Virazol - instructions for use, dose, side effects, contraindications

Pharmacodynamics:Virazol® has a wide spectrum of activity against various RNAs (arenaviruses, bunyaviruses, retroviruses, paramyxoviruses, etc.) and DNA (adenovirus, herpes virus, cytomegalovirus, etc.) containing viruses. The drug depresses the replication of viruses-pathogens of extremely dangerous hemorrhagic fevers both in vitro and in vivo. The prophylactic and therapeutic activity of Virazole® is shown in experiments on primates for haemorrhagic fevers caused by arenaviruses: Lassa fever, Bolivian hemorrhagic fever; Bunyaviruses: fever of the Rift Valley, Crimea-Congo hemorrhagic fever, and also hantaviruses: hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome.

Various strains of highly pathogenic arena and bunyaviruses Lassa, Machupo,Crimea-Congo, Hantaan, Seoul, Puumula, Dobrava and Sin Nombre, isolated from wild rodents and sick people in different geographical regions of the world, are highly sensitive to Virazol®.

Virazol® rapidly penetrates into virus-infected cells, and is easily phosphorylated by intracellular adenosine kinase to mono-, di- and triphosphate metabolites.

Ribavirin triphosphate is a potent competitive inhibitor of inosine monophosphate dehydrogenase, viral RNA polymerase and viral mRNA-guanyltransferase. Inhibition of the latter stops the capping of Mink, which leads to a significant depletion of intracellular reserves of guanosine triphosphate, inhibition of the synthesis of the virus-specific protein and viral RNA. Ribavirin is also built into the viral genome, causing fatal mutations.

Ribavirin inhibits the replication of new virions, which leads to a decrease in viral load; the drug selectively inhibits the synthesis of viral RNA, without suppressing the synthesis of RNA in healthy cells.

Virazol® in the treatment of hemorrhagic fever with renal syndrome significantly reduces the severity of the disease: reduced duration of symptoms such as fever, oliguria, back pain, stomach and headache.The pronounced decrease in urea and creatinine indicates a decrease in the degree of renal damage. The risk of developing hemorrhages in patients using Virazol® is significantly reduced.

Pharmacokinetics:With intravenous administration of Virazole®, the maximum plasma concentration is reached at the end of the infusion and is 43 and 72 μmol / L for doses of 600 mg and 1200 mg, respectively. The drug is distributed in the plasma, the secrets of the mucous membrane of the respiratory tract and erythrocytes. The half-distribution period is about 0.2 hours. A large amount of the active metabolite - ribavirin triphosphate - accumulates in the erythrocytes, reaching a constant concentration after about 4 days, and remains there for several weeks after application.

Significant concentration (after long-term use) can be detected in cerebrospinal fluid (67% of that in plasma).

Metabolized intracellularly by reversible phosphorylation with the formation of mono-, di- and triphosphate (active) metabolites; is also metabolized to 1,2,4-triazolecarboxamide. Inactivation is carried out by de-rososylation followed by hydrolysis and rupture of the triazole ring.With intravenous administration, the elimination half-life (T1 / 2) is 0.5-2 h.

It binds to plasma proteins in small amounts.

After intravenous administration, 19% of the drug in unchanged form is excreted by the kidneys within 24 hours and 24% - within 48 hours. The renal excretion pathway is also characteristic of the metabolite 1,2,4-triazolecarboxamide.

The half-life is 0.5 to 2 hours.

It is not excreted by hemodialysis. In patients with renal insufficiency, the area under the pharmacokinetic curve "concentration-time" (AUC) and the maximum concentration in the blood plasma (Cmax) increase, which is caused by a decrease in the true clearance. In patients with hepatic insufficiency, pharmacokinetics does not change.

Indications:Hemorrhagic fever with kidney syndrome.

Contraindications:- Hypersensitivity to ribavirin or to any of the components of the drug;

- pregnancy, lactation period;

- XCH IIb-III st., Myocardial infarction;

- renal failure (creatinine clearance <50 ml / min);

- severe hepatic insufficiency (decompensated cirrhosis of the liver);

- severe anemia;

- children's and adolescence (up to 18 years);

- autoimmune diseases (including autoimmune hepatitis);

- non-treatable thyroid disease;

- severe depression with suicidal intentions.

Carefully:- women of reproductive age (pregnancy is not desirable);

- Patients with decompensated diabetes mellitus (with attacks of ketoacidosis);

- CHF;

- COPD, thromboembolism of the pulmonary artery;

- Thyroid gland diseases (including thyrotoxicosis);

- coagulation disorders, thrombophlebitis;

- hemoglobinopathy (thalassemia, sickle-cell anemia);

- Myelodepression;

- Depression, propensity to suicide (including in the anamnesis);

- concomitant HIV infection (combined with highly active antiretroviral therapy - risk of lactate-acidosis);

- elderly age.

Dosing and Administration:Virazol® concentrate for solution for infusion is administered intravenously. The dose of Virazole® concentrate for the preparation of a solution for infusions for each patient is calculated individually, depending on the body weight. Before administration, a concentrated solution of Virazole for infusions should be diluted with 5% dextrose solution for injection or 0.9% solution of sodium chloride for injection.

The total volume of the injected solution is adjusted to 100 ml. The resulting solution is administered by infusion through a perfusor for 30 minutes.

With jet injection of Virazole®, patients may experience chills, so it is recommended to inject the drug slowly for 10-15 minutes.

The concentrate of Virazole® for intravenous infusions does not contain preservatives, and after dilution it should be used within 24 hours.

The initial loading dose is 33 mg / kg body weight. Six hours after this dose, 16 mg / kg body weight is administered every 6 hours for 4 days (16 doses in total). 8 hours after the administration of the last of these doses, the drug is started at 8 mg / kg every 8 hours for 3 days (9 doses).

(Table 1).

Table 1

_Day\^Time

8:00

14:00

20:00

2:00

mg / kg

_Day\^Time

8:00

16:00

00:00

mg / kg

Treatment with Virazol® in this dose can be continued depending on the patient's condition and the appointment of the attending physician, but should not exceed 14 days.

Side effects:From the nervous system: headache, insomnia, asthenic syndrome,depression, irritability, confused consciousness, increased smooth muscle tone, tremor, paresthesia, hyperesthesia, hypoesthesia, fainting.

From the cardiovascular system: decrease in blood pressure, brady- or tachycardia, cardiac arrest.

On the part of the system of blood and hematopoiesis: Hemolytic anemia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia.

From the respiratory system: pneumothorax, dyspnea, bronchospasm, pulmonary edema, hypoventilation syndrome, lung atelectasis.

From the digestive system: anorexia, nausea, vomiting, hyperbilirubinemia, abdominal pain, constipation, taste perversion, pancreatitis, flatulence, dryness of the oral mucosa, stomatitis, glossitis, bleeding from the gums.

Allergic reactions: photosensitivity, skin rash, urticaria, hyperemia, erythema multiforme, anaphylaxis, toxic epidermal necrolysis.

From the genitourinary system: "hot flashes", dysmenorrhea, amenorrhea, menorrhagia, prostatitis.

From the musculoskeletal system: arthralgia, myalgia.

From the sense organs: lesions of the lacrimal gland, conjunctivitis, visual impairment, hearing impairment / loss, tinnitus.

Other: hair loss, hair structure disorder, hypothyroidism, thirst, fungal infection, viral infection (including herpes), flu-like syndrome, sweating, lymphadenopathy.

Overdose:Cases of an overdose of Virazole® are not described.

Interaction:The administration of ribavirin during treatment with zidovudine and / or stavudine is accompanied by a decrease in their phosphorylation, which may lead to an increase in HIV viremia and require a change in the treatment regimen.

When combined with interferon alpha-2b or peginterferon alfa-2b-synergism action.

Increases the concentration of phosphorylated metabolites of purine nucleosides (including didanosine, abacavir) and the associated risk of developing lactic acidosis.

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%).

Special instructions:It is used only in a hospital with a specialized resuscitation department.

Medical staff working with the drug should take into account its teratogenicity.

Men and women of childbearing age during treatment and for 7 months after the end of therapy should use reliable methods of contraception.

Laboratory tests (clinical blood counts with calculating the leukocyte formula and platelet count, electrolyte analysis, determination of creatinine content, functional liver samples) should be performed before the start of therapy, at 2 and 4 weeks and then regularly.

During treatment with ribavirin, the maximum decrease in hemoglobin (Hb) in most cases occurs after 4-8 weeks from the start of treatment. With a decrease in Hb below 110 g / l, the dose of the drug should be temporarily reduced by 400 mg per day, with a decrease in Hb below 100 g / l, reduce the dose to 50% of the original dose. If the intolerance of ribavirin remains intact after dose adjustment, as well as the fall of Hb below 85 g / L, the drug should be discontinued.

When acute manifestation of hypersensitivity (hives, angioedema, bronchospasm, anaphylaxis), the drug should be discontinued. Transient rashes do not serve as a basis for interrupting treatment.

Effect on the ability to drive transp. cf.and fur:During treatment, people who experience fatigue, drowsiness, or disorientation should refrain from doing work that requires increased attention and speed of psychomotor reactions (including driving, controlling the mechanisms).

Form release / dosage:Concentrate for the preparation of a solution for infusions of 100 mg / ml.

Packaging:For 12 ml in colorless glass bottles of hydrolytic glass, class 1, Hept. F., sealed with gray plugs of butyl rubber with fluoropolymer coating from the inside, with the rolling off of aluminum caps.

5 bottles of the drug are placed in a tray of plastic. The tray along with the instructions for use are placed in a cardboard box.

Storage conditions:In a dry, the dark place at a temperature of 15 to 25 0C.

Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N015481 / 01

Date of registration:15.02.2011

Expiration Date:Unlimited

The owner of the registration certificate:MEDA Pharmaceuticals Switzerland GmbHMEDA Pharmaceuticals Switzerland GmbH Switzerland

Manufacturer: & nbsp

MEDA PHARMACEUTICALS SWITZERLAND, GmbH Switzerland

Representation: & nbspMEDA Pharmaceuticals Switzerland GmbH MEDA Pharmaceuticals Switzerland GmbH Switzerland

Information update date: & nbsp19.02.2017

Illustrated instructions

Instructions

Virazol® (Virazole®)