Rebetol 40 mg/ml oral solution

Rebetol oral solution contains the active ingredient ribavirin. Rebetol 40 mg/ml oral solution stops the multiplication of many types of viruses, including hepatitis C virus.
Rebetol must not be used without peginterferon alfa-2b or interferon alfa-2b, i.e. Rebetol must not be used alone.

Rebetol in combination with peginterferon alfa-2b or interferon alfa-2b is indicated for use in children 3 years of age and older and adolescents, previously untreated for chronic hepatitis C (HCV) infection.

Rebetol is not recommended for use in patients under the age of 3 years.

Do not take Rebetol

If any of the following apply to you or the child you are caring for, do not take Rebetol, and tell your doctor if you:

• had serious nervous or mental problems, such as severe depression, thoughts of suicide or attempted suicide.
• are allergic (hypersensitive) to ribavirin or any of the other ingredients of Rebetol.
• are pregnant or planning to become pregnant (see section ?Pregnancy and breast-feeding?).
• are breast-feeding.
• had a problem with your heart during the past 6 months.
• have severe medical conditions that leave you very weak.
• have severe kidney disease and/or are on haemodialysis.
• have a serious problem with your liver other than chronic hepatitis C.
• have any blood disorders, such as anaemia (low blood count), thalassemia, sickle-cell anaemia.
• have autoimmune hepatitis or any other problem with your immune system.
• are taking medicine that suppresses your immune system (that protects you against infection and some diseases).

Reminder: Please read the ?Do not use? section of the Package Leaflet for peginterferon alfa-2b or interferon alfa-2b before you begin combination treatment with Rebetol.

Take special care with Rebetol

Seek medical help immediately if you develop symptoms of a severe allergic reaction (such as difficulty in breathing, wheezing or hives) while taking this treatment.

You should tell your doctor if you or the child you are caring for:

• are an adult who has or had severe nervous or mental disorder, confusion, unconsciousness, or have had thoughts of suicide or have attempted suicide.
• have ever had depression or develop symptoms associated with depression (e.g. feeling of sadness, dejection, etc.) while on treatment with Rebetol.
• are a woman of childbearing age (see section ?Pregnancy and breast-feeding?).
• are a male and your female partner is of childbearing age (see section ?Pregnancy and breast-feeding).
• had a previous serious heart condition or have cardiac disease.
• are older than 65 years or if you have problems with your kidneys.
• have or have had any serious illness.
• have thyroid problems.

During treatment with Rebetol in combination therapy with an alpha interferon, dental and gum disorders, which may lead to loss of teeth, have been reported. In addition, dry mouth that could have a damaging effect on teeth and membranes of the mouth has been reported during long-term treatment with Rebetol in combination therapy with an alpha interferon. 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.

During treatment with Rebetol in combination therapy with an alpha interferon, patients may experience eye problems, or loss of vision in rare instances. If you receive ribavirin in combination with an alpha interferon, you should have a baseline eye examination. Any patient complaining of decrease or loss of vision must have a prompt and complete eye examination. Patients with pre-existing eye disorders (e.g., diabetic or hypertensive retinopathy) should receive periodic eye exams during combination therapy with ribavirin and an alpha interferon. Combination therapy with ribavirin and an alpha interferon should be discontinued in patients who develop new or worsening eye disorders.

Reminder: Please read the ?Take special care? section of the Package Leaflet for peginterferon alfa-2b or interferon alfa-2b before you begin combination treatment.

