Prospect: information for the patient

Sinergina 100 mg tablets

Fenitoína

Read this prospect carefully before starting to take this medication, as it contains important information for you.

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

1.What Sinergina is and for what it is used

2.What you need to know before starting to take Sinergina

3.How to take Sinergina

4.Possible adverse effects

5.Storage of Sinergina

6.Contents of the package and additional information

Sinergina contains the active ingredient phenytoin.

Phenytoin belongs to a group of medications called antiepileptics, which are used to treat epilepsy.

This medication is indicated for the treatment of the following types of epilepsy: generalized tonic-clonic seizures (grand mal seizure), complex partial seizures, as well as for the treatment and prevention of seizures in neurosurgery.

Do not take Sinergina

• if you are allergic (hypersensitive) to phenytoin or any of the other components of this medication (listed in section 6).
• if you are allergic to hydantoin-type medications.
• if you are taking a medication for HIV infection called delavirdine.

Warnings and precautions

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

• if you have liver disease, other serious diseases, or are an elderly patient. If during treatment you notice symptoms suggestive of hepatitis, such as jaundice (yellowing of the skin and white of the eyes), you must immediately consult your doctor,
• if you have porphyria (a hereditary disease that affects hemoglobin biosynthesis),
• if you are diabetic, as phenytoin can elevate blood glucose levels,
• if you consume large amounts of alcohol or consume small amounts regularly,
• if you are undergoing cranial radiation therapy or reducing your corticosteroid treatment,
• if you are of black race, have a depressed immune system, or have had a family member or you have had a history of hypersensitivity syndrome (HSS) or drug eruption with eosinophilia and systemic symptoms (DRESS) (a syndrome that usually presents with fever, skin rash, lymph node involvement, and other organ involvement, such as the liver, kidneys, heart, lungs, and blood abnormalities), as you have a higher risk of developing this syndrome. If during treatment you present with fever, skin rash with lymph node swelling, which may be signs of drug hypersensitivity, you must immediately consult your doctor,
• severe skin eruptions that can be life-threatening (Stevens-Johnson syndrome and toxic epidermal necrolysis) have been described with the use of this medication. Severe skin effects occur rarely during phenytoin treatment. Initially, they appear as red, circular spots with a central blister. Other additional signs that may appear are mouth, throat, nose, genital, and conjunctivitis (swollen, red eyes) lesions. These life-threatening skin eruptions often occur with flu-like symptoms. The risk may be associated with a variant of a gene in some subjects of Thai or Chinese origin. If you are of this ancestry and have previously been analyzed and know that you have the genetic variant (HLA-B*1502), talk to your doctor before taking phenytoin. If you develop skin eruptions or these symptoms, immediately go to a doctor and inform them that you are taking this medication,
• if during treatment you suffer from confusion (such as delirium, psychosis, etc.), which may be a sign of excessive phenytoin in the blood, you must immediately consult your doctor,
• a small number of people treated with antiepileptics, such as Sinergina, have had suicidal thoughts or attempted suicide. If at any time you have these thoughts, immediately contact your doctor,
• there is a risk of fetal damage if Sinergina is used during pregnancy. Women of childbearing age should use effective contraceptive methods during Sinergina treatment (see "Pregnancy and lactation"),
• if you are of Taiwanese, Japanese, Malay, or Thai origin and have been shown to be a carrier of the CYP2C9*3 mutation.

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

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

Interaction with laboratory tests

Sinergina may interfere with certain laboratory tests that you undergo.

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

Other medications and Sinergina

Before using a new medication with Sinergina, consult your doctor.

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication, including those purchased without a prescription.

Sinergina and certain medications may influence each other (interactions), causing a mismatch in the levels of both medications in the blood.

The following medications may increase phenytoin levels:

