Phenytoin Altan 50 mg/mL solution for injection

Patient Information Leaflet

Introduction

Patient Information Leaflet

Fenitoína Altan 50 mg/ml Injection Solution

Phenytoin

Package leaflet contents

1. What Fenitoína Altan is and what it is used for
2. What you need to know before starting to use Fenitoína Altan
3. How to use Fenitoína Altan
4. Possible side effects
5. How to store Fenitoína Altan
6. Contents of the pack and other information

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

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

This medicine is indicated for:

• Treatment of various types of epilepsy.

• Treatment and prevention of seizures affecting the entire body or parts of it, associated with muscle rigidity and which may lead to loss of consciousness. Treatment and prevention of seizures in neurosurgery.

• Treatment of irregular heartbeats (atrial and ventricular arrhythmias), particularly when caused by intoxication due to medications used in the treatment of heart conditions (digoxin).

2. What you need to know before using Fenitoína Altan.

Do not use Fenitoína Altan:

• If you are allergic to phenytoin or to any of the other ingredients of this medicine (listed in section 6).
• If you have a heart condition such as: reduced heart rate, conduction block, or neurological seizures due to rhythm disturbances (Adam-Stokes syndrome).

Warnings and precautions

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

• If you have liver or kidney problems. Your doctor will perform periodic monitoring.

• If you suffer from other serious illnesses or are elderly. If during treatment you notice symptoms suggestive of hepatitis, such as jaundice (yellowing of the skin and whites of the eyes), you must consult your doctor immediately.

• Cases of heart problems have been reported, such as low blood pressure (hypotension), bradycardia (slower than normal heart rate), and asystole (cardiac arrest), commonly associated with phenytoin toxicity. If you experience these symptoms during treatment, consult your doctor immediately.

• If you are receiving treatment with vitamin D or its derivatives, as their simultaneous use with phenytoin may cause progressive softening of the bones, potentially leading to fractures.

• If you have diabetes, since phenytoin may cause hyperglycemia by increasing blood glucose levels.

• If you are pregnant or breastfeeding.

  • Life-threatening skin rashes (Stevens-Johnson syndrome and toxic epidermal necrolysis) have been reported with phenytoin use. These initially appear as red spots or circular lesions, often with a central blister.
  • Additional signs may include sores in the mouth, throat, nose, genitals, and conjunctivitis (swollen, red eyes). These potentially life-threatening skin rashes are often accompanied by flu-like symptoms. The rash may progress to widespread blistering or skin peeling. The highest risk period for severe skin reactions is during the first weeks of treatment. The risk may be associated with a genetic variant (HLA-B*1502) in some individuals of Thai or Chinese descent. If you are of this ancestry and have previously been tested and know you carry this genetic variant, speak with your doctor before taking phenytoin.
  • If you have previously developed Stevens-Johnson syndrome or toxic epidermal necrolysis while taking phenytoin, you must never use this medicine again.
  • If you develop a rash or these skin symptoms, stop taking phenytoin immediately, seek medical attention, and inform the doctor that you are taking this medicine. Abrupt discontinuation of treatment may trigger an epileptic seizure.
  • If you are of Taiwanese, Japanese, Malaysian, or Thai descent and tests have shown you carry the CYP2C9*3 mutation.
  • If you have kidney disease or other serious illnesses or are elderly. If during treatment you notice symptoms suggestive of hepatitis, such as jaundice (yellowing of the skin and whites of the eyes), consult your doctor immediately.
  • If you have porphyria.
  • If you are undergoing cranial radiotherapy or tapering off corticosteroid treatment.
  • If you are of African descent, have a weakened immune system, or if you or a family member have previously had drug hypersensitivity syndrome (HSS) or drug reaction with eosinophilia and systemic symptoms (DRESS) (a syndrome typically presenting with fever, skin rash, lymph node swelling, and involvement of organs such as the liver, kidneys, heart, lungs, and blood abnormalities), as you may be at higher risk of developing this syndrome. If during treatment you develop fever and skin rash with swollen lymph nodes, which may indicate drug hypersensitivity, consult your doctor immediately.

