RIBAVIRIN 400 MG FILM-COATED TABLETS - patient leaflet, side effects, dosage

What is in this leaflet:

• 1. What Ribavirin is and what it is used for

• 2. What you need to know before you take Ribavirin

• 3. How to take Ribavirin

• 4. Possible side effects

• 5. How to store Ribavirin

• 6. Contents of the pack and other information

1. what ribavirin is and what it is used for

Ribavirin, which is the antiviral active substance of Ribavirin, inhibits the multiplication of manytypesof viruses, including the hepatitis C viruses (which can cause an infection of the liver called hepatitis C).

Ribavirinis used in combination with other medicines except peginterferon alfa-2a and peginterferon alfa-2bto treat certain chronic forms of hepatitis C.

Ribavirin should only be used in combination with other medicines except peginterferon alfa-2a and peginterferon alfa-2bto treat hepatitis C. Itshould not be taken alone.

Refer also to the package leaflets of the other medicinesexcept peginterferon alfa-2a and peginterferon alfa-2b that are used in combination with Ribavirin.

2. what you need to know before you take ribavirin if you are allergic to ribavirin or to any of the other ingredients of this medicine (listed insection 6).

• If you are pregnant or breast-feeding (see section “Pregnancy, breast-feeding and fertility”).
• If you have had a heart attack or have suffered from any other severe heart disease in theprevious six months.
• If you have a blood disorder such as sickle cell anaemia or thalassaemia(we­akening and destruction of red blood cells).

Refer also to the package leaflets of the other medicines that are used in combination with Ribavirin. Do not take Ribavirin in combination with medicines called interferons or pegylated interferons if you have advanced liver disease (e.g. your skin has become yellow and you have excess fluid in your abdomen).

Warnings and precautions

Talk to your doctor or pharmacistbefore taking Ribavirin

• If you are a woman of child-bearing age (see section “Pregnancy, breast-feeding and fertility”).
• If you are a man and your female partner is of childbearing age (see section “Pregnancy, breastfeeding and fertility”).
• If you have a heart problem. In this case you will need to be monitored carefully. A heart recording (ECG or electrocardiogram) is recommended prior to and during treatment.
• If you develop a heart problem along with intense fatigue. This may be due to anaemia caused by Ribavirin.
• If you have ever had anaemia (the risk of developing anaemia is higher in women compared to men, in general).
• If you have a problem with your kidneys. Ribavirin treatment may need to be decreased.
• If you have had an organ transplant (such as liver or kidney) or have one planned in the nearfuture.
• If you develop symptoms of an allergic reaction such as difficulty in breathing, wheezing,sudden swelling of the skin and mucous membranes, itching or rashes. Ribavirintreatment mustbe stopped immediately and you should seek medical help immediately.
• If you have ever had depression or develop symptoms associated with depression (e.g. feelingsof sadness, dejection, etc) while on treatment with Ribavirin(see section 4).
• If you are an adult who has or had a history of substance abuse (e.g. alcohol or drugs).
• If you are under the age of 18. The efficacy and safety of Ribavirinin combination withpeginterferon alfa-2a or interferon alfa-2a have not been sufficiently evaluated in patients underthe age of 18 years.
• If you are co-infected with HIV and are being treated with any anti HIV medicinal products.
• If you have been withdrawn from previous therapy for hepatitis C because of anaemia or lowblood count.

Before treatment with Ribavirin, kidney function must be tested in all patients. Your doctor must alsotest your blood before starting treatment with Ribavirin. The blood tests should be repeated after 2 and4 weeks of treatment, and thereafter as frequently as your doctor thinks is necessary.

If you are a woman of childbearing age, you must have a pregnancy test before starting treatment withRibavirin, every month during treatment and during the 4 months after treatment (see section “Pregnancy, breast-feeding and fertility”).

