FIRDAPSE 10 mg TABLETS

2. What you need to know before you take FIRDAPSE

Do not take FIRDAPSE

• If you are allergic to amifampridine or any of the other ingredients of this medicine (listed in section 6).

• If you have uncontrolled asthma.
• If you have epilepsy.
• In combination with medicines that can alter the heart's electrical activity (prolongation of the QT interval detectable on the electrocardiogram), such as:
• • Sultopride (a medicine indicated for the treatment of certain behavioral disorders in adults)

• Anti-arrhythmic medicines (e.g., disopyramide)
• Medicines for treating digestive problems (e.g., cisapride, domperidone)

• Medicines for treating infections: antibiotics (e.g., rifampicin) and antifungals (e.g., ketoconazole)

• In combination with medicines with a therapeutic dose close to the maximum safe dose.
• If you were born with a heart problem (congenital QT syndromes).

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

Warnings and precautions

Consult your doctor or pharmacist before starting to take FIRDAPSE.

Tell your doctor if you have:

• Asthma.
• A history of epileptic seizures (convulsions).
• Kidney problems.
• Liver problems.

Your doctor will closely monitor your response to FIRDAPSE and may need to adjust the dose of the medicines you are taking. Your doctor will also monitor your heart at the start of treatment and then once a year.

If you have LEMS but no cancer, your doctor will carefully assess the possible risk of you developing cancer with FIRDAPSE before starting treatment.

Tell any doctor you consult that you are using FIRDAPSE.

Stop treatment and consult your doctor immediately if:

• You have epileptic seizures (convulsions).
• You have asthma.

Taking FIRDAPSE with other medicines

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

Some medicines may interact with FIRDAPSE if taken together. The following medicines should not be combined with FIRDAPSE:

• Medicines that can alter the heart's electrical activity (prolongation of the QT interval detectable on the electrocardiogram), such as sultopride, disopyramide, cisapride, domperidone, rifampicin, and ketoconazole (see "Do not take FIRDAPSE").

It is especially important that you tell your doctor if you are taking any of the following medicines or plan to start taking them:

• Medicines for malaria (e.g., halofantrine and mefloquine).
• Tramadol (a pain reliever).
• Antidepressants: tricyclic antidepressants (e.g., clomipramine, amoxapine), selective serotonin reuptake inhibitors (e.g., citalopram, dapoxetine), and atypical antidepressants (e.g., bupropion).

• Medicines for mental problems (e.g., haloperidol, carbamazepine, chlorpromazine, clozapine).
• Medicines for treating Parkinson's disease: anticholinergics (e.g., trihexyphenidyl, mesylate), MAO-B inhibitors (e.g., selegiline, deprenyl), COMT inhibitors (e.g., entacapone).

• Medicines for treating allergies: antihistamines (e.g., terfenadine, astemizole, cimetidine).
• Medicines for relaxing muscles (e.g., mivacurium, pipercuronium, suxamethonium), sedatives (e.g., barbiturates).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

You should not use FIRDAPSE if you are pregnant. You will need to use an effective method of contraception during the entire treatment period. If you become pregnant during treatment, tell your doctor immediately.

It is not known whether FIRDAPSE is excreted in human breast milk. You and your doctor will need to weigh the benefits and risks of continuing to take FIRDAPSE during breastfeeding.

Driving and using machines

This medicine may cause drowsiness, dizziness, epileptic seizures (convulsions), and blurred vision, which could affect your ability to drive or use machines. Do not drive or use machines if you experience these side effects.

3. How to take FIRDAPSE

Follow the instructions for administration of this medicine exactly as told by your doctor.

If you are unsure, consult your doctor or pharmacist again.

Your doctor will tell you the dose you should take based on the severity of your symptoms and certain genetic factors. This dose will be suitable only for you.

The initial dose is 5 mg of amifampridine (half a tablet) three times a day (i.e., 15 mg per day). Your doctor may increase this dose gradually, first to 5 mg (half a tablet) four times a day (i.e., 20 mg per day). Then, your doctor may continue to increase your total daily dose by adding 5 mg (half a tablet) per day, every 4 or 5 days.

