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نشرة الممارس الصحي نشرة معلومات المريض بالعربية نشرة معلومات المريض بالانجليزية صور الدواء بيانات الدواء
  SFDA PIL (Patient Information Leaflet (PIL) are under review by Saudi Food and Drug Authority)

Loxol belongs to a group of medicines called anti-epileptics. It is used to treat two conditions - epilepsy and bipolar disorder.

Loxol treats epilepsy by blocking the signals in the brain that trigger epileptic seizures (fits)

  • For adults and children aged 13 years and over, Loxol can be used on its own or with other medicines, to treat epilepsy. Loxol can also be used with other medicines to treat the seizures that occur with a condition called Lennox-Gastaut syndrome.
  • For children aged between 2 and 12 years, Loxol can be used with other medicines, to treat those conditions. It can be used on its own to treat a type of epilepsy called typical absence seizures.

Loxol also treats bipolar disorder

People with bipolar disorder (sometimes called manic depression) have extreme mood swings, with periods of mania (excitement or euphoria) alternating with periods of depression (deep sadness or despair). For adults aged 18 years and over, Loxol can be used on its own or with other medicines, to prevent the periods of depression that occur in bipolar disorder. It is not yet known how lamotrigine works in the brain to have this effect.


Do not take Loxol

  • If you are allergic (hypersensitive) to lamotrigine or any of the other ingredients of this medicine (listed in section 6).

If this applies to you:

Tell your doctor and don’t take Loxol.

Warnings and Precautions

Talk to your doctor or pharmacist before taking Loxol:

  • If you have any kidney problems
  • If you have ever developed a rash after taking lamotrigine or other medicines for bipolar disorder or epilepsy  
  • If you experience a rash or sunburn after taking lamotrigine and having been exposed to sun or artificial light (e.g. solarium). Your doctor will check your treatment and may advise you to avoid sunlight or protect yourself against the sun (e.g. use of a sunscreen and/or to wear protective clothing)
  • If you have ever developed meningitis after taking lamotrigine (read the description of these symptoms in section 4 of this leaflet: Rare side effects)
  • If you are already taking medicine that contains lamotrigine
  • If you have a condition called Brugada syndrome, or other heart problems. Brugada syndrome is a genetic disease that results in abnormal electrical activity within the heart. ECG abnormalities which may lead to arrhythmias (abnormal heart rhythm) can be triggered by lamotrigine.

If any of these applies to you:

Tell your doctor, who may decide to lower the dose or that Loxol is not suitable for you.

Important information about potentially life-threatening reactions

A small number of people taking lamotrigine get an allergic reaction or potentially life-threatening skin reaction, which may develop into more serious problems if they are not treated. These can include Stevens–Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). You need to know the symptoms to look out for while you are taking Loxol.

Read the description of these symptoms in section 4 of this leaflet under ‘Potentially life-threatening reactions: get a doctor’s help straight away’.

Haemophagocytic lymphohistiocytosis (HLH)

There have been reports of a rare but very serious immune system reaction, in patients taking lamotrigine.

Contact your doctor or pharmacist immediately if you experience any of the following symptoms while taking lamotrigine: fever, rash, neurological symptoms (e.g. shaking or tremor, confusional state, disturbances of brain function).

Thoughts of harming yourself or suicide

Anti-epileptic medicines are used to treat several conditions, including epilepsy and bipolar disorder. People with bipolar disorder can sometimes have thoughts of harming themselves or committing suicide. If you have bipolar disorder, you may be more likely to think like this:

  • When you first start treatment
  • If you have previously had thoughts about harming yourself or about suicide
  • If you are under 25 years old.

If you have distressing thoughts or experiences, or if you notice that you feel worse or develop new symptoms while you’re taking Loxol:

See a doctor as soon as possible or go to the nearest hospital for help.

You may find it helpful to tell a family member, caregiver or close friend that you can become depressed or have significant changes in mood, and ask them to read this leaflet. You might ask them to tell you if they are worried about your depression or other changes in your behaviour.

A small number of people being treated with anti-epileptics such as lamotrigine have also had thoughts of harming or killing themselves. If at any time you have these thoughts, immediately contact your doctor.

If you’re taking Loxol for epilepsy

The seizures in some types of epilepsy may occasionally become worse or happen more often while you’re taking Loxol. Some patients may experience severe seizures, which may cause serious health problems. If your seizures happen more often or if you experience a severe seizure while you’re taking Loxol:

See a doctor as soon as possible.

Loxol should not be given to people aged under 18 years to treat bipolar disorder. Medicines to treat depression and other mental health problems increase the risk of suicidal thoughts and behaviour in children and adolescents aged under 18 years.

Other medicines and Loxol

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines including herbal medicines or other medicines bought without a prescription.

Your doctor needs to know if you are taking other medicines to treat epilepsy or mental health problems. This is to make sure you take the correct dose of Loxol. These medicines include:

  •     Oxcarbazepine, felbamate, gabapentin, levetiracetam, pregabalin, topiramate or zonisamide, used to treat epilepsy
  •     Lithium, olanzapine or aripiprazole used to treat mental health problems
  •     Bupropion, used to treat mental health problems or to stop smoking
  •     Paracetamol, used to treat pain and fever

Tell your doctor if you are taking any of these.

