Instructions Inosine pranobex syrup 50 mg/ml 100 ml
Composition
active ingredient: inosine pranobex;
1 ml of syrup contains inosine pranobex 50 mg;
excipients: confectioner's sugar; methyl parahydroxybenzoate (E 218); propyl parahydroxybenzoate (E 216); citric acid, monohydrate; sodium hydroxide; banana flavoring; purified water.
Dosage form
Syrup.
Main physicochemical properties: colorless to yellowish syrup, with a banana odor and a slightly bitter taste.
Pharmacotherapeutic group
Antimicrobials for systemic use. Antivirals for systemic use. Direct-acting antivirals.
ATX code J05A X05.
Pharmacological properties
Pharmacodynamics.
The drug INOSINE PRANOBEX contains methisoprinol (inosine pranobex), which is a synthetic purine derivative and has immunomodulatory and antiviral effects that result from pronounced stimulation of the host immune response in vivo.
In clinical studies, inosine pranobex has been shown to correct cellular immune deficiency or dysfunction by inducing Th1-type responses, leading to maturation and differentiation of T lymphocytes and potentiation of lymphoproliferative responses in mitogenic or antigen-active cells. In addition, the drug has been shown to regulate cytotoxicity mechanisms of T lymphocytes and NK cells, the function of CD8+ suppressor lymphocytes and CD4+ helper lymphocytes, and to increase IgG and surface complement markers. In in vitro studies, inosine pranobex has been shown to enhance the production of IL-1 and IL-2 cytokines, while simultaneously increasing the expression of the IL-2 receptor. In in vivo studies, the secretion of endogenous gamma interferon (IFN-γ) was significantly increased and the secretion of IL-4 was reduced. The drug has also been shown to enhance chemotaxis and phagocytosis of neutrophils, monocytes, and macrophages.
In vivo studies have shown that inosine pranobex activates reduced synthesis of messenger RNA (mRNA) of lymphocyte proteins and the efficiency of the translation process with simultaneous inhibition of viral RNA synthesis in the following mechanisms (their involvement requires further research):
incorporation of inosine-bound orotic acid into polyribosomes;
inhibition of the addition of polyadenylic acid to viral template RNA;
restructuring of mesothelial protein complexes involved in signaling through a specific T-cell receptor (TcR) in lymphocyte intramembranous vesicles (IMPs), which almost triples their density.
Inosine pranobex inhibits cGMP phosphodiesterase in vitro only at high concentrations; this effect is not evident at drug concentrations that provide immunopharmacological activity in vivo.
Pharmacokinetics.
Absorption: When inosine is administered orally, pranobex is rapidly and completely absorbed (≥ 90%) from the gastrointestinal tract into the blood. Similarly, 94–100% of the dose of its components, DIP (N, N-dimethylamino-2-propanol) and PABA (para-aminobenzoic acid), administered intravenously, is recovered in the urine after oral administration in rhesus macaques.
Distribution: When administered to monkeys, radiolabeled material was detected in the following organs (in order of decreasing specific activity): kidney, lung, liver, heart, spleen, testes, pancreas, brain, and skeletal muscle.
Metabolism: Following oral administration of 1 g of radiolabeled inosine pranobex to humans, plasma concentrations of DIP and PABA were found to be 3.7 μg/mL (2 hours) and 9.4 μg/mL (1 hour), respectively.
In the course of dose tolerance studies, it was found that the peak post-dose increase in uric acid concentration as an indicator of methisoprinol metabolism is nonlinear and can vary within ± 10% for 1–3 hours.
Excretion. The daily urinary excretion of PABA and its main metabolite at steady state at a dosage of 4 g/day was approximately 85% of the administered dose. 95% of radioactive DIP was recovered in the urine as unchanged substance and the N-oxide metabolite. The half-life of DIP is 3.5 hours, PABA is 50 minutes. The main metabolites of inosine pranobex in humans are the N-oxide for DIP and the ortho-acylglucuronide for PABA. Since the inosine molecule is metabolized by purine biodegradation to uric acid, experiments with radiolabeled inosine pranobex in humans are uninformative. In animals, up to 70% of the administered inosine pranobex can be excreted in the urine as uric acid after oral administration of the tablet form, and the remainder as the common metabolites xanthine and hypoxanthine.
