Brivirac

Package leaflet: Information for the user

Brivirac 125 mg tablets

Brivudine
DO NOT TAKE BRIVIRAC (BRIVUDINE) IF you have recently undergone, are currently undergoing, or are scheduled to undergo (within 4 weeks) a specific antitumor chemotherapy. DO NOT TAKE BRIVIRAC IF YOU HAVE AN ACTIVE FUNGAL INFECTION and have recently taken or are currently taking medicines containing flucytosine for the treatment of a fungal infection (see section 2, including the red box). THE INTERACTION between Brivirac (brivudine) and certain antitumor medicines or flucytosine is POTENTIALLY FATAL.
Please read this leaflet carefully before taking this medicine because
it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Never give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Brivirac is and what it is used for
2. What you need to know before taking Brivirac
3. How to take Brivirac
4. Possible side effects
5. How to store Brivirac
6. Contents of the pack and other information

1. What Brivirac is and what it is used for

Brivirac contains the active substance brivudine. Brivirac has an antiviral effect and prevents the virus that causes shingles (the varicella-zoster virus) from multiplying.
Brivirac is used in adults who do not have immune system disorders (the body's defences) for the early treatment of shingles (herpes zoster).

2. What you need to know before taking Brivirac

DO NOT take Brivirac:
if you have recently undergone, are currently undergoing, or are scheduled to undergo (within 4
weeks) a specific antitumor chemotherapy (e.g. capecitabine, 5-fluorouracil (5-FU),
tegafur, etc.) (see red box and section “Other medicines and Brivirac”)
if you currently have a fungal infection and have recently taken or are currently taking antifungal therapy with flucytosine (see red box and section “Other medicines and Brivirac”)
if you are allergic (hypersensitive) to the active substance brivudine
if you are allergic (hypersensitive) to any of the excipients in Brivirac (see section 6)
if you are pregnant or breastfeeding
if you are under 18 years of age.

DO NOT take Brivirac:
► if you have recently taken, are currently taking, or are about to take (within 4 weeks)
certain antitumor medicines (chemotherapy), particularly capecitabine, 5-fluorouracil (5-FU)
or other fluoropyrimidines administered orally, by injection, or topically as creams, ointments,
eye drops, or any other form of topical medicine
► if you currently have a fungal infection and have recently taken or are currently taking
antifungal therapy with flucytosine
► if you have recently taken, are currently taking, or are about to take (within 4 weeks)
a medicine for warts or a medicine for actinic keratosis or Bowen’s disease containing
fluoropyrimidines (5-fluorouracil or others)
► if your immune system (i.e. your body’s defences against infections) is severely
compromised, for example, if you have recently taken or are currently taking:

• antitumor medicines (chemotherapy), or

• immunosuppressive medicines (medicines that suppress or reduce the function of the immune system)

In particular:

• You must NOT take Brivirac together with medicines containing fluoropyrimidines (e.g. capecitabine, 5-FU, tegafur, flucytosine) (even during treatment-free intervals when you are not taking capecitabine tablets or receiving 5-FU infusions or other fluoropyrimidine formulations, or when you have recently taken such medicines)
• If you have taken Brivirac, you must wait at least 4 weeks after completing Brivirac treatment before taking capecitabine, 5-FU, or other fluoropyrimidines. See also section “Do not take Brivirac (brivudine)”

Warnings and precautions
Do not take Brivirac and consult your doctor or pharmacist:

• if you have recently taken, are currently taking, or are about to take (within 4 weeks) chemotherapeutic medicines (oral, injectable, or topical such as creams, ointments, eye drops, or any other form of topical medicine)
• if you currently have a fungal infection and have recently taken or are currently taking antifungal therapy with flucytosine (see section “Do not take Brivirac”, the red box, and section “Other medicines and Brivirac”). Do not take Brivirac if a skin rash has already fully developed (onset of crust formation). If in doubt, consult your doctor.
• Consult your doctor before taking Brivirac if you suffer from chronic liver disease (e.g. chronic hepatitis).
• You must not take Brivirac for longer than 7 days, as extending treatment beyond the recommended duration of 7 days increases the risk of developing hepatitis (see also section 4).

