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

Excipients: lactose monohydrate (modified) 121,00 mg / 102.00 mg, silicon dioxide colloidal 2,00 mg / 1.00 mg, giprolase 5,50 mg / 15.00 mg, talcum powder 3,00 mg / 4.00 mg, magnesium stearate 2,00 mg / 8.00 mg.

Gelatine capsule: lid (dyeing Helidone pink No. 28 0,0153%, color of diamond blue № 1 0,1143%, titanium dioxide (E171) 1,4425%, gelatin q.s. before 100,0%); body (titanium dioxide (E171) 2,9079%, gelatin q.s. before 100,0%).

Description:

Dosage 200 mg: hard gelatin capsules 2 with an opaque blue lid and a white body.

Dosage 400 mg: hard gelatin capsules 0 with an opaque blue lid and a white body.

Contents of capsules: a homogeneous powder of white color.

Pharmacotherapeutic group:An antiviral agent.

ATX: & nbsp

J.05.A.B Nucleosides and nucleotides

J.05.A.B.04 Ribavirin

Pharmacodynamics:

Ribavirin is a synthetic analogue of nucleosides, active in vitro for some RNA (ribonucleic acid) - and DNA (deoxyribonucleic acid) - containing viruses. Neither ribavirin, nor its intracellular nucleoside metabolites in physiological concentrations cause inhibition of enzymes specific for the hepatitis virus C (HCV), or suppression of HCV.Monotherapy with ribavirin does not lead to the elimination of the virus (RNA virus of hepatitis C (RNA-HCV) in serum) or improvement of histological characteristics of the liver after 6-12 months of ribavirin and during 6 months of follow-up. The use of ribavirin as the sole therapeutic agent for hepatitis C, including its chronic form, is ineffective. However, combined treatment with ribavirin and peginterferon alfa-2b or interferon alpha-2b HCV is more effective than monotherapy with peginterferon alfa-2b or interferon alpha-2b. The mechanism by which ribavirin in combination with peginterferon alfa-2b or interferon alpha-2b has an antiviral effect, in particular against the hepatitis virus C (HCV), is unknown.

Pharmacokinetics:

Suction. After ingestion it is easily absorbed in the gastrointestinal tract (GIT), quickly distributed into all tissues, including cerebrospinal fluid and the brain. The time to reach the maximum concentration (C_max) in blood plasma for ingestion 1-1,5 h. Average value C_max in the blood plasma around 5 μmol / l at the end 1 Weeks of admission in a dose 200 mg every 8 h and about 11 μmol / l at the end 1 Weeks of admission in a dose 400 mg every 8 h.

Distribution. Absolute bioavailability approximately 45-65%, which, apparently, is due to the effect of primary passage through the liver. There is a linear relationship between dose and area under the concentration-time curve (AUC) when taking single doses of ribavirin from 200 mg to 1200 mg. The volume of distribution is approximately 5000 l. Does not bind to blood plasma proteins. Transport outside the blood plasma occurs with the participation of a counterbalancing nucleoside transporter type es (nitrobenzylthioinosine sensitive). This type of transporter is present in all types of cells. Distributed in blood plasma, the secretion of the mucous membrane of the respiratory tract and erythrocytes. With repeated introduction ribavirin accumulates in plasma in large quantities. When administered, a steady-state ribavirin concentration in the blood plasma was reached by the end 4 of the week. A significant amount of the active metabolite of ribavirin - triphosphate accumulates in erythrocytes, reaching a plateau to 4 day and staying in them for several weeks after the end of the application.

Metabolism. Ribavirin is metabolized intracellularly by phosphorylation to form mono-, di- and triphosphate (active) metabolites, as well as up to 1,2,4- triazolecarboxamide. It is inactivated by deibosylation followed by hydrolysis and rupture of the triazole ring.

Excretion. Removing ribavirin from the body is slow. Half-life (T_1/2) depends on the tissues. It is excreted by the kidneys in the form of metabolites and unchanged. 10% excreted with feces. In an unchanged form, about 7% Ribavirin is excreted in 24 h and about 10% behind 48 h. For oral administration of a single dose T_1/2is 27-36 h, when reaching a stable concentration - 151 - 298 h, which indicates its slow release from other parts of the body, except for blood plasma. The renal excretion pathway is also characteristic of the metabolite 1, 2,4-triazolecarboxamide.

When taking ribavarin patients with renal insufficiency AUC and C_maxRibavirin increase, which is due to a decrease in true clearance. The concentration of ribavirin in the blood plasma during hemodialysis does not change significantly.

In patients with hepatic impairment the pharmacokinetics of ribavirin does not change. After taking a single dose with food containing fats, the pharmacokinetics of ribavirin vary significantly (AUC and C_max increase by 70%, absolute bioavailability increases to 75%).

Indications:

Chronic hepatitis C (CHC) (in combination with peginterferon alfa-2b or interferon alpha-2b):

- in patients who have not previously been treated with peginterferon alfa-2b or interferon alpha-2b;

- in patients who have a favorable response to previous treatment with peginterferon alfa-2b or interferon alpha-2b, but who subsequently had an exacerbation of the disease;

- in patients who had previously treated with peginterferon alfa-2b or interferon alpha-2 was ineffective.

Contraindications:

Hypersensitivity to ribavirin and other components; severe heart diseases, including those with unstable and uncontrolled currents, existing, at least 6 months preceding treatment with ribavirin (including chronic heart failure (XCH) IIb)III degree, acute myocardial infarction, unstable angina, cardiomyopathy); chronic renal failure (CRF) (creatinine clearance (KK) less 50 ml / min), including hemodialysis; hemoglobinopathy (including thalassemia, sickle cell anemia); function violationhepatic liver or decompensated hepatic cirrhosis; patients with concomitant HIV (human immunodeficiency virus) - infection, cirrhosis and liver failure (not less than 6 ballon the Child-Pugh scale); heavy mental illness or severe mental disorders in the history (including severe depression, suicidal ideation and suicidal attempts); autoimmune diseases (including autoimmune hepatitis) in the anamnesis; diseases of the thyroid gland, if they are not amenable to drug treatment; lactose intolerance, lactase deficiency, glucose-galactose malabsorption; children's age until 18 years; pregnancy, the period of breastfeeding.

Carefully:

When used in women of reproductive age, decompensated diabetes mellitus (with attacks of ketoacidosis); chronic obstructive pulmonary disease; XCH I- II degree; CRF (QC is more 50 ml / min), mild and moderate liver dysfunction; violation of the blood coagulation system, including thrombophlebitis, pulmonary embolism, myelosuppression; in patients with concomitant HIV infection during combined high-activity antiretroviral therapy (BAAPT) (due to toxic effects on the mitochondrial apparatus and an increased risk of lactic acidosis); elderly age.

Pregnancy and lactation:

Significant teratogenic and embryotoxic effects on the human fetus are grounds for contraindication of the use of ribavirin during pregnancy.

There is no data on the penetration of ribavirin into breast milk. It is necessary to stop breastfeeding the baby when ribavirin is needed.

Dosing and Administration:Inside, 2 times a day (morning and evening), not chewing and washing with water, while eating.
The drug Trivorin is used only in combination with peginterferon alfa-2b or interferon alpha-2b, so you should read the instructions for the medical use of these drugs.
Interferon alfa-2b or peginterferon alfa-2b is injected subcutaneously: interferon alfa-2b - 3,000,000 IU 3 times a week; peginterferon alfa-2b - 1.5 μg / kg body weight once a week.
Treatment with the drug Trivorin should be carried out under the supervision of a doctor who has experience in the treatment of patients with HCV.
The dose of Trivorin depends on the patient's body weight (see Table 1).
Table number 1.
Recommended doses of the drug Trivorin, depending on the body weight of the patient

Body weight (kg)	Daily dose (mg / day)	Dosing regimen
less 65	800	by 400 mg in the morning and 400 mg in the evening
from 65 to 85	1000	by 400 mg in the morning and 600 mg in the evening
from 86 before 105	1200	by 600 mg in the morning and 600 mg in the evening
more 105	1400	by 600 mg in the morning and 800 mg in the evening

Duration of treatment is from 24 to 48 weeks.
The duration of the course of treatment depends on the clinical course of the disease, the response to ongoing therapy and its tolerability. Recommended duration of treatment:
- in patients who had not previously been treated - at least 24 weeks, in patients with genotype 1 - not less than 48 weeks;
- in patients who have a favorable response to previous treatment, but who subsequently had an exacerbation of the disease, as well as the ineffectiveness of previous treatment - from 24 to 48 weeks.
Situations that may require adjustment of the dosing regimen
After 6 months of therapy, a patient should be examined for a virologic response. In the absence of a virologic response, a decision should be made to discontinue combination therapy with Trivorin and interferon alfa-2b or peginterferon alfa-2b.
If serious adverse events or laboratory abnormalities occur during the use of Trivorin, the dose should be adjusted or the drug should be stopped until the elimination of adverse events.
Table number 2.
Correction of the dosing regimen

Laboratory indicators	Reduce the dose of only the drug Trivorin before 600 mg / day *, if	Dose reduction only interferon alpha-2b before 1,5 million IU / dose or peginterferon alfa-2b on 50%	Discontinuation of Trevorin and interferon alfa-2b, if
Concentration of hemoglobin (Hb)	less 10 g / dL	-	less 8,5 g / dL
Concentration Hb in patients with heart disease in stable form	concentration Hb decreased no less than 2 g / dL for any 4 weeks during treatment (continuous use of a reduced dose)		less 12 g / dL through 4 weeks after dose reduction
Number of leukocytes	-	less 1,5 x 10⁹/ l	less 1,0 x 10⁹/ l
Number of neutrophils	-	less 0,75 x 10⁹/ l	less 0,5 x 10⁹/ l
Platelet count	-	less 50 x 10⁹/ l	less 25 x 10⁹/ l
Concentration of bound bilirubin	-	-	2,5 x VGN **
Concentration of free bilirubin	more 5 mg / dL		more 4 mg / dL (for more 4 weeks)
Concentration of creatinine	-	-	more 2,0 mg / dL
Alanine aminotransferase /	-	-	2 x (basic
Aspartate aminotransferase			value) and more
			10 x VGN **

* - the first dose reduction is recommended at 200 mg / day (except for patients taking 1,400 mg / day, whose first dose reduction should be 400 mg / day); if necessary, the second dose reduction is recommended at 200 mg / day; in patients in whom the dose is reduced to 600 mg / day, it is necessary to take the drug Trivorin in the 200 mg mode in the morning and 400 mg in the evening.
** - the upper limit of the norm. If after correcting the dose tolerance of the drug Trivorin does not improve, it is necessary to consider the question of discontinuing the use of this drug and interferon alfa.
In patients with impaired renal function
There is insufficient data on the safety and efficacy of ribavirin in patients with CRF (creatinine concentrations greater than 2 mg / dl or KK less than 50 mL / min), including in patients on hemodialysis.
In patients with mild to moderate renal impairment (QC greater than 50 mL / min), Trivorin should be started (or continued if kidney failure develops during treatment) according to the scheme, depending on body weight (see Table 1).Treatment should be accompanied by monitoring of Hb concentration, creatinine concentration and measures of dosage adjustment (see Table 2) throughout the treatment period.
In patients with liver failure it is recommended to start using the drug Trivorin according to the scheme depending on the body weight (see Table No. 1). Treatment should be conducted with caution (see section "Special instructions") and be accompanied by measures of correction of the dosing regimen (see Table 2) throughout the treatment period.
In elderly patients it is recommended to start using the drug Trivorin according to the scheme depending on the body weight (see Table No. 1). Treatment should be conducted with caution (see section "Special instructions") and be accompanied by measures of correction of the dosing regimen (see Table 2) throughout the treatment period.

Side effects:

Adverse events with combined therapy for both primary and repeat treatment are similar, and can be associated with both ribavirin and interferon alpha-2b or peginterferon alfa-2b, as well as their combination.

The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - no less than 10%; often - not less than 1%, but less 10%; infrequently - not less than 0,1%, but less 1%; rarely - not less than 0,01%, but less 0,1%; very rarely - less than 0,01%.

Infections: very often - a viral infection, herpes simplex, pharyngitis; often - bacterial infection (including sepsis), fungal infection, infectious and inflammatory diseases of the respiratory tract (rhinitis, sinusitis, bronchitis), urinary tract, otitis media, influenza; rarely - pneumonia *.

On the part of the blood system and lymphatic system:very often - anemia; often - hemolytic anemia, lymphadenopathy; very rarely - aplastic anemia *; frequency is not established - aplasia of red bone marrow, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura.

From the immune system: rarely - sarcoidosis *, rheumatoid arthritis (the first time or exacerbation of the disease); frequency is not established - Vogt-Koyanagi-Harada syndrome, systemic lupus erythematosus, vasculitis, urticaria, Quincke's edema, bronchospasm, anaphylaxis.

From the nervous system: very often - headache, dizziness, impaired concentration, depression, insomnia, anxiety, emotional imbalance; often amnesia, memory impairment, syncope, ataxia, migraine, hypesthesia, hyperesthesia, paresthesia, dysphonia, drowsiness, tremor, dysgeusia, loss of taste sensations, suicidal thoughts, psychosis, behavioral disorders, aggressive behavior, confusion, anxiety, irritability, change mood, nervousness, sleep disturbance, tearfulness, apathy, decreased libido; infrequently - peripheral neuropathy, suicidal attempt, panic attack, hallucinations; rarely - convulsions *, bipolar affective disorder; very rarely - cerebral hemorrhage *, cerebrovascular ischemia *, encephalopathy *, polyneuropathy *, suicide *; frequency is not established - mononeuropathy, paralysis of the facial nerve, obsession with the thought of murder, mania, change in mental activity.

From the side of the organ of vision: often - conjunctivitis, pain in the eyes, irritation of the mucous membrane of the eyes, dryness of the mucous membrane of the eyes, violation of lacrimation, impaired vision; rarely - bleeding in the retina *, retinopathy (including,macular edema) *, retinal artery occlusion *, retinal vein occlusion *, optic neuritis *, optic disc swelling *, decreased visual acuity, loss of visual fields *, swelling retina.

From the organ of hearing: often - vertigo, disorder or loss of hearing, tinnitus, pain in the ears.

From the cardiovascular system (SSS): often - chest pain, heart murmur, palpitation, tachycardia, lowering blood pressure (BP), increasing blood pressure; infrequently - myocardial infarction *; rarely - cardiomyopathy *, arrhythmia *; very rarely - myocardial ischemia *, peripheral circulatory disturbance *; frequency not established - pericardial effusion *, pericarditis *.

On the part of the respiratory, thorax and mediastinal organs: very often - shortness of breath, cough; often - increased secretion of mucus in the airways, stasis of mucus in the airways and sinus sinuses, respiratory failure, rhinitis, nasal congestion, pharyngo-laryngeal pain; rarely - pulmonary infiltrates *, interstitial pneumonitis *.

From the gastrointestinal tract: very often - diarrhea, vomiting, nausea, abdominal pain, dryness of the oral mucosa; often - ulcerative stomatitis,colitis, pain in the right hypochondrium, dyspepsia, gastroesophageal reflux *, glossitis, cheilitis, bleeding from the gums, gingivitis, unformed stool, constipation, flatulence; infrequently - pancreatitis; rarely ischemic colitis *; very rarely - ulcerative colitis *; frequency not established - periodontitis *, tooth decay *.

From the liver and bile ducts: often - hepatomegaly, jaundice; very rarely - hepatitis (including fatal).

From the skin and subcutaneous tissues: very often - alopecia, itching, rash, dry skin; often - psoriasis, worsening of psoriasis, eczema, photosensitivity, maculopapular rash, exanthema, night sweats, dermatitis, acne, furunculosis *, erythema, increased sweating, bruises, hair structure *, nail structure disorder; rarely - sarcoidosis of the skin; very rarely - Stevens-Johnson syndrome *, toxic epidermal necrolysis *, multiforme exudative erythema *.

From the side of the musculoskeletal system: very often - arthralgia, musculoskeletal pain; often - arthritis, back pain, muscle spasm, pain in the limbs; infrequently - pain in the bones, muscle weakness; rarely rhabdomyolysis *, myositis *.

From the urinary system: frequent urination, polyuria; rarely - renal dysfunction *, renal failure *; very rarely - nephrotic syndrome *.

From the endocrine system: often - hypothyroidism, hyperthyroidism.

From the side of metabolism and nutrition: very often - anorexia; often - dehydration, increased appetite; infrequently - diabetes mellitus.

On the part of the reproductive system: often - amenorrhea, menorrhagia, ovarian dysfunction, dysmenorrhea, pain in the mammary glands; in men - impotence, prostatitis, erectile dysfunction, sexual dysfunction *.

Laboratory indicators: very often - a decrease in concentration Hb, neutropenia; often - leukopenia, thrombocytopenia, lymphopenia, hyperbilirubinemia *, increased thyroid stimulating hormone (TSH) concentration, increased thyroglobulin concentration (TG), hyperglycemia, hyperuricemia **, hypocalcemia; infrequently - hypertriglyceridemia, an increase in the concentration of antibodies to TG.

Other: very often - fast fatigue, chills, fever, flu-like reactions, asthenia, irritability, weight loss *; often - chest pain, chest discomfort, epistaxis, thirst, non-thin neoplasm, peripheral edema, general malaise.

* - adverse reactions identified in post-marketing applications.

** - there are reports of an increase in the concentration of uric acid and indirect bilirubin due to hemolysis. Usually the decline of these indicators to the norm occurred during the 4 weeks after the end of therapy. Only a small number of patients with elevated uric acid concentrations had clinical gout symptoms that did not require dose adjustment or treatment withdrawal.

Patients with concomitant HIV infection. In patients with concomitant HIV infection, ribavirin with peginterferon alfa-2b were noted with frequency more 5% candidiasis of the oral mucosa (14%), acquired lipodystrophy (13%), decrease in the number Cd+ lymphocytes (8%), loss of appetite (8%), increase in activity of gamma-glutamyltranspeptidase (9%), backache (5%), increased activity of amylase (6%), an increase in the concentration of lactic acid in the blood plasma, cytolytic hepatitis (6%), increased lipase activity (6%) and pain in the upper and lower extremities (6%).

Overdose:

The known maximum accepted dose - 10 g of ribavirin in capsules (50 capsules for 200 mg) and 39000000 ME interferon alfa-2b in the form of a solution for injection (13 subcutaneous injections for 3000000 ME) within one day.No undesirable phenomena associated with overdose were noted.

Antidote is not known, hemodialysis and peritoneal dialysis are not effective, treatment is symptomatic.

Interaction:

With the simultaneous use of ribavirin and peginterferon alfa-2b and / or interferon alpha-2b no pharmacokinetic interaction was observed.

In the clinical use of various drugs in therapeutic doses in combination with ribavirin, no significant interactions were found.

Research in vitro on microsomal enzymes of the liver showed that cytochrome P450 isoenzymes do not participate in the metabolism of ribavirin, and it is not their inhibitor. Thus, the emergence of any interaction with drugs involving cytochrome P450 is unlikely.

Ribavirin in vitro is able to inhibit the phosphorylation of zidovudine and / or stavudine. The competitive interaction of these drugs can lead to an increase in viral load. It is necessary to change the treatment regimen and carry out a careful control of the concentration of RNA-HCV in the blood plasma.

Ribavirin increases the concentration of phosphorylated metabolites of purine nucleosides,therefore, the risk of developing lactic acidosis with the simultaneous use of ribavirin with analogs of purine nucleosides (for example, didanosine or abacavir) increases. The simultaneous use of ribavirin and didanosine is not recommended because of the threat of mitochondrial toxicity, in particular, severe hepatic insufficiency, peripheral neuropathy, pancreatitis, symptomatic hyperlactemia / lactic acidosis. Ribavirin and stavudine should be avoided in order to limit the risk of developing mitochondrial toxicity.

The combination of ribavirin with zidovudine is not recommended because of the increased risk of developing anemia.

When used simultaneously with azathioprine, azithioprine myelotoxicity increases.

