Package Insert: Information for the User

Ribavirin NORMON 200 mg Film-Coated Tablets

Ribavirin

Read this package insert carefully before starting to take the medication.

- Keep this package insert as you may need to read it again.

- If you have any doubts, consult your doctor or pharmacist.

- This medication has been prescribed to you and should not be given to others, even if they have the same symptoms, as it may harm them.

- If you consider that any of the adverse effects you are experiencing are severe or if you notice any adverse effect not mentioned in this package insert, inform your doctor or pharmacist.

1. What is ribavirin NORMON and for what it is used

2. Before taking ribavirin NORMON

3. How to take ribavirin NORMON

4. Possible adverse effects

5. Storage of ribavirin NORMON

6. Additional information

Ribavirina NORMON contains an active ingredient called ribavirin that slows down the multiplication of many types of viruses, including the hepatitis C virus. Ribavirina NORMON should not be used without interferon alfa-2b, that is, it should not be used alone.

Untreated patients:

Ribavirina NORMON is used in combination with interferon alfa-2b to treat patients aged 3 years and older who have chronic hepatitis C infection (CHC) of all types except genotypes 1, 4, 5, and 6, who have not been previously treated.

Previously treated patients:

Ribavirina NORMON is used, in combination with interferon alfa-2b, to treat adult patients with chronic hepatitis C, who have previously responded to treatment with a single interferon alfa, but whose disease has relapsed.

There is no information on safety or efficacy for the use of ribavirin with other forms of interferon (that is, different from alfa-2b).

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

Do not take ribavirin NORMON

If any of the following occurs to you or the child in your care, do not take ribavirin NORMON and inform your doctor if:

• you are allergic (hypersensitive) to ribavirin or to any of the other components of ribavirin NORMON.

• you are pregnant or plan to become pregnant (see section “Pregnancy and breastfeeding”).

• you are in the lactation period.

• you have had any heart problems in the last 6 months.

• you have severe health problems that leave you very weakened.

• you have severe kidney disease and/or if you are undergoing hemodialysis.

• you have a severe liver problem other than chronic hepatitis C.

• you have any blood disorder, such as anemia (low blood cell count), thalassemia, sickle cell anemia.

• you have autoimmune hepatitis or any other immune system problem.

• you are taking a medication that suppresses the immune system (which protects you from infection and some diseases).

Children and adolescents should not take the concomitant administration of ribavirin NORMON and interferon alpha when there is or have had a history of severe nervous or mental problems, such as severe depression, suicidal thoughts or intentions.

Reminder: Please read the “Do not use” section of the Prospectus of interferon alpha-2b before starting concomitant administration with ribavirin.

Be especially careful with ribavirin NORMON

Seek immediate medical attention if you develop severe allergic reaction symptoms (such as difficulty breathing, wheezing or urticaria) while taking this treatment.

Children and adolescents with a weight under 47 kg:

Ribavirin NORMON is not recommended for use. There is an oral solution of ribavirin available on the market for children over 3 years and adolescents with a weight under 47 kg.

You must inform your doctor if you or the child in your care:

• are an adult who has or has had a severe nervous or mental problem, confusion, loss of consciousness, or has had suicidal thoughts or attempted suicide.

• during treatment with ribavirin, you have ever had depression or develop symptoms associated with depression (e.g. feeling sad, disheartened, etc.).

• are a woman of childbearing age (see section “Pregnancy and breastfeeding”).

• are a man and your female partner is of childbearing age (see section “Pregnancy and breastfeeding”).

• have had a severe heart disease in the past or have a heart disease.

• are over 65 years old or have any kidney problems.

• have or have had any severe disease.

• have thyroid problems.

During treatment with ribavirin in concomitant administration with an interferon alpha, there have been reports of dental and gum disorders, which can lead to tooth loss. Additionally, there have been reports of dry mouth, which can have a detrimental effect on teeth and oral mucosa during long-term treatment with ribavirin and concomitant administration with an interferon alpha. You must brush your teeth properly twice a day and have regular dental check-ups. Some patients may experience vomiting. If you experience this reaction, make sure to rinse your mouth thoroughly.

During treatment with ribavirin in concomitant administration with an interferon alpha, rare cases of eye problems such as vision loss have been reported. If you are receiving ribavirin in combination with an interferon alpha, you must undergo an initial eye examination. Any patient who complains of vision loss or decreased vision must undergo a complete eye examination promptly. Patients with pre-existing eye disorders (e.g. diabetic or hypertensive retinopathy) must undergo regular eye examinations during combination therapy with ribavirin and an interferon alpha. Concomitant administration with ribavirin and an interferon alpha must be discontinued in patients who develop new eye disorders or if existing ones worsen.

