PHENYTOIN ALTAN 50 mg/mL INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the Patient

Phenytoin Altan 50 mg/ml Solution for Injection

Phenytoin

Contents of the Package Leaflet

1. What is Phenytoin Altan and what it is used for
2. What you need to know before you start using Phenytoin Altan
3. How to use Phenytoin Altan
4. Possible side effects
5. Storage of Phenytoin Altan
6. Contents of the pack and further information

1. What is Phenytoin Altan and what it is used for

Phenytoin Altan contains the active substance phenytoin. It belongs to a group of medicines called antiepileptics.

This medicine is indicated for:

• Treatment of different types of epilepsy.
• Treatment and prevention of convulsions that affect the whole body or parts of it with muscular rigidity and may lead to loss of consciousness. Treatment and prevention of convulsions in neurosurgery.

• Treatment of irregular heartbeats (atrial and ventricular arrhythmias), especially when caused by poisoning with medicines used to treat heart problems (digoxin).

2. What you need to know before starting to use Fenitoína Altan.

Do not use Fenitoína Altan:

• If you are allergic to phenytoin or to any of the other components of this medication (included in section 6).
• If you have any heart disease such as: decreased heart rate, blockage in the transmission of impulses and neurological convulsions due to rhythm alterations (Adam-Stokes syndrome).

Warnings and precautions

Consult your doctor or pharmacist before starting to use this medication.

• If you have liver or kidney problems. Your doctor will perform periodic checks.
• If you have other serious illnesses or are an elderly patient. If during treatment you notice symptoms suggestive of hepatitis, such as jaundice (yellowish coloration of the skin and whites of the eyes), you should consult your doctor immediately.
• If there have been cases of heart problems, such as low blood pressure (hypotension), such as bradycardia (slower than usual heart rate) and asystole (cardiac arrest), commonly associated with phenytoin toxicity. If during treatment you suffer from these symptoms, you should consult your doctor immediately.
• If you are receiving treatment with vitamin D or derivatives, as their simultaneous use with phenytoin could cause progressive softening of the bones with possible fractures.
• If you have diabetes, as phenytoin may cause you to have a hyperglycemic situation by increasing blood glucose levels.

• If you are pregnant or breastfeeding.
  • Severe skin reactions that can threaten the patient's life (Stevens-Johnson syndrome and toxic epidermal necrolysis) have been described with the use of phenytoin, initially appearing 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 reactions are often accompanied by flu-like symptoms. The rash can progress to generalized blistering or skin peeling. The period of greatest risk of severe skin reactions is during the first weeks of treatment. The risk may be associated with a variant of a gene 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 have developed Stevens-Johnson syndrome or toxic epidermal necrolysis with the use of phenytoin, you should not use this medication again at any time.
  • If you develop rashes or these skin symptoms, stop taking phenytoin, go to a doctor immediately, and inform them that you are taking this medication. Abruptly stopping treatment can precipitate an epileptic crisis.
  • 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 have kidney disease or have other serious illnesses or are an elderly patient. If during treatment you notice symptoms suggestive of hepatitis, such as jaundice (yellowish coloration of the skin and whites of the eyes), you should consult your doctor immediately.
  • If you have porphyria.
  • If you are undergoing cranial radiotherapy or are reducing your treatment with corticosteroids.
  • If you are black, your immune system is depressed, or 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 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 swollen lymph nodes, which can be signs of hypersensitivity to the medication, you should consult your doctor immediately.

Do not consume alcoholic beverages while being treated with this medication (see use with food and beverages).

There have been reports of irritation and inflammation at the injection site, with and without leakage of the phenytoin solution from the vein. This irritation can range from mild sensitivity to extensive tissue destruction, so inadequate administration of this medication should be avoided to prevent these effects.

Administration of this medication via the intramuscular route is not recommended, as its effect takes too long to manifest.

