Interferon toxicity

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..Deat hs There was one patient death, a suicide, among patients receiving peg-interferon and two patient deaths in the interferon group (one murder/suicide and one sudden death)Results and Conclusions: Safety.

No deaths, serious or severe adverse events were observed. Adverse events moderate to mild in severity typical of Interferon toxicity were observed. The treatment groups would be compared with respect to the distribution of severity scores (absent, mild, moderate, severe) for flu-like symptoms and psychiatric disorders. AOther Serious Adverse Events The highest incidence of serious adverse events among all organ

systems 27 L occurred in the neuropsychiatric category (about 2% in each treatment group). Serious adverse events in other body systems occurred at a frequency 51%. The individual types of serious adverse events included: suicide attempt, suicidal ideation, severe depression; relapse of drug addiction/overdose; nerve palsy (facial, oculomotor); cardiomyopathy, myocardial infarction, retinal ischemia, retinal vein thrombosis, transient ischemic attack, supraventricular arrhythmias, loss of consciousness; neutropenia,

infection (pneumonia, abscess); autoimmune thrombocytopenia, hyperthyroidism, rheumatoid arthritis, interstitial nephritis, lupus-like syndrome, aggravated psoriasis; urticaria. Additional details of these events are provided in the narratives of serious adverse events. ----- Forwarded Message ----To: "miralax " <miralax >Sent: Fri, May 4, 2012 7:28:30 AMSubject: was jailed for aggressive behavior

Study Conduct: All 64 subjects who were enrolled in 195-060 advanced to 195140. Fifty-four subjects completed 195-140. The reasons for discontinuation were as follows. One subject (0.035 pg/kg peg-interferon) was lost to follow-up, four (0.1 pg/kg) and three (0.25 pg/kg peg-interferon) subjects were treatment

failures, one subject (0.25 pg/kg peg-interferon) did not wish to continue, and one subject (interferon alfa-2b) was jailed for aggressive behavior. Drug Substance: PEG-lntronTM, peg-interferon alfa-2b, is a covalent conjugate of

recombinant interferon alfa-2b with monomethoxy polyethylene glycol product. The biological activity of peg-interferon alfa-2b is derived from its interferon alfa-2b moiety. Interferon alfa-2b has been classified as an alpha interferon and is a water- soluble protein with a molecular weight of approximately 19,000 daltons produced by recombinant DNA techniques.

Interferon alfa-2b is obtained from the bacterial fermentation of a strain of Escherichia co/i bearing a genetically engineered plasmid containing an interferon alfa-2b gene from human leukocytes. The average molecular weight of the PEG-Intron molecule is approximately 31,000 daltons. Renal elimination accounts for approximately 30% of the clearance. Single-dose PEG-lntron pharmacokinetics following a subcutaneous 1 .O pg/kg dose suggest the clearance of PEG-lntron is reduced in patients with impaired renal function (creatinine clearance c 50 ml/minute). Pharmacokinetic evaluations for pediatric subjects have not been performed. There were

no significant pharmacokinetic differences between male and female patients with chronic hepatitis C. 3 Chronic Viral H Conclusions: The reported frequency of adverse events for peg-interferon alfa-2b and interferon alfa-2b were similar. Pegylated interferon alfa-2b has reduced clearance relative to non-pegylated interferon permitting

reduced dosing frequency at doses that appear to be pharmacologically active. http://www.interferon.ws/pdf/PegIntReview_fda.pdf