Pegintron (pegintron)

	Pegintron (pegintron) PEGINTRON (PegIntron) Synonym : Peginterferon alfa-2b, Peginterferon alpha-2b The composition and the form of : Powder dried for solution for injection (1 February). peginterferon - alfa-2b (in the form of dried powder) : 50 � g, 80 � g, 100 g, 120 ug. Support substances : sodium gidrofosfat; Digidrofosfat sodium; Sucrose; Polisorbat 80 in vials, packed contour yacheykovoy 1 a bottle, complete with a solvent (water injection) in ampoules of 0.7 ml; in one stack of cardboard package. Powder dried for solution for injection (1 dye pen) peginterferon - alfa-2b (in the form of dried powder) : 50 � g, 80 � g, 100 g, 120 g, 150 g Support substances : sodium gidrofosfat; Digidrofosfat sodium; Sucrose; Polisorbat 80 in double-pumps handles complete with a solvent (water for injection, 0.7 ml), with sterile needles and 2 napkins; in one stack of cardboard package. Description pharmaceutical form : Liofilizat white, or almost white, not containing foreign matter. The solvent (water injection) - transparent colourless solution not containing visible particles. Description : Peginterferon alfa-2b is covalent Algae recombinant interferon alfa-2b and monometoksipolietilenglikolya. The average molecular mass of about 31300 Da. The drugs act : Immunomoduliruyuschee. Pharmacokinetics : PegIntron � is a well-known pegilirovannym (ie connected with polyethylene) derived interferon alfa-2b and consists mainly of monopegilirovannyh molecules. T1 / 2 � PegIntrona of plasma exceeds T1 / 2 nepegilirovannogo alfa-2b interferon. PegIntron � can depegilirovatsya releases alfa-2b interferon. Biological activity pegilirovannyh isomers qualitatively similar to the one free alfa-2b interferon, but weaker. After S / to the introduction Cmax serum peaking 15-44 h and maintained for a period of 48-72 hours Cmax and AUC PegIntrona � dose increases proportionally. The apparent volume of distribution averaged 0.99 l / kg. In reconsidering the application is granted immunoreaktivnyh interferon, but the biological activity increased slightly. T1 / 2 PegIntrona � averages about 30.7 hours (from 27 to 33 h), the clear-clearance 22.0 ml / h / kg. D. Mechanisms interferon is not fully described. But, the proportion of renal clearance of about 30% of the total clearance PegIntrona �. When a single dose application of 1.0 � g / kg in patients with impaired renal function revealed an increase in Cmax, AUC and T1 / 2-proportion of kidney failure. When used in the same dose (1.0 g / kg) over four weeks (one injection per week) decreased clearance PegIntrona � by 17% in patients with renal failure secondary to the seriousness of (Cl creatinine, 30-49 ml / min ), and 44% in patients with severe renal insufficiency (creatinine Cl 10-29 ml / min) compared with those with normal renal function. In the group of patients with severe renal insufficiency creatinine clearance was similar in patients in hemodialysis, and in patients who have not been hemodialysis. In monotherapies be lower dose PegIntrona � in patients with renal insufficiency medium and heavy gravity (see Recommendations for corrective doses). Pharmacokinetics PegIntrona � in patients with liver function expressed violations not studied. Pharmacokinetics PegIntrona � in a single p / dose to use in the 1.0 ug / kg did not depend on age, so changes doses in older people is not required. Pharmacokinetics PegIntrona � in patients under the age of 18 years were not investigated. Neutralizing antibodies to interferon analyzed in serum samples of patients receiving PegIntron � in a clinical study. These antibodies neutralize anti-interferon activity. The frequency of detection of neutralizing antibodies in patients receiving PegIntron � dose of 0.5 mg / kg of 1.1%. Farmakodinamika : Recombinant interferon alfa-2b from clone E. coli, which contains genetically engineer plazmidny hybrid encoding human leukocyte interferon alfa-2b. Studies in vitro and in vivo showed that the biological activity of interferon is PegIntrona alfa-2b �. Cellular Effects due to the binding of interferon specific receptors on the surface of cells. Other studies have demonstrated their vidospetsifichnost interferon. However, certain types of monkeys, such makaki- Rh, farmakodinamicheskim sensitive to the effects of human interferon type 1. Contact with skin cell, interferon, a sequence of intracellular events, which include the induction of certain enzymes. I believe that this process, at least in part, oposreduet