Patient Information Leaflet

Epanutin™ Ready Mixed Parenteral 250mg/5ml Solution for Injection or Infusion
Phenytoin sodium

Please read this leaflet carefully. It contains important information about your treatment. If you have any questions, or if you are not sure about anything, ask your doctor or pharmacist.

What is in the pack?

The name of your medicine is Epanutin Ready Mixed Parenteral 250mg/5ml Solution for Injection or Infusion. It comes in a small glass bottle (ampoule). Each 5ml ampoule contains 250mg of the active ingredient Phenytoin sodium, i.e. 50 mg/ml. The medicine also contains the other ingredients propylene glycol, ethanol (alcohol), sodium hydroxide and water for injection.

Each pack contains 10 ampoules.

What is Epanutin Ready Mixed Parenteral?

Epanutin Ready Mixed Parenteral is one of the group of medicines known as antiepileptic drugs. When given by injection it can also be used to treat rhythm problems of the heart.

What is Epanutin Ready Mixed Parenteral used for?

Epanutin Ready Mixed Parenteral is used to treat severe epileptic seizures or fits (status epilepticus). It is also used to treat and prevent seizures for short periods of time when antiepileptic drugs cannot be taken by mouth. It can be used to treat certain, very specific, changes in the rhythm of the heart (cardiac arrhythmias), particularly when these are caused by the drug digoxin.

Epanutin can also be used to control or prevent seizures during or after brain surgery and/or severe head injury.

Before using Epanutin Ready Mixed Parenteral

You may have been given Epanutin Ready Mixed Parenteral as a single dose to control status epilepticus. In this case, you will only be able to read this leaflet after you have had the product given to you. The questions below will have been considered by your doctor before you were given Epanutin Ready Mixed Parenteral, but the urgent need for treatment may have been more important than some of the normal cautions. Check them now, especially if you are going to continue to be given Epanutin Ready Mixed Parenteral (or any other form of the active ingredient, Phenytoin).

• Are you pregnant, trying to become pregnant, or breast-feeding?
• Have you ever had a reaction to phenytoin, phenytoin sodium, Epanutin Ready Mixed Parenteral or any of its ingredients, or any other Epanutin preparation?
• Are you taking any other medicines? There is a list of medicines which Epanutin Ready Mixed Parenteral interacts with in the next section.
• Do you have a heart condition? (Epanutin Ready Mixed Parenteral can be used to treat some cardiac arrhythmias, but may make some worse.)
• Do you have low blood pressure or heart failure?
• Do you drink large amounts of alcohol?
• Do you suffer from liver disease?
• Do you have porphyria (an inherited disease that affects haemoglobin biosynthesis)? Your doctor will tell you if you suffer from this.

If you answer YES to any of these questions talk to your doctor at once.

A number of the ingredients in this product (other than the active ingredient phenytoin) are known to have certain effects:

• propylene glycol, which may cause alcohol-like symptoms
• sodium, this medicine contains up to 1.1mmol sodium (24.6mg) per 5ml ampoule. This should be considered if you are on a controlled-sodium diet.
• This medicine contains 8.8% ethanol (alcohol), ie 440.4mg per 5ml ampoule, which is equivalent to around 8.8ml beer or 3.7ml wine. It may be harmful if you suffer from alcoholism and should be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease.

Can you take Epanutin Ready Mixed Parenteral with other medicines?

Epanutin sometimes affects the action of other medicines and sometimes Epanutin is affected by other medicines. Always tell your pharmacist you have taken Epanutin when you buy medicines at the chemist. If you require an operation or visit your dentist or doctor let them know that you have received Epanutin Ready Mixed Parenteral.

 

Epanutin may interact with other medicines used to treat:

• epilepsy (carbamazepine, lamotrigine, phenobarbital, sodium valproate, valproic acid, succinimides e.g. ethosuximide, and vigabatrin)
• fungal infections (e.g. amphotericin B, fluconazole, itraconazole, ketoconazole and miconazole)
• tuberculosis and other infections (chloramphenicol, isoniazid, rifampicin, sulphonamides, doxycycline and ciprofloxacin)
• asthma and bronchitis (theophylline)
• pain and inflammation (phenylbutazone, salicylates and steroids)
• stomach ulcers (omeprazole, sucralfate and the medicines known as H2 antagonists e.g. cimetidine, ranitidine, famotidine and some antacids)
• sleeplessness, depression and psychiatric disorders (chlordiazepoxide, clozapine, diazepam, disulfiram, fluoxetine, methylphenidate, paroxetine, phenothiazines, trazodone, tricyclic antidepressants and viloxazine)
• cancer (antineoplastic agents)
• organ and tissue transplants, to prevent rejection (ciclosporin)
• heart and circulation problems (dicoumarol, amiodarone, reserpine, digitoxin, furosemide, quinidine, warfarin and calcium channel blockers e.g. diltiazem and nifedipine.)
• diabetes (tolbutamide)
• The active ingredient, phenytoin may also interact with some hormone replacement therapies (oestrogens), oral contraceptives (the birth control pill), the anaesthetic agent, halothane, muscle relaxants used for surgery (neuromuscular blockers), methadone and some products available without a prescription (folic acid, antacids, theophylline, vitamin D, salicylates e.g. aspirin)

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.

If you are taking any of these medicines, tell your doctor or pharmacist. Your doctor may test your blood to see if any medicines you take are affected by or affect Epanutin Ready Mixed Parenteral.

Epanutin Ready Mixed Parenteral may also interfere with certain laboratory tests that you may be given.

Drinking a lot of alcohol can affect the concentrations of Phenytoin (the active ingredient of Epanutin Ready Mixed Parenteral) in your blood.

How Epanutin Ready Mixed Parenteral is given

You will be in hospital when you are given this medicine.

A diluted solution will be injected into one of your large veins (intravenously) or into your muscle (intramuscularly).

When injected into your vein it is given slowly at a rate less than 50mg per minute. Heart rhythm, breathing and blood pressure are carefully monitored. A concentration of between 10 and 20mg/litre is usually thought to be best for Epanutin to work properly.

Sometimes Epanutin Ready Mixed Parenteral is injected as a solution over a period of time (this is an infusion), diluted in 50-100ml of saline. The concentration of phenytoin in the solution should not be greater than 10mg/ml.

Intramuscular injection is sometimes necessary if you cannot continue to take Epanutin by mouth. Epanutin is not normally used intramuscularly for longer than a week. When switching from oral Epanutin to intramuscular injection, the dose needs to be increased approximately by a half. When switching back to oral Epanutin, the dose should be reduced to half the original oral dose for the same amount of time that the intramuscular injections were given. This is because phenytoin continues to be released by your muscles for sometime after the injections have been given.

Status Epilepticus:

A dose of 10 to 15mg per kg of body weight is given intravenously at a rate not exceeding 50mg per minute in adults. This is followed by more Epanutin given every 6 to 8 hours either by injection or by mouth.

Other treatments are often tried before Epanutin Ready Mixed Parenteral. If none of these stop the seizure and Epanutin does not work, other treatments will be tried.

The intramuscular route is not recommended for the treatment status epilepticus because not enough of the medicine gets into the blood quickly enough.

Cardiac arrhythmias (variations to normal heartbeat):

An intravenous injection is given at a dose based on body weight (usually 3.5 to 5mg per kg of body weight). This may be repeated a second time.

Neurosurgery:

Intramuscular injections of Epanutin Ready Mixed Parenteral may be given approximately every four hours during neurosurgery and for two or three days afterwards. The dose may be reduced and adjusted according to your blood levels.

Elderly (over 65 years):

Your doctor will not need to change your dose, but side effects may occur more often in elderly people.

Children:

No dosage adjustment is required, but children tend to breakdown the medicine faster than adults and this may mean that your doctor has to change the number or timing of the Epanutin doses.

Neonates (Very young babies):

Intravenous Epanutin should not be given to neonates at a rate faster than 1 to 3mg per kg body weight per minute. The starting dose is usually 15 to 20mg per kg of baby weight.

Intravenous Epanutin is more reliably absorbed than oral Epanutin in very young babies.

Side-effects

Epanutin Ready Mixed Parenteral may cause irritation at the site where it is injected, especially if it escapes from a vein into surrounding tissue. This irritation may be minor or more serious. If you experience this tell your doctor immediately.

When given too quickly by intravenous injection, blood pressure may be reduced and a severe reaction involving the heart, blood vessels and central nervous system may occur. Rarely, this has resulted in death, especially in old or in very ill patients.