The following severe side effects are associated in particular with Ribavirin use in combination with interferon alfa-2a or peginterferon alfa-2a, please refer to the package leaflet of these medicinal products for more detailed information on these safety issues:

• Psychiatric and central nervous system effects (such as depression, suicidal thoughts, attempted suicide and aggressive behavior, etc.). 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
• Severe ocular disorder
• Dental and periodontal disorders: Dental and gum disorders have been reported in patients receivingRibavirin and peginterferon alfa-2a combination therapy. You should brush your teeth thoroughly twicedaily and have regular dental examinations. In addition some patients may experience vomiting. Ifyouhave this reaction, be sure to rinse your mouth thoroughly afterwards.
• Growth inhibition in children and adolescents that may be irreversible in some patients

Other medicines and Ribavirin

Tell your doctor or pharmacist if you are taking, have recently taken or might take any othermedicines.

Patients who also have HIV infection: Tell your doctor if you are being treated for HIV.

Lactic acidosis (a buildup of lactic acid in the body, leading to the blood becoming acidic) andworsening liver function are side effects associated with HAART (Highly Active AntiRetroviral­Therapy), an HIV treatment regimen. If you are receiving HAART, the addition of Ribavirin topeginterferon alfa-2a or interferon alfa-2a may increase your risk of lactic acidosis or liver failure.Your doctor will monitor you for signs and symptoms of these conditions.

If you take zidovudine or stavudine, because you are HIV positive or suffering from AIDS it is possible that Ribavirin can decrease the effect of these medicines. Therefore your blood will be checked regularly to make sure the HIV infection is not getting worse. If it does get worse, your doctor may decide to stop your treatment with Ribavirin. In addition, patients receiving zidovudine in combination with Ribavirin and alfa interferons are at increased risk of developing anaemia.

Co-administration of Ribavirin and didanosine, (which is a treatment for HIV) is not recommended. Certain side effects of didanosine (e.g. liver problems, tingling and painful arms and/or feet, pancreatitis) may occur more frequently.

Patients receiving azathioprine in combination with Ribavirinand peginterferon are at increased risk of developing severe blood disorders.

Refer also to the package leaflets of the other medicines that are used in combination with Ribavirin.

Ribavirin may remain in your body for up to 2 months, therefore you should check with your doctor or pharmacist before starting treatment with any of the other medicines mentioned in this leaflet.

Ribavirin with food and drink

Ribavirin film-coated tablets are normally taken at two times in the day with food (morning and evening) and should be swallowed whole.

Pregnancy, breast-feeding and fertility

Ribavirin can be very harmful to the unborn child; it may cause birth defects. Therefore, if you are afemale patient , it is very important to avoid becoming pregnant during treatment and during the 4months after treatment. Ribavirin can damage the sperm and so harm the embryo (unborn child).Therefore, if you are a male patient , it is very important for your female partner to avoid becomingpregnant during your treatment and during the 7 months after treatment.

If you are a woman of childbearing age who is taking Ribavirin, you must have a negative pregnancytest before treatment, each month during therapy and for the 4 months after treatment is stopped. Youmust use an effective contraceptive during the time you are taking the treatment and for 4 months afterstopping treatment. This can be discussed with your doctor. If your male partner is being treated withRibavirin, please see the section “If you are a man ”.

If you are a man who is taking Ribavirin, do not have sex with a pregnant woman unless you use acondom. This will lessen the chance for ribavirin to be left in the woman’s body. If your femalepartner is not pregnant now but is of childbearing age, she must be tested for pregnancy each monthduring treatment and for the 7 months after treatment has stopped. You or your partner must use aneffective contraceptive during the time you are taking the treatment and for 7 months after stoppingtreatment. This can be discussed with your doctor. Please see “if you are a woman ” if your femalepartner is treated with Ribavirin.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, askyour doctor or pharmacist for advice before taking this medicine.

It is not known whether Ribavirin is excreted in human milk. Women should not breast-feed whiletaking Ribavirin as this may harm the baby. If treatment with Ribavirin is necessary, breast-feedingshould be stopped.

Refer also to the package leaflets of the other medicines that are used in combination with Ribavirin for the treatment of hepatitis C.

Driving and using machines

Ribavirin has very little effect on your ability to drive or use machines.

However, the other medicines you take with Ribavirin may have an effect. Check the package leaflets of the other medicines you are using in combination with Ribavirin.

3. how to take ribavirin

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure. Your doctor will decide the correct dose for you depending on your body weight and type of virus.

