Intron A and Roferon A

What Is Interferon Alfa?
Which Patients with Hepatitis B Should Use Interferon?
What Are the Doses Used?
What Are the Side Effects of Treatment?
Intron A Prescribing Information

WARNING - Alpha interferons, including INTRON® A, cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many but not all cases these disorders resolve after stopping INTRON A therapy.

What Is Interferon Alfa?

Natural interferon is a protein produced by the body's cells in response to viral infections. There are three types: alfa, beta and gamma. Commercially-produced (genetically-engineered) interferon alfa mimics the activity of naturally-occuring interferon alfa produced by the body, although the mechanism of action of the drug is not well understood.

Intron A (interferon alfa-2b) is one commercial form of interferon approved by the US Food and Drug Administration for the treatment of Hepatitis B and C.

Roferon A (interferon alfa-2a), and Infergen ("consensus" interferon) are also FDA-approved for treatment of chronic hepatitis C, but not for chronic hepatitis B.

Which Patients with Hepatitis B Should Use Interferon?

Less than 50% of patients with chronic hepatitis B infection are eligible for interferon therapy. Patients should have infection documented for at least six months, elevated liver enzymes (AST or SGOT, and ALT or SGPT tests) and an actively replicating virus in their blood (hepatitis "e" antigen [HBeAg] and/or hepatitis B virus DNA [HBV DNA] positive tests).

Patients with normal liver enzymes are less likely to respond to therapy. Patients with low hepatitis B virus DNA levels and elevated liver enzymes are more likely to benefit than those with high HBV DNA levels.

A biopsy­where a needle is inserted into the liver to obtain a small sample of tissue­is helpful to determine liver damage prior to treatment. Patients with acute infection, cirrhosis or other major medical problems should not be treated.

What Are the Doses Used?

The FDA-approved dose of standard interferon alfa for treatment of hepatitis. FDA-approved treatment for hepatitis B is five million units daily for 16 weeks. The dose may be modified for significant side effects.

However, lower doses may result in lower rates of response. Higher doses, more frequent doses, longer therapy, and combination therapies are being tested.

What Are the Side Effects of Treatment?

The most common serious side effect is depression, particularly in patients with a prior history. Most patients will have muscle aches, fatigue and low grade fevers. These can be minimized by taking low doses of acetaminophen (e.g. Tylenol) at night. Nausea and diarrhea are common as is irritation of the skin at the injection site.

Patients may experience significant weight loss, and if this occurs the dose should be adjusted. Patients often complain of irritability and headaches. A small number of patients may develop thyroid disease.

Normal thyroid function should be documented prior to treatment. Hair loss is not uncommon, but usually reversible. Few side effects are severe or persist after treatment.

When Is Treatment Not Indicated?

Patients with chronic hepatitis B or C, with fluid in the abdomen (ascites), bleeding from dilated veins in the esophagus (variceal bleeding), or mental confusion (encephalopathy) should be treated only in a clinical trial.

Others not suitable for treatment are those with symptomatic heart, lung or kidney disease, with human immunodeficiency virus (HIV) infection or organ transplant recipients on prednisone, cyclosporine and FK-506 and patients on antidepressants or with a history of suicide attempts.

Interferon should not be given to women considering pregnancy, nor to the intended father. Patients with active substance abuse (alcohol or illegal drugs) should not be offered this therapy.

What Can Be Expected from Treatment?

Approximately 40%-50% of patients with chronic hepatitis C receiving full dose therapy will have a normalization of their liver enzymes, usually by the third month. With normal liver tests, the virus may become undetectable in blood. If no response is seen by three months, most researchers advocate stopping therapy.

A few patients who respond to therapy may see their liver enzymes rise towards the end of treatment. The reason for this is unknown. When interferon is stopped after six months, more than half of the patients with hepatitis C who have responded will experience a rise in their liver tests. Patients will usually respond again if given further therapy. Therefore, 10%-15% will have a long lasting positive response. Longer treatments will likely result in longer positive responses. However, there is no evidence that this affects the relapse rate when treatment is stopped. Few patients will eradicate the virus using this therapy alone.

What Happens if Interferon Is Not Given?

The long term prognosis of hepatitis C is poorly understood. However, hepatitis C is generally a slowly progressive disease, with evolution over years if not decades. There is no proof that six months of treatment with interferon alters this.

The changes vary from mild chronic hepatitis (least amount of liver damage) to moderate or severely active chronic hepatitis, with or without fibrosis or cirrhosis (most amount of liver scar damage). It is not known who will develop complications including chronic liver disease, liver failure and liver cancer.

What New Drugs Are Available?

Much is unknown about treatment with interferon. Therefore, when possible, patients should consider participating in clinical trials.

Different kinds of interferons and other new drugs, by themselves or in combination with other drugs, are being evaluated for both hepatitis B and C.