Ribavirin Normon 200 mg film-coated tablets EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Ribavirin NORMON 200 mg film-coated tablets EFG

Ribavirin

Read the entire leaflet carefully before you start taking this medicine.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you and should not be given to other people, even if they have the same symptoms as you, because it may harm them.
• If you consider any of the side effects you experience to be severe, or if you notice any side effects not listed in this leaflet, inform your doctor or pharmacist.

Leaflet contents:

1. What ribavirin NORMON is and what it is used for
2. Before taking ribavirin NORMON
3. How to take ribavirin NORMON
4. Possible side effects
5. How to store ribavirin NORMON
6. Further information

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

Ribavirina NORMON contains an active substance called ribavirin that inhibits the replication of many types of viruses, including the hepatitis C virus. Ribavirina NORMON must not be used without interferon alfa-2b; that is, it should not be used alone.

Patients not previously treated:

Ribavirina NORMON is used in combination with interferon alfa-2b to treat patients aged 3 years and older who have chronic hepatitis C virus (HCV) infection of all types except genotypes 1, 4, 5, and 6, and 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 previously responded to treatment with interferon alfa alone, but in whom the disease has recurred.

There is no safety or efficacy information available for the use of ribavirin in combination with other forms of interferon (i.e., different from alfa-2b).

2. BEFORE TAKING ribavirina NORMON

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

Do not take ribavirina NORMON

Do not take ribavirina NORMON and inform your doctor if any of the following apply to you or to the child under your care:

• You are allergic (hypersensitive) to ribavirin or to any of the other components of ribavirina NORMON.
• You are pregnant or planning to become pregnant (see section “Pregnancy and breastfeeding”).
• You are breastfeeding.
• You have had heart problems within the last 6 months.
• You have serious health problems that leave you severely weakened.
• You have severe kidney disease and/or are undergoing hemodialysis.
• You have a serious liver disease other than chronic hepatitis C.
• You have any blood disorder, such as anemia (low blood cell count), thalassemia, or sickle cell anemia.
• You have autoimmune hepatitis or any other immune system disorder.
• You are taking a medication that suppresses the immune system (which protects you against infection and certain diseases).

Children and adolescents should not take ribavirina NORMON in combination with interferon alfa if they have or have a history of serious neurological or psychiatric disorders, such as severe depression, suicidal thoughts, or suicidal intentions.

Reminder: Please read the “Do not use” section of the interferon alfa-2b package leaflet before starting combination treatment with ribavirina.

Take special care with ribavirina NORMON

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

Children and adolescents weighing less than 47 kg:

Use of ribavirina NORMON is not recommended. An oral solution of ribavirin is available on the market for children over 3 years of age and adolescents weighing less than 47 kg.

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

• Are an adult who has or has had a serious neurological or psychiatric disorder, confusion, loss of consciousness, or have had suicidal thoughts or attempted suicide.
• Have previously experienced depression during treatment with ribavirin or develop symptoms associated with depression (e.g., feelings of sadness, hopelessness, etc.).
• Are a woman of childbearing potential (see section “Pregnancy and breastfeeding”).
• Are a man and your female partner is of childbearing potential (see section “Pregnancy and breastfeeding”).
• Have previously had a serious heart condition or have a heart disease.
• Are over 65 years of age or have kidney problems.
• Have or have had any serious illness.
• Have thyroid problems.

During treatment with ribavirin in combination with interferon alfa, dental and gum disorders have been reported, which may lead to tooth loss. In addition, dry mouth has been reported, which may have a detrimental effect on teeth and oral mucosa during long-term treatment with ribavirin and combination therapy with interferon alfa. You should brush your teeth properly twice daily and have regular dental check-ups. In addition, some patients may experience vomiting. If you experience this side effect, make sure to rinse your mouth thoroughly afterwards.

