Pegetron (Merck Canada, 200 mg / 80 mcg, 200 mg / 100 mcg, 200 mg / 120 mcg): Uses, Side Effects and Dosage

ABOUT THIS MEDICATION

What the medication is used for:

• adult patients with chronic hepatitis C who have either not received previous treatment or who failed prior treatment with interferon alpha (pegylated or non-pegylated) and ribavirin combination therapy.

Patients with the following characteristics are more likely to benefit from retreatment: previous relapse, previously treated with interferon therapy (non-pegylated), lower fibrosis score, lower baseline viral load, or infection with HCV genotype 2 or 3.

Patients with the following characteristics are less likely to benefit from retreatment: previous non-response, previously treated with pegylated interferon therapy, significant bridging fibrosis or cirrhosis, or infection with HCV genotype 1 infection.

Hepatitis C is a viral disease that causes inflammation of the liver. It develops into a chronic continuing condition in a great majority of patients. Patients with chronic hepatitis C may develop cirrhosis, liver cancer, or possibly even liver failure. Liver failure due to hepatitis C is currently the leading cause of liver transplants in Canada. PEGETRON may reduce hepatitis C virus in your blood stream to levels that cannot be measured by laboratory tests. However, it is not

yet proven if it will cure your disease or prevent the complications associated with infection.

What it does:

PEGETRON therapy consists of two active medications, PEGETRON (ribavirin) Capsules and PEGETRON (peginterferon alfa-2b) Powder for Solution. PEGETRON (ribavirin) Capsules is an antiviral agent (fights infection), but does not work when used by itself to treat chronic hepatitis C. Peginterferon alfa-2b generally helps the body’s immune system to fight infections. It is not known exactly how the combined products work together to fight the hepatitis C infection.

PEGETRON therapy may reduce the amount of hepatitis C virus in the blood stream to below the level that can be measured by a laboratory test.

It is not yet known if PEGETRON therapy will cure hepatitis C or prevent cirrhosis, liver failure, or liver cancer that can result from being infected with the hepatitis C virus.

It is also unknown if PEGETRON therapy will prevent one infected person from infecting another person with hepatitis C.

When it should not be used:

Do not use these medicines:

• If you or your partner are pregnant.
• If you or your partner plan to become pregnant during treatment or during the 6 months after treatment.
• If you or your partner become pregnant during treatment. PEGETRON therapy can cause serious harm to your unborn child. Therefore, both you and your partner must use effective contraception during this time.
• If you are allergic to any of the ingredients in PEGETRON (ribavirin) Capsules or PEGETRON (peginterferon alfa-2b) Powder for Solution or to any alpha interferon. Please see labels.
• If you have autoimmune hepatitis (hepatitis caused by cells in your body attacking each other) or any other problem with your immune system; if you are taking medicine that suppresses your immune system (your immune system protects you against infection and some diseases).
• If you have a severe nervous or mental disorder.
• If you have thyroid disease that is not well controlled with medicines.

• If you have advanced uncontrolled liver

  disease (other than hepatitis C).

• If you have severe kidney disease.
• If you are breastfeeding.

What the medicinal ingredients are:

• peginterferon alfa-2b Powder for Solution and
• ribavirin Capsules

What the important non-medicinal ingredients are: Each PEGETRON (ribavirin) Capsules contain a small amount of lactose.

For a full listing of non-medicinal ingredients see Part 1 of the product monograph or labels.

What dosage forms it comes in:

PEGETRON (ribavirin) Capsules plus PEGETRON (peginterferon alfa-2b) Powder for Solution in Vials

Each PEGETRON Capsule contains 200 mg of ribavirin.

PEGETRON Powder for Solution is supplied as a powder of peginterferon alfa-2b at strengths of 50, 80, 100, 120, and 150 mcg for single use. Before reconstitution, PEGETRON Powder for Solution may appear either as a white, tablet-shaped solid that is whole or in pieces, or as a white powder. The powder is contained in a 2 mL vial.

PEGETRON (ribavirin) Capsules plus PEGETRON (peginterferon alfa-2b) Powder for Solution in REDIPEN^® Single Dose Delivery System

Each PEGETRON Capsule contains 200 mg of ribavirin.

PEGETRON (peginterferon alfa-2b) REDIPEN^® Single Dose Delivery System consists of a dual-chamber glass cartridge with a chamber containing PEGETRON as a white to off-white lyophilized powder and another chamber containing Sterile Water for Injection. The cartridge is provided in a pen device for reconstitution, dose preparation and subcutaneous administration. It is available in strengths of 50, 80, 100, 120, and 150 mcg for single use.