various cellular effects of interferon, including suppressing the replication of the virus in infected cells, inhibition of cell proliferation and ummunomodulating properties such as increasing phagocytal specific activity of macrophages and lymphocytes dependent on the target cells. Any or all of these effects may oposredovat therapeutic activity of interferon. Recombinant interferon alfa-2b also suppresses viral replication in vitro and in vivo. Although the exact mechanism of action of interferon anti-recombinant alfa-2b not known, however, believe that the drug alters the metabolism of body cells. This leads to the suppression of virus replication; If it does occur, the resulting appeared unable to get out of the cell. Farmakodinamiku PegIntrona � in increasing doses studied in a single application from healthy volunteers by studying temperature changes in the oral cavity, concentrations of effector proteins such as serum neopterin and 2'5'- oligoadenilatsintetaza, and the number of leukocyte and neutrophiles. In patients receiving PegIntron, there was a slight increase in body temperature dozozavisimoe. After a single injection PegIntrona � dose of 0.25 to 2.0 ug / kg / week noted dozozavisimoe increasing concentrations of whey neopterina. Reducing the number of leukocyte neutrophiles and by the end of the 4 th week correlated with the dose PegIntrona �. Indication : chronic hepatitis B. Treatment of chronic hepatitis B patients aged 18 years in the absence of decompensation liver disease. Chronic hepatitis C. The treatment of chronic hepatitis C patients aged 18 years in the absence of decompensation liver disease. Personal best treatment for chronic hepatitis C is a combination of interferon therapy drugs alfa-2b (including peginterferon alfa-2b) and ribavirin. In appointing the combination therapy should be guided by instructions on the use of medical ribavirin. Contraindications : Increased susceptibility to a drug component. Increased sensitivity to any interferon. Autoimmune hepatitis or other autoimmune disease in history. Severe mental illness or personality disorders expressed in the thymus, particularly severe depression, suicidal thoughts or attempts. Severe cardiovascular disease, or uncontrolled volatile during the previous six months. Violation of thyroid function, which can not be maintained at normal levels through medication. Violation of kidney function-Cl creatinine less than 50 ml / min (when used in combination with ribavirin). Asthma cholesterol. Epilepsy and / or breach of central nervous system function. Pregnancy (including a male partner, which it is treated PegIntronom � in combination with ribavirin). Breastfeeding. Application of pregnancy and breast : The study in primates has been shown that interferon alfa-2b has abortifacient action. Rather, PegIntron � also possesses such action. So PegIntron � should not be used during pregnancy. PegIntron � can be applied to women of reproductive age in the event that throughout the treatment they are using effective methods of contraception. Details of the withdrawal of the drug in breast milk does not. Therefore, to breastfeeding women should stop treatment PegIntronom � or breastfeeding, the expected benefits of treatment for the mother and the potential risk to the infant. In connection with the expressed teratogenic and embriotoksicheskim of HCV, resulting in congenital deformities and loss of fruit in animals when used in dose of 1 / 20 of the recommended therapeutic dose combination therapies PegIntronom � and ribavirin during pregnancy context. PegIntronom � therapy in combination with ribavirin should begin only after receiving negative pregnancy test. Women of childbearing age receiving treatment PegIntronom � in combination with ribavirin, and their male partners to use effective contraception for the duration of treatment and during at least 6 months after the end, because ribavirin accumulates in the cells and removed from the body extremely slowly. During all this time to repeat the test every month pregnancy. It should take all possible measures to prevent pregnant women from the male partner who is receiving treatment PegIntronom � and ribavirin. This requires that each of them enjoyed effective means of contraception. Side Effects : Monoterapiya. Basically, the undesirable phenomenon was light or moderately expressed, and do not require the cessation of treatment. The most frequent unwelcome developments (? 