Vilarib 200 mg capsules, hard

Vilarib contain the active ingredient ribavirin. Vilarib stops the multiplication of many types of viruses, including hepatitis C virus. Vilarib must not be used without interferon alfa-2b, i.e. Vilarib must not be used alone.

Previously untreated patients :

The combination of Vilarib with interferon alfa-2b is used to treat patients 3 years of age and older who have chronic hepatitis C (HCV) infection. For children and adolescents weighing less than 47 kg a solution formulation is available.

Previously treated adult patients:

The combination of Vilarib with interferon alfa-2b is used to treat adult patients with chronic hepatitis C, who have previously responded to treatment with an alpha interferon alone, but whose condition has recurred.

There is no safety or efficacy information on the use of Vilarib with pegylated or other forms of interferon (i.e., not alfa-2b).

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

Do not take Vilarib:

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

• are allergic (hypersensitive) to ribavirin or any of the other ingredients of this medicine (listed in section 6).
• 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).

Children and adolescents must not take combination therapy with Vilarib and alpha interferon when there is existence or history of serious nervous or mental problems, such as severe depression, thoughts of suicide or attempted suicide.

Reminder: Please read the “Do not use” section of the Package Leaflet for interferon alfa-2b before you begin combination treatment with Vilarib.

Warnings and precautions

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.

Children and adolescents weighing less than 47 kg:

The use of Vilarib is not recommended. An oral solution of ribavirin is available for children 3 years of age and older and adolescents weighing less than 47 kg.

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

• are an adult who has or had a 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 Vilarib.
• 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 Vilarib in combination therapy with an alfa 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 Vilarib 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 Vilarib 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 “Warnings and precautions” section of the Package Leaflet for interferon alfa-2b before you begin combination treatment.

Other medicines and Vilarib

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 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 Vilarib 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 Vilarib 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 Vilarib 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 alfa interferons alone or in combination with ribavirin may increase the risk in this patient subset.

Reminder: Please read the “Other medicines” section of the Package Leaflet for interferon alfa-2b before you begin combination treatment.

Vilarib with food and drink

Vilarib must be taken with food.

Pregnancy and breast-feeding

If you are pregnant you must not take Vilarib. Vilarib 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 ribavirin and for 7 months after stopping treatment. This should be discussed with your doctor (see “Do not take Vilarib”).

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

Driving and using machines

Vilarib does not affect your ability to drive or use machines; however, 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.

Vilarib contains lactose.

If you have been told by your doctor that you have an intolerance to some sugars, discuss with your doctor before taking this medicinal product.

General information about taking Vilarib

If the child you are caring for is under the age of 3 years, do not administer.

Always take this medicine exactly as your doctor or pharmacist has told you. 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 Vilarib 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 your doctor to know if this treatment is working.
• Depending upon the results of these tests, your doctor may change/adjust the number of capsules you or the child you are caring for take, prescribe a different pack size of <Product name>, and/or change the length of time to take this treatment.
• If you have or develop severe kidney or liver problems, this treatment will be stopped.

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

1. Look for the line that shows how much the adult or child/adolescent weighs. Reminder: If the child is under the age of 3 years, do not administer.
2. Read across on the same line to see how many capsules to take.

Reminder: If your doctor’s instructions are different from the amounts in the below table, follow your doctor’s instructions.

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

Vilarib for oral use - dose based on body weight

If the adult
weighs	Usual
(kg)	daily Vilarib dose	Number of 200 mg capsules
< 65	800 mg	2 capsules in the morning and 2 capsules in the evening
65 – 80	1,000 mg	2 capsules in the morning and 3 capsules in the evening
81 - 105	1,200 mg	3 capsules in the morning and 3 capsules in the evening
> 105	1,400 mg	3 capsules in the morning and 4 capsules in the evening
If the
child/adolescent	Usual
weighs (kg)	daily Vilarib dose	Number of 200 mg capsules
47 – 49	600 mg	1 capsule in the morning and 2 capsules in the evening
50 – 65	800 mg	2 capsules in the morning and 2 capsules in the evening
> 65	see adult dose and	corresponding number of hard capsules

Take your prescribed dose by mouth with water and during your meal. Do not chew the capsules. For children or adolescents who cannot swallow a hard capsule, an oral solution of ribavirin is available.

Reminder: Vilarib is only to be used in combination with interferon alfa-2b for hepatitis C virus infection. For complete information be sure to read the “How to use” section of the Package Leaflet for interferon alfa-2b.

Interferon medicine that is used in combination with Vilarib 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 Vilarib than you should

Tell your doctor or pharmacist as soon as possible.

If you forget to take Vilarib

If you are self-administering treatment, or if you are the caregiver of a child taking Vilarib in combination with interferon 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 interferon alfa-2b.

Like all medicines, this medicine 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 Ribavirin 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 ribavirin 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 Ribavirin in combination with 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 you notice any of the following side effects occuring 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	(affects more than 1 user in 10)
Common	(affects 1 to 10 users in 100)
	5

Uncommon	(affects 1 to 10 users in 1,000)
Rare	(affects 1 to 10 users in 10,000)
Very rare	(affects less than 1 user in 10,000)
Not known	(frequency cannot be estimated from the available data).

