Pegasys® (peginterferon alfa-2a)

Full Prescribing Information, including Boxed WARNINGS

Pegasys in Hepatitis C Pegasys® (peginterferon alfa-2a) is a once-a-week medication approved by the U.S. Food and Drug Administration to treat adults who have a chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) who show signs of liver damage with no prior treatment with interferon. Pegasys is also used in patients coinfected with HCV and HIV. Pegasys works to reduce the amount of HCV in the blood, helping the body fight the virus¹. Pegasys may be taken alone or in combination with Copegus® (ribavirin) tablets for HCV, an antiviral drug that works by slowing down the growth of the virus¹. Patients in clinical studies, including genotypes 1-4, had a better than 50 percent chance of reducing HCV to undetectable levels.^1,2,3

Pegasys is the most prescribed interferon therapy for HCV in the United States and has been used in approximately 1 million patients worldwide⁴. Pegasys is also the most frequently studied interferon in combination with oral antivirals in development⁵. An estimated 4 million people in the United States have been infected with HCV, and about 75 percent of the infected population is unaware that they have the disease. Chronic viral hepatitis infections are three to five times more frequent than HIV in the United States.⁶

Mechanism of Action Interferon is a natural protein produced by white blood cells in the body that helps fight off infection. For some infections, such as HCV, patients can inject more interferon into their bodies to help fight the virus. The interferon in Pegasys is slightly different from the interferon that the body makes because it is pegylated⁷. Pegasys is a pegylated interferon that is created by a process called pegylation, in which polyethylene glycol (PEG) molecules attach to synthetic interferon. Pegylation technology helps keep the drug in the bloodstream longer, allowing Pegasys to be given once-weekly, and makes it more effective against HCV than a non-pegylated form of interferon.^1,8

Pegasys "Firsts" in Hepatitis Pegasys in combination with Copegus is the first and only regimen approved by the FDA for the treatment of chronic HCV in patients co-infected with clinically stable HIV. Pegasys in combination with Copegus is the first pegylated interferon regimen FDA approved for patients chronically infected with HCV who have severely damaged but still functioning livers (i.e., compensated Child Pugh Class A cirrhosis). Pegasys is also the only pegylated interferon indicated for the treatment of adult patients with chronic HBV who have livers that are damaged but still functioning (compensated liver disease), evidence of HBV multiplying (viral replication) and liver inflammation.^1,9

Clinical Trial Data Pegasys was granted FDA approval in 2002 for use alone or in combination with Copegus in patients with chronic HCV based on two prospective randomized controlled registration trials.^1,2,3

• In the first study, Pegasys 180 mcg weekly and daily Copegus 1000-1200 mg combination therapy was shown to be tolerated as well as interferon alfa-2b plus daily ribavirin 1000-1200 mg and yielded higher sustained virologic response (SVR), or continued undetectable HCV viral load six months after treatment was completed8, compared with interferon alfa-2b plus ribavirin. Genotype 1 (most difficult to treat) SVR for Pegasys plus ribavirin vs. interferon alfa-2b plus ribavirin was 46% vs. 21% (p = .01), and genotype 2 or 3 SVR Pegasys plus ribavirin vs. interferon alfa-2b plus ribavirin was 76% vs. 45% (p = .005).^1,2
• In the second study, Pegasys 180 mcg weekly for 24 or 48 weeks plus a low dose 800mg/day or standard weight-based dose (1,000 or 1,200mg/day) of ribavirin was compared. The study found that HCV treatment with Pegasys plus Copegus may be individualized by genotype. Patients with genotype 1 treated for 48 weeks and a standard dose of ribavirin achieved an SVR of 52% [95% CI: 46 - 58%] and were more likely to achieve an SVR when treated for 48 weeks vs. 24 wks (p < .001) and when treated with standard weight based vs. low dose ribavirin (p=.005). In patients with genotype 2 or 3, response rates were more uniform. Genotype 2 or 3 patients treated for 24 weeks with a low dose of ribavirin achieved an SVR of 84% [CI: 77% -92%], which was the highest response rate observed in the study and not significantly different than longer treatment durations or higher ribavirin dose regimens.^1,3

Pegasys has demonstrated efficacy in a broad range of patient types with HCV, even those with poor prognostic factors such as those with HCV genotype 1 and patients with high viral load, cirrhosis or bridging fibrosis of the liver, patients who are heavy weight (more than 85 kg/187 lbs) and patients with HCV genotype 1 who are African American or Latino.^1,3,10,11,12

Indications Pegasys® (peginterferon alfa-2a) is a prescription medication that is used alone or with COPEGUS® (ribavirin, USP) to treat some adults with chronic (lasting a long time) hepatitis C infection who have certain types of liver problems and have not taken alpha interferon, and also in some adults coinfected with chronic hepatitis C and HIV. If you have chronic hepatitis C, you should not take PEGASYS by itself unless you are not able to take COPEGUS.

