Pegetron

Summary

Treatment for hepatitis C virus (HCV) is a combination of two drugs—a long-acting form of interferon called peginterferon and another drug called ribavirin. In Canada, the combination of peginterferon and ribavirin is sold together (bundled) in a box and called Pegetron. The long-acting interferon is taken by injection once weekly, while ribavirin comes in the form of capsules and is taken twice daily. Side effects from combination therapy include fever, headache, tiredness and sometimes depression.

What is inside the box of Pegetron?

Pegetron is the brand name of a combination of the following two drugs which are sold together:

• a long-lasting form of alpha interferon called peginterferon (pegylayed interferon-alfa-2b)
• a nuke (or nucleoside analogue) called ribavirin

The rest of this Fact Sheet focuses on peginterferon and ribavirin.

How does peginterferon work?

Alpha interferon is the name of a chemical messenger, or cytokine, made by cells in your body. This cytokine has at least two important roles:

• It protects your cells from infection by HCV.
• It helps your immune system fight HCV.

The “peg” in peginterferon stands for polyethylene glycol. When peg is attached to interferon, it provides a protective barrier that shields the interferon from being broken down, thus prolonging the time it remains in the blood. Regular interferon needs to be injected at least three times weekly. Peginterferon only has to be injected once a week and appears to be stronger than regular interferon.

How do people with HIV use peginterferon?

Your doctor has prescribed peginterferon for you because you have HCV infection. He or she has decided that you require treatment to help reduce liver damage caused by HCV. For more information about HCV and the liver, see the Hepatitis C Fact Sheet and CATIE's hepatitis C website www.hepcinfo.ca.

Because peginterferon would be destroyed in your stomach if it were swallowed, it must be injected under the skin, once weekly. Speak to your clinic nurse, who can teach you how to inject yourself or may be able to inject the drug for you—whichever method is best for you. This drug is usually taken at bedtime for up to one year. To make peginterferon more effective at treating HCV, your doctor will also prescribe another drug called ribavirin.

To ensure that combination therapy with peginterferon and ribavirin is working, your doctor will have your blood tested on a regular basis.

What is ribavirin and how is it used?

Ribavirin, also known as Copegus, is a type of drug called a “nuke” (or nucleoside analogue). When taken by itself, ribavirin is a weak drug. However, when taken together with peginterferon, the combination is powerful. Most people with HIV take ribavirin at doses between 800 and 1,200 mg/day, depending on their weight. Ribavirin is taken orally with meals.

Injecting peginterferon

Your nurse will teach you how to inject peginterferon under the skin. As well, the manufacturer, Schering-Plough, has prepared booklets and brochures to help you with self-injecting. Ask your nurse or doctor for these materials. The best places on the body to inject peginterferon include the following:

• upper leg or thigh;
• outer part of the upper arm;
• abdomen (but not the belly button or waist).

Do not inject peginterferon into the same place all the time; you should change injection sites in a regular pattern. Some clinics may let you come in once a week so the clinic nurse can inject you, if you prefer.

Warnings

Although potent, combination therapy for HCV with peginterferon and ribavirin is not for everyone with HCV.

1. Mental health

We are about to describe a series of problems that may occur in some people who use peginterferon and ribavirin. Once you have started combination therapy for HCV, if you notice any of these problems, talk to your doctor right away:

• you become easily upset or angry;
• you have unexpected feelings of sadness;
• you feel hopeless;
• you have thoughts about harming yourself or others (such as thinking about starting to use street drugs again if you were using in the past);
• you have thoughts about suicide.

2. Lactic acidosis

Lactic acidosis is the name given to a condition where high levels of lactic acid build up in the blood. In general, it is a rare side effect that may be associated with the use of nukes used to treat HIV, such as AZT, ddI, ddC, d4T and 3TC. It can occur in people with HIV who use the nuke ribavirin, particularly if they also use the nukes ddI (didanosine, Videx, Videx EC) and/or d4T (stavudine, Zerit). These drugs damage the energy-producing parts, or power plant, of a cell. When a cell can't produce enough power, it begins to malfunction and can die. The following signs/symptoms can develop when a person has lactic acidosis:

• unexpected tiredness;
• nausea and/or vomiting;
• abdominal pain;
• shortness of breath.

If you have these symptoms, talk to your doctor right away.

Blood tests can help your doctor determine whether you have lactic acidosis. The following levels may indicate this problem:

• lactate levels of 5 mmol/L or greater;
• bicarbonate levels of 20 mmol/L or lower.

3. Pregnancy

If you are pregnant or think that you may be pregnant and you are taking peginterferon and ribavirin, talk to your doctor right away. These drugs should not be used by the following people:

• pregnant women;
• women who may become pregnant and their male partners.

This is because the combination of these drugs can severely damage the fetus. Pregnancy should not be planned while you or your partner are on therapy. If you are planning to have a baby, you should wait up to six months after therapy has been stopped. Ribavirin can also be toxic to sperm.

4. Heart, stroke and blood problems

Some people who have used peginterferon have developed heart problems, including low blood pressure, rapid heart beats and chest pain. Ribavirin in combination with peginterferon can cause anaemia (a drop in the number of red blood cells). Peginterferon can also lower levels of white blood cells, including a group called neutrophils, increasing your risk of developing infections. As well, this drug can reduce levels of platelets in your blood. Because platelets are needed to help your blood clot, less-than-normal levels of platelets increase your risk of bleeding. Tell your doctor right away if you have any of these problems.

Some people who have used Pegetron have developed bleeding in the brain (a stroke). These people had few or no risk factors for stroke and they have happened in young people. Signs and symptoms of a stroke include the following:

• sudden numbness or weakness of face, arm or leg, especially on one side of the body;
• sudden confusion or trouble speaking or understanding speech;
• sudden trouble seeing in one or both eyes;
• sudden trouble walking, dizziness, or loss of balance or coordination;
• sudden severe headache with no known cause.

If you have any of these go to your nearest emergency department immediately.

5. Infections

A temporary fever is a normal reaction to interferon treatment. However, a high fever or a fever that does not go away needs to be investigated to ensure that there is not some other cause, such as an infection. If you have a high or persistent fever while using interferon, tell your nurse and doctor.

6. Skin rash

Rash can occur in people using Pegetron. In rare cases the rash may be serious. If you have a severe rash with blisters, fever, or sores in your mouth, nose or eyes (or your eyes become red) contact your doctor right away.

7. Changes in vision

Some people who use peginterferon may develop blurred vision or other problems seeing. If this happens, tell your doctor right away.

Side effects

1. Common side effects of interferon that occurred in clinical trials were those belonging to a flu-like syndrome as follows:

• unexpected tiredness;
• headache;
• fever;
• muscle and/or bone pain;
• chills.

These side effects tend to appear between six and eight hours after injection with peginterferon. Some doctors recommend that their patients pre-medicate, that is, take pain-relievers such as ibuprofen (Advil, Motrin) before injecting peginterferon, to prevent or reduce these side effects. Taking peginterferon at bedtime may also be helpful. Drinking plenty of healthful fluids—water, juices, herbal teas—that do not contain caffeine is useful when taking peginterferon therapy. Make sure to get a balance of rest and at least some mild exercise.

Other side effects of Pegetron may include the following:

• coughing;
• reduced appetite;
• shortness of breath;
• minor, temporary hair loss;
• dry and itchy skin.

2. Interferon and the brain

Pegetron can temporarily affect the brain and some people also develop the following symptoms:

• difficulty falling asleep;
• reduced ability to concentrate;
• problems thinking clearly;
• increased feelings of irritability;
• depression.

The depression may require treatment while you are taking peginterferon. If you have had depression before taking Pegetron let your doctor know, so that together you can come up with options to prevent or treat this problem.

3. Other side effects

The combination of peginterferon and ribavirin will temporarily affect your bone marrow and can cause a drop in white and red blood cells. Regular blood tests are important to monitor this problem. The dose of ribavirin may be reduced if your blood counts fall too low. Your thyroid gland and the hormones it produces will also be affected by this treatment. All in all, regular visits to your doctor for checkups are very important while you are taking peginterferon and ribavirin.

Always tell your doctor and nurse about your side effects.