During treatment with ribavirin in combination with interferon alfa, in rare cases, patients may experience eye problems such as vision loss. If you are receiving ribavirin in combination with interferon alfa, you should have an initial eye examination. Any patient who reports decreased or lost vision should undergo a prompt and complete eye examination. Patients with pre-existing eye disorders (e.g., diabetic or hypertensive retinopathy) should have periodic eye examinations during combination therapy with ribavirin and interferon alfa. Combination treatment with ribavirin and interferon alfa should be discontinued in patients who develop new eye disorders or whose existing conditions worsen.

Reminder: Please read the “Take special care” section of the interferon alfa-2b package leaflet before starting combination treatment with ribavirina NORMON.

Use of other medicines

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

• Are currently using or have recently used any other medicines, including those obtained without a prescription.

• Are receiving azathioprine in combination with ribavirin and pegylated interferon alfa, and therefore may have an increased risk of developing severe blood disorders.

• Are infected with Human Immunodeficiency Virus (HIV-positive) and Hepatitis C Virus (HCV) and are being treated with anti-HIV medication(s) – [nucleoside reverse transcriptase inhibitor (NRTI), and/or highly active antiretroviral therapy (HAART)]:

• Taking ribavirina NORMON in combination with interferon alfa and anti-HIV medication(s) may increase the risk of lactic acidosis, liver failure, and development of blood abnormalities (reduction in the number of red blood cells carrying oxygen, certain white blood cells fighting infections, and blood-clotting cells called platelets).

• With zidovudine or stavudine, it has not been established whether ribavirin alters the action of these medications. Therefore, your blood will be monitored regularly to ensure that your HIV infection is not worsening. If it does worsen, your doctor will decide whether your ribavirin treatment should be changed. In addition, patients receiving zidovudine with ribavirin in combination with interferons alfa may have an increased risk of developing anemia (low number of red blood cells). Therefore, the use of zidovudine and ribavirin in combination with interferons alfa is not recommended.

• Due to the risk of lactic acidosis (build-up of lactic acid in the body) and pancreatitis, the use of ribavirin with didanosine is not recommended, and the use of ribavirin with stavudine should be avoided.

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

Adding treatment with interferon alfa alone or in combination with ribavirin may increase the risk in this group of patients.

Reminder: Please read the “Use of other medicines” section of the interferon alfa-2b package leaflet before starting combination treatment with ribavirina NORMON.

Use of ribavirina NORMON with food and drink

This medicine should be taken with food.

Pregnancy and breastfeeding

If you are pregnant, you must not take ribavirina NORMON. Ribavirina NORMON may cause harm to the fetus (embryo).

Both men and women must take special precautions regarding sexual activity if there is any possibility of pregnancy:

• Girl or woman of childbearing potential:

A pregnancy test must be performed and yield a negative result before starting treatment, each month during treatment, and for 9 months after stopping treatment. Discuss this with your doctor.

• Men:

Do not have sexual intercourse with a pregnant woman unless you use a condom.

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

If your partner is not pregnant but is of childbearing potential, she must have a pregnancy test every month during treatment and for 6 months after stopping treatment.

You and your female partner must each use an effective method of contraception during the time you are taking ribavirin and for 6 months after stopping treatment.

Discuss this with your doctor (see section “Do not take ribavirina NORMON”).

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

Driving and using machines

Ribavirina NORMON does not affect your ability to drive or operate machinery; however, interferon alfa-2b may affect your ability to drive or operate machinery. Therefore, do not drive or operate machinery if this treatment causes you to feel tired, drowsy, or confused.

3. How to TAKE ribavirina NORMON

General information on taking ribavirina NORMON:

If the child under your care is under 3 years of age, do not administer this medicine.

Always follow your doctor's instructions for taking ribavirina NORMON exactly. Consult your doctor or pharmacist if you have any doubts.

Do not take a dose higher than recommended, and take the medicine only for the prescribed duration. Your doctor has determined the correct dose of ribavirina based on your weight or that of the child under your care.