Phenytoin serum levels above therapeutic doses can produce confusion states referred to as delirium, psychosis, or alterations of the nervous system. Consequently, it is recommended to determine phenytoin serum levels at the first sign of acute toxicity.

A common complication in treatment with phenytoin is gum inflammation, with a higher incidence in patients under 23 years of age. Similarly, there may be an increased incidence of microbial infections and gum bleeding due to a decrease in white blood cells caused by hydantoin anticonvulsants. In these cases, dental interventions should be postponed until blood counts return to normal.

Consult your doctor, even if any of the aforementioned circumstances have occurred to you at some point.

A small number of people treated with antiepileptics such as Fenitoína Altan have had thoughts of self-harm or suicide. If at any time you present these thoughts, contact your doctor as soon as possible.

This medication contains less than 23 mg of sodium (1 mmol) per 100 mg or 250 mg unit dose; that is, it is essentially "sodium-free".

There is a risk of fetal harm if phenytoin is used during pregnancy. Women of childbearing age must use effective contraceptive methods during treatment with phenytoin (see "Pregnancy, breastfeeding, and fertility").

Children:

Phenytoin is not recommended for administration to children because it contains alcohol as an excipient.

Other medications and Fenitoina Altan:

Before using a new medication along with Fenitoína Altan, you should consult your doctor.

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

Fenitoína Altan and certain medications can influence each other (interactions), causing an imbalance in the levels of both medications in the blood.

Phenytoin is a potent inducer of liver enzymes that metabolize medications and can reduce the levels of medications that are metabolized by these enzymes.

The following medications can increase phenytoin levels:

• Analgesics/anti-inflammatory medications 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, ethosuximide, 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, phenothiazines, disulfiram, methylphenidate, trazodone, and viloxazine.
• Calcium channel blockers/cardiovascular agents such as amiodarone, dicumarol (vitamin K antagonist), 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 omeprazole.
• Selective serotonin reuptake inhibitors such as fluoxetine, fluvoxamine, and sertraline.
• Acute alcohol consumption.

The following medications can decrease phenytoin levels:

• Antibiotics such as ciprofloxacin and rifampicin.
• Anticonvulsants such as vigabatrin.
• Antineoplastics such as bleomycin, carboplatin, cisplatin, doxorubicin, and methotrexate.
• Anti-ulcer 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 medications can 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 medications can have their blood levels and/or effects altered by the administration of phenytoin. (Not all medications are listed below. Consult your doctor or pharmacist):

• Antibiotics such as doxycycline, rifampicin, and tetracycline.
• Oral anticoagulants such as warfarin, apixaban, dabigatran, edoxaban, and rivaroxaban.
• Anticonvulsants such as carbamazepine, lacosamide, lamotrigine, phenobarbital, sodium valproate, and 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 digitoxin, 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 (glibenclamide), and tolbutamide.
• Psychotropics/antidepressants such as clozapine, paroxetine, quetiapine, and sertraline.
• Vitamin D.
• Folic acid.
• Everolimus.

These lists are not intended to be complete or exhaustive. The Technical Data Sheet of the specific medications should be consulted.

Some medications used to treat depression (tricyclic antidepressants) may precipitate the appearance of convulsions in certain patients, so the doctor may decide to change the dose of phenytoin.

The simultaneous administration of lidocaine with phenytoin by intravenous route can lead to excessive cardiac depression.

Interaction with laboratory tests:

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

Phenytoin can reduce serum levels of protein-bound iodine. It can also produce lower-than-normal results in dexamethasone or metyrapone tests. Phenytoin can 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.

Use of phenytoin with food, beverages, and alcohol

During treatment with this medication, you should avoid consuming alcohol. High alcohol consumption can increase phenytoin levels in the blood, while chronic alcohol consumption can decrease them.

If you have received enteral nutrition preparations and/or nutritional supplements, you may have lower-than-expected plasma levels of phenytoin. 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 medication in your blood.

