Epanutin ready Mixed Parenteral 250 mg / 5 ml solution for injection or infusion – patient leaflet, side effects, dosage

1. What Epanutin RMP is and what it is used for

This medicine is a solution for injection or infusion containing phenytoin, which belongs to a group of medicines called antiepileptic drugs.

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

Epanutin RMP can also be used to treat specific heart rhythm problems (cardiac arrhythmias) when these are caused by the drug digoxin, or when these do not respond well to treatment with other medicines, or when other treatments cannot be used.

You should consult your doctor if you are unsure why you have been given Epanutin RMP, if you do not feel better or if you feel worse.

2. What you need to know before you are given Epanutin RMP

Do not take Epanutin RMP

• If you are allergic to phenytoin, or any of the other ingredients of this medicine (listed in section

  6).

• If you are allergic to other medicines for epilepsy.
• If you suffer from certain conditions that affect the heart rhythm for example a decreased heart rate (sinus bradycardia), heart block (sinoatrial block or A-V block) or Adams-Stoke Syndrome. • If you are taking medicines for HIV infection such as delavridine.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before you are given Epanutin RMP if you suffer from or have suffered in the past from any of the following conditions:

• Low blood pressure or heart failure
• Liver disease where the dosage may need to be adjusted
• Kidney disease
• Diabetes
• Porphyria (an inherited disease that affects haemoglobin biosynthesis)
• Heart rhythm problems (Epanutin RMP can treat some rhythm problems, but can make others worse)
• Alcohol dependence.
• If you are of Taiwanese, Japanese, Malaysian or Thai origin and tests have shown that you carry the genetic variant CYP2C9*3.

You should be administered Epanutin RMP with caution if you suffer from kidney or liver problems.

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

Potentially life-threatening skin rashes (Stevens Johnson syndrome, toxic epidermal necrolysis) have been reported with the use of Epanutin, appearing initially as reddish target-like spots or circular patches often with central blisters on the trunk. Additional signs to look for include ulcers in the mouth, throat, nose, genitals and conjunctivitis (red and swollen eyes). These potentially life-threatening skin rashes are often accompanied by flu-like symptoms, including fever at the initiation of treatment. The rash may progress to widespread blistering or peeling of the skin. The highest risk for occurrence of serious skin reactions is within the first weeks of treatment. If you have developed Stevens-Johnson syndrome or toxic epidermal necrolysis with the use of Epanutin, you must not be re-started on Epanutin at any time.

If you develop a rash or these skin symptoms, stop taking Epanutin, seek urgent advice from a doctor and tell him that you are taking this medicine. Consult your doctor before discontinuing Epanutin. If you suddenly stop taking this medicine you may have a seizure.

In the general population, serious skin side effects can rarely occur during treatment with Epanutin; for signs and symptoms of serious skin reactions and what action to take please see section 4. In people of Chinese or Asian origin this risk may be associated with a variant in genes. If you are of such origin and tests have shown that you carry been tested previously carrying this genetic variant (HLA B*1502) discuss this with your doctor before taking Epanutin.

If you are taking phenytoin at the same time as you receive radiation therapy to your head and the dose of another medication called corticosteroids is reduced, you may more likely to develop a severe skin rash called erythema multiform or one that causes blistering called Stevens Johnson Syndrome or Toxic Epidermal Necrosis (see Possible Side Effects in section 4).

Because of the risks of cardiac and local toxicity associated with Epanutin RMP, oral phenytoin should be used whenever possible.

There is a risk of harm to the unborn child if Epanutin is used during pregnancy. Women of childbearing age should use effective contraception during treatment with Epanutin (see Pregnancy, contraception in women, and breast-feeding).

Other medicines and Epanutin RMP

Tell your doctor if you are taking, have recently taken or might take any other medicines including medicines obtained without a prescription.