You will have routine blood tests to monitor your blood, kidney, and liver function.

• You will undergo regular blood tests so your doctor can assess whether this treatment is working.
• Depending on the results of these tests, your doctor may change/adjust the number of tablets for you or for the child under your care, prescribe a different formulation of ribavirina, and/or modify the duration of treatment.
• If you develop severe kidney or liver problems, this treatment will be discontinued.

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

1. Find the row corresponding to the weight of the adult or child/adolescent.

Remember: Do not administer if the child is under 3 years of age.

2. Read across the same row to see how many tablets should be taken.

Remember: If your doctor's instructions differ from those in 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, an oral solution of ribavirin is available on the market.

Reminder: Ribavirin NORMON is only used in combination with alpha-2b interferon for chronic hepatitis C infection. For complete information, read the “How to use” section of the alpha-2b interferon package leaflet.

Medicines containing interferons used in combination with ribavirin NORMON may cause increased tiredness; if you are self-injecting the medicine or administering it to a child, do so at bedtime.

If you take more ribavirin NORMON than you should

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take ribavirin NORMON

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

4. Possible adverse effects

Please also read the section “Possible adverse effects” in the interferon alfa-2b Package Leaflet.

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

Contact your doctor immediately if you experience any of the following adverse effects during combination treatment with an interferon alfa-containing product:

• chest pain or persistent cough; changes in heart rhythm, fainting,
• confusion, feeling depressed; suicidal thoughts or aggressive behavior, suicide attempt, thoughts threatening the lives of other people,
• sensations of numbness or tingling,
• sleep disorders, difficulty thinking or concentrating,
• severe stomach pain; black or tarry stools; blood in stools or urine; lower back pain or flank pain,
• pain or difficulty urinating,
• severe nosebleeds,
• development of fever or chills after several weeks of treatment,
• visual or hearing 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 fewer than 1 in 10,000 patients)

Frequency not known (frequency cannot be estimated from available data)

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

Adverse effects reported very commonly:

• reduction in red blood cells (which may cause fatigue, difficulty breathing, dizziness), or in neutrophils (which may make you more susceptible to various infections),
• difficulty concentrating, feeling anxious or nervous, mood changes, feeling depressed or irritable, feeling tired, trouble sleeping or staying asleep,
• cough, dry mouth, pharyngitis (sore throat),
• diarrhea, dizziness, fever, flu-like symptoms, headache, nausea, severe chills, viral infection, 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 and muscle pain, skin rash.

Adverse effects reported commonly:

• decrease in blood cells involved in clotting called platelets (which may lead to easy bruising and spontaneous bleeding), decrease in certain white blood cells called lymphocytes that help fight infections, decreased thyroid gland activity (which may make you feel tired, depressed, increase cold sensitivity and other symptoms), excess sugar or uric acid (as in gout) in the blood, low blood calcium levels, severe anemia,
• fungal or bacterial infections, crying, agitation, amnesia, memory disturbance, nervousness, abnormal behavior, aggressive behavior, angry reaction, feeling confused, loss of interest, mental disorder, mood changes, strange dreams, self-harm ideation, drowsiness, trouble sleeping, loss of interest in sex or inability to engage in sexual activity, dizziness (sensation of spinning),
• blurred or abnormal vision, eye pain, irritation or infection, dry or watery eyes, changes in hearing or voice, ringing in the ears (tinnitus), ear infection, ear pain, cold sores (herpes simplex), altered taste, loss of taste, bleeding gums or mouth sores, burning sensation in the tongue, tongue pain, swollen gums, dental problems, migraine, respiratory infections, sinusitis, nosebleeds, non-productive cough, nasal congestion or discharge, rapid breathing or difficulty breathing, thirst, dental disorders,
• heart murmur (abnormal heart sound), chest pain or discomfort, feeling faint, malaise, hot flashes, heat intolerance or excessive sweating, increased heart rate, low or high blood pressure, palpitations (strong or rapid heartbeat), increased sweating,
• abdominal bloating, constipation, stomach upset, intestinal gas (flatulence), increased appetite, irritable bowel, prostate gland irritation, jaundice (yellowing of the skin), soft stools, pain under the right ribs, liver inflammation, stomach discomfort, frequent urge to urinate, urinating more than usual, urinary tract infection, urine abnormalities,
• painful, irregular or absent menstrual periods, heavier and prolonged menstrual bleeding, painful menstruation, vaginal or ovarian disorders, breast pain, erectile dysfunction,
• abnormal hair texture, acne, arthritis, bruising, eczema (inflamed, red, itchy, dry skin, possibly with oozing lesions), hives, increased or decreased sensitivity to touch, nail changes, muscle spasms, numbness or tingling sensation, limb pain, injection site pain, joint pain, tremors in hands, psoriasis, swollen or puffy hands or ankles, sensitivity to sunlight, skin rash with raised spots, skin redness or skin changes, facial swelling, gland swelling (swollen lymph nodes), muscle twitching, tumor (non-specific), unsteadiness when walking, fluid disorder.

