2010/06/05

PEGINTERFERON ALFA-2a

Pharmacological action

Immunomodulator with antiviral action. It is a pegylated interferon alfa-2a, formed by conjugation with PEG (bis-monometoksipolietilenglikolya) with interferon alfa-2a.

Interferon alfa-2a produced biosynthetic method for recombinant DNA technology and is a derivative product of a cloned human leukocyte interferon gene introduced and expressed in cells of Escherichia coli.

Interferons bind to specific receptors on the cell surface, triggering a complex intracellular signaling mechanisms and rapid activation of gene transcription. Interferon stimulated genes modulate many biological effects, including inhibition of viral replication in infected cells, suppression of cell proliferation and immunomodulation.

In clinical trials, is effective in treating patients with chronic hepatitis C (including those with compensated cirrhosis of the liver).


Statement

Chronic hepatitis C without cirrhosis or compensated cirrhosis (class A on the scale of Child-Pugh) in adults (as monotherapy or in combination with ribavirin as first-line treatment).


Dosage regimen

Enter n / k. Depending on the clinical situation, the recommended dose is 45-180 mg 1 time a week n / k.


Side effect

From the side of the central nervous system and peripheral nervous system: frequent - asthenia, somnolence, memory impairment, paresthesia, breach of taste sensations, fatigue, hypoesthesia, tremor, anxiety, mood changes, nervousness, aggressiveness, and in some cases - behavioral disorders (including commit suicide and suicide attempts), peripheral neuropathy, described cases of a brain hemorrhage.

On the part of the respiratory system: often - cough, shortness of breath, sore throat, nasopharyngitis, and in some cases - pneumonia, interstitial pneumonitis with fatal outcome.

On the part of the digestive system: often - dry mouth, bleeding gums, ulcerative stomatitis; in some cases - abnormal liver function, fatty liver, cholangitis, erosive and ulcerative lesions, gastrointestinal bleeding, reversible reaction from the pancreas (eg, increase in activity of amylase and lipase without any pain or abdominal pain).

Since the cardiovascular system: often - heartbeat, and in some cases - arrhythmias, endocarditis, pulmonary embolism.

On the part of the hemopoietic system: possible neutropenia, leukopenia, thrombocytopenia.

On the part of the organ of vision: often - visual impairment, inflammatory diseases of the eye, in some cases - corneal ulcer,

On the part of metabolism: often - increased sweating (including night) may be clinically significant changes in laboratory parameters of thyroid function, in some cases - diabetes mellitus.

Dermatological reactions: often - dermatitis, rashes, dry skin, photosensitivity.

On the part of the body as a whole: often - weight loss, chest pain, flu-like syndrome, malaise, chills.

Other: often - decreased libido, hot flushes, muscle cramps, pain in the neck, in some cases - the autoimmune reaction, infection, coma, myositis.


Contraindications

Autoimmune hepatitis, decompensated liver disease (Class B and C on the scale of Child-Pugh) before or during treatment, hypo-or hyperthyroidism, decompensated diabetes, hypercreatininemia (more than 1.5 times higher FHG), Children age 3 years, increased sensitivity to interferon alfa, a product life Escherichia coli, a polyethylene glycol.


Application of pregnancy and breastfeeding

Health and Safety in pregnancy has not been established. The application is only possible in cases where the intended benefits to the mother outweighs the potential risk to the fetus.

It is not known whether the allocated peginterferon alfa-2a with breast milk, so use with caution during lactation.

Women of childbearing age in the period of treatment should use reliable methods of contraception.

In experimental studies found that the introduction of peginterferon alfa-2a (and other interferon alpha) female monkeys indicated lengthening the menstrual cycle, accompanied by a decrease and a later onset of maximal concentrations of 17β-estradiol and progesterone. After the application of the menstrual cycle returned to normal. The introduction of interferon alfa-2a at doses up to 25 mln.ED / kg / day for 5 months had no effect on fertility of male rhesus macaques.

Teratogenic effects have been studied. The use of interferon alfa-2a resulted in a significant increase in the number of spontaneous abortions in rhesus monkeys. In offspring born in the period, no teratogenic effects were noted.


Cautions

Use under the supervision of a qualified doctor with experience in the use of such drugs.

With caution to patients with a history of depression, the cardiovascular system, autoimmune diseases, psoriasis, at least 1500/mkl neutropenia, thrombocytopenia less than 90 000/mkl, Hb less than 10 g / dl, while myelotoxicity drugs.

Monotherapy is shown in the case of intolerance or contraindications to ribavirin. Efficacy and safety of children and adolescents under the age of 18 years, and the effectiveness of monotherapy or combination with ribavirin in patients after liver transplantation or other organs, patients with concomitant infection with HIV or hepatitis B virus is not installed.

If therapy with thyroid can not be adequately treated, peginterferon alfa-2a should be abolished.

With the development of anaphylactoid reactions peginterferon alfa-2a should be abolished and assign the appropriate drug therapy.

If you experience persistent or increasing pulmonary infiltrates or pulmonary function disorders peginterferon alfa-2a should be abolished.

Prior therapy should be standard common clinical and biochemical blood tests. In the course of therapy common clinical blood tests should be repeated every 2 weeks, and biochemical - every 4 weeks, should periodically conduct additional tests.

Note that holding therapy is possible only under the following laboratory tests: platelet count> 90,000 cells / ml (in patients with cirrhosis or transition to cirrhosis -> 75 000 cells / ml), absolute neutrophil count> 1500 cells / ml, creatinine level in the serum of less than 1.5 times the upper limit of normal, the concentrations of TSH and T4 within the normal range (or if adequate control of thyroid function).

Safety and efficacy in children and adolescents under the age of 18 is not installed.

Effects on ability to drive a car and management mechanisms

Patients who develop dizziness, drowsiness, confusion and weakness, should not engage in potentially hazardous activities.


Drug Interactions

With simultaneous use with theophylline may increase its concentration in blood plasma (may require dosage adjustment of theophylline).