The recommended dose ranges between 800mg to 1200 mg/day depending on the other medicines except peginterferon alfa-2a and peginterferon alfa-2b you are using in combination with Ribavirin.

For 200 mg:

• – 800 mg/day: Take 2 Ribavirin 200 mg tablets in the morning and 2 tablets in the evening

• – 1000 mg/day: Take 2 Ribavirin 200 mg tablets in the morning and 3 tablets in the evening

• – 1200 mg/day: Take 3 Ribavirin 200 mg tablets in the morning and 3 tablets in the evening

For 400 mg:

The recommended dose ranges between 800 mg to 1200 mg/day depending on the other medicines except peginterferon alfa-2a and peginterferon alfa-2byou are using in combination with Ribavirin.

• – 800 mg/day: Take 1 Ribavirin 400 mg tablet in the morning and 1 tablet in the evening

• – 1000 mg/day: Patients are advised to take Ribavirin 200 mg tablets

• – 1200 mg/day: Patients are advised to take Ribavirin 200 mg tablets

In the case of combination therapy with other medicinesexcept peginterferon alfa-2a and peginterferon alfa-2b, please follow the dosing regimen recommended by your doctor and refer also to the package leaflets of the other medicinesexcept peginterferon alfa-2a and peginterferon alfa-2b.

Swallow the tablets whole and take the tablets with food.

As ribavirin is teratogenic (may cause abnormalities in the unborn child), the tablets should be handled with care and should not be broken or crushed. If you accidentally touch damaged tablets, wash thoroughly with soap and water any part of your body which came in contact with the contents of the tablet. If any powder from the tablets gets in your eyes, rinse your eyes thoroughly with sterile water, or plain water if sterile water is not available.

The amount of time you have to continue taking Ribavirin film-coated tablets varies, depending on the type of virus you are infected with, which other medicine except peginterferon alfa-2a and peginterferon alfa-2b you are being treated with,on treatment response and whetheryou have been treated before. Please check with your doctor and follow the recommended duration oftreatment.

If you are over the age of 65 you should consult your doctor before using Ribavirin.

If you have the impression that the effect of Ribavirin is too strong or too weak, talk to your doctor orpharmacist.

If side-effects occur during treatment, your doctor may adapt the dose or stop treatment.

Refer also to the package leaflets of the other medicines except peginterferon alfa-2a and peginterferon alfa-2bthat are used in combination with Ribavirin.

If you take more Ribavirin than you should

Contact your doctor or pharmacist as soon as possible.

If you forget to take Ribavirin

Do not take a double dose to make up for a forgotten dose. If you miss a dose, take it as soon as you remember and take the next dose at the normal time.

If you stop taking Ribavirin

Only your doctor can decide when your treatment should be discontinued. Never stop the treatment yourself because the disease, for which you are being treated, can come back or get worse.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

During treatment, your doctor will take blood samples regularly to check for changes in your whiteblood cells (cells that fight infection), red blood cells (cells that carry oxygen), platelets (bloodclottin­gcells), liver function or changes in other laboratory values.

Refer also to the package leaflets of the other medicines that are used in combination with Ribavirin for information on the side effects for those products.

The side effects listed in this section were observed primarily when Ribavirin was used in combination with interferon alfa-2a or peginterferon alfa-2a.

Tell your doctor immediately if you notice any of the following side effects occur: severe chest pain;persistent cough; irregular heartbeat; trouble breathing;

confusion; depression; severe stomach pain;blood in stools (or black, tarry stools); severe nosebleed; fever or chills; problems with your eyesight. These side effects can be serious and you may need urgent medical attention.

