Brand name: Peg Intron
Active ingredient (generic name): Peginterferon alfa-2b
Manufacturer: Schering Plough
Importer: Behestan Darou
Pharmacotherapeutic group: Interferons
Pharmaceutical form: 50, 80, 100, 120, 150mcg vials
Pharmacodynamic:
Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. Studies with other interferons have demonstrated species specificity. However, certain monkey species, e.g., Rhesus monkeys are susceptible to pharmacodynamic stimulation upon exposure to human type 1 interferons.
Once bound to the cell membrane, interferon initiates a complex sequence of intracellular events that include the induction of certain enzymes. It is thought that this process, at least in part, is responsible for the various cellular responses to interferon, including inhibition of virus replication in virus-infected cells, suppression of cell proliferation and such immunomodulating activities as enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of lymphocytes for target cells. Any or all of these activities may contribute to interferon's therapeutic effects.
Recombinant interferon alfa-2b also inhibits viral replication in vitro and in vivo. Although the exact antiviral mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism. This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell.
Pharmacokinetic:
Following subcutaneous administration, maximal serum concentrations occur between 15-44 hours post-dose, and are sustained for up to 48-72 hours post-dose.
The mechanisms involved in clearance of interferons in man have not yet been fully elucidated. However, renal elimination may account for a minority (approximately 30 %) of PegInteron apparent clearance.
Therapeutic indication:
PegIntron is indicated for the treatment of adult patients who have elevated transaminases without liver decompensation and who are positive for serum HCV-RNA or anti-HCV, including naiiv patients with clinically stable HIV co-infection.
The best way to use Peg Intron in this indication is in combination with ribavirin.
Adverse reaction:
The most common treatment-related adverse reactions reported during clinical trials with Peg Intron combination with ribavirin in adults, seen in more than half of the study subjects, were fatigue, headache, and injection site reaction. Additional adverse reactions reported in more than 25 % of subjects included nausea, chills, insomnia, anaemia, pyrexia, myalgia, asthenia, pain, alopecia, anorexia, weight decreased, depression, rash and irritability. The most frequently reported adverse reactions were mostly mild to moderate in severity and were manageable without the need for modification of doses or discontinuation of therapy. Fatigue, alopecia, pruritus, nausea, anorexia, weight decreased, irritability and insomnia occur at a notably lower rate in patients treated with Peg Intron monotherapy compared to those treated with combination therapy .
Contraindication:
Hypersensitivity to the active substance or to any interferon or to any of the excipients;
- A history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease in the previous six months;
- Severe, debilitating medical conditions;
- Autoimmune hepatitis or a history of autoimmune disease;
- Severe hepatic dysfunction or decompensated cirrhosis of the liver;
- Pre-existing thyroid disease unless it can be controlled with conventional treatment;
- Epilepsy and/or compromised central nervous system (CNS) function;
- HCV/HIV patients with cirrhosis and a Child-Pugh score 6.
Paediatric patients:
- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal ideation or suicidal attempt.
Combination therapy with ribavirin: Also see ribavirin Summary of the Product Characteristics (SPC) if Peg Intron is to be administered in combination with ribavirin in patients with chronic hepatitis C.
Special warnings:
Psychiatric and Central Nervous System (CNS):
Severe CNS effects, particularly depression, suicidal ideation and attempted suicide have been observed in some patients during Peg Intron therapy, and even after treatment discontinuation mainly during the 6-month follow-up period. Other CNS effects including aggressive behavior (sometimes directed against others such as homicidal ideation), bipolar disorders, mania, confusion and alterations of mental status have been observed with alpha interferons. Patients should be closely monitored for any signs or symptoms of psychiatric disorders. If such symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the prescribing physician and the need for adequate therapeutic management should be considered. If psychiatric symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with Peg Intron be discontinued, and the patient followed, with psychiatric intervention as appropriate.
Patients with existence of, or history of severe psychiatric conditions: If treatment with peginterferon alfa-2b is judged necessary in patients with existence or history of severe psychiatric conditions, this should only be initiated after having ensured appropriate individualized diagnostic and therapeutic management of the psychiatric condition.
Pregnancy and lactation:
Pregnancy
There are no adequate data from the use of interferon alfa-2b in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Interferon alfa-2b has been shown to be abortifacient in primates. Peg Intron is likely to also cause this effect.
The potential risk in humans is unknown. Peg Intron is to be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Combination therapy with ribavirin:
Ribavirin causes serious birth defects when administered during pregnancy, therefore ribavirin therapy is contraindicated in women who are pregnant.
Breast-feeding
It is not known whether the components of this medicinal product are excreted in human milk. Because of the potential for adverse reactions in breast-fed infants, breast-feeding should be discontinued prior to initiation of treatment.
Storage temperature:
Store in a refrigerator (2°C - 8°C). Do not freeze.
After reconstitution:
- Chemical and physical in-use stability has been demonstrated for 24 hours at 2-8C
- From a microbiological point of view, the product is to be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8C.
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