Mizodin

Package leaflet: Information for the user

Mizodin
250 mg, tablets
Primidonum
Please read all of this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents

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

1. What Mizodin is and what it is used for

Mizodin contains the active substance primidone, which is a derivative of barbituric acid. The medicine has anticonvulsant properties. It is well absorbed from the gastrointestinal tract. Maximum blood concentration occurs approximately 3 hours after oral administration.

Indications:

• Treatment of generalized tonic-clonic seizures (grand mal), nocturnal myoclonic seizures, complex partial (psychomotor) seizures, and simple partial seizures. Mizodin may be used as monotherapy or in combination with other antiepileptic drugs.

2. Important information before taking Mizodin

When not to take Mizodin

• if the patient is allergic to primidone, barbiturates, or any of the other ingredients of this medicine (listed in section 6);
• if the patient has porphyria (a disorder characterized by abnormal production of heme – a component of haemoglobin).

Warnings and precautions
Mizodin should be used with caution:

• if the patient has impaired kidney and/or liver function – due to the risk of accumulation of barbiturate metabolites in the body;
• if the patient has hyperkinesia (increased motor excitability), as primidone may worsen its symptoms;
• if the patient has respiratory disorders (e.g. asthma, pulmonary emphysema), because respiratory depression may occur – slowed and shallow breathing, apnoea, and death due to suffocation;
• in children, elderly patients (over 65 years of age), and debilitated patients, as it may cause paradoxical reactions (see section 4: Possible side effects). During treatment with primidone, life-threatening skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome) may occur, which initially present as reddish spots resembling targets or circular lesions, often with central blisters, localized on the trunk. Additional objective symptoms to watch for include: oral, throat, nasal, and genital mucosal ulcers, and conjunctivitis (red and swollen eyes). Life-threatening skin rashes are often accompanied by influenza-like symptoms. The rash may progress into extensive areas covered with blisters or skin peeling. The highest risk of severe skin reactions occurs during the first weeks of treatment. If the patient has previously experienced Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome during treatment with primidone or another medicine containing phenobarbital, re-initiation of treatment with these medicines must never be attempted. If the patient develops a rash or the above-mentioned skin symptoms, primidone must be discontinued immediately and medical advice must be sought promptly, informing the doctor about the use of this medicine.
  Long-term use of primidone may reduce its effectiveness (development of tolerance). Long-term use of primidone may lead to psychological and physical dependence. Abrupt discontinuation of this medicine may cause withdrawal symptoms (see section: Stopping Mizodin). Mizodin may cause orthostatic hypotension (dizziness or fainting when rising from a sitting or lying position); therefore, caution should be exercised when standing up. Megaloblastic anaemia may develop during treatment with primidone (see section 4: Possible side effects). If this occurs, the doctor may advise discontinuation of Mizodin. Primidone may affect certain laboratory test results (see section: Mizodin and other medicines). During long-term treatment with Mizodin, the doctor should periodically order blood tests (complete blood count and blood biochemistry every 6 months, as well as measurement of folic acid, phenobarbital, and primidone levels).

Mizodin and other medicines
Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines you plan to take.
Mizodin enhances the effects of medicines that depress the central nervous system, such as:

• sleeping pills and sedatives;
• sedating antihistamines (used, among others, for treating allergies);
• opioid analgesics (strong painkillers, such as morphine).

Mizodin reduces the effectiveness of the following medicines. If the patient is taking any of these medicines, the doctor may need to increase their dose:

• corticosteroids (steroids, used, among others, in the treatment of rheumatic disease);

• anticoagulants (medicines used to reduce blood clotting);

• corticotropin (a pituitary hormone – ACTH);

• cyclosporine (a medicine used in organ transplant recipients);

• dacarbazine (a cytostatic used, among others, in the treatment of malignant melanoma);

• doxycycline (an antibiotic used to treat bacterial infections);

• metronidazole (a medicine used to treat infections caused by certain bacteria and protozoa);

• oral contraceptives containing oestrogens (a change in contraceptive method may be necessary).
  Particular caution is required when Mizodin is used concomitantly with any of the following medicines:

• MAO inhibitors (medicines used to treat depression, e.g. furazolidone, procarbazine, and selegiline), as they may prolong the effect of primidone;

• tricyclic antidepressants (medicines used to treat depression), as they may reduce the effect of primidone;

• other antiepileptic medicines (e.g. carbamazepine, valproic acid derivatives), as they may alter the type of epileptic seizure; therefore, monitoring of blood levels of these medicines and possible adjustment of the primidone dose by the doctor is necessary. Carbamazepine reduces, while valproic acid derivatives enhance, the effect of primidone;

• phenobarbital (a medicine used in epilepsy treatment) may alter the type of epileptic seizure and enhance the sedative effect of both phenobarbital and Mizodin;

• St. John's wort (Hypericum perforatum – an ingredient of herbal medicines used for digestive disorders and depression treatment) may reduce the effect of Mizodin;

• carbonic anhydrase inhibitors (medicines used in glaucoma treatment) may cause decreased bone mass;

• prolonged use of primidone prior to administration of anaesthetics (halothane, enflurane, and methoxyflurane) increases the risk of liver and kidney damage.
  During long-term treatment with Mizodin, the doctor may recommend supplementation with vitamin D and folic acid (to correct deficiencies caused by Mizodin).
  Primidone affects the results of certain laboratory tests:

• reduces absorption of labelled cyanocobalamin Co;

• response to metyrapone may be reduced (due to increased metyrapone metabolism);

• false-positive reaction to phentolamine may occur; therefore, the medicine should be discontinued 24 to 72 hours before the test;

• blood bilirubin levels may decrease (due to activation of glucuronyltransferase – the enzyme responsible for bilirubin conjugation).

Mizodin and alcohol
Do not consume any alcoholic beverages while taking this medicine.

Pregnancy and breastfeeding

If the patient is pregnant, breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before taking this medicine.

Pregnancy
Primidone taken during pregnancy may cause severe congenital malformations and may affect the child's development. Congenital malformations reported in studies include cleft lip (split upper lip) and cleft palate (split in the roof of the mouth), as well as heart defects. Other congenital malformations reported include developmental abnormalities of the penis (hypospadias), smaller than normal head size, facial abnormalities, and nail and finger defects. If a woman takes primidone during pregnancy, the risk of giving birth to a child with congenital malformations requiring treatment is higher than in other women. In the general population, the baseline risk of severe developmental defects is 2–3%. In women taking primidone, this risk is approximately three times higher.
Newborns born to mothers who used primidone during pregnancy may also be at increased risk of being smaller than expected.
Neurodevelopmental disorders (developmental delays due to impaired brain development) have been reported in children exposed to primidone during pregnancy. Research findings on the risk of neurodevelopmental disorders remain inconsistent.
Primidone should not be used during pregnancy unless other medicines are ineffective.
In case of pregnancy, consult the doctor immediately. The doctor should discuss the potential effects of primidone on the unborn child and carefully weigh the risks and benefits of treatment. Do not stop taking primidone without consulting your doctor, as abrupt discontinuation may increase the risk of seizures, which could harm both the patient and her unborn child.
If a woman took primidone during the third trimester of pregnancy, the pregnancy should be monitored to detect potential newborn complications such as seizures, excessive crying, muscle weakness, and sucking difficulties.

Women of childbearing potential, contraception
Women of childbearing potential should use effective contraception during treatment with primidone and for two months after discontinuation. Primidone may affect the efficacy of hormonal contraceptives, such as oral contraceptive pills, reducing their effectiveness in preventing pregnancy. Discuss with your doctor the most appropriate contraceptive method to use during primidone treatment.
If the patient is a woman of childbearing potential and plans to become pregnant, she should consult her doctor before stopping contraception and before attempting conception, to consider switching to alternative appropriate treatment to avoid exposing the unborn child to primidone.
During long-term treatment with Mizodin, serum folic acid levels decrease. Folic acid requirements increase during pregnancy. The doctor may recommend folic acid and vitamin B supplementation during pregnancy (to correct deficiencies caused by Mizodin).
Primidone used late in pregnancy may cause neonatal dependence and withdrawal symptoms, as well as bleeding.
Primidone used during delivery may cause respiratory disturbances in the newborn.

Mizodin should not be used during breastfeeding, as the medicine passes into breast milk and may cause excessive drowsiness in the infant.

Driving and operating machinery
Mizodin may cause drowsiness and prolonged reaction time; therefore, driving vehicles or operating machinery should be avoided during treatment.

Sodium content
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning it is considered "sodium-free".

3. How to take Mizodin

This medicine should always be taken according to the doctor's instructions. If in doubt, consult
your doctor or pharmacist.
The dosage is determined individually by the doctor for each patient.
Recommended dosage
Adults and children over 9 years of age:
3 tablets (750 mg) up to 6 tablets (1500 mg) per day.
Unless otherwise directed by a doctor, the medicine should be taken according to the following scheme:

Do not use more than 6 tablets (1500 mg) per day.
Overdose of Mizodin
If an overdose of the medicinal product is taken, contact a doctor immediately.
Symptoms of overdose:

• disorientation (impaired orientation in time, place, situation or self);
• double vision, nystagmus (involuntary eye movement);
• breathing difficulties;
• symptoms similar to alcohol intoxication;
• coma;
• respiratory centre paralysis;
• presence of primidone and PEMA (phenylethylmalonyl amide) crystals in urine – confirmed by laboratory testing.

Missed dose of Mizodin
If a dose is missed, take the medicine as soon as possible. If it is almost time for the next dose, skip the missed dose.
Take the next dose at the usual time.
Do not take a double dose to make up for a missed dose.
Discontinuation of Mizodin
Sudden discontinuation of Mizodin may lead to withdrawal symptoms. Therefore, any change in dosage or discontinuation of the medicinal product must be carried out gradually and under medical supervision.
If you have any further doubts regarding the use of this medicinal product, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Adverse effects mainly occur at the beginning of treatment.
Common adverse effects (may occur in up to 1 in 10 patients):

• drowsiness;
• apathy (lack of interest, loss of motivation);
• ataxia (difficulty maintaining balance, unsteady gait);
• visual disturbances, nystagmus;
• nausea.

Uncommon adverse effects (may occur in up to 1 in 100 patients):

• headache, dizziness;
• vomiting;
• allergic reactions manifesting as maculopapular skin rash (similar to the rash seen in measles or scarlet fever);
• paradoxical reactions (restlessness, agitation, aggressive behaviour), particularly in children and elderly patients (over 65 years of age).

Rare adverse effects (may occur in up to 1 in 1,000 patients):

• personality changes with psychotic reactions;
• megaloblastic anaemia (manifesting as weakness, easy fatigue, pallor of the skin and mucous membranes, dizziness, loss of taste sensation, burning sensation of the tongue, diarrhoea or constipation);
• changes in blood count (detected in laboratory tests);
• abnormal liver function tests: gamma-glutamyl transferase and alkaline phosphatase (detected in blood tests);
• joint pain;
• bone demineralization (reduced calcium in bones leading to bone deformities);
• Dupuytren's contracture (contracture of the finger joints);
• exfoliative dermatitis (manifesting as itching, erythema spreading over all body parts, and peeling of the epidermis);
• Stevens-Johnson syndrome (appearance of blisters on the skin and (or) mucous membranes which, when ruptured, form painful lesions (erosions); fever, muscle and joint pain often occur simultaneously);
• toxic epidermal necrolysis (also known as Lyell's syndrome - extensive peeling and necrosis of the epidermis);
• systemic lupus erythematosus (a chronic disease caused by disorders of the immune system affecting multiple organs).

Frequency unknown (cannot be estimated from available data):

• life-threatening skin rashes have occurred (drug reaction with eosinophilia and systemic symptoms) (see section 2). If skin lesions and (or) mucous membrane lesions occur, contact a doctor immediately.

There have been reports of bone disorders including osteopenia, osteoporosis ("thinning" of bones), and fractures. Patients should consult a doctor or pharmacist if undergoing long-term antiepileptic therapy, if they have osteoporosis, or if they are taking steroids.

Reporting of adverse effects

If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309
website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Mizodin

Keep the medicine out of sight and reach of children.
Store below 25 °C.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Mizodin contains

• The active substance is primidone. Each tablet contains 250 mg of primidone.
• The other ingredients are: magnesium stearate, gelatin, rice starch, potato starch, sodium carboxymethyl starch.

What Mizodin looks like and contents of the pack
Mizodin tablets are round, white, biconvex tablets, with a dividing line on one side and the inscription "Mizodin" on the other side. The tablets are packed in Al/PCW foil blisters containing 20 tablets each. The medicinal product pack contains 60 tablets (3 blisters) placed together with the package leaflet in a cardboard box.

Marketing Authorisation Holder and Manufacturer
Zakłady Farmaceutyczne „UNIA” Spółdzielnia Pracy
ul. Chłodna 56/60
00-872 Warsaw
tel.: 22 620 90 81 ext. 190
fax: 22 654 92 40
e-mail: [email protected]
The package leaflet for Mizodin is available in the Audio Leaflet system via the nationwide, toll-free telephone number: 800 706 848.