Patient Information Leaflet

FENITOÍNA ALTAN 50 mg/ml INJECTABLE SOLUTION

Fenitoína

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

This medication is indicated for:

• Treatment of different types of epilepsy.
• Treatment and prevention of seizures that affect the entire body or some of its parts with muscle rigidity and may lead to loss of consciousness. Treatment and prevention of seizures in neurosurgery.

Treatment of irregular heartbeats (atrial and ventricular arrhythmias), especially those caused by medication used to treat heart problems (digoxin) overdose.

No use Fenitoína Altan:

• If you are allergic to phenytoin or any of the other components of this medication (listed 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 disturbances (Adam-Stokes syndrome).

Advertencias y precauciones

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

• If you have severe liver or heart problems or low blood pressure (hypotension). Your doctor will perform regular checks.
• If you are receiving treatment with vitamin D or derivatives, as simultaneous use with phenytoin may cause progressive softening of bones with possible fractures.
• If you have diabetes, as phenytoin may cause hyperglycemia by increasing blood glucose levels.

- If you are pregnant or breastfeeding.

• Severe skin eruptions that may threaten the patient's life (Stevens-Johnson syndrome and toxic epidermal necrolysis) have been described with the use of phenytoin, initially appearing as red circular spots with a central blister.
• Other signs that may appear include mouth, throat, nose, genital, and conjunctivitis (swollen and red eyes).
• These skin eruptions that may threaten the patient's life often occur with flu-like symptoms. The rash may progress to generalized blistering or skin peeling.
• The highest risk period for severe skin reactions is during the first weeks of treatment.
• If you have developed Stevens-Johnson syndrome or toxic epidermal necrolysis with the use of phenytoin, do not use this medication again at any time.
• If you develop rashes or these skin symptoms, stop taking phenytoin, immediately see a doctor, and inform them that you are taking this medication. Stopping treatment abruptly may precipitate a seizure.
• If you are of Taiwanese, Japanese, Malay, or Thai origin and have been shown to be a carrier of the CYP2C9*3 mutation.

Do not drink alcoholic beverages while taking this medication (see use with food and beverages).

Do not administer phenytoin to children as it contains alcohol as an excipient.

Severe skin irritation and inflammation at the injection site, with and without the solution leaking from the vein, have been described. This irritation may range from mild sensitivity to extensive tissue destruction, so avoid improper administration of this medication to prevent these effects.

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

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

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

Consult your doctor, even if any of the previously mentioned circumstances have occurred at any time.

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

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

Use of Fenitoina Altan with other medications

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

While taking phenytoin, you should use the following medications with special caution:

• Chloramphenicol and sulfonamide: antibiotics that may cause an increase in phenytoin blood levels, making its effect too strong. The effect of antibiotics may be reduced by the presence of phenytoin.
• Rifampicin and doxycycline: antibiotics whose effect may be reduced by the presence of phenytoin.
• Dicumarol (cumarin anticoagulants): antagonist of vitamin K that may cause an increase in phenytoin blood levels, making its effect too strong.
• Disulfiram: medication used for alcoholism treatment that may cause an increase in phenytoin blood levels, making its effect too strong.
• Tolbutamide: medication in the sulfonilurea group used for diabetes treatment that may cause an increase in phenytoin blood levels, making its effect too strong.
• Isoniazid: antituberculosis medication that may cause an increase in phenytoin blood levels, making its effect too strong.
• Phenylbutazone and salicylates: non-steroidal anti-inflammatory medications that may cause an increase in phenytoin blood levels, making its effect too strong.
• Chlordiazepoxide, diazepam, and phenothiazines: benzodiazepine-derived medications that may cause an increase in phenytoin blood levels, making its effect too strong.
• Carbamazepine: benzodiazepine-derived medication that may reduce the effect of phenytoin.
• Estrogens: female sex hormones that may cause an increase in phenytoin blood levels, making its effect too strong. The effect of estrogens may be reduced by the presence of phenytoin.
• Ethosuximide, succinimide: anticonvulsant medications that may cause an increase in phenytoin blood levels, making its effect too strong.
• Halothane: anesthetic medication that may cause an increase in phenytoin blood levels, making its effect too strong.
• Methylphenidate: psychostimulant medication used for attention deficit hyperactivity disorder (ADHD) treatment that may cause an increase in phenytoin blood levels, making its effect too strong.
• H2 antagonists: antihistamines that may cause an increase in phenytoin blood levels, making its effect too strong.
• Trazodone: antidepressant medication that acts by inhibiting serotonin reuptake and may cause an increase in phenytoin blood levels, making its effect too strong.
• Amiodarone: medication used for cardiac arrhythmia treatment that may cause an increase in phenytoin blood levels, making its effect too strong.
• Fluoxetine: selective serotonin reuptake inhibitor medication that may cause an increase in phenytoin blood levels, making its effect too strong.
• Reserpine: medication used as an antipsychotic and antihypertensive that may reduce the effect of phenytoin.
• Diazoxide: antihypertensive medication that may reduce the effect of phenytoin.
• Folic acid: vitamin that may reduce the effect of phenytoin.
• Sucralfate: medication used for gastrointestinal ulcer treatment that may reduce the effect of phenytoin.
• Valproic acid and valproate sodium: antiepileptic medications that may decrease phenytoin levels.
• Phenobarbital: antiepileptic medication that may alter phenytoin blood levels.
• Tricyclic antidepressants at high doses: simultaneous administration with phenytoin may cause seizures.
• Lidocaine: simultaneous administration with phenytoin by intravenous route may lead to excessive cardiac depression.
• Corticosteroids: steroid hormones whose effect may be reduced by the presence of phenytoin.
• Oral contraceptives: their effect may be reduced by the presence of phenytoin.
• Quinidine and digitoxin: antiarrhythmic medications whose effect may be reduced by the presence of phenytoin.
• Vitamin D: its effect may be reduced by the presence of phenytoin.
• Furosemide and theophylline: diuretics whose effect may be reduced by the presence of phenytoin.
• Anticoagulants, for example, rivaroxaban, dabigatran, apixaban, and edoxaban
• Lacosamide
• Ticagrelor

Phenytoin may interfere with the following laboratory tests: metyrapone, dexamethasone, iodine bound to proteins, glucose, alkaline phosphatase, and GGT.

Uso de fenitoína con alimentos, bebidas y alcohol

During treatment with this medication, avoid taking alcohol. A high dose of alcohol may increase phenytoin blood levels, while chronic alcohol consumption may decrease them.

Embarazo, lactancia y fertilidad

Embarazo

Consult your doctor or pharmacist before using this medication.

Like other antiepileptic medications, there is a relationship between the administration of phenytoin and the occurrence of congenital malformations, so it should not be used as a first-line medication during pregnancy, especially during the first trimester, and the benefit-risk ratio should be evaluated in each case.

If phenytoin is being administered to prevent grand mal seizures, do not suspend antiepileptic medication, as it may precipitate status epilepticus, which carries the risk of maternal and fetal hypoxia.

During pregnancy, seizures may increase in frequency due to altered absorption or metabolism of phenytoin. Therefore, it is essential to determine serum levels to establish the dose for each patient. After delivery, the dose may need to be adjusted to the pre-pregnancy dose.

Phenytoin administered before delivery causes a lack of vitamin K and related clotting factors. This increases the risk of hemorrhage during delivery for the mother or newborn; to prevent it, vitamin K may be administered to the mother in the last month of pregnancy and to the newborn immediately after birth.

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

Phenytoin may cause severe congenital anomalies. If you take phenytoin during pregnancy, your baby has up to three times the risk of having a congenital anomaly compared to women who do not take an antiepileptic medication. Severe congenital anomalies, such as growth, 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 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. The possibility of an effect on neurological development cannot be ruled out.

Lactancia

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

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

Conducción y uso de máquinas

Phenytoin may cause symptoms such as drowsiness, dizziness, or visual disturbances, and may decrease your reaction time. These effects, as well as the underlying disease, may impair your ability to drive vehicles or operate machinery. Therefore, do not drive, operate machinery, or engage in other activities that require special attention until your doctor evaluates your response to this medication.

Fenitoían Altan contiene etanol y propilenglicol

This medication contains 10% ethanol (ethyl alcohol) corresponding to 165 mg per 2 ml ampoule, which is 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 individuals with alcoholism.

The alcohol content should be taken into account in 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 recommended by your doctor. Your doctor may perform additional checks while you are taking this medication.

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

Follow exactly the administration instructions of this medication 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 crises)

Adults: An initial 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 initial dose should be continued for 24 hours with a maintenance dose of 5-7 mg/kg/day administered intravenously in 3 or 4 doses.