Some medicines interact with Loxol or make it more likely that people will have side effects. These include:

  •     Valproate, used to treat epilepsy and mental health problems
  •     Carbamazepine, used to treat epilepsy and mental health problems
  •     Phenytoin, primidone or phenobarbitone, used to treat epilepsy
  •     Risperidone, used to treat mental health problems
  •     Rifampicin, which is an antibiotic
  •     Medicines used to treat Human Immunodeficiency Virus (HIV) infection (a combination of lopinavir and ritonavir or atazanavir and ritonavir)
  •     Hormonal contraceptives, such as the Pill (see below).

Tell your doctor if you are taking any of these or if you start or stop taking any.

Hormonal contraceptives (such as the Pill) can affect the way Loxol works

Your doctor may recommend that you use a particular type of hormonal contraceptive or another method of contraception, such as condoms, a cap or coil. If you are using a hormonal contraceptive like the Pill, your doctor may take samples of your blood to check the level of Loxol. If you are using a hormonal contraceptive or if you plan to start using one:

Talk to your doctor, who will discuss suitable methods of contraception with you.

Loxol can also affect the way hormonal contraceptives work, although it’s unlikely to make them less effective. If you are using a hormonal contraceptive and you notice any changes in your menstrual pattern, such as breakthrough bleeding or spotting between periods:

Tell your doctor. These may be signs that Loxol is affecting the way your contraceptive is working.

Pregnancy and breast-feeding

If you are pregnant, think you may be pregnant or are planning to have a baby ask your doctor or pharmacist for advice before taking this medicine.

  •     You should not stop treatment without discussing this with your doctor. This is particularly important if you have epilepsy.
  •     Pregnancy may alter the effectiveness of lamotrigine, so you may need blood tests and your dose of Loxol may be adjusted.
  •     There may be a small increased risk of birth defects, including a cleft lip or cleft palate, if Loxol is taken during the first 3 months of pregnancy.
  •     Your doctor may advise you to take extra folic acid if you’re planning to become pregnant and while you’re pregnant.

If you are breast-feeding or planning to breast-feed ask your doctor or pharmacist for advice before taking this medicine. The active ingredient of Loxol passes into breast milk and may affect your baby. Your doctor will discuss the risks and benefits of breast-feeding while you’re taking Loxol and will check your baby from time to time, whether drowsiness, rash or poor weight gain occurs, if you decide to breast-feed. Inform your doctor if you observe any of these symptoms in your baby.

Driving and using machines

Loxol can cause dizziness and double vision.

Don’t drive or use machines unless you are sure you’re not affected.

If you have epilepsy, talk to your doctor about driving and using machines.

Loxol contains lactose, sodium and FD & C yellow no.6 lake

Loxol contains lactose. Each tablet of Loxol 25 mg, 50 mg, 100 mg and 200 mg Tablets contains 13.5 mg, 27 mg, 54 mg or 108 mg lactose; respectively. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Loxol contains sodium. Each tablet of Loxol 25 mg, 50 mg, 100 mg and 200 mg Tablets contains 0.5547 mg, 1.1094 mg, 2.2188 mg or 4.4376 mg sodium: respectively. This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

Loxol 100 mg Tablets contains FD & C yellow no.6 lake. Each tablet of Loxol 100 mg Tablets contains 0.4 mg FD & C yellow no.6 lake, which may cause allergic reactions.


Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

How much Loxol to take

It may take a while to find the best dose of Loxol for you. The dose you take will depend on:

  •     Your age
  •     Whether you are taking Loxol with other medicines
  •     Whether you have any kidney or liver problems.

Your doctor will prescribe a low dose to start and gradually increase the dose over a few weeks until you reach a dose that works for you (called the effective dose). Never take more Loxol than your doctor tells you to.

The usual effective dose of lamotrigine for adults and children aged 13 years or over is between 100 mg and 400 mg each day.

For children aged 2 to 12 years, the effective dose depends on their body weight - usually, it’s between 1 mg and 15 mg for each kilogram of the child’s weight, up to a maximum maintenance dose of 200 mg daily.

Loxol is not recommended for children aged under 2 years.

How to take your dose of Loxol

Take your dose of Loxol once or twice a day, as your doctor advises. It can be taken with or without food.

Your doctor may also advise you to start or stop taking other medicines, depending on what condition you’re being treated for and the way you respond to treatment.

  •     Swallow your tablets whole. Don’t break, chew or crush them. For Loxol 100 mg Tablets; the score line is only there to help you break the tablet if you have difficulty swallowing it whole.
  •     Always take the full dose that your doctor has prescribed. Never take only part of a tablet.  

If you take more Loxol than you should

Contact a doctor or nearest hospital emergency department immediately. If possible, show them the Loxol packet.

If you take too much Loxol you may be more likely to have serious side effects which may be fatal.

Someone who has taken too much Loxol may have any of these symptoms:

  •     Rapid, uncontrollable eye movements (nystagmus)
  •     Clumsiness and lack of co-ordination, affecting their balance (ataxia)
  •     Heart rhythm changes (detected usually on ECG)
  •     Loss of consciousness, fits (convulsions) or coma.

If you forget to take Loxol

Don’t take extra tablets to make up for a missed dose. Just take your next dose at the usual time.

In case you forget to take multiple doses of Loxol:

  •     Ask your doctor for advice on how to start taking it again. It’s important that you do this.

If you stop taking Loxol

Loxol must be taken for as long as your doctor recommends. Don’t stop unless your doctor advises you to.