• Analgesics/anti-inflammatory agents such as azapropazon, phenylbutazone, and salicylates.
• Anestheticssuch as halothane.
• Antibiotics such aschloramphenicol, erythromycin, isoniazid, sulfadiazine, sulfamethizole, sulfamethoxazole-trimethoprim, sulfafenazol, sulfisoxazole, and sulfonamides.
• Anticonvulsants such as felbamate, oxcarbazepine, valproate sodium, succinimides, and topiramate.
• Antifungals such asamphotericin B, fluconazole, itraconazole, ketoconazole, miconazole, and voriconazole.
• Antineoplastics such as capecitabine and fluorouracil.
• Benzodiazepines/psychotropics such aschlor Diazepoxide, diazepam, disulfiram, methylphenidate, trazodone, and viloxazine.
• Bloqueantes de canales de calcio/agentes cardiovasculares such asamiodarone, dicumarol, diltiazem, nifedipine, ticlopidine.
• Antagonistas-H2 such as cimetidine.
• Inhibidores de la reductasa HMG-Co such as fluvastatin.
• Hormones such as estrogens.
• Inmunosupresores such as tacrolimus.
• Antidiabetic oral agents such astolbutamide.
• Inhibidores de la bomba de protones such as omeprazole.
• Inhibidores de la recaptación de serotoninasuch as fluoxetine, fluvoxamine, sertraline.
• Alcohol (acute ingestion).

The following medications may decrease phenytoin levels:

• Antibiotics such as ciprofloxacin, rifampicin.
• Anticonvulsants such as vigabatrin.
• Antineoplastics such as bleomycin, carboplatin, cisplatin, doxorubicin, and methotrexate.
• Agents antiulcerous such as sucralfate.
• Antiretrovirals such as fosamprenavir, nelfinavir, and ritonavir.
• Bronchodilators such as theophylline.
• Agents cardiovasculares such as reserpine.
• Ácido fólico.
• Agents hiperglucemiantes such as diazoxide.
• Hierba de San Juan.
• Alcohol (chronic ingestion).
• Preparados con calcio, including some antiacids.

The following medications may increase or decrease phenytoin levels:

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

The following medications may alter the levels in the blood and/or effects of the medication::

• Antibiotics such as doxycycline, rifampicin, and tetracycline.
• Anticoagulants, for example, rivaroxaban, dabigatran, apixaban, and edoxaban.
• Anticonvulsants such as carbamazepine, lamotrigine, phenobarbital, valproate sodium, valproic acid.
• Antifungals of the azole family, such as posaconazole and voriconazole.
• Antihelmintics such as albendazole, praziquantel.
• Antineoplastics such as teniposide.
• Antiretrovirals such as delavirdine, efavirenz, fosamprenavir, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, and saquinavir.
• Bronchodilators such as theophylline.
• Bloqueantes de canales de calcio/agentes cardiovasculares such as digitoxin, digoxin, mexiletine, nicardipine, nimodipine, nisoldipine, quinidine, and verapamil.
• Corticosteroids.
• Anticoagulants cumarínicos.
• Ciclosporina.
• Diuréticos such as furosemide.
• Inhibidores de la reductasa HMG-Co such as atorvastatin, fluvastatin, and simvastatin.
• Hormones such as estrogens and oral contraceptives.
• Agents hiperglucemiantes such as diazoxide.
• Inmunosupresores.
• Bloqueantes neuromusculares such as alcuronium, cisatracurium, pancuronium, rocuronium, and vecuronium.
• Analgésicos opioides such as methadone.
• Antidiabetic oral agents such aschlorpropamide, glibenclamide, and tolbutamide.
• Psychotropics/antidepressants such as clozapine, paroxetine, quetiapine, and sertraline.
• Vitamina D.
• Lacosamide (antiepileptic)
• Ticagrelor (inhibidor de la agregación plaquetaria)

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

Administration ofSinerginawith food, drinks, and alcohol

Acute alcohol ingestion may increase phenytoin levels, while chronic alcohol ingestion may decrease them, so you should not consume alcohol during treatment with this medication.

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

Pregnancy, lactation, and fertility

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

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

Pregnancy

If you think you may be pregnant or are planning to become pregnant, inform your doctor before taking Sinergina; they will advise you on the potential risks to you and your baby. This medication should only be administered to pregnant women if, in the doctor's opinion, the expected benefit to the mother outweighs any possible risk to the fetus.

Sinergina may cause severe congenital anomalies. If you take Sinergina during pregnancy, your baby has up to three times the 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 may occur together as part of a hydantoin syndrome.

Severe 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 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.

Fertility

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

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 treatments that will not expose the fetus to phenytoin.

Lactation

It is not recommended to take Sinergina during lactation.

Driving and operating machinery

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

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. It is very important that you strictly comply with them. Inform your doctor of any reason that may prevent you from taking this medication, such as an operation.

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

This medication 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 starting dose of treatment is 300 mg of Sinergina per day divided into three equal doses (1 tablet 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.

