modulating effect on the synthesis of some oncogenes, leading to normalization of neoplastic cell transformation and inhibition of tumor growth.

Stimulates the process of antigen presentation to immunocompetent cells, modulates the activity of killer cells involved in antiviral immunity.

When administered intramuscularly, the rate of absorption from the injection site is uneven.

The time to reach maximum plasma concentration is 4-8 hours.

70% of the administered dose is distributed in the systemic circulation.

Half-life is 4-12 hours.

It is excreted mainly by the kidneys by glomerular filtration.

Indications for Use: Hairy cell leukemia, chronic myeloid leukemia, viral hepatitis B, active viral hepatitis C, primary (essential) and secondary thrombocytosis, transitional form of chronic granulocytic leukemia and myelofibrosis, multiple myeloma, kidney cancer; AIDS-related Kaposi's sarcoma, mycosis fungoides, reticulosarcoma, multiple sclerosis, prevention and treatment of influenza and acute respiratory viral infection.

Interaction: Interferes with the metabolism of cimetidine, phenytoin, warfarin, theophylline, diazepam, propranolol.

Side Effects: Lethargy, fever, chills, loss of appetite, muscle pain, headache, joint pain, sweating, nausea, vomiting, changes in taste, dry mouth, weight loss, diarrhea, abdominal pain, constipation, flatulence, increased peristalsis, heartburn, liver dysfunction, hepatitis, dizziness, visual disturbances, ischemic retinopathy, depression, drowsiness, impaired consciousness, nervousness, sleep disturbance, allergic skin reactions (rash, itching).

Contraindications: Hypersensitivity, severe heart disease (incl.

history), acute myocardial infarction, severe dysfunction of the liver, kidneys or hematopoietic system, epilepsy and/or others.

dysfunction of the central nervous system; chronic hepatitis against the background of decompensated cirrhosis of the liver; chronic hepatitis in patients receiving or recently receiving immunosuppressant therapy (with the exception of short-term pre-treatment with steroids).

Restrictions on use: Pregnancy, breastfeeding (breastfeeding should be stopped), childhood.

Overdose: No information.

Special Instructions: Combinations with drugs acting on the central nervous system and immunosuppressants should be avoided.

Throughout the course, it is necessary to monitor the content of blood cells and liver function.

To mitigate side effects (flu-like symptoms), simultaneous administration of paracetamol is recommended.

Interferon Alfa-2b

This document, provided by Lexicomp®, contains all the necessary information about the drug, including indications, directions for use, side effects, and when to contact your healthcare provider.

Trade names: USA

Intron A

Trade names: Canada

Intron A (Hsa-Free) [DSC]; Intron A Pen [DSC]; Intron A [DSC]

Warning

The use of alpha interferon may lead to the emergence or worsening of mental disorders. Suicide or thoughts of suicide, thoughts of harming others, depression, violent acts, hallucinations, and other mood or behavioral disturbances occurred during treatment and for 6 months after the last dose. There was also a case of relapse into drug addiction. Alpha interferon drugs may also cause or worsen infections, circulatory disorders, and autoimmune diseases. Sometimes this can be deadly. If you suspect your child has any of these health conditions, contact your child's healthcare provider immediately. Side effects have occurred, such as increased or decreased blood pressure, increased or irregular heart rhythm, chest pain, angina, breathing problems, myocardial infarction, and stroke. Please read the section of this leaflet carefully that tells you which situations require you to contact your child's healthcare provider. Often, but not always, these side effects become less severe after you stop taking this drug.

What is this drug used for?

Used to treat infectious hepatitis B and C.
If your child has received this drug for any other reason, ask the doctor about the benefits and risks. Talk to your doctor if you have questions or concerns about your child's use of this drug.

What should I tell the doctor BEFORE my child takes this drug?

If your child is allergic to this drug, any of its ingredients, other drugs, foods or substances. Tell your doctor about your child's allergies and how they manifested themselves.
If your child has ever had any of the following health problems: Autoimmune disease or liver problems.
If your child has any of the following health conditions: diabetes or thyroid disease.
If your child has had an organ transplant.

This list of medications and diseases that may adversely affect the use of this drug is not exhaustive.

Talk to your doctor or pharmacist about all the medications your child takes (prescription and over-the-counter medications, natural products, and vitamins) and any health concerns your child may have. You need to make sure that this drug is safe for your child's medical conditions and in combination with other drugs he is already taking. Do not start, stop, or change the dosage of any medicine your child is taking without your doctor's approval.

What should I know or do while my child is taking this drug?

