Leaflet: information for the user

Epanutin 100 mg hard capsules

Fenitoína sódica

Read this leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What Epanutin is and what it is used for

2. What you need to know before you start taking Epanutin

3. How to take Epanutin

4. Possible side effects

5. Storage of Epanutin

6. Contents of the pack and additional information

Epanutin contains the active ingredient phenytoin.

Phenytoin belongs to a group of medicines called antiepileptics, which are used to treat epilepsy. Specifically, Epanutin is indicated for the treatment of the following types of epilepsy: generalized tonic-clonic seizures (grand mal seizure), complex partial seizures, as well as for the treatment and prevention of seizures in neurosurgery.

Do not take Epanutin

• if you are allergic to phenytoin or any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to medicines of the hydantoin type.
• if you are taking a medicine for the treatment of HIV infection called delavirdine

Warnings and precautions

Consult your doctor or pharmacist before starting to take Epanutin

• if you have liver or kidney disease, or other serious diseases, or if you are an elderly patient. If during treatment you notice symptoms suggestive of hepatitis, such as jaundice (yellowing of the skin and the white of the eyes), you must consult your doctor immediately,
• if you have porphyria,
• if you are diabetic, as phenytoin may raise blood glucose levels,
• if you consume large amounts of alcohol or drink it in small amounts but regularly,
• if you are undergoing radiation therapy to the brain or are reducing your treatment with corticosteroids,
• if you are of Taiwanese, Japanese, Malay or Thai origin and tests have shown that you are a carrier of the CYP2C9*3 mutation,
• if you are black, have a depressed immune system, or have a family history or have had in the past a hypersensitivity syndrome (HSS) or drug eruption with eosinophilia and systemic symptoms (DRESS) (a syndrome that usually presents with fever, skin rash, lymph node swelling and other organ involvement, such as the liver, kidneys, heart, lungs and blood abnormalities), as you have a higher risk of developing this syndrome. If during treatment you present with fever, skin rash with lymph node swelling, which may be signs of drug hypersensitivity, you must consult your doctor immediately,
• cases of heart problems, such as bradycardia (abnormally slow heart rate) and asystole (heart stoppage), have been described, commonly associated with phenytoin toxicity. If during treatment you suffer from these symptoms, you must consult your doctor immediately,
• cases of life-threatening skin eruptions (such as Stevens-Johnson syndrome and toxic epidermal necrolysis) have been described with the use of Epanutin. Severe skin effects occur rarely during phenytoin treatment. Initially, they appear as red, circular spots with a central blister. Other additional signs that may appear are mouth, throat, nose, genital and conjunctivitis (swollen and red eyes) lesions. These life-threatening skin eruptions, often accompanied by flu-like symptoms, may be associated with a genetic variant in some subjects of Taiwanese or Chinese origin. If you are of this ancestry and have previously been tested and know that you have the genetic variant (HLA-B*1502), talk to your doctor before taking phenytoin.Ifyou develop these skin eruptions or symptoms, go to a doctor immediately and inform them that you are taking this medicine.Consult your doctor before stopping treatment with Epanutin,
• if during treatment you suffer from confusion (such as delirium, psychosis, etc.), which may be a sign of excessive phenytoin levels in the blood, you must consult your doctor immediately,
• a small number of people treated with antiepileptic drugs such as Epanutinhave had thoughts of self-harm or suicide. If at any time you experience these thoughts, contact your doctor as soon as possible.
• there is a risk of fetal damage if Epanutin is used during pregnancy. Women of childbearing age should use effective contraceptive methods during Epanutin treatment (see “Pregnancy and lactation”).

During Epanutin treatment, it is essential to maintain good oral hygiene. This will help prevent the occurrence of adverse effects in the oral area, such as gum thickening.

It is very important that your doctor monitors your treatment at regular visits and performs regular blood tests to rule out the occurrence of blood abnormalities, monitor liver function, and in some cases, control the Epanutin dose.