Children and adolescents
Do not give Brivirac to children and adolescents aged 0 to 18 years, as safety and efficacy have not been established in this age group.

Other medicines and Brivirac
Before starting treatment with Brivirac, inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription. This is extremely important because Brivirac can enhance the toxic effects of other medicines.

IMPORTANT NOTE:
Special warning for patients undergoing antitumor chemotherapy or with fungal infections
(see also the red box above):
Brivirac must not be used in patients who have recently taken, are currently taking, or are about to take (within 4 weeks) certain chemotherapeutic medicines.
The harmful effects of these medicines (fluoropyrimidines) can increase significantly and may be fatal, including:
5-fluorouracil (5-FU), including topical formulations
capecitabine
tegafur
other 5-fluoropyrimidines
combinations of any of the above substances with other active ingredients.

Brivirac must not be taken with medicines containing the active substance flucytosine used to treat fungal infections.

Do not take Brivirac and contact your doctor immediately if:

• you have recently undergone, are currently undergoing, or will undergo (within 4 weeks) treatment with any of the above medicines
• you have recently undergone or are currently undergoing antifungal treatment with flucytosine

If you have accidentally taken Brivirac together with any of the medicines listed above:

• stop taking both medicines immediately
• consult a doctor immediately
• go to hospital for immediate medical care (to protect against systemic infections and dehydration).

Symptoms and signs of 5-fluorouracil (and other fluoropyrimidine) toxicity due to these interactions include:

• malaise; diarrhoea; inflammation of the mouth and/or oral mucosa; fatigue; increased susceptibility to infections; tiredness (reduction in white blood cell count and bone marrow depression); skin rash and redness over the entire body, with painful skin, followed by large blisters leading to extensive skin peeling (toxic epidermal necrolysis) (see also section 4).

Post-marketing experience indicates a possible interaction between brivudine and dopaminergic drugs used for Parkinson’s disease, which may trigger an attack of chorea (abnormal, involuntary dance-like movements, particularly of the arms, legs, and face).

Brivirac with food and drink
You may take Brivirac with or without food.

Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Do not use Brivirac during pregnancy.
Do not use Brivirac if you are breastfeeding. The active substance in Brivirac may pass into your baby’s milk.

Driving and using machines
Dizziness and drowsiness have been observed in some patients taking Brivirac, although these are not common. If you experience these side effects, do not drive, operate machinery, or perform any work requiring secure support. Consult your doctor.

Brivirac contains lactose
This medicine contains lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

3. How to take Brivirac

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
The recommended dose is:
1 tablet of Brivirac 125 mg once daily for 7 days.
Take the Brivirac tablet at approximately the same time each day.
Brivirac may be taken with or without food.
Swallow the tablet whole with a sufficient amount of liquid, for example, a glass of water.
You must start treatment as soon as possible, meaning that, if possible, you should begin taking Brivirac:
within 3 days of the appearance of the first skin signs of shingles (rash), or
within 2 days of the appearance of the first blisters.
Complete the full 7-day course of treatment even if you feel better before it ends.
If symptoms persist or worsen during the treatment week, consult your doctor.
Taking the recommended dose of Brivirac reduces the risk of developing postherpetic neuralgia in patients over 50 years of age. Postherpetic neuralgia is persistent pain that develops in the area previously affected by herpes zoster after the skin rash has improved.

Duration of treatment
This medicine is intended for short-term use only. It should be taken for only 7 days. Do not take this medicine for a second course of treatment.

Use in children and adolescents
Do not take Brivirac if you are under 18 years of age.

If you take more Brivirac than you should
If you take more tablets than prescribed, contact your doctor immediately. He or she will decide whether further action is needed.

If you forget to take Brivirac
If you forget to take your tablet at the usual time, take it as soon as you remember. Take the next tablet the following day at approximately the same time as the previous day. Continue with this new administration time until the end of the 7-day treatment course.
Do not take a double dose to make up for a forgotten tablet.
If you repeatedly forget to take your daily dose, inform your doctor.