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

Cases of irritation and inflammation at the injection site, with or without leakage of phenytoin solution from the vein, have been reported. This irritation can range from mild tenderness to extensive tissue damage; therefore, improper administration of this medicine must be avoided to prevent these effects.

Intramuscular administration of this medicine is not recommended, as its effect takes too long to manifest via this route.

Serum phenytoin levels above the therapeutic range may cause confusion, delirium, psychosis, or nervous system disturbances. Therefore, serum phenytoin levels should be measured at the first sign of acute toxicity.

A common complication of phenytoin treatment is gum inflammation, with higher incidence in patients under 23 years of age. Additionally, increased risk of microbial infections and gum bleeding may occur due to decreased white blood cell counts caused by hydantoin anticonvulsants. In such cases, dental procedures should be postponed until blood counts return to normal.

Consult your doctor, even if any of the above circumstances have occurred to you previously.

A small number of patients treated with antiepileptic medicines such as Fenitoína Altan have experienced suicidal thoughts or self-harm ideation. If you experience such thoughts at any time, contact your doctor immediately.

This medicine contains less than 23 mg of sodium (1 mmol) per 100 mg or 250 mg dose unit; thus, it is essentially “sodium-free”.

There is a risk of fetal harm if phenytoin is used during pregnancy. Women of childbearing potential must use effective contraception during treatment with phenytoin (see “Pregnancy, breastfeeding, and fertility”).

Children:

Phenytoin is not recommended for use in children due to the presence of alcohol as an excipient.

Other medicines and Fenitoína Altan:

Before using any new medicine together with Fenitoína Altan, you must consult your doctor.

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Fenitoína Altan and certain medicines may interact, affecting blood levels of both drugs.

Phenytoin is a potent inducer of hepatic enzymes involved in drug metabolism and may reduce blood levels of medicines metabolized by these enzymes.

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

• Analgesics/anti-inflammatories 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, dicoumarol (vitamin K antagonist), diltiazem, nifedipine, and 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.
• Serotonin reuptake inhibitors such as fluoxetine, fluvoxamine, and sertraline.
• Alcohol (acute intake).

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

• Antibiotics such as ciprofloxacin and rifampicin.
• Anticonvulsants such as vigabatrine.
• 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.
• Alcohol (chronic intake).
• Calcium-containing preparations, including some antacids.

The following is a summary of medicines that may either 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 medicines whose blood levels and/or effects may be altered by phenytoin administration. (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, and rivaroxaban.
• Anticonvulsants such as carbamazepine, lacosamide, lamotrigine, phenobarbital, sodium valproate, and valproic acid.
• Antifungals from 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.
• Cyclosporine.
• Diuretics such as furosemide.
• HMG-Co 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, glyburide (glibenclamide), and tolbutamide.
• Psychotropics/antidepressants such as clozapina, paroxetine, quetiapine, and sertraline.
• Vitamin D.
• Folic acid.
• Everolimus.

These lists are not intended to be complete or exhaustive. Refer to the Technical Data Sheet of the specific medicines.

Some medicines used to treat depression (tricyclic antidepressants) may trigger seizures in certain patients, so the doctor may decide to adjust the phenytoin dose.

Concomitant intravenous administration of lidocaine and phenytoin may lead to excessive cardiac depression.

Interaction with laboratory tests:

Fenitoína Altan may interfere with certain laboratory tests.

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

Use of phenytoin with food, drinks, and alcohol

During treatment with this medicine, alcohol consumption should be avoided. High alcohol intake may increase phenytoin blood levels, while chronic alcohol intake may decrease them.

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

Pregnancy, breastfeeding, and fertility

Pregnancy

Consult your doctor or pharmacist before using this medicine.

Like other antiepileptics, phenytoin use has been associated with congenital malformations. Therefore, it should not be used as a first-choice medicine during pregnancy, especially during the first trimester, and the benefit-risk ratio should be evaluated in each case.

If you are taking phenytoin to prevent grand mal seizures, antiepileptic medication should not be discontinued, as this may trigger status epilepticus, which poses a risk of oxygen deprivation to both mother and fetus.

During pregnancy, seizure frequency may increase due to altered absorption or metabolism of phenytoin. Therefore, it is very important to monitor serum levels to determine the appropriate dose for each patient. After delivery, the dose used prior to pregnancy may need to be reinstated.

