Sinergina 100 mg tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Sinergina 100 mg tablets

Phenytoin

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

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, talk to your doctor or pharmacist, even if they are effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Sinergina is and what it is used for

Sinergina contains the active substance phenytoin.

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

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

2. What you need to know before taking Sinergina

Do not take Sinergina

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

Warnings and precautions

Talk to your doctor or pharmacist before starting to take this medicine.

• if you have liver disease, 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.
• if you have porphyria (a hereditary disorder affecting hemoglobin biosynthesis).
• if you are diabetic, as phenytoin may increase glucose levels.
• if you consume large amounts of alcohol or drink small amounts regularly.
• if you are undergoing cranial radiotherapy or reducing corticosteroid therapy.
• if you are of Black race, have a suppressed immune system, or if you or a family member have previously had a 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 other organs such as the liver, kidneys, heart, lungs, and blood abnormalities), as you have a higher risk of developing this syndrome. If during treatment you develop fever or skin rash with swollen lymph nodes, which may be signs of drug hypersensitivity, you must consult your doctor immediately.
• life-threatening skin rashes (Stevens-Johnson syndrome and toxic epidermal necrolysis) have been reported with the use of this medicine. Serious skin reactions occur rarely during treatment with phenytoin. Initially, they appear as red spots or circular lesions, often with a central blister. Other possible signs 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 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 develop skin rashes or these symptoms, seek medical attention immediately and inform your doctor that you are taking this medicine.
• if during treatment you experience confusion (e.g., delirium, psychosis), which may indicate excessive levels of phenytoin in the blood, consult your doctor immediately.
• a small number of patients treated with antiepileptic medicines such as Sinergina have had thoughts of harming themselves or suicide. If you experience such thoughts at any time, contact your doctor immediately.
• there is a risk of fetal harm if Sinergina is used during pregnancy. Women of childbearing potential must use effective contraception during treatment with Sinergina (see "Pregnancy and breastfeeding").
• if you are of Taiwanese, Japanese, Malay, or Thai origin and testing has shown you carry the CYP2C9*3 mutation.

During treatment with this medicine, it is important to maintain good oral hygiene. This can help prevent adverse effects in the mouth, such as gum enlargement.

It is very important that your doctor monitors your treatment during regular visits and performs regular blood tests to rule out blood abnormalities, monitor liver function, and occasionally adjust the most appropriate dose of Sinergina.

Interference with laboratory tests

Sinergina may interfere with certain laboratory tests you undergo.

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

Other medicines and Sinergina

Before using any new medicine with Sinergina, you must consult your doctor.

Tell your doctor or pharmacist if you are using, have recently used, or might need to use any other medicines, including those obtained without a prescription.

Sinergina and certain medicines may interact with each other, causing imbalances in the blood levels of both drugs.

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

• Analgesics/anti-inflammatory drugs such as azapropazone, phenylbutazone, and salicylates.
• Anesthetics such as halothane.
• Antibiotics such as chloramphenicol, erythromycin, isoniazid, sulfadiazine, sulfamethizole, sulfamethoxazole-trimethoprim, sulfaphenazole, sulfisoxazole, and sulfonamides.
• Anticonvulsants such as felbamate, oxcarbazepine, sodium valproate, succinimides, and topiramate.
• Antifungals such as amphotericin B, fluconazole, itraconazole, ketoconazole, miconazole, and voriconazole.
• Antineoplastics such as capecitabine and fluorouracil.
• Benzodiazepines/psychotropics such as chlordiazepoxide, diazepam, disulfiram, methylphenidate, trazodone, and viloxazine.
• Calcium channel blockers/cardiovascular agents such as amiodarone, dicumarol, diltiazem, nifedipine, and ticlopidine.
• H2 antagonists such as cimetidine.
• HMG-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 vigabatrin.
• Antineoplastics such as bleomycin, carboplatin, cisplatin, doxorubicin, and methotrexate.
• Antiulcer agents such as sucralfate.
• Antiretrovirals such as 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:

• Antibiotics such as doxycycline, rifampicin, and tetracycline.
• Anticoagulants, e.g., rivaroxaban, dabigatran, apixaban, and edoxaban.
• Anticonvulsants such as carbamazepine, lamotrigine, phenobarbital, sodium valproate, and valproic acid.
• Azole antifungals such as posaconazole and voriconazole.
• Anthelmintics such as albendazole and praziquantel.
• Antineoplastics such as teniposide.
• 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, mexiletine, nicardipine, nimodipine, nisoldipine, quinidine, and verapamil.
• Corticosteroids.
• Coumarin anticoagulants.
• 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, and tolbutamide.
• Psychotropics/antidepressants such as clozapine, paroxetine, quetiapine, and sertraline.
• Vitamin D.
• Lacosamide (antiepileptic).
• Ticagrelor (platelet aggregation inhibitor).