Taking other medicines

Please tell your doctor or pharmacist if you or the child you are caring for:

• are taking or have recently taken any other medicines, including medicines obtained without a prescription
• are receiving azathioprine in combination with ribavirin and pegylated alpha interferons and, therefore may be at an increased risk of developing severe blood disorders.
• are infected with both Human Immunodeficiency Virus (HIV-positive) and Hepatitis C Virus (HCV) and are being treated with an anti-HIV medicinal product(s) - [nucleoside reverse transcriptase inhibitor ( NRTI), and/or highly active anti-retroviral therapy ( HAART)]:
• Taking Rebetol in combination with an alpha interferon and an anti-HIV medicinal product(s) may increase the risk of lactic acidosis, liver failure, and blood abnormalities development (reduction in number of red blood cells which carry oxygen, certain white blood cells that fight infection, and blood clotting cells called platelets).
• With zidovudine or stavudine, it is not certain if Rebetol will change the way these medicines work. Therefore, your blood will be checked regularly to be sure that the HIV infection is not getting worse. If it gets worse, your doctor will decide whether or not your Rebetol treatment needs to be changed. Additionally, patients receiving zidovudine with ribavirin in combination with alpha interferons could be at increased risk of developing anaemia (low number of red blood cells). Therefore the use of zidovudine and ribavirin in combination with alpha interferons is not recommended.
• Due to the risk of lactic acidosis (a build-up of lactic acid in the body) and pancreatitis, the use of ribavirin and didanosine is not recommended and the use of ribavirin and stavudine should be avoided.
• Co-infected patients with advanced liver disease receiving HAART may be at increased risk of worsening liver function. Adding treatment with an alpha interferon alone or in combination with ribavirin may increase the risk in this patient subset.

Reminder: Please read the ?Taking other medicines? section of the Package Leaflet for peginterferon alfa-2b or interferon alfa-2b before you begin combination treatment with Rebetol.

Taking Rebetol with food and drink

Rebetol must be taken with food.

Pregnancy and breast-feeding
If you are pregnant, you must not take Rebetol. Rebetol can be very damaging to your unborn baby (embryo).

Both female and male patients must take special precautions in their sexual activity if there is any possibility for pregnancy to occur:

• Girl or woman of childbearing age: You must have a negative pregnancy test before treatment, each month during treatment, and for the 4 months after treatment is stopped. This should be discussed with your doctor.
• Men: Do not have sex with a pregnant woman unless you use a condom. This will lessen the possibility for ribavirin to be left in the woman?s body. If your female partner is not pregnant now but is of childbearing age, she must be tested for pregnancy each month during treatment and for the 7 months after treatment has stopped. You and your female partner must each use an effective contraceptive during the time you are taking Rebetol and for 7 months after stopping treatment. This should be discussed with your doctor (see section ?Do not take Rebetol?).

If you are a woman who is breast-feeding, you must not take Rebetol. Discontinue breast-feeding before starting to take Rebetol.

Driving and using machines
Rebetol does not affect your ability to drive or use machines; however, peginterferon alfa-2b or interferon alfa-2b may affect your ability to drive or use machines. Therefore, do not drive or use machines if you become tired, sleepy, or confused from this treatment.

Important information about some of the ingredients of Rebetol 40 mg/ml oral solution This medicinal product contains sucrose and sorbitol, these are types of sugars.
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

General information about taking Rebetol:
If the child you are caring for is under the age of 3 years, do not administer.

Always take Rebetol exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.
Do not take more than the recommended dosage and take the medicine for as long as prescribed. Your doctor has determined the correct dose of Rebetol based on how much you or the child you are caring for weighs.
Standard blood tests will be taken to check your blood, kidney and liver function.

• Blood tests will be done regularly to help the doctor to know if this treatment is working.
• Depending upon the results of these tests, your doctor may change/adjust the dose to be taken and/or the length of time to take this treatment.
• If you have or develop severe kidney or liver problems, this treatment will be stopped.

The usual dose, according to how much the patient weighs, is shown in the table below:

1. Look for the line that shows how much the patient weighs.

2. Read across on the same line to see how much to measure for the usual morning and evening doses. Reminder: If your doctor?s instructions are different from the amounts on the table, follow your doctor?s instructions.

