Symla

Package leaflet: information for the patient

Symla, 25 mg, tablets
Symla, 50 mg, tablets
Symla, 100 mg, tablets
Lamotrigine
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet so that you can read it again if necessary.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents

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

1. What Symla is and what it is used for

Symla belongs to a group of medicines called antiepileptic drugs. It is used in the treatment of two conditions – epilepsy and bipolar affective disorder.

• The action of Symla in treating epilepsy involves blocking abnormal electrical impulses in the brain that cause epileptic seizures.
• In adults and children aged 13 years and older, Symla may be used alone or in combination with other medicines for the treatment of epilepsy. Symla may also be used in combination with other medicines for the treatment of seizures associated with a condition called Lennox-Gastaut syndrome.
• In children aged 2 to 12 years, Symla may be used in combination with other medicines for the treatment of these conditions. It may also be used as monotherapy in the treatment of a type of epilepsy known as typical absence seizures.

Symla is also used in the treatment of bipolar affective disorder.
In patients with bipolar affective disorder (sometimes called manic-depressive psychosis), there are extreme mood swings, with episodes of mania (excitement or euphoria) alternating with episodes of depression (deep sadness or despair).
In adults aged 18 years and older, Symla can be used either alone or in combination with other medicines to prevent depressive episodes in bipolar affective disorder. The mechanism by which Symla produces this effect in the brain has not yet been fully understood.

2. Information before taking Symla

When not to take Symla

• if the patient is allergic (hypersensitive) to lamotrigine or any of the other ingredients of this medicine (listed in section 6).

In this case:
➢ inform the treating doctor and do not take Symla.
Warnings and precautions
Before starting treatment with Symla, discuss with the doctor or pharmacist if:

• the patient has any kidney disease,
• the patient has ever experienced a rash after taking lamotrigine or other medicines used to treat bipolar disorder or epilepsy,
• the patient developed a rash or sunburn after exposure to sunlight or artificial light (e.g. in a solarium) following lamotrigine intake. The doctor will review the patient's treatment and may advise avoiding sunlight or using sun protection (e.g. sunscreen or protective clothing),
• the patient has ever had meningitis after taking lamotrigine (please read the description of symptoms in section 4 of this leaflet: Rare adverse reactions),
• the patient is taking a medicine containing lamotrigine,
• the patient has a condition called Brugada syndrome or other heart diseases. Brugada syndrome is a genetically determined heart condition characterized by disturbances in the heart's electrical activity. Abnormal ECG findings are associated with arrhythmia (irregular heartbeat), which may be triggered by taking lamotrigine.

If any of the above conditions apply:
➢ inform the treating doctor, who may recommend reducing the dose or
decide that Symla is not suitable for the patient.
Important information about life-threatening reactions
A small number of patients taking Symla may develop an allergic reaction or a potentially life-threatening skin reaction, which may worsen if left untreated. These include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). The patient should be aware of the symptoms of these conditions and monitor for them during treatment with Symla.
This risk may be associated with a genetic variant found in individuals of Asian origin (particularly Han Chinese and Thai). If the patient is of such origin and has previously been found to carry this genetic variant (HLA-B*1502), this should be discussed with the treating doctor before starting Symla.
➢ Please read the description of these symptoms in section 4 of this leaflet, under “Life-threatening reactions: contact your doctor immediately”.
Haemophagocytic lymphohistiocytosis (HLH)
Cases of a rare but very serious immune system reaction have been reported in patients taking lamotrigine.
➢ If the patient develops the following symptoms while taking lamotrigine: fever, rash, neurological symptoms (e.g. tremors or chills, confusion, brain dysfunction), contact the doctor or pharmacist immediately.
Thoughts of self-harm or suicide
Antiepileptic medicines are used to treat various conditions, including epilepsy and bipolar disorder. Patients with bipolar disorder may occasionally experience thoughts of self-harm or suicide. Such thoughts may occur more frequently:

• when starting treatment for the first time,
• if the patient previously had thoughts of self-harm or suicide,
• if the patient is under 25 years of age. If the patient experiences disturbing thoughts or feelings, or if their condition worsens or new symptoms appear during treatment with Symla:

➢ seek medical help immediately by visiting the doctor or the nearest hospital.
It may be helpful to inform a relative, caregiver, or friend that the patient may experience depression or significant mood changes, and ask them to read this leaflet. The patient may ask them to inform him or her if they notice depression or worrying changes in behaviour.
A small number of patients treated with antiepileptic medicines such as Symla have experienced thoughts of self-harm or suicide. If such thoughts occur at any time, the patient should contact their treating doctor immediately.
Use of Symla in the treatment of epilepsy
In certain types of epilepsy, seizures may sometimes worsen or occur more frequently during treatment with Symla. Some patients may experience severe seizures that could pose a serious health risk. If seizures become more frequent or if a severe seizure occurs during treatment with Symla:
➢ seek medical advice as soon as possible.
Symla must not be used to treat bipolar disorder in patients under 18 years of age. Medicines used to treat depression or other psychiatric disorders may increase the risk of suicidal thoughts or behaviour in children and adolescents under 18 years of age.
Symla and other medicines
Tell the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including herbal remedies or other non-prescription medicines.
The treating doctor must be aware if the patient is taking other medicines used to treat epilepsy or psychiatric disorders. This will allow the appropriate dose of Symla to be determined. These medicines include:

• oxcarbazepine, felbamate, gabapentin, levetiracetam, pregabalin, topiramate or zonisamide, used to treat epilepsy,
• lithium, olanzapine or aripiprazole, used to treat psychiatric disorders,
• bupropion, used to treat psychiatric disorders or nicotine dependence.
  ➢ Inform the treating doctor if the patient is taking any of these medicines.

The patient should also inform the doctor if they are taking paracetamol, a medicine used to treat pain and fever.
Some medicines interact with Symla or increase the risk of adverse reactions. These include:

• valproate, used to treat epilepsy and psychiatric disorders,
• carbamazepine, used to treat epilepsy and psychiatric disorders,
• phenytoin, primidone or phenobarbital, used to treat epilepsy,
• risperidone, used to treat psychiatric disorders,
• rifampicin, an antibiotic,
• medicines used to treat human immunodeficiency virus (HIV) infection (lopinavir with ritonavir or atazanavir with ritonavir),
• hormonal contraceptives, such as the "birth control pill" (see below).
  Inform the treating doctor if the patient is taking, has taken, or is starting to take any of these medicines.

Hormonal contraceptives (such as the birth control pill) may affect the action of Symla
The treating doctor may recommend a specific type of hormonal contraceptive or another method of contraception, such as condoms, a diaphragm, or an intrauterine device. If the patient is using hormonal contraceptives such as the birth control pill, the treating doctor may recommend blood tests to monitor Symla levels. If the patient is using or plans to start using hormonal contraceptives:
➢ discuss with the treating doctor the most appropriate contraceptive method.
Symla may also affect the action of hormonal contraceptives, although it is unlikely to reduce their effectiveness. If the patient is using hormonal contraceptives and notices any changes in her menstrual cycle, such as bleeding or intermenstrual spotting:
➢ inform the treating doctor. These symptoms may indicate an effect of Symla on the contraceptive.
Pregnancy and breastfeeding
➢ If the patient is pregnant, suspects she may be pregnant, or is planning to become pregnant, she should consult her treating doctor or pharmacist before taking this medicine.

• Do not stop treatment without first consulting the treating doctor. This is particularly important if the patient has epilepsy.
• Pregnancy may affect the effectiveness of Symla, so blood tests and dose adjustments may be necessary.
• There may be an increased risk of congenital malformations, including cleft lip and palate, if Symla is taken during the first three months of pregnancy.
• If the patient plans to become pregnant or is pregnant, the treating doctor may recommend additional folic acid supplementation.

If the patient is breastfeeding or planning to breastfeed, she should consult her doctor or pharmacist before taking this medicine. The active substance in Symla passes into breast milk and may affect the infant. The doctor will discuss the risks and benefits of breastfeeding while taking Symla. If the patient decides to breastfeed, the infant will be monitored periodically for excessive sleepiness, rash, or poor weight gain. If any of these symptoms occur in the infant, inform the doctor.
Driving and operating machinery
Symla may cause dizziness and double vision.
➢ Do not drive or operate machinery unless the patient is certain these symptoms do not occur.
If the patient has epilepsy, they should discuss driving and operating machinery with their doctor.
Symla contains lactose monohydrate
If the patient has previously been diagnosed with intolerance to certain sugars, they should consult their doctor before taking this medicine.
Symla contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, meaning the medicine is considered "sodium-free".

3. How to use Symla

This medicine should always be used exactly as your doctor has instructed. If you are unsure, you should
contact your doctor or pharmacist.
What dose of Symla should be used
Determining the appropriate dose of Symla for a patient may take time. The dose a patient takes depends on:

• the patient's age,
• whether the patient is taking Symla in combination with other medicines,
• whether the patient has any kidney or liver disease.

