Document: leaflet MAH BRAND_PL 00057-0551 change

• HEALTHCARE PROFESSIONAL TECHNICAL LEAFLET_PL 00057-0551
• leaflet MAH BRAND_PL 00057-0551

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PACKAGE LEAFLET: INFORMATION FOR THE USER

UNITED KINGDOM / IRELAND

49 Pro-Epanutin™ 75 mg/ml

Concentrate for Solution for Infusion/Solution for Injection

(fosphenytoin sodium)

1. What Pro-Epanutin is and what it is used for

Pro-Epanutin is one of a group of medicines called anti-epileptic drugs; these medicines are used to treat epilepsy.

Pro-Epanutin is used to treat severe epileptic seizure or fits (status epilepticus). It can also be used to control or prevent seizures during or after brain surgery and/or severe head injury. Pro-Epanutin is also used to control or prevent seizures for short periods of time when antiepileptic drugs cannot be taken by mouth.

You should consult your doctor if you are unsure why you have been given Pro-Epanutin.

2. Before you are given Pro-Epanutin

Do not take Pro-Epanutin

•    If you are allergic (hypersensitive) to fosphenytoin sodium, phenytoin or any of the other ingredients of Pro-Epanutin.

•    If you suffer from a condition affecting your heart rhythm.

•    If you suffer from a disorder of red blood cell formation (acute intermittent porphyria).

•    If you are taking delavirdine, an antiviral medicine used to treat human immunodeficiency virus (HIV) infection.

Take special care with Pro-Epanutin

A small number of people being treated with anti-epileptics such as fosphenytoin have had thoughts of harming or killing themselves. If at any time you have these thoughts, immediately contact your doctor.

Serious skin side effects can rarely occur during treatment with Pro-Epanutin. This risk may be associated with a variant in genes in a subject with Chinese origin.

If you are of such origin and have been tested previously carrying this genetic variant (HLA-B*1502), discuss this with your doctor before taking Pro-Epanutin.

Medicines are not always suitable for everyone. Your doctor needs to know before you take Pro-Epanutin if you suffer from or have suffered in the past from any of the following conditions:

•    Liver disease.

•    Heart disease or stroke.

•    Low blood pressure or heart failure.

•    Kidney disease.

•    Low protein (albumin) in your blood.

•    Diabetes.

•    Special diet which restricts your phosphate intake.

Taking other medicines

Some medicines can affect the way Pro-Epanutin works, or Pro-Epanutin itself can reduce the effectiveness of other medicines taken at the same time. These include:

•    Medicines used for heart and circulation problems (felbamate, digoxin, amiodarone, furosemide, quinidine, warfarin, diazoxide, atorvastatin, fluvastatin, simvastatin, mexiletine and calcium channel blockers e.g. diltiazem, nisoldipine, nifedipine, nicardipine, nimodipine and verapamil).

•    Medicines used for epilepsy (carbamazepine, lamotrigine, oxcarbazepine, phenobarbital, sodium valproate, topiramate and valproic acid, succinimides e.g. ethosuximide and vigabatrin).

•    Medicines used to treat fungal infections (amphotericin B, fluconazole, itraconazole, ketoconazole, miconazole, posaconazole and voriconazole).

•    Medicines used to treat human immunodeficiency virus (HIV) infection (delavirdine, efavirenz, fosamprenavir, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir and saquinavir).

•    Medicines used for tuberculosis and other infections (albendazole, chloramphenicol, isoniazid, rifampicin, praziquantel, erythromycin, doxycycline, ciprofloxacin, tetracycline and sulphonamides e.g sulfaphenazole, sulfadiazine, sulfamethizole and sulfamethoxazole-trimethoprim).

•    Medicines used for stomach ulcers (omeprazole, the medicines known as H2 antagonists e.g. cimetidine, ranitidine, famotidine and some antacids).

•    Medicines used for asthma and bronchitis (theophylline).

•    Medicines used for pain and inflammation (phenylbutazone, salicylates e.g. azapropazone, ticlopidine, aspirin and steroids).

•    Medicines used for sleeplessness, depression and psychiatric disorders (chlordiazepoxide, clozapine, diazepam, disulfiram, fluoxetine, fluvoxamine, sertraline, methadone, methylphenidate, paroxetine, phenothiazines, quetiapine, trazodone, St John's Wort, tricyclic antidepressants and viloxazine).

•    Medicines used for diabetes (tolbutamide, chlorpropamide, glibenclamide).

•    Some hormone replacement therapies (oestrogens), oral contraceptives (the birth control pill).

•    Medicines used for organ and tissue transplants, to prevent rejection (ciclosporin, tacrolimus), corticosteroids.

•    Medicines used for cancer (antineoplastic agents e.g. bleomycin, capecitabine, carboplatin, cisplatin, doxorubicin, methotrexate and teniposide).

•    Muscle relaxants used for surgery (neuromuscular blockers e.g. cisatracurium, pancuronium, rocuronium and vecuronium), some anaesthetic medicines (halothane).

•    Some products available without a prescription (folic acid, theophylline, vitamin D).

Your doctor may need to test the amount of phenytoin in your blood to help decide if any of these medicines are affecting your treatment.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

The herbal preparation St John's wort (Hypericum perforatum) should not be taken at the same time as this medicine. If

you already take St John's wort, consult your doctor before stopping the St John's wort preparation.

Pro-Epanutin may also interfere with certain laboratory tests that you may be given.

Drinking Alcohol with Pro-Epanutin

Drinking a lot of alcohol can also affect the concentration of fosphenytoin in your blood.