3. If you have any questions about the dose, ask your doctor.

Rebetol oral solution Usual Dosage in Children If the patient weighs this many kg Measure and give this dose Morning Dose Evening Dose 10-12 2 ml 2 ml 13-14 3 ml 2 ml 15-17 3 ml 3 ml 18-20 4 ml 3 ml 21-22 4 ml 4 ml 23-25 5 ml 4 ml 26-28 5 ml 5 ml 29-31 6 ml 5 ml 32-33 6 ml 6 ml 34-36 7 ml 6 ml 37-39 7 ml 7 ml 40-41 8 ml 7 ml 42-44 8 ml 8 ml 45-47 9 ml 8 ml

1. Measure: You can measure the dose with the oral dosing syringe provided.

The plastic oral dosing syringe consists of two parts, an opaque barrel, and a white plunger rod that fits into the barrel. The rod is marked with 0.5 ml markings starting at 1.5 ml at the very top of the rod and ending at 10 ml. A. Insert the assembled dosing syringe into the bottle of Rebetol oral solution.

B. While keeping the tip in the liquid, pull the rod out. As the solution fills the syringe, you will see the numbers on the rod go up, such as 1.5 ml, 2.0 ml, 2.5 ml, etc. Reminder Your doctor may have changed the amount based on recent test results. C. Pull the rod out until you can read the correct number of ml for the dose you are measuring. D. Take the oral syringe out of the bottle and check to see that the correct amount appears in the bottom of the syringe. If you have too much or too little, try again until you have the correct amount. 2. Deliver Try not to let the oral syringe touch the inside of the mouth. Hold the syringe to your mouth and release the dose into your mouth or the mouth of the patient you are caring for by pushing in the rod. Swallow the dose. 3. Rinse If the syringe has touched the inside of the mouth, rinse it with water before inserting it in the bottle again. The syringe should be rinsed with water after each use to avoid stickiness.

4. Taking all your medicine: Take or give the prescribed dose by mouth in the morning and evening, with a meal.

Reminder: Rebetol oral solution is used in combination with peginterferon alfa-2b or interferon alfa-2b for injection for hepatitis C virus infection. For complete information be sure to read the ?How to use? section of the Package Leaflet for peginterferon alfa-2b or interferon alfa-2b.

Interferon medicine that is used in combination with Rebetol may cause unusual tiredness; if you are injecting this medicine yourself or giving it to a child, use it at bedtime.

If you take more Rebetol than you should

Tell your doctor or pharmacist as soon as possible.

If you forget to take Rebetol
If you are self-administering treatment, or if you are the caregiver of a child taking Rebetol in combination with interferon alfa-2b or peginterferon alfa-2b, take/administer the missed dose as soon as possible during the same day. If an entire day has gone by, check with your doctor. Do not take a double dose to make up for a forgotten dose.

Please read the ?Possible side effects? section of the Package Leaflet for peginterferon alfa-2b or interferon alfa-2b.

Like all medicines, Rebetol used in combination with an alpha interferon product can cause side effects, although not everybody gets them. Although not all of these unwanted effects may occur, they may need medical attention if they do occur.

Psychiatric and Central Nervous System:

Some people get depressed when taking Rebetol in combination treatment with an interferon, 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.

Children and adolescents are particularly prone to develop depression when being treated with Rebetol and interferon alpha. Immediately contact the doctor or seek emergency treatment if they display any unusual behavioural symptoms, feel depressed, or feel they want to harm themselves or others.

Growth and development (children and adolescents):

During the one year of treatment with Rebetol in combination with either peginterferon alfa-2b or interferon alfa-2b, some children and adolescents did not grow or gain weight as much as expected. Some children did not reach their projected height within 1-5 years after completing treatment.

Contact your doctor immediately if any of the following side effects occurring during combination treatment with an alpha interferon product:

• chest pain or persistent cough, changes in the way your heart beats, fainting,
• confusion, feeling depressed, suicidal thoughts or aggressive behaviour, attempt suicide, thoughts about threatening the life of others,
• feelings of numbness or tingling,
• trouble sleeping, thinking or concentrating,
• severe stomach pain; black or tar-like stools, blood in stool or urine, lower back or side pain,
• painful or difficult urination,
• severe bleeding from your nose,
• fever or chills beginning after a few weeks of treatment,
• problems with your eyesight or hearing,
• severe skin rash or redness.

