Algeron

Algeron – the drug with the immunostimulating, antiviral action applied at treatment of primary chronic active hepatitis C.

Form of release and structure

Algeron release in the form of solution for hypodermic introduction: transparent, from light yellow color to colourless (in sterile ternary syringes from neutral colourless glass on 0,4, 0,5, 0,6, 0,8 or 1 ml, on 1 syringe in blister strip packagings from a polymeric film, on 1 or 4 packagings in a cardboard pack; in colourless glass bottles on 1 ml, on 1 or 4 bottles in blister strip packagings, on 1 packaging in a cardboard pack).

Structure of 1 ml of solution:

• Active ingredient: цепэгинтерферон alpha 2b – 0,2 mg;
• Additional components: a dihydrate of an edetat of dinatrium – 0,056 mg, polysorbate of 80 - 0,05 mg, sodium acetate trihydrate – 2,617 mg, sodium chloride – 8 mg, glacial acetic acid – to pH 5,0, water for injections – to 1 ml.

Indications to use

Algeron appoint the adult in combination with ribaviriny for treatment of primary chronic active hepatitis C from positive HCV RNA in cases of lack of signs of a decompensation of a disease of a liver.

Contraindications

Absolute:

• The cirrhosis proceeding with a liver failure at HIV coinfection / chronic hepatitis C (at the Chayld-Pyyu index> 6);
• Dekompensirovanny cirrhosis (on a scale of Chayld-Pyyu the class B and C or bleeding from varicose expanded veins);
• Autoimmune hepatitis or other autoimmune diseases in the anamnesis;
• Functional disturbances of a thyroid gland which it is medicamentous do not manage to be supported at the normal level;
• Functional disturbances of the central nervous system and/or epilepsy;
• Serious mental diseases, in particular, suicide attempts or thoughts, depressions (including in the anamnesis);
• Malignant new growths;
• Performing treatment at men whose partners are pregnant;
• Serious illnesses of cardiovascular system, including the uncontrollable and unstable forms existing at least for half a year preceding therapy;
• Serious illnesses of kidneys (including a renal failure, need of carrying out a hemodialysis, clearance of creatinine <50 ml/min.);
• The expressed oppression of a marrowy hemopoiesis (thrombocytes <^25×109/л, neutrophils <^0,5×109/л, hemoglobin <85 g/l);
• Rare hereditary diseases, such as lactose intolerance, glyukozo-galaktozny malabsorption or deficit of lactase;
• Hemoglobinopathies (for example, sickemia, thalassemia);
• Age up to 18 years;
• Pregnancy and period of a lactation;
• Hypersensitivity to drug components, and also to a ribavirin.

Relative (Algeron appoint with care in the presence of the following diseases / states):

• Diabetes mellitus in the presence of a tendency to development of a ketoatsidotichesky coma;
• Serious illnesses of lungs (for example, chronic obstructive diseases of lungs);
• Thrombocytes <^90×109/л, neutrophils <^1,5×109/л, hemoglobin <100 g/l;
• HIV coinfection / chronic hepatitis C with number of CD4+ of lymphocytes is less than 200 cells / мкл or less than 100 cells / мкл at the HIV RNA level more than 5000 copies/ml;
• The disturbance blood connected with coagulant system (for example, at the postponed embolism of a pulmonary artery, thrombophlebitis);
• The combined use with miyelotoksichny medicines.

Route of administration and dosage

Algeron enter subcutaneously, into the area of a hip or a front abdominal wall. Intravenously it is impossible to administer the drug. Places for an injection are recommended to be alternated.

Has to appoint drug and to control its further use the doctor with experience of therapy of patients with hepatitis C.

The recommended mode of dosing of Algeron (0,0015 mg/kg once a week) in combination with ribaviriny (the minimum volume of the syringe/weight / a one-time dose/volume of solution):

The syringe on 0,4 ml:

• 40 kg: 0,06 mg / 0,3 ml;
• 41-46 kg: 0,07 mg / 0,35 ml;
• 47-53 kg: 0,08 mg / 0,4 ml.

The syringe on 0,5 ml:

• 54-60 kg: 0,09 mg / 0,45 ml;
• 61-66 kg: 0,1 mg / 0,5 ml.

The syringe on 0,6 ml:

• 67-73 kg: 0,11 mg / 0,55 ml;
• 74-80 kg: 0,12 mg / 0,6 ml.

The syringe on 0,8 ml:

• 81-86 kg: 0,13 mg / 0,65 ml;
• 87-93 kg: 0,14 mg / 0,7 ml;
• 94-100 kg: 0,15 mg / 0,75 ml;
• 101-106 kg: 0,16 mg / 0,8 ml.