Pregnancy, breastfeeding, and fertility

Pregnancy

Consult your doctor or pharmacist before using this medication.

Like other antiepileptics, there is a relationship between the administration of phenytoin and the appearance of congenital malformations, so it should not be used as a medication of choice during pregnancy, especially during the first trimester, and the benefit/risk ratio should be assessed in each case.

If phenytoin is being administered to prevent grand mal seizures, the antiepileptic medication should not be suspended, as it can precipitate a status epilepticus, which carries the risk of causing a lack of oxygen in the mother and fetus.

During pregnancy, the frequency of seizures may increase due to an alteration in the absorption or metabolism of phenytoin. Therefore, it is very important to determine serum levels in order to establish the dose in each patient. After delivery, it will probably be necessary to administer the dose prior to pregnancy.

Phenytoin administered before delivery can cause a lack of vitamin K and, therefore, of the coagulation factors related to this vitamin. This increases the risk of bleeding during delivery for the mother or in the newborn; to avoid this, vitamin K can be administered to the mother in the last month of pregnancy and to the newborn immediately after birth.

Fenitoína Altan contains ethanol and propylene glycol and should be taken into account in the case of pregnant women (see section 2 - Fenitoína Altan contains ethanol and propylene glycol).

Phenytoin can produce severe congenital anomalies. If you take phenytoin during pregnancy, your baby has up to 3 times more risk of having a congenital anomaly than women who do not take an antiepileptic medication. Severe congenital anomalies have been reported, such as growth anomalies, skull, face, nail, finger, and heart anomalies. Some of these can occur at the same time as part of a fetal hydantoin syndrome.

There have been reports of neurological development problems (brain development) 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.

Breastfeeding

The use of this medication in breastfeeding women is not recommended, as phenytoin passes into breast milk in low concentrations.

Fenitoína Altan contains alcohol and propylene glycol and should be taken into account in the case of breastfeeding women (see section 2 - Fenitoína Altan contains ethanol and propylene glycol).

Driving and using machines

Phenytoin can produce symptoms such as drowsiness, dizziness, or vision changes, and decrease reaction capacity. These effects, as well as the disease itself, can make it difficult for you to drive vehicles or operate machines. Therefore, do not drive, operate machines, or engage in other activities that require special attention until your doctor assesses your response to this medication.

Fenitoína Altan contains ethanol and propylene glycol

This medication contains 10% ethanol (ethyl alcohol), which corresponds to 165 mg per 2 ml ampoule, equivalent to 4 ml of beer or 1.7 ml of wine, and 405 mg per 5 ml ampoule, equivalent to 10 ml of beer or 4.2 ml of wine.

This medication is harmful to people with alcoholism.

The alcohol content should be taken into account in the case of pregnant women, breastfeeding women, children, and high-risk groups, such as patients with liver disease or epilepsy.

This medication contains 830.4 mg of propylene glycol in each 2 ml ampoule and 2076 mg in each 5 ml ampoule.

If you are pregnant or breastfeeding, do not take this medication unless it is recommended by your doctor. Your doctor may perform additional checks while you are taking this medication.

If you have liver or kidney failure, do not take this medication unless it is recommended by your doctor. Your doctor may perform additional checks while you are taking this medication.

3. How to use Fenitoína Altan.

Follow the administration instructions of this medication exactly as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

To establish a correct dosage regimen, your doctor will need to perform periodic blood tests.

• Status epilepticus and tonic-clonic seizures (epileptic seizures)

Adults: A loading dose of approximately 18 mg/kg/24 h should be administered intravenously at a rate not exceeding 50 mg/min (lasting about 20 minutes in a 70 kg patient). The loading dose should be continued 24 hours later with a maintenance dose of 5-7 mg/kg/day intravenously divided into 3 or 4 administrations.

Newborns and children:A loading dose of 15-20 mg/kg usually produces therapeutic plasma concentrations (10-20 μg/ml). The injection rate should be less than 3 mg/kg/min.