All release forms:

Tell all of your child's health care providers that your child is taking this drug. These are your child's doctors, nurses, pharmacists and dentists.
Make sure your child avoids tasks or activities that require concentration until you see how this drug affects your child. This includes riding a bicycle, playing sports, or using objects such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
Increases in triglyceride levels have been associated with this drug. If your child ever has elevated triglyceride levels, tell your child's doctor.
Get your baby's blood tested frequently. Check with your child's doctor.
Alcohol may interact with this drug. Make sure your child does not drink alcohol.
Do not give your child marijuana or other forms of cannabis, or prescription or over-the-counter drugs that may slow down your child's performance.
High blood sugar levels have occurred with this drug. This includes the development or worsening of existing diabetes mellitus.
Monitor your child's blood sugar as directed by your doctor.
Your child may be at increased risk of developing infections. Make sure your child washes their hands frequently. Avoid crowded places and contact with people with infections, colds or flu.
Your baby may become more likely to bleed. Make sure your child is careful and avoids injury. Make sure your child uses a soft toothbrush.
Take care of your child's teeth. Visit your dentist regularly.
If your child is vomiting, make sure he rinses his mouth thoroughly.
This drug may cause damage to the eyes, leading to decreased vision or blindness. If your child has or has ever had vision problems, tell the doctor. If your child experiences any vision problems, consult a doctor immediately.
In some cases, the drug may affect growth rate in children and adolescents. They may need to have their growth rate checked regularly. Consult your doctor.
Whether this drug can prevent the development of liver failure or other liver problems such as cancer is unknown. Consult your doctor.
This drug does not prevent the spread of diseases such as HIV or hepatitis, which are transmitted through the blood. Items such as needles, toothbrushes and razors must be individual.
This drug can be used in combination with ribavirin. If your child is also taking ribavirin, discuss the possible risks and side effects with your doctor.

If your child is or may be sexually active:

This drug does not prevent the spread of diseases such as HIV or hepatitis, which are sexually transmitted. Be sure to warn your child not to have sexual intercourse without using a latex or polyurethane condom.
Your child must use birth control while taking this drug.

If your daughter is pregnant or breastfeeding:

Consult your doctor if your daughter is pregnant, becomes pregnant, or is breastfeeding. The benefits and risks for your daughter and her baby will need to be discussed.

Powder:

This drug is made from human plasma (one of the components of blood) and may contain viruses that cause illness. The drug is screened, tested and processed to reduce the risk of infection. Consult your doctor.

Which side effects should I report to my child's healthcare provider immediately?

WARNING/CAUTION:

Although rare, this drug may cause very serious and sometimes fatal side effects in some people. Contact your child's doctor or get medical help right away if your child has any of the following signs or symptoms that may be associated with a very serious side effect:

Signs of an allergic reaction, such as rash, hives, itching, red and swollen skin with blistering or peeling, possibly accompanied by fever, wheezing or wheezing, tightness in the chest or throat, difficulty breathing, swallowing or speaking, unusual hoarseness, swelling in the areas of the mouth, face, lips, tongue or throat.
Signs of infection, such as fever, chills, very severe sore throat, ear or sinus pain, cough, increased amount of sputum or change in color, pain when urinating, mouth sores or a sore that won't heal.
Signs of pancreas problems (pancreatitis), such as severe stomach pain, severe back pain, severe stomach upset, and vomiting.
Signs of high blood sugar include confusion, drowsiness, increased thirst and hunger, increased urination, facial flushing, rapid breathing, and fruity breath.
Symptoms of thyroid disease, such as weight changes, nervousness, restlessness, restlessness, weakness, thinning hair, depression, neck swelling, difficulty concentrating, thermoregulation problems, menstrual irregularities, tremors or sweating.
New or worsening mental disorders, mood swings or behavioral changes.
Any unexplained bruising or bleeding.
Black, tarry or bloody stools.
Vomiting blood or vomit in the form of coffee grounds.
Weakness on 1 side of the body, difficulty speaking or thinking, trouble maintaining balance, drooping on one side of the face, or blurred vision.
Shortness of breath, sudden weight gain, or swelling of the arms or legs.
Strong headache.
Severe abdominal pain.
Unusual burning, numbness, or tingling sensations.
Memory impairment or loss.
Confusion.
Difficulty walking.
Difficulty urinating or changes in the amount of urine produced.
Anxiety.
Changes in the appearance of teeth and gums.
Changes in vision.
Very bad and sometimes fatal liver problems have occurred while you took this drug. If your child shows signs of liver problems, such as dark urine, feeling tired, lack of appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin or eyes, call your child's doctor right away.
Lung problems have occurred in some patients using this drug. In some cases this resulted in death. Contact your child's doctor immediately if your child has signs of lung disease, such as shortness of breath or other breathing problems, a new or worsening cough, or an increase in body temperature.