As with all medicines, side-effects are reported with the use of Epanutin Ready Mixed Parenteral. These might be:

• Effects related to the action of phenytoin, the active ingredient of Epanutin Ready Mixed Parenteral, on the central nervous system (brain). These include: unusual eye movements, unsteadiness, difficulty in controlling movements, shaking, abnormal or uncoordinated movements, slurred speech, confusion, pins and needles or numbness, drowsiness, dizziness or vertigo (dizziness in high places), sleeplessness, nervousness, twitching muscles, headaches, loss of feeling in the hands or feet.

• Some of the above side-effects may also occur when the concentration of phenytoin in your blood is too high.
• When extremely high amounts of phenytoin are in the blood, extreme confusion sometimes referred to as delirium, psychosis or encephalopathy (a brain disease) has been reported. On rare occasions, when the amount of phenytoin in the blood has remained high for a long time, irreversible brain injury has occurred. Your doctor may test your blood to see how much phenytoin is in it and change any future doses of Epanutin Ready Mixed Parenteral.
• If you are elderly, or have kidney or liver disease you may experience these side-effects at lower doses of Epanutin than otherwise.

• Skin rash or itchiness - many sorts of skin rash have been reported with the use of Epanutin Ready Mixed Parenteral. Some are minor (for example, measles-like or mild dermatitis) but others, although rare, are more serious such as Stevens Johnson Syndrome, or toxic epidermal necrolysis (TEN), which causes blistering and can affect the mouth and tongue. Rash may also be a first sign of other side-effects of Epanutin. If you get a rash, your doctor may stop giving you Epanutin until it clears up. If the rash recurs, does not clear up or a serious reaction is suspected, your doctor may advise you not to take Epanutin or phenytoin again.
• Hypersensitivity reaction or syndrome. Fever, skin rash, swollen glands may occur, usually within the first two months of treatment. Changes in liver function, increased numbers of white blood cells and joint pains may occur as part of this syndrome.

• Inflammation in various parts of your body including the joints, skin and kidneys, a condition known as systemic lupus erythematosus, may occur on rare occasions. A rash may be the first sign of this condition, but it may also be noticed as fever, pain in the joints and general ill health.
• Inflammation of the walls of the arteries and problems with the body's defence against infection (the immune system) have also been seen.
• Although still rare, you may be more likely to get this syndrome, skin rash or liver damage, if you are black.

• Swelling of the lymph glands (a part of your body's natural defence system) and other disorders of the lymph glands may occur. This may be accompanied by fever or rash and may affect your liver as described above, as a hypersensitivity reaction, but may also be a sign of a problem with your lymph glands.
• Abnormalities of the blood including decreases in the number of red cells, white cells or platelets (parts of the blood which helps it to clot). The first signs you might notice could be bruising, fever, pallor or sore throat. Your doctor may take regular blood samples to test for this.
• Hepatitis (inflammation of the liver) or liver damage which may be recognised by yellowing of the skin and whites of the eyes and changes in liver function.
• Nausea, vomiting, constipation.
• Inflammation of the kidneys.
• Breathing problems, mainly inflammation of the lining of the lung.
• Rare side-effects have included: changes in the hands with difficulty in straightening the fingers, changes in facial features, enlarged lips or gums, increased or abnormal body or facial hair, changes in the shape of the penis and painful erection, a condition affecting your joints known as polyarthropathy.
• Increased levels of blood sugar, or decreased levels of blood calcium or folic acid.
• Epanutin Ready Mixed Parenteral may alter the amount of vitamin D in your body. If you also do not get enough vitamin D in your diet or from exposure to sunlight, you may suffer from bone pain or fractures. Rickets (abnormal development of bone) may occur if this effect is prolonged.

Do not be alarmed by this list - most people take Epanutin without any problems.

If you get any of these, or any other problems, tell your doctor or pharmacist straight away and continue to take your medicine.

How to store Epanutin Ready Mixed Parenteral

• The storage of Epanutin Ready Mixed Parenteral will not be your responsibility. However, it should not be stored above 25°C, and the ampoule should be kept in the outer carton.
• The product should be kept out of the reach and sight of children
• This medicine should not be used after the last day of the month shown in the expiry date. This will be printed on the carton and on the ampoule label.