Your doctor will initially prescribe a low dose and then gradually increase it over several weeks until reaching the dose effective for the patient (called the effective dose). You must never take a higher dose of Symla than the one prescribed by your doctor.
Typically, the effective dose of Symla in adults and children aged 13 years and older ranges from
100 mg to 400 mg per day.
In children aged 2 to 12 years, the effective dose depends on body weight—usually from 1 mg to 15 mg
per kilogram of body weight, up to a maximum maintenance dose of 200 mg per day.
The use of Symla is not recommended in children under 2 years of age.
How to take Symla
Symla should be taken once or twice daily, as directed by your doctor. The medicine may be taken
with or without food.
Your doctor may also recommend starting or stopping other medicines, depending on the indication and the patient's response to treatment.
Symla tablets have a division line and can be divided into equal doses.

• Tablets should be swallowed whole or divided, with a small amount of water. Do not chew or crush the tablets.
• You must always take the full dose prescribed by your doctor. Never take only part of the prescribed dose.

Taking more Symla than prescribed
➢ Contact your doctor or the nearest hospital emergency department immediately. If possible, show the Symla packaging.
Taking too high a dose of Symla may increase the risk of serious adverse effects, which could be fatal.
In a person who has taken an excessive dose of Symla, the following may occur:

• rapid, involuntary eye movements (nystagmus),
• unsteadiness, lack of coordination, inability to maintain balance (ataxia),
• heart rhythm disturbances (usually detected during an ECG),
• loss of consciousness, seizures, or coma.

Missing a dose of Symla
Missing a single dose of Symla
➢ Do not take a double dose to make up for the missed dose. Take the next dose at the usual time.
Missing several doses of Symla
➢ Consult your doctor regarding resuming treatment with Symla. This is important for the patient.
Do not stop taking Symla unless your doctor advises you to do so
Symla should be taken for as long as your doctor recommends. Do not discontinue treatment unless instructed by your doctor.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.
Using Symla in the treatment of epilepsy
When stopping Symla, it is important that the dose be gradually reduced over approximately two weeks.
Suddenly stopping Symla may cause a recurrence or worsening of epileptic symptoms.
Using Symla in the treatment of bipolar affective disorders
It may take some time before Symla starts to work, so improvement is unlikely to occur immediately.
When ending treatment with Symla, there is no need to gradually reduce the dose. However, you should still consult your doctor if you intend to stop taking Symla.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
Life-threatening reactions: contact a doctor immediately.
In a small number of patients taking Symla, an allergic reaction or potentially life-threatening skin reaction may occur, which may worsen if left untreated.
These symptoms may occur more frequently during the first few months of treatment with Symla, especially if the patient has been given too high a dose, the dose has been increased too quickly, or if the patient is taking Symla in combination with another medicine called valproate. Some of these symptoms occur more frequently in children, so parents should pay particular attention to them.
Such reactions include:

• skin rash or redness of the skin, which may progress to severe skin reactions, including widespread rash with blisters and peeling of the outer layer of skin, particularly around the mouth, nose, eyes, and genital organs (Stevens-Johnson syndrome), extensive peeling of the skin (affecting more than 30% of body surface area – toxic epidermal necrolysis), or widespread rash accompanied by abnormalities affecting the liver, blood, and other organs (drug reaction with eosinophilia and systemic symptoms, also known as DRESS syndrome),
• ulceration of the mouth, throat, nose, or genital organs,
• pain in the mouth or redness and swelling of the eyes (conjunctivitis),
• high fever (fever), flu-like symptoms, or drowsiness,
• swelling of the face, enlarged lymph nodes in the neck, armpits, and groin,
• unexpected bleeding, bruising, or blue discoloration of the fingers,
• sore throat or more frequent than usual infections (such as colds),
• increased liver enzyme levels observed in blood tests,
• increased number of white blood cells (eosinophilia),
• enlarged lymph nodes,
• abnormalities affecting body organs, including the liver and kidneys.

In many cases, these are symptoms of less severe adverse reactions. However, it should be remembered
that they are potentially life-threatening and, if left untreated, may progress to serious conditions,
such as organ failure. If any of these symptoms occur:
➢ Contact a doctor immediately. The treating physician may decide to perform tests assessing liver, kidney, or blood function and may recommend discontinuation of Symla. If the patient develops Stevens-Johnson syndrome or toxic epidermal necrolysis, the doctor will inform them that lamotrigine must never be used again.
Hemophagocytic lymphohistiocytosis (HLH) (see section 2. Important information before taking Symla).
Very common adverse reactions
(may occur in more than 1 in 10 patients):

• headache,
• skin rash.

Common adverse reactions
(may occur in up to 1 in 10 patients):

• aggression or irritability,
• feeling drowsy,
• dizziness,
• tremor,
• difficulty falling asleep (insomnia),
• feeling of restlessness,
• diarrhoea,
• dry mouth,
• nausea or vomiting,
• feeling tired,
• back, joint, or other pain.

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

• lack of coordination and unsteady movements (ataxia),
• double or blurred vision,
• unusual hair loss or thinning (alopecia),
• skin rash or sunburn after exposure to sunlight or artificial light (photosensitivity).

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

• life-threatening skin reaction (Stevens-Johnson syndrome); also refer to information at the beginning of section 4,
• a group of symptoms occurring simultaneously: fever, nausea, vomiting, headache, neck stiffness, and extreme sensitivity to bright light. This may be caused by inflammation of the membranes surrounding the brain and spinal cord (meningitis). These symptoms usually resolve after stopping treatment, but if they persist or worsen, contact a doctor,
• rapid, involuntary eye movements (nystagmus),
• itchy eyes with discharge (conjunctivitis).

Very rare adverse reactions
(may occur in up to 1 in 10,000 patients):

• life-threatening skin reaction (toxic epidermal necrolysis); also refer to information at the beginning of section 4,
• drug reaction with eosinophilia and systemic symptoms (DRESS); see section 4,
• high fever; also refer to information at the beginning of section 4,
• swelling of the face, enlarged lymph nodes in the neck, armpits, and groin (generalized lymphadenopathy); also refer to information at the beginning of section 4,
• liver function abnormalities shown in blood tests or liver failure; also refer to information at the beginning of section 4,
• severe blood clotting disorder that may cause unexpected bleeding or bruising (disseminated intravascular coagulation); also refer to information at the beginning of section 4,
• changes in blood test results – including reduced number of red blood cells (anaemia), reduced number of white blood cells (leucopenia, neutropenia, agranulocytosis), reduced number of platelets (thrombocytopenia), reduced number of all blood cells (pancytopenia), and bone marrow disorder known as aplastic anaemia,
• hallucinations (“seeing” or “hearing” things that are not real),
• disorientation,
• feeling unsteady or loss of balance during movement,
• involuntary, repetitive body movements and (or) sounds or words (tics), involuntary muscle contractions affecting the eyes, head, and trunk (choreoathetosis), or other unusual body movements such as jerks, tremors, or stiffness,
• increased frequency of seizures in patients previously diagnosed with epilepsy,
• worsening of symptoms in patients diagnosed with Parkinson’s disease,
• pseudotumour cerebri syndrome (symptoms may include back or joint pain, sometimes accompanied by fever and (or) general malaise),
• hemophagocytic lymphohistiocytosis (HLH) (see section 2. Important information before taking Symla).

Other adverse reactions
Other adverse reactions occurred in a small number of patients, but with unknown frequency.

• Bone disorders including osteopenia and osteoporosis (weakened bones) and fractures have been reported. If the patient is on long-term treatment with antiepileptic medicines, has osteoporosis, or is taking steroids, they should discuss this with their doctor or pharmacist,
• Kidney inflammation (tubulointerstitial nephritis), or simultaneous inflammation of the kidneys and eye (tubulointerstitial nephritis and uveitis),
• Nightmares,
• Weakened immunity due to lower levels of antibodies in the blood called immunoglobulins, which help protect the body against infections,
• Red nodules or spots on the skin (pseudolymphoma).

Reporting adverse reactions
If any adverse symptoms occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions 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 reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of this medicine.

5. How to store the medicine Symla

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton and blister pack following EXP. The expiry date refers to the last day of the stated month.
No special storage instructions are required for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such practices help protect the environment.

6. Contents of the pack and other information

What Symla contains

• The active substance is lamotrigine, in the amount of 25 mg, 50 mg or 100 mg for Symla 25 mg, Symla 50 mg and Symla 100 mg, respectively.
• The other ingredients are: lactose monohydrate, microcrystalline cellulose, hydrated yellow iron oxide (E 172), povidone K30, sodium carboxymethyl starch (type A), magnesium stearate, talc, colloidal anhydrous silica.

What Symla looks like and contents of the pack
Symla 25 mg, Symla 50 mg: light yellow, round, flat tablets with a division line on one side.
The tablet can be divided into equal doses.
Symla 100 mg: light yellow square-shaped tablets, convex on one side, flat on the other, with two crossing division lines. The tablet can be divided into two equal doses (each containing 50 mg of lamotrigine) or into four equal doses (each containing 25 mg of lamotrigine).
Symla 25 mg: packs containing 30, 50, 60, 90 or 100 tablets.
Symla 50 mg: packs containing 30, 50, 60, 90 or 100 tablets.
Symla 100 mg: packs containing 30, 50, 60, 90 or 100 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Importer
Marketing Authorisation Holder
Farmak International Sp. z o.o.
ul. Koszykowa 65
00-667 Warsaw
tel.: +48 22 822 93 06
e-mail: [email protected]

Importer
Farmak International Sp. z o.o.
ul. Chełmżyńska 249
04-458 Warsaw