Possible side effects listed below are grouped by frequency of occurrence Very common Common Uncommon Rare Very rare Not known affects more than 1 user in 10 affects 1 to 10 users in 100 affects 1 to 10 users in 1,000 affects 1 to 10 users in 10,000 affects less than 1 user in 10,000 frequency cannot be estimated from the available data

The following side effects have been reported with the combination of Rebetol and an interferon alfa-2b product in children and adolescents:

Very commonly reported side effects:

• decreases in the number of red blood cells (that may cause fatigue, shortness of breath, dizziness), decrease in neutrophils (that make you more susceptible to different infections),
• decrease in thyroid gland activity (which may make you feel tired, depressed, increase your sensitivity to cold and other symptoms),
• feeling depressed or irritable, feeling sick to stomach, feeling unwell, mood swings, tired feeling, trouble falling asleep or staying asleep, virus infection, weakness,
• diarrhoea, dizziness, fever, flu-like symptoms, headache, loss of or increase in appetite, loss of weight, decrease in the rate of growth (height and weight), pain on right side of ribs, pharyngitis (sore throat), shaking chills, stomach pain, vomiting,
• dry skin, hair loss, irritation, pain or redness at the site of injection, itching, muscle pain, muscle aches, pain in joints and muscles, rash.

Commonly reported side effects:

• decrease in blood clotting cells called platelets (that may result in easy bruising and spontaneous bleeding),
• excess of triglycerides in the blood, excess of uric acid (as in gout) in the blood, increase in thyroid gland activity (which may cause nervousness, heat intolerance and excessive sweating, weight loss, palpitation, tremors),
• agitation, anger, aggressive behaviour, behaviour disorder, difficulty concentrating, emotional instability, fainting, feeling anxious or nervous, feeling cold, feeling confused, feeling of restlessness, feeling sleepy, lack of interest or attention, mood changes, pain, poor quality sleep, sleepwalking, suicide attempt, trouble sleeping, unusual dreams, wanting to harm yourself,
• bacterial infections, common cold, fungal infections, abnormal vision, dry or teary eyes, ear infection, eye irritation or pain or infection, change in taste, changes in your voice, cold sores, coughing, inflamed gums, nose bleed, nose irritation, oral pain, pharyngitis (sore throat), rapid breathing, respiratory infections, scaling lips and clefts in the corners of the mouth, shortness of breath, sinusitis, sneezing, sores in mouth, sore tongue, stuffy or runny nose, throat pain, toothache, tooth abscess, tooth disorder, vertigo (spinning feeling), weakness,
• chest pain, flushing, palpitations (pounding heart beat), rapid heart rate,
• abnormal liver function,
• acid reflux, back pain, bedwetting, constipation, gastroesophageal or rectal disorder, incontinence, increased appetite, inflammation of the membrane of the stomach and intestine, stomach upset, loose stools,
• urination disorders, urinary tract infection,
• difficult, irregular, or no menstrual period, abnormally heavy and prolonged menstrual periods, disorder of vagina, inflammation of the vagina, testis pain, development of male body traits,
• acne, bruising, eczema (inflamed, red, itchy and dryness of the skin with possible oozing lesions), increased or decreased sensitivity to touch, increased sweating, increase in muscle movement, tense muscle, irritation or itching at the site of injection, limb pain, nail disorder, numbness or tingling feeling, pale skin, rash with raised spotted lesions, shaky hands, redness of skin or skin disorder, skin discolouration, skin sensitive to sunlight, skin wound, swelling due to a build-up of excess water, swollen glands (swollen lymph nodes), tremor, tumour (unspecified).

Uncommonly reported side effects:

• abnormal behaviour, emotional disorder, fear, nightmare,
• bleeding of the mucous membrane that lines the inner surface of the eyelids, blurred vision, drowsiness, intolerance to light, itchy eyes, facial pain,
• chest discomfort, difficult breathing, lung infection, nasal discomfort, pneumonia, wheezing,
• low blood pressure,
• enlarged liver,
• painful menstruation,
• itchy anal area (pinworms or ascarids), blistering rash (shingles), decreased sensitivity to touch, muscle twitching, pain in skin, paleness, peeling of skin, redness, swelling.

The additional following side effects have occurred with the combination of Rebetol and an alpha interferon product in adults but not in children:

Commonly reported side effects:

• decrease in certain white blood cells called leukocytes that help fight infection, excess of sugar in the blood, low calcium level in the blood,
• amnesia, crying, bleeding gums, feeling faint, anger, memory impaired, mental disorder,
• cardiac murmur (abnormal heart beat sounds), difficult breathing, low or high blood pressure,
• blurred vision, changes in your hearing, ringing in ears, earache, bloating, burning sensation on tongue, change in taste, taste loss, dry mouth, migraine, nonproductive cough, thirst,
• abnormal urine, passing more urine than usual,
• irritated colon, irritation of prostate gland, intestinal gas (flatus),
• jaundice (yellow skin),
• disorder of ovary, breast pain, lack of interest in sex or inability to perform, erectile problem,
• abnormal hair texture, arthritis, psoriasis, muscle spasm, puffy or swollen hands and ankles, swollen face, unsteady when walking, water impairment.

Uncommonly reported side effects:

• hearing or seeing images that are not present,
• heart attack, panic attack,
• hypersensitivity reaction to the medication
• inflammation of pancreas, pain in bone, diabetes mellitus,
• muscle weakness.

Rarely reported side effects:

• seizure (convulsions)
• pneumonia,
• rheumatoid arthritis, kidney problems,
• dark or bloody stools, intense abdominal pain,
• sarcoidosis (a disease characterised by persistent fever, weight loss, joint pain and swelling, skin lesions and swollen glands),
• vasculitis.

Very rarely reported side effects:

• suicide.

Not known side effects:

• thoughts about threatening the life of others,
• mania (excessive or unreasonable enthusiasm),
• pericarditis (inflammation of the lining of the heart), pericardial effusion [a fluid collection that develops between the pericardium (the lining of the heart) and the heart itself.

The attempt to harm yourself has also been reported in adults, children, and adolescents.

Rebetol in combination with an alpha interferon product may also cause:

• aplastic anaemia, pure red cell aplasia (a condition where the body stopped or reduced the production of red blood cells); this causes severe anaemia, symptoms of which would include unusual tiredness and a lack of energy,
• delusions,
• upper and lower respiratory tract infection,
• inflammation of the pancreas,
• severe rashes which may be associated with blisters in the mouth, nose, eyes and other mucosal membranes (erythema multiforme, Stevens Johnson syndrome), and toxic epidermal necrolysis (blistering and peeling of the top layer of skin).

The following other side effects have also been reported with the combination of Rebetol and an alpha interferon product:

• abnormal thoughts, hearing or seeing images that are not present, altered mental status, disorientation,
• angioedema (swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in swallowing or breathing), stroke (cerebrovascular events),
• Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin and the membranes of the ears, brain and spinal cord),
• bronchoconstriction and anaphylaxis (a severe, whole-body allergic reaction), constant cough,
• eye problems including damage to the retina, obstruction of the retinal artery, inflammation of the optic nerve, swelling of the eye and cotton wool spots (white deposits on the retina),
• enlarged abdominal area, heartburn, trouble having bowel movement or painful bowel movement,
• acute hypersensitivity reactions including urticaria (hives), bruises, intense pain in a limb, leg or thigh pain, loss of range of motion, stiffness, sarcoidosis (a disease characterised by persistent fever, weight loss, joint pain and swelling, skin lesions and swollen glands).