Reminder: Please read the “Be especially careful” section of the Prospectus of interferon alpha-2b before starting concomitant administration with ribavirin NORMON.

Use of other medications

Inform your doctor or pharmacist if you or the child in your care:

- are using or have recently used other medications, including those purchased without a prescription.

- are receiving azathioprine in combination with ribavirin and pegylated interferon alpha, and therefore may have a higher risk of developing severe blood disorders.

- are HIV-positive and hepatitis C-positive and are being treated with antiretroviral medication(s) (NRTI, and/or TARGA):

- Taking ribavirin NORMON in combination with interferon alpha and antiretroviral medication(s) may increase the risk of lactic acidosis, liver failure, and blood abnormalities (reduction of red blood cells that carry oxygen, certain white blood cells that fight infections, and platelets).

- With zidovudine or stavudine, it has not been proven whether ribavirin changes the way these medications work. Therefore, your blood will be regularly monitored to ensure that your HIV infection is not worsening. If it worsens, your doctor will decide whether your treatment with ribavirin should be changed or not. Additionally, patients receiving zidovudine with ribavirin in combination with interferons alpha may have a higher risk of developing anemia (low red blood cell count). Therefore, the use of zidovudine and ribavirin in combination with interferons alpha is not recommended.

- Due to the risk of lactic acidosis and pancreatitis, the use of ribavirin and didanosine is not recommended and the use of ribavirin and stavudine should be avoided.

- Patients co-infected with advanced liver disease who are receiving TARGA may have an increased risk of worsening liver function.

Adding a treatment with an interferon alpha only or in combination with ribavirin may increase the risk in this group of patients.

Reminder: Please read the “Use of other medications” section of the Prospectus of interferon alpha-2b before starting concomitant administration with ribavirin NORMON.

Use of ribavirin NORMON with food and beverages

This medication should be taken with meals.

Pregnancy and breastfeeding

If you arepregnant, you must not take ribavirin NORMON. Ribavirin NORMON may cause harm to the fetus (embryo).

Both men and women must takespecial precautionsin their sexual activity if there is any possibility of pregnancy:

- Female or woman of childbearing age:

You must undergo a pregnancy test and have a negative result before starting treatment, every month during treatment, and for 9 months after treatment is discontinued. This should be discussed with your doctor.

- Men:

You must not have sexual relations with a pregnant woman unless youuse a condom.

This will reduce the possibility of ribavirin passing to the woman's body.

If your partner is not pregnant but is of childbearing age, you must undergo a pregnancy test every month during treatment and for 6 months after treatment is discontinued.

You and your female partner must use an effective contraceptive method during the time you take ribavirin and for 6 months after treatment is discontinued.

Consult your doctor (see section “Do not take ribavirin NORMON”).

If you are a woman who is breastfeeding, you must not take ribavirin. You must stop breastfeeding before starting to take ribavirin NORMON.

Driving and operating machinery

Ribavirin NORMON does not affect your ability to drive or operate machinery; however, interferon alpha-2b may affect your ability to drive or operate machinery. Therefore, do not drive or operate machinery if this treatment causes you fatigue, drowsiness, or confusion.

General Information on Taking Ribavirin NORMON:

If the child in your careis under 3 years old, do not administer it.

Follow exactly the administration instructions for ribavirin NORMON indicated by your doctor. Consult your doctor or pharmacist if you have doubts.

Do not take a dose above the recommended one and take the medication for the period prescribed. Your doctor has determined the correct dose of ribavirin based on your weight or that of the child in your care.

You will haveroutine blood teststo check your blood, renal, and hepatic functions.

- Regular blood tests will be performed to help your doctor know if this treatment is working.

- Based on the results of these tests, your doctor may change/adjust the number of tablets for you or the child in your care, prescribe a different presentation of ribavirin, and/or change the duration of treatment.

- If you develop severe renal or hepatic problems, this treatment will be suspended.

Theusual dose, based on the patient's weight, is shown in the table below:

1. Find the line that shows the adult or child/adolescent weight.

Remember: If the child is under 3 years old, do not administer it.

2. Read the same line to see how many tablets you should take.

Remember: If your doctor's instructions are different from the table below, follow your doctor's instructions.

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

Take the prescribed dose orally, with water, and during meals. Do not chew the tablets. For children or adolescents who cannot swallow a tablet, a ribavirin oral solution is available on the market.