The syringe on 1 ml:

• 107-113 kg: 0,17 mg / 0,85 ml;
• 114-120 kg: 0,18 mg / 0,9 ml;
• 121-126 kg: 0,19 mg / 0,95 ml;
• 127-133 kg: 0,2 mg / 1 ml.

Each bottle / syringe with solution is intended only for single use. To mix the solution which is contained in the bottle/syringe or it is not necessary to enter it in parallel with other medicines.

Administration of solution in painful points, areas with small knots and consolidations or the reddened, decoloured sites of skin is not recommended.

It is impossible to apply a double dose of Algeron.

Without consultation with the doctor it is not necessary to cancel therapy.

Ribavirin accept inside, along with meal, daily. The daily dose is defined by body weight (a single dose morning/evening):

• To 65 kg: 400 mg / 400 mg;
• 65-85 kg: 400 mg / 600 mg;
• 86-105 kg: 600 mg / 600 mg;
• From 105 kg: 600 mg / 800 mg.

Duration of a therapeutic course is defined by a virus genotype:

• HCV 1 genotype: the early virologic answer (disappearance by 12th week of treatment of HCV RNA or decrease in virus load of 2 _log10 (by 100 times) and more) can predict achievement of the steady answer. In this case it is recommended to continue treatment within 9 months (the general duration of a course – 48 weeks). If the early virologic answer is absent, achievement of remission is improbable;
• Genotype of HCV 2 and 3: at the early virologic answer by 12th week of therapy it is recommended to be seen off for 12 more weeks (the general duration of a course – 24 weeks). More long treatment has no advantages;
• HCV 4 genotype: patients with a genotype 4, in general, will respond to treatment difficult. As a rule, adhere to the same tactics of treatment, as at a genotype 1.

In cases of development of the undesirable phenomena or deviations of laboratory indicators of moderate severity it is necessary to lower Algeron's doses or a ribavirin or to suspend therapy. The question of increase in a dose, up to initial, can be considered after normalization of a state or laboratory indicators.

Correction of the mode of dosing is required at development of hematologic disturbances.

About 600 mg at decrease in hemoglobin to level less than 100 g/l are recommended to lower a daily dose of a ribavirin. At decrease in this indicator less than 85 g/l Algeron and рибавирин cancel. Extra care is demanded by patients with diseases of cardiovascular system.

At increase in concentration of free bilirubin up to 85,5 µmol/l about 600 mg are recommended to lower a daily dose of a ribavirin.

Algeron and рибавирин cancel at the progressing increase in activity of alaninaminotranspherase or aspartate aminotransferase more than twice from a reference value or it is more, than by 10 times from the upper bound of norm.

In cases of developing of a moderately severe depression Algeron's dose is reduced. Therapy is cancelled at development of a heavy depression, and also emergence of suicide thoughts.

At a slight renal failure (clearance of creatinine> of 50 ml/min.) when carrying out a combination therapy concerning development of anemia it is necessary to be careful.

Side effects

Side effects when performing the combined therapy of 0,0015 mg/kg a week of Algeron with ribaviriny in most cases had the easy or moderately expressed character and the terminations of treatment did not demand.

Possible side reactions (it is very frequent (≥1/10), it is frequent (≥1/100; <1/10), infrequently (≥1/1000; <1/100), it is rare (≥1/10 000; <1/1000), it is very rare (<1/10 000)):

• Alimentary system: very often – diarrhea, nausea; often – heartburn, a loss of appetite, dryness in a mouth, an abdominal pain;
• Central and peripheral nervous system: very often – a headache, a depression, irritability, emotional lability; often – dizziness;
• Cardiovascular system: often – arterial hypotension, tachycardia;
• Lymphatic and hemopoietic system: very often – a leukopenia, anemia, a neutropenia, thrombocytopenia. Most often reduction of hematologic indicators is noted in the first month of therapy, after dose adjustment within 1-2 months they improve;
• Respiratory system: very often – dry cough;
• Skeletal and muscular system: very often – muscular and joint pains;
• Mucous membranes: often – stomatitis, conjunctivitis, an ulitis, a blepharitis;
• Skin and hypodermic fatty tissue: very often – a skin itch, a peeling and a xeroderma, rash; often – an alopecia;
• Laboratory indicators: very often – a gipertriglitseridemiya, a hypoglycemia; often – changes of levels of hormones of a thyroid gland (increase in concentration of TTG), a hyperglycemia;
• Reactions in an injection site: very often – an inflammation in an injection site; often – infiltrate, pain, an itch in an injection site;
• General symptoms: very often – fever, an adynamy, a grippopodobny syndrome, increased fatigue, reduction of weight.