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Very common side effects with the combination of pegylated alfa interferon and ribavirin (may affectmore than 1 in 10 people) are:

Blood disorders: Anaemia (low

red cell count), neutropenia (low white blood cell count)

Metabolic disorders: Loss of appetite Psychiatric disorders: Feeling depressed (feeling low, feeling bad about yourself or feeling hopeless), inability to sleep

Nervous system

disorders:	Headache, difficulty concentrating and dizziness
Respiratory disorders: Gastrointestinal	Cough, shortness of breath
disorders:	Diarrhoea, nausea, abdominal pain
Skin disorders:	Loss of hair, and skin reactions (including itching, dermatitis and dry skin).
Musculoskeletal disorders:	Pain in joints and muscles
General disorders:	Fever, weakness, tiredness, shaking, chills, pain, and irritability (getting easily upset)

Common side effects with the combination of pegylated alfa interferon and ribavirin (may affect up to1 in 10 people):

Infections: Upper respiratory infection,

bronchitis, fungal infection of the mouth and herpes (acommon recurring viral infection affecting the lips, mouth)

Blood disorders: Low platelet count (affecting the

clotting ability) and enlarged lymph glands.

Endocrine disorders: Overactive and underactive thyroid gland

Psychiatric disorders: Mood /emotion changes, anxiety, aggression, nervousness, decreased sexualdesire

Poor memory, fainting, decreased muscle strength, migraine, numbness, tingling, burning sensation, tremor, changes in the sense of taste, nightmares, sleepiness

Blurry vision, eye pain, eye inflammation and dry eyes. Sensation of room spinning, ear pain, ringing in ears

Rapid heart rate, pulsation of the heart beats, swelling in the extremities.

Vascular disorders: Flushing, low blood pressure Respiratory disorders: Shortness of breath with activity, nose bleeds, nose and throat inflammation, infections of the nose and sinuses (air-filled spaces found in the bones of the head and face), runny nose, sore throat

Gastrointestinal

Vomiting, indigestion, difficulty swallowing, mouth ulceration, bleeding gums, inflammation of tongue and mouth, flatulence (excess amount of air or gases), constipation, dry mouth.

Rash, increased sweating, psoriasis, hives, eczema, sensitivity to sunlight, night sweats

disorders: Back pain, joint inflammation, muscle

weakness, bone pain, neck pain, muscle pain, muscle cramps

Reproductive system

disorders: Impotence (inability to maintain an

erection)

General disorders: Chest pain, flu-like illness, malaise (not feeling well), lethargy, hot flushes, thirst, weight decreased

Uncommon side effects with the combination of pegylated alfa interferon and ribavirin (may affect up to 1 in 100 people):

Infections: Lower respiratory tract infections,

urinary tract infection, skin infections

Immune disorders: Sarcoidosis (areas of inflamed tissue occurring throughout the body), inflammationof the thyroid.

Endocrine disorders: Diabetes (high blood sugar)

Metabolic disorders: Dehydration

Psychiatric disorders: Thoughts of suicide, hallucinations (abnormal perceptions), anger

Nervous system

disorder: Peripheral neuropathy (disorder of

the nerves affecting the extremities)

Eye disorder: Bleeding in the retina (back of the

eye)

Ear and labyrinth disorders: Hearing loss

Vascular disorder: High blood pressure

Respiratory disorder: Wheezing

Gastrointestinal

disorders: Gastrointestinal bleeding,

inflammation of the lips, inflammation of thegums

Liver disorders: Poor functioning of the liver

Rare side effects with the combination of pegylated alfa interferon and ribavirin (may affect up to 1 in 1000 people):

Infection of the heart, infection of the external ear

Severe reduction in red blood cells, white blood cells and platelets

Severe allergic reaction, systemic lupus erythematosus (an illness where thebody attacks its own cells), rheumatoid arthritis (an autoimmune disease)

Suicide, psychotic disorders (severe problems with personality and deteriorationin normal social

functioning).

Nervous system

disorders: Coma (a deep prolonged

unconsciousness), seizures, facial palsy

Eye disorders: Inflammation and swelling of the optic

nerve, inflammation of the retina, ulceration ofthe cornea

Cardiac disorders: Heart attack, heart failure, heart pain, rapid heart rhythm, rhythm disorders orinflammation of the lining of the heart

Vascular disorders: Bleeding in the brain.vasculitis (inflammation of the blood vessels)

Respiratory disorders: Interstitial pneumonia (inflammation of the lungs with fatal outcome), bloodclots in the lung

Gastrointestinal

Eye disorders:	Loss of vision
Nervous System
disorders:	Stroke
Skin disorders:	Toxic epidermal necrolysis/ Stevens

Johnson Syndrome/ erythema multiforme (aspectrum of rashes with varying degrees of severity which may be associated with blisters in themouth, nose, eyes and other mucosal membranes), angioedema (swelling in the skin and mucosa)

Side effects with unknown frequency:

Blood disorders: Pure red cell aplasia (a severe form

of anaemia where red blood cell production isdecreased or stopped); it can result in symptoms such as feeling very tired with no energy.

Immune System disorders: liver and kidney transplant rejections,

Vogt Koyanagi Harada Syndrome

-a rare disease characterized by loss of vision, hearing, and skin pigmentation.

Psychiatric disorders: mania (episodes of exaggerated elevation of mood) and bipolar disorders (episodes of exaggerated elevation of mood alternating with sadness or hopelessness).

Eye disorders: Rare form of retinal detachment with

fluid in the retina

Digestive system

disorders: Ischemic colitis (insufficient blood

supply to the bowels), ulcerative colitis (inflammation of the large intestine that causes ulcers, resulting in diarrhoea), change in colour of the tongue

Musculoskeletal

Serious muscle damage and pain. kidneys stop functioning adequately, other complaints that suggest kidney problems.

If you are infected with both viruses, HCV and HIV, and are receiving HAART (Highly Active Anti- Retroviral Therapy), the addition of ribavirin to peginterferon alfa-2a or interferon alfa-2a therapy may cause fatal liver failure, peripheral neuropathy (numbness, tingling or pain in hands or feet), pancreatitis (symptoms may include stomach pain, nausea and vomiting), lactic acidosis (a buildup of lactic acid in the body, leading to the blood becoming acidic), influenza, pneumonia, affect lability (alterations in mood), apathy (lethargy), pharyngolaryngeal pain (pain in the back of your mouth and throat), cheilitis (dry and cracked lips), acquired lipodystrophy (increased amount of fat in upper back and neck) and chromaturia (change in colour of your urine) as side effects.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Yellow Card Scheme Website: or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store ribavirin

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 label, carton, bottle after EXP. The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other information- the active substance is ribavirin.

Each film-coated tablet contains 200 mg of ribavirin.

Each film-coated tablet contains 400 mg of ribavirin.

• – The other ingredients are

What Ribavirin looks like and contents of the pack

Film-coated tablet.

Ribavirin 200 mg:

Light pink colored, capsule shaped, film-coated tablets debossed with ‘F’ on one side and ‘10’ on the other side.

Ribavirin 400 mg:

Reddish brown colored, oval shaped, beveled biconvex, film-coated tablets debossed with ‘F’ on one side and ‘11’ on the other side.

Ribavirin film-coated tablets are available in clear PVC -Aluminium foil blister pack and HDPE bottle packs with polypropylene closure.

Pack sizes:

Blister pack : 14, 20, 28, 42, 56, 84, 112, 140 and 168 film-coated tablets

HDPE bottle pack:

200 mg: 28, 42, 56, 112, 168 and 500 film-coated tablets 400 mg: 14, 28, 56, 84 and 500 film-coated tablets

Not all pack sizes may be marketed

Marketing Authorisation Holder

Milpharm Limited

Ares Block, Odyssey Business Park

West End Road

Ruislip HA4 6QD

United Kingdom

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

or

Milpharm Limited

Ares Block, Odyssey Business Park

West End Road

Ruislip HA4 6QD

United Kingdom

or

ARROW Generiques

26 avenue Tony Garnier

69007 Lyon – France

This leaflet was last revised in 08/2018.

Stomach ulcer, inflammation of the

pancreas

Liver disorders: Liver failure, bile duct inflammation,

fatty liver

Musculoskeletal disorders: Inflammation of the muscles

Injury or poisoning: Substance overdose

Very rare side effects with the combination of pegylated alfa interferon and ribavirin (may affect up to 1 in 10,000 people):

Blood disorders: Aplastic anaemia (failure of the bone

marrow to produce red blood cells, white bloodcells and platelets).

Immune System

disorders: Idiopathic (or thrombotic)

thrombocytopenic purpura (increased bruising, bleeding, decreased platelets, anaemia and extreme weakness)