The maintenance doses will be 5 mg/kg/24 h

• Neurosurgery

Adults:Administer a loading dose, 15-18 mg/kg/24 h, divided into 3 doses (1/2 dose initially, 1/4 dose at 8 h and 1/4 dose at 16 h); continue with maintenance doses of 5-7 mg/kg/24 h, fractionated into 3 doses (one every 8 h), i.e., at 24, 32, 40 hours and subsequent ones.

Newborns and children: loading dose 15 mg/kg/24 h and maintenance dose 5 mg/kg/24 h.

• Arrhythmias

Administer 50 to 100 mg every 10 to 15 minutes until the arrhythmia reverts or a maximum dose of 1000 mg is reached. The injection should be performed with maximum precautions, advising continuous ECG and blood pressure monitoring. The injection rate should not exceed 25-50 mg/min.

• Elderly patients and/or with liver failure

In elderly, very ill, debilitated patients, or those with severe liver disease, the total dose should be reduced, as well as the administration rate to 25 mg per minute or even up to 5-10 mg per minute to decrease the possibility of adverse effects.

If you use more Fenitoína Altan than you should

If you have used more phenytoin than you should, go to your doctor or pharmacist as soon as possible, indicating the medication and the amount ingested. You can also call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

The initial symptoms are: involuntary eye movements, muscle spasms, and difficulty speaking. Other symptoms are tremors, excessive flexion, numbness, stuttering speech, nausea, and vomiting. In these cases, the doses should be reduced or treatment suspended. The treatment consists of maintaining respiration and blood circulation and taking adequate supportive measures.

If you forget to use Fenitoína Altan

Do not use a double dose to make up for forgotten doses.

If you interrupt treatment with Fenitoína Altan

Consult your doctor to indicate how to restart treatment.

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

4. Possible adverse effects

Like all medications, this medication can cause adverse effects, although not all people suffer from them.

The main signs of toxicity associated with intravenous administration of phenytoin are alterations in the heart and circulation and/or decrease in the functions of the central nervous system. When administered rapidly, it can cause a drop in blood pressure (hypotension).

Skin rashes that can threaten the patient's life (Stevens-Johnson Syndrome, toxic epidermal necrolysis) (see section 2) may appear.

Bone disorders, including osteopenia and osteoporosis (decalcification of bones) and fractures, have been reported. Consult your doctor or pharmacist if you are undergoing prolonged treatment with antiepileptics, have a history of osteoporosis, or are taking steroids.

Very common: affects more than 1 patient in 10

Common: affects 1 to 10 patients in 100

Uncommon: affects 1 to 10 patients in 1000

Rare: affects 1 to 10 patients in 10,000

Very rare: affects less than 1 patient in 10,000

Unknown: cannot be determined from available data

The following adverse effects related to phenytoin have also been described:

Very common (affects more than 1 patient in 10)

• Cardiovascular disorders:hypotension (avoid rapid administration).

• Nervous system disorders:Involuntary eye movements (nystagmus), inability to coordinate movements (ataxia), stuttering speech, decreased coordination, and mental confusion, vertigo, insomnia, nervousness, and headache.

Common (affects 1 to 10 patients in 100)

• Gastrointestinal disorders:Nausea, vomiting, constipation.

• Skin and subcutaneous tissue disorders:Skin rash sometimes with fever.

Rare (affects 1 to 10 patients in 10,000)

• Cardiovascular disorders: decreased heart function and ventricular fibrillation. These complications are more frequently produced in the elderly or seriously ill.

• Blood and lymphatic system disorders:Some complications found have been fatal. Alterations in blood test results and lymph node disease may appear.

• Hepatobiliary disorders: liver damage.

• Nervous system disorders: involuntary movements, including sudden movements, rigidity, tremors, and shock-like tremors in the wrists.

• General disorders and administration site conditions: Local irritation, inflammation, allergy, tissue destruction, and eschar.