10% of patients) were : headache, pain and inflammation at the injection, increased fatigability, vomiting, fever, depression, pain in joints, nausea, Alopecia, musculoskeletal pain, irritability, flu symptoms, insomnia, diarrhoea, abdominal pain, fatigue, pain, lower body mass index, anorexia, anxiety, a violation of concentration, dizziness, reactions at the injection. Less frequent unwelcome developments (? 2% <10% of patients) were : itch, dry skin, nausea, sweating, pain in the right podrebere, neutropenia, rash, vomiting, dry mouth, emotional lability, nervousness, dizziness, viral infection, DROWSINESS, changes in the thyroid gland, chest pain, neuralgia, tides, parestezii, cough, stir, sinusitis, hypertension, hyperesthesia, fog view sputannost consciousness exist abdomen, lower libido, erythema, pain in the eyes, lethargy, gipesteziya unstable chair, conjunctivitis, mortgage nose, constipation, menorragiya, menstrual irregularities. Seldom have been serious violations of the central nervous system, including suicidal thoughts and attempts, aggressive behavior, sometimes aimed at others, psychosis, including hallucinations. In addition, 4 and 7% of patients receiving doses of PegIntron � 0.5 and 1.0 ug / kg, respectively, there granulotsitopeniya (<0.75 � 109 / l), and the 1 and 3% of patients, thrombocytopenia (<70.109 / l). Rare undesirable phenomena observed therapy with interferon alfa-2b were seizures, pancreatitis, gipertriglitseridemiya, top, diabetes and peripheral neuropathy. Combination therapy with ribavirin. In addition to the unfortunate events that have occurred in monotherapies PegIntronom �, in combination therapy also noted the following undesirable phenomenon : tachycardia, rhinitis, taste perversion (these unwanted phenomena met with a frequency of 5 to 10%), hypotension, monster, hypertension , defeated lachrymal gland, tremor, bleeding gums, glossit, disease, ulcerative stomatitis, violation / hearing loss, noise in the head, heart, thirst, aggressive behaviour, fungal infections, prostate, middle ear, bronchitis, respiratory violations rinoreya, eczema, increased fractures hair, the reactions of hypersensitivity to sunlight and the sky (these unwanted phenomena met with a frequency of 2 to 5% of cases). Very rarely combined treatment of ribavirin and interferon alfa-2b may be associated with religious anaemia. Monotherapy and combination therapy with ribavirin. Seldom-ophthalmic violations, including Retinopathy (including swelling disc visual nerve), retinal bleeding in the eye, Be'er retinal vein or artery, focal retinal changes, reducing or limiting the field of view, optic neuritis, a swelling drive visual nerve. Side effects of the cardiovascular system, in particular feel most likely linked to the previous cardiovascular disease and earlier treatment of possessing kardiotoksicheskim action. Rarely in patients who did not have cardiovascular disease in history, there cardiomyopathy, which may be reversible after therapy of interferon alpha. Very rarely seen : rabdomioliz, GACVS, the effects on the kidney, renal failure, ischemic heart disease, myocardial infarction, ischemic brain, cerebral haemorrhage, encephalopathy, or coronary Ulcerative colitis, sarcoidosis (or worsening sarcoidosis), multiformnaya glue erythema, Stivensa- Johnson syndrome, toxic It'sa nekroliz, necrosis at the injection. When using alpha interferon had a wide range of autoimmune and indirect immune system organism violations, including idiopathic trombotsitopenicheskuyu tromboticheskuyu trombotsitopenicheskuyu glory and glory. Networking : With repeated sharing PegIntrona � and Rebetola (HCV) farmakokineticheskogo of interaction between them have been detected. Patients who are HIV receiving highly active antiretroviral therapy (HAART), increased risk of milk acid disorders. Therefore, if you add a combination of PegIntron � + ribavirin to HAART should proceed with caution. The study of repeated doses PegIntrona � (for the 1.5 mg / kg one time a week for four weeks) suppression activity cytochromes CYP1A2, CYP3A4, or N-atsetiltransferazy not revealed, the increase in activity cytochromes CYP2C8/C9 and CYP2D6. Therefore, be careful when appointing PegIntrona � with LS, in the metabolism involving CYP2C8/C9 or CYP2D6. Overdosing : In clinical studies have reported cases of unintentional drug overdoses. In all the cases of excess of the recommended therapeutic dose of no more than 2 times. Severe reactions were not. Undesirable phenomena were alone, and do not require removal therapy