If you’re taking Loxol for epilepsy

To stop taking Loxol, it is important that the dose is reduced gradually, over about 2 weeks. If you suddenly stop taking Loxol, your epilepsy may come back or get worse.

If you’re taking Loxol for bipolar disorder

Loxol may take some time to work, so you are unlikely to feel better straight away. If you stop taking Loxol, your dose will not need to be reduced gradually. But you should still talk to your doctor first, if you want to stop taking Loxol.


Like all medicines, this medicine can cause side effects, but not everyone gets them.

Potentially life-threatening reactions: get a doctor’s help straight away.

A small number of people taking lamotrigine get an allergic reaction or potentially life-threatening skin reaction, which may develop into more serious problems if they are not treated.

These symptoms are more likely to happen during the first few months of treatment with lamotrigine, especially if the starting dose is too high or if the dose is increased too quickly or if lamotrigine is taken with another medicine called valproate. Some of the symptoms are more common in children, so parents should be especially careful to watch out for them.

Symptoms of these reactions include:

  • Skin rashes or redness, which may develop into life-threatening skin reactions including widespread rash with blisters and peeling skin, particularly occurring around the mouth, nose, eyes and    genitals (Stevens-Johnson syndrome), extensive peeling of the skin (more than 30% of the body surface - toxic epidermal necrolysis) or extended rashes with liver, blood and other body organs involvement (Drug Reaction with Eosinophilia and Systemic Symptoms which is also known as DRESS hypersensitivity syndrome)
  •  Ulcers in the mouth, throat, nose or genitals
  •  A sore mouth or red or swollen eyes (conjunctivitis)
  •  A high temperature (fever), flu-like symptoms or drowsiness
  •  Swelling around your face or swollen glands in your neck, armpit or groin
  •  Unexpected bleeding or bruising, or the fingers turning blue
  •  A sore throat or more infections (such as colds) than usual
  •  Increased levels of liver enzymes seen in blood tests
  •  An increase in a type of white blood cell (eosinophils)
  •  Enlarged lymph nodes
  •  Involvement of the organs of the body including liver and kidneys.

In many cases, these symptoms will be signs of less serious side effects but you must be aware that they are potentially life-threatening and can develop into     more serious problems, such as organ failure, if they are not treated. If you notice any of these symptoms:

  • Contact a doctor immediately. Your doctor may decide to carry out tests on your liver, kidneys or blood and may tell you to stop taking Loxol. In case you have developed Stevens-Johnson syndrome or toxic epidermal necrolysis your doctor will tell you that you must never use lamotrigine again.

 Haemophagocytic lymphohistiocytosis (HLH) (see section 2: What you need to know before you take Loxol).

Very common side effects

These may affect more than 1 in 10 people:

  •     Headache
  •     Skin rash.

Common side effects

These may affect up to 1 in 10 people:

  •     Aggression or irritability
  •     Feeling sleepy or drowsy
  •     Feeling dizzy
  •     Shaking or tremors
  •     Difficulty in sleeping (insomnia)
  •     Feeling agitated
  •     Diarrhoea
  •     Dry mouth
  •     Feeling sick (nausea) or being sick (vomiting)
  •     Feeling tired
  •     Pain in your back or joints, or elsewhere.

Uncommon side effects

These may affect up to 1 in 100 people:

  •     Clumsiness and lack of co-ordination (ataxia)
  •     Double vision or blurred vision
  •     Unusual hair loss or thinning (alopecia)
  •     Skin rash or sunburn after exposure to sun or artificial light (photosensitivity).

Rare side effects

These may affect up to 1 in 1,000 people:

  • A life-threatening skin reaction (Stevens-Johnson syndrome): (see also the information at the beginning of section 4)
  • A group of symptoms together including: fever, nausea, vomiting, headache, stiff neck and extreme sensitivity to bright light. This may be caused by an inflammation of the membranes that cover the brain and spinal cord (meningitis). These symptoms usually disappear once treatment is stopped however if the symptoms continue or get worse contact your doctor
  • Rapid, uncontrollable eye movements (nystagmus)
  • Itchy eyes, with discharge and crusty eyelids (conjunctivitis).

Very rare side effects

These may affect up to 1 in 10,000 people:

  •     A life-threatening skin reaction (toxic epidermal necrolysis): see also the information at the beginning of section 4
  •     Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): (see also the information at the beginning of section 4)
  •     A high temperature (fever): (see also the information at the beginning of section 4)
  •     Swelling around the face (oedema) or swollen glands in the neck, armpit or groin (lymphadenopathy): (see also the information at the beginning of section 4)
  •     Changes in liver function, which will show up in blood tests, or liver failure: (see also the information at the beginning of section 4)
  •     A serious disorder of blood clotting, which can cause unexpected bleeding or bruising (disseminated intravascular coagulation): (see also the information at the beginning of section 4)  
  •     Haemophagocytic lymphohistiocytosis (HLH) (see section 2: What you need to know before you take Loxol)
  •   Changes which may show up in blood tests - including reduced numbers of red blood cells (anaemia), reduced numbers of white blood cells (leucopenia, neutropenia, agranulocytosis), reduced               numbers of platelets (thrombocytopenia), reduced numbers of all these types of cell (pancytopenia) and a disorder of the bone marrow called aplastic anaemia
  •     Hallucinations (‘seeing’ or ‘hearing’ things that aren’t really there)
  •     Confusion
  •     Feeling ‘wobbly’ or unsteady when you move about
  •     Uncontrollable body movements (tics), uncontrollable muscle spasms affecting the eyes, head and torso (choreoathetosis) or other unusual body movements such as jerking, shaking or stiffness
  •     In people who already have epilepsy, seizures happening more often
  •     In people who already have Parkinson’s disease, worsening of the symptoms
  •     Lupus-like reaction (symptoms may include: back or joint pain which sometimes may be accompanied by fever and/or general ill health).