The following side effects have been reported with the combination of Vilarib and an alpha interferon product in adults:

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),
• difficulty concentrating, feeling anxious or nervous, mood swings, feeling depressed or irritable, tired feeling, trouble falling asleep or staying asleep,
• cough, dry mouth, pharyngitis (sore throat),
• diarrhoea, dizziness, fever, flu-like symptoms, headache, nausea, shaking chills, virus infection, vomiting, weakness,
• loss of appetite, loss of weight, stomach pain,
• dry skin, irritation, pain or redness at the site of injection, hair loss, 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, decrease in certain white blood cells called lymphocytes that help fight infection, decrease in thyroid gland activity (which may make you feel tired, depressed, increase your sensitivity to cold and other symptoms) excess of sugar or uric acid (as in gout) in the blood, low calcium level in the blood, severe anaemia,
• fungal or bacterial infections, crying, agitation, amnesia, memory impaired, nervousness, abnormal behaviour, aggressive behaviour, anger, feeling confused, lack of interest, mental disorder, mood changes, unusual dreams, wanting to harm yourself, feeling sleepy, trouble sleeping, lack of interest in sex or inability to perform, vertigo (spinning feeling),
• blurred or abnormal vision, eye irritation or pain or infection, dry or teary eyes, changes in your hearing or voice, ringing in ears, ear infection, earache, cold sores (herpes simplex), change in taste, taste loss, bleeding gums or sores in mouth, burning sensation on tongue, sore tongue, inflamed gums, tooth problem, migraine, respiratory infections, sinusitis, nose bleed, nonproductive cough, rapid or difficult breathing, stuffy or runny nose, thirst, tooth disorder,
• cardiac murmur (abnormal heart beat sounds), chest pain or discomfort, feeling faint, feeling unwell, flushing, increased sweating, heat intolerance and excessive sweating, low or high blood pressure, palpitations (pounding heart beat), rapid heart rate,
• bloating, constipation, indigestion intestinal gas (flatus), increased appetite, irritated colon, irritation of prostate gland, jaundice (yellow skin), loose stools, pain on the right side around your ribs, enlarged liver, stomach upset, frequent need to urinate, passing more urine than usual, urinary tract infection, abnormal urine,
• difficult, irregular, or no menstrual period, abnormally heavy and prolonged menstrual periods, painful menstruation, disorder of ovary or vagina, breast pain, erectile problem,
• abnormal hair texture, acne, arthritis, bruising, eczema (inflamed, red, itchy and dryness of the skin with possible oozing lesions),hives, increased or decreased sensitivity to touch, nail disorder, muscle spasms, numbness or tingling feeling, limb pain, pain at the site of injection, pain in joints, shaky hands, psoriasis, puffy or swollen hands and ankles, sensitivity to sunlight, rash with raised spotted lesions, redness of skin or skin disorder, swollen face, swollen glands (swollen lymph nodes), tense muscles, tumour (unspecified), 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,
• diabetes, 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 following side effects have been reported with the combination of Vilarib and 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 corner 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), fingers and toes very sensitive to cold, 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, inflamed gums,
• 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 attempt to harm yourself has also been reported in adults, children, and adolescents. Vilarib 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), 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 Vilarib 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).

Vilarib in combination with 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 you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton or bottle.

Do not store above 30°C.

Do not use this medicine without advice of your doctor or pharmacist if you notice any change in the appearance of the capsules.

What Vilarib contains

• The active substance is ribavirin. Each hard capsule contains 200 mg ribavirin.
• The other ingredients (excipients) are: croscarmellose sodium, lactose monohydrate, microcrystalline cellulose, povidone. The capsule shell contains gelatine and titanium dioxide (E171). The capsule shell imprint contains shellac, propylene glycol, strong ammonia solution, yellow iron oxide (E172), indigotine (E132), titanium dioxide (E171).

What Vilarib looks like and contents of the pack

The Vilarib capsules, hard is a white, opaque, hard capsule imprinted with green ink.

The Vilarib capsules, hard is available in different pack sizes containing 84, 112, 140 or 168 capsules of 200 mg to be swallowed.

Not all pack sizes may be marketed.

Your physician will prescribe the pack size which is best for you.

Marketing Authorization Holder

PharmaSwiss Česká republika s.r.o. Jankovcova 1569/2c

170 00 Prague 7

Czech Republic

Manufacturer

ICN Polfa Rzeszów S.A. ul. Przemysłowa 35-959 Rzeszów

This medicinal product is authorized in the Member States of the EEA under the following names:

NL: Vilarib 200 mg capsules, hard BG: Vilarib 200 mg kапсула, твърда CZ: Vilarib 200 mg tvrdé tobolky HU: Vilarib 200 mg kemény kapszula PL: Vilarib

RO: Vilarib 200 mg capsulă

SK: Vilarib 200 mg tvrdé kapsuly

Deze bijsluiter is voor het laatst goedgekeurd in oktober 2013