COPEGUS is a medicine used with another medicine called PEGASYS to treat chronic hepatitis C infection in people whose liver still works normally, and who have not been treated before with a medicine called an interferon alpha.

Important Safety Information PEGASYS, like other alpha interferons, may cause or make fatal or life-threatening problems worse (like mental, immune system, heart, liver, lung, intestinal and infections). If patients show signs or symptoms of these conditions, their doctor may stop their medication. In most patients, but not all, these conditions get better after they stop taking PEGASYS.

COPEGUS can be extremely harmful and cause birth defects in an unborn baby. Female patients and the female partners of male patients should avoid getting pregnancy. Ribavirin is known to cause anemia (low red blood cells), which can make heart disease.

COPEGUS in combination with PEGASYS may cause birth defects or death of a patient's unborn baby. Females must have pregnancy tests before, during and for 6 months after PEGASYS/COPEGUS combination therapy. During treatment and for 6 months after treatment, female and male patients must:

• use 2 forms of birth control, one being a condom with spermicide.
• inform their healthcare provider if pregnancy occurs while taking PEGASYS/COPEGUS or within 6 months after stopping PEGASYS/COPEGUS therapy. Patients or their healthcare provider should contact the Ribavirin Pregnancy Registry by calling 1-800-593-2214.

Mental health problems and suicide: PEGASYS therapy may cause patients to develop mood or behavioral problems including:

• irritability (getting upset easily)
• depression (feeling low, feeling bad about themselves or feeling hopeless), and anxiety
• aggressive behavior
• former drug addicts may fall back into drug addiction or overdose
• thoughts of hurting themselves or others, or suicide

Heart problems: Some people who take PEGASYS may get heart problems, including:

• high blood pressure
• fast heart rate or abnormal heart beat
• chest pain
• heart attacks

Stroke or symptoms of a stroke: Symptoms may include weakness, loss of coordination, and numbness.

New or worsening autoimmune problems: Some people taking PEGASYS develop autoimmune problems (a condition where the body's immune cells attack other cells or organs in the body), such as rheumatoid arthritis, lupus, and psoriasis.

Infections: Some people who take PEGASYS may get an infection. Symptoms may include:

• fever
• chills
• burning and painful urination
• urinating often
• coughing up yellow or pink mucus (phlegm)

PEGASYS can cause serious side effects. Some of these side effects may cause death. Patients must tell their healthcare provider right away if they have any of these symptoms while taking PEGASYS.

People must not take PEGASYS if they:

• have certain other liver problems
• have certain types of hepatitis caused by their immune system attacking their liver (autoimmune hepatitis)
• have had a serious allergic reaction to another alpha interferon medicine or to any of the ingredients in PEGASYS. Symptoms of a serious allergic reaction to alpha interferon may include: itching, swelling of the face, tongue, throat, trouble breathing, feeling dizzy or faint, and chest pain.

People must not take PEGASYS in combination with COPEGUS if they:

• are pregnant, or planning to get pregnant during treatment or during the 6 months after treatment
• are a male patient with a female sexual partner who is pregnant or plans to become pregnant at any time while they are being treated with COPEGUS or during the 6 months after their treatment has ended
• have certain blood disorders such as thalassemia major or sickle-cell anemia
• take didanosine (Videx® or Videx® EC)

People must not give PEGASYS to a baby under 1 year of age. PEGASYS contains benzyl alcohol, which can cause nervous system problems and other problems that can lead to death.

Patients must tell their healthcare provider about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.