Other side effects

Other side effects have occurred in a small number of people but their exact frequency is unknown:

  •    There have been reports of bone disorders including osteopenia and osteoporosis (thinning of the bone) and fractures. Check with your doctor or pharmacist if you are on long-term anti-epileptic       medication, have a history of osteoporosis or take steroids  
  •     Inflammation of the kidney (tubulointerstitial nephritis), or inflammation of both the kidney and the eye (tubulointerstitial nephritis and uveitis syndrome)
  •     Nightmares
  •     Lower immunity because of lower levels of antibodies called immunoglobulins in the blood which help protect against infection.

 


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

Store below 30°C.

Store in the original package.

Do not use this medicine after the expiry date which is stated on the package after “EXP”. The expiry date refers to the last day of that month.

Do not use this medicine if you notice any visible signs of deterioration.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.


The active substance is lamotrigine.

Each tablet of Loxol 25 mg Tablets contains 25 mg lamotrigine.

Each tablet of Loxol 50 mg Tablets contains 50 mg lamotrigine.

Each tablet of Loxol 100 mg Tablets contains 100 mg lamotrigine.

Each tablet of Loxol 200 mg Tablets contains 200 mg lamotrigine.

The other ingredients are lactose, sodium starch glycolate, povidone, microcrystalline cellulose, yellow iron oxide (in Loxol 50 mg Tablets only), FD & C yellow no.6 lake (in Loxol 100 mg Tablets only), FD & C blue no.2 lake (in Loxol 200 mg Tablets only) and magnesium stearate.


Loxol 25 mg Tablets are white round tablets, embossed with “JPI062” on one side in clear PVC/PVDC-aluminum blisters. Loxol 50 mg Tablets are round beige biconvex tablets, embossed with “JPI063” on one side in clear PVC/PVDC-aluminum blisters. Loxol 100 mg Tablets are round peach tablets with break line, embossed with “JPI064” on one side in clear PVC/PVDC-aluminum blisters. Loxol 200 mg Tablets are round blue tablets, embossed with “JPI065” on one side in clear PVC/PVDC-aluminum blisters. Pack size: 30 Tablets.

Marketing Authorization Holder and Manufacturer

Jazeera Pharmaceutical Industries
Al-Kharj Road
P.O. Box 106229
Riyadh 11666, Saudi Arabia
Tel: + (966-11) 8107023, + (966-11) 2142472
Fax: + (966-11) 2078170
e-mail: SAPV@hikma.com

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly (see details below). By reporting side effects, you can also help provide more information on the safety of this medicine.

  •     Saudi Arabia

The National Pharmacovigilance Centre (NPC)

SFDA Call Center: 19999

E-mail: npc.drug@sfda.gov.sa

Website: https://ade.sfda.gov.sa

  •     Other GCC States

Please contact the relevant competent authority.


This leaflet was last revised in 01/2023; version number Un2.0.
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

لوكسول ينتمي إلى مجموعة من الأدوية تسمى مضادات الصرع. هو يستخدم لعلاج حالتين هما – الصرع والاضطراب ثنائي القطب.

لوكسول يعالج الصرع من خلال منع الإشارات الدماغية التي تسبب نوبات الصرع (التشنجات)

  •  للبالغين والأطفال بعمر 13 سنة وأكبر، يمكن استخدام لوكسول بمفرده أو مع غيره من الأدوية، لعلاج الصرع. يمكن أيضاً استخدام لوكسول مع غيره من الأدوية لعلاج نوبات الصرع التي تحدث مع حالة معروفة باسم متلازمة لينوكس-غاستو.
  • للأطفال الذين تتراوح أعمارهم بين سنتين و12 سنة، يمكن استخدام لوكسول مع غيره من الأدوية لعلاج تلك الحالات. يمكن استخدامه بمفرده لعلاج نوع من أنواع الصرع معروف باسم النوبات الصرعية النموذجية المصحوبة بغيبة.

لوكسول يعالج أيضاً الاضطراب ثنائي القطب

الأشخاص الذين يعانون من الاضطراب ثنائي القطب (أحياناً ما يسمى الهوس الاكتئابي) يعانون من تقلبات مزاجية بالغة، يصابون خلالها بفترات من الهوس (الإثارة أو النشوة) بالتناوب مع فترات اكتئاب (حزن عميق أو يأس). للبالغين بعمر 18 سنة فأكبر، يمكن استخدام لوكسول بمفرده أو مع غيره من الأدوية، للوقاية من فترات الاكتئاب التي يتعرض لها الشخص المصاب باضطراب ثنائي القطب. ليس من المعروف بعد كيف يعمل لاموتريجين في الدماغ ليتميز بهذا التأثير.

لا تتناول لوكسول

  • إذا كنت تعاني من حساسية (حساسية مفرطة) للاموتريجين أو لأي من المواد الأخرى المستخدمة في تركيبة هذا الدواء (المدرجة في القسم 6).

إذا كان ذلك ينطبق عليك:

أخبر طبيبك ولا تتناول لوكسول.

