Active ingredients: Primidone
Mysoline 250 mg tablets
Why is Mysoline used? What is it for?
Mysoline contains the active substance primidone which belongs to a group of medicines used to treat seizures.
Mysoline is used to treat certain types of epilepsy and seizures, such as:
- Big bad
- Psychomotor epilepsy (temporal lobe epilepsy)
- Idiopathic, post-traumatic epilepsies associated with clear signs of brain injury or with changes in the EEG pattern (if you are resistant to other therapies)
- Focal and Jacksonian crises
- Myoclonic and akinetic seizures Talk to your doctor if you feel no better or feel worse.
Contraindications When Mysoline should not be used
Do not take Mysoline
- if you are allergic to the active substance, to barbiturates (medicines used for insomnia or to treat epilepsy) or to any of the other ingredients of this medicine (listed in section 6);
- if you have porphyria (a rare inherited disorder of blood metabolism).
Precautions for use What you need to know before you take Mysoline
Talk to your doctor or pharmacist before taking Mysoline.
Pay particular attention:
- in case of prolonged treatment because this medicine can be addictive;
- if you are a woman and you are taking oral contraceptives, because during treatment with this medicine you may no longer be protected against pregnancy and bleeding between periods may occur (see section 2 "Other medicines and Mysoline");
- if you have or have had thoughts of harming (self-harming) or killing yourself. Whenever these thoughts occur to you, contact your doctor immediately;
- if you are elderly or debilitated or if you have breathing, kidney or liver problems (see section 3 "How to take Mysoline" - "Use in the elderly and in patients with breathing, kidney or liver problems").
Children
Caution is required in children, for whom the doctor may prescribe a lower dose.
Interactions Which drugs or foods can change the effect of Mysoline
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
This is important because some medicines can alter the way Mysoline works, or Mysoline can alter the way other medicines work.
In particular, tell your doctor if you are taking:
- medicines used to thin the blood (anticoagulants),
- medicines containing steroids
- medicines for bacterial infections (antibiotics)
- oral contraceptives
- medicines used against seizures (anticonvulsants) such as phenytoin, because Mysoline reduces their effectiveness;
- medicines that depress the central nervous system such as barbiturates or alcohol, as the effect may be increased.
Mysoline with alcohol
This medicine may increase the effects of alcohol. Ask your doctor for advice before drinking alcohol.
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
If you are planning to become pregnant it is important that you first talk to your doctor about continuing antiepileptic therapy.
This medicine should not be used during pregnancy unless strictly necessary and under medical supervision.
Only take this medicine during pregnancy if your doctor prescribes it for you, as it may increase the risk of malformations in your baby (cleft lip, heart and blood vessel malformations, nervous system development problems).
Pregnant women may have a decrease in folic acid in their blood when taking Mysoline. In addition, babies of mothers who have taken this medicine during the last period of pregnancy may develop withdrawal symptoms after birth.
Occasionally, clotting problems have been observed in the offspring of mothers who took seizure medication during pregnancy.
Do not suddenly stop taking this medicine as this can cause a sudden onset of convulsions, which can have serious consequences for you and your baby (see section 3 "If you stop taking Mysoline").
Feeding time
The primidone contained in this medicine passes into breast milk and the infant may cause drowsiness or weakness. If you notice these symptoms in your baby, stop breastfeeding.
Driving and using machines
This medicine can reduce your alertness and the alertness of your reflexes. These effects may impair your ability to drive or use machines.
Do not drive or use machines if any of these effects occur.
Dose, Method and Time of Administration How to use Mysoline: Posology
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
The dose, frequency of use and duration of therapy will be determined by your doctor according to your disease.
The dose is usually divided into two intakes per day (morning and evening).
The start of treatment will be gradual. Treatment will begin with a low dose, which may be half a tablet (125 mg) per day to be taken in the late evening for the first 3 days.
This dose will be adjusted by your doctor until you have achieved control of your disease:
Adults: increase the daily dosage of half a tablet every 3 days up to a dose of 2 tablets a day, to be taken in the morning and in the evening. Then increase every 3 days by one tablet until the optimal dosage for seizure control is reached (maximum dose 6 tablets / day). Children: the daily dosage can be increased by half a tablet at intervals of 3 days, until the effect is achieved. therapeutic (maximum dose 4 tablets / day).
The recommended doses for maintenance treatment are:
Use in the elderly and in patients with respiratory, kidney or liver problems
If you are elderly or have breathing, kidney or liver problems, you will be prescribed a reduced dose.
If you forget to take Mysoline
Do not take a double dose to make up for a forgotten dose.
If you stop taking Mysoline
Do not abruptly stop taking this medicine without first talking to your doctor, as this can cause sudden onset of seizures.
