After a single subcutaneous injection of 180 micrograms of peginterferon alfa-2a healthy individuals in the presence of serum testosterone cypionate half life concentration of the drug begins to be determined in 3-6 hours. Serum concentrations reach 80% of maximum within 24 hours. Absorption of peginterferon alfa-2a is long, the maximum serum concentration observed after 72-96 hours after dosing. The absolute bioavailability of peginterferon alfa-2a and 84% similar to that of interferon alpha-2a.
peginterferon alfa-2a is found predominantly in the blood and extracellular fluids. The volume of distribution at steady state (V ss ) after intravenous injection of 6-14 liters. According to mass spectrometry, tissue distribution and autoradiolyuminografii obtained in studies in rats, peginterferon alfa-2a detected in high concentrations in the blood and in the liver, kidney and bone marrow.
Features of peginterferon alfa-2a metabolism is not fully understood; However, studies in rats indicate that the radiolabelled drug is excreted mainly by the kidneys.
Systemic clearance of peginterferon alfa-2a in humans is 100 times lower than that of the interferon alfa-2a. After intravenous administration, the terminal half-life in healthy volunteers 60-80 hours compared with 3.4 hours for normal interferon. After subcutaneous administration the terminal half-life of about 160 hours (from 84 to 353 hours). The terminal half-life after subcutaneous administration may not show excretion and absorption of the duration of peginterferon alfa-2a.
With the introduction of peginterferon alfa-2a 1 once a week there is a dose-dependent increase in systemic exposure in healthy volunteers and in patients with chronic hepatitis B or C. Patients with chronic hepatitis B and C after 6-8 weeks of therapy with peginterferon alfa-2a once weekly achieved the equilibrium concentration which is 2-3 times higher than after a single injection.After 8 weeks of treatment once a week to further the introduction of cumulation of the drug occurs.
Renal impairment is associated with a slight decrease in clearance (CL / F) and an increase in half-life.
In patients with a creatinine clearance of 20-40 ml / min, there is a decrease in clearance of peginterferon alfa-2a by 25% as compared to patients without renal dysfunction. In patients with end-stage renal disease receiving hemodialysis sessions, there is a decrease in clearance of peginterferon alpha-2a at 25-45%. Pharmacokinetics were similar in the appointment of Pegasys ® at a dose of 135 mcg in patients with end-stage chronic renal failure and in the appointment of 180 mcg in patients without renal impairment.
pharmacokinetic performance of Pegasys ® in men and women after a single subcutaneous injection comparable.
patients older than 62 years, the absorption of Pegasys ® after a single subcutaneous injection of 180 micrograms was delayed but stable compared to young healthy volunteers (t max of 115 hours vs. 82 hours). The area under the curve “concentration – time» (AUC) is slightly increased in patients older than 62 years (1663 vs. 1295 ng x h / ml), but the maximum concentrations in patients younger and older than 62 years are the same (9.1 and 10.3 ng / mL, respectively) . Based on the exposure data, pharmacodynamic response and tolerability reduce initial dose in these patients is not required.
Patients with cirrhosis and without cirrhosis
pharmacokinetics of Pegasys in healthy subjects and patients with hepatitis B or C the same. In patients with compensated cirrhosis, the pharmacokinetic characteristics are the same as in patients without cirrhosis (class A on a scale Child-Pugh).
The injection site
Subcutaneous Pegasys ® should be limited to an area of the abdominal wall and the anterior thighs as the extent of absorption based on AUC, it was 20-30% higher when injected into the region. Drug concentration was lower in the studies in which PEGASYS subcutaneously injected in the shoulder region.
Chronic hepatitis C
chronic hepatitis C in adults with positive HCV RNA, with or without cirrhosis compensated cirrhosis, including those with clinically stable HIV co-infection (monotherapy or combination with ribavirin).
The combination with ribavirin in patients who have not received prior therapy, or after failure of previous monotherapy with interferon alpha (pegylated or non-pegylated) or combined with ribavirin therapy.