At Algeron's use in a dose of 0,002 mg/kg a week in addition to the disturbances described above the following side effects were also recorded: pains in heart, a menorrhagia, disturbances in injection sites in the form of cyanosis, dot hemorrhage, a furuncle.

The disturbances observed at a combination therapy of similar drugs of peginterferon an alpha - 2b with ribaviriny:

• Alimentary system: very often – nausea, an abdominal pain, diarrhea, appetite reduction; often – an unstable chair, dyspepsia, locks, vomiting, dryness in a mouth, abdominal distention, a stomacace, bleeding of gums, stomatitis, a glossitis; seldom – pancreatitis; very seldom – ulcer and ischemic colitis; with an unspecified frequency – disturbances of teeth and a periodontium;
• Central and peripheral nervous system: very often – sleeplessness, a depression, a headache, dizziness, irritability, disturbance of concentration of attention, feeling of alarm; often – a hypesthesia, disturbance of flavoring feelings, paresthesia, an ataxy, emotional lability, confusion of consciousness, decrease a libido, a tremor, an agressive behavior, drowsiness, a hyperesthesia, excitability, apathy, a syncope; seldom – suicide attempts and thoughts, psychosis (including hallucinations, the agressive behavior sometimes directed on people around), peripheral neuropathy, convulsive attacks; very seldom – cerebrovascular ischemia, a hematencephalon, polyneuropathy, encephalopathy; with an unspecified frequency – paralysis of a facial nerve, neuropathy (including mononeuropathy);
• Respiratory system: very often – cough, short wind, pharyngitis; often – a rhinorrhea, rhinitis, bronchitis, sinusitis, respiratory disturbances, a nose congestion, unproductive cough; very seldom – a pneumonitis, pulmonary infiltrates, an intersticial pneumonitis;
• Skeletal and muscular system: very often – musculoskeletal and joint pains; often – arthritis;
• Lymphatic and hemopoietic system: very often – anemia, a neutropenia; often – thrombocytopenia, a neutropenia, a lymphadenopathy; very seldom – a pancytopenia, aplastic anemia, a trombotichesky and idiopathic Werlhof's disease;
• Cardiovascular system: often – tachycardia, heartbeat, arterial hypertensia / hypotension, inflows; seldom – a cardiomyopathy, arrhythmia;
• Endocrine system: often – a hyperthyroidism, a hypothyroidism;
• Hypodermic fatty tissue and skin: very often – an alopecia, a xeroderma, an itch, rash; often – eczema, psoriasis, deterioration in a course of already existing psoriasis, reactions of a photosensitization, erythematic and makulopapulezny rash, dermatitis, the increased perspiration, an acne, disturbances of skin, nails and structure of hair, a furunculosis, a hematoma; seldom – a miositis, рабдомиолиз; very seldom – a toxic epidermal necrolysis, Stephen-Johnson's syndrome, a multiformny exudative erythema;
• Gepatobiliarny system: often – jaundice, a hepatomegalia;
• Immune system: very seldom – a sarcoidosis (development or an aggravation); with an unspecified frequency – a syndrome of Fogta-Koyanagi-Harady, a vasculitis, a system lupus erythematosus, a pseudorheumatism (development or an aggravation), reactions of acute hypersensitivity, including a small tortoiseshell, a bronchospasm, a Quincke's disease, an anaphylaxis;
• Urinary system and kidneys: often – the speeded-up urination, a polyuria; seldom – a renal failure, an impaired renal function; very seldom – a nephrotic syndrome;
• Reproductive system: often – a hypermenorrhea, an amenorrhea, a dysmenorrhea, dysfunction of ovaries, mammary gland pain, disturbances of a vagina (at women); prostatitis, impotence, disturbances of sexual function (at men);
• Acoustic organs: often – a sonitus, a loss/hearing disorder, average otitis;
• Organs of sight: often – conjunctivitis, eye pain, sight misting, defeat of the lacrimal gland; seldom – a retinopathy, an eye retinal apoplexy, obstruction of veins or arteries of a retina, focal changes of a retina, an optic neuritis, restriction of fields of vision or decrease in visual acuity, a papilledema;
• Laboratory indicators: often – a hyperbilirubinemia, increase in activity of alaninaminotranspherase, a hyperuricemia, changes of levels of hormones of a thyroid gland (hyper - and a hypothyroidism), hyper - and a hypoglycemia, a hypocalcemia; very seldom – a hyper lactacidemia, a gipertriglitseridemiya, a lactacidemia;
• CD4 + lymphocytes: often – reversible decrease in absolute quantity of CD4+ of lymphocytes without change of their percentage. These changes have completely reversible character; the negative impact on the level of virus loading of HIV at patients with HIV coinfection / chronic hepatitis C in time and after the end of therapy was not noted;
• Reactions in an injection site: very often – an inflammation and pain in an injection site;
• General disturbances: very often – a grippopodobny syndrome, fever, an adynamy, increased fatigue, a fever, weight reduction; often – an indisposition, pains in right hypochondrium and a thorax, thirst;
• Others: often – fungal/viral infections.