• Skin and subcutaneous tissue disorders: widespread skin peeling.

Very rare (affects less than 1 patient in 10,000) or unknown frequency (cannot be estimated from available data)

• Immune system disorders: Anaphylactic reaction and anaphylaxis, angioedema, chronic inflammatory disease that can affect many organs in the body (Systemic Lupus Erythematosus), inflammation of tissues surrounding arteries with nodule production (periarteritis nodosa), and abnormalities in immunoglobulins (immunizing proteins), Drug Hypersensitivity Syndrome (HSS) / Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), and urticaria (hives).

• Hepatobiliary disorders: toxic liver inflammation.

• Skin and subcutaneous tissue disorders: gum inflammation, acute skin and mucous membrane inflammation (Stevens-Johnson Syndrome, toxic epidermal necrolysis), blisters, and tissue destruction, and hypertrichosis.

• Nervous system disorders:Cerebellar atrophy, cerebellar dysfunction (ataxia), cerebellar degeneration, vertigo, myoclonus, paresthesia, somnolence, peripheral neuropathy, and predominantly sensory peripheral neuropathy, and taste disorders.

• Musculoskeletal and connective tissue disorders:Coarsening of the features, lip thickening, gum inflammation, alterations in penile erection (Peyronie's disease), bone metabolism disorders, such as hypocalcemia, hypophosphatemia, and decreased levels of vitamin D metabolites.

• Blood and lymphatic system disorders: a decrease in the number of a type of red blood cell (pure red cell aplasia), macrocytosis, and megaloblastic anemia, pseudolymphoma, and lymphoma, and Hodgkin's disease.

If you consider that any of the adverse effects you suffer from is serious or if you notice any adverse effect not mentioned in this prospectus, inform your doctor or pharmacist.

Reporting of adverse effects

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

5. Conservation of Fenitoína Altan.

Keep this medication out of sight and reach of children.

This medication does not require special storage conditions.

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.

Do not use this medication if you observe that the solution is cloudy or precipitates appear.

Medications should not be thrown down the drain or into the trash. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Fenitoína Altan

The active ingredient is sodium phenytoin.

The other components are: ethanol, propylene glycol (E-1520), sodium hydroxide to adjust pH to 12, and water for injectable preparations.

Appearance of the product and package contents

Fenitoína Altan is presented in the form of an injectable solution for administration exclusively by the intravenous route.It is found in packages of 1 and 50 ampoules of 5 ml containing 250 mg of phenytoin and in packages of 1 and 50 ampoules of 2 ml containing 100 mg of phenytoin.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Altan Pharmaceuticals, S.A.

c/ Cólquide, 6. Portal 2, 1ª planta – Oficina F

Edificio Prima

28230 - Las Rozas. MADRID

Spain

Manufacturer:

Laboratorio Reig Jofré, S.A.

c/ Gran Capitán, nº 10. 08970 Sant Joan Despí. (Barcelona)

Spain

Date of the last revision of this prospectus: September 2025

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

This information is intended only for healthcare professionals:

The phenytoin solution is only compatible with physiological serumat a final concentration of 1-10 mg/ml. No other solution for intravenous perfusion is recommended due to the low solubility of the medication at pH below 10.

It should be administered slowly: in adults, the rate should not exceed 50 mg/min; in children and the elderly, the rate should not exceed 1-3 mg/Kg/min.

The solution can be administered directly intravenously. It can also be administered by perfusion, diluting exclusively in physiological serum to a final concentration between 1-10 mg/ml.It is recommended to administer physiological serum before and after perfusion through the same catheter or needle to avoid local venous irritation due to the alkalinity of the solution.

Determination of phenytoin plasma levels is recommended to ensure efficacy and adjust subsequent maintenance doses as needed. Therapeutic serum levels are between 10 and 20 µg/ml.

During perfusion administration, it is recommended to monitor vital signs and ECG.