Package Insert: Information for the User

Mysoline 250 mg Tablets

Primidone

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

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed for 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 package insert. See section 4.

1. What is Mysoline and for what it is used

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

3. How to take Mysoline

4. Possible adverse effects

5. Storage of Mysoline

6. Contents of the package and additional information

Mysoline tablets contain primidone as the active ingredient, which belongs to a group of medicines called anticonvulsants.

Mysoline is used for the treatment of certain types of epilepsy, seizures, or convulsions.

Do not take Mysoline

• If you are allergic (hypersensitive) to primidone, to a substance called phenobarbital, or to any of the other components of this medication (listed in section 6).
• If you have porphyria (a rare and hereditary disorder of metabolism) or if someone in your family has it.
• If you are taking Mysoline simultaneously:

• barbiturates (used to treat congenital deficiency of bile acid synthesis),
• St. John's Wort (herb used to treat depression),
• isavuconazole or voriconazole (antifungal medications),
• cobicistat, nelfinavir, or rilpivirine (used to treat HIV infection),
• delamanid (used to treat tuberculosis),
• telaprevir, daclatasvir, dasabuvir, ombitasvir-paritaprevir, ledipasvir (used to treat hepatitis),
• lurasidone (used to treat schizophrenia),
• sofosbuvir (used to treat hepatitis C infection).

Warnings and precautions

This medication is not effective in certain forms of epilepsy. Your doctor will evaluate the need for this treatment for you.
Consult your doctor immediately if the frequency of your seizures increases or if different types appear.

Consult your doctor or pharmacist before starting to take Mysoline:

• If you have had respiratory, renal, or liver problems
• If you are pregnant or trying to become pregnant (see the information included later).

Inform hospital staff that you are taking Mysoline.

Your doctor may prescribe vitamin D supplements (in case of long-term treatment).

A small number of people treated with antiepileptic medications like primidone have had thoughts of self-harm or suicide. If you ever have these thoughts, contact your doctor immediately.

Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome) have been reported with the use of Mysoline, which initially appear as red spots similar to dianas or circular patches often with blisters on the trunk.

• Other signs to look for include mouth, throat, nose, genital, and conjunctivitis (red and inflamed eyes).
• These severe skin reactions are often accompanied by symptoms similar to a cold. The rash may progress to blisters or generalized skin peeling.
• The greatest risk of severe skin reactions occurs within the first few weeks of treatment.
• If you have developed Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome with the use of Mysoline or any other medication containing phenobarbital, do not take these medications again.

If you experience a rash or these skin symptoms,stop using primidone andimmediately see your doctor and explain that you are taking this medication.

Other medications and Mysoline

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

This is important because some medications may affect the functioning of Mysoline, or Mysoline may affect how other medications work.

Particularly inform your doctor if you are using any of the following:

• other medications used to treat epilepsy or other types of seizures (such as phenytoin, felbamate, valproic acid, carbamazepine, perampanel, oxcarbazepine, stiripentol, tiagabine, zonisamide),
• anticoagulants to prevent blood clots (such as acenocoumarol, phenindione, warfarin),
• barbiturates or benzodiazepines (such as sleeping pills),
• medications used to treat intense pain, cough, or as a substitute for morphine addiction (such as methadone, oxycodone, or fentanyl),
• antibiotics (such as metronidazole, doxycycline, telithromycin),
• medications for asthma (such as theophylline),
• medications containing hormones (such as oral contraceptive pills, estrogen-progestins, progestins, ulipristal),
• thyroid hormones,
• medications used to treat mental health problems or depression (such as tricyclic antidepressants, clozapine, lamotrigine, mianserin, quetiapine, sertraline),
• medications containing steroids,
• medications used to treat cancer (such as abiraterone, axitinib, eribulin, ifosfamide, bosutinib, crizotinib, dabrafenib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, pazopanib, ruxolitinib, sorafenib, sunitinib, vandetanib, regorafenib, vemurafenib, vismodegib, cabozantinib, ceritinib, ibrutinib, olaparib, ponatinib, cabazitaxel, docetaxel, irinotecan, procarbazine),
• bedaquiline (used to treat tuberculosis),
• quinine (used to treat malaria),
• medications used to treat viral infections such as HIV or hepatitis C (such as boceprevir, dolutegravir, lopinavir, maraviroc, ritonavir, simeprevir),
• antifungal medications (albendazole, itraconazole, posaconazole),
• anticoagulants (such as apixaban, dabigatran, rivaroxaban, or ticagrelor),
• folates (vitamin B9),
• medications used to reduce immunity (immunosuppressants, such as cyclosporine, tacrolimus, sirolimus, everolimus),
• deferasirox (iron chelator),
• ivacaftor (medication used to treat cystic fibrosis),
• medications used to treat heart disease, high blood pressure, or to regulate heart rhythms (such as class IA antiarrhythmics, calcium channel blockers, bosentan, digoxin, dronedarone, ivabradine, macitentan, nimodipine, propafenone, ranolazine, or beta-blockers (metoprolol, propranolol)),
• antiparasitic agent (albendazole, praziquantel).

Taking Mysoline with food and drinks

Alcohol may interfere with Mysoline. Drinking alcoholic beverages is not recommended during treatment.

Pregnancy, breastfeeding, and fertility

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

Women of childbearing age should use an effective contraceptive method during treatment. Mysoline may make oral contraceptives ineffective. Therefore, you should use another effective contraceptive method while taking Mysoline. Consult your doctor (see "Other medications and Mysoline").

Women of childbearing age should use an effective contraceptive method during treatment and for two months after treatment. Mysoline may affect the functioning of hormonal contraceptives, such as oral contraceptives, and make them less effective in preventing pregnancy. Talk to your doctor, who will study with you the most suitable method of contraception to use while taking Mysoline.

Women of childbearing age who intend to become pregnant should consult their doctor before stopping contraception and becoming pregnant, about the possibility of switching to other treatments that do not expose the unborn baby to primidone (and therefore to its main metabolite, phenobarbital).

If taken during pregnancy, primidone, which is metabolized mainly to phenobarbital, may cause severe birth defects and affect the child's development as it grows. The birth defects reported in studies include cleft lip (harelip) and cleft palate (harelip in the roof of the mouth) and heart abnormalities. Other congenital anomalies, such as hypospadias (abnormality of the penis), low head size, and facial, nail, and finger abnormalities, have also been reported. Women taking phenobarbital during pregnancy have a higher risk than other women of having a child with birth defects that require medical treatment. In the general population, the basic risk of significant malformations is 2-3%. This risk increases three times in women taking phenobarbital.

Do not stop your treatment abruptly and contact your doctor immediately. Your doctor will consider interrupting treatment or evaluate the potential benefit of continuing treatment in the absence of a less risky alternative for the fetus, in which case:

• During pregnancy: your doctor will adjust your dose to obtain the minimum effective dose for you and establish a specialized prenatal follow-up that is appropriate for your specific case and the treatment you are following.
• Before delivery: you should take vitamin K to prevent bleeding that this medication may cause during the first 24 hours of your baby's life.
• After delivery: an injection of vitamin K may also be prescribed for your baby at birth to prevent any bleeding.

You should not breastfeed while taking this medication. Consult your doctor immediately if you are breastfeeding or if you want to breastfeed.

Babies born to mothers treated with phenobarbital during pregnancy may also be at risk of being smaller than expected.

Severe developmental disorders (delays in development due to disorders in brain development) have been reported in children exposed to phenobarbital (primidone in Mysoline is mainly converted to phenobarbital) during pregnancy. Studies related to the risk of developmental disorders are contradictory.

Mysoline should not be used during pregnancy unless no other treatment is effective.

Talk to your doctor immediately if you are pregnant. Your doctor should study the possible effects of Mysoline tablets on unborn children and consider the risks and benefits of treatment. Do not stop taking primidone until you have consulted your doctor, as abrupt discontinuation may increase the risk of developing seizures, which can have harmful effects on you and the unborn child.

If you take Mysoline during the last trimester of pregnancy, you should undergo appropriate follow-up to detect potential disorders in the newborn, such as seizures, excessive crying, muscle weakness, and sucking disorders.