Cases of facial, mouth (lips, gums, tongue) and neck swelling that may lead to life-threatening respiratory difficulties have been reported in people receiving phenytoin treatment. If at any time you experience these signs or symptoms, contact your doctor immediately.

Interaction with laboratory tests:

Epanutin may interfere with certain laboratory tests that you undergo.

Phenytoin may reduce serum levels of iodine-bound proteins. It may also produce lower-than-normal test results for dexamethasone or metirapone. Phenytoin may produce increased blood glucose levels or serum concentrations of alkaline phosphatase and gamma-glutamyl transpeptidase (GGT), as well as affect blood calcium and glucose metabolism tests.

Use of Epanutin with other medicines

Before using a new medicine with Epanutin, consult your doctor.

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medicine.

Epanutin and certain medicines may influence each other (interactions), causing an imbalance in the levels of both medicines in the blood.

Medicines that may increase phenytoin levels:

• Analgesics/anti-inflammatory agents such as azapropazone, phenylbutazone, and salicylates.
• Anesthetics such as halothane.
• Antibiotics such as chloramphenicol, erythromycin, isoniazid,sulfadiazine, sulfamethizole, sulfamethoxazole-trimethoprim, sulfafenazol, sulfisoxazole, andsulfonamides.
• Anticonvulsants such as felbamate, oxcarbazepine, valproate sodium,succinimides, andtopiramate.
• Antifungals such as amphotericin B, fluconazole, itraconazole, ketoconazole, miconazole, and voriconazole.
• Antineoplastics, such ascapecitabine andfluorouracil.
• Benzodiazepines/Psychotropics such as chlordiazepoxide, diazepam, disulfiram, methylphenidate, trazodone, and viloxazine.
• Calcium channel blockers/ cardiovascular agents such as amiodarone, dicumarol, diltiazem, nifedipine, ticlopidine.
• H2 antagonists such as cimetidine.
• HMG-Co reductase inhibitors such as fluvastatin.
• Hormones such as estrogens.
• Immunosuppressants such as tacrolimus.
• Oral antidiabetics such as tolbutamide.
• Proton pump inhibitors such as omeprazole.
• SSRI inhibitors such as fluoxetine, fluvoxamine, sertraline.
• Alcohol (acute ingestion).

Medicines that may decrease phenytoin levels:

• Antibiotics such as ciprofloxacin, rifampicin.
• Anticonvulsants such as vigabatrin.
• Antineoplastics such as bleomycin, carboplatin, cisplatin, doxorubicin, and methotrexate.
• Antiulcer agents such as sucralfate.
• Antiretrovirals:fosamprenavir, nelfinavir, and ritonavir
• Bronchodilators such as theophylline.
• Cardiovascular agents such as reserpine.
• Folic acid.
• Hypoglycemic agents such as diazoxide.
• St. John's Wort.
• Alcohol (chronic ingestion).
• Preparations containing calcium, including some antacids.

Medicines that may increase or decrease phenytoin levels:

• Antibiotics such as ciprofloxacin.
• Anticonvulsants such as carbamazepine, phenobarbital, valproate sodium, and valproic acid.
• Antineoplastics.
• Psychotropics such as chlordiazepoxide, diazepam, and phenothiazines.

Medicines whose levels in the blood and/or whose effects may be altered by the administration of phenytoin.(Not all medicines are listed below. Consult your doctor or pharmacist):

