EPANUTIN 100 mg HARD CAPSULES

Introduction

Package Leaflet: Information for the User

Epanutin 100 mg Hard Capsules

Phenytoin Sodium

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

1. What is Epanutin and what is it used for
2. What you need to know before you take Epanutin
3. How to take Epanutin
4. Possible side effects
5. Storing Epanutin
6. Contents of the pack and other information

1. What is Epanutin and what is it used for

Epanutin contains the active substance 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 seizures), complex partial seizures, as well as for the treatment and prevention of seizures in neurosurgery.

2. What you need to know before you take Epanutin

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, have other serious illnesses, or are an elderly patient. If during treatment you notice symptoms suggestive of hepatitis, such as jaundice (yellowing of the skin and whites of the eyes), you should 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 if you do so in small amounts but habitually.
• if you are undergoing cranial radiotherapy 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 of black race, your immune system is depressed, a family member or you have had a history of drug hypersensitivity syndrome (HSS) or drug rash with eosinophilia and systemic symptoms (DRESS) (a syndrome that usually presents with fever, skin rash, lymph node involvement, and involvement of other organs, such as the liver, kidneys, heart, lungs, and blood abnormalities), as you are at higher risk of presenting this syndrome. If during treatment you present with fever, skin rash with lymph node swelling, which can be signs of hypersensitivity to the medicine, you should consult your doctor immediately.
• cases of heart problems, such as bradycardia (slower than normal heart rate) and asystole (heart stoppage), commonly associated with phenytoin toxicity, have been reported. If during treatment you suffer from these symptoms, you should consult your doctor immediately.
• skin rashes that can be life-threatening (such as Stevens-Johnson syndrome and toxic epidermal necrolysis) have been reported with the use of Epanutin. Serious skin effects occur rarely during treatment with phenytoin. Initially, they appear as red spots or circular patches, often with a central blister. Other additional signs that may appear are sores in the mouth, throat, nose, genitals, and conjunctivitis (swollen and red eyes). These life-threatening skin rashes are often accompanied by flu-like symptoms. The risk may be associated with a genetic variant in some subjects of Thai or Chinese origin. If you are of this descent and have been previously analyzed and know that you have the genetic variant (HLA-B*1502), talk to your doctor before taking phenytoin. If you develop rashes or these skin symptoms, go immediately to a doctor and inform them that you are taking this medicine. Consult your doctor before stopping treatment with Epanutin.
• if during treatment you suffer from a state of confusion (such as delirium, psychosis, etc.), which can be a sign of excessive phenytoin in the blood, you should consult your doctor immediately.
• a small number of people treated with antiepileptics such as Epanutin have had thoughts of self-harm or suicide. If at any time you present these thoughts, contact your doctor as soon as possible.
• there is a risk of harm to the fetus if Epanutin is used during pregnancy. Women of childbearing age must use effective contraceptive methods during treatment with Epanutin (see "Pregnancy and breastfeeding").

During treatment with Epanutin, it is essential to maintain good oral hygiene. This way, you can prevent the appearance of adverse effects in the oral area, such as gum thickening.

It is very important that your doctor controls your treatment in periodic visits and performs regular analyses to rule out the appearance of blood alterations, monitor liver function, and in some cases to control the most suitable dose of Epanutin.

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

Interaction with laboratory tests:

Epanutin may interfere with certain laboratory tests that are performed on you.

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

Using Epanutin with other medicines

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

Inform your doctor or pharmacist if you are using, have recently used, 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.