Some medicines can affect the way Epanutin RMP works, or Epanutin RMP itself can reduce the effectiveness of other medicines taken at the same time. These include (Not all medicines are listed here. Talk with your doctor or pharmacist):

• Medicines used for heart and circulation problems (e.g. dicoumarol, amiodarone, reserpine, digitoxin, digoxin, disopyramide, mexiletine, nisoldipine, furosemide, quinidine, warfarin and calcium channel blockers including diltiazem and nifedipine)
• Medicines used to prevent blood clots, anticoagulants (e.g. apixaban, dabigatran, edoxaban, rivaroxaban, warfarin) and antiplatelets (e.g. ticagrelor)
• Medicines used for epilepsy (e.g. carbamazepine, lamotrigine, phenobarbital, sodium valproate, valproic acid, oxcarbazepine, topiramate, succinimides including ethosuximide, and vigabatrin) • Medicines used to treat fungal infections (e.g. amphotericin B, fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole,miconazole)
• Medicines used for tuberculosis and other infections (e.g. chloramphenicol, isoniazid, rifampicin, sulfonamides, sulfadiazine, sulfamethizole, sulfamethoxazole-trimethoprim, sulfaphenazole, sulfisoxazole, doxycycline, ciprofloxacin)
• Medicines used for stomach ulcers (e.g. omeprazole, sucralfate and the medicines known as H₂ antagonists including cimetidine, ranitidine, famotidine and some antacids) • Medicines used for asthma and bronchitis (e.g. theophylline)
• Medicines used for pain and inflammation (e.g. phenylbutazone, salicylates including aspirin and steroids)
• Medicines used for sleeplessness, depression and psychiatric disorders (e.g. chlordiazepoxide, clozapine, diazepam, disulfiram, fluoxetine, methylphenidate, paroxetine, phenothiazines, quetiapine, trazodone, tricyclic antidepressants, fluvoxamine, sertraline and viloxazine) • Medicines used for diabetes (e.g. tolbutamide)

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

  Pregnancy, contraception in women, and breast-feeding)

• Medicines used for organ and tissue transplants, to prevent rejection (e.g. ciclosporin, tacrolimus) • Medicines used for cancer (e.g. antineoplastic agents including teniposide, fluorouracil, capecitabine, bleomycin, carboplatin, cisplatin, doxorubicin, methotrexate) • Medicines used to lower high blood cholesterol and triglycerides (e.g. atorvastatin, fluvastatin, simvastatin)
• Medicines used in the treatment of HIV infection (e.g. delavirdine, efavirenz, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir)

• Medicines used to expel parasitic worms from the body (e.g. albendazole, praziquantel) • Muscle relaxants used for surgery (neuromuscular blockers), some anaesthetic medicines

  (halothane) and methadone

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

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

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.

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

Epanutin RMP with food, drink and alcohol

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

Pregnancy, contraception in women, and breast-feeding

Pregnancy

Epanutin can cause major birth defects.

Taking phenytoin during pregnancy increases the chance that the baby may have physical birth abnormality.

Studies with women treated with phenytoin for epilepsy during pregnancy have shown that around 6 babies in every 100 will have serious physical birth abnormalities. This compares to 2-3 babies in every 100 born to women who don’t have epilepsy.

The most common types of serious physical birth abnormalities (major congenital malformations) report for phenytoin include abnormalities of the lip and palate, heart, skull, nail and finger disorders and growth abnormalities.

Some of these may occur together as part of a fetal hydantoin syndrome. Your unborn baby should be closely monitored if you have taken Epanutin while pregnant. Epanutin should not be used during pregnancy unless nothing else works for you.

Taking more than one epilepsy medicine at the same time may also increase the risk of physical birth abnormalities. Where possible, your doctor will consider using one epilepsy medicine only to control your epilepsy.

Your doctor may advise you to take folic acid if you’re planning to become pregnancy and while you’re pregnant. Your doctor may adjust your epilepsy medicine when you take folic acid.

Some studies observed that taking phenytoin during pregnancy increases the chance that the baby have problems affecting learning and thinking abilities.