• Antibiotics such as doxycycline, rifampicin, and tetracycline.
• Oral anticoagulants such as warfarin, apixaban, dabigatran, edoxaban, rivaroxaban.
• Anticonvulsants such as carbamazepine,lacosamide,lamotrigine, phenobarbital, valproate sodium, valproic acid.
• Antifungals of the azole family, such as posaconazole and voriconazole.
• Antihelmintics such as albendazole and praziquantel.
• Antineoplastics such as teniposide.
• Antiplatelet agents such as ticagrelor.
• Antiretrovirals such asdelavirdine, efavirenz, fosamprenavir, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, and saquinavir.
• Bronchodilators such as theophylline.
• Calcium channel blockers/ cardiovascular agents such as digitoxin, digoxin, disopyramide, mexiletine, nicardipine, nimodipine, nisoldipine, quinidine, and verapamil.
• Corticosteroids.
• Ciclosporin.
• Diuretics such as furosemide.
• HMG-Co reductase inhibitors such as atorvastatin, fluvastatin, and simvastatin.
• Hormones such as estrogens and oral contraceptives.
• Hypoglycemic agents such as diazoxide.
• Immunosuppressants.
• Neuromuscular blockers such as alcuronium, cisatracurium,pancuronium, rocuronium, and vecuronium.
• Opioid analgesics such as methadone.
• Oral antidiabetics such as chlorpropamide, glibenclamide, and tolbutamide.
• Psychotropics/antidepressants such as clozapine, paroxetine, quetiapine, and sertraline.
• Vitamin D.
• Folic acid.

Some medicines used to treat depression (tricyclic antidepressants) may precipitate the occurrence of seizures in certain patients, so your doctor may decide to change the dose of phenytoin.

Use of Epanutin with food, drinks, and alcohol

Acute alcohol ingestion may increase phenytoin levels, while chronic alcohol ingestion may decrease them, so you should not drink alcohol during Epanutin treatment.

If you have received enteral nutrition preparations and/or nutritional supplements, you may experience lower-than-expected plasma phenytoin levels. Therefore, it is recommended that phenytoin not be administered with enteral nutrition preparations and/or vitamin supplements. Your doctor may need to monitor your medication levels.

Pregnancy, lactation, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medicine.

Consult your doctor if you are pregnant or planning to become pregnant; they will inform you of the potential risks to you and your baby.Epanutin should only be administered to pregnant women if, in the doctor's opinion, the expected benefit to the mother outweighs any possible risk to the fetus.

Epanutin may cause severe congenital abnormalities. If you take Epanutin during pregnancy, your baby may be up to three times more likely to have a congenital abnormality than women who do not take an antiepileptic medication. Severe congenital abnormalities, such as growth abnormalities, skull, face, nail, finger, and heart abnormalities, have been reported. Some of these may occur together as part of a hydantoin syndrome.

Severe neurological developmental problems (brain development) have been reported in babies born to mothers who used phenytoin during pregnancy. Some studies have shown that phenytoin negatively affects neurological development in children exposed to phenytoin in the womb, although other studies have not found this effect. It cannot be ruled out that there may be an effect on neurological development.

If you are a woman of childbearing age and are not planning to become pregnant, you should use effective contraceptive methods during Epanutin treatment. Epanutin may affect the way oral contraceptives, such as the pill, work and make them less effective in preventing pregnancy. Consult your doctor, who will consider with you the type of contraceptive most suitable for you while taking Epanutin.

If you are a woman of childbearing age and are planning to become pregnant, consult your doctor before stopping contraception and before becoming pregnant about changing to other suitable treatments to avoid exposing the fetus to phenytoin.

If you are pregnant or think you may be pregnant, inform your doctor immediately. Do not stop taking your medicine until your doctor has considered it with you. Stopping your medicine without consulting your doctor could cause seizures that may be dangerous to you and the fetus. Your doctor may decide to change your treatment.

It is not recommended to take Epanutin during breastfeeding.

Driving and operating machinery

Phenytoin may cause symptoms such as drowsiness, dizziness, or visual disturbances, and may impair your ability to react. These effects, as well as the underlying disease, may make it difficult for you to drive vehicles or operate machinery. Thereforeno drive or operate machinery, or engage in other activities that require special attention, until your doctor assesses your response to this medicine.

Epanutin contains lactose.

This medicine contains lactose. If your doctor has told you that you have a certain sugar intolerance, consult them before taking this medicine.