The following is a summary of the medicines that may increase phenytoin levels:

• Pain relievers/anti-inflammatory drugs such as azapropazone, phenylbutazone, and salicylates.
• Anesthetics such as halothane.
• Antibiotics such as chloramphenicol, erythromycin, isoniazid, sulfadiazine, sulfamethizole, sulfamethoxazole-trimethoprim, sulfaphenazole, sulfisoxazole, and sulfonamides.
• Anticonvulsants such as felbamate, oxcarbazepine, sodium valproate, succinimides, and topiramate.
• Antifungals such as amphotericin B, fluconazole, itraconazole, ketoconazole, miconazole, and voriconazole.
• Antineoplastics, such as capecitabine and fluorouracil.
• Benzodiazepines/psychotropics such as chlordiazepoxide, diazepam, disulfiram, methylphenidate, trazodone, and viloxazine.
• Calcium channel blockers/cardiovascular agents such as amiodarone, dicumarol, diltiazem, nifedipine, and ticlopidine.
• H2 antagonists such as cimetidine.
• HMG-CoA reductase inhibitors such as fluvastatin.
• Hormones such as estrogens.
• Immunosuppressants such as tacrolimus.
• Oral antidiabetics such as tolbutamide.
• Proton pump inhibitors such as omeprazol.
• Selective serotonin reuptake inhibitors such as fluoxetine, fluvoxamine, and sertraline.
• Acute alcohol consumption.

The following is a summary of the medicines that may decrease phenytoin levels:

• Antibiotics such as ciprofloxacin and 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.
• Hyperglycemic agents such as diazoxide.
• St. John's Wort.
• Chronic alcohol consumption.
• Preparations containing calcium, including some antacids.

The following is a summary of the medicines that may increase or decrease phenytoin levels:

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

The following is a summary of the drugs whose blood levels and/or 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, sodium valproate, valproic acid.
• Antifungals of the azole family, such as posaconazole and voriconazole.
• Anthelmintics such as albendazole and praziquantel.
• Antineoplastics such as teniposide.
• Antiplatelet agents such as ticagrelor.
• Antiretrovirals such as delavirdine, efavirenz, fosamprenavir, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, and saquinavir.
• Bronchodilators such as theophylline.
• Calcium channel blockers/cardiovascular agents such as digoxin, disopyramide, mexiletine, nicardipine, nimodipine, nisoldipine, quinidine, and verapamil.
• Corticosteroids.
• Cyclosporin.
• Diuretics such as furosemide.
• HMG-CoA reductase inhibitors such as atorvastatin, fluvastatin, and simvastatin.
• Hormones such as estrogens and oral contraceptives.
• Hyperglycemic 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, gliburide, 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 appearance of seizures in certain patients, so your doctor may decide to change the dose of phenytoin.

Using Epanutin with food, drinks, and alcohol

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

If you have received enteral nutrition preparations and/or nutritional supplements, you may have lower-than-expected phenytoin plasma levels. Therefore, it is recommended that phenytoin not be administered with enteral nutrition preparations and/or vitamin supplements. It may be necessary for your doctor to monitor the levels of the medicine in your blood.

Pregnancy, breastfeeding, and fertility

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.

Consult your doctor if you are pregnant or wish to become pregnant; he will indicate the potential risks to which you and your baby are exposed. Epanutin should only be administered to pregnant women if, in the doctor's judgment, the expected benefit to the mother is greater than any possible risk to the fetus.

Epanutin may cause serious congenital anomalies. If you take Epanutin during pregnancy, your baby has up to 3 times the risk of having a congenital anomaly compared to women who do not take an antiepileptic medicine. Serious congenital anomalies have been reported, such as growth anomalies, skull, face, nail, finger, and heart anomalies. Some of these may occur simultaneously as part of a fetal hydantoin syndrome.

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

If you are a woman of childbearing age and are not planning to become pregnant, you should use an effective contraceptive method during treatment with Epanutin. Epanutin may affect how hormonal contraceptives, such as the birth control pill, work and make them less effective in preventing pregnancy. Consult your doctor, who will consider with you the most suitable contraceptive method to use 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 you have discussed it with your doctor. Stopping your medicine without consulting your doctor could lead to seizures that could be dangerous for you and the fetus. Your doctor may decide to change your treatment.

Epanutin is not recommended during breastfeeding.