WARNINGS AND PRECAUTIONS

Serious Warnings and Precautions

Some people get depressed when taking PEGETRON (pegylated interferon alfa-2b alone or in combination treatment with ribavirin, and in some cases people had thoughts about threatening the life of others, suicidal thoughts or aggressive behaviour (sometimes directed against others).

Some patients have actually committed suicide. Be sure to seek emergency care if you notice that you are becoming depressed or have suicidal thoughts or change in your behaviour. You may want to consider asking a family member or close friend to help you stay alert to signs of depression or changes in your behaviour.

What is the most important information I should know about PEGETRON therapy?

1. 1. PEGETRON Therapy could seriously harm your unborn child.
2. • If you or your partner are pregnant, you should not receive PEGETRON (ribavirin) Capsules and PEGETRON (peginterferon alfa-2b) Powder for Solution.
3. •

   Pregnancy should not be planned while you or your partner are on therapy or for 6 months after therapy.

4. • If you or your partner become pregnant while on therapy or during the 6 months after stopping therapy, consult your doctor immediately.
5. • If you are a woman of childbearing age, you must have a negative pregnancy test before treatment and a pregnancy test each month during treatment.
6. • Both you and your partner must use effective contraception during treatment and for the 6 months after treatment is completed. You should discuss with your doctor how you or you partner can prevent getting pregnant.
7. 2. PEGETRON (ribavirin) Capsules cause anemia, which is a decrease in the number of red blood cells you have. This can be dangerous, especially for patients who already have heart or circulatory (cardiovascular) problems. Talk with you doctor before taking PEGETRON therapy if you have or have ever had any cardiovascular problems.

What should I avoid while taking PEGETRON therapy?

• You or your partner should avoid becoming pregnant while taking PEGETRON therapy and for 6 months after stopping therapy. PEGETRON therapy can cause serious birth defects or harm to your unborn child or difficulty with pregnancy. Thus, you must use effective contraception during this time. If you or your partner become pregnant during treatment or during the 6 months after treatment, you should immediately report the pregnancy to your doctor. Your doctor should call Schering-Plough Canada Inc., Merck Canada Inc., Medical Information Department at 1-800-463-5442.

• You should not inject yourself with any

  medicine that appears discolored or irregular. Tell your doctor, pharmacist or health professional if you notice any change in the appearance of the PEGETRON (ribavirin) Capsules or PEGETRON (peginterferon alfa-2b) Powder for Solution.

• Tell your doctor about any other medications

  you are taking.

• Ask your doctor if there are other things you

  should avoid.

Medicines are sometimes prescribed for purposes other than those listed in this package leaflet. Remember, this medicine is for you and must be used as prescribed by your doctor. Never give it to anyone else.

BEFORE you use PEGETRON talk to your doctor or pharmacist if you have any of the following medical conditions or other serious medical problems:

• Previous heart attack, or other heart

  problems, because therapy may cause heart problems to become worse.

• Blood disorders; including anemia (low red

  blood cell count), thalassemia (Mediterranean anemia), and sickle-cell anemia, because therapy may further reduce the number of red blood cells you have. This may make you feel dizzy or weak and could worsen any heart problems you might have.

• Kidney problems.
• Liver problems (except hepatitis C infection).

• Nervous or mental problems (such as

  depression, anxiety, etc.), because the therapy could make these problems worse.

• Body organ transplant and are taking

  medicine that keeps your body from rejecting your transplant (suppresses your immune system).

• Thyroid disease.
• Cancer.

• Infection with hepatitis B virus and/or human

  immunodeficiency virus (the virus that causes AIDS).

• If you have had problems with your immune

  system.

  • If you have diabetes or high blood pressure, your doctor may ask you to have periodic eye examinations.
  • If you have high blood fat levels (such as elevated triglycerides or cholesterol levels).
  • If you had any serious illness affecting your breathing or your blood.
  • If you have psoriasis or sarcoidosis, it may become worse while you are using PEGETRON.
  • Be sure to tell your doctor if you are taking the Chinese herbal medication Shosaikoto (also known as Xiao-Chai-Hu-Tang).

Dental and gum disorders, which may lead to loss of teeth, have been reported in patients receiving PEGETRON. In addition, dry mouth could have a damaging effect on teeth and membranes of the mouth during long-term treatment with PEGETRON. You should brush your teeth thoroughly twice daily and have regular dental examinations. In addition some patients may experience vomiting. If you have this reaction, be sure to rinse your mouth thoroughly afterwards.

INTERACTIONS WITH THIS MEDICATION

Drugs that may interact with PEGETRON include: medications metabolized by CYP1A2, CYP2C8/9 and CYP2D6, reverse transcriptase inhibitors such as zidovudine and stavudine, purine nucleoside analogues such as didanosine and abacavir, and Highly Active Anti-Retroviral Therapy.

Co-administration of ribavirin and didanosine is not recommended due to the risk of lactic acidosis (a build-up of lactic acid in the body) and pancreatitis.

Tell your doctor or pharmacist if you are taking SEBIVO* (telbivudine) for chronic hepatitis B because taking this medicine together with pegylated interferon alfa-2b may increase your risk of developing peripheral neuropathy (numbness, weakness, tingling, and/or burning sensations, or pain in the arms and/or legs). The combined use of these medications is not recommended.

PROPER USE OF THIS MEDICATION

The following instructions explain how to reconstitute and inject PEGETRON (peginterferon alfa-2b) Powder for Solution yourself. Please read the instructions carefully and follow them step by step. Your doctor or his/her assistant will instruct you how to self-inject PEGETRON (peginterferon alfa-2b) Powder for Solution. Do not attempt to inject yourself unless you are sure you understand the procedure and requirement of self-injection.

If you are using PEGETRON in Vials, see the PEGETRON Powder for Solution in Vials section.

If you are using PEGETRON REDIPEN^®, see the PEGETRON REDIPEN^® Single Dose Delivery System section.

Carefully follow the instructions provided.

PEGETRON Powder for Solution in Vials Each vial must be reconstituted with 0.7 mL of diluent (Sterile Water for Injection) and up to 0.5 mL of solution will be administered. A small volume is lost during preparation of PEGETRON (peginterferon alfa-2b) solution when the dose is measured and injected. Thus, each unit contains an excess amount of diluent and PEGETRON (peginterferon alfa-2b) Powder for Solution to ensure delivery of the labeled dose in 0.5 mL of PEGETRON (peginterferon alfa-2b) Injection. The labeled strength will be contained in 0.5 mL of the reconstituted solution.

The reconstituted solution for each of the available strengths will have a concentration of 50 mcg/0.5 mL, 80 mcg/0.5 mL, 100 mcg/0.5 mL, 120 mcg/0.5 mL or 150 mcg/0.5 mL.

Preparing PEGETRON Powder for Solution

1. 1.

   Find a comfortable, well-lit place and assemble

   supplies (vial, diluent, syringe, alcohol swabs and disposal container).

2. 2.

   The supplies you will need are provided in the

   PEGETRON package; you should place them on a clean work area. The PEGETRON package contains 2 vials of PEGETRON Powder for Solution, 2 vials of Sterile Water for Injection (1 mL/vial) (DILUENT), 4 disposable syringes, and 4 alcohol swabs. These syringes have a needle already attached that cannot be removed and are for single use only.

3. 3.

   Check the date printed on the PEGETRON

   carton to make sure that the expiration date has not passed.

4. 4.

   Wash your hands thoroughly with soap and

   water, rinse and dry with a clean towel.

5. 5.

   Remove the protective wrapper from ONE of

   the syringes provided and use for the following steps.

   1. 6. Remove the protective plastic cap from the top of both the supplied diluent (Sterile Water for Injection) and the PEGETRON Powder for Solution vials, leaving the rubber stopper and aluminum ring in place.
   2. 7.

      Clean the rubber stopper on the top of each vial with an alcohol swab (Figure A).

      Figure A

   3. 8.

      Remove the protective cap from the needle by pulling the cap straight off, and fill the syringe with air by pulling the plunger to 0.7 mL mark (Figure B).

      Figure B

   4. 9.

      Hold the DILUENT vial upright. Do not touch the cleaned top of the vial with your hands (Figure C).

      Figure C

   1. 10.

      With vial on flat surface, insert the needle through the rubber stopper of the diluent vial, and inject the air in the syringe into the vial (Figure D).

      Figure D

6. 11.

   With needle in vial, turn the vial upside

   down in one hand. Your other hand will be free to move the plunger. Make sure the tip of the needle is in the liquid.

7. 12.

   Withdraw only 0.7 mL of diluent by

   pulling the plunger back to exactly 0.7 mL mark (Figure E). The marks on the side of the syringe indicate the amount of DILUENT withdrawn.

   Figure E

8. 13.

   Remove the needle from the vial (Figure F).

   Discard the remaining diluent.

   Figure F

9. 14.

   To prepare the PEGETRON Powder for

   Solution, insert the needle through the rubber stopper of the PEGETRON vial, and gently place the needle tip against the glass wall of the vial (Figure G).

   Figure G

10. 15.

    Slowly inject 0.7 mL of diluent into the vial

    of PEGETRON aiming the stream of liquid at the glass wall of the vial. It is best not to aim the stream directly at the white solid or powder, or to inject the liquid quickly, as this causes a greater amount of bubbles.

11. 16.

    Remove the needle from the vial. Grasp

    sleeve firmly and twist flanges to loosen the sleeve. Fully retract needle into sleeve until it locks in the protected position. When the

    BD Safety-Lok^* Syringe safety lock indicator green band fully covers the red band and an audible click is heard, the sleeve is locked into position

    1. 17. Place empty syringe with needle in disposal container. Check with your nurse or pharmacist for proper disposal. The diluent vial, syringe protective cap and used alcohol swab are intended for single use and must be discarded. A new syringe will be used for injection of the medication.
    2. 18.

       The solution may appear cloudy or bubbly for a few minutes. To complete the dissolution of the powder, gently swirl the vial of PEGETRON with a circular motion (Figure H). Do not shake, but gently turn the vial upside down. The contents should now be completely dissolved.

       Figure H

    3. 19. Once the solution has settled, wait for all the bubbles to rise to the top of the solution. You should have a clear solution with a small ring of tiny bubbles around the top.
    4. 20. When the PEGETRON powder is completely dissolved, it will be clear, colorless and without particles. Visually inspect the reconstituted solution prior to administration: do not use it if you see particles or the solution is not colorless; call your doctor, nurse, or pharmacist.
    5. 21.

       The solution will be ready for injection once it has reached room temperature (about 10 minutes). Since the product contains no preservatives or antimicrobials, it is best to withdraw the appropriate dose from the vial as soon as the solution is ready.

       Filling the Syringe with PEGETRON

    6. 22. After the PEGETRON powder is completely dissolved, clean the vial's rubber stopper with an alcohol swab again.
    7. 23.

       Take another syringe provided and unwrap it.

       You will use it to give yourself the injection.

12. 24.

    Remove the protective cap from the needle and

    fill the syringe with air by pulling the plunger to the number (mL) that corresponds to your prescribed dose (Figure I).

    Figure I

13. 25.

    Hold the PEGETRON vial upright. Do not

    touch the cleaned top of the vial with your hands (Figure J). With the vial on a flat surface, push the needle through the rubber stopper of PEGETRON vial and inject the air into the vial (Figure K).

    Figure J Figure K

14. 26.

    With the needle in the vial, turn the

    PEGETRON vial and the syringe upside down in one hand. Your other hand will be free to move plunger.

15. 27.

    Be sure the tip of needle is in the

    PEGETRON solution.

16. 28.

    While holding the vial and syringe with one

    hand, slowly pull the plunger back to withdraw into the syringe very slightly more than the dose of PEGETRON your doctor told you to use (Figure L). The marks on the side of the syringe indicate the amount of PEGETRON withdrawn.

    Figure L

17. 29.

    Remove the needle from the vial (Figure M)

    and hold the syringe with the needle pointing

    upwards. Do not touch the needle. Check for air bubbles in the syringe. If you see any bubbles, pull the plunger slightly back and gently tap the syringe, with the needle pointing upwards, until bubbles disappear (Figure N). Then, push the plunger slowly back up to the correct dose.

    Figure M Figure N

    1. 30. Replace the cover on the needle and put the syringe on a clean flat surface. Discard any unused solution.
    2. 31.

       The solution should be at room temperature up to 25^°C (77 °F). If the solution is cold, warm the syringe between your palms. You are now ready to inject the dose.

       Injecting the PEGETRON Dose

    3. 32.

       Select an injection site.

       • The best sites for giving yourself an injection are those areas with a layer of fat between the skin and muscle, like your thigh, outer surface of you upper arm (you may need the assistance of another person to use this site), and abdomen (Figure O). Do not inject yourself in the area near your navel or waistline. If you are very thin, you should only use the thigh or outer surface of the arm for injection.

         Figure O

Do not inject in area that is red or sore. Change your injection site each time. Use the same site only once every six or seven weeks.

1. 33. Clean and disinfect the skin where the injection is to be given with an alcohol swab using a circular motion (approximately for 10 seconds) (Figure P). Allow area to dry.

Figure P

1. 34. Remove the protective cap from the needle.
2. 35.

   Hold the syringe between thumb and

   forefinger, like holding a pencil

3. 36.

   With the other hand, grab the skin where the

   injection will be made. Pinch a 5-cm (2 inches) fold of loose skin.

4. 37.

   Hold the needle at a 45 to 90 degree angle to

   the skin about 5 cm (2 inches) above the skin surface, insert the needle into the pinched skin with a quick jab as if throwing a dart. The entire needle or at least ¾ of it should go into the skin (Figure Q).

   Figure Q

5. 38.

   After the needle is in, remove the hand that

   you used to pinch your skin and use it to hold the syringe barrel.

6. 39.

   Inject the medicine by slowly pushing the

   plunger all the way down the syringe barrel (Figure R).

   Figure R

7. 40.

   After injecting solution, pull the needle

   straight out of the skin.

8. 41.

   Press the injection site with a small bandage

   or sterile gauze if necessary for several

   seconds (Figure S). Do not massage the injection site.

   Figure S

   1. 42.

      If there is bleeding, cover with an adhesive bandage.

      Cleaning up

   2. 43. Grasp sleeve firmly and twist flanges to loosen the sleeve. Fully retract needle into sleeve until it locks in the protected position. When the BD Safety-Lok^* Syringe safety lock indicator green band fully covers the red band and an audible click is heard, the sleeve is locked into position.
   3. 44.

      Place the empty syringe with the needle in the disposal bottle. Check with your nurse or pharmacist for proper disposal. The vials and injection materials are intended for single use and must be discarded. Do not leave used supplies or the disposal bottle for syringes in an open area.

      PEGETRON (peginterferon alfa-2b)

      REDIPEN^® Single Dose Delivery System

How to use the PEGETRON REDIPEN^®

The following instructions explain how to inject yourself with the single use PEGETRON REDIPEN^®. Please read the instructions carefully and completely before attempting to use the pen and follow them step by step. Your doctor or his/her assistant will instruct you on how to self-inject with the PEGETRON REDIPEN^®. Do not attempt to inject yourself unless you are sure you understand the procedure and requirements for self-injection.

The PEGETRON REDIPEN^® is intended for use by one person only and must not be shared. Use the injection needle and alcohol swabs provided in the packaging only for the PEGETRON REDIPEN^®. Be sure the solution is at room temperature at the time of injection. Your doctor will have told you what dose you require for your therapy.

Note: The color of the dosing button is different for each strength of the PEGETRON REDIPEN^®.

Step 1: Mixing

It is important that you keep the PEGETRON REDIPEN^® upright (as shown in Figure 1) during mixing, unless otherwise instructed.

• Take the PEGETRON REDIPEN^® out of the

  refrigerator. Allow the medicine to come to room temperature.

• Wash your hands with soap and water.

• Place the PEGETRON REDIPEN^® upright in

  the holder of the tray provided in the pack (the dosing button will be on the bottom) (Figure 1).

  Figure 1

• You may want to hold the REDIPEN^® using the

  grip. To mix the powder and the liquid, press the two halves together firmly by pressing down until you hear the REDIPEN^® click. The two stoppers should come together.

• Wait for several seconds until the powder is

  completely dissolved.

  • Gently turn the PEGETRON REDIPEN^® upside down twice. To avoid excessive foaming, do not shake.
  • Maintaining the PEGETRON REDIPEN^® upright, check the mixed PEGETRON solution through the window. If there is still foam, wait until it settles. The solution should be clear and colorless. Do not use the pen if the solution is discolored or contains any particles.
  • Keeping the PEGETRON REDIPEN^® upright in the holder provided in the packaging, disinfect the rubber membrane of the PEGETRON REDIPEN^® with one alcohol swab.
  • Take the injection needle provided in the tray and remove its protective paper tab.

  • Maintaining the PEGETRON REDIPEN^® upright in the holder, gently push the injection needle onto the REDIPEN^® and screw it securely in place (Figure 2).

    Figure 2

Keep the PEGETRON REDIPEN^® pointed up.

• Do not take off the outer needle cap at this point.
• You may see some liquid trickle out from under the cap, as the air has been expelled out of the pen.
• Wait about 5 seconds for this process to finish.

• Check through the window to be sure that the two stoppers are together. If they are not together, do not use this pen because you may not be able to dial your dose

  (Figure 3).

Figure 3

Step 2: Setting the dose

• Remove the PEGETRON REDIPEN^® from

  the holder.

• Holding the PEGETRON REDIPEN^® firmly,

  pull the dosing button out as far as it will go, until you see a dark ring on the pen. The dosing button should be easy to pull out without excessive force being required (Figure 4).

Figure 4 Note: Do not push the dosing button back in

at this time. You will push it in when you are ready to self-inject the PEGETRON.

• Turn the dosing button until your prescribed

  dose is aligned with the dosing tab. The button should turn easily without excessive force being required (Figure 5).

  Figure 5 Note: If you cannot easily pull out the dosing

  button or dial the dose, do not use excessive force and do not use this pen because it may not deliver the correct dose.

  Step 3: Injecting the solution

  • Select the injection site. Your doctor will have told you which sites to use (e.g., thigh or abdomen).

    Note: Change your injection site each time.

  • Clean the injection site skin with the second alcohol swab.

•

• Pull off the outer needle cap (Figure 6).

  Figure 6

• There may be some liquid around the inner needle cap. This liquid is not part of your dose, this is extra. This is normal, as the air has been expelled out of the needle.
• Once the injection site is dry, pull off the yellow inner needle cap carefully exposing the injection needle.

• Hold the PEGETRON REDIPEN^® with your fingers wrapped around the pen body and your thumb on the dosing button (Figure 7).

  Figure 7

• With your other hand, pinch a fold of loose skin.
• Insert the needle into the pinched skin at an angle of 45° to 90°.
• Press the dosing button down slowly and firmly until the button can no longer move.

• Maintain pressure on the dosing button for

  an additional 5 seconds to ensure that you get the complete dose.

• Remove the needle from your skin.

• Press the injection site with a small bandage or

  sterile gauze if necessary for a few seconds.

• Do not massage the injection site. If

  there is bleeding, cover with an adhesive bandage.

• Discard the PEGETRON REDIPEN^®

  with the needle safely in a closed rigid container.

Usual dose:

Your doctor has determined the correct dose of PEGETRON (ribavirin) Capsules and PEGETRON (peginterferon alfa-2b) Powder for Solution based on your weight and the regimen (plan of treatment) that you are following for hepatitis C.

Your doctor may adjust your dose and length of time you take this treatment according to your response. Blood tests will be done regularly to help your doctor to know if it is working and if the dose needs to be changed. At the end of the first 24 weeks of treatment, your doctor will decide whether the treatment will be continued for another 24 weeks (total of 48 weeks). Most patients are treated for 48 weeks.

If you have or develop severe kidney or liver problems, this treatment will be stopped. This treatment is not recommended for use in patients under the age of 18 years.

Based on the results of the clinical trial, the recommended dose of PEGETRON

(peginterferon alfa-2b) Powder for Solution is 1.5 mcg/kg/week in combination with PEGETRON (ribavirin) Capsules, which are dosed by patient weight. PEGETRON (peginterferon alfa-2b) Powder for Solution should be administered as subcutaneous injection once a week. PEGETRON

(ribavirin) Capsules are taken daily.

PEGETRON capsules are to be administered orally, 800 - 1,400 mg, each day in two divided doses with food (morning and evening).

PATIENTS WHO HAVE NEVER BEEN TREATED

HCV Genotype 1

Recommended Dose

PEGETRON (peginterferon alfa-2b) Powder for Solution: 1.5 mcg/kg/week

PEGETRON (ribavirin) Capsules: 800 - 1,400 mg daily based upon patient weight

Dosing Recommendations^‡

‡: The daily dose for PEGETRON (ribavirin) Capsules approximately falls within 13 ± 2 mg/kg/day. 1: When reconstituted as instructed

*: Should be calculated based on the body weight of an individual patient

PATIENTS WHO HAVE NEVER BEEN TREATED HCV non-Genotype 1

Recommended Dose

PEGETRON (peginterferon alfa-2b) Powder for Solution: 1.5 mcg/kg/week

PEGETRON (ribavirin) Capsules: 800 - 1,200 mg daily based upon patient weight

Dosing Recommendations^‡

‡: The daily dose for PEGETRON (ribavirin) Capsules approximately falls within 13 ± 2 mg/kg/day. 1: When reconstituted as instructed

PATIENTS WHO FAILED PRIOR TREATMENT

Any HCV Genotypes

Recommended Dose

PEGETRON (peginterferon alfa-2b) Powder for Solution: 1.5 mcg/kg/week

PEGETRON (ribavirin) Capsules: 800 - 1,400 mg daily based upon patient weight

Dosing Recommendations^‡

‡: The daily dose for PEGETRON (ribavirin) Capsules approximately falls within 13 ± 2 mg/kg/day.

1: When reconstituted as instructed

*: Should be calculated based on the body weight of an individual patient

It is important to follow your dosing schedule and your doctor’s instructions on how to take your medications. Take the medicine for as long as prescribed and do not exceed the recommended dosage.

Take the PEGETRON (ribavirin) Capsules by mouth with water and during your meal. Do not chew the capsules.

PEGETRON (peginterferon alfa-2b) Powder for Solution is given at a dose of 1.5 mcg/kg once a week. PEGETRON (peginterferon alfa-2b) Powder for Solution is for subcutaneous use. This means that it is injected through a short injection needle into the fatty tissue just under your skin. If you are injecting this medicine yourself, you will be instructed how to prepare and give the injection.

If you are injecting PEGETRON (peginterferon alfa-2b) Powder for Solution yourself, please be sure that the dose that has been prescribed for you is clearly provided on the package of medicine you receive. Inject PEGETRON (peginterferon alfa-2b) Powder for Solution on the same day each week. Injecting it at the same time of day each

week will help you not to forget to take it. Take the dose as soon as you remember, then continue your treatment as usual. Do not take a double dose to make up for forgotten individual doses. Contact your doctor or pharmacist if needed.

Overdose:

The primary effects of overdose were an increased incidence and severity of adverse events reported at the therapeutic doses of PEGETRON.

In case of drug overdose, contact a health care practitioner, hospital emergency department or regional Poison Control Centre immediately, even if there are no symptoms.

Missed Dose:

If you miss a dose of PEGETRON (ribavirin) Capsules, take the missed dose as soon as possible during the same day. If an entire day has gone by, check with your doctor about what to do. Do not double the next dose. If you miss a dose of PEGETRON (peginterferon alfa-2b) Powder for Solution, take the missed dose as soon as possible during the same day or on the next day, and continue the dosing schedule provided to you by your doctor. If several days go by, check with your doctor about what to do. Do not double the next dose.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

What are the possible side effects of PEGETRON therapy?

Like all medicines, PEGETRON can have side effects. Although not all of these side effects may occur, they may need medical attention if they do occur.

Check with your doctor immediately if any of the following side effects occur during treatment:

• chest pain or persistent cough;

• symptoms of a severe allergic reaction (such

  as difficulty breathing, wheezing, or hives);

• symptoms associated with a cold or other

  respiratory infection, such as difficulty breathing or cough;

• shortness of breath;

• fever or chills beginning after a few weeks of

  treatment;

• changes in the way your heart beats;

• feeling depressed or hopeless, or thinking

  about death (suicidal thoughts or attempts);

• confusion, aggressiveness (sometimes directed

  against others), hallucination

• trouble sleeping;

• severe stomach pain, black or tar-like stools,

  blood in stool or urine, feelings of numbness or tingling;

• severe bleeding from your nose;

• lower back or side pain, painful or difficult

  urination;

• problems with your eyesight or hearing;

• you notice that you are unusually tired and

  pale, and bruise easily.

Other events that may occur with this treatment are:

• irritation or pain at the site of injection;

• general discomfort, such as headache, fatigue

  or sleepiness, chills, fever, “flu-like” symptoms, weakness, pain around the ribs on the right side, feeling generally unwell, flushing, increased sweating;

• high or low blood pressure;
• dizziness, vertigo or faintness;

• sore tongue or mouth, dry mouth, thirst, loss of

  appetite, weight loss, nausea (feeling sick), vomiting, stomach or abdominal pain, indigestion, gas, diarrhea, loose stools, constipation;

• muscle ache, pain or stiffness, joint pain,

  arthritis;

• irritability, anxiety, agitation, nervousness,

  mood swings, difficulty concentrating, lack of interest in life;

• loss of hair or change in hair;

• skin disorders, including itching or rash, dry

  skin, redness, brown spots on skin, increased or decreased sensitivity to touch, sensitivity to light, eczema, psoriasis;

• disorders of the respiratory tract, including

  hoarseness, sore throat, cough, runny nose, stuffy nose, sinus infection, bronchitis, pneumonia;

  • viral or fungal infection, herpes simplex (fever blister); or
  • menstrual disorder.

Some patients may have: change in sense of taste or smell, inflammation, infection, pain, or dryness of the eye, tear disorder, blurred vision, earache, middle ear infection, allergic reaction, puffiness of hands and feet, inflamed or bleeding gums, tooth abscess, rectal sores, decreased sex drive, impotence, irritation of the vagina, migraine headache, gout, change in thyroid function.

Very rarely, cases of stroke (cerebrovascular events) have been reported.

Very rarely, PEGETRON (peginterferon alfa-2b) Powder for Solution, alone or with ribavirin, may cause aplastic anemia. Aplastic anemia is a condition caused by the failure of the bone marrow to make new red blood cells, white blood cells and platelets. Pure red cell aplasia has also been reported. Pure red cell aplasia is a condition in which severe and sudden anemia (characterized by symptoms such as severe tiredness/fatigue, and shortness of breath on mild exertion) develops due to failure of the bone marrow to produce red blood cells.

Additionally, the following events have been reported with PEGETRON (peginterferon alfa-2b) Powder for Solution: facial palsy (weakness and slumping on one side to the face), severe allergic reactions such as angioedema (an allergic skin disease characterized by patches of circumscribed swelling involving the skin and its subcutaneous layers, the mucous membranes, and sometimes the internal organs), toxic epidermal

necrolysis/Stevens Johnson Syndrome/erythema multiforme (a spectrum of rashes with varying degree of severity including death which may be associated with blisters in the mouth, nose, eyes and other mucosal membranes and sloughing of the affected area of the skin) and blindness.

Additionally, Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin and the membranes of the ears, brain and spinal cord) has been reported with PEGETRON (peginterferon alfa-2b) Powder for Solution use.

If you notice any side effects not mentioned in this patient information, please inform your doctor or pharmacist.

HOW TO STORE IT

Storage of PEGETRON Packages:

Store the PEGETRON (ribavirin) Capsules plus PEGETRON (peginterferon alfa-2b) Powder for Solution package refrigerated between 2°C and 8°C (36°F and 46°F).

Storage of PEGETRON (ribavirin) Capsules: When separated, PEGETRON (ribavirin) Capsules should be stored in the refrigerator between 2°C and 8°C (36°F and 46°F) or at controlled room temperature between 15°C and 30°C (59°F and 86°F).

Storage of PEGETRON (peginterferon alfa-2b) Powder for Solution in Vials:

When separated and before reconstitution^†, the individual carton of PEGETRON (peginterferon alfa-2b) Powder for Solution should be stored in the refrigerator at 2°C to 8°C (36°F to 46°F). After reconstitution with Sterile Water for Injection, the reconstituted product is to be used immediately. Since no preservative is present, it is recommended that administration of the solution occurs as soon as possible and within 3 hours of reconstitution. For reconstitution under controlled and validated aseptic conditions such as a hospital pharmacy, the chemical and physical in-use stability of the reconstituted solution has been demonstrated 24 hours at 2°C - 8°C (36°F - 46°F).

Discard any unused portion.

Do not use past expiry date on the label.

FROZEN STORAGE OF THE FILLED SYRINGES IS NOT RECOMMENDED.

^† Reconstitution means adding a liquid (diluent) to a dry powder.

Stability and storage for PEGETRON REDIPEN^®:

Store the PEGETRON REDIPEN^® at 2°C to 8°C (36°F to 46°F). Once reconstituted PEGETRON REDIPEN^® should be used immediately but may be stored at 2°C - 8°C (36°F - 46°F) for up to 24 hours. Do not freeze.

Do not use past expiry date on the label.

REPORTING SUSPECTED SIDE EFFECTS

You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways:

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• Report online at www.healthcanada.gc.ca/medeffect
• Call toll-free at 1-866-234-2345

• Complete a Canada Vigilance Reporting Form and

  • Fax toll-free to 1-866-678-6789, or
  • Mail to: Canada Vigilance Program Health Canada Postal Locator 0701D Ottawa, Ontario K1A 0K9

Postage paid labels, Canada Vigilance Reporting Form and the adverse reaction reporting guidelines are available on the MedEffect^™ Canada Web site at www.healthcanada.gc.ca/medeffect.

NOTE: Should you require information related to the management of side effects, contact your health professional. The Canada Vigilance Program does not provide medical advice.

MORE INFORMATION

For this document plus the full product monograph, prepared for health professionals, please contact the sponsor, Merck Canada Inc. at: 1-800-463-5442.

PEGETRON^® is a registered trademark of Schering-Plough Ltd., used under license by Schering-Plough Canada Inc.

REDIPEN^® is a registered trademark of Schering-Plough Canada Inc.

*All other trademarks are the property of their respective owners.

Last revised: January 1, 2011