This medicine contains less than 23 mg of sodium (1 mmol) per capsulewhich is, essentially “sodium-free”.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. It is very important that you strictly comply with them. Inform your doctor of any cause that makes it impossible to take this medication, such as an operation.

In case of doubt, consult your doctor or pharmacist again.

Epanutin should be taken with at least half a glass of water. If you tend to present nausea or stomach heaviness, you can take the medication during or after meals.

Adults:

The starting dose of treatment is 300mg of Epanutin per day in three equal doses (1 capsule every 8 hours before meals). Your doctor will indicate the maintenance dose you need, not exceeding the maximum dose of 600mg per day.

In cases where the patient shows a tendency to nausea and stomach heaviness, the dose can be administered during or after meals.

For patients who need to quickly reach high serum levels of phenytoin in a state of equilibrium, the recommended loading dose is 1,000mg of phenytoin orally, divided into three doses [400 mg (4 capsules), 300 mg (3 capsules), and 300 mg (3 capsules)], at intervals of two hours. This must be done in hospitalized patients as it is necessary to monitor the serum levels of the drug. After 24 hours of administration of the oral loading dose, your doctor will establish the maintenance dose.

Use in children and adolescents:

The initial dose is 5mg/kg/day, divided into 2 or 3 equal doses. From here, the maintenance dose should be established by your doctor on an individualized basis, not exceeding the maximum dose of 300mg.

The recommended daily maintenance dose is between4 to8 mg/Kg/day. If the daily dose cannot be divided equally, the larger dose should be given at night.

This presentation is not suitable for use in newborns, infants, children, and adolescents who are not capable of taking the entire capsule or for patients who, due to their weight, the dose adjustment is not possible with this presentation.For example, patients weighing less than 40 kilograms due to the impossibility of dividing the dose into at least two separate doses.This pharmaceutical form is not suitable for patients with swallowing problems.

Patients with liver or kidney problems

Inform your doctor if you have liver or kidney problems as your doctor may need to adjust the dose.

If you take more Epanutin than you should

If you have taken more Epanutin than you should, consult your doctor or pharmacist immediately.

The initial symptoms are: involuntary eye movements, lack of muscular coordination, difficulty speaking, tremors, exaggerated reflexes, drowsiness, numbness, prolonged dreams, slurred speech, blurred vision, nausea, and vomiting. The patient may reach a state of coma and hypotension.Cases of slow heart rate and cardiac arrest have been reported.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service. Phone: (91) 562 04 20. It is recommended to bring the packaging and the medication leaflet to the healthcare professional.

If you forgot to takeEpanutin

Take the dose as soon as you remember. If you are close to the next dose, do not take the missed dose and wait for the next dose continuing with your established dosing regimen. Do not take a double dose to compensate for the missed doses.

If you interrupt the treatment with Epanutin

Do not interrupt the treatment with Epanutin unless your doctor tells you to. If you interrupt the treatment with Epanutin abruptly, you may increase the frequency of seizures. If your doctor considers it necessary to interrupt the treatment with this medication, he will decide on the most suitable alternative treatment for you.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Inform your doctor immediatelyif you experience any of the following symptoms after taking this medicine, as they may be serious:

• if you experience fever, skin rash, and/or swollen lymph nodes, especially during the first two months of treatment, as they may be signs of a medication hypersensitivity reaction.
• if you experience mental confusion or severe mental alteration, as this may be a sign that you have high levels of phenytoin in your blood. Your doctor will analyze your blood to determine the amount of phenytoin and, if necessary, may reduce the dose of the medicine or even discontinue treatment.
• if you notice bruises, fever, or oral bleeding. These may be the first signs of a blood disorder, including a decrease in the number of red blood cells,a decrease in the number of a type of red blood cell (pure red cell aplasia),white blood cells, or platelets. Your doctor will perform periodic blood tests to detect these effects.
• if you experience nausea, vomiting, abdominal pain, loss of appetite, diarrhea, feeling tired or weak, yellow discoloration of the skin and eyes, increased liver volume, as they may be signs of liver problems.
• if you develop a severe skin rash with blisters (which also affects the mouth and tongue). These may be symptoms of a condition known as Stevens-Johnson syndrome or toxic epidermal necrolysis (TEN).
  

