Hepavirin

Hepavirin is an antiviral drug with a direct type of action. Contains the component ribavirin.

Indications Hepavirin

It is used in individuals with chronic hepatitis subtype C (exclusively in combination with the use of peginterferon α-2β (individuals over 18 years of age) or interferon α-2β (adolescents and children over 3 years of age)) against the background of compensated liver disease.

People who have not previously been prescribed alpha interferons.

For adults: combination with peginterferon α-2β or interferon α-2β in case of increased serum ALT levels, as well as HCV-RNA.

Children over 3 years of age: together with interferon α-2β if HCV RNA is present in the blood serum.

People who have not responded to previous treatment with alpha-interferon.

Adults: together with interferon α-2β, in case of previous monotherapy with α-interferon with a positive effect (with stabilization of ALT levels at the end of therapy), but the development of relapse later.

Persons with clinically stable HIV infection.

Combination with peginterferon α-2β for the treatment of adults with chronic hepatitis C.

Release form

The therapeutic product is released in capsules of 140 pieces per bottle or 1000 capsules per polyethylene bag.

Pharmacodynamics

Ribavirin is a synthetic analogue of nucleoside substances and has a wide range of therapeutic activity against DNA and RNA viruses.

Ribavirin inhibits the binding of DNA and RNA viruses by competitively inhibiting the activity of IMP dehydrogenase.

Pharmacokinetics

The ribavirin component is absorbed at a high rate after oral administration, with plasma Cmax values observed after 1-3 hours (in case of repeated use).

Average bioavailability values are approximately 64%. After a single administration of ribavirin with a fatty meal, AUC values and serum Cmax increase.

Ribavirin is almost not synthesized in the blood with plasma protein. The movement of the component occurs mainly through the equilibrating nucleoside transporter of the es subtype, which is located inside almost all types of cells. Perhaps, it is this mechanism of action that explains the high indicator of the distribution volume of the drug.

In individuals with hepatitis C virus subtype who took ribavirin orally in a dose of 0.6 g, 2 times per day, the equilibrium plasma level of the drug is noted after 1 month. With such use, the half-life after discontinuation of drug use is 298 hours, from which it can be concluded that the excretion of the drug is quite slow.

There is no data on whether the drug penetrates the placenta or into breast milk.

The metabolic processes of ribavirin occur in 2 stages: reversible phosphorylation, as well as deribosylation-type cleavage together with hydrolysis of the amide category, which forms a triazole metabolic product of a carboxyl nature.

About 61% of the orally administered ribavirin (in a 0.6 g dose), pre-labeled with a radioisotope, is excreted in the urine in humans over a period of 336 hours (with 17% of the substance unchanged). Metabolic products, carboxamide with carboxylic acid, are also excreted in the urine.

In people with renal insufficiency, the pharmacokinetic characteristics of the drug after a single use change (AUCtf values, as well as Cmax increase) compared to healthy function (the CC indicator is >90 ml/minute). The level of ribavirin is not subject to significant changes during hemodialysis.

Dosing and administration

Treatment with the drug should be supervised by a doctor with experience in treating people with hepatitis subtype C.

Hepavirin is prohibited to be prescribed as monotherapy, because ribavirin as a single drug for hepatitis subtype C is not effective.

The medicine is taken with food, daily, 2 times a day (in the morning and in the evening). The size of the dosage portion is determined taking into account the patient's weight.

The substance is used in combination with peginterferon α-2β and interferon α-2β. The selection of complex treatment is carried out individually for each patient. In this case, the expected safety and therapeutic effectiveness of the selected combination are taken into account.

Use Hepavirin during pregnancy

Hepavirin is prohibited for use by lactating and pregnant women. The use of the drug can only be started after confirmation of the absence of pregnancy. During therapy and for six months after its completion, women of childbearing age, as well as their partners, must use at least 2 reliable contraceptives.

Due to the existing risk of adverse effects on the infant, breastfeeding should be discontinued before starting treatment.

Contraindications

Main contraindications:

• the presence of intolerance to the ribavirin component or other medicinal components;
• severe heart disease (including uncontrolled or unstable forms), observed for at least six months before the start of therapy;
• hemoglobinopathy (for example, Cooley's anemia or sickle cell anemia);
• those with a debilitating disease in a severe form (also in individuals with chronic renal failure or with a CC level of less than 50 ml/minute);
• severe liver dysfunction or decompensated form of liver cirrhosis;
• use in adolescents and children who have clinical or anamnestic evidence of a severe mental disorder (especially suicidal thoughts, depression or suicide attempts);
• autoimmune hepatitis or other autoimmune pathologies present in the anamnesis (due to combination with interferon α-2β).

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Side effects Hepavirin

Most often, due to the use of Hepavirin, hemolytic anemia occurs (hemoglobin level less than 10 g/l). The development of the disorder can occur after 1-2 weeks from the start of therapy. Due to the occurrence of anemia, complications may develop that affect the respiratory and mental systems, as well as the nervous system and cardiovascular system.

