Side Effects: Peginterferon and Ribavirin
Side effects are seen in almost 80 percent of people treating with peginterferon and ribavirin. As patients we need to recognize these symptoms early on in order to avoid discontinuation or a dose reduction in therapy. Compliance to HCV treatment is an important factor for achieving SVR.
What we know is 100% compliance with the peginterferon and ribavirin regime always produces better results than 80 or 90% compliance.
From : Melissa Palmer, MDClinical Professor of MedicineDepartment of Hepatology
Importance of Adherence to HCV Regimens
"Approximately 60% of patients with HCV in the United States adhered to prescribed therapy",''Indeed, studies have demonstrated that exposure to weight-based ribavirin vs fixed-dose ribavirin is associated with improved early virologic response and SVR rates"
'Reduction of the incidence and severity of treatment-induced anemia with erythropoietin has been shown to encourage adherence and to enable patients to remain on higher doses of ribavirin''
''Therefore, to improve adherence, practitioners must evaluate all HCV-infected patients at baseline and during therapy for psychiatric symptoms and initiate antidepressants or antipsychotics promptly, as needed.''
Read Full Article Adherence to Hepatitis C Therapy
From the American College of Gastroenterology
Peginterferon suppresses the bone marrow and ribavirin causes hemolysis. As a result, it is essential that
blood counts be assessed at regular intervals during HCV treatment. When treatment is first initiated blood
counts should be assessed at a minimum of once monthly until the hemoglobin, WBC, absolute neutrophil
count and platelet count are stable. However, some physicians will assess blood counts more frequently, at
2 week intervals, until these values are stable. Liver chemistries can be monitored less frequently but
for convenience are generally assessed at the same frequency as hematologic testing.
Thyroid function should be assessed at baseline and at 3 month intervals
unless patients develop symptoms of either hypo- or hyperthyroidism.
Pregnancy testing should be performed by females who are capable of conception at monthly
Hepatitis C Treatment and Anemia
During your hepatitis C treatment period, you will have your blood drawn on a regular basis to
check many lab values, including hemoglobin. It is important to have the labs drawn when instructed
by your doctor’s office.
Why Your Body Needs Hemoglobin
Just like a car, your body needs fuel to run. Hemoglobin, or Hb, is important because it transports oxygen in your blood to all
parts of your body. Think of the oxygen carried by hemoglobin as the fuel your body needs to stay alive and run efficiently.
Hemoglobin is a substance found in your red blood cells that carries most of your oxygen. Although other substances
in your body, such as water and plasma, also carry oxygen, hemoglobin is unique because it can carry four times as
much oxygen throughout the body.
How Hemoglobin Fuels Your Body
Because Hemoglobin contains iron, it is an excellent vehicle for transporting oxygen and carbon dioxide. When red blood
cells fill the air sacs of your lungs, they take up oxygen. The hemoglobin in the red cells combines with the oxygen to form
a compound called oxyhemoglobin. When the red cells travel through the rest of your body, they give up the oxygen to the
tissues. In the tissues, hemoglobin takes up carbon dioxide (waste material) and releases it in the air sacs of the lungs.
The carbon dioxide is then exhaled.
What Causes Anemia
Anemia is caused by low levels of red blood cells, or hemoglobin, in your blood. A severely anemic person’s blood
cannot carry enough oxygen to meet the needs of the body tissues. As a result, over time the person becomes tired
physically and mentally, and feels cold. When on interferon and ribavirin treatment for Hepatitis C, a
reduction in hemoglobin very commonly occurs and in most cases, it is maintained at levels below the normal laboratory
ranges, returning to normal after treatment is completed or stopped. Anemia is an expected side effect of treatment with
interferon and ribavirin.
In addition to anemia caused by interferon and ribavirin, anemia can be caused by kidney disease, lack of vitamin B12
or folic acid in your diet, an inherited blood disorder such as sickle cell anemia, blood loss from an injury or accident,
gastrointestinal bleeding, or lack of iron.
Symptoms of Anemia
Have you ever held your breath for longer than a minute? Do you remember how you were afterward? With anemia, you
would feel tired all the time. Even extra sleep will not help an anemic person feel better. If you are anemic, you may
• Extreme fatigue and weakness
• Feeling tired
• Difficulty sleeping
• Difficulty thinking clearly
• Dizziness or fainting
Treatment for Anemia
Your doctor will monitor your hemoglobin levels by looking at your blood test results. It is not uncommon for hemoglobin
values less than normal to be followed closely without any change in medication or other treatments. He may reduce the
dose of ribavirin. However, there may be a time when your doctor discusses a separate treatment called Procrit® or Epogen® for the anemia and the side effects you are experiencing. Procrit® or Epogen® is identical to erythropoietin (e-RItH-ro-POIe-tin), the substance your kidneys normally make. It stimulates your bone marrow to make new red blood cells. As a result, more red blood cells can carry oxygen to the body, which may increase your energy level and provide relief from the symptoms of anemia, such as fatigue and shortness of breath. Procrit® or Epogen® is available only by prescription. It is an injection given underneath the skin like the injection of interferon you are already receiving. Your doctor will tell you what dosage is right for you. Studies have shown that you feel better during hepatitis
C treatment when taking these medicines.