PegIntronom �. Dosing and Administration : P / as Therapy PegIntronom � to be launched doctor with experience treating patients with hepatitis B and C, and thereafter be under his control. Chronic hepatitis B PegIntron � introduces a dose of 0.5 or 1.0 � g / kg one time a week for 24 to 52 weeks. Dose chosen because of the efficiency and safety. Patients with difficult to treat chronic hepatitis B, caused by a virus genotype C or D, to achieve therapeutic effect may require a higher dosage and longer course of treatment. Recommended alternate location for injection. Chronic hepatitis C Monotherapy. PegIntron � introduces a dose of 0.5 or 1.0 � g / kg one time a week for at least six months. Dose choice in terms of efficiency and safety. If, after the first 6 months of treatment is elimination of the virus RNA serum, the treatment continues for the next 6 months (a total of over 1 year); If the elimination of the virus RNA is not happening, treatment ceased. If the treatments are undesirable phenomenon, or changes in laboratory indicators PegIntrona � dose adjustments (see Recommendations for corrective doses); While undesirable effects or their re-emergence after the dose treatment PegIntronom � cease. Applications for violations kidney function. see Recommendations for dose adjustment. The application for a breach of liver function. The safety and effectiveness of treatment PegIntronom � from such patients have not been studied, so apply PegIntron � should not be. Applications in older patients (65 years and older). Dependence PegIntrona � pharmacokinetics of age have not been identified. The results of pharmacokinetic studies in older people after a single S / to the introduction PegIntrona � indicate that the selection dosage of age is required. The use in patients under the age of 18. PegIntron � is not recommended to assign children and adolescents at age 18, because experience of the preparation of such patients is not available. Recommended every time to choose a new site for S / by injection. Combination therapy with ribavirin. When combination therapy with ribavirin PegIntron � is designated as S / injection dose of 1.5 � g / kg one time a week. Ribavirin should take into daily. Daily dose of ribavirin in combination therapy calculated on the basis of body weight. Admission ribavirin combined with the admission of food. When combination therapy can also be guided by the joint table for dispensing PegIntrona � and ribavirin. Recommended duration of treatment Patients infected with the virus genotype 1 : in patients infected with genotype 1 virus, which, after 12 weeks of treatment, no elimination of the virus RNA serum, the emergence of resistant virologic response for continuing treatment highly unlikely. Patients with virologic response after 12 weeks of treatment, therapy should continue for a period of 9 months (total duration of 48 weeks of treatment). Patients with low concentrations of the virus (not more than 2 million copies / ml), which, after 4 weeks of treatment occurred off the virus RNA and RNA virus is not identified in the next period-up to 24 weeks of treatment, therapy after the 24 th week of the year can be terminated (total length of the course-24 weeks) or continue for another 24 weeks (total length of the course-48 weeks). However, it should be borne in mind that the risk of relapse after 24 weeks of treatment than after the 48-week course. Patients infected with the virus genotype 2 or 3 : the recommended duration of treatment for all patients in this group, 24 weeks. Patients infected with the virus genotype 4 : generally observed that the patients in this group are difficult to treat. Limited clinical data (66 patients) indicate the possibility of this patient group the same tactics treatment, and that in the group of patients infected with the virus genotype 1. Recommendations for corrective doses If severe unwanted phenomena or deviations in laboratory performance during the application PegIntrona � or PegIntrona � and ribavirin dose should be adjusted or suspend the intake to stop unwanted phenomena. If after adjusting dose therapy improves portability, application PegIntrona � and / or HCV should be discontinued. Correction dose of renal failure. In monotherapies in patients with renal insufficiency average severity (Cl creatinine, 30-50 ml / min), the initial dose PegIntrona � should be reduced by 25%. In patients with severe renal insufficiency (creatinine Cl - 10-29 ml / min), including patients who