Phenytoin administered before delivery causes vitamin K deficiency and, consequently, deficiency of vitamin K-dependent clotting factors. This increases the risk of bleeding during delivery for the mother or in the newborn. To prevent this, vitamin K may be administered to the mother during the last month of pregnancy and to the newborn immediately after birth.

Fenitoína Altan contains ethanol and propylene glycol, which must be considered in pregnant women (see section 2 – Fenitoína Altan contains ethanol and propylene glycol).

Phenytoin may cause serious congenital anomalies. If you take phenytoin during pregnancy, your baby has up to three times higher risk of congenital malformations compared to babies of women not taking antiepileptic medicines. Serious congenital anomalies have been reported, including growth retardation, skull, facial, nail, finger, and heart abnormalities. Some of these may occur together as part of 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 neurological development in children exposed in utero, while others have not found such an effect. A potential effect on neurological development cannot be ruled out.

Breastfeeding

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

Fenitoína Altan contains alcohol and propylene glycol, which must be considered in breastfeeding women (see section 2 – Fenitoína Altan contains ethanol and propylene glycol).

Driving and use of machines

Phenytoin may cause symptoms such as drowsiness, dizziness, or visual disturbances, and may reduce reaction ability. These effects, along with the underlying disease, may impair your ability to drive or operate machinery. Therefore, do not drive or operate machinery, or engage in other activities requiring special attention, until your doctor evaluates your response to this medicine.

Fenitoína Altan contains ethanol and propylene glycol

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

This medicine is harmful for individuals with alcoholism.

The alcohol content should be considered in pregnant or breastfeeding women, children, and high-risk groups such as patients with liver disease or epilepsy.

This medicine contains 830.4 mg of propylene glycol in each 2 ml vial and 2076 mg in each 5 ml vial.

If you are pregnant or breastfeeding, do not take this medicine unless recommended by your doctor. Your doctor may perform additional monitoring while you are taking this medicine.

If you have hepatic or renal insufficiency, do not take this medicine unless recommended by your doctor. Your doctor may perform additional monitoring while you are taking this medicine.

3. How to use Fenitoína Altan.

Follow exactly the instructions for administering this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again.

To establish an appropriate dosing 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 (this will last about 20 minutes in a 70 kg patient). The loading dose should be followed 24 hours later by a maintenance dose of 5–7 mg/kg/day administered intravenously in 3 or 4 divided doses.

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.

Maintenance doses will be 5 mg/kg/24 h.

• Neurosurgery

Adults: Administer a loading dose of 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, divided into 3 doses (every 8 hours), i.e., at 24, 32, 40 hours, and thereafter.

Newborns and children: Loading dose 15 mg/kg/24 h and maintenance doses of 5 mg/kg/24 h.

• Arrhythmias

Administer 50 to 100 mg every 10 to 15 minutes until the arrhythmia resolves or until a maximum dose of 1000 mg is reached. The injection must be performed with maximum caution, with continuous ECG and blood pressure monitoring recommended. The injection rate must not exceed 25–50 mg/min.

• Elderly patients and/or with hepatic impairment

In elderly patients, severely ill, debilitated, or those with serious liver disease, the total dose and rate of administration should be reduced to 25 mg per minute or even as low as 5–10 mg per minute to reduce the risk of adverse effects.

If you use more Fenitoína Altan than you should

If you have used more phenytoin than you should, contact your doctor or pharmacist as soon as possible, indicating the medicine and the amount taken. You may also call the Toxicology Information Service at telephone number 91 562 04 20, specifying the medicine and the amount ingested.

Initial symptoms are: involuntary eye movements, muscle spasms, and difficulty speaking. Other symptoms include tremor, excessive flexion, numbness, slurred speech, nausea, and vomiting. In such cases, doses should be reduced or treatment discontinued. Management consists of maintaining respiration and blood circulation and providing appropriate supportive measures.

If you forget to use Fenitoína Altan

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

If you stop using Fenitoína Altan

Consult your doctor for instructions on how to restart treatment.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

The main signs of toxicity associated with intravenous administration of phenytoin are disturbances in the heart and blood circulation and/or decreased functions of the central nervous system. When administered rapidly, a drop in blood pressure (hypotension) may occur.