Before administering this medication, tell your doctor or pharmacist if you are allergic to epoetin, human albumin, or
any other drugs. Always tell your doctor and pharmacist what prescription and non-prescription medications you are taking,
Administering Your Medication
Store the medication in the refrigerator. Do not allow the medication to freeze. Take your next dose from the refrigerator
1 hour before using it; place it in a clean, dry area to allow it to warm to room temperature. Avoid shaking the vial. Use a
vial only once, and do not reenter a needle into a vial. Discard unused portions and outdated medication.
Before you administer your medication, look at the solution closely. It should be clear and free of floating material.
Observe the solution container to make sure there are no leaks. Do not use the solution if it is discolored, if it contains
particles, or if the container leaks. Use a new solution and contact the pharmacy to report the damaged one.
It is important that you use your medication exactly as directed.
Do not change your dosing schedule without talking to your doctor’s office. Do not stop your therapy on your own because
your ability to continue interferon and ribavirin could be hampered. Call the doctor if you have any questions or concerns.
Side effects are uncommon but they can occur. Procrit® or Epogen® sometimes causes a flu-like reaction with chills,
shivering, sweating, muscle aches, and bone aches. These effects may appear 1–2 hours after an injection and usually go
away within 12 hours. They may go away during treatment as your body adapts to the medication. However, tell your doctor if
any of these problems continues or worsens. Your doctor should carefully monitor your blood pressure and hemoglobin for rapid increases, which should be avoided. An extremely rare side effect of Procrit® or Epogen® is to cause your red blood cells to stay very low. Your doctor will monitor your blood to detect this. Complete Product Information is available from your
pharmacist. The information will provide you with a complete list of possible side effects and other details concerning the
(fever, chills, headaches, fatigue, muscle aches)
• One hour before your injection, take 2
regular strength acetaminophen (Tylenol®
or generic), or 2 ibuprofen (Advil®, Motrin®,
or generic). You may repeat every 4-6 hours
after your injection as needed.
• Do not take more than 2000 mg of
acetaminophen in 24 hour period.
• Do not take more than 1600 mg of
ibuprofen in 24 hour period.
• *If you take both acetaminophen and
ibuprofen in the same 24 hour period,
do not take more than half the maximum
daily dose listed above for each product.*
• Increase your daily intake of fluids (nonalcoholic
We recommend 8–10 glasses (8 oz.) of
water or other clear beverages each day.
• Take pegylated interferon injections in the
evening or at bedtime to sleep through
most of the flu-like symptoms.
Depression & Irritability
Depression is the most common psychiatric disorder precipitated by peginterferon and ribavirin therapy.
Many patients develop depression as a side effect of insomnia and severe fatigue associated with anemia.
Treating insomnia and enabling these patients to obtain better sleep significantly improves depression
in many patients. Many anti-depressants enhance sleep as a side effect and these agents are very
effective in treating depression in patients receiving peginterferon and ribavirin with insomnia. In patients
whose depression appears unrelated to insomnia, other antidepressive agents will likely be more effective.
(signs of depression include feelings of deep and
constant sadness, hopelessness, crying, major
changes in mood, loss of interest in things you
enjoy, trouble sleeping/concentrating)
• Avoid stressful situations if possible, and
learn relaxation techniques.
• Include light exercise in your daily routine.
• Become a volunteer for someone less
fortunate than yourself.
• Seek professional help. Be sure to
notify the clinic if these feelings persist,
there may be medications available by
prescription to help you.
• If you experience thoughts of harming or
killing yourself or others, call the clinic
Mild Hair Thinning
• Shorter hairstyles may reduce hair loss.
• Don’t wash your hair excessively. If you
wash your hair daily, try switching to every
• Avoid using blow dryers and chemical
treatments on your hair.
• Hair growth will return after treatment is
Loss of Appetite
(10-15 lb. weight loss is common)
• Eat frequent small meals throughout the
day, even if you aren’t hungry. “Grazing”
rather than 3 large meals is often helpful.
• A light walk or short exercise before meals
can increase appetite and decrease nausea.
• Try protein powder shakes, or dietary
supplements (Ensure®, Boost®, Sustacal®,
Slim Fast®) in addition to regular meals.