There was no interaction between ribavirin and non-nucleoside reverse transcriptase inhibitors or protease inhibitors. Therefore, simultaneous use of ribavirin and these drugs for the treatment of patients with concomitant HIV infection is possible.

Medicines containing magnesium and aluminum compounds, simethicone, reduce bioavailability, AUC ribavirin. However, this interaction is not clinically relevant.

The possibility of drug or other interaction with ribavirin may persist until 2 months (5 x T_1/2 ribavirin) after discontinuation of ribavirin - due to delayed excretion.

Special instructions:

Ribavirin is used in combination with peginterferon alfa-2b (1,5 mkg / kg per week) or interferon alpha-2b (3000000 ME 3 times a week). Data on the efficacy and safety of ribavirin in combination with other interferons (not alpha-2b) not available.

Trevorin should be treated with a doctor.

Before starting treatment in all patients, it is necessary to conduct a clinical blood test, determine the content of electrolytes, the concentration of creatinine, uric acid in the serum, determine the baseline liver function. Acceptable reference concentration Hb women do not less than 12 g / dl, in men not less than 13 g / dL, the number of platelets is not less than 100,000 / mm³, neutrophils not less than 1500 / mm³. Laboratory research should be conducted through 2 and 4 weeks after the start of treatment and further in accordance with clinical feasibility. During treatment it is necessary to periodically determine the concentration of RNA-HCV.

The use of ribavirin even in low doses (1/20 of the recommended dose) during pregnancy can cause the development of birth defects and / or fetal death. The use of Trivorin in women begins only in the case of a negative test result for pregnancy. Women of reproductive age who receive ribavirin, as well as their sexual partners should be instructed about the need to apply a minimum 2 effective methods of contraception to prevent the onset of pregnancy during treatment and during 4 months after treatment with ribavirin. During this period, it is necessary to conduct pregnancy tests on a monthly basis. If the pregnancy still occurs during treatment or during 4- month period after completion of treatment, the patient should be informed of the significant risk of teratogenic effects of ribavirin on the fetus.

In animal experiments ribavirin caused changes in sperm in doses below therapeutic. Ribavirin accumulates intracellularly and is excreted from the body very slowly. Men taking the drug Trivorin, as well as their sexual partners of reproductive age needinform about the necessity of compulsory use of effective methods of contraception, including condoms, to minimize the risk of ribavirin entering the vagina, both during treatment and during 7 months after its completion. If the pregnancy does occur during treatment or within a 7-month period after the end of treatment, the patient should be informed of the significant risk of teratogenic effects of ribavirin on the fetus.

Before starting treatment with ribavirin in combination with peginterferon alfa-2b or interferon alpha-2b it is necessary to carry out diagnostic measures to identify violations of the patient's mental state and provide him with adequate individual psychiatric care. During treatment and during 6 months after treatment, it is necessary to carefully monitor the behavior of patients in connection with the possibility of developing mental disorders in order to provide patients with individual psychiatric care in time.

If after an attempt to eliminate these symptoms against the background of treatment fails or their progression is observed, it is recommended to stop using antiviral drugs.

Hemolysis is the main toxic effect of ribavirin. During treatment with ribavirin, the maximum decrease in concentration Hb In most cases, after 4-8 weeks from the start of treatment. Reduction in concentration Hb depends on the dose of ribavirin. When the concentration decreases Hb less 110 mg / ml should temporarily reduce the dose of the drug Trivorin on 400 mg / day, with a decrease in concentration Hb less 100 mg / ml should be reduced dose to 50%. In most cases, recommended dose changes ensure a reduction in concentration Hb. When the concentration decreases Hb less 85 mg / ml Trivorin should be discontinued.

With an increase in the concentration of uric acid due to hemolysis, it is necessary to assess the presence of risk factors for the development of gout in patients.