What are some other side effects of this drug?

Any medicine can have side effects. However, many people experience little or no side effects. Contact your child's doctor or get medical help if any of these or other side effects bother your child, or if they do not go away:

Feeling dizzy, drowsy, tired, or weak.
Changes in the ability to perceive taste.
Weight loss.
Dry mouth.
Nausea or vomiting.
Diarrhea or constipation.
No feeling of hunger.
Irritation at the injection site.
Hair thinning.
Sleep disorders.
Flu-like symptoms. This includes headache, weakness, high temperature, fever, aches and sweating. A mild pain reliever may help.

This list of possible side effects is not exhaustive. If you have any questions about side effects, ask your child's doctor. Check with your child's doctor about side effects.

You can report any side effects to your national health authority.

What is the best way to give this drug?

Give this drug to your child as directed by the doctor. Read all the information provided to you. Follow all instructions strictly.

All release forms:

For injection.
If you give your child shots yourself, your child's doctor or nurse will teach you how to give the shots.
Continue giving this drug as directed by your child's doctor or other health care provider, even if your child feels well.
Allow to reach room temperature before injection. Do not heat this medication.
Change the injection site with each injection.
Do not inject into areas of the skin that are irritated, bleeding, red, infected, or scarred.
Do not use if solution is cloudy, leaking, or contains particles.
Do not use if solution changes color.
Wash your hands before and after use.
Dispose of needles in a sharps/needles disposal container. Needles and other items cannot be reused. When the container is full, dispose of it according to local regulations. If you have questions, consult your doctor or pharmacist.
Try to have your child drink plenty of non-caffeine fluids every day unless the doctor tells you to drink less fluids.

Powder:

This medication must be mixed with sterile water before use. The sterile water provided with this medication is for one-time use only. Throw away any unused portions of sterile water after a single use.

Pre-filled syringes or pen:

Do not share pens or cartridges with others, even if the needle has been replaced. When exchanging these devices, transmission of infections from one person to another may occur. This also applies to infections that you may not even suspect your child has.

What if my child misses a dose of a drug?

Give the missed dose as soon as possible.
If it is time for your child to take the next dose, do not take the missed dose and then go back to your child's regular dosing schedule.
Do not give double doses at the same time or additional doses.
If you miss giving your child this drug for several days in a row, talk to your doctor before starting the drug again.

How should I store and/or throw away this drug?

All release forms:

Store in the refrigerator. Do not freeze.
Keep all medications in a safe place. Keep all medications out of the reach of children and pets.
Dispose of unused or expired medications. Do not pour into toilet or drain unless instructed to do so. If you have questions about disposing of your medications, consult your pharmacist. Your area may have drug recycling programs.

Powder:

You should know how long the drug can be stored and how to store it after mixing. If in doubt, consult your doctor or pharmacist.
Discard any unused portions from an opened ampoule after use.

Solution:

You should find out how long the drug can be stored and how to store it after opening the package. If in doubt, consult your doctor or pharmacist.

Pre-filled syringes or pen:

Immediately after use, place it back in the refrigerator.
Throw away any unused portions after 28 days.

General information about medications

If your child's symptoms or problems do not improve or worsen, contact your child's doctor.
Do not share your child's medicine with others or give anyone else's medicine to your child.
Some medicines may come with other patient information leaflets. If you have questions about this drug, ask your child's doctor, nurse, pharmacist, or other health care professional.
If you think you have overdosed on this drug, call a poison control center or get medical help right away. Be prepared to tell or show what drug you took, how much, and when it happened.

Consumer Use of Information and Limitation of Liability

This summary information includes summary information about the diagnosis, treatment and/or drug. It is not a comprehensive source of data and should be used as a tool to help the user understand and/or evaluate potential diagnostic and treatment options. It does NOT include all information about conditions, treatments, medications, side effects, or risks that may apply to a particular patient. It should not be considered medical advice or a substitute for medical advice, diagnosis or treatment provided by a physician based on a physician's examination and assessment of the patient's specific and unique circumstances. Patients should consult with their physician for complete information about their health, medical issues and treatment options, including any risks or benefits of medication use. This information is not a guarantee that a treatment or drug is safe, effective, or approved for use in any particular patient. UpToDate, Inc. and its affiliates disclaim any warranties or liabilities with respect to this information or its use. The use of this information is subject to the Terms of Use found at https://www.wolterskluwer.com/en/solutions/lexicomp/about/eula.