• Eliminate any metallic taste in your mouth
by brushing regularly. Some people have
found that eating a small amount of dark
chocolate, yogurt, or honey before a meal
helps to reduce the metallic taste. Fresh
lemon in ice water is also helpful.
Nausea, Vomiting, and Diarrhea
• Drink plenty of fluids (non-alcoholic and
• Taking your ribavirin with food may
• For occasional diarrhea, switch to bland
foods such as bananas, rice, applesauce,
and dry toast or crackers until diarrhea
resolves. Then gradually return to a
• Take over-the-counter medications for
nausea and diarrhea. If these do not help,
call the clinic for prescription medications.
• Any vomiting or diarrhea lasting more than
3 days should be reported to the clinic
Dry, Itchy Skin and Mild Rash
Also see :
Hepatitis C : Dry Mouth/Causes and Solutions
•Take short, warm (not hot) baths or
showers. Use a moisturizing soap (ie,
Dove® or Aveeno®).
• Use unscented skin lotions. Eucerin®,
Curel®, and LacHydrin® creams are very
• Be sure to use sunscreen (at least SPF
15), as patients on medication are more
prone to burning.
• Try over-the-counter hydrocortisone creams
or Benadryl® spray.
• If itching persists, call the clinic for further
advice and/or prescription medications.
Skin Irritation at the Injection Site
• Painless, red irritation of the skin at the
site of the injection is common.
• This resolves on its own within 7-10 days.
To minimize this reaction, remember to
rotate the site of your injections.
• Chest pain is an uncommon side effect of
the medication that should be reported
immediately to the clinic. Proceed to the
nearest emergency room if necessary.
Insomnia (inability to sleep)
• The medicines for hepatitis C can sometimes
interfere with your normal sleep
cycle. Getting a good night’s rest will help
with some of the flu like symptoms. If you
have trouble sleeping, call your clinic for
Chronic Diseases Exacerbated or Precipitated by Antiviral Therapy
Several chronic conditions can be exacerbated or precipitated by peginterferon and ribavirin therapy. Some of these diseases may require that the patient be seen by a specialist in that area to assess the risk of HCV treatment on that disease and to treat the disease if an exacerbation occurs
As the hemoglobin declines, patients with coronary artery
disease may experience angina. Patients with known
coronary artery disease may wish to consult a cardiologist
prior to initiating treatment.
Peginterferon reduces the seizure threshold. Patients with
a history of seizures may develop seizures after initiating
peginterferon treatment even if their seizure disorder had been
controlled for many years. Patients with a history of seizures
should be seen by a neurologist prior to initiating HCV
treatment and possibly on a regular basis during treatment.
Peginterferon may precipitate and exacerbate many psychiatric
disorders. The most common psychiatric symptom experienced
by patients receiving peginterferon is depression.
This can develop even in patients without a prior history
of depression. Depression may be so severe that suicidal
thoughts may develop. Uncontrolled psychiatric disease is
a contraindication to utilizing peginterferon. Patients with
active but well controlled psychiatric disease should see a
psychiatrist prior to initiating peginterferon and for at least
several weeks after treatment is initiated to identify patients
who might need adjustment of psychiatric medications.
Peginterferon has been reported to cause blurred vision and
changes to the vascular supply of the retina. Patients with
hypertension and diabetes mellitus are at increased risk
for retinal disease. It is recommended that patients with a
history of hypertension and/or diabetes mellitus undergo a
retinal examination prior to initiating peginterferon therapy.
However, not all experts agree this is necessary and would
only consult an ophthalmologist if a patient developed visual
changes during treatment.
Treatment with peginterferon may precipitate the onset
of diabetes mellitus or alter the patient’s eating patterns
and glucose utilization and lead to either hypo- or
hyperglycemia in a patient with previously controlled
diabetes. Patients with insulin resistance, type-2
diabetes and an elevated hemoglobin-A1-C have been
shown to have a lower SVR during treatment. For this
reason, patients with poorly controlled diabetes and
markedly elevated hemoglobin A1-C should probably
see an endocrinologist for better diabetes management
before initiating treatment.
Peginterferon may exacerbate as well as precipitate
autoimmune disorders. As a result, autoimmune diseases
are generally considered relative contraindications to HCV
treatment. Many patients with chronic HCV have severe
myalgias, arthralgias and a positive rheumatoid factor. HCV
is known to cause these findings in the absence of true
rheumatoid arthritis and many patients with chronic HCV are
incorrectly diagnosed with rheumatoid arthritis when this was
simply secondary to chronic HCV. Eradication of HCV RNA
in these patients is associated with resolution of arthralgias
and loss of rheumatoid factor. Having the patient see a
rheumatologist to clarify if the patient has true rheumatoid
arthritis or a reactive arthritis secondary to HCV may be
necessary in some patients