If you stop taking Brivirac
Do not stop taking Brivirac without first consulting your doctor. For the treatment to be fully effective, the medicine must be taken for 7 days.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Stop taking Brivirac and contact your doctor immediately if you experience an allergic
reaction with signs and symptoms including itching or skin redness (rash), increased sweating, swelling (of hands, feet, face, tongue, lips, eyelids or larynx), or difficulty breathing (see also section 4). These symptoms may be serious and require urgent medical attention.

The following side effect has been commonly observed (may affect up to 1 in 10 people):
nausea (feeling unwell).

The following side effects have been observed uncommonly (may affect up to 1 in 100 people):
a decrease in the number of a type of white blood cells (granulocytes)
an increase in the number of certain types of white blood cells (eosinophils, lymphocytes, monocytes)
a decrease in the number of red blood cells (anaemia)
allergic reactions including:

• skin itching (pruritus)
• skin redness (erythematous rash)
• increased sweating
• swelling of: hands, feet, face, tongue, lips, eyelids, larynx (laryngeal oedema)
• cough, difficulty breathing and/or shortness of breath
• loss of appetite
• anxiety
• insomnia, drowsiness
• headache
• dizziness
• vertigo
• abnormal sensations such as burning, numbness, tingling sensations, more frequently in arms and legs (paraesthesia)
• increased blood pressure
• indigestion (dyspepsia), vomiting, stomach ache
• diarrhoea
• excess gas in the stomach or intestines (flatulence)
• constipation
• chronic liver disease with fat accumulation (fatty liver)
• increased blood levels of certain substances produced by the liver (increased liver enzymes)
• weakness, tiredness (fatigue)
• flu-like symptoms (malaise, fever, body aches and chills)

The following side effects have been observed rarely (may affect up to 1 in 1,000 people):
► low blood pressure
► decrease in the number of platelets in the blood
► hallucinations, delirium
► confusion
► tremor
► altered sense of taste
► ear pain
► inflammation of the liver (hepatitis), increased bilirubin in the blood
► bone pain

The following side effects have also been reported, although their frequency is unknown (frequency cannot be estimated from the available data):
► loss of balance
► inflammation of blood vessels (vasculitis)
► rapidly developing liver failure
► localized skin inflammation that occurs repeatedly at the same site over time (fixed eruption), skin inflammation with peeling (exfoliative dermatitis), severe rash affecting the entire body and inside the mouth due to an allergic reaction (erythema multiforme), ulceration of the skin, mouth, eyes and genital areas (Stevens-Johnson syndrome)
► restlessness
► mood changes
► depressed mood
► feelings of aggression, agitation, anxiety
► fainting

• Reporting of side effects

If you get any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Brivirac

Keep out of the reach and sight of children.
Do not use this medicine after the expiry date stated on the carton and blister. The expiry date refers to the last day of that month.
Store the blister pack in the outer packaging to protect the medicine from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Brivirac contains
The active substance is brivudine.
Each Brivirac tablet contains 125 mg of brivudine.
The other components are:
microcrystalline cellulose
lactose monohydrate
povidone K 24-27
magnesium stearate

Description of the appearance of Brivirac and packaging contents
Brivirac 125 mg tablets are round, flat, white or almost white with bevelled edges.
The tablets are contained in a blister pack within a carton.
Brivirac is available in packs containing 1 and 7 tablets, and in multiple packs comprising 5 cartons, each containing 7 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
Laboratori Guidotti S.p.A. – Via Livornese, 897 – Pisa – La Vettola
Selling Agent:
A. Menarini Industrie Farmaceutiche Riunite S.r.l. – Via Sette Santi, 3 – Florence
Manufacturer:
Berlin-Chemie AG, Glienicker Weg 125 – 12489 Berlin (Germany)

This medicinal product is authorized in the European Economic Area (EEA) Member States under the following names:
Germany Premovir
Austria Mevir
Belgium Zerpex
Greece Brivir
Italy Brivirac
Luxembourg Zerpex
Portugal Bridic
Spain Nervinex