Driving and operating machinery

Primidone 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, operate machinery, or engage in other activities that require special attention until your doctor evaluates your response to this medication.

Always follow exactly the administration instructions for Mysoline as indicated by your doctor.

If in doubt, consult your doctor or pharmacist again.

Swallow the tablets whole with a little water. The tablet can be divided into equal doses.

The dose will be determined by your doctor and adjusted gradually on an individual basis.

Mysoline is usually taken twice a day. Try to take the tablets at the same time every day.

Initially, the dose may be as low as half a tablet. Your doctor will adjust it until your condition is controlled. The usual maintenance doses are as follows:

Older adults, weakened patients, and patients with renal or hepatic disease:

They may need lower doses. Please consult your doctor.

If you take more Mysoline than you should

If you take an amount greater than the normal dose, contact your doctor or go to the nearest hospital.

If you forget to take Mysoline

If you forget to take a dose, take it as soon as you remember. Do not take a double dose to make up for the missed doses.

If you interrupt treatment with Mysoline

Do not stop treatment with Mysoline, even if you feel well, unless your doctor tells you to. You may have developed a dependence on Mysoline and may experience withdrawal symptoms if you stop treatment too abruptly. To prevent this, treatment with Mysoline should be gradually reduced.

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

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

Very rare(may affect up to 1 in 10,000 people)

• Severe skin reactions that can be fatal (Stevens-Johnson syndrome, toxic epidermal necrolysis) (see section 2).

Unknown frequency(cannot be estimated from available data)

• Lethargy (apathy), coordination disorders, visual disturbances, eye tremors.
• Nausea.

• Headache, dizziness, somnolence..
• Vomiting.
• Allergic skin reaction.
• Dermatitis exfoliativa (common redness and peeling of the skin).
• Severe skin reactions that can be fatal (drug reaction with eosinophilia and systemic symptoms) (see section 2).
• Itching (pruritus).
• Decreased number of some blood cells (red blood cells, white blood cells, or platelets) or development of lymph nodes.
• Mood changes or behavior disorders, libido disorders.
• Pain in the joints or bones, Dupuytren's contracture (a thickening of fibrous tissue in the palm of the hand that causes the retraction of one or more fingers).
• Lupus erythematosus (a disease that causes inflammation of various parts of the body, including the skin, joints, lungs, kidneys, heart, and liver).
• Elevated liver enzyme levels (gamma GT, alkaline phosphatase).
• Suicidal thoughts
• Confusion
• Hallucinations
• Balance disturbances
• Allergic reactions that may include fever, rash, increased number of some blood cells (eosinophils), increased liver enzymes.
• There have been reports of bone disorders, including osteopenia and osteoporosis (bone thinning) and fractures. Consult your doctor or pharmacist if you are taking long-term antiepileptic medications, have a history of osteoporosis, or are taking steroids.
• Osteomalacia (softening of the bones due to vitamin D deficiency).
• Decreased appetite, fatigue.

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 that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicinal Products for Human Use:https://www.notificaram.es. By reporting adverse 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.

Do not store at a temperature above 25 °C.

Do not use this medication after the expiration date that appears on the box 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 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 packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Mysoline

The active ingredient is primidone. Each tablet contains 250 mg of primidone.

The other components are calcium carmelose, gelatin, magnesium stearate, povidone, and stearic acid.

Appearance of the product and contents of the packaging

The tablets are round, white, and uncoated. One side of the tablet has the letter “M” printed on either side of a fracture line. The other side is flat.

Mysoline is presented in packs of 100 tablets.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Laboratoires SERB,

40 Avenue George V,

75008 Paris – FRANCE

Responsible for manufacturing

allphamed PHARBIL Arzneimittel GmbH

Hildebrandstrasse 10-12

37081 Göttingen - GERMANY

Local representative

LABORATORIOS RUBIÓ, S.A.

Carrer Indústria 29 - Polígon Industrial Comte de Sert

08755 Castellbisbal, Barcelona – SPAIN

Date of the last review of this leaflet:07/2024

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