الاحتياطات والتحذيرات

تحدث مع طبيبك أو الصيدلي قبل تناول لوكسول:

  • إذا كنت تعاني من أي مشاكل في الكلى
  • إذا كنت قد أصبت بطفح جلدي بعد تناولك لاموتريجين أو أدوية أخرى لعلاج الاضطراب ثنائي القطب أو الصرع  
  • إذا عانيت من طفح جلدي أو حروق من شمس بعد تناول لاموتريجين وتعرضت لأشعة الشمس أو الضوء الصناعي (مثل، المشمسة). سوف يتحقق طبيبك من علاجك وقد ينصحك بتجنب أشعة الشمس أو حماية نفسك من الشمس (مثل، استخدام واقي شمس و/أو أن ترتدي ملابس واقية)
  • إذا كنت قد أصبت بالتهاب السحايا بعد تناول لاموتريجين (اقرأ وصف هذه الأعراض في القسم 4 من هذه النشرة: الآثار الجانبية النادرة)
  • إذا كنت تتناول بالفعل دواء يحتوي على لاموتريجين
  •  إذا كنت مصاباً بحالة تسمى متلازمة بروغادا، أو أمراض قلبية أخرى. متلازمة بروغادا هي مرض جيني يؤدي إلى نشاط كهربائي غير طبيعي في القلب. قد تسبب الاضطرابات في مخطط كهربية القلب إلى اضطراب في نظم القلب (اضطراب النظم القلبي)، والتي يمكن أن يحفزها لاموتريجين.

إذا كان أي مما سبق ينطبق عليك:

أخبر طبيبك، الذي قد يقرر تخفيض الجرعة التي تتناولها أو يقرر أن لوكسول غير مناسب لحالتك.

معلومات هامة عن ردود فعل مهددة للحياة يحتمل التعرض لها

يصاب عدد قليل من الأشخاص الذين يتناولون لاموتريجين برد فعل تحسسي أو برد فعل جلدي محتمل ومهدد للحياة، والذي قد يتفاقم ويتطور إلى مشاكل أكثر خطورة إذا لم يتم علاجه. يمكن أن تتضمن هذه متلازمة ستيفنز - جونسون، تقشر الأنسجة المتموتة البشروية التسممي، والتفاعلات الدوائية مع ظهور أعراض جهازية وكثرة اليوزينيات. قد تحتاج إلى معرفة أعراض ردود الفعل هذه للتنبه إلى وقوعها أثناء تناول لوكسول.

اقرأ وصف هذه الأعراض في القسم 4 من هذه النشرة تحت عنوان ’ردود فعل محتملة ومهددة للحياة: يجب أن تتلقى مساعدة الطبيب على الفور‘.

كثرة المنسجات اللمفاوية البلعمية المكونة للدم

هنالك تقارير عن رد فعل نادر لجهاز المناعة، لكنه خطير جداً، لدى المرضى الذين يتناولون لاموتريجين.

تواصل مع طبيبك أو الصيدلي فوراً إذا تعرضت لأي من الأعراض التالية أثناء تناول لاموتريجين: حمّى، طفح جلدي، أعراض عصبية (مثل الارتجاف أو الرعشة، حالة من الارتباك، اضطرابات في وظائف الدماغ).

أفكار بإيذاء نفسك أو بالانتحار

تستخدم الأدوية المضادة للصرع لعلاج العديد من الحالات، التي تتضمن الصرع والاضطراب ثنائي القطب. أحياناً ما تراود الأشخاص المصابين بالاضطراب ثنائي القطب أفكار بإيذاء أنفسهم أو بالانتحار. إذا كنت مصاباً بالاضطراب ثنائي القطب، فسيكون من المرجح أن تراودك هذه الأفكار في الحالات التالية:

  •  عند بداية العلاج لأول مرة
  •  إذا كانت تراودك في السابق أفكار بإيذاء نفسك أو بالانتحار
  •  إذا كان عمرك أقل من 25 سنة.

إذا كانت لديك أفكار أو تجارب مزعجة، أو إذا لاحظت أنك تشعر بتفاقم حالتك أو تظهر عليك أعراض جديدة أثناء تناول لوكسول:

راجع طبيبك في أقرب فرصة ممكنة أو اذهب إلى أقرب مستشفى لطلب المساعدة.

قد يفيدك أن تُخبر أحد أفراد عائلتك، مقدم الرعاية الصحية أو أحد أصدقائك المقربين بأنك يمكن أن تصاب بالاكتئاب أو بتغيرات شديدة في المزاج، وتطلب منهم قراءة هذه النشرة. يمكنك أن تطلب منهم إخبارك إذا كانوا قلقين بشأن اكتئابك أو غيرها من التغييرات في سلوكك.

عدد قليل من المرضى ممن تم علاجهم بالأدوية المضادة للصرع مثل لاموتريجين كان أيضاً لديهم أفكار تتعلق بإيذاء النفس أو الانتحار. تواصل مع طبيبك فوراً في حال راودتك أي من هذه الأفكار.

إذا كنت تتناول لوكسول لعلاج الصرع

قد تتفاقم النوبات في بعض أنواع الصرع أحياناً أو قد يتكرر حدوثها بتكرار أكبر أثناء تناولك لوكسول. قد يتعرض بعض المرضى لنوبات شديدة، والتي قد تسبب مشاكل صحية خطيرة. إذا كنت تعاني من تكرار النوبات أو تعرضت لنوبة تشنجات شديدة أثناء تناول لوكسول:

فراجع طبيبك في أقرب فرصة ممكنة.