Treatment should be reduced gradually and under medical supervision.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Overdose What to do if you have taken too much Mysoline
If you take more Mysoline than prescribed, tell your doctor immediately or go to the nearest hospital. Take this sheet with you.
Symptoms of an overdose can be: disturbances in coordination of movements (ataxia), unconsciousness (loss of consciousness), severe difficulty in breathing (respiratory depression) and coma.
Side Effects What are the side effects of Mysoline
Like all medicines, this medicine can cause side effects, although not everybody gets them.
At the beginning of treatment with Mysoline the following may occur: drowsiness, irritability, inattention.
Side effects reported are:
- symptoms of toxicity to the nervous system, in particular disturbances in coordination of movements (ataxia), dizziness, headache (headache);
- rhythmic and involuntary oscillations of the eyes (nystagmus);
- visual disturbances;
- nausea and vomit;
These effects tend to pass spontaneously, but, in the case of strong individual sensitivity to the drug, they can be so serious as to require discontinuation of treatment;
- severe skin reactions, including severe rashes.
Rarely have also been reported:
- a severe alteration of the organism called "systemic lupus erythematosus";
- joint pain (arthralgia);
- personality changes, including psychotic reactions;
- swollen legs (edema in the lower limbs);
- thirst;
- excessive urine production (polyuria);
- decreased sexual potency;
- anemia characterized by abnormally shaped red blood cells (megaloblastic anemia) and other changes in the blood (blood dyscrasias).
There have been reports of bone disease including osteopenia and osteoporosis (thinning of the bones) and fractures. Contact your doctor or pharmacist if you have been on antiepileptic medication for a long time, or if you have a history of osteoporosis, or if you are taking steroids.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the website: www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
This medicine does not require any special storage conditions.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after "Expiry". The expiry date refers to the last day of that month.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Deadline "> Other information
What Mysoline contains
- The active ingredient is primidone. Each tablet contains 250 mg of primidone.
- The other ingredients are: povidone, gelatin, carmellose calcium, magnesium stearate, stearic acid.
What Mysoline looks like and contents of the pack
Mysoline comes in a box containing 30 tablets in blister packs.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT -
MYSOLINE 250 MG TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
1 tablet contains:
Primidone 250 mg
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Tablets.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Mysoline is indicated in the treatment of grand mal and psychomotor epilepsy (temporal lobe epilepsy).
The high efficacy of Mysoline in these forms has also been clinically documented in patients resistant to other therapies, suffering from idiopathic, post-traumatic forms, associated with clear signs of brain injury or with specific modifications of the EEG trace.
Mysoline can also be used in the therapy of focal or Jacksonian seizures, myoclonic and akinetic seizures.
04.2 Posology and method of administration -
Treatment with Mysoline should always be conducted on an individual basis in relation to the patient's clinical response. In general, the evaluation of the effectiveness of the drug can be carried out after a few weeks of therapy. In many patients Mysoline has proved effective alone, otherwise it should be combined with other anticonvulsants.
Treatment should be started gradually.
Dosage
INITIAL DOSAGE
Adults:
For the first 3 days, start with half a tablet daily late in the evening. Increase the daily dosage of half a tablet every 3 days up to a dose of 2 tablets a day, to be taken in the morning and in the evening. Then increase every 3 days by one tablet until the optimal dosage for seizure control is reached (maximum dose 6 tablets / day).
Pediatric population:
Children up to 9 years: for the first 3 days start with half a tablet a day; subsequently, the daily dosage can be increased by half a tablet at intervals of 3 days, until the therapeutic effect is achieved (maximum dose 4 tablets / day).
AVERAGE MAINTENANCE DOSAGE
Adults:
3-6 tablets / day.
Pediatric population:
Children up to 2 years 1-2 tablets / day
Children from 2 to 5 years 2-3 tablets / day
Children from 6 to 9 years 3-4 tablets / day
Children over 9 years 3-6 tablets / day
The daily dosage should not exceed 2 g.
Method of administration
It is advisable to divide the daily dosage into two equal doses, to be taken in the morning and in the evening.
In some patients, it may be convenient to give larger doses when seizures are more frequent. For instance:
-administration in a single dose in the evening, or with higher doses in the evening, in the case of nocturnal attacks;
- if the attacks are associated with particular situations, such as the menstrual cycle, it is often useful to slightly increase the dosage during this period.
Elderly and debilitated patients:
Dosage reduction may be required in the elderly and in patients who are debilitated or with impaired renal, hepatic or respiratory function.
Patients already being treated with other anticonvulsant drugs:
If the patient's symptoms are not sufficiently controlled by other anticonvulsant drugs or significant side effects have arisen, Mysoline can be combined with or replace the current treatment.