Adverse effects reported uncommonly:

• hearing or seeing things that are not present (hallucinations),
• heart attack, panic attack,
• hypersensitivity reaction to the medicine,
• 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 swollen joints, skin lesions and swollen glands),
• vasculitis.

Adverse effects reported very rarely:

• suicide.

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

• thoughts threatening the lives of other people,
• mania (excessive or unreasonable enthusiasm),
• pericarditis (inflammation of the lining around the heart), pericardial effusion [accumulation of fluid between the pericardium (the sac around the heart) and the heart itself].

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

Adverse effects reported very commonly:

• reduction in red blood cells (which may cause fatigue, difficulty breathing, dizziness), or in neutrophils (which may make you more susceptible to various infections),
• decreased thyroid gland activity (which may make you feel tired, depressed, increase cold sensitivity and other symptoms),
• feeling depressed or irritable, stomach pain, feeling unwell, mood changes, feeling tired, inability to sleep or stay asleep, viral infection, weakness,
• diarrhea, dizziness, fever, flu-like symptoms, headache, loss or increase in appetite, weight loss, reduced growth rate (height and weight), pain under the right ribs, pharyngitis (sore throat), severe chills, stomach pain, vomiting,
• dry skin, hair loss, irritation, pain or redness at the injection site, itching, muscle pain, muscle discomfort, joint and muscle pain, skin rash.

Adverse effects reported commonly:

• decrease in blood cells involved in blood clotting called platelets (which may lead to easy bruising and spontaneous bleeding),
• elevated blood triglycerides, elevated blood uric acid (as in gout), increased thyroid gland activity (which may cause nervousness, heat intolerance, excessive sweating, weight loss, palpitations, tremors),
• nervousness, irritability, aggressive behavior, behavioral changes, difficulty concentrating, emotional instability, fainting, feeling anxious or nervous, feeling cold, confusion, loss of interest, restlessness, drowsiness, lack of interest or attention, mood changes, sadness, poor-quality sleep, sleepwalking, suicidal ideation, trouble sleeping, unusual dreams, self-harm ideation,
• bacterial infections, common cold, fungal infections, abnormal vision, dry or watery eyes, ear infection, eye pain, irritation or infection, altered taste, voice changes, cold sores, cough, swollen glands, nosebleeds, mouth pain, pharyngitis (sore throat), rapid breathing, respiratory infections, cracked lips and mouth corner fissures, rapid breathing, sinusitis, sneezing, mouth ulcers, tongue sores, nasal congestion or discharge, sore throat, toothache, dental abscess, dental disorders, dizziness (feeling of spinning), weakness,
• chest pain, facial redness, palpitations (strong heartbeats), high pulse,
• abnormal liver function,
• acid reflux, back pain, bedwetting, constipation, gastroesophageal or rectal disorder, incontinence, increased appetite, inflammation of the stomach and intestinal lining, stomach discomfort, soft stools,
• urinary problems, urinary tract infection,
• painful, irregular or absent menstrual periods, heavier and prolonged menstrual bleeding, vaginal disorders, vaginal inflammation, testicular pain, development of male physical characteristics,
• acne, itching, eczema (inflamed, red, itchy, dry skin, possibly with oozing lesions), increased or decreased tactile sensitivity, increased sweating, increased muscle movements, muscle tension, limb pain, nail changes, numbness or tingling, skin lesions, skin rash with raised colored spots, hand tremors, skin redness or skin changes, skin discoloration, photosensitivity, pale skin, swelling due to excessive fluid accumulation, gland swelling (swollen lymph nodes), tremor, tumor (non-specific).