conducted hemodialysis, the initial dose PegIntrona � should be reduced by 50%. If during treatment in serum creatinine of greater than 2 mg / dl, PegIntronom � therapy should be discontinued. Combination therapy PegIntronom � and ribavirin patients with Cl creatinine below 50 ml / min should not take place. Instructions for preparing solution for injection PegIntron � glucose pens. Dried powder and solvent are in the mix and pumps to handle the introduction. PegIntron � in vials. Dried powder PegIntrona � should only engage in the attached cells. PegIntron � can be mixed with other drugs. Using 0.7 ml syringe sterile water for injection enter into a bottle with PegIntronom �. Bottle vstryahivayut gently until the dissolution of the powder. Time dissolution should not exceed 10 minutes (usually powder dissolves faster). The required dose of gaining the sterile syringe. For use of up to 0.5 ml. Like any other drugs for parenteral use, ready solution should look to the introduction. A solution must be transparent, colorless and not visible particles. In the event of a change in color or appearance of visible particulates solution must not be used. Ready solution should be used immediately. If it is not immediately prepared to use solution, it can be stored no longer than 24 hours at a temperature of 2-8 � C. The solution remaining after the introduction, the application is not and must be disposed in accordance with the current regulations. Precautions : Mental area and central nervous system. If necessary supplies PegIntrona � patients with severe mental disorders (including patients with reference to such violations in anamnesis), the treatment can be initiated only after a careful examination of individual and the treatment of mental disorder. Some patients during therapy PegIntronom � experienced severe violations of the central nervous system, particularly depression, suicidal thoughts and suicide attempts. When treating interferon alpha also met other violations of the central nervous system, including aggressive behavior, sometimes aimed at others, sputannost consciousness and other changes in mental condition. Some patients, particularly the elderly, have been elevated dose interferon alfa-2b, noted a marked decline in pain sensitivity coma, encephalopathy. While the phenomenon mostly reversible, in some patients for a full recovery could take up to three weeks. When mental changes or central nervous system violations, including signs of depression, to ensure continuous monitoring of such patients during treatment and during the 6 months after the end, given the potential seriousness of such unwanted phenomena. While maintaining or increasing symptoms, particularly depression, suicidal intentions or aggressive behaviour should be removed, treated PegIntronom �, and the timely intervention of a psychiatrist. Cardiovascular system. When treating PegIntronom �, and interferon alfa-2b, patients suffering or have suffered congestive heart failure, heart attacks and / or adults, should be under constant surveillance. For patients with heart disease before and during treatment are recommended electrocardiography. Adults (mainly nadzheludochkovye) tend to be routine therapy, but may require lifting PegIntrona �. Increased susceptibility immediate type. In rare cases, interferon therapy alfa-2b complicated reaction immediate type of hypersensitivity (eg krapivnitsey, angionevroticheskim swelling, bronchospasm, arginine). When such reactions in the face of PegIntrona � PegIntron � should be lifted immediately and appoint appropriate symptomatic therapy. Fleeting television does not require the termination of treatment. Kidney function. The study recommended that the functions of all kidney patients before therapy PegIntronom �. In patients with kidney function violate them should be closely monitored. If necessary, reduce the dose PegIntrona � (see Recommendations for corrective doses). The function of the liver. When signs of decompensation liver disease should stop treating PegIntronom �. Rush. While the fever may occur within grippopodobnogo syndrome, which is often recorded in the treatment of interferon, however, need to rule out other causes of persistent fever. Hydration. Patients who are receiving therapy PegIntronom �, an adequate hydration, because some patients there hypotension associated with a decrease in fluid in the body. In such cases, it may be necessary to substitute a liquid. Diseases, which result in permanent disability. PegIntron � should be used with caution in those diseases that lead to disability as lung diseases (such as COPD), or diabetes mellitus with the tendency to develop ketoacidosis. It should also be careful in patients with blood coagulability violations (such as throm, pulmonary embolism) or expressed mielosupressiey. Changes in the lungs. In rare cases, patients who received interferon alpha in the lungs developed infiltrates unknown etiology, pnevmonity or pneumonia, including fatal. If you have fever, cough, breathlessness and respiratory symptoms of all patients should be a chest X-ray. If there is light in the radiograph infiltrates or violations of lung function for such patients should be more closely monitored and, if necessary, reverse interferon alpha. Although such reactions more frequent in patients with chronic hepatitis C receiving interferon alpha, however, they also registered the drug for the treatment of patients with cancer. Immediate removal and treatment of interferon alpha GKS lead to the disappearance of undesirable phenomena of light. Autoimmunity. When treating interferon alpha noted the emergence of IgG. Clinical manifestations of autoimmune diseases appear more often in the treatment of interferon in patients predisposed to the development of autoimmunity. Changes in body. Any patient zhaluyuschemusya at reducing or limiting the field of view, there should be an eye examination. These undesirable reactions more often associated with the disease, so patients diabetes or arterial blood pressure before treatment PegIntronom � to a survey eye. Changes from the teeth and periodonta. In patients receiving combination therapy peginterferonom and ribavirin, there were lesions of the teeth and okolozubnyh tissue. Aedificators mouth with a long and ribavirin combination therapy peginterferonom alfa-2b can damage teeth and the mucous membranes of the oral cavity. Patients must clean teeth brushed 2 times a day and receive regular dental examination. Patients who have been vomiting, must then carefully propolaskivat mouth. Changes in the thyroid gland. A chronic hepatitis C patients receiving interferon alfa-2b sometimes grown as a violation of thyroid, or hypothyroidism-Ray. In clinical studies of interferon alfa-2b overall frequency of thyroid function was 2.8%. They controlled with a standard therapy. The mechanism of interferon alpha on thyroid function is unknown. Before treatment PegIntronom � in patients should be identified Whey tireotropnogo hormone levels. If there is any violation of the functions of the thyroid gland is recommended that a standard therapy in such cases. PegIntron � should not be appointed if the therapy does not support activity tireotropnogo hormone at normal level. Tireotropnogo hormone levels should be determined as soon as symptoms of thyroid function in the face of the treatment of interferon alpha. If there is a violation of thyroid function PegIntronom � treatment can be extended if the content tireotropnogo hormone to maintain a normal level by conventional therapy. Psoriasis and sarcoidosis. Given the description of the deterioration of psoriasis and sarcoidosis in the treatment of interferon alfa-2b apply PegIntron � in patients with psoriasis or sarcoidosis should only if the expected benefits outweigh the potential risks. Organ transplantation. The effectiveness and safety of PegIntrona � (in combination with ribavirin or monotherapies) to recipients in organ transplants is not known until the end. Preliminary figures show an increase in cases of exclusion transplanted kidneys. It was also reported divestiture of transplanted liver, but a causal connection with interferon alpha is unknown. Laboratory studies. All patients before and during treatment PegIntronom � recommended general and biochemical blood tests and study the functions of the thyroid gland. Eligible are basic values of blood : platelets? 100,000 in mm3, neutrophiles-? In 1500 mm3, Thyrotropic hormone-within normal limits. There are instances gipertriglitseridemii and increase triglitseridemii, sometimes expressed. Therefore, all patients should be encouraged to monitor the level of lipids in the blood. The impact on the ability to drive and use sophisticated technology. When tiredness, sleepiness or nervous consciousness in the face PegIntronom � therapy is not recommended to drive or complex technology. Shelf life : 3 years Storage conditions : when the temperature 2-8 � C
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