Drug interactions

Both peginterferon and ribavirin can temporarily weaken the bone marrow. Use of the anti-HIV drug AZT (zidovudine, Retrovir and also found in the combination pills Combivir and Trizivir) may make this worse.

Ribavirin may weaken the activity of the anti-blood-clotting drug warfarin (Coumadin).

Dosage

Your liver specialist will help you decide which doses of peginterferon and ribavirin are best for you. The boxes containing these drugs are colour-coded by weight of the person. Each box contains the right dose of each of the two drugs that you will use.

The dose of peginterferon normally used is between 1 and 1.5 micrograms (mcg) per kilo of body weight, injected under the skin once a week. This is written as 1–1.5 μg/kg/week.

The dose of ribavirin used with peginterferon usually ranges between 800 and 1,200 mg/day. Ribavirin is taken orally with meals.

Store your box of Pegetron in the refrigerator. When separated from the box, ribavirin capsules may be stored either in the fridge or at room temperature—between 15º and 30º C.

Availability

In Canada, Pegetron and ribavirin are approved for treating HCV. Conditions for subsidized access to these medicines are different in each province and territory—speak to your infectious disease or liver specialist to find out more. CATIE’s online module Federal, Provincial and Territorial Drug Access Programs also contains information about Canadian drug coverage.

References

Soriano V, Puoti M, Sulkowski M, et al. Care of patients coinfected with HIV and hepatitis C virus: 2007 updated recommendations from the HCV–HIV International Panel. AIDS 2007 May 31;21(9):1073–89.

Levy DE. Whence interferon? Variety in the production of interferon in response to viral infection. Journal of Experimental Medicine 2002;195(4):F15–F18.

Zeuzem S, Feinman SV, Rasenack J, et al. Peginterferon alfa-2a in patients with chronic hepatitis C. New England Journal of Medicine 2000; 343(23):1666–1672.

Heathcote EJ, Shiffman ML, Cooksley WG, et al. Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis. New England Journal of Medicine 2000;343(23):1673–1680.

Perry CM and Jarvis B. Peginterferon-alfa-2a (40kD): a review of its use in the management of chronic hepatitis C. Drugs 2001;61(15):2263–2288.

Patten SB. Psychiatric side effects of interferon treatment. Current Drug Safety 2006 May;1(2):143–50.

Lau JYN, Tam RC, Liang TJ and Hong Z. Mechanism of action of ribavirin in the combination treatment of chronic HCV infection. Hepatology 2002;35(5):1002–1009.

Lafeuillade A, Hittinger G and Chadapaud S. Increased mitochondrial toxicity with ribavirin in HIV/HCV coinfection. Lancet 2001;357:280–281.

Kakuda TN and Brinkman Kees. Mitochondrial toxic effects and ribavirin. Lancet 2001;357;1802–1803.

Salmon-Céron D, Chauvelot-Moachon L, Abad S, et al. Mitochondrial toxic effects and ribavirin. Lancet 2001;357;1803–1804.

Guyader D, Poisignon Y, Cano Y and Saout L. Fatal lactic acidosis in an HIV-positive patient treated with interferon and ribavirin for chronic hepatitis C. Journal of Hepatology 2002;37:289–292.

Bini EJ, Mehandru S. Incidence of thyroid dysfunction during interferon alfa-2b and ribavirin therapy in men with chronic hepatitis C: a prospective cohort study. Archives of Internal Medicine 2004 Nov 22;164(21):2371–2376.

Carella C, Maziotti G, Morisco F, et al. The addition of ribavirin to interferon-alpha therapy in patients with patients with hepatitis C virus-related chronic hepatitis does not modify the thyroid autoantibody pattern, but increases the risk of developing hypothyroidism. European Journal of Endocrinology 2002;146:743–749.

Narayana K, D’Souza UJA and Rao KPS. Ribavirin-induced sperm shape abnormalities in Wistar rat. Mutation Research 2002;193–196.

Schulman S. Inhibition of warfarin activity by ribavirin. Annals of Pharmacotherapy 2002;36(1):72–74.

Birgerson LE. Important drug warning. Dear Healthcare professional letter January 2008.

Schering-Plough. PegIntron (peginterferon alfa-2b). Full prescribing information. December 2008.