Pegasys (peginterferon alfa-2a)

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Drugs Approved by the FDA
Drug Name: Pegasys (peginterferon alfa-2a)
The following information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company: Roche
Approval Status: Approved October 2002
Treatment for: Hepatitis C

General Information
Pegasys (peginterferon alfa-2a) was approved in October 2002 for the treatment of adults with chronic hepatitis C who have compensated liver disease and have not previously been treated with interferon alpha, including patients with compensated cirrhosis. Pegasys is a pegylated interferon that remains active in the bloodstream longer and at a more constant level than interferon alpha.
Pegasys is available as premixed solution. It is administered at a dose of 180 ug as a subcutaneous injection once a week for a recommended duration of 48 weeks.
Clinical Results
Three pivotal phase III clinical studies of Pegasys demonstrated that the sustained virological response (defined as undetectable serum hepatitis C RNA levels post-treatment [on or after study week 68]) in the Pegasys treated subjects was as high as 38% in the overall population versus 19% in the interferon alfa-2a group. Subjects with cirrhosis who were treated with Pegasys showed a sustained virological response as high as 30% versus 8% in the interferon alfa-2a group. Subjects with genotype 1 treated with Pegasys showed showed a sustained virological response of up to 23%, compared to 6% in the interferon alfa-2a group.
In addition, studies indicated that it can be determined at week 12 of treatment whether a subject is unlikely to attain a sustained virological response with Pegasys. This could prevent subjects from continuing a therapy to which they will most likely be unresponsive.
Side Effects
In clinical studies, the following adverse events were reported most often:
o        Headache
o        Fatigue
o        Myalagia
o        Pyrexia
o        Rigors
o        Arthralgia
o        Nausea
o        Alopecia
o        Injection-site reaction
o        Neutropenia
o        Insomnia
o        Depression
o        Anorexia
o        Irritability
Alpha interferons, including Pegasys, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders.
Mechanism of Action
Pegasys is produced when interferon alfa-2a undergoes the process of pegylation in which one or more chains of polyethylene glycol (also known as PEG) are attached to another molecule. In Pegasys, a large, branched, mobile PEG is attached to the interferon alfa-2a molecule, providing a selectively protective barrier against rapid absorption, metabolism and elimination. At the same time, the PEG maintains the ability of the interferon alfa-2a to attack the virus.
Additional Information
For further information about Pegasys, please visit the Roche web site at www.roche.com.
AVAILABLE FORMS
Single-dose vials: 180 mcg/ml
INDICATIONS, ROUTES, AND DOSAGES
Hepatitis C, in patients with compensated hepatic disease who haven’t previously been treated with interferon alfa--
Adults: 180 mcg S.C. once a week for 48 weeks.
ADJUST-A-DOSE:
In patient with neutrophil count between 500 and 750 cells/mm3, give 135 mcg S.C. each week; if neutrophil count falls below 500 cells/mm3, suspend treatment and restart at 90 mcg S.C. each week when neutrophil count returns to at least 1,000 cells/mm3.
   In patient with platelet count under 50,000 cells/mm3, give 90 mcg S.C. each week; stop drug if platelet count falls below 25,000 cells/mm3.
   In patient with end-stage renal disease requiring dialysis, give 135 mcg S.C. each week, and monitor patient closely.
   In patient with hepatic disease, give 90 mcg S.C. each week if ALT is above baseline levels; stop drug if ALT continues to rise or is accompanied by increased bilirubin or hepatic decompensation.
CONTRAINDICATIONS AND PRECAUTIONS
Contraindicated in patients allergic to peginterferon alfa-2a or to any of its components and in those with autoimmune hepatitis or decompensated hepatic disease.
   Use cautiously in patients with bone marrow suppression (neutrophils fewer than 1,500 cells/mm3, platelets fewer than 90,000 cells/mm3, or baseline hemoglobin below 10 g/dl). Also use cautiously in patients with preexisting cardiac disease; thyroid disease; diabetes mellitus; autoimmune disorders; pulmonary disease; preexisting ophthalmologic disorders; impaired renal function, or a history of depression or suicidal ideation. Use cautiously in pregnant or breast-feeding patients.
INTERACTIONS
Drug-drug. Theophylline: May increase theophylline levels and lead to toxicity. Monitor patient closely and decrease theophylline dose as appropriate.
ADVERSE REACTIONS
CNS: fatigue, fever, pain, asthenia, headache, dizziness, insomnia, memory impairment, concentration impairment, depression, irritability, anxiety, depressed mood, suicidal ideation, cerebral hemorrhage, coma.
CV: arrhythmia, endocarditis.
EENT: corneal ulcer, retinopathy.
GI: nausea, diarrhea, abdominal pain, vomiting, dry mouth, anorexia, hepatic decompensation, GI bleeding, pancreatitis, colitis.
Hematologic: neutropenia, thrombocytopenia.
Musculoskeletal: myalgia, arthralgia, back pain.
Respiratory: pulmonary embolism.
Skin: alopecia, pruritus, increased sweating, dermatitis, rash.
Other: rigors, injection-site reaction, autoimmune phenomena, diabetes mellitus, hypersensitivity reactions.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE-THREATENING.