Reminder: Ribavirin NORMON is only used in combination with interferon alfa-2b for chronic hepatitis C infection. For a complete information, read the "How to use" section of the interferon alfa-2b Prospectus.

Medicines with interferons used in combination with ribavirin NORMON may cause excessive fatigue; if you inject the medicine yourself or administer it to a child, do it at bedtime.

If you take more ribavirin NORMON than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medicine and the amount ingested.

If you forgot to take ribavirin NORMON

If you are self-administering this treatment, or if you are in charge of a child taking ribavirin in combination with interferon alfa-2b, take/administer the missed dose as soon as possible on the same day. If a day has passed, consult your doctor. Do not take a double dose to compensate for the missed doses.

Please also read the section “Possible Adverse Effects” of the Prospectus for interferon alfa-2b.

Like all medicines, ribavirin NORMON used in combination with an interferon alfa product may cause adverse effects, although not everyone will experience them. Although not all the side effects listed below will occur, some of them, if they do occur, may require medical attention.

Seek medical attention immediatelyif you experience any of the following adverse effects during treatment with a product containing interferon alfa:

- persistent chest pain or cough; changes in heart rhythm, fainting,

- confusion, feeling depressed; suicidal thoughts or aggressive behavior, attempted suicide, threatening thoughts towards other people,

- numbness or tingling,

- sleep disturbances, difficulty thinking or concentrating,

- severe stomach pain; black or tar-like stools; blood in stools or urine; lower back or side pain,

- difficulty urinating or painful urination,

- severe nosebleed,

- appearance of fever or chills after several weeks of treatment,

- visual or auditory disturbances,

- severe skin rash or redness.

The possible adverse effects listed below are grouped by frequency of occurrence:

Very Common(affects more than 1 in 10 patients)

Common(affects between 1 and 10 in 100 patients)

Uncommon(affects between 1 and 10 in 1,000 patients)

Rare(affects between 1 and 10 in 10,000 patients)

Very Rare(affects less than 1 in 10,000 patients)

Frequency Not Known(the frequency cannot be estimated from available data)

The following adverse effects have been reported with the combination of ribavirin and a product containing interferon alfa in adults:

Adverse effects reported very frequently:

- reduction in the number of red blood cells (which can cause fatigue, difficulty breathing, dizziness), or neutrophils (which can make you more susceptible to different infections),

- difficulty concentrating, feeling anxious or nervous, mood changes, feeling depressed or irritable, feeling tired, sleep problems or staying asleep,

- cough, dry mouth, pharyngitis (throat pain),

- diarrhea, dizziness, fever, flu-like symptoms, headache, nausea, chills, viral infections, vomiting, weakness,

- loss of appetite, weight loss, stomach pain,

- dry skin, irritation, pain, or redness at the injection site, hair loss, itching, muscle pain, muscle discomfort, joint pain and muscle pain, skin rash.

Adverse effects reported frequently:

- decrease in platelets (which can cause easy bruising and spontaneous bleeding), decrease in certain white blood cells called lymphocytes that help fight infections, decrease in thyroid gland activity (which can make you feel tired, depressed, increase your sensitivity to cold, and other symptoms), high blood sugar or uric acid levels (like gout) in the blood, low calcium levels in the blood, severe anemia,

- fungal or bacterial infections, crying, agitation, amnesia, memory alteration, nervousness, abnormal behavior, aggressive behavior, anger reaction, feeling confused, loss of interest, mental disorder, mood changes, strange dreams, desire to self-harm, drowsiness, sleep problems, loss of interest in sex or inability to engage in it, vertigo (feeling like everything is spinning),

- blurred or abnormal vision, eye pain, irritation, or infection, dry or watery eyes, changes in hearing or voice, ringing in the ears, ear infection, ear pain, herpes simplex (febrile herpes), taste alteration, loss of taste, bleeding gums or mouth sores, tongue pain, gum inflammation, dental problems, migraine, respiratory infections, sinusitis, nasal hemorrhage, non-productive cough, nasal obstruction or discharge, rapid breathing or difficulty breathing, thirst, dental problems,

- abnormal heart sounds, chest pain or discomfort, feeling faint, feeling unwell, hot flashes, intolerance to heat or excessive sweating, increased heart rate, low or high blood pressure, palpitations (strong heartbeats), excessive sweating,

- intestinal distension, constipation, gastrointestinal disorder, gas (flatulence), increased appetite, irritable bowel syndrome, prostate gland irritation, jaundice (yellow skin), soft stools, pain in the right side of the chest, liver inflammation, stomach discomfort, frequent urination, urinating more than usual, urinary tract infection, altered urine.