ينبغي عدم إعطاء لوكسول لعلاج الاضطراب ثنائي القطب للأشخاص الذين يقل عمرهم عن 18 سنة. أدوية علاج الاكتئاب وغيرها من مشاكل في الصحة العقلية تزيد من خطر الأفكار الانتحارية ومشاكل السلوك في الأطفال والمراهقين بعمر أقل من 18 سنة.

الأدوية الأخرى ولوكسول

أخبر طبيبك أو الصيدلي إذا كنت تتناول، تناولت مؤخراً أو قد تتناول أي أدوية أخرى بما في ذلك الأدوية العشبية أو غيرها من الأدوية التي تصرف بدون وصفة طبية.

يحتاج طبيبك إلى معرفة ما إذا كنت تتناول أدوية أخرى لعلاج الصرع أو لعلاج مشاكل الصحة العقلية. هذا للتأكد من أنك تتناول الجرعة الصحيحة من لوكسول. تتضمن هذه الأدوية:

  • أوكسكاربازيبين، فيلبامات، جابابنتين، ليفيتيراسيتام، بريجابالين، توبيرامات أو زونيساميد، المستخدمون لعلاج الصرع
  • ليثيوم، أولانزابين، أو أريبيبرازول، المستخدمون لعلاج المشاكل الصحية العقلية
  • بوبروبيون، يستخدم لعلاج مشاكل الصحة العقلية أو للمساعدة في التوقف عن التدخين
  • باراسيتامول، يستخدم لعلاج الألم والحمى

أخبر طبيبك إذا كنت تتناول أيّاً من هذه الأدوية.

تتفاعل بعض الأدوية مع لوكسول أو تزيد من احتمالية تعرض المرضى للآثار الجانبية. تتضمن هذه:

  •     فالبروات، المستخدم لعلاج الصرع ومشاكل الصحة العقلية
  •     كاربامازيبين، المستخدم لعلاج الصرع ومشاكل الصحة العقلية
  •     فينيتوين، بريميدون أو فينوباربيتون، المستخدمون لعلاج الصرع
  •     ريسبريدون، المستخدم لعلاج مشاكل الصحة العقلية
  •     ريفامبيسين، وهو مضاد حيوي
  •     الأدوية التي تستخدم لعلاج عدوى فيروس نقص المناعة البشرية (مزيج من لوبينفير وريتونافير أو أتازانافير وريتونافير)
  •     موانع الحمل الهرمونية، مثل حبوب منع الحمل (انظر أدناه).

أخبر طبيبك إذا كنت تتناول أيّاً من هذه الأدوية أو إذا بدأت أو توقفت عن تناولها.

موانع الحمل الهرمونية (مثل حبوب منع الحمل) يمكن أن تؤثر على طريقة عمل لوكسول

قد يوصي طبيبك باستخدام نوع معين من موانع الحمل الهرمونية أو غيرها من وسائل منع الحمل، مثل الواقي الذكري، غطاء عنق الرحم أو اللولب. إذا كنت تستخدمين وسيلة منع حمل هرمونية مثل الحبوب، فقد يحتاج طبيبك إلى طلب فحص عينات من دمك للتحقق من مستوى لوكسول. إذا كنت تستخدمين إحدى وسائل منع الحمل الهرمونية أو إذا كنت تخططين في بدء استخدامها، ينبغي عليك اتباع ما يلي:

تحدثي مع طبيبك، الذي سيناقش معك الطرق المناسبة لمنع الحمل.

يمكن أيضاً أن يؤثر لوكسول على طريقة عمل وسائل منع الحمل الهرمونية، على الرغم من أنه من غير المرجح أن يقلل من فعاليتها. إذا كنت تستخدمين وسيلة منع حمل هرمونية، ولاحظت أي تغيرات في نمط الطمث لديك، مثل نزيف مفاجئ أو حدوث بقع دموية بين فترات الطمث:

أخبري طبيبك. قد تكون هذه علامات على أن لوكسول يؤثر على طريقة عمل وسائل منع الحمل.

الحمل والرضاعة

استشيري طبيبك أو الصيدلي إذا كنتِ حاملاً، تعتقدين بأنك حامل أو تخططين للحمل قبل تناولك لهذا الدواء.

  • ينبغي عليك عدم إيقاف تناول الدواء دون استشارة طبيبك. هذا مهم بشكل خاص إذا كنت مصابة بالصرع.
  • قد يغير الحمل من فعالية لاموتريجين، ولهذا فقد تحتاجين إلى إجراء فحوصات للدم وإلى تعديل جرعة لوكسول.
  • قد يكون هناك خطر متزايد بسيط لإصابة جنينك بعيوب خلقية، التي تتضمن الشفة الأرنبية أو شقوق سقف الحلق، إذا تناولت لوكسول خلال الثلاثة أشهر الأولى من الحمل.
  • قد ينصحك طبيبك بتناول جرعة إضافية من حمض الفوليك إذا كنت حاملاً أو تخططين للحمل.