Chronic hepatitis B
Chronic hepatitis B HBeAg-positive or HBeAg-negative adult patients with compensated liver disease and evidence of viral replication, increased ALT and histologically verified liver inflammation and / or fibrosis.
: Hypersensitivity to interferon alpha, a genetically engineered drug, obtained by E. coli, to polyethylene glycol or any other component of the formulation.
Severe hepatic insufficiency or uncompensated cirrhosis.
Cirrhosis of the sum of scores> 6 on the scale of Child-Pugh in patients co-infected with HIV-HCV.
hypo-, hyperthyroidism, diabetes decompensated
severe heart disease in the phase of decompensation, including unstable poorly controlled flow in the previous 6 months.
Children under 3 years, because the drug contains excipient benzyl alcohol.
The period of lactation.
In addition to the combination of Pegasys with ribavirin
should be considered contraindications to ribavirin.
With care in cardiovascular testosterone cypionate half life diseases; autoimmune diseases; psoriasis; history of depression; neutrophil count less than 1500 cells / microliter, platelets less than 90,000 cells / L, hemoglobin less than 12 g / dL; in combination with drugs myelotoxicity; CD4 + lymphocytes number less than 200 cells / ml or less than 100 CD4 + cells / ml and HIV-1 RNA than 5000 copies / mL (HIV-1 Monitor Test, v.5) in patients co-infected with HIV-CHC.
Pregnancy and lactation
Effect of Pegasys ® on fertility has not been studied. When assigning peginterferon alfa-2a, as well as other interferon alfa marked elongation of the menstrual cycle, with a decrease in the later onset and the maximum concentrations of 17b-estradiol and progesterone in animals. After discontinuation of the drug was observed normalization of the menstrual cycle.
Influence of peginterferon alfa-2a on male fertility have not been investigated. However, administration of interferon alpha-2a for 5 months had no effect on fertility in animals.
Teratogenic effects of Pegasys have not been studied. The use of interferon alfa-2a resulted in a significant increase in the number of spontaneous abortions in rhesus monkeys. Offspring born in time, no teratogenic effects were observed. However, in the treatment of Pegasys ® , like other alpha interferons, women of childbearing potential should use effective methods of contraception. PEGASYS ® should not be administered during pregnancy.
It is not known whether Pegasys displayed or components of the drug in breast milk. To eliminate the unwanted effects of Pegasys ® and ribavirin for the child during breast-feeding should be discontinued or breastfeeding or therapy, taking into account the potential benefits of therapy for the mother.
For combination with ribavirin: Category X.
At ribavirin in animal studies revealed marked teratogenic effects and the ability to cause the death of the fetus. Ribavirin is contraindicated in pregnant women, and men, who are pregnant partner.
Ribavirin therapy should not be administered until a negative pregnancy test carried out immediately prior to the intended start of therapy. Women are able to bear children, or male partner whose ability to bear children, to be informed of the teratogenic effects of ribavirin and the need for effective contraception (at least 2 ways) during treatment and during the 6 months after the end of therapy (see. The instructions for medical the use of ribavirin).
Dosing and dosing regimen (for persons over 18 years of age)
Treatment Pegasys should be under the supervision of a qualified physician with experience in treatment of patients with chronic hepatitis B and C. In the case of the use of PEGASYS ® in combination with ribavirin should also read the instructions for medical the use of ribavirin.
Standard sharp dosing
The drug is administered subcutaneously (s / c) to the anterior abdominal wall or thighs 1 time per week. Before the introduction of the drug should be inspected for the absence of extraneous matter and discoloration.
Patients should be carefully instructed in the importance of proper storage and disposal of the materials used and to warn against any reuse of needles and syringes.
Chronic hepatitis B
In HBeAg-positive and HBeAg-negative chronic hepatitis B – 1 times per week for 48 weeks at a dose of 180 testosterone cypionate half life micrograms.
Chronic hepatitis C