Rebetol in combination with peginterferon alfa-2b or interferon alfa-2b may also cause:

• dark, cloudy or abnormally coloured urine,
• difficulty breathing, changes in the way your heart beats, chest pain, pain down left arm, jaw pain,
• loss of consciousness,
• loss of use, drooping or loss of power of facial muscles, loss of feeling sensation,
• loss of vision. You or your caregiver should call your doctor immediately if you have any of these symptoms.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use Rebetol after the expiry date which is stated on the label. Once the bottle has been opened, the oral solution can be used for 1 month.

Do not store above 30ºC.

Do not use Rebetol without advice of your doctor or pharmacist if you notice any change in the appearance of the solution.

What Rebetol contains

• The active substance is ribavirin 40 mg/ml.
• The other ingredients are: Sodium citrate, citric acid, anhydrous, sodium benzoate, glycerol, sucrose, sorbitol liquid (crystallising), propylene glycol, purified water, natural and artificial bubble gum flavouring

What Rebetol looks like and contents of the pack

Rebetol 40 mg/ml oral solution is packaged in 118 ml size amber glass bottles containing 100 ml of oral solution.
A 10 ml oral dosing syringe is provided to measure the dose.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder SP Europe 73, rue de Stalle B-1180 Bruxelles Belgium Manufacturer SP S.A. 2, rue Louis Pasteur F-14200 Hérouville St Clair France

For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

BelgiëBelgiqueBelgien Rue de StalleStallestraat 73 B-1180 BruxellesBrusselBrüssel TélTel 32-02 370 92 11 LuxembourgLuxemburg Rue de Stalle 73 B-1180 BruxellesBrüssel BelgiqueBelgien TélTel 32-02 370 92 11

Magyarország Alkotás u. 53. H-1123 Budapest Tel. 36 1 457-8500 . .. 53, . 2 BG- 1407 . 359 2 806 3030

eská republika Ke tvanici 3 CZ-186 00 Praha 8 Tel 420 221771250 Malta 168 Christopher Street MT-VLT02 Valletta Tel 356-21 23 21 75

Danmark Lautrupbjerg 2 DK-2750 Ballerup Tlf 45-44 39 50 00 Nederland Walmolen 1 NL-3994 DL Houten Tel 31-0800 9999000

Deutschland Thomas-Dehler-Straße 27 D-81737 München Tel 49-089 627 31-0 Norge Pb. 398 N-1326 Lysaker Tlf 47 67 16 64 50

Eesti Järvevana tee 9 EE-11314 Tallinn Tel 372 654 96 86 Österreich Am Euro Platz 2 A-1120 Wien Tel 43-0 1 813 12 31

63 GR-174 55 T. 30-210 98 97 300 Polska Ul. Tamowa 7 PL-02-677 Warszawa Tel. 48-022 478 41 50

España Josefa Valcárcel, 38 E-28027 Madrid Portugal Rua Agualva dos Açores 16 P-2735-557 Agualva-Cacém

Tel 34-91 321 06 00 Tel 351-21 433 93 00

France 34 avenue Léonard de Vinci F-92400 Courbevoie Tél 33-01 80 46 40 40 România os. Bucureti-Ploieti, nr. 17-21, Bneasa Center, et. 8, sector 1 RO-013682 Bucureti Tel. 40 21 233 35 30

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Ísland Hörgatún 2 IS-210 Garðabær Sími 354 535 70 00 Slovenská republika Strakova 5 SK-811 01 Bratislava Tel 421 2 5920 2712

SuomiFinland PL 46PB 46 FIN-02151 EspooEsbo PuhTel 358 09 804 650 Italia Via fratelli Cervi snc, Centro Direzionale Milano Due Palazzo Borromini I-20090 Segrate Milano Tel 39-02 21018.1

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Latvija Bauskas 58a -401 Rga, LV-1004 Tel 371-7 21 38 25 United Kingdom Shire Park Welwyn Garden City Hertfordshire AL7 1TW - UK Tel 44-01 707 363 636

Lietuva

K-stu-io g. 65/40
LT-08124 Vilnius
Tel. + 370 52 101868

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