Adverse effects reported uncommonly:

• abnormal behaviors, emotional disorders, fears, nightmares,
• bleeding from mucous membranes lining the inner surface of the eyelids, blurred vision, drowsiness, light sensitivity, itchy eyes, facial pain, swollen gums,
• chest pain, difficulty breathing, lung infection, nasal pain, pneumonia, wheezing,
• low blood pressure,
• enlarged liver,
• menstrual pain,
• anal itching (pinworms or roundworms), blisters (shingles), decreased sensitivity to touch, muscle spasms, skin pain, pallor, skin peeling, redness and inflammation of the skin.

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

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

• aplastic anemia, red cell aplasia (a condition in which the body stops or reduces production of red blood cells; resulting in severe anemia, symptoms of which include unusual tiredness and lack of energy),
• delusions, upper and lower respiratory tract infections,
• pancreatitis,
• severe skin rashes that may be associated with blistering in the mouth, nose, eyes, and other mucous membranes (erythema multiforme, Stevens-Johnson syndrome), toxic epidermal necrolysis (blistering and peeling of the outer layer of skin).

The following adverse effects have also been reported for ribavirin in combination with an interferon alfa-containing 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 may cause difficulty swallowing or breathing), stroke (cerebrovascular accident),
• Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disease affecting the eyes, skin, ear membranes, brain, and spinal cord),
• bronchoconstriction and anaphylaxis (severe, whole-body allergic reaction), persistent cough,
• eye problems including retinal damage, retinal artery occlusion, optic neuritis, eye inflammation and retinal exudates (white deposits in the retina),
• abdominal distension, stomach acidity, 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 swollen joints, skin lesions, and swollen 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, pain under the left arm, jaw pain,
• loss of consciousness,
• paralysis, reduced or loss of facial muscle strength, loss of sensation,
• vision loss.

You or your caregiver should call your doctor immediately if you experience any of these symptoms.

The adverse effects listed in this section were primarily observed when ribavirin was used in combination with interferon-containing medicines.

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

Please also refer to the package leaflets of the other medicines used in combination with ribavirin for information on their adverse effects.

5. Storage of ribavirin NORMON

Keep out of the reach and sight of children.

No special storage conditions are required.

Do not use ribavirin NORMON 200 mg tablets after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. ADDITIONAL INFORMATION

Composition of ribavirin NORMON

• The active substance is ribavirin 200 mg.
• The other components (excipients) are: Core: microcrystalline cellulose, calcium hydrogen phosphate dihydrate, low-substituted hydroxypropylcellulose, povidone, colloidal silica, magnesium stearate. Coating: hypromellose, titanium dioxide, macrogol 6000, talc, and red iron oxide (E-172).

Appearance of the medicinal product and contents of the pack

Ribavirin NORMON 200 mg are light pink, elongated, biconvex coated tablets supplied in packs of 168 tablets.

Marketing Authorization Holder and Manufacturer

LABORATORIOS NORMON, S.A.
Ronda de Valdecarrizo, 6 – 28760 Tres Cantos – Madrid (SPAIN)

Date of the most recent revision of this leaflet: June 2021