Gepavirin

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

Indications Hepavirin

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

People who have not previously been prescribed the use of α-interferon.

For an adult: combination with peginterferon α-2β or interferon α-2β with increased serum ALT, as well as HCV-RNA.

Children older than 3 years of age: together with interferon α-2β, if HCV-RNA is present inside the blood serum.

People who were not helped by previous treatment with α-interferon.

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

Persons with a clinically stable HIV infection.

Combination with peginterferon α-2β for therapy in adults of people with hepatitis C subtype C in a chronic degree.

Release form

The release of a therapeutic agent is realized in capsules of 140 pieces inside a bottle or 1000 capsules inside bags of polyethylene.

Pharmacodynamics

Ribavirin is an artificial analogue of nucleoside substances and has a large range of therapeutic activity against DNA and RNA viruses.

Ribavirin inhibits the binding of DNA and RNA viruses, carrying out a competitive slowdown in the activity of IMP dehydrogenase.

Pharmacokinetics

The high-speed ribavirin component is absorbed after ingestion, plasma Cmax values are noted after 1-3 hours (in the case of multiple use).

The average bioavailability values are around 64%. After 1-time use of ribavirin with a fat dish, the AUC values increase, as well as the serum Cmax value.

Ribavirin is almost not synthesized inside the blood with plasma protein. The movement of the component mainly occurs through the balancing nucleoside transporter of the es subtype, which is located within almost all cell types. Perhaps it is this mechanism of influence that explains the high indicator of the distribution volume of drugs.

In individuals with hepatitis C subtype C, who consumed ribavirin orally in portions of 0.6 g, 2 times a day, the equilibrium plasma level of the drug is noted after the 1st month. With such an application, the half-life after stopping the use of the drug is 298 hours, from which it can be concluded that the drug is rather slow to excrete.

There is no evidence whether the medicine penetrates the placenta or into the breast milk.

Ribavirin metabolic processes occur in 2 stages: phosphorylation of a reversible nature, as well as decomposition by the type of deribosylation along with hydrolysis of the amide category, in which the triazole metabolic product of carboxyl character is formed.

About 61% of ingested ribavirin (in a portion of 0.6 g), previously labeled with a radioisotope, is excreted in humans with urine for a period of 336 hours (while in unchanged condition - 17% of the substance). Metabolic products, carboxamide with carboxylic acid, are also excreted in the urine.

In people with kidney failure, the pharmacokinetic characteristics of drugs after 1-time use change (AUCtf values, as well as Cmax increase) in comparison with healthy function (CC index is> 90 ml / minute). Ribavirin levels are not significantly altered during hemodialysis.

Dosing and administration

Treatment with the use of the drug should be monitored by a doctor with therapy experience in persons suffering from hepatitis subtype C.

Hepavirin is forbidden to be prescribed in the form of monotherapy, because ribavirin as the only drug in hepatitis subtype C is not effective.

The medication is used together with food, every day, 2 times a day (in the morning and also in the evening). The size of the dosage portion is determined by taking into account the weight of the patient.

The substance is used in combination with peginterferon α-2β and interferon α-2β. Selection of complex treatment is performed individually for each patient. This takes into account the expected safety and therapeutic efficacy of the selected combination.

Use Hepavirin during pregnancy

Hepavirin is prohibited to use lactating and pregnant women. You can start using the drug only after confirming the absence of pregnancy. During therapy and for half a year after its completion, women who are in childbearing age, as well as their partners, should use at least 2 reliable contraceptives.

Due to the existing risk of a negative effect on the infant, breastfeeding should be canceled before starting treatment.

Contraindications

Main contraindications:

• the presence of intolerance in relation to the component of ribavirin or other medicinal components;
• severe heart disease (among them uncontrolled or unstable forms), occurring for at least six months before starting therapy;
• hemoglobinopathy (for example, Quli anemia or sickle-cell anemia);
• severe debilitating nature of the disease (also in patients with chronic renal function insufficiency or with a CC level of less than 50 ml / minute);
• a disorder in the liver of a severe character or decompensated form of hepatic cirrhosis;
• use in adolescents and children who have clinical or anamnestic evidence of a severe mental disorder (especially suicidal thoughts, depression, or suicidal attempts);
• autoimmune hepatitis or other autoimmune pathologies present in history (due to combination with interferon α-2β).

[1], [2], [3], [4]

Side effects Hepavirin

Most often, due to the use of Hepavirin, anemia of a hemolytic nature occurs (hemoglobin index is less than 10 g / l). The development of a disorder can occur after 1-2 weeks from the moment of initiation of therapy. Due to the occurrence of anemia, complications may occur that affect the respiratory and mental systems, as well as NA and SSS.