Patients must especially tell their healthcare provider if they take:

• the anti-hepatitis B medicine telbivudine (Tyzeka®)
• theophylline (Theo-24®, Elizophyllin®, Uniphyl®, Theolair™). Their healthcare provider may need to monitor the amount of theophylline in the patient's body and make changes to their theophylline dose.
• any anti-HIV medicines
• methadone hydrochloride (Methadose™, Dolophine® hydrochloride)
• azathioprine (Azasan®, Imuran®)

Patients should avoid the following while taking PEGASYS, or PEGASYS with COPEGUS:

• If they are pregnant do not start taking or continue taking PEGASYS alone or in combination with COPEGUS. COPEGUS in combination with PEGASYS may cause birth defects or death of the unborn baby.
• Avoid becoming pregnant while taking PEGASYS, alone or in combination with COPEGUS. PEGASYS, alone or in combination with COPEGUS, may harm the unborn child (death or serious birth defects) or cause the patient to lose their baby (miscarry).
• Patients must not breast-feed their baby while on PEGASYS, alone or in combination with COPEGUS.
• Drinking alcohol, including beer, wine and liquor. This may make a patient's liver disease worse.
• Taking other medicines. Patients must take only medicines prescribed or approved by their healthcare provider. These include prescription and nonprescription medicines and herbal supplements.

PEGASYS can cause serious side effects including:

• blood problems: PEGASYS can affect the bone marrow and cause low red blood cell, low white blood cell, and platelet counts.
• thyroid problems
• blood sugar problems: Some people may develop high blood sugar or diabetes.
• serious eye problems: PEGASYS may cause eye problems that may lead to vision loss or blindness.
• serious liver problems, worsening of liver problems, including liver failure and death
• lung problems including:
• trouble breathing
• pneumonia
• inflammation of lung tissue
• new or worse high blood pressure of the lungs (pulmonary hypertension). This can be severe and may lead to death.
• inflammation of the pancreas (pancreatitis)
• inflammation of the intestines (colitis)
• serious allergic reactions and skin reactions
• nerve problems: People who take PEGASYS or other alpha interferon products with telbivudine (Tyzeka®) for hepatitis B can develop nerve problems such as continuing numbness, tingling, or burning sensation in the arms or legs (peripheral neuropathy).

Patients must tell their healthcare provider right away if they believe they may have any of the problems listed above.

The most common, but less serious, side effects of PEGASYS include:

• flu-like symptoms
• tiredness and weakness
• stomach problems
• loss of appetite
• skin reactions
• hair thinning
• trouble sleeping

Patients must tell their healthcare provider if they have any side effect that bothers them or that does not go away.

Please see the PEGASYS and COPEGUS full Prescribing Information and Medication Guide, including Boxed WARNINGS for additional Important Safety Information.

PEGASYS® and COPEGUS® are registered trademarks of Hoffman-La Roche Inc. All other brands for listed products are trademarks or registered trademarks (as indicated) of their respective owners and are not trademarks of Genentech, Inc. or Hoffmann-La Roche Inc.

 

1. Pegasys Prescribing Information. http://www.gene.com/gene/products/information/pegasys/pdf/pi.pdf. Accessed on March 4, 2010.
   
   
Fried MW, et al. Peginterferon Alfa-2a Plus Ribavirin for Chronic Hepatitis C Virus Infection. N Engl J Med 2002; 347 (13):975-982.


2. Hadziyannis SJ, et al. Peginterferon-2a and Ribavirin Combination Therapy in Chronic Hepatitis C: A Randomized Study of Treatment Duration and Ribavirin Dose. Ann Intern Med 2004;140(5):346-355.
   
   
3. Data on file. Genentech, a member of the Roche Group.
   
   
4. Clinical Trials. Available at: http://clinicaltrials.gov/ct2/. Accessed March 4, 2010.
   
   
5. Colvin, HM, Mitchell, AE. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. http://www.nap.edu/openbook.php?record_id=12793&page=1. Accessed March 4, 2010.
   
   
6. Pegassist. http://www.pegassist.com/what-is-pegasys/how-does-pegasys-work.aspx. Accessed March 4, 2010.
   
   
7. Swan, T. Care and Treatment for Hepatitis C and HIV Coinfection. U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau, April 2006.
   
   
8. PegIntron Prescribing Information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/103949s5172lbl.pdf. Accessed March 4, 2010.
   
   
9. Conjeevaram HS, et al. Peginterferon and Ribavirin Treatment in African American and Caucasian American Patients With Hepatitis C Genotype 1. Gastroenterology 2006;131(2):470-477.
   
   
10. Jeffers LJ, et al. Peginterferon Alfa-2a (40 kd) and Ribavirin for Black American Patients With Chronic HCV Genotype 1. Hepatology 2004;39(6):1702-1708.
    
    
11. Rodriguez-Torres M, et al. Peginterferon Alfa-2a and Ribavirin in Latino and Non-Latino Whites With Hepatitis C. N Engl J Med 2009;360:257-67.