Skin rashes may occur that could be life-threatening (Stevens-Johnson Syndrome, toxic epidermal necrolysis) (see section 2).

Bone abnormalities have been reported, including osteopenia and osteoporosis (bone demineralization) and fractures. Consult your doctor or pharmacist if you are on long-term treatment with antiepileptic drugs, have a history of osteoporosis, or are taking steroids.

Very common: affects more than 1 in 10 people
Common: affects 1 to 10 in 100 people
Uncommon: affects 1 to 10 in 1,000 people
Rare: affects 1 to 10 in 10,000 people
Very rare: affects less than 1 in 10,000 people
Not known: frequency cannot be estimated from available data.

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

Very common (affects more than 1 in 10 people)

• Cardiovascular disorders: hypotension (avoid rapid administration).

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

Common (affects 1 to 10 in 100 people)

• Gastrointestinal disorders: nausea, vomiting, constipation.

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

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

• Cardiovascular disorders: reduced heart function and ventricular fibrillation. These complications occur more frequently in elderly or seriously ill patients.

• Blood and lymphatic system disorders: some complications reported have been fatal. Abnormalities in blood test results and lymph node disease may occur.

• Hepatobiliary disorders: liver damage.

• Nervous system disorders: involuntary movements, including sudden jerky movements, rigidity, tremor, and wrist tremors.

• General disorders and administration site conditions: local irritation, inflammation, allergy, tissue necrosis, and phlebitis.

• Skin and subcutaneous tissue disorders: widespread skin peeling.

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

• Immune system disorders: anaphylactic reaction and anaphylaxis, angioedema, chronic inflammatory disease that may affect many organs of the body (Systemic Lupus Erythematosus), inflammation of tissues surrounding arteries with nodule formation (periarteritis nodosa), immunoglobulin abnormalities (immunizing proteins), drug hypersensitivity syndrome (HSS)/drug reaction with eosinophilia and systemic symptoms (DRESS), and urticaria (hives).

• Hepatobiliary disorders: toxic liver inflammation.

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

• Nervous system disorders: cerebellar atrophy, cerebellar dysfunction (ataxia), cerebellar degeneration, dizziness, myoclonus, paresthesia, somnolence, peripheral polyneuropathy, predominantly sensory peripheral polyneuropathy, and taste disturbances.

• Musculoskeletal and connective tissue disorders: coarsening of facial features, lip enlargement, gingival inflammation, penile erection disorders (Peyronie's disease), disturbances in bone metabolism 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 any of the adverse effects you experience to be severe, or if you notice any adverse effect not mentioned in this leaflet, 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 leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Fenitoína Altan.

Keep this medicine out of sight and reach of children.

This medicine does not require special storage conditions.

Do not use this medicine after the expiry date stated on the packaging after EXP.

The expiry date refers to the last day of the month indicated.

Do not use this medicine if you notice that the solution is cloudy or if precipitates appear.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the container and additional information

Composition of Fenitoína Altan

The active substance is sodium phenytoin.

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

Appearance of the product and contents of the container

Fenitoína Altan is available as an injectable solution for intravenous use only. It is supplied in packs of 1 and 50 vials of 5 ml containing 250 mg of phenytoin, and in packs of 1 and 50 vials 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, 1st floor – Office 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 most recent revision of this leaflet: September 2025

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

This information is intended for healthcare professionals only:

Phenytoin solution is compatible only with physiological saline, at a final concentration of 1–10 mg/ml. No other intravenous infusion solutions are recommended due to the low solubility of the drug at pH levels below 10.

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

The solution may be administered directly via intravenous route. It may also be given by infusion, diluted exclusively in physiological saline at a final concentration between 1–10 mg/ml. It is advisable to administer physiological saline before and after the infusion through the same catheter or needle to prevent local venous irritation due to the alkalinity of the solution.

Plasma level determination of phenytoin is recommended to ensure efficacy and to adjust subsequent maintenance doses accordingly. Therapeutic serum levels range between 10 and 20 µg/ml.

During infusion, monitoring of vital signs and ECG is recommended.