Other side effects that may occur are:

• General disorders and administration site conditions:allergic reaction.
• Nervous system disorders:nystagmus (abnormal eye movements), ataxia (instability), slurred speech, decreased coordination, dizziness, vertigo, insomnia, transient nervousness, involuntary muscle contractions (uncontrolled movements of different parts of the body), headache, paresthesia (tingling or decreased sensitivity, usually in one foot or hand), somnolence. Rarely, cases of different types of dyskinesias (uncontrolled movements or postures of different parts of the body) have been reported. In very long-term treatments: peripheral sensory polyneuropathy (alteration of pain and touch sensation). Alteration of taste.
• Skin and subcutaneous tissue disorders:life-threatening skin rash with blisters (this occurs especially around the mouth and tongue),facial skin thickening, lip thickening, gum thickening, hirsutism (excessive hair growth in localized or generalized areas), urticaria.
• Reproductive and breast disorders:Peyronie's disease (fibrotic hardening of the penis that causes curvature or deviation of the penis duringerection).
• Gastrointestinal disorders:vomiting, nausea, constipation.
• Immune system disorders:systemic lupus erythematosus (immune disorder affecting multiple organs), nodular periarthritis (a type of arterial inflammation), alterations in immunoglobulins (proteins produced in the immune response).Difficulty breathing, swelling of the neck, face, or lips.

-Musculoskeletal and connective tissue disorders:osteoporosis (bone decalcification) and other alterations, including decreased levels of calcium, phosphorus, vitamin D, and fractures, have been reported.

-Complementary examinations: taking phenytoin may cause abnormal results from thyroid tests.

Other side effects in children and adolescents

The reported adverse events are generally similar in children and adults. Gingival hyperplasia occurs more frequently in pediatric patients and those with poor oral hygiene.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not store at a temperature above 25°C.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medications should not be disposed of through drains or in the trash.Deposit the packaging and medications you no longer need at the SIGRE collection pointof the pharmacy. If in doubt, please ask your pharmacist how to dispose of the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Epanutin

• The active principle is phenytoin sodium.
• The other components are lactose monohydrate and magnesium stearate. The capsule is composed of gelatin (E441), titanium dioxide (E171), erythrosine (E127), sodium dodecyl sulfate, and quinoline yellow (E104).
• The components of the ink (color code 10A1) are: shellac in ethanol, iron oxide black (E172), n-butyl alcohol, propylene glycol, anhydrous alcohol, isopropyl alcohol, 28% ammonium hydroxide, and purified water.

or

• The components of the ink (color code 1014) are: shellac, anhydrous alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, concentrated ammonium solution, iron oxide black (E172), potassium hydroxide, and purified water.

Appearance of the product and contents of the packaging

The hard capsules consist of an orange-transparent cap and a white opaque body, both printed in black with "Epanutin 100".

They are presented in a white high-density polyethylene (HDPE) bottle closed with a white polypropylene cap and containing 1 g of silica gel as a desiccant. Each package contains 100 hard capsules.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Viatris Healthcare Limited

Damastown Industrial Park

Mulhuddart, Dublin 15

Dublin

Ireland

Responsible for manufacturing

Pfizer Manufacturing Deutschland GmbH,

Mooswaldallee 1

79108 Freiburg Im Breisgau

Germany

You can request more information about this medication by contacting the local representative of the holder of the marketing authorization:

Viatris Pharmaceuticals, S.L.

Calle General Aranaz, 86

28027 Madrid

Spain

Last review date of this leaflet: September 2021

Detailed and updated information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/