The maximum recommended dose is 60 mg per day (i.e., a total of six tablets taken at intervals throughout the day). Daily doses above 20 mg should be divided into two to four separate doses. No more than 20 mg should be taken in a single dose (two tablets).

The tablets have a score line that allows them to be broken in half. The tablets should be swallowed with a little water and taken with food.

Patients with liver or kidney problems:

FIRDAPSE should be used with caution in patients with kidney or liver problems. A starting dose of 5 mg (half a tablet) of FIRDAPSE per day is recommended in patients with moderate or severe kidney or liver problems. In patients with mild kidney or liver problems, a starting dose of 10 mg (5 mg twice a day) of FIRDAPSE is recommended. In these patients, the dose of FIRDAPSE should be increased more slowly than in patients without liver or kidney problems, with increments of 5 mg every 7 days. If you experience any side effects, consult your doctor, as you may need to stop increasing the dose.

If you take more FIRDAPSE than you should

If you take more FIRDAPSE than you should, you may experience vomiting or stomach pain. If you experience any of these symptoms, contact your doctor or pharmacist immediately.

If you forget to take FIRDAPSE

If you forget to take FIRDAPSE, do not take a double dose to make up for the missed doses; continue taking the treatment as instructed by your doctor.

If you stop treatment with FIRDAPSE

If you stop treatment, you may experience symptoms such as fatigue, slow reflexes, and constipation. Do not stop treatment without consulting your doctor.

If you have any further questions about 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.

Stop treatment and consult your doctor immediately if:

• You have epileptic seizures (convulsions).
• You have asthma.

Very common side effects that may affect more than 1 in 10 people are:

• Numbness or tingling around the mouth and in the limbs (hands and feet).

• Reduced sense of touch or sensation.
• Nausea.
• Dizziness.
• Increased sweating, cold sweats.

Common side effects that may affect up to 1 in 10 people are:

• Stomach pain.
• Cold hands and feet.

Other side effects are:

The intensity and incidence of most side effects depend on the dose you are taking. The following side effects have also been reported (frequency cannot be estimated from the available data):

• Raynaud's syndrome (a circulatory disorder that affects the fingers and toes).
• Diarrhea.
• Epileptic seizures (convulsions).
• Cough, excessive or viscous mucus in the respiratory tract, asthma attacks in asthmatic patients or those with a history of asthma.
• Blurred vision.
• Abnormal heart rhythms, rapid or irregular heartbeats (palpitations).
• Weakness, fatigue, headache.
• Anxiety, sleep disorders, drowsiness.
• Chorea (a movement disorder), myoclonus (muscle spasms or contractions).
• Elevated levels of certain liver enzymes (transaminases) observed in blood tests.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of FIRDAPSE

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

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of the month shown.

Do not store above 30°C. Store in the original package to protect from light and moisture.

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

6. Contents of the pack and further information

Composition of FIRDAPSE

• The active substance is amifampridine. Each tablet contains amifampridine phosphate equivalent to 10 mg of amifampridine.

• The other ingredients are microcrystalline cellulose, anhydrous colloidal silica, and calcium stearate.

Appearance of the product and pack contents

White, round, flat on one side and scored on the other side tablet.

The tablets can be divided into two equal halves.

Thermoformed unit dose blisters (aluminum-PVC/PVDC laminated blisters) with 10 tablets.

A carton contains 100 tablets in 10 strips of 10 tablets each.

Marketing authorization holder and manufacturer

Marketing authorization holder:

BioMarin International Limited

Shanbally, Ringaskiddy

County Cork, P43 R298

Ireland

Manufacturers:

EXCELLA GmbH & Co. KG

Nürnberger Strasse 12

90537 Feucht

Germany

BioMarin International Limited

Shanbally, Ringaskiddy, Co. Cork, P43 R298

Ireland

Date of last revision of this leaflet:MM/AAAA

This medicine has been authorized under "exceptional circumstances".

This means that due to the rarity of your disease, it has not been possible to obtain complete information on this medicine.

The European Medicines Agency will review any new information that may become available every year and this leaflet will be updated as necessary.

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.