Anemia associated with taking Trivorin can exacerbate existing cardiovascular diseases, for example CHF. Therefore, before the start of treatment and during treatment, an electrocardiogram should be examined to prevent the development of severe complications from the CCC. In some cases, if the condition worsens CCC antiviral therapy may be discontinued.Laboratory tests (clinical analysis of blood counting the leukocyte count and number of platelets, determination of the content of electrolytes, creatinine concentration, functional liver samples) should be performed before starting therapy, on 2 and 4 weeks and on regularly as needed. The use of Trivorin is possible if the concentration Hb not less than 120 g / dL in women, 130 g / dL in men, platelet count no less than 100,000 / mm³, the number of neutrophils is not less than 1500 / mm³.

To prevent the development of retinopathy, it is necessary to assess the condition of the organ of vision before treatment and during treatment. If the symptoms of retinopathy progress, the use of combination therapy is recommended to be discontinued.

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

If infiltrates are detected in the lungs and their function is disrupted, treatment with ribavirin should be discontinued.

In connection with the possible deterioration of kidney function in elderly patients, the use of kidney function, in particular QC, is necessary before using the drug.

Before the beginning of treatment it is necessary to conduct a study of liver function, and in patients with HCV, supplement this study with liver biopsy. All patients who have severe liver function abnormalities should receive careful monitoring. Treatment should be discontinued if the patient has an increase in clotting time and changes in other parameters of the blood coagulation system, which may be a sign of decompensation of liver function.

Patients with concomitant HIV infection who undergo combined therapy for ribavirin and peginterferon alfa-2b and / or interferon alpha-2b, are at high risk of mitochondrial toxicity, lactic acidosis and liver decompensation. It is necessary to regularly monitor liver function. In patients with progressive hepatic insufficiency treatment should be discontinued. Decompensation of liver function in patients with concomitant HIV infection and cirrhosis of the liver receiving HAART can rapidly progress with the addition of monotherapy of peginterferon alfa-2b and / or interferon alpha-2b or a therapeutic complex of ribavirin and peginterferon alfa-2b and / or interferon alpha-2b. Therefore, such patients need to apply a new treatment regimen aimed at restoring liver function.

In patients with HIV co-infection, HAART and therapeutic range of peginterferon alfa-2b and / or interferon alpha-2b and ribavirin, due to the high risk of neutropenia, thrombocytopenia and anemia should be regular monitoring of blood parameters. In most cases, anemia (concentration Hb less 9,4 g / dl), neutropenia (absolute number of neutrophils less than 500 / m³) and thrombocytopenia (platelet count less than 50,000 / m³) Are moderately expressed (according to WHO criteria), in most cases, dose reduction adjusted and rarely lead to early discontinuation of the treatment.

Blood Changes develop more frequently with ribavirin in combination with peginterferon alfa-2b, than when used with interferon alpha-2b.

The use of ribavirin in combination with peginterferon alfa-2b can be accompanied by a reversible decrease in the absolute number CD4 + cells during the first 4 weeks, which is not combined with a decrease in the percentage of these cells. The number CD4 + cells is increased after dose reduction or discontinuation of therapy. Combined therapy of ribavirin with peginterferon alfa-2b It does not have an obvious negative impact on the concentration of HIV RNA both during treatment and after its completion. Data on the safety of treatment in patients with concomitant HIV infection with a number CD4 + cells less than 200 / μl are limited.

Before the beginning of the course of treatment, it is necessary to evaluate the function of the thyroid gland and determine the concentration of TSH. If necessary, it is necessary to treat the existing dysfunction of the thyroid gland.

Patients should be informed of the need for careful oral care, regular rinsing and tooth cleaning (at least 2 once a day), and also regularly visit the dental office to prevent the development of inflammatory diseases of the oral cavity. In addition, it is necessary to inform the patient about the need to thoroughly rinse the mouth after vomiting.

Effect on the ability to drive transp. cf. and fur:

It is necessary to refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions,since During the treatment period, drowsiness and dizziness may occur.

Form release / dosage:

Capsules 200 mg and 400 mg.

Packaging:

By 6 capsules in aluminum foil blisters and PVC films (contour squares) or strips (contour non-cellular packaging).

By 3 blister or strip together with the instruction for use are placed in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

2 of the year. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000444

Date of registration:05.07.2010

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

LEMERY, S.A. de C.V. Mexico

Information update date: & nbsp13.08.2015

Illustrated instructions

Instructions

Trivorin (Trivorin)