Problems with neurodevelopment (development of the brain) have been reported in babies born to mothers who used phenytoin during pregnancy. Some studies have shown that phenytoin negatively affects neurodevelopment of children exposed to phenytoin in the womb, while other studies have not found such an effect. The possibility of an effect on neurodevelopment cannot be ruled out.

There have been isolated reports of tumours, including tumours affecting nerve tissue, in children whose mothers received phenytoin during pregnancy.

If you take Epanutin during pregnancy, your baby is also at risk for bleeding problems right after birth. Your doctor may give you and your baby a medicine to prevent this. Moreover, your child should be closely monitored.

Contraception in women

If you are of childbearing age, you should discuss your treatment options and effective methods of birth control with your doctor. Epanutin may result in a failure of hormonal contraceptives, hence you should be counselled regarding the use of other effective contraceptive methods. If you are pregnant, consult your doctor promptly. You should not stop taking your medicine until you have discussed this with your doctor. Stopping your medication without consulting your doctor could cause seizures which could be dangerous to you and the pregnancy. Your doctor may decide to change your treatment. Closer monitoring of your unborn child could also be considered.

Breast-feeding

Epanutin passes into breast milk. You should not take Epanutin if you are breast-feeding.

Driving and using machines

Epanutin RMP may cause dizziness or drowsiness, therefore do not drive or use any tools or machines until instructed by the doctor.

Epanutin RMP contains ethanol, propylene glycol and sodium

This medicine contains 400.0mg of alcohol (ethanol, 96%) in each 5 mL solution which is equivalent to 10%. The amount in 5 mL of this medicine is equivalent to 11 mL beer or 4.5 mL wine.

The amount of alcohol in this medicine is not likely to have an effect in adults and adolescents, and its effects in children are not likely to be noticeable. It may have some effects in younger children, for example feeling sleepy.

The alcohol in this medicine may alter the effects of other medicines. Talk to your doctor or pharmacist if you are taking other medicines.

If you are pregnant or breast-feeding, talk to your doctor or pharmacist before taking this medicine.

If you are addicted to alcohol, talk to your doctor or pharmacist before taking this medicine

This medicinal product also contains 2.072 g propylene glycol in each 5 mL solution of phenytoin, which is equivalent to 414.0 mg of propylene glycol per mL.

If your child is less than 5 years old, talk to your doctor or pharmacist before giving them this medicine, in particular if they are being given other medicines that contain propylene glycol or alcohol.

If you are pregnant or breast-feeding, do not take this medicine unless recommended by your doctor. Your doctor may carry out extra checks while you are taking this medicine.

If you suffer from liver or kidney disease, do not take this medicine unless recommended by your doctor. Your doctor may carry out extra checks if you need to receive Epanutin for more than 24 hours.

Propylene glycol in this medicine can have the same effects as drinking alcohol and increase the likelihood of side effects.

Use this medicine only if recommended by a doctor. Your doctor may carry out extra checks while you are taking this medicine.

This medicine contains less than 1 mmol sodium (23mg) per 5 mL solution, this is to say essentially ‘sodium-free’.

3. How Epanutin RMP is given

You will be in hospital when you are given Epanutin RMP.

Epanutin RMP will be either injected into one of your large veins (intravenously) or into your muscle (intramuscularly). When given as an intravenous infusion, Epanutin RMP must be diluted with normal saline. Intramuscular or intravenous Epanutin RMP should not be added to dextrose or dextrose-containing solutions as this could interfere with the dose of this medicine.

.

The dose and concentration of the solution of Epanutin RMP 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 (drip).

Your doctor may take samples of your blood to see how much phenytoin is in the blood and help decide the right maintenance dose for you.

Sometimes it is necessary to give Epanutin RMP into your muscle if you cannot continue to take it by mouth. This is not normally continued for longer than one week. When switching from oral Epanutin to intramuscular injection, the dose needs to be increased by approximately 50%. When switching back to oral Epanutin, the dose should be reduced to half the original oral dose for the same period of time that the intramuscular injection was given. This is because phenytoin continues to be released from your muscles for sometime after the injections have been given.

