Composition, form of production and packaging
Lyophilizate for the preparation of a suspension for ingestion in the form of a powder or a porous mass from white to light yellow; flaking, complete or partial, from the surface of the glass of the vial with the formation of a tabloid-like structure, is hygroscopic.
ribavirin 500 mg
[PRING] sodium chloride - 30 mg, lecithin lipoid C100 (phospholipids (mixture with a percentage of phosphatidylcholine at least 94%)) - 900 mg, cholesterol - 100 mg,? -tocopherol acetate - 9 mg, methyl parahydroxybenzoate - 7 mg, lactose monohydrate - 870 mg.
500 mg - bottles (1) - packs of cardboard.
500 mg - bottles (6) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2008.
Antiviral drug, a synthetic analogue of nucleosides with a pronounced antiviral effect.
Ribavirin easily penetrates into virus-infected cells and is rapidly phosphorylated by intracellular adenosine kinase to ribavirin mono-, di- and triphosphate. These metabolites, especially ribavirin triphosphate, have a pronounced antiviral activity. The mechanism of action of ribavirin has not been elucidated. It was found that ribavirin inhibits inosine monophosphate dehydrogenase (IMP), this effect leads to a marked decrease in the level of intracellular guanosine triphosphate (GTP), which in turn is accompanied by suppression of the synthesis of viral RNA and virus-specific proteins. Ribavirin inhibits the replication of new virions, which reduces the viral load, selectively inhibits the synthesis of viral RNA, without affecting the synthesis of RNA in normal human cells.
Ribavirin has a wide spectrum of activity against various DNA and RNA-containing viruses. The most sensitive to ribavirin DNA viruses are herpes simplex virus, adenoviruses, CMV, smallpox viruses, Marek's diseases; RNA viruses - influenza A, B viruses, paramyxoviruses (parainfluenza, mumps, Newcastle disease), reoviruses, arenaviruses (Lassa fever virus, Bolivian hemorrhagic fever), bunyaviruses (Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus), hantaviruses (hemorrhagic fever virus with renal or pulmonary syndrome) paramyxoviruses, oncogenic RNA viruses. Ribavirin-insensitive DNA viruses - Varicella zoster, pseudorabies virus, cowpox; RNA viruses - enteroviruses, rhinoviruses, encephalitis virus of the forest Semliki.
Ribavirin has activity against the hepatitis C virus (HCV). The mechanism of action of ribavirin against HCV is not fully elucidated. It is assumed that triphosphate accumulating in the course of phosphorylation of ribavirin competitively suppresses the formation of guanosine triphosphate, thereby reducing the synthesis of viral RNAs. It is also believed that the mechanism of synergistic action of ribavirin and interferon alpha against HCV is due to the increased phosphorylation of ribavirin by interferon.
Ribavirin is easily and almost completely absorbed from the digestive tract after ingestion of a single dose. Absolute bioavailability is approximately 65-75%. Free ribavirin does not bind to blood plasma proteins, liposomal ribavirin binds to blood proteins and is quickly distributed in the body (C max was observed in RES organs).
Removing ribavirin from the body is slow. The drug is excreted in the urine, both unchanged and in the form of metabolites, and only about 10% is excreted with feces.
- chronic hepatitis C (for primary therapy of previously untreated interferon alfa-2b patients, with exacerbation after a course of monotherapy with interferon alpha-2b in patients not susceptible to monotherapy with interferon alpha-2b). Treatment is carried out in combination with interferon alpha-2b.
The drug is taken orally at the same time as eating.
Immediately before use, 10-20 ml of distilled or cooled boiled water is added to the contents of the vial. When shaking for 1 to 5 minutes, a uniform suspension should form.
The dose of the drug is 1000 mg / day (1 bottle in the morning and 1 bottle in the evening). Simultaneously, interferon alfa-2b (Reaferon-EU, LeifferonВ®) is administered at 3 million ME 3 times a week. The duration of the course of combination therapy, as a rule, is 24-48 weeks. (for previously untreated patients and patients with genotype 2 and 3 virus not less than 24 weeks, and for patients with the virus of genotype 1 - 48 weeks). When immunity to interferon alfa-2b monotherapy or with relapse of the disease, the course duration is at least 6 months.
From the nervous system: headache, dizziness, general weakness, malaise, insomnia, asthenia, depression, irritability, anxiety, emotional lability, nervousness, agitation, aggressive behavior, confused consciousness, suicidal tendencies, increased smooth muscle tone, tremor, paresthesia, hyperesthesia, hypesthesia, syncope.
From the cardiovascular system: a decrease or increase in blood pressure, bradycardia or tachycardia, a feeling of palpitations.
From the hemopoiesis: hemolytic anemia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia, aplastic anemia.
On the part of the respiratory system: dyspnea, cough, pharyngitis, bronchitis, otitis media, sinusitis, rhinitis.
On the part of the digestive system: dryness of the oral mucosa, decreased appetite, nausea, vomiting, diarrhea, abdominal pain, constipation, taste distortion, pancreatitis, flatulence, stomatitis, glossitis, gum bleeding, hyperbilirubinemia.
From the sense organs: lesions of the lacrimal gland, conjunctivitis, visual impairment, hearing loss / loss, tinnitus.
From the musculoskeletal system: arthralgia, myalgia.