Driving and using machines

Phenytoin may cause symptoms such as drowsiness, dizziness, or vision changes, and may decrease your reaction ability. These effects, as well as the underlying disease, may impair your ability to drive vehicles or operate machines. Therefore, do not drive or operate machines, nor 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 an intolerance to certain sugars, consult with them before taking this medicine.

This medicine contains less than 23 mg of sodium (1 mmol) per capsule, which is essentially "sodium-free".

3. How to take Epanutin

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. It is very important that you follow them strictly. Inform your doctor of any reason that may prevent you from taking 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 experience nausea or stomach heaviness, you can take the medication during or after meals.

Adults:

The initial treatment dose is 300 mg of Epanutin per day in three equal doses (1 capsule every 8 hours before meals). Your doctor will indicate the maintenance dose you need, which should not exceed the maximum dose of 600 mg 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 at steady state, the recommended loading dose is 1,000 mg of phenytoin orally, divided into three doses [400 mg (4 capsules), 300 mg (3 capsules), and 300 mg (3 capsules)], at two-hour intervals. This should be done in hospitalized patients as monitoring of serum drug levels is necessary. After 24 hours of oral loading dose administration, your doctor will establish the maintenance dose.

Use in children and adolescents:

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

The recommended daily maintenance dose is between 4 and 8 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 able to take the whole capsule or for patients whose weight does not allow dose adjustment 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 muscle 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 heartbeat and cardiac arrest have been reported.

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

If you forget to take Epanutin

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

If you interrupt treatment with Epanutin

Do not interrupt treatment with Epanutin unless your doctor tells you to. If you suddenly stop treatment with Epanutin, you may increase the frequency of seizures. If your doctor considers it necessary to interrupt treatment with this medication, they 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.

4. Possible adverse effects

Like all medications, this medication can produce adverse effects, although not all people experience them.

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

Other adverse effects that may appear 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, motor twitching (uncontrolled movements of different parts of the body), headache, paresthesia (tingling or decreased sensitivity generally in a foot or hand), drowsiness. Rarely, cases of different types of dyskinesia (uncontrolled movements or postures of different parts of the body) have been reported. In very prolonged treatments: peripheral polyneuropathy predominantly sensory (alteration of pain and touch sensation). Alteration of taste.
• Skin and subcutaneous tissue disorders:life-threatening skin rashes with blisters (which occurs especially around the mouth and tongue), facial feature hardening, lip thickening, gum thickening, hirsutism (excessive localized or generalized hair growth), urticaria.
• Reproductive system and breast disorders:Peyronie's disease (fibrous hardening of the penis that causes deviation or curvature of the penis during erection).
• Gastrointestinal disorders:vomiting, nausea, constipation.
• Immune system disorders:systemic lupus erythematosus (immunological disease with involvement of various organs), periarteritis nodosa (a type of inflammation of the arteries), alterations in immunoglobulins (proteins produced in the immune response). Difficulty breathing, swelling of the neck, face, or lips.

• Musculoskeletal and connective tissue disorders: osteoporosis (decalcification of bones) and other alterations, including decreased levels of calcium, phosphorus, vitamin D, and fractures have been reported.
• Investigations: taking phenytoin may cause abnormal thyroid test results.

Other adverse 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 in those with poor oral hygiene.

Reporting of adverse effects

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

5. Conservation of Epanutin

Keep this medication out of 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 thrown down the drain or into the trash. Deposit the packaging and medications you no longer need at the SIGRE point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Packaging contents and additional information

Epanutin composition

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

or

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

Product appearance and packaging contents

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

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

Marketing authorization holder and manufacturer

Marketing authorization holder

Viatris Healthcare Limited

Damastown Industrial Park

Mulhuddart, Dublin 15

Dublin

Ireland

Manufacturer

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 marketing authorization holder:

Viatris Pharmaceuticals, S.L.

Calle General Aranaz, 86

28027 Madrid

Spain

Date of the last revision of this prospectus:September 2021

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