Bioavailability. Steady-state urinary recovery of PABA and its metabolite was > 90% of the expected solution values. DIP and its metabolite were ≥ 76%. Plasma AUC values of DIP were ≥ 88%, PABA ≥ 77%.
Indication
The drug INOSYN PRANOBEX is indicated for the treatment of reduced or dysfunctional cellular immunity and for the treatment of clinical symptoms in the following diseases:
primary and secondary viral respiratory infections;
genital warts (condyloma acuminata) - external lesions (except for meatal and perianal localization) - as monotherapy or as an adjunct to conventional local or surgical treatment;
Mucosal infections, subclinical vulvovaginal infections, or infections caused by HPV (human papillomavirus) associated with the endocervix;
viral hepatitis;
measles with a complicated course or with complications;
subacute sclerosing panencephalitis (SSPE).
Contraindication
The medicine should not be used:
patients who have shown hypersensitivity to the active substance or to any of the excipients of the medicinal product;
patients during an acute attack of gout;
patients with elevated levels of uric acid in the blood (hyperuricemia).
Interaction with other medicinal products and other types of interactions
Use with caution in patients taking xanthine oxidase inhibitors (e.g. allopurinol) and agents that increase urinary uric acid excretion, including thiazide diuretics (e.g. hydrochlorothiazide, chlorthalidone, indapamide) and loop diuretics (furosemide, torasemide, ethacrynic acid).
The drug should not be taken during immunosuppressant therapy, as the simultaneous use of immunosuppressants may affect its expected therapeutic effect due to the peculiarities of pharmacokinetic mechanisms (use is possible only after completion of therapy).
Concomitant use of the drug with zidovudine (azidothymidine - AZT) enhances the formation of nucleotides by zidovudine through various mechanisms due to increased bioavailability of zidovudine in blood plasma and increased intracellular phosphorylation in blood monocytes. This leads to an increase in the effects of zidovudine under the influence of the drug.
Application features
The drug may cause a transient increase in serum and urine uric acid levels, but they usually remain within the normal range (the upper limit is 8 mg/dl or 0.42 mmol/l, respectively), especially in the elderly and younger men. The increase in uric acid levels is a result of the catabolic metabolism of the inosine component of the active substance to uric acid and is not a result of drug-induced changes in enzyme activity or renal clearance. Therefore, inosine pranobex should be used with caution in patients with a history of gout, hyperuricemia, urolithiasis, and impaired renal function. During treatment, uric acid levels should be closely monitored in such patients.
Some patients may experience acute hypersensitivity reactions (angioedema, anaphylactic shock, urticaria). In such cases, drug therapy should be discontinued.
Kidney stones may form with prolonged treatment. Regular monitoring of serum and urinary uric acid levels, liver function, blood counts and renal function should be performed in each patient during long-term treatment.
Excipients.
The drug INOSYN PRANOBEX contains methyl parahydroxybenzoate (E 218) and propyl parahydroxybenzoate (E 216), therefore it may cause allergic reactions (possibly delayed).
This medicine contains confectioner's sugar. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine. May be harmful to your teeth. 1 ml of syrup contains 663 mg of confectioner's sugar. Use with caution in patients with diabetes.
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Use during pregnancy or breastfeeding
The effect of inosine on fetal development and fertility in humans has not been studied. It is not known whether inosine pranobex passes into breast milk. The drug should not be used during pregnancy and breastfeeding unless the doctor considers that the expected benefit outweighs the potential risks.
Ability to influence reaction speed when driving vehicles or other mechanisms
The drug has no or negligible influence on the ability to drive or use machines.
Method of administration and doses
The medicine is intended for oral use.
The daily dose depends on body weight, the course and severity of the disease, and the patient's condition.
The daily dose should be divided evenly into doses throughout the day.
Adults, including the elderly: the recommended daily dose is 50 mg/kg body weight (1 ml/kg), usually 3 g/day (20 ml syrup 3-4 times a day). The maximum daily dose is 4 g.