The recommended dose is as follows:

Adults

Severe epileptic seizure or fits (Status Epilepticus)

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

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

Cardiac arrhythmias (variations to normal heartbeat)

A dose of 3.5 to 5 mg per kg of body weight is given intravenously, at a rate not exceeding 50 mg/min. This may be repeated a second time.

Neurosurgery

A dose of 100 to 200 mg may be given into your muscle (intramuscularly) approximately every 4 hours during surgery and for two to three days afterwards to prevent seizures. This dosage may then be reduced to a maintenance dose of 300 mg daily and adjusted according to your blood levels.

Elderly

Lower or less frequent dosing may be needed in some elderly patients due to decreased clearance of Epanutin RMP. Your doctor may not need to change your dose, but side effects can occur more often in the elderly.

Kidney or liver problems

Make sure your doctor knows if you have liver or kidney problems as you may need your dose adjusted.

Use in neonates (very young babies), babies, children and adolescents

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. The drug should be injected slowly intravenously at a rate of 1 to 3 mg/kg/minute or 50 mg/min, whichever is slower.

Severe epileptic seizure or fits (Status Epilepticus)

The starting dose is usually 15 to 20 mg per kg of body weight.

The recommended initial maintenance dose of Epanutin is 2 to 4 mg/kg and should be given 12 hours after the starting dose and then continued every 12 hours (4 to 8 mg/kg/day).

Your doctor will inject the drug slowly intravenously for the starting dose at a rate of 1-3 mg/kg/min not exceeding 50 mg/min, whichever is slower and for the maintenance dose at a rate of 1-2 mg/kg/min not exceeding 50 mg/min, whichever is slower to minimise the risks of low blood pressure and heart rhythm problems.

For directions of proper use of medicine intended for healthcare professionals, please refer to section 6 of this PIL

If you are given more Epanutin RMP than you should

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

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

4. Possible side effects

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

Tell your doctor immediately if you experience any of the following symptoms after being given this medicine.

• Sudden wheeziness, difficulty in breathing, swelling of eyelids, face or lips, rash or itching

  (especially affecting the whole body). There is a higher incidence of this in black patients. • 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.

• If you develop potentially life-threatening skin rashes that causes blistering (this can affect the mouth and tongue). These may be signs of a condition known as Stevens Johnson Syndrome, or toxic epidermal necrolysis (TEN). These have been reported very rarely. • If you notice bruising, fever, you are looking pale or you have a severe sore throat. These may be the first signs of an abnormality of the blood, including decreases in the number of red blood cells, white cells or platelets. Your doctor may take regular blood samples to test for these effects.
• 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), you may also experience pain and inflammation of the joints, these may be signs of a hypersensitivity reaction (e.g. drug reaction or rash with Eosinophilia and Systemic Symptoms (DRESS)) or be related to a condition called systemic lupus erythematosus (SLE).
• Areas of red skin with small elevated sterile pustules (small blisters filled with white/yellow fluid). There tends to be more disease in skin folds. Swelling of the face can occur as well (Acute Generalized Exanthematous Pustulosis (AGEP)).
• If you experience confusion or have a severe mental illness, as this may be a sign that you have high amounts of phenytoin in your blood. On rare occassions, when the amount of the 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.