- difficult or irregular menstrual periods, heavier or prolonged menstrual periods, painful menstruation, altered ovaries or vagina, breast pain, erectile dysfunction,

- abnormal hair texture, acne, arthritis, petechiae, eczema (inflamed, red, itchy, and dry skin with possible lesions that suppurate), urticaria, increased or decreased sensitivity to touch, nail alterations, muscle spasms, numbness or tingling, pain in the extremities, pain at the injection site, joint pain, shaky hands, psoriasis, inflamed or swollen hands or feet, sensitivity to sunlight, skin rash with raised lesions, skin redness or alteration, facial inflammation, lymph node inflammation (inflamed lymph nodes), muscle contractions, non-specific tumor, gait instability, fluid imbalance.

Adverse effects reported uncommonly:

- hearing or seeing things that are not present,

- heart attack, anxiety attack,

- hypersensitivity reaction to the medication,

- pancreatitis, bone pain, diabetes mellitus,

- muscle weakness.

Adverse effects reported rarely:

- seizures (convulsions),

- pneumonia,

- rheumatoid arthritis, kidney problems,

- dark or bloody stools, severe abdominal pain,

- sarcoidosis (a disease characterized by persistent fever, weight loss, painful and inflamed joints, skin lesions, and inflamed lymph nodes),

- vasculitis.

Adverse effects reported very rarely:

- suicide.

Adverse effects with unknown frequency (cannot be estimated from available data):

- threatening thoughts towards other people,

- mania (excessive or unreasonable enthusiasm),

- pericarditis (inflammation of the heart lining), pericardial effusion (accumulation of fluid between the pericardium and the heart).

The following adverse effects have been reported with the combination of ribavirin and interferon alfa-2b in children and adolescents:

Adverse effects reported very frequently:

- reduction in the number of red blood cells (which can cause fatigue, difficulty breathing, dizziness), or neutrophils (which can make you more susceptible to different infections),

- decrease in thyroid gland activity (which can make you feel tired, depressed, increase your sensitivity to cold, and other symptoms),

- feeling depressed or irritable, stomach pain, feeling unwell, mood changes, feeling tired, difficulty sleeping or staying asleep, viral infections, weakness,

- diarrhea, dizziness, fever, flu-like symptoms, headache, loss or increase of appetite, weight loss, decreased growth rate (height and weight), pain in the right side of the chest, pharyngitis (throat pain), chills, stomach pain, vomiting.

- dry skin, hair loss, irritation, pain, or redness at the injection site, itching, muscle pain, muscle discomfort, joint pain and muscle pain, skin rash.

Adverse effects reported frequently:

- decrease in platelets (which can cause easy bruising and spontaneous bleeding),

- high triglyceride levels in the blood, high uric acid levels in the blood (like gout), increased thyroid gland activity (which can cause nervousness, intolerance to heat, excessive sweating, weight loss, palpitations, tremors),

- nervousness, irritability, aggressive behavior, behavioral changes, difficulty concentrating, emotional instability, dizziness, feeling anxious or nervous, feeling cold, feeling confused, loss of interest, feeling restless, feeling sleepy, lack of interest or attention, mood changes, sadness, poor sleep quality, somnambulism, suicidal thoughts, sleep problems, strange dreams, desire to self-harm,

- bacterial infections, common cold, fungal infections, abnormal vision, dry or watery eyes, ear infection, eye pain, irritation, or infection, taste alterations, voice alterations, herpes febrile, cough, swollen lymph nodes, nasal hemorrhage, mouth pain, pharyngitis (throat pain), rapid breathing, respiratory infections, cracked lips and mouth sores, rapid breathing, sinusitis, sneezing, mouth sores, tongue pain, nasal obstruction or discharge, throat pain, tooth pain, abscessed teeth, dental alterations, vertigo (feeling like everything is spinning), weakness.

- chest pain, facial redness, palpitations (strong heartbeats), high blood pressure,

- abnormal liver function,

- gastroesophageal reflux, back pain, nocturia, constipation, gastrointestinal or rectal disorder, incontinence, increased appetite, inflammation of the stomach and intestinal mucosa, stomach discomfort, soft stools,

- urinary tract problems, urinary incontinence,

- difficult or irregular menstrual periods, heavier or prolonged menstrual periods, altered vagina, testicular pain, development of male physical characteristics,

- acne, itching, eczema (inflamed, red, itchy, and dry skin with possible lesions that suppurate), increased or decreased sensitivity to touch, excessive sweating, muscle spasms, muscle tension, pain in the extremities, nail alterations, numbness or tingling, skin lesions with raised lesions, hands or feet inflammation or swelling, sensitivity to sunlight, skin redness or alteration, skin paleness, fluid retention, lymph node inflammation (inflamed lymph nodes), tremors, non-specific tumor.