Special instructions

The profile of safety of Algeron (monotherapy or in combination with ribaviriny) for patients is younger than 18 years, and also patients after transplantation of a liver or other bodies is not studied.

Algeron's appointment to patients with heavy mental disturbances (including the patients having instructions on such disturbances in the anamnesis) is possible only after carrying out careful individual inspection and the corresponding treatment of a mental disorder.

With a depression in the anamnesis it is necessary to watch a condition of patients regarding emergence of symptoms of a depression during therapy and for half a year after its termination. At increase or preservation of symptoms, in particular a depression, an agressive behavior or suicide intentions, it is necessary to cancel Algeron and to provide timely survey by the psychiatrist.

At heart troubles before the beginning and during treatment carrying out an ECG is recommended. The anemia caused by reception of a ribavirin can aggravate the course of cardiovascular diseases. At an aggravation of symptoms therapy is cancelled.

In case of a bronchospasm, a small tortoiseshell, anaphylactic reactions, a Quincke's disease it is necessary to cancel immediately Algeron and to immediately appoint the corresponding treatment. At passing rash cancellation of therapy is not required.

At reduced function of kidneys, and also patients aged from 50 years at Algeron's use with ribaviriny need to trace carefully a state concerning possible development of anemia.

Prior to therapy carrying out a research of function of kidneys is recommended to all patients. Less than 50 ml/min. do not appoint a combination therapy at clearance of creatinine.

In case of development of a liver failure treatment is cancelled.

Also during therapy it is necessary to consider development of the following disturbances / states:

• Fever: at persistent fever it is necessary to exclude existence of other reasons;
• Hydration: it is recommended to provide adequate hydration (to avoid development of the arterial hypotension connected with reduction of volume of liquid in an organism);
• Pulmonary diseases: at development of respiratory symptoms, including cough, fever and asthma, it is necessary to carry out a thorax X-ray analysis;
• Autoimmune disorders: in some cases there can be autoantibodies (in most cases with predisposition to development of autoimmune disorders). At psoriasis and a sarcoidosis Algeron appoint with care, at an aggravation therapy cancellation is possible;
• Infections (virus/bacterial/fungal): in cases of development of heavy complications Algeron cancel;
• Changes from an organ of sight: in cases of emergence of complaints it is necessary to conduct ophthalmologic examination;
• Changes from a periodontium and teeth: carrying out regular surveys at the stomatologist (because of high probability of development of pathological changes is recommended from peridental fabrics and teeth);
• Condition of a thyroid gland: development of a hypothyroidism or hyperthyroidism is possible. In cases if activity of thyritropic hormone does not manage to be maintained at the normal level, Algeron cancel;
• Pancreatitis: at emergence of symptoms of pancreatitis therapy is cancelled;
• Laboratory researches: standard clinical and biochemical analyses of blood need to be carried out before purpose of a course, and also during therapy.

Algeron's use can be followed by development of ulcer and hemorrhagic and/or ischemic colitis within 12 weeks from the moment of an initiation of treatment. Typical signs of manifestation of colitis: availability of blood in Calais, abdominal pains, fever. At emergence of similar complaints Algeron cancel at once.

If during performing therapy development of dizziness, weakness, confusion of consciousness, drowsiness is observed, control of motor transport and works with mechanisms and cars it is necessary to refuse.

Medicinal interaction

At the combined use of Algeron with some substances / medicines development of the following effects is possible:

• Medicines in which metabolism isoenzymes of CYP2D6 or CYP2C8/C9 participate: increase in activity of these isoenzymes is noted (the combination demands care);
• Theophylline: inhibition of activity of an isoenzyme 1A2 _{of P450 cytochrome} and increase in the area under a curve "concentration time" (AUC) of theophylline (it is necessary to carry out control of its concentration and to adjust a dose);
• Methadone: increase in the average levels of its metabolites (control of symptoms of intoxication is required);
• Highly active anti-retrovirus therapy (VAART) at sick HIV: increase in risk of development of lactic acidosis (the combination demands care).

The combination of a ribavirin with didanoziny is not recommended (possibly development of peripheral neuropathy, fatal liver failure, a symptomatic lactacidemia and pancreatitis).

Terms and storage conditions

To store in protected from light, the place, unavailable to children, at a temperature of 2-8 °C, not to freeze.

Period of validity – 2 years.