On the part of the genitourinary system: hot flashes, decreased libido, dysmenorrhea, amenorrhea, menorrhagia, prostatitis.
Allergic reactions: skin rash, erythema, urticaria, hyperthermia, bronchospasm, anaphylaxis, photosensitivity, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Other: hair loss, alopecia, hair structure disorder, dry skin, hypothyroidism, chest pain, thirst, fungal infection, viral infection (including herpes), influenza such a syndrome, sweating, lymphadenopathy, transplant rejection after transplant liver and / or kidney.
- chronic heart failure II-III stage;
- myocardial infarction;
- renal failure (CC less than 50 ml / min);
- severe anemia;
- liver failure;
Decompensated cirrhosis of the liver;
- autoimmune diseases (including autoimmune hepatitis);
- non-treatable thyroid disease;
- severe depression with suicidal intentions;
- deficiency of lactase;
- glucose-galactose malabsorption;
- children's and adolescence (up to 18 years);
- lactation period;
- Hypersensitivity to the drug.
With caution appoint the drug to women of reproductive age (the onset of pregnancy is undesirable), with decompensated diabetes mellitus (with attacks of ketoacidosis), COPD, pulmonary embolism, chronic heart failure, thyroid disorders (including thyrotoxicosis), blood clotting disorders, thrombophlebitis, myelodepression, hemoglobinopathy (including thalassemia, sickle cell anemia), patients with depression, suicidal tendencies (including in history); patients with concomitant HIV infection (combined with highly active antiretroviral therapy, there is a risk of developing lactic acidosis), elderly patients.
PREGNANCY AND LACTATION
The drug is contraindicated for use in pregnancy and lactation.
APPLICATION FOR CHILDREN
It is forbidden to use the drug for children under the age of 18 years.
APPLICATION IN ELDERLY PATIENTS
Use with caution in elderly patients. In connection with the possible deterioration in the function of the kidneys in the elderly, the use of the drug should be monitored by the function of the kidneys (including KK).
Before the initiation of hepatitis C therapy, the need for histological confirmation of the diagnosis should be assessed (treatment of patients with the genotype of virus 2 or 3 can begin without prior biopsy of the liver).
Men and women of reproductive age during therapy and within 7 months after the end of treatment should use effective contraceptive means, taking into account the teratogenicity of ribavirin.
Against the background of ribavirin therapy, the maximum reduction in hemoglobin in most cases is observed after 4-8 weeks. from the beginning of treatment. With a decrease in hemoglobin below 100 mg / ml, the dose should be reduced by 50% of the initial dose. In most cases, recommended dose changes ensure the recovery of hemoglobin. With a decrease in hemoglobin below 85 mg / ml, the drug should be discontinued. When acute manifestations of hypersensitivity reactions (hives, angioedema, bronchospasm, anaphylaxis), the drug should be stopped immediately. Transient rashes do not serve as a basis for interrupting treatment.
The content of alpha-tocopherol acetate in the formulation in the amount of 9 mg in the vial is due to its use as an antioxidant. This amount, determined experimentally, prevents the oxidation of the liposomal vesicles contained in the finished dosage form, consisting of phospholipids. The amount of alpha-tocopherol acetate taken with the drug during the day (in 2 bottles contains 18 mg) is 6% of the maximum daily intake indicated in the Methodological Recommendations "Norms of Physiological Needs for Energy and Food Substances for Various Populations of the Russian Federation".
Control of laboratory indicators
Clinical analysis of blood counting the leukocyte count and number of platelets, determination of electrolytes, creatinine content, functional liver samples should be performed before the start of therapy, for 2 and 4 weeks. reception and then regularly. In connection with the possible deterioration in the function of the kidneys in the elderly, the use of the drug should be monitored by the function of the kidneys (including KK).
Influence on ability to drive vehicles, mechanisms
During the period of application of the drug to patients experiencing fatigue, drowsiness or disorientation, it is necessary to refrain from engaging in potentially dangerous activities requiring an increased concentration of attention and speed of psychomotor reactions.
Cases of overdose were not observed. Given that the active substance is ribavirin, then overdose may increase the severity of dose-related side effects.
Treatment: discontinuation of the drug; if necessary, conduct symptomatic therapy.
When combined with ribavirin and interferon alfa-2b, synergism is observed.
In the clinical use of various drugs in therapeutic doses in combination with ribavirin, no significant interaction was found.
The administration of ribavirin during the administration of zidovudine and / or stavudine to patients with concomitant HIV infection is accompanied by a decrease in the phosphorylation of these drugs, which leads to HIV viremia and requires a change in the treatment regimen. With simultaneous use, medicines containing magnesium and aluminum compounds, as well as simethicone reduce the bioavailability of the drug. Increases the concentration of phosphorylated metabolites of purine nucleosides (including didazosin, abacavir) and increases the associated risk of developing dairy acidosis.
With simultaneous application with azotioprine increases the myelotoxicity of the latter.
Does not affect the enzymatic activity of the liver with the participation of cytochrome P450. Simultaneous food intake with a high fat content increases the bioavailability of ribavirin (AUC and C max are increased by 70%).
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in a place protected from light and inaccessible to children at a temperature of up to 25 В° C. Shelf life - 2 years
Not applicable after expiry date.