استشيري طبيبك أو الصيدلي قبل تناول هذا الدواء إذا كنت تقومين بالرضاعة الطبيعية أو تخططين للرضاعة الطبيعية. المادة الفعّالة في لوكسول تنتقل إلى حليب الثدي وقد تؤثر على طفلك. سيناقش طبيبك معك مخاطر وفوائد الرضاعة الطبيعية أثناء تناول لوكسول وسيفحص طفلك من وقت إلى آخر، سواء للتحقق من تعرضه للنعاس، زيادة سريعة أو ضعف في اكتساب الوزن، إذا قررت إرضاعه طبيعيّاً. أخبري طبيبك إذا لاحظت إصابة رضيعك بأي من هذه الأعراض.

القيادة واستخدام الآلات

يمكن أن يسبب لوكسول دوخة وازدواجية في الرؤية.

لا تقم بالقيادة أو استخدام الآلات ما لم تكن متأكداً من عدم تأثرك بالدواء.

إذا كنت مصاباً بالصرع، ناقش مع طبيبك إمكانية القيادة واستخدام الآلات.

يحتوي لوكسول على اللاكتوز، الصوديوم وصبغة FD&C صفراء رقم 6

يحتوي لوكسول على اللاكتوز. يحتوي كل قرص من لوكسول 25 ملغم، 50 ملغم، 100 ملغم و200 ملغم أقراص على 13,5 ملغم، 27 ملغم، 54 ملغم أو 108 ملغم لاكتوز؛ على التوالي. إذا أخبرك طبيبك بأن لديك عدم تحمل لبعض السكريات، فتواصل مع طبيبك قبل تناول هذا المستحضر الدوائي.

يحتوي لوكسول على الصوديوم. يحتوي كل قرص من لوكسول 25 ملغم، 50 ملغم، 100 ملغم و200 ملغم أقراص على 0,5547 ملغم، 1,1094 ملغم، 2,2188 ملغم أو 4,4376 ملغم صوديوم؛ على التوالي. يحتوي هذا الدواء على أقل من 1 ملمول صوديوم (23 ملغم) لكل قرص، وبذلك يمكن اعتباره ’خالٍ من الصوديوم‘ بشكل أساسي.

يحتوي لوكسول 100 أقراص على صبغة FD&C صفراء رقم 6. يحتوي كل قرص من لوكسول 100 ملغم أقراص على 0,4 ملغم صبغة FD&C صفراء رقم 6، والتي قد تسبب تفاعلات حساسية.  

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قم دائماً بتناول دوائك كما وصفه لك طبيبك أو كما أخبرك الصيدلي تماماً.  تأكد من طبيبك أو الصيدلي إذا لم تكن متأكداً.

مقدار جرعة لوكسول

قد يستغرق الأمر وقتاً لمعرفة الجرعة الأنسب لك من لوكسول. تعتمد الجرعة التي ستتناولها على:

  •     عمرك.
  •     إذا ما كنت تتناول لوكسول مع غيره من الأدوية.
  •     إذا كنت تعاني من أي مشاكل في الكلى أو الكبد.

في البداية سيصف لك الطبيب جرعة منخفضة ثم يقوم بزيادة الجرعة تدريجيّاً على مدار بضعة أسابيع وذلك حتى تصل إلى الجرعة المناسبة لك (المعروفة بالجرعة الفعّالة). لا تتناول جرعة أكبر من لوكسول من التي وصفها لك طبيبك.

الجرعة الفعّالة المعتادة من لاموتريجين للبالغين والأطفال الذين تتجاوز أعمارهم 13 سنة تتراوح بين 100 ملغم و400 ملغم يوميّاً.

للأطفال الذين تبلغ أعمارهم من 2 إلى 12 سنة، تعتمد الجرعة الفعّالة على وزن أجسامهم – عادة، ما تتراوح بين 1 ملغم و15 ملغم لكل كغم من وزن الطفل، والحد الأقصى لجرعة المداومة يبلغ 200 ملغم يوميّاً.

لا يوصى باستخدام لوكسول للأطفال ممن يقل عمرهم عن سنتين .

كيفية تناول جرعة لوكسول

تناول جرعتك من لوكسول مرة أو مرتين يوميّاً، حسب توجيهات طبيبك. يمكن تناوله مع الطعام أو بدونه.

قد ينصحك طبيبك أيضاً بالبدء أو بالتوقف عن تناول أدوية أخرى، اعتماداً على الحالة التي تتعالج منها وعلى كيفية استجابتك للعلاج.

  • قم بابتلاع الأقراص كاملة. لا تقم بكسر، مضغ، أو تحطيم الأقراص. في لوكسول 100 ملغم أقراص؛ يساعدك الخط المحزز على كسر القرص فقط إذا وجدت صعوبةً في ابتلاعه كاملاً.
  •     دائماً تناول الجرعة الكاملة التي وصفها لك طبيبك. لا تتناول جزء من القرص فقط.  

إذا تناولت جرعة زائدة من لوكسول

اتصل مع الطبيب أو مع قسم الطوارئ لأقرب مستشفى فوراً. إذا أمكن، أظهر لهم علبة لوكسول.

إذا تناولت الكثير من لوكسول، قد يكون لديك احتمالية أكبر للإصابة بأعراض جانبية خطيرة ويحتمل أن تكون مميتة.

قد يتعرض أي شخص يتناول الكثير من لوكسول لأي من الأعراض التالية:

  •     حركات للعين سريعة ولا يمكن السيطرة عليها (رأرأة)
  •     الخرق وفقدان تناسق الحركة، مما يؤثر على التوازن (ترنح المشية)
  •     تغيرات في نظم القلب (غالباً يتم الكشف عنها من خلال مخطط كهربية القلب)
  •     فقدان الوعي، تشنجات (نوبات تشنج) أو غيبوبة.