• disorders in the lymph and hematopoietic system: anemia or decreased hemoglobin levels. Thrombocyto-, neutro- or lymphopenia, aplastic anemia, thrombocytopenic purpura and lymphadenopathy are observed occasionally;
• problems affecting the functioning of the cardiovascular system: palpitations, arrhythmia, myocarditis with tachycardia, and in addition peripheral edema, infarction, cardiomyopathy and decreased or increased blood pressure;
• respiratory disorders: nasal congestion, difficulty breathing, pain in the chest and throat, bronchitis with sinusitis, as well as rhinorrhea, runny nose, unproductive cough and pneumonia;
• CNS lesions: migraine attacks, confusion or drowsiness, headaches, hypoesthesia or hyperesthesia, fever and dizziness. In addition, paresthesia, insomnia, seizures, ischemia and stroke, tremor, ataxia, encephalopathy and mental status disorder;
• mental health problems: depression, malaise, nervousness, hostility or apathy, as well as emotional instability, agitation, nightmares, psychosis, aggressive behavior and hallucinations. Also, some patients with complex treatment have had suicidal thoughts and suicide attempts;
• immune lesions: SLE, Quincke's edema, rheumatoid arthritis, vasculitis, and in addition sarcoidosis, anaphylaxis and bronchial spasm;
• endocrine disorders: thyrotoxicosis, hypothyroidism or diabetes;
• metabolic disorders: increased levels of indirect bilirubin or uric acid, hyperglycemia, chromaturia or anorxia, as well as polyuria, acquired lipodystrophy, hypocalcemia, dehydration, weight loss and increased appetite;
• problems with visual function: xerophthalmia, visual impairment and pain in the eyes;
• auditory disorders: tinnitus, hearing impairment or loss, and vertigo;
• gastrointestinal disorders: taste disorders, ulcerative stomatitis, diarrhea and abdominal pain. In addition, cheilitis, periodontal disease and bleeding gums, thirst, dyspepsia and gingivitis, as well as nausea, tooth decay, colitis, flatulence, constipation and vomiting. Along with this, hepatotoxicosis, hepatomegaly or hyperbilirubinemia and pancreatitis (rarely) may occur;
• lesions of subcutaneous tissues and epidermis: rashes, psoriasis, itching, urticaria, hyperhidrosis, acne and alopecia, as well as eczema, dermatitis and photosensitivity. Stevens-Johnson syndrome, maculopapular rashes, erythema multiforme, TEN and hair structure disorders are also noted;
• disorders of the musculoskeletal system: arthritis, arthralgia, myositis or myalgia, as well as muscle pain;
• problems with the urogenital system: polyuria, amenorrhea, prostatitis, infections in the urogenital tract, impotence, menstrual disorders, dysmenorrhea, decreased libido and sexual disorders of a non-specific nature;
• Other symptoms: infections (fungal or respiratory, herpes simplex, conjunctivitis and otitis media with sinusitis), flu-like illnesses, nasopharyngitis, asthenia, feeling of general weakness, fainting, nosebleeds, tumors and flatulence.

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Overdose

Poisoning with Hepavirin can lead to potentiation of the negative signs of the drug.

To eliminate the disorders, the drug is discontinued and then symptomatic measures are carried out.

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Interactions with other drugs

Antacids.

The bioavailability of ribavirin in a 0.6 g dose is reduced when co-administered with an aluminum- or magnesium-containing antacid or with simethicone; AUCtf values are reduced by 14%. It is suggested that the reduction in bioavailability in this test is due to a delay in the movement of ribavirin or to a change in pH. However, this interaction is not considered to be clinically significant.

Analogues of nucleoside substances.

Ribavirin may inhibit the phosphorylation of stavudine and zidovudine in vitro. The clinical significance of this finding is not fully understood, but it suggests that concurrent use of the drug with these agents may result in increased plasma HIV levels. Therefore, careful monitoring of plasma HIV RNA levels is necessary in individuals using Hepavirin with either of these drugs.

If plasma HIV RNA levels increase, the need for combination therapy with reverse transcriptase inhibitors should be reconsidered.

Administration of nucleoside analogues in monotherapy or in combination with other nucleosides may cause lactic acidosis. The ribavirin component increases the levels of phosphorylated metabolic products of purine-type nucleosides. This effect may potentiate the likelihood of developing lactic acidosis caused by purine-type nucleosides (for example, abacavir or didanosine).

Combining the drug with didanosine is prohibited. There are data on the development of mitochondrial toxicity (pancreatitis or lactic acidosis); in some cases, these disorders have led to death.

People with HIV infection who are taking HAART are also at increased risk of developing lactic acidosis. Therefore, combination therapy with HAART should be used with great caution.

The likelihood of developing interactions with the drug remains for 2 subsequent months from the end of therapy (corresponding to 5 half-lives of ribavirin), which is associated with the long half-life of the drug.

The medication is prohibited to be combined with stavudine, zidovudine or didanosine.

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Storage conditions

Hepavirin must be stored in a place closed to children. Temperature values are within the range of 15-30°C.

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Shelf life

Hepavirin can be used within 24 months from the date of release of the drug.

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Analogues

The analogs of the drug are Harvoni, Ribavirin, Olysio, Copegus, Grateziano with Ferrovir, and in addition to this, Incivo, Pegasys, Sofolanork and Intron A. In addition, the list includes Wellferon, Maxvirin, Sofosvel with Infergen, Daclatasvir, Alfarekin and Realdiron with Zadaxin, as well as Sovaldi.