Newborns and children:An initial 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 an initial dose, 15-18 mg/kg/24 h, divided into 3 doses (1/2 dose initially, 1/4 dose at 8 hours and 1/4 dose at 16 hours); continue with maintenance doses of 5-7 mg/kg/24 h, divided into 3 doses (one every 8 hours), i.e., at 24, 32, 40 hours and subsequent.

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

- Arrhythmias

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

- Elderly patients and/or liver insufficiency

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

If you use more Fenitoína Altan than you should

If you have used more fenitoína 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 the treatment suspended. Treatment consists of maintaining respiration and blood circulation and taking the necessary supportive measures.

If you forgot to use Fenitoína Altan

Do not use a double dose to compensate for the missed doses.

If you interrupt the treatment with Fenitoína Altan

Consult your doctor to indicate how to restart the treatment.

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

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

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

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

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

Very common: affects more than 1 in 10 patients

Common: affects 1 to 10 patients in 100

Uncommon: affects 1 to 10 patients in 1,000

Rare: affects 1 to 10 patients in 10,000

Very rare: affects fewer than 1 in 10,000 patients

Unknown: cannot be determined from available data.

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

Very common (affects more than 1 in 10 patients)

• CARDIOVASCULAR DISORDERS:hypotension (avoid rapid administration).

• NEUROLOGICAL DISORDERS:involuntary eye movements (nystagmus), inability to coordinate movements (ataxia), stuttering speech, decreased coordination, and mental confusion, dizziness, insomnia, nervousness, and headache.

Common (affects 1 to 10 patients in 100)

• GASTROINTESTINAL DISORDERS:nausea, vomiting, constipation.

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

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

• CARDIOVASCULAR DISORDERS: decreased heart function and ventricular fibrillation. These complications usually occur more frequently in the elderly or severely ill.

• BLOOD AND LYMPHATIC SYSTEM DISORDERS:some complications found have been fatal. Skin eruptions and lymph node disease may appear.

• HEPATOBIILIARY DISORDERS: liver damage.

• NEUROLOGICAL DISORDERS: involuntary movements, including sudden movements, rigidity, tremors, and tremors in the wrists.

-GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS:local irritation, inflammation, allergy, tissue destruction, and scabbing.

• Skin and subcutaneous tissue disorders:widespread skin peeling.

Very rare (affects fewer than 1 in 10,000 patients) or unknown (cannot be estimated from available data)

• IMMUNE SYSTEM DISORDERS:chronic inflammatory disease that can affect many organs of the body (Systemic Lupus Erythematosus), inflammation of tissues surrounding arteries with nodule production (periarteritis nodosa), and abnormalities in immunoglobulins (antibody proteins).

• HEPATOBIILIARY DISORDERS:toxic liver inflammation.

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

• MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS:facial roughness, lip swelling, gum inflammation, and alterations in penile erection (Peyronie's disease).

• BLOOD AND LYMPHATIC SYSTEM DISORDERS:decreased number of a type of red blood cell (pure red cell aplasia).

If you consider that any of the side effects you are experiencing are severe or if you notice any

side effect not mentioned in this prospectus, inform your doctor or pharmacist.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, 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: 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.

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 have formed.

Medications should not be disposed of through drains or trash. Ask your pharmacist how to dispose of the packaging and medications you no longer need. In this way, you will help protect the environment.

Fenitoína Altan Composition

The active ingredient is sodium phenytoin.

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

Product appearance and packaging contents

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

Marketing authorization holder and manufacturer responsible

Marketing authorization holder:

Altan Pharmaceuticals, S.A.

c/ Cólquide, 6. Portal 2, 1st floor – Office F

Edificio Prima

28230 - Las Rozas. MADRID

Spain

Manufacturer responsible:

Laboratorio Reig Jofré, S.A.

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

Spain

Last review date of this leaflet: August / 2021

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

This information is intended solely for healthcare professionals:

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

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

The solution can be administered directly via intravenous injection. It can also be administered by infusion by diluting exclusivelyin physiological saline at a final concentration between 1-10 mg/ml.It is recommended to administer physiological saline through the same catheter or needle before and after the infusion to avoid local venous irritation due to the alkalinity of the solution.

It is recommended to determine the plasma levels of phenytoin to ensure efficacy and adjust the maintenance doses as necessary. Therapeutic levels in serum range from 10 to 20µg/ml.

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