إذا نسيت تناول لوكسول

لا تقم بتناول أقراص زائدة للتعويض عن الجرعة المفقودة. تناول فقط جرعتك التالية في موعدها المعتاد.

في حال نسيت تناول عدد من جرعات لوكسول:

  •     استشر طبيبك بشأن كيفية البدء في تناوله مرة أخرى. من المهم أن تلتزم بهذه التعليمات.

إذا توقفت عن تناول لوكسول

ينبغي عليك تناول لوكسول بقدر ما يوصي طبيبك بذلك. لا تتوقف عن تناول الدواء ما لم يشر عليك طبيبك بهذا.

إذا كنت تتناول لوكسول لعلاج الصرع

للتوقف عن تناول لوكسول، من المهم تقليل الجرعة تدريجيّاً، على مدى حوالي أسبوعين تقريباً. إذا توقفت عن تناول لوكسول فجأة، فقد تعود أو تتفاقم نوبات الصرع.

إذا كنت تتناول لوكسول لعلاج الاضطراب ثنائي القطب

يستغرق لوكسول بعض الوقت ليبدأ فاعليته، لذلك لا يحتمل أن تشعر بتحسن فور تناوله. إذا توقفت عن تناول لوكسول، فلن تحتاج إلى تقليل جرعتك تدريجيّاً. لكن ما يزال ينبغي عليك التحدث مع طبيبك أولاً، إذا أردت التوقف عن تناول لوكسول.

مثل جميع الأدوية، قد يسبب هذا الدواء آثاراً جانبية، إلا أنه ليس بالضرورة أن تحدث لدى جميع مستخدمي هذا الدواء.

ردود الفعل التحسسية المحتملة والمهددة للحياة: اطلب مساعدة الطبيب على الفور.

يصاب عدد قليل من الأشخاص الذين يتناولون لاموتريجين برد فعل تحسسي أو برد فعل جلدي محتمل ومهدد للحياة، والذي قد يتفاقم ويتطور إلى مشاكل أكثر خطورة إذا لم يتم علاجه.

من المرجح أن تحدث هذه الأعراض خلال الأشهر القليلة الأولى من العلاج باستخدام لاموتريجين، خاصة إذا كانت الجرعة الابتدائية عالية جداً أو إذا تم زيادة الجرعة بسرعة كبيرة أو إذا تم تناول لاموتريجين مع دواء آخر يسمى فالبروات. بعض الأعراض أكثر شيوعاً عند الأطفال، لذلك يجب أن يحرص الوالدان بشكل خاص على مراقبتها.

تتضمن أعراض ردود الفعل هذه:

  •  طفح جلدي أو احمرار، الذي قد يتطور إلى ردود فعل جلدية مهددة للحياة بما في ذلك الطفح الجلدي المنتشر على نطاق واسع مع ظهور بثور وتقشّر الجلد، لا سيما تلك التي تحدث حول الفم، الأنف، العينين والأعضاء التناسلية (متلازمة ستيفنز جونسون)، تقشر بالغ للجلد (أكثر من 30% من سطح الجسم - تقشر الأنسجة المتموتة البشروية التسممي) أو الطفح الجلدي الممتد مع إصابة الكبد، الدم وأعضاء الجسم الأخرى (تفاعلات دوائية مع كثرة اليوزينيات و ظهور أعراض جهازية والتي تعرف أيضاً باسم متلازمة فرط التحسس للتفاعلات الدوائية مع كثرة اليوزينيات و ظهور أعراض جهازية)
  •    تقرحات في الفم، الحلق، الأنف أو الأعضاء التناسلية
  •    ألم في الفم أو احمرار أو تورم العينين (التهاب الملتحمة)
  •    ارتفاع درجة الحرارة (الحمّى)، أعراض تشبه الإنفلونزا أو النعاس
  •    تورم حول الوجه أو تورم غدد الرقبة، الإبط أو العانة
  •    نزيف أو تكدمات غير متوقعة، أو تلون الأصابع باللون الأزرق
  •    ألم في الحلق أو التعرض لعدوى متزايدة (مثل نزلات البرد) بشكل فوق المعتاد
  •     تم ملاحظة ارتفاع مستويات إنزيمات الكبد في فحوصات الدم
  •     زيادة في نوع من خلايا الدم البيضاء (اليوزينيات)
  •     تضخم الغدد اللمفاوية
  •     إصابة أعضاء الجسم مثل الكبد والكليتين.

في كثير من الحالات، ستكون هذه الأعراض علامات على آثار جانبية أقل خطورة لكن يجب أن تدرك أنها قد تكون مهددة للحياة إذا لم يتم علاجها، ويمكن أن تتطور إلى مشاكل أكثر خطورة، مثل فشل الأعضاء. إذا لاحظت أيّاً من هذه الأعراض:

  •  تواصل مع طبيبك فوراً. قد يقرر طبيبك إجراء بعض الفحوصات على كبدك، كليتيك أو دمك وقد يطلب منك التوقف عن تناول لوكسول. في حالة إصابتك بمتلازمة ستيفنز جونسون أو بمرض تقشر الأنسجة المتموتة البشروية التسممي، سيخبرك طبيبك أنه يجب عليك التوقف عن استخدام لاