[Posted 12/19/2012]ISSUE:FDA received reports of serious skin reactions, some fatal, in patients taking the hepatitis C drug telaprevir (Incivek) in combination with the drugs peginterferon alfa and ribavirin (Incivek combination treatment). Some patients died when they continued to receive telaprevir combination treatment after developing a worsening, or progressive rash and systemic symptoms (symptoms affecting the entire body).
See the FDA Drug Safety Communication Data Summary section for additional information at: Web Site
FDA is adding a boxed warning to the telaprevir drug label stating that Incivek combination treatment must be immediately stopped in patients experiencing a rash with systemic symptoms or a progressive severe rash.
BACKGROUND:Telaprevir is a hepatic C virus NS3/4A protease inhibitor indicated in combination with peginterferon alfa and ribavirin for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including patients who have cirrhosis, are treatment-naive, or who have been previously received interferon-based treatment.
RECOMMENDATIONS:Make sure your patients know that rash may occur with telaprevir combination treatment, and explain the signs and symptoms of severe skin reaction and when to seek care.
If serious skin reactions occur, all three components of telaprevir combination treatment, including peginterferon alfa and ribavirin, must be immediately discontinued, and the patient should receive urgent medical care. Consideration should also be given to stopping any other medications that may be associated with serious skin reactions. For more information visit the FDA website at: Web Siteand Web Site.
Peginterferon alfa-2a may cause or worsen the following conditions which may be serious or cause death: infections; mental illness including depression, mood and behavior problems, or thoughts of hurting or killing yourself; starting to use street drugs again if you used them in the past; ischemic disorders (conditions in which there is poor blood supply to an area of the body) such as angina (chest pain), heart attack, or colitis (inflammation of the bowels); and autoimmune disorders (conditions in which the immune system attacks one or more parts of the body) that may affect the blood, joints, kidneys, liver, lungs, muscles, skin, or thyroid gland.Tell your doctor if you have an infection; or if you have or have ever had an autoimmune disease; atherosclerosis (narrowing of the blood vessels from fatty deposits); cancer; chest pain; colitis; diabetes; heart attack; high blood pressure; high cholesterol; HIV (human immunodeficiency virus) or AIDS (acquired immunodeficiency syndrome); irregular heartbeat; mental illness including depression, anxiety, or thinking about or trying to kill yourself; liver disease other than hepatitis B or C; or heart, kidney, lung or thyroid disease. Also tell your doctor if you drink or have ever drunk large amounts of alcohol, or if you use or have ever used street drugs or have overused prescription medications. If you experience any of the following symptoms, call your doctor immediately: bloody diarrhea or bowel movements; stomach pain, tenderness or swelling; chest pain; irregular heartbeat; changes in your mood or behavior; depression; irritability; anxiety; thoughts of killing or hurting yourself ; hallucinating (seeing things or hearing voices that do not exist); frenzied or abnormally excited mood; loss of contact with reality; aggressive behavior; difficulty breathing; fever, chills, cough, sore throat, or other signs of infection; unusual bleeding or bruising; dark-colored urine; light colored bowel movements; extreme tiredness; yellowing of the skin or eyes; severe muscle or joint pain; or worsening of an autoimmune disease.
Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests to check your body's response to peginterferon alfa-2a.
Your doctor and pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with peginterferon alfa-2a and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website ( Web Site) or the manufacturer's website to obtain the Medication Guide.
Talk to your doctor about the risks of using peginterferon alfa-2a.
Use with ribavirin (Copegus, Rebetol):
You may take peginterferon with another medication called ribavirin (Copegus, Rebetol). Ribavirin may help peginterferon work better to treat your condition, but it may also cause serious side effects. The rest of this section tells about the risks of taking ribavirin. Your doctor and pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with ribavirin and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website ( Web Site) or the manufacturer's website to obtain the Medication Guide
Ribavirin may cause anemia (condition in which there is a decrease in the number of red blood cells). Tell your doctor if you have ever had a heart attack and if you have or have ever had high blood pressure, breathing problems, any condition that affects your blood such as sickle cell anemia (inherited condition in which the red blood cells are abnormally shaped and cannot bring oxygen to all parts of the body) or thalassemia (Mediterranean anemia; a condition in which the red blood cells do not contain enough of the substance needed to carry oxygen), or heart disease. If you experience any of the following symptoms, call your doctor immediately: excessive tiredness, pale skin, headache, dizziness, confusion, fast heartbeat, weakness, shortness of breath, or chest pain.
For female patients who are taking ribavirin:
Do not take ribavirin if you are pregnant or plan to become pregnant. You should not start taking ribavirin until a pregnancy test has shown that you are not pregnant. You must use two forms of birth control and be tested for pregnancy every month during your treatment and for 6 months afterward. Call your doctor immediately if you become pregnant during this time. Ribavirin may cause harm or death to the fetus.
For male patients who are taking ribavirin:
Do not take ribavirin if your partner is pregnant or plans to become pregnant. If you have a partner who can become pregnant, you should not start taking ribavirin until a pregnancy test shows that she is not pregnant. You must use two forms of birth control, including a condom with spermicide during your treatment and for 6 months afterward. Your partner must be tested for pregnancy every month during this time. Call your doctor immediately if your partner becomes pregnant. Ribavirin may cause harm or death to the fetus.
Peginterferon alfa-2a is used alone or in combination with ribavirin (a medication) to treat chronic (long-term) hepatitis C infection (swelling of the liver caused by a virus) in people who show signs of liver damage and who have not been treated with interferon alpha (medication similar to peg-interferon alfa-2a) in the past. Peginterferon alfa-2a is also used to treat chronic hepatitis B infection (swelling of the liver caused by a virus) in people who show signs of liver damage. Peginterferon alfa-2a is in a class of medications called interferons. Peginterferon is a combination of interferon and polyethylene glycol, which helps the interferon stay active in your body for a longer period of time. Peginterferon works by decreasing the amount of hepatitis C virus (HCV) or hepatitis B virus (HBV) in the body. Peginterferon alfa-2a may not cure hepatitis C or hepatitis B or prevent you from developing complications of hepatitis C or hepatitis B such as cirrhosis (scarring) of the liver, liver failure, or liver cancer. Peginterferon alfa-2a may not prevent the spread of hepatitis C or hepatitis B to other people.
Peginterferon alfa-2a comes as a solution (liquid) in a vial and a prefilled syringe to inject subcutaneously (into the fatty layer just under the skin). It is usually injected once a week, on the same day of the week, and at around the same time of day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use peginterferon alfa-2a exactly as directed. Do not use more or less of this medication or use it more often than prescribed by your doctor.
Your doctor will probably start you on an average dose of peginterferon alfa-2a. Your doctor may decrease your dose if you experience serious side effects of the medication. Be sure to tell your doctor how you are feeling during your treatment and ask your doctor or pharmacist if you have questions about the amount of medication you should take.
Continue to use peginterferon alfa-2a even if you feel well. Do not stop using peginterferon alfa-2a without talking to your doctor.
Only use the brand and type of interferon that your doctor prescribed. Do not use another brand of interferon or switch between peginterferon alfa-2a in vials and prefilled syringes without talking to your doctor. If you switch to a different brand or type of interferon, your dose may need to be changed.
You can inject peg-interferon alfa-2a yourself or have a friend or relative give you the injections. Before you use peg-interferon alfa-2a for the first time, read the written instructions that come with it. Ask your doctor or pharmacist to show you or the person who will be injecting the medication how to inject it. If another person will be injecting the medication for you, be sure that he or she knows how to avoid accidental needlesticks to prevent the spread of hepatitis.
You can inject peginterferon alfa-2a anywhere on your stomach or thighs, except your navel (belly button) and waistline. Use a different spot for each injection. Do not use the same injection spot two times in a row. Do not inject peginterferon alfa-2a into an area where the skin is sore, red, bruised, scarred, infected, or abnormal in any way.
Never reuse syringes, needles, or vials of peginterferon alfa-2a. Throw away used needles and syringes in a puncture resistant container, and throw away used vials of medication in the trash. Talk to your doctor or pharmacist about how to dispose of the puncture resistant container.
Before you use peginterferon alfa-2a, look at the solution in the vial or the prefilled syringe closely. It should be clear and free of floating particles. Check the vial or syringe to make sure there are no leaks and check the expiration date. Do not use the solution if it is expired, discolored, cloudy, contains particles, or is in a leaky vial or syringe. Use a new solution, and show the damaged or expired one to your doctor or pharmacist.
To prepare peginterferon alfa-2a in vials for injection, follow these steps:
- Find a clean, comfortable area and collect the supplies you will need: unused syringe, unused needle, and several alcohol pads.
- Remove a vial of peginterferon alfa-2a from the refrigerator.
- Warm the vial of peginterferon alfa-2a by rolling it gently in the palms of your hands for about 1 minute. Do not shake the vial.
- Wash your hands with soap and warm water. Dry your hands with a paper towel and use the towel to turn off the faucet.
- Flip off the plastic top covering the vial opening and clean the rubber stopper with an alcohol pad.
- Remove the needle and syringe from their packaging. If the needle and syringe were packaged separately, attach the needle to the end of the syringe. Remove the clear protective needle cap from the end of the needle. If there is an orange cap attached to the end of the syringe above the needle, do not remove it. This is to protect you from accidental needle sticks.
- Pull the syringe plunger back so that the end of it is lined up with the mark on the syringe barrel that matches your prescribed dose. If you are not sure which mark on the syringe matches your dose, stop and call your doctor or pharmacist before you inject any medication.
- Hold the syringe straight up and down and push the needle down through the center of the medication vial stopper.
- Be sure that the tip of the needle is in the empty space above the liquid in the vial. Push down slowly on the plunger to inject all the air from the syringe into the vial .
- Keep the needle inside the vial and turn both the vial and the needle upside down. Hold the vial and syringe straight up. Make sure the needle tip is in the medication liquid, not in the space above it, to prevent bubbles from forming in the syringe.
- Slowly pull back on the plunger to fill the syringe with medication up to the mark that matches your dose.
- Pull the syringe straight out of the vial. Do not touch the needle to anything.
- Remove air bubbles from the syringe by holding the syringe with the needle pointing up to the ceiling. Use your thumb and finger to gently tap the syringe to bring air bubbles to the top. Push the plunger slightly to push air bubbles out of the syringe without squirting out any liquid.
- Keep the syringe pointing up until you are ready to give your dose. See below for injection instructions.
To prepare a prefilled syringe of peginterferon alfa-2a, follow these steps:
- Find a clean comfortable area and collect the supplies you will need: prefilled syringe, needle with needle guard, and several alcohol pads.
- Remove a prefilled syringe from the refrigerator and warm it by gently rolling it in your hands for 1 minute. Be careful not to shake the syringe.
- Wash your hands with soap and warm water. Dry your hands with a paper towel and use the towel to turn off the faucet.
- Remove the needle from the package, but keep the plastic cap on the needle until you are ready to inject the medication.
- Remove the rubber cap on the tip of the syringe and throw it away.
- Put the needle on the end of the syringe barrel so that it fits tightly. Keep the syringe in a horizontal position until you are ready to use it. If you need to set the syringe down, make sure the plastic needle cap (shield) is covering the needle. Do not touch the needle to anything.
- Remove the plastic cap from the needle shield, but do not remove the orange needle guard attached to the syringe above the needle.
- Hold the syringe with the needle pointing toward the ceiling. Using your thumb and finger, tap the syringe to bring any air bubbles to the top. Press the plunger in slightly to push any air bubbles out of the syringe.
- Slowly and carefully push down on the plunger rod until the edge of the plunger is lined up with the mark on the syringe barrel that matches your dose. If you are not sure which mark on the syringe matches your dose, stop and call your doctor or pharmacist before you inject any medication. Do not save or reuse any medication that you squirt out of the syringe.
- Do not let the needle touch any surface. See below for injection instructions.
To inject a dose of peginterferon alfa-2a, follow these steps:
- Gently tap the skin in the place where you plan to inject peginterferon alfa-2a. Use an alcohol pad to clean the skin in the injection spot and allow it to air dry for 10 seconds.
- Hold the needle with the point facing up. Use your thumb and forefinger to pinch up a fold of skin at the injection spot.
- Hold the syringe like a pencil at a 45 or 90 degree angle to your skin. In one quick motion, insert the needle as far as it will go into the pinched area of skin. Pull back slightly on the syringe plunger. If blood comes into the syringe, the needle has entered a blood vessel. Do not inject. Pull out the needle and throw away the syringe and needle in a puncture proof container. Choose a different spot to inject your medication and start the injection process over using new supplies. If no blood appears, let go of the pinched skin and slowly push the plunger all the way down so that all of the medication is injected.
- Pull the needle out at the same angle you put it into your skin. Wipe the injection spot with an alcohol pad.
- If you used a syringe with an orange needle-stick protection device, put the free end of the orange needle guard on a flat surface and push down on it until it clicks and covers the needle.
- Throw away your syringe and needle in a puncture-proof container right away. If you used a vial of peginterferon alfa-2a, throw it away. Each vial can only be used once.
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
Before using peginterferon alfa-2a,
- tell your doctor and pharmacist if you are allergic to peginterferon alfa-2a, other alpha interferons, any other medications, benzyl alcohol, or polyethylene glycol (PEG).Ask your doctor if you are not sure if a medication you are allergic to is an alpha interferon.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: clozapine (Clozaril); cyclobenzaprine (Flexeril); imipramine (Tofranil); certain medications for HIV or AIDS such as abacavir (Ziagen, in Epzicom, in Trizivir), didanosine (ddI or Videx), emtricitabine (Emtriva, in Truvada), lamivudine (Epivir, in Combivir, in Epzicom, in Trizivir), stavudine (Zerit), tenofovir (Viread, in Truvada), zalcitabine (HIVID), and zidovudine (Retrovir, in Combivir, in Trizivir); methadone (Dolophine, Methadose); mexilitene (Mexitil); naproxen (Aleve, Anaprox, Naprosyn, others); riluzole (Rilutek); tacrine (Cognex); and theophyilline (TheoDur, others). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor or pharmacist if you have ever had an organ transplant (surgery to replace an organ in the body). Also tell your doctor if you have or have ever had any of the conditions mentioned in the IMPORTANT WARNING section or any of the following: anemia (red blood cells do not bring enough oxygen to other parts of the body), or problems with your eyes or pancreas.
- tell your doctor if you are pregnant, plan to become pregnant or are breast-feeding. Peginterferon alfa-2a may harm the fetus or cause you to miscarry (lose your baby). Talk to your doctor about using birth control while you are taking this medication. You should not breastfeed while you are taking this medication.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking peginterferon alfa-2a.
- you should know that peginterferon alfa-2a may make you dizzy, confused, or drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
- you should know that you may experience flu-like symptoms such as headache, fever, chills, tiredness, muscle aches, and joint pain during your treatment with peginterferon alfa-2a. If these symptoms are bothersome, ask your doctor if you should take an over-the-counter pain and fever reducer before you inject each dose of peginterferon alfa-2a. You may want to inject peginterferon alfa-2a at bedtime so that you can sleep through the symptoms.
Drink plenty of fluids while you are taking this medication.
If you remember the missed dose no longer than 2 days after you were scheduled to inject it, inject the missed dose as soon as you remember it. Then inject your next dose on your regularly scheduled day the following week. If more than 2 days have passed since the day you were scheduled to inject the medication, ask your doctor or pharmacist what you should do. Do not use a double dose or use more than one dose in 1 week to make up for a missed dose.
Peginterferon alfa-2a may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- bruising, pain, redness, swelling, or irritation in the place you injected peginterferon alfa-2a
- upset stomach
- change in the way things taste
- dry mouth
- loss of appetite
- weight loss
- dry or itchy skin
- hair loss
- difficulty falling asleep or staying asleep
- difficulty concentrating or remembering
Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them, or those listed in the IMPORTANT WARNING section, call your doctor immediately:
- blurred vision ,vision changes, or loss of vision
- pale skin
- fast heartbeat
- lower back pain
- swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
- difficulty swallowing
Peginterferon alfa-2a may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online [at Web Site] or by phone [1-800-332-1088].
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it in the refrigerator, but do not freeze it. Do not leave peginterferon alfa-2a outside of the refrigerator for more than 24 hours (1 day). Keep peginterferon alfa-2a away from light. Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
If the victim has not collapsed, call the doctor who prescribed this medication. The doctor may want to order lab tests.
Symptoms of overdose may include
- unusual bleeding or bruising
- fever, sore throat, chills, cough, or other signs of infection
Do not let anyone else use your medication. Ask your pharmacist any questions you have about refilling your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
AHFS® Consumer Medication Information. © Copyright, The American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland. All Rights Reserved. Duplication for commercial use must be authorized by ASHP.
Selected Revisions: February 15, 2013.