Adverse effects reported uncommonly:

- abnormal behavior, emotional disorders, fears, nightmares,

- bleeding from the mucous membranes that connect the inner surface of the eyelids, blurred vision, drowsiness, intolerance to light, eye itching, facial pain, inflamed gums,

- chest pain, difficulty breathing, lung infection, nasal pain, pneumonia, wheezing,

- low blood pressure,

- enlarged liver,

- menstrual pain,

- anal itching (pinworms or ascariasis), blisters (chickenpox), decreased sensitivity to touch, muscle spasms, skin pain, paleness, desquamation, skin redness, and inflammation.

Self-harm has also been reported in adults, children, and adolescents.

Ribavirin in combination with an interferon alfa product may also cause:

- aplastic anemia, red blood cell aplasia (a disease in which the body interrupts or decreases the production of red blood cells; which causes severe anemia, characterized by unusual fatigue and lack of energy,

- delirium, upper and lower respiratory tract infections,

- pancreatitis,

- severe skin rash that may be associated with mouth, nose, eye, and other mucous membrane lesions (erythema multiforme, Stevens-Johnson syndrome), toxic epidermal necrolysis (appearance of blisters and skin peeling).

The following adverse effects have also been reported for ribavirin in combination with an interferon alfa product:

- abnormal thoughts, hearing or seeing things that are not present, altered mental state, disorientation,

- angioedema (swelling of hands, feet, ankles, face, lips, mouth, or throat that can cause difficulty swallowing or breathing), cerebral hemorrhage (stroke),

- Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disease that affects the eyes, skin, and ear membranes, brain, and spinal cord),

- bronchospasm and anaphylaxis (severe allergic reaction throughout the body), persistent cough,

- eye problems, including retinal damage, retinal artery occlusion, optic nerve inflammation, eye inflammation, and retinal exudates (white deposits on the retina),

- abdominal distension, acid reflux, difficult or painful defecation,

- acute hypersensitivity reactions such as itching (urticaria), bruising, severe pain in a limb, leg or thigh pain, loss of mobility, stiffness, sarcoidosis (a disease characterized by persistent fever, weight loss, painful and inflamed joints, skin lesions, and inflamed lymph nodes),

Ribavirin in combination with interferon alfa-2b may also cause:

- dark, cloudy, or unusual-colored urine,

- difficulty breathing, changes in heart rhythm, chest pain, left arm pain, jaw pain,

- loss of consciousness,

- paralysis, muscle weakness, facial muscle weakness, numbness, or loss of sensation,

- loss of vision.

You or the person caring for you should call your doctor immediately if you experience any of these symptoms.

The adverse effects listed in this section were mainly observed when ribavirin was used in combination with medications containing interferon.

When ribavirin was used in combination with other medications to treat hepatitis C (also known as direct-acting antivirals) in clinical studies in adults, the most frequently reported adverse effects associated with ribavirin were anemia (low red blood cell count), nausea, vomiting, fatigue, insomnia (difficulty sleeping), cough, shortness of breath, itching, and rash.

See the prospectuses of the other medications used in combination with ribavirin for information on the adverse effects of those medications.

Keep out of the reach and sight of children.

No special storage conditions are required.

Do not use ribavirina NORMON 200 mg tablets after the expiration date appearing on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

Composition of ribavirina NORMON

-The active ingredient is ribavirina 200 mg.

-The other components (excipients) are:Core:microcrystalline cellulose, calcium dihydrogen phosphate, low-substituted hydroxypropyl cellulose, povidone, colloidal silica, magnesium stearate.Covering:hypromellose, titanium dioxide, macrogol 6000, talc, and iron oxide red (E-172).

Appearance of the product and contents of the package

Ribavirina NORMON 200 mg are pinkish-colored, elongated, and biconvex coated tablets that are presented in packages of 168 tablets.

Holder of the marketing authorization and responsible for manufacturing

Laboratorios Normon, S.A.

Ronda de Valdecarrizo, 6 – 28760 Tres Cantos – Madrid (SPAIN)

Date of the last review of this leaflet: June 2021