For patients who need to quickly reach high serum levels of phenytoin in a state of equilibrium, the recommended loading dose is 1000 mg of phenytoin orally, divided into three doses [400 mg (4 tablets), 300 mg (3 tablets), and 300 mg (3 tablets)], at intervals of 2 hours. This must be done in hospitalized patients as it is necessary to monitor the serum levels of the drug. After 24 hours of administration of the oral loading dose, your doctor will establish the maintenance dose.

Use in elderly people

The dose of Sinergina in elderly patients who may be taking other medications needs to be adjusted by your doctor.

Use in children and adolescents

The initial dose is 5 mg/kg/day divided into 2-3 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/day.

The recommended daily maintenance dose is 4 mg/kg/day to 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 or for patients for whom the dose adjustment is not possible with this presentation. For example, patients weighing less than 40 kg, due to the impossibility of dividing the dose into at least two separate doses.

The grooves serve only to divide the tablet if it is difficult to swallow it whole.

If you take more Sinergina than you should

It is dangerous to take Sinergina at doses higher than those prescribed. The initial symptoms are: involuntary eye movements, muscle coordination difficulties, speech difficulties, tremors, exaggerated reflexes, drowsiness, numbness, prolonged dreams, slurred speech, blurred vision, nausea, and vomiting. The patient may reach a state of coma and hypotension.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Sinergina

Do not take a double dose to compensate for the missed doses. If you forget to take a dose, take it as soon as you remember, unless you are close to the next dose, in which case do not take the missed dose and wait for the next dose, continuing with your established dosing regimen. In case of doubt, consult your doctor or pharmacist.

If you interrupt the treatment with Sinergina

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

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

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

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

• if you experience fever, skin rash, and/or swollen lymph nodes, especially during the first two months of treatment, as they may be signs of a medication hypersensitivity reaction.

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

Other side effects that may occur are:

• General disorders and administration site conditions: allergic reaction.
• Nervous system disorders: nystagmus (abnormal eye movements), ataxia (instability), slurred speech, decreased coordination, dizziness, vertigo, insomnia, transient nervousness, involuntary muscle contractions (uncontrolled movements of different parts of the body), headache, paresthesias (tingling or decreased sensitivity, usually in one foot or one hand), somnolence. Rarely, cases of different types of dyskinesias (uncontrolled movements or postures of different parts of the body) have been reported. In very long-term treatments: peripheral sensory polyneuropathy (alteration of pain and touch sensation). Alteration of taste.
• Skin and subcutaneous tissue disorders:facial skin thickening, lip thickening, gum thickening, hirsutism (excessive hair growth in localized or generalized areas).
• Reproductive and breast disorders: Peyronie's disease (fibrotic hardening of the penis that causes curvature or deviation of the penis during erection).
• Gastrointestinal disorders: vomiting, nausea, constipation.
• Immune system disorders: systemic lupus erythematosus (a disease that affects multiple organs), polyarteritis nodosa (a type of inflammation of the arteries), alterations in immunoglobulins (proteins produced in the immune response).
• Musculoskeletal and connective tissue disorders: osteoporosis (bone decalcification) and other alterations, including decreased levels of calcium, phosphorus, vitamin D, and fractures. Consult your doctor or pharmacist if you are on long-term antiepileptic treatment, have a history of osteoporosis, or take steroids.
• Blood and lymphatic system disorders: decrease in the number of a type of red blood cell (pure red cell aplasia).
• Vascular disorders: vasculitis (inflammation of blood vessel walls).

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 those with poor oral hygiene.

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 System for Pharmacovigilance of Medicines for Human Use:https://www.notificaRAM.es/. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

This product does not require special conditions for conservation.

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

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.

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

Composition of Sinergina 100 mg tablets

• The active ingredient is phenytoin. Each tablet contains 100 mg of phenytoin.
• The other components are: microcrystalline cellulose, magnesium stearate, and povidone K 29/32.

Appearance of the product and content of the packaging

Sinergina 100 mg are round, biconvex, slightly convex tablets, 8 mm in diameter, and white in color. They are presented in a packaging containing 100 tablets in a PVC/AL blister.

Holder of the marketing authorization

Faes Farma, S.A.

Autonomia Etorbidea, 10

48940 Leioa (Bizkaia)

Spain

Responsible for manufacturing

Faes Farma, S.A.

Maximo Agirre Kalea, 14

48940 Leioa (Bizkaia)

Spain

Last review date of this leaflet: November 2022

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