It is advisable to initially associate Mysoline with the drug already in use following the described gradual administration scheme. Once an appreciable clinical effect has been reached and a dosage of Mysoline considered sufficient, the previous therapy can be suspended, always gradually, over a period of two weeks: a too rapid suspension could cause the onset of a state of disease.
Sometimes, when the previous treatment is interrupted, the dose of Mysoline must be increased. However, if the previous treatment is largely represented by phenobarbital, both its discontinuation and the substitution of Mysoline therapy, to prevent "excessive interaction sleepiness, must be done more quickly and at the same time an evaluation should be made. accurate dosage of Mysoline.
04.3 Contraindications -
Hypersensitivity to the active substance, to barbiturates in general, or to any of the excipients listed in section 6.1.
Patients with porphyria.
04.4 Special warnings and appropriate precautions for use -
Observe the common precautions of anticonvulsant therapy with barbiturate derivatives; after prolonged administration tolerance and drug dependence may develop.
Abrupt discontinuation of treatment in epileptic patients can induce a status of epilepticus.
The association with other psychotropic drugs requires particular caution and vigilance on the part of the physician to avoid unexpected undesirable effects from interaction.
The drug should be used with caution and dosage reduction may be required in children, the elderly, debilitated patients or with impaired renal, hepatic or respiratory function.
In women taking oral contraceptives and anticonvulsant drugs, intermenstrual bleeding and failure of contraceptive therapy have been reported: this is probably determined by the inducing action of liver enzymes caused by anticonvulsants, which may result in an accelerated hormonal metabolism.
The drug should be used with caution and dosage reduction may be required in the elderly, in debilitated patients or with impaired renal, hepatic or respiratory function.
Cases of suicidal ideation and behavior have been reported in patients receiving antiepileptic drugs in their various indications. A meta-analysis of randomized clinical trials versus placebo also highlighted the presence of a modest increase in the risk of suicidal ideation and behavior.
The mechanism of this risk has not been established and the available data do not exclude the possibility of an increased risk with Mysoline.
Therefore, patients should be monitored for signs of suicidal ideation and behavior and appropriate treatment should be considered if so. Patients (and caregivers) should be instructed to notify their treating physician if signs of suicidal ideation or behavior emerge.
Pediatric population
The drug should be used with caution and dosage reduction may be required in children.
04.5 Interactions with other medicinal products and other forms of interaction -
Phenobarbital, the metabolite of primidone, is an enzyme inducer, therefore the efficacy of some drugs (anticoagulants, adrenal steroids, antibiotics, oral contraceptives and anticonvulsants such as phenytoin) can be reduced by progressive acceleration of the metabolism.
The effects of other substances having a depressive action on the central nervous system, such as alcohol and barbiturates, can be enhanced by the administration of primidone.
04.6 Pregnancy and breastfeeding -
Pregnancy
Patients who may become pregnant or who are of childbearing age should be given specific advice.
The need for antiepileptic treatment should be re-evaluated when the patient plans to become pregnant.
The risk of congenital defects is increased by a factor of 2 to 3 times in the offspring of mothers treated with an antiepileptic, the most frequently reported being cleft lip, cardiovascular malformations and neural tube defects.
The possible responsibility of anticonvulsant therapy must therefore be kept in mind and the continuation of treatment should be considered.
Prolonged anticonvulsant therapy may be associated with a reduction in serum folate levels.
Since folic acid requirements have increased during pregnancy, it is recommended that patients at risk be subjected to regular checkups and, although controversial, folic acid and vitamin B12 should be considered.
In infants whose mothers were given Mysoline during the last period of pregnancy, treatment withdrawal symptoms may occur.
Anticonvulsant therapy during pregnancy has sometimes been associated with coagulation disorders in newborns. For this reason, pregnant patients must be treated during the last month of pregnancy and until delivery with vitamin K1. In the absence of this pretreatment, it is advisable to administer 10 mg of vitamin K1 at delivery and 1 mg per day. newborn soon after birth.
Polytherapy with antiepileptic drugs may be associated with a higher risk of congenital malformations of monotherapy. Therefore it is important that monotherapy is practiced whenever possible.
Abrupt discontinuation of antiepileptic therapy should not be practiced due to the danger of the resumption of seizures which could have serious consequences for both mother and baby.
Feeding time
Primidone passes into breast milk, so if you observe drowsiness or weakness in nursing infants, stop breastfeeding.
04.7 Effects on ability to drive and use machines -
Treatment with Mysoline, as with other anticonvulsants, can lead to decreased alertness; therefore the quickness of reflexes, such as that required for the driver of motor vehicles, can be attenuated.
04.8 Undesirable effects -
If side effects occur they are usually limited to the early stages of treatment: patients may present with drowsiness, irritability, inattention. Neurotoxic symptoms such as ataxia, dizziness, headache, nystagmus, visual disturbances, nausea and vomiting have been reported but are usually transient even when intense.
However, in cases of idiosyncrasy, acute and severe neurotoxic symptoms may occur such that treatment must be discontinued. Dermatological reactions, including severe skin rashes, and rarely systemic changes such as systemic lupus erythematosus, have been reported. Cases of arthralgia and personality changes, including psychotic reactions, have been reported rarely.
Other rare side effects include lower extremity edema, thirst, polyuria, and decreased sexual potency. In exceptional cases, megaloblastic anemia may occur, such as with phenytoin and phenobarbital. This anemia can usually be corrected by administering folic acid or vitamin B12 at the same time, but in rare cases it may be necessary to discontinue therapy.
In some cases, better results have been obtained by administering both folic acid and vitamin B12 at the same time (see also the paragraph "Pregnancy"). There have been isolated reports of other blood dyscrasias.
There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in patients on long-term Mysoline therapy. The mechanism by which Mysoline affects bone metabolism has not been identified.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose -
In the event of an overdose, various degrees of CNS depression may occur which, depending on the ingested dose, manifests itself as ataxia, loss of consciousness, respiratory depression and coma.
Treatment of overdose involves aspiration of gastric contents and usual supportive measures. There is no specific antidote.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: Antiepileptics, barbiturates and derivatives, ATC code: N03AA03
Mechanism of action
Mysoline is an anticonvulsant drug, the active ingredient of which is primidone.
Primidone is transformed into two active metabolites: phenobarbital and phenylethylmalonamide. The latter also enhances phenobarbital activity in experimental animals.
The exact mechanism of action of Mysoline, like that of other anticonvulsants, is not yet known. However, it is likely that the effects on the neuronal membrane, particularly as regards the modifications of ion fluxes, play a fundamental role.
Pharmacodynamic effects
Mysoline, like other anticonvulsants, can induce liver enzymes and, although there is insufficient evidence to suggest a direct causal relationship, there is a theoretical risk of causing liver damage.
Mysoline can also affect the metabolism of vitamin D which can predispose to the development of bone disorders.
Clinical efficacy and safety
In laboratory animals, Mysoline has been shown to be very active in preventing convulsions from electrical or chemical stimuli (pentamethylenetetrazole).
05.2 "Pharmacokinetic properties -
Absorption
Mysoline is rapidly absorbed from the gastrointestinal tract. Maximum plasma concentrations are reached approximately 3 hours after ingestion.
Distribution
Primidone is well distributed in all organs and tissues: it crosses the blood-brain and placental barrier and is excreted in breast milk.
Biotransformation
Primidone undergoes metabolic transformation with the formation of two active derivatives: phenobarbital and phenylethylmalonamide. Both metabolites accumulate in the body during chronic treatment.
After initiation of therapy, there may be a delay of several days in the appearance of phenobarbital in plasma.
Elimination
The half-life of primidone in plasma is approximately 10 hours, a time shorter than that of its major metabolites.
Primidone and phenylethylmalonamide bind to plasma proteins only to a small extent, while about half of phenobarbital binds to them.
About 40% of the drug is excreted unchanged in the urine.
05.3 Preclinical safety data -
The toxicity of primidone has been studied in numerous animal species and was found to be exceptionally low. In terms of unique oral doses to induce minimal neurological or other toxicity, Mysoline is 22 times less toxic than phenobarbital in mice, and 18 times less toxic in rats.
If acute lethal doses are compared with effective doses (ratio LD50 / ED50, with the convulsion test from electrical stimulus in the rat), a therapeutic index oscillating between 300 and 400: 1 for the single oral dose results.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Povidone, gelatin, calcium carmellose, magnesium stearate, stearic acid.
06.2 Incompatibility "-
Not relevant.
06.3 Period of validity "-
5 years.
06.4 Special precautions for storage -
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package -
Carton containing 30 tablets of 250 mg in blister packs (aluminum / milk white PVC).
06.6 Instructions for use and handling -
No special instructions.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
Pharmaceutical Laboratory SIT S.r.l. - Via Cavour 70 - 27035 Mede (PV).
08.0 MARKETING AUTHORIZATION NUMBER -
Mysoline 250 mg tablets - 30 tablets: A.I.C. n. 009340011
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
Date of first authorization: 1 October 1991
Date of most recent renewal: 1 June 2010
10.0 DATE OF REVISION OF THE TEXT -
01 February 2015
