Rebetol

Rebetol is an antiviral medication.

Indications of the rebetola

It is used exclusively in combination with preparations of α-2b interferon or α-2b peginterferon in such disorders:

• a chronic form of hepatitis type C in individuals who had previously been treated with α-2b interferon / peginterferon, and had a positive response to this therapy (stabilization of ALT indices) - with the development of recurrence of the disease;
• previously untreated type C hepatitis in the chronic stage, which proceeds without the development of signs of decompensation of liver activity, but with seropositivity for HCV RNA, as well as elevated ALT values - if there is also fibrosis or a pronounced inflammatory process against the background of the disease.

Release form

The release is carried out in capsules, in quantities of 140 pieces in a separate box.

Pharmacodynamics

Rebetol is a means of artificial origin, it belongs to the group of analogogunucleosides, which have in vitro activity with respect to some DNA- or RNA-containing viruses. When used in standard doses, no specific symptoms of enzyme inhibition are observed, which are observed with HCV, or signs of replication of this virus - neither under the action of ribavirin nor under the influence of its metabolites.

In monotherapy with ribavirin in the period of 0.5-1, and in addition, subsequent monitoring of the patient for 6 months showed no improvement in the histological readings of the liver, and in addition to the elimination of HCV RNA.

The use of only ribavirin for therapy in hepatitis type C (also its chronic stage) did not give the desired result. In this case, complex treatment in people with HCV, in which ribavirin was supplemented with α-2b interferon / peginterferon, showed higher efficacy in comparison with monotherapy, in which the patient was assigned exclusively α-2b interferon / peginterferon.

A mechanism that promotes the development of antiviral effects in such a combination of drugs has not yet been identified.

Pharmacokinetics

When consumed inside a single dose of ribavirin, a weak absorption is observed (a peak value is noted after 1.5 hours) with a rapid subsequent distribution of the drug inside the body. The medicine is rather slowly excreted.

Absorption of ribavirin is almost complete, only 10% of the drug is excreted with feces. At the same time, the level of absolute bioavailability of the drug is within 45-65%, possibly in connection with the effect of the first hepatic transmission. After the use of single portions of drugs in the range of 0.2-1 g there is a linear relationship between the dosage size and AUC. The distribution volume is about 5000 liters. The medicine is not synthesized with the protein inside the plasma.

When the drug was distributed from the systemic blood stream, a thorough study of erythrocytes was carried out, demonstrating that the drug is mainly displaced by equilibrium transmitters of the nucleoside form es. This element is found in almost all cells of the body.

Ribavirin has 2 ways of metabolic transformation: hydrolytic processes (de-ribosylation, as well as hydrolysis of amides), during which the excretion of the carboxyl product of the disintegration of the triazole type occurs, as well as the reversible phosphorylation. The decay products of the drug element (triazolcarboxylic acid together with triazole carboxamide), like himself, are excreted in the urine.

With multiple-dose ribavirin, a noticeable accumulation of drugs within the plasma is observed. Values of bioavailability in a single, as well as reusable application of drugs have a ratio of 1 k6.

With daily intake of 1.2 g of the drug, at the end of the first month of the course, equilibrium values of LS inside the plasma are observed, which are about 2200 ng / ml. The half-life after discontinuation of Rebetol is approximately 298 hours. This indicates that the substance is slowly excreted from the fluids with tissues (except for the plasma only).

In individuals with kidney disease (CC level less than 90 ml / minute) there is an increase in the maximum values of drugs inside the plasma, as well as its AUC. The procedure of hemodialysis almost does not affect the peak indices of the drug inside the plasma.

Dosing and administration

Take capsules orally, 2 times in 24 hours (in the morning, and also in the evening) - with food. The range of daily portions of drugs varies within the limits of 0.8-1.2 g. Against the background of taking the medication should be performed sc administration of α-2b interferon in the amount of 3,000,000 IU three times in 7 days or α-2b peginterferon at a rate of 1.5 mg / kg once during the period of the first week.

When combined with α-2b interferon, people whose weight does not exceed 75 kg, should take Rebetol according to the scheme of 0.4 g in the morning and 0.6 g in the evening. Persons weighing more than 75 kg - 0.6 g in the morning and 0.6 g in the evening.