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, pins and needles or numbness, drowsiness, dizziness, vertigo, sleeplessness, nervousness, twitching muscles, headaches and change in taste.
• Effects on your skin: life-threatening skin rashes that causes blistering (this can affect the mouth and tongue), skin rash including measles-like rash which is usually mild, hives. • Effects on your stomach and intestines: Feeling sick, being sick and constipation. • Effects on your blood and lymph system: swelling of the lymph glands, a decrease in the number of a type of red blood cell (pure red cell aplasia).
• Effects on your liver and kidney: inflammation of the kidneys and liver, liver damage or liver failure which can lead to death (seen as yellowing of the skin and whites of the eye). • Effects on your reproductive system and breasts: changes in the shape of the penis, painful erection.
• Effects on your hands, face and body: 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.
• Effects on medical tests: Increased levels of blood sugar, or decreased levels of blood calcium, phosphates, folic acid and vitamin D. Taking Phenytoin may cause abnormal thyroid test results. • Effects on your respiratory system: problems breathing including complete stopping of breathing, inflammation of the lining of the lung.
• Effects on your immune system: problems with the body’s defence against infection, inflammation of the wall of the arteries and immunoglobin abnormalities.
• Effect on your heart and circulation: low blood pressure, enlargement of blood vessels. Your blood pressure may also be lowered and experience heart problems when Epanutin is injected into your vein too quickly.
• Effects on your bones: There have been reports of bone disorders including osteopenia and osteoporosis (thinning of the bone) and fractures. Check with your doctor or pharmacist if you are on long-term antiepileptic medication, have a history of osteoporosis, or take steroids. • Effects on injection site: Intramuscular phenytoin administration may cause pain, dying or sloughing of skin cells, and formation of an infection at the injection site.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard 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 Epanutin RMP

The storage of Epanutin RMP will not be your responsibility.

The pharmacist will ensure that your medicine is kept out of the sight and reach of children.

The pharmacist will ensure that your medicine is not stored above 25°C, and not used after the expiry date which is stamped on the pack after EXP. The expiry date refers to the last day of that month. The pharmacist will also ensure that Epanutin RMP is kept in the original package.

Do not throw away any medicine via wastewater. The pharmacist or nurse will throw away any medicine you no longer use. These measures will help protect the environment.

Epanutin RMP is for single use only. Any unused solution should be discarded immediately after initial use.

6. Contents of the pack and other information

What Epanutin RMP 250 mg/5 ml Solution for injection or infusion contains

Each 5 ml ampoule contains 250 mg of the active ingredient phenytoin sodium i.e. 50 mg/ml.

The other ingredients are propylene glycol, ethanol (alcohol), sodium hydroxide and water for injection.

What Epanutin RMP looks like and contents of the pack

Epanutin RMP 250 mg/5 ml Solution is available in packs containing 10 ampoules.

Marketing Authorisation Holder

Viatris Products Limited,

Station Close,

Potters Bar,

EN6 1TL,

United Kingdom.

Manufacturer

Actavis Italy S.p.A.

Viale Pasteur 10

20014 Nerviano (Milan)

ITALY

This leaflet last revised in 12/2025.

The following information is intended for healthcare professionals only.

Directions for proper use of medicine (refer to section 3 of this PIL and section 4.2 Posology and method of administration of the SmPC).

For parenteral administration

Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit. Parenteral Epanutin is suitable for use as long as it remains free of haziness and precipitate. Upon refrigeration or freezing a precipitate might form; this will dissolve again after the solution is allowed to stand at room temperature. The product is still suitable for use. Only a clear solution should be used. A faint yellow colouration may develop; however, this has no effect on the potency of this solution.

Because of the risk of local toxicity, intravenous phenytoin should be injected slowly directly into a large peripheral or central vein through a large-gauge needle or intravenous catheter.

Each injection or infusion of intravenous Epanutin should be preceded and followed by an injection of sterile saline through the same needle or catheter to avoid local venous irritation due to alkalinity of the solution.

Rapid infusion may be associated with adverse cardiovascular events (refer to section 2 of this PIL)

Parenteral Epanutin should neither be mixed with other drugs nor be added to dextrose or dextrose-containing solutions due to the potential for precipitation of phenytoin acid.

Instructions for dilution

For infusion administration the parenteral phenytoin should be diluted in 50 - 100 ml of normal saline, with the final concentration of phenytoin in the solution not exceeding 10 mg/ml. Administration should commence immediately after the mixture has been prepared and must be completed within one hour (the infusion mixture should not be refrigerated). An in-line filter (0.22 - 0.50 microns) should be used.

The diluted form is suitable for use as long as it remains free of haziness and precipitate.