Pregnancy and Breast-feeding

If you think you might be pregnant, or are planning to get pregnant, tell your doctor before you take Pro-Epanutin.

You should not take Pro-Epanutin if you are breast-feeding.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Pro-Epanutin may cause dizziness or drowsiness, especially during the first few weeks of treatment. If you experience these symptoms, do not drive or use any tools or machinery.

3. How Pro-Epanutin is given

You will be in hospital when you are given Pro-Epanutin. Pro-Epanutin will be either injected into one of your large veins (intravenously) or into your muscle (intramuscularly). When given intravenously, Pro-Epanutin must be diluted.

The dose and concentration of the solution of Pro-Epanutin you are given will be decided by your doctor and will be written as the equivalent dose of phenytoin sodium (PE). The dose will be as mg per dose if given as an injection or mg per ml of solution if given as an infusion.

Adults

Severe epileptic seizure or fits (Status epilepticus)

Pro-Epanutin is usually given after treatment with either diazepam or lorazepam injection.

The usual first dose (loading dose) of Pro-Epanutin to treat severe or continuous seizures (status epilepticus) is 15 mg PE per kilogram of your body weight injected into your vein (this is called a loading dose). This is followed by more doses of Pro-Epanutin given into your vein or into your muscle or by doses of phenytoin given by mouth (these are called maintenance doses).

If Pro-Epanutin does not stop your seizures, other treatments will be tried.

Brain surgery or head trauma

If your seizures are less severe or Pro-Epanutin is used to treat or prevent seizures occurring during or following brain surgery or trauma to the head, the usual first dose (loading dose) of Pro-Epanutin may be between 10 and 15 mg PE per kilogram of your body weight. This may be injected either into your vein or into your muscle. This is followed by more doses (these are called maintenance doses) of Pro-Epanutin given into your vein or into your muscle or by doses of phenytoin given by mouth.

Maintenance doses

The usual maintenance dose of Pro-Epanutin is 4 to 5 mg PE per kilogram of your body weight per day. Your doctor may take a sample of your blood to help decide the right dose for you.

If your doctor decides that you need to continue treatment, you will be transferred to treatment by mouth as soon as possible. This will be with phenytoin because Pro-Epanutin cannot be taken by mouth.

Replacement of oral phenytoin treatment

If you are given Pro-Epanutin because you cannot take phenytoin by mouth, you will not need a loading dose and the dose you are given will be the same as your dose of phenytoin. Because the dose of Pro-Epanutin is given in PE (phenytoin sodium equivalents), the number of mg PE of Pro-Epanutin you are given should be the same as the number of mg of phenytoin sodium you take by mouth.

Children

The doses of Pro-Epanutin per kilogram of body weight are the same for children as for adults.

Pro-Epanutin is given to children by a drip (infusion) into the vein (intravenous) only.

Elderly patients over 65 years, the very ill and patients with kidney or liver disease.

The dose of Pro-Epanutin may be reduced or the injection given into the vein at a slower rate.

Always take Pro-Epanutin exactly as your doctor has told you. You should check with your doctor or pharmacist if you are still not sure.

If you are given more Pro-Epanutin than you should

Pro-Epanutin is dangerous in overdose. If you think you have been given too much Pro-Epanutin, contact your doctor immediately.

If you have any further questions on how to take this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Pro-Epanutin can cause side effects,

although not everybody gets them.

Tell your doctor immediately if you experience any of the

following symptoms after taking this medicine. Although they

may be rare, these symptoms can be serious.

•    If you develop a severe skin rash that may cause blistering, (this can affect the mouth and tongue). These may be signs of a condition known as Erythema multiforme, Stevens Johnson Syndrome, or toxic epidermal necrolysis (TEN).

Your doctor will stop your treatment in these cases.

•    If you notice bruising, fever, you are looking pale or a severe sore throat. These may be the first signs of an abnormality of the blood, including decreases in the number of red cells, white cells or platelets. Your doctor may take regular blood samples to test for these effects.

•    Skin rash and fever with swollen glands, yellow skin and eyes, particularly in the first two months of treatment, as these may be signs of a hypersensitivity reaction. If these are severe and you also experience pain and inflammation of the joints this could be related to a condition called systemic lupus erythematosus.

•    If you experience skin discolouration, swelling and pain where the injection was given which then starts to spread down your arm to your hands and fingers. This may mean you have a condition known as “purple glove syndrome”. In most cases this will improve on its own but in some cases it can be serious and require urgent medical treatment.

•    Skin rash, fever, swollen glands, increase in a type of white blood cell (eosinophilia), and inflammation of internal organs (liver, lungs, heart, kidneys and large intestine), as they may be signs of a hypersensitivity reaction.

•    If you experience a state of confusion or severe mental illness, as this may be a sign that you have high amounts of phenytoin in your blood. On rare occasions, when the amount of phenytoin in the blood remains high, irreversible brain injury has occurred. Your doctor may test your blood to see how much phenytoin is in the blood and may change your dose.

•    Sudden wheeziness, difficulty in breathing, swelling of eyelids, face or lips, rash or itching (especially affecting the whole body) as this may be a sign of a hypersensitivity reaction.

Other side-effects that may occur are:

•    Effects on your nervous system: Unusual eye movements, unsteadiness, difficulty in controlling movements, shaking, abnormal or uncoordinated movements, slurred speech, confusion, loss of sensation in the tongue, pins and needles or numbness, drowsiness, dizziness, vertigo, sleeplessness, nervousness, twitching muscles, headaches, convulsions, abnormal/irrational thoughts, mood swings.

•    Effects on your skin: skin rash including measles-like reactions which are mild.

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You will find more about PRO-EPANUTIN on the back of this leaflet

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