In the case of combination with α-2b peginterferon, the drug is taken according to the following scheme:

• Persons weighing less than 65 kg - 0.4 grams in the morning, and also in the evening;
• persons with a weight in the range of 65-85 kg - 0.4 g in the morning and 0.6 g in the evening;
• people weighing more than 85 kg - 0.6 g in the morning, as well as in the evening.

Treatment usually lasts for a maximum of 12 months, with various individual limitations, determined by the course of the pathology, sensitivity to drugs and the patient's reaction to the effects of drugs.

After a period of six months of treatment, the patient should be examined to determine his virologic response. In the absence of a reaction, it is necessary to consider the option of abolishing therapy.

If the examination reveals the presence of serious negative symptoms or deviation of the values of laboratory tests, you need to change the dosage regimen of the drug or for a while to cancel the treatment.

If there is a decrease in the Hb level by more than 10 g / dl, the daily portion of the drug should be reduced to 0.6 g, taking 0.2 g in the morning, and 0.4 g in the evening. If the Hb level drops below 8.5 g / dl, treatment should be stopped.

If the patient has stable CCC disease, it is required to change the size of the medicinal portions in cases when the Hb level decreases to 2 g / dl during the 1st month of therapy.

When hematological disorders with the number of leukocytes, platelets or neutrophils are less, respectively, 1500, 50 000 and 750 μl, it is necessary to reduce the dosage of interferons. If the white blood cells, platelets, as well as neutrophils are smaller, respectively, 1000, 25 000, and 500 μl - it is required to stop treatment.

Treatment should also be stopped in the case of a 2.5-fold increase in the values of direct bilirubin (in comparison with VGN).

If the indirect bilirubin is increased by more than 5 mg / dL, the daily portion of the drug should be reduced to 0.6 g, and with a regular increase in this value by more than 4 mg / dL during the first month, therapy should be discontinued.

If there is an increase in hepatic transaminase activity that is more than twice the normal value, or there is an increase in the CC level by more than 2 mg / dl, it is necessary to complete the drug intake.

If there are no noticeable improvements after the adjustments to the portions have been performed, complex therapy should be abolished.

[1]

Use of the rebetola during pregnancy

Prescribe Rebetol to nursing mothers and pregnant women is prohibited.

Contraindications

The main contraindications:

• heart diseases in severe degree (this includes both resistant to therapy, as well as unstable types of pathologies) observed in the patient during a period of at least 6 months before the appointment of drugs;
• hemoglobinopathy (including thalassemia and sickle cell form of anemia);
• resistant to the therapy of thyroid disease;
• kidney disease in severe forms (among those with CRF with a level of CC less than 50 ml / minute, as well as with the implementation of hemodialysis procedures);
• Depression in severe degree, against which there is a propensity to suicide (also available in history);
• disorders in the liver in a severe degree;
• pathologies of autoimmune character (among them autoimmune form of hepatitis);
• decompensated stage of hepatic cirrhosis;
• the presence of hypersensitivity to ribavirin or other elements of the drug;
• children under 18 years of age.

Particular care is needed when using complex treatment in the following disorders:

• pulmonary diseases in severe form (among them chronic stages of obstructive pathologies);
• other heart diseases;
• Diabetes mellitus, on the background of which ketoacidosis can develop;
• oppression of the hematopoietic function of the bone marrow;
• concomitant antiretroviral therapy for HIV with high activity (because this increases the likelihood of developing a lactic acid form of acidosis);
• problems with blood loss (presence of thrombophlebitis or thromboembolism, etc.).

Side effects of the rebetola

The development of the following adverse events is usually observed during the combined use of Rebetol with α-2b interferon / peginterferon:

• defeat of the hematopoietic organs: the development of neutrophilic, thrombocyto-, leuko- or granulocytopenia, and in addition anemia (and its aplastic form) and hemolysis (this is the main side effect);
• disorders of the function of the NC: the appearance of tremors, headaches, suicidal thoughts, paresthesias, dizziness, as well as hypesthesia or hyperesthesia. There can be aggression, a sense of nervousness, anxiety, confusion, irritability, emotional instability and emotional arousal. In addition, insomnia or depression occurs, and concentration also worsens;
• violations of the digestive function: the emergence of vomiting or nausea, diarrhea or bloating, constipation and abdominal pain, as well as dyspeptic symptoms. At the same time, glossitis, stomatitis, anorexia or pancreatitis can develop, and in addition taste flavors and bleeding in the gum area;
• disorders in the endocrine system: fluctuations in thyrotropin, against which the development of thyroid disorders may develop, which will require treatment, and in addition the development of hypothyroidism;
• violations of the function of the CCC: the development of tachycardia, the appearance of a heartbeat or pain behind the sternum, and in addition to syncope and changes in blood pressure (decrease or increase);
• defeat of the respiratory system: development of pharyngitis, runny nose, cough, dyspnoea, bronchitis or sinusitis;
• reactions of the genitals: the development of amenorrhea, prostatitis, menorrhagia, and in addition a decrease in libido, the appearance of tides and changes in the menstrual cycle;
• manifestations of musculature and bones: the development of myalgia or arthralgia, as well as an increase in smooth muscle tone;
• affections of the senses: ear noises, visual disturbances, hearing problems or its complete loss, the development of disorders affecting the lacrimal gland or conjunctivitis;
• disorders on the skin surface: rashes or itching, erythema polyforma, eczema, alopecia, and in addition Stevens-Johnson syndrome, photosensitivity, damage to the hair structure, dry skin, erythema, TEN and herpetic infection;
• the testimony of laboratory tests: an increase in the values of uric acid, and in addition indirect bilirubin, arising from hemolysis (normalization of these parameters occurs within 1 month after the completion of therapy);
• others: development of infection (fungal or viral origin), lymphadenopathy, allergy symptoms, otitis media, asthenia, fever and hyperhidrosis, as well as influenza-like syndrome. In addition, there is a feeling of thirst, malaise and weakness, as well as a chill. Possible weight loss, the occurrence of pain at the site of injection and the appearance of dryness of the oral mucosa.

Interactions with other drugs

With oral intake of a single dose of drugs, the level of its bioavailability was increased when combined with fatty foods. The Cmax values also increased and, by 70%, the AUC level. Most likely, such a reaction is caused by a slowing down of the processes of ribavirin transfer or by deviations in the values of gastric pH. It was not possible to determine the pharmacokinetic significance of these indications. Although in clinical trials, the effectiveness of the drug was not an emphasis on the use of drugs with or without food, it is recommended to take capsules in combination with food - possibly in connection with the acceleration of the process of achieving Cmax values inside the plasma.

The study of drug interactions with other drugs is limited only to tests involving α-2b interferon / peginterferon, and antacid agents in addition.

The intake of 0.6 g of Rebetol, together with antacids containing simethicone or the synthesis of magnesium with aluminum, led to a 14% decrease in the level of bioavailability of the main drug. As with fatty foods, this phenomenon can be attributed to reactions to changes in gastric pH values or to a deviation in the movement of a drug substance. These effects are not of clinical significance.

With repeated use of α-2b interferon / peginterferon along with Rebetol, no significant pharmacokinetic interactions were observed.

In vitro studies have shown that ribavirin can inhibit zidovudine phosphorylation with stavudine. The full picture of this interaction could not be clarified, but the obtained information allows us to conclude that the combination of drug data may increase the HIV indices inside the plasma. Therefore, when the drug is combined with zidovudine or stavudine, it is necessary to regularly monitor plasma RNA-HIV values. If their level increases, it is necessary to adjust the conditions of complex treatment.

Ribavirin is able to increase the values of phosphorylated purine nucleoside metabolites, which increases the likelihood of developing a lactic acidosis form caused by purine nucleosides (such as didanosine or abacavir, etc.).

Due to the fact that the drug is slowly excreted, it can maintain the ability to interact with other drugs for at least 2 consecutive months.

In vitro tests have demonstrated that Rebetol has no effect on hemoprotein P450.

[2], [3]

Storage conditions

Rebetol is required to be kept in the usual conditions for medicines. The temperature should not be above 30 ° C.

Shelf life

Rebetol can be used for 2 years after the release of the drug.

Reviews

Rebetol has rather limited information about its use - in connection with the specificity of the drug. Therefore, it is impossible to obtain full information about its merits and demerits. The small number of reviews available on the Internet makes it clear that the drug is highly effective, but it is quite dangerous, because it has many side effects.