Children: the recommended daily dose is 50 mg/kg body weight (1 ml/kg), divided equally into 3–4 doses according to the table below:
Body weight, kg
Dosage regimen
Less than 9 kg
2.5 ml of syrup 3-4 times a day
9‒14 kg
5 ml of syrup 3-4 times a day
14‒21 kg
7.5 ml of syrup 3-4 times a day
Over 21 kg
Same dose as for adults
To measure the dose, use the dosing device with a measuring scale included in the medicine kit.
Duration of treatment
Acute diseases. For diseases with a short course, the course of treatment is from 5 to 14 days. After the symptoms of the disease have subsided, treatment should be continued for another 1-2 days or longer, at the doctor's discretion.
Viral diseases with a long course. Treatment should be continued for 1-2 weeks after the symptoms of the disease have subsided, or longer, at the discretion of the doctor.
Recurrent diseases. At the beginning of treatment, the same recommendations are followed as in the case of acute diseases. During maintenance therapy, the dose can be reduced to 500-1000 mg/day. At the first signs of relapse, it is necessary to resume taking the daily dose recommended in the case of acute diseases, and it should be continued for 1-2 days after the disappearance of symptoms. The course of treatment can be repeated several times if necessary and depending on the patient's condition, on the recommendation of a doctor.
Chronic diseases. The recommended dose is 50 mg/kg body weight according to the following regimens:
asymptomatic diseases: take for 30 days with a break of 60 days;
Diseases with mild symptoms: take for 60 days with a break of 30 days;
Diseases with severe symptoms: take for 90 days with a 30-day break.
The course of treatment should be repeated as many times as necessary, with constant monitoring of the patient's condition and indications for extending therapy.
Dosage for special indications
External genital warts (condyloma acuminata) or HPV infections associated with the endocervix: use 3 g/day for 14-28 days as monotherapy or as an adjunct to topical therapy or surgical treatment according to the following regimens:
for the treatment of low-risk patients (patients without immunodeficiency or patients with a low risk of relapse), the drug is used continuously for 14-28 days for 3 months, followed by a two-month treatment-free period, during which the lesions decrease or disappear;
or
For the treatment of high-risk patients* (immunocompromised patients or those at high risk of relapse), the drug is administered 5 days a week for 2 consecutive weeks each month or 5 days a week every other week for 3 months. If necessary, treatment courses can be repeated several times.
*The “high-risk” profile for recurrence or cervical dysplasia in patients with genital HPV infection is similar to that of other diseases and includes the following diseases and conditions:
Genital HPV infection lasting more than 2 years, or if there are 3 or more recurrences in the anamnesis.
Decreased immunity caused by:
recurrent or chronic infections;
other sexually transmitted diseases (STDs);
chemotherapy for cancer;
chronic alcoholism.
Poorly controlled diabetes.
Atopy.
Long-term use of oral contraceptives (2 years or more).
The level of folic acid in erythrocytes is below 660 nmol/l.
Having multiple sexual partners or changing your regular sexual partner.
Frequent vaginal intercourse (≥ 2–6 times per week).
Anal sex.
The patient has a history of skin warts in childhood.
Age over 20 years.
Smoking.
In subacute sclerosing panencephalitis, the daily dose is 100 mg/kg body weight, the maximum dose is 60-80 ml/day. Treatment is long-term, continuous, with regular monitoring of the patient's health and review of further treatment. The recommended daily dose may be increased, especially in severe cases.
Children: See section “Method of administration and dosage”.
Overdose
No cases of overdose have been observed. Based on the results of toxicology studies in animals, serious adverse reactions are unlikely, except for an increase in uric acid levels in the body. Treatment is symptomatic and supportive.
Side effects
The only side effect of inosine pranobex that occurs most frequently in both adults and children is a temporary increase (usually within normal limits) in serum and urine uric acid levels, which return to their original normal values within a few days after the end of treatment.
The frequency of adverse reactions is given according to the following classification: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (˂1/10000), frequency unknown (cannot be estimated from the available data).
