Peg-interferon alfa-2a (Pegasys®)

Manufacturer: Roche, Inc., Nutley, NJ

Indication: The drug is used for the treatment of adults with chronic hepatitis C who have never been previously treated with interferon and who have compensated liver disease (a damaged but still functioning liver). The drug is also effective in patients with compensated cirrhosis.

Drug Class: Peg-interferon alfa-2a, with a molecular weight (MW) of approximately 60 kD, is a covalent conjugate of recombinant alfa-2a interferon (MW, approximately 20 kD) with a single branched bis-monomethoxy polyethylene glycol chain (MW, approximately 60 kD). The PEG moiety is linked at a single site to the interferon moiety via a stable amide bond to lysine. Interferon alfa-2a is produced using recombinant DNA technology in which a cloned human leukocyte interferon gene is inserted and expressed in Escherichia coli.

Uniqueness of Drug: Peg-interferon alfa-2a is a pegylated interferon that remains active in the bloodstream longer, and at a more constant level, than standard interferon alfa. With the pegylated form, fewer injections are required. The Food and Drug Administration (FDA) has approved peg-interferon alfa-2a on the basis of three pivotal phase III clinical trials that demonstrated its effectiveness in patients with chronic hepatitis C, including cirrhotic patients with compensated liver disease.

Precautions: A “black box” warning for alpha interferons, including peg-interferon alfa-2a, states that they may cause or exacerbate life-threatening or fatal neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be closely monitored with periodic clinical and laboratory evaluations. For patients with persistently severe or worsening signs or symptoms of these conditions, therapy should be discontinued. In many cases, these disorders resolve after peg-interferon alfa-2a is withdrawn. Patients with and without previous psychiatric illness should be monitored for such serious or potentially life-threatening conditions as depression, suicidal ideation, and suicidal attempts.

Peg-interferon alfa-2a should be used with extreme caution in patients who report a history of depression. Neuropsychiatric adverse events observed with alpha interferon treatment include relapse of drug addiction, drug overdose, aggressive behavior, psychoses, hallucinations, bipolar disorders, and mania. Physicians should monitor all patients for evidence of depression and other psychiatric symptoms. Patients should be advised to report any sign or symptom of depression or suicidal ideation to their prescribing physicians. In severe cases, therapy should be stopped immediately and psychiatric intervention instituted. canadian pharmacy

Peg-interferon alfa-2 suppresses bone marrow function and may result in severe cytopenia. Very rarely, alpha interferons may be associated with aplastic anemia. The manufacturer advises that a complete blood count (CBC) be obtained before treatment and monitored routinely during therapy.

Peg-interferon alfa-2a should be used with caution in patients with baseline neutrophil counts below 1,500 cells/mm3, baseline platelet counts below 90,000 cells/mm3, or baseline hemoglobin levels below 10 g/dl. Peg-interferon alfa-2a therapy should be discontinued, at least temporarily, if severe decreases in neutrophil or platelet counts occur.

Hypertension, supraventricular arrhythmias, chest pain, and myocardial infarction have been observed in patients who have been treated with peg-interferon alfa-2a. The drug should be administered with caution to patients with pre-existing cardiac disease. Severe acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) have been rarely observed during alpha interferon therapy. If such a reaction occurs, therapy with peg-interferon alfa-2a should be discontinued and appropriate medical therapy should be instituted immediately.

Peg-interferon alfa-2a can cause or aggravate hypothyroidism and hyperthyroidism. Hyperglycemia, hypoglycemia, and diabetes mellitus have been known to develop in patients treated with peg-interferon alfa-2a. Patients with these conditions at the baseline who cannot be effectively treated by medication should not begin peg-interferon alfa-2a therapy. If these conditions develop during treatment and cannot be controlled with medication, therapy may need to be discontinued. Development or exacerbation of autoimmune disorders (e.g., myositis, hepatitis immune thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus) have been reported in patients receiving alpha interferon. Peg-interferon alfa-2a should be used with caution in patients with autoimmune disorders. buy tadacip

Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, and sarcoidosis, sometimes resulting in respiratory failure or death, may be induced or exacerbated by peg-interferon alfa-2a or by alpha interferon therapy. If persistent or unexplained pulmonary infiltrates or pulmonary impairment develops, treatment should be discontinued. Hemorrhagic or ischemic colitis, sometimes fatal, has been observed within 12 weeks of initiation of alpha interferon treatment. Peg-interferon alfa-2a should be discontinued immediately if the patient experiences abdominal pain, bloody diarrhea, and fever— the typical manifestations of colitis. The colitis usually resolves within one to three weeks of discontinuation of alpha interferon therapy.

Ulcerative colitis has also been seen in patients receiving alpha interferon. Pancreatitis, sometimes fatal, has occurred during alpha interferon treatment. Peg-interferon alfa-2a therapy should be suspended if symptoms or signs suggestive of pancreatitis are observed, and it should be discontinued if a diagnosis of pancreatitis is confirmed.

Treatment with peg-interferon alfa-2a or other alpha interferons can induce or exacerbate a decrease in or a loss of vision; retinopathy, including macular edema, retinal artery or retinal vein thrombosis, retinal hemorrhages, and cotton-wool spots; optic neuritis; and papilledema. All patients should receive a baseline eye examination. Patients with pre-existing ophthal-mologic disorders (e.g., diabetic or hypertensive retinopathy) should receive periodic ophthalmologic examinations during alpha interferon treatment. If ocular symptoms develop, patients should receive a prompt and complete eye examination. Peg-interferon alfa-2a treatment should be discontinued if new or worsening ophthalmologic disorders develop. tadalis sx

Dosage and Administration: The recommended dose of peg-interferon alfa-2a is 180 mcg (1.0 ml) once weekly for 48 weeks by subcutaneous administration in the abdomen or thigh. There are no safety and efficacy data on treatment for longer than 48 weeks. Discontinuing therapy should be considered after week 12; virological results are available if the patient has not demonstrated a response.

When a dose must be modified because of moderate to severe clinical or laboratory adverse reactions, reducing the initial dose to 135 mcg (0.75 ml) is generally adequate, although it is sometimes necessary to reduce the dose to 90 mcg (0.5 ml).

P&T Committee Considerations: More than 170 million people worldwide are infected with the hepatitis C virus (HCV), which progresses to chronic liver disease in most of these patients. Thus, HCV infection is the cause of significant long-term morbidity and mortality. The major concern with HCV infection is the lack of viral clearance during early infection, which may result in chronic hepatitis C, cirrhosis, end-stage liver disease, and hepatocellular carcinoma.

Interferon-alpha and the mainstays of HCV therapy. Peg-interferon alfa-2a represents an alpha interferon that remains active in the bloodstream longer and at a more constant level than standard interferon alfa. Although a combination of peg-interferon alfa-2a and the antiviral ribavirin canadian will eventually prove to be better in the treatment of HCV, peg-interferon alfa-2a should be placed on the formulary to treat HCV infection.

Compared with the unmodified interferon that has been used until now, peg- interferon alfa-2a shows better characteristics in the treatment of chronic hepatitis C. The modified drug has a biological half-life approximately ten times greater than the 8.5 hour half-life of the unmodified drug, which must be injected three times a week; peg-interferon alfa-2a needs to be injected only once a week. An improved response rate is also superior because of the absence of the serum fluctuations that occur with the unmodified drug.

The cost of peg-interferon alfa-2a is $291 per vial. Each vial delivers a single subcutaneous dose of 180 mcg of the drug in a volume of 1 ml.