• disorders of the lymph and hematopoietic system: anemia or decrease in hemoglobin. Thrombocyte, neutro or lymphopenia, anemia of aplastic character, thrombocytopenic form of purpura and lymphadenopathy are singly noted;
• problems affecting the work of the cardiovascular system: heartbeat, arrhythmia, myocarditis with tachycardia, and in addition, peripheral edema, heart attack, cardiomyopathy and a decrease or increase in blood pressure values;
• impaired respiratory function: nasal congestion, breathing disorder, pain in the sternum and throat, bronchitis with sinusitis, as well as rhinorrhea, runny nose, cough of unproductive type and pneumonia;
• CNS lesions: migraine attacks, feeling of confusion or drowsiness, headaches, hypoesthesia or hyperesthesia, fever and dizziness. In addition, paresthesia, insomnia, convulsions, ischemia and stroke, tremor, ataxia, encephalopathy and mental disorder;
• mental problems: a state of depression, anxiety, nervousness, hostility or apathy, as well as emotional instability, agitation, nightmares, psychosis, aggressive behavior and hallucinations. Also, individual patients with complex treatment had thoughts about suicide and suicidal attempts;
• immune lesions: SLE, angioedema, rheumatoid arthritis, vasculitis, and in addition sarcoidosis, anaphylaxis and bronchial spasm;
• endocrine disorders: thyrotoxicosis, hypothyroidism, or diabetes;
• metabolic disorders: an increase in the values of indirect bilirubin or uric acid, hyperglycemia, chromaturia or anorkia, and in addition polyuria, acquired lipodystrophy, hypocalcemia, dehydration, weight loss and increased appetite;
• problems with visual function: xerophthalmia, visual disturbance and pain in the eyes;
• hearing disorders: ear noise, derangement or loss of hearing and vertigo;
• disorders of the gastrointestinal tract: taste disorder, ulcerative stomatitis, diarrhea and pain in the abdominal area. In addition, cheilitis, periodontal disease and bleeding gums, thirst, dyspepsia and gingivitis, as well as nausea, tooth damage, colitis, flatulence, constipation and vomiting. Along with this, hepatotoxicosis, hepatomegaly, or hyperbilirubinemia and pancreatitis may occur (rarely);
• lesions of the subcutaneous tissue and epidermis: rashes, psoriasis, pruritus, urticaria, hyperhidrosis, acne and alopecia, as well as eczema, dermatitis and photosensitivity. Also noted is Stevens-Johnson syndrome, a rash of a maculopapular nature, erythema multiforme, PET, and a violation of the hair structure;
• ODA activity disorders: arthritis, arthralgia, myositis or myalgia, and muscle pain;
• problems with the work of the urogenital system: polyuria, amenorrhea, prostatitis, infections in the urogenital tract, impotence, menstrual disorders, dysmenorrhea, weakening of libido and sexual disorders that are non-specific;
• other symptoms: infections (fungal or respiratory, common herpes, conjunctivitis, and otitis media with sinusitis), flu-like illness, nasopharyngitis, asthenia, general weakness, fainting, nosebleeds, swelling and flatulence.

[5]

Overdose

Hepavirin poisoning can lead to potentiation of negative symptoms of drugs.

To eliminate the disorders, the medication is canceled and then symptomatic measures are taken.

[6], [7]

Interactions with other drugs

Antacid agents.

The level of bioavailability of ribavirin in a portion of 0.6 g decreases with combined use with an aluminum or magnesium-containing antacid or simethicone; AUCtf values are reduced by 14%. There is an assumption that the decrease in bioavailability in this test was due to the delay in the movement of ribavirin or due to changes in pH. In this case, it is believed that this interaction does not have clinical significance.

Analogs of nucleoside substances.

Ribbonirin in vitro testing can inhibit the phosphorylation of stavudine with zidovudine. The clinical significance of such information is not definitively determined, but they suggest that the competitive use of a drug with these substances may cause an increase in the plasma values of HIV. Because of this, it is necessary to closely monitor the RNA-HIV counts inside the blood plasma in individuals who use Hepavirin along with any of these drugs.

In the case of an increase in plasma values of RNA-HIV, the need for a combination treatment with substances that inhibit reverse transcriptase should be reconsidered.

The introduction of analogs of nucleoside drugs in monotherapy or in combination with other nucleosides can cause the appearance of lactic acidosis. The ribavirin component increases the values of phosphorylated metabolic products of purine-type nucleosides. This effect may potentiate the likelihood of the development of lactic acidosis caused by purine nucleosides (for example, abacavir or didanosine).

It is forbidden to combine the drug with didanosine. There is evidence of the development of mitochondrial-type toxicity (pancreatitis or lactic acidosis); in some cases, these violations led to death.

People with HIV who use HAART also increase the likelihood of developing lactic acidosis. Because of this, complex treatment in combination with HAART should be performed with great care.

The probability of development of interaction with the drug persists for the next 2 months from the moment of termination of therapy (corresponds to 5 terms of ribavirin half-life), which is associated with a long half-life of drugs.

The drug should not be combined with stavudine, zidovudine or didanosine.

[8], [9], [10], [11],

Storage conditions

Hepavirin is required to be kept in a place that is closed to children. Temperature values - within the limits of 15-30 ° С.

[12]

Shelf life

Hepavirin can be used within a 24-month period from the date of release of the drug.

[13], [14], [15], [16]

Analogs

Analogues of the medication are Harvoni, Ribavirin, Olizio, Kopegus, Gratetsiano with Ferrovir, and Inviso, Pegasys, Sofolanork and Intron A. In addition, Wellferon, Maksvirin, Sofosvel with Infergen, Daclatasvir, Alfarekin and Derfine, and Brainworm and Brainworm and Brainworm are in the list. Sovaldi.