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

Taking Sinergina with food, drinks, and alcohol

Acute alcohol intake may increase phenytoin levels, while chronic alcohol intake may decrease them. Therefore, you should not consume alcohol during treatment with this medicine.

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

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

If you are pregnant or think you might be, inform your doctor immediately. Do not stop taking the medicine until you have discussed it with your doctor. Stopping your medicine without medical advice could cause seizures, which may 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. Your doctor will advise you of the potential risks to you and your baby. This medicine should only be given to pregnant women if, in the doctor’s judgment, the expected benefit to the mother outweighs any possible risk to the fetus.

Sinergina may cause serious congenital malformations. If you take Sinergina during pregnancy, your baby has up to three times the risk of congenital malformations compared to babies of women not taking antiepileptic medicines. Serious congenital malformations have been reported, including abnormalities in growth, skull, face, nails, fingers, and heart. Some of these may occur together as part of a fetal hydantoin syndrome.

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

Fertility

If you are a woman of childbearing potential and do not plan to become pregnant, you must use contraception during treatment with Sinergina. This medicine may affect the effectiveness of hormonal contraceptives, such as the birth control pill, making them less effective in preventing pregnancy. Consult your doctor, who will discuss with you the most appropriate type of contraception to use while taking Sinergina.

If you are a woman of childbearing potential and plan to become pregnant, consult your doctor before stopping contraception and before becoming pregnant about switching to other suitable treatments to avoid fetal exposure to phenytoin.

Breastfeeding

Sinergina is not recommended during breastfeeding.

Driving and using machines

Phenytoin may cause symptoms such as drowsiness, dizziness, or visual disturbances, and may reduce reaction ability. These effects, as well as the underlying illness itself, may impair your ability to drive or operate machinery. Therefore, do not drive or operate machinery, or engage in other activities requiring special alertness, until your doctor has assessed your response to this medicine.

3. How to take Sinergina

Follow exactly the instructions for using this medicine given by your doctor or pharmacist. It is very important that you strictly adhere to them. Inform your doctor of any circumstances that may prevent you from taking this medicine, such as surgery, for example.

If in doubt, consult your doctor or pharmacist again.

This medicine should be taken with at least half a glass of water. If you are prone to nausea or stomach heaviness, you may take the medicine during or after meals.

Adults

The initial 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 determine the maintenance dose you require, which must not exceed the maximum daily dose of 600 mg.

For patients who need to rapidly achieve high serum levels of phenytoin at steady state, the recommended loading dose is 1000 mg of phenytoin administered orally, divided into three doses [400 mg (4 tablets), 300 mg (3 tablets), and 300 mg (3 tablets)], given at 2-hour intervals. This should only be performed in hospitalized patients, as monitoring of serum drug levels is required. Twenty-four hours after administration of the oral loading dose, your doctor will establish the maintenance dose.

Use in elderly patients

The dose of Sinergina in elderly patients, who may be taking other medications, must 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 this starting point, the maintenance dose should be individually established by your doctor, not exceeding the maximum daily dose of 300 mg.

The recommended daily maintenance dose is 4 mg/kg/day to 8 mg/kg/day. If the daily dose cannot be evenly divided, the larger dose should be taken at night.

This formulation is not suitable for use in newborns, infants, children, and adolescents, or for patients for whom dose adjustment based on body weight is not feasible with this formulation. For example, patients weighing less than 40 kg, due to the inability to divide the dose into at least two separate administrations.

The score lines on the tablets are intended solely to facilitate tablet splitting if you have difficulty swallowing it whole.

If you take more Sinergina than you should

Taking Sinergina in doses higher than prescribed is dangerous. Initial symptoms include: involuntary eye movements, lack of muscle coordination, difficulty speaking, tremors, exaggerated reflexes, drowsiness, numbness, excessively prolonged sleep, slurred speech, blurred vision, nausea, and vomiting. The patient may progress to coma and hypotension.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at: 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to take Sinergina

Do not take a double dose to make up for missed doses. If you forget to take a dose, take it as soon as you remember, unless it is almost time for your next dose. In that case, do not take the missed dose; simply take the next dose at the scheduled time and continue with your established dosing regimen. If in doubt, consult your doctor or pharmacist.

If you stop taking Sinergina

Do not stop treatment with Sinergina unless instructed by your doctor. Abruptly discontinuing the medicine may increase the frequency of seizures. If your doctor decides that treatment with this medicine should be discontinued, they will determine the most appropriate alternative treatment for you.

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

4. Possible adverse effects

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

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

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

• if you experience mental confusion or severe mental disturbance, as this may indicate high levels of phenytoin in your blood. Your doctor will perform blood tests to determine your phenytoin levels and, if necessary, may reduce your dose or even discontinue treatment.

• if you notice bruising, fever, or oral bleeding. These may be early signs of a blood disorder, including a reduced 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, diarrhoea, fatigue or weakness, yellowing of the skin and eyes (jaundice), or liver enlargement, as these may indicate liver problems.

• if you develop a severe skin rash with blistering (also affecting the mouth and tongue). These may be symptoms of a condition known as Stevens-Johnson syndrome or toxic epidermal necrolysis (TEN).

Other adverse effects that may occur include:

• General disorders and administration site conditions: allergic reaction.

• Nervous system disorders: nystagmus (abnormal eye movements), ataxia (lack of coordination), slurred speech, decreased coordination, dizziness, vertigo, insomnia, transient nervousness, motor twitching (involuntary movements of different body parts), headache, paresthesia (tingling or reduced sensation, usually in a hand or foot), somnolence. Rarely, various types of dyskinesias (involuntary movements or postures of different body parts) have been reported. With very long-term treatment: predominantly sensory peripheral polyneuropathy (altered sensation to pain and touch). Alteration of taste.

• Skin and subcutaneous tissue disorders: coarsening of facial features, thickening of the lips, gum enlargement, hypertrichosis (excessive hair growth, localized or generalized).

• Reproductive system and breast disorders: Peyronie's disease (fibrous thickening of the penis causing curvature during erection).

• Gastrointestinal disorders: vomiting, nausea, constipation.

• Immune system disorders: systemic lupus erythematosus (an immune disease affecting various organs), polyarteritis nodosa (a type of arterial inflammation), immunoglobulin abnormalities (changes in immune response proteins).

• Musculoskeletal and connective tissue disorders: osteoporosis (bone demineralization) and other bone changes, including decreased levels of calcium, phosphorus, vitamin D, and fractures, have been reported. Consult your doctor or pharmacist if you are on long-term antiepileptic treatment, have a history of osteoporosis, or are taking corticosteroids.

• Blood and lymphatic system disorders: decrease in 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

Reported adverse events are generally similar in children and adults. Gingival hyperplasia occurs more frequently in paediatric patients and in those with poor oral hygiene.

Reporting of adverse effects

If you experience any adverse effect, talk to 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: https://www.notificaRAM.es/. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Sinergina

No special storage conditions are required.

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

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.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at the SIGRE collection point at your pharmacy. If you have any doubts, ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Sinergina 100 mg tablets

• The active substance 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 contents of the pack

Sinergina 100 mg are round, biconvex, slightly convex tablets, 8 mm in diameter and white in colour. They are supplied in a pack containing 100 tablets in PVC/AL blisters.

Marketing Authorization Holder

Faes Farma, S.A.

Autonomia Etorbidea, 10

48940 Leioa (Bizkaia)

Spain

Manufacturer

Faes Farma, S.A.

Maximo Agirre Kalea, 14

48940 Leioa (Bizkaia)

Spain

Or

Faes Farma, S.A.

Parque Científico y Tecnológico de Bizkaia

Ibaizabal Bidea, Edificio 901

48160 Derio (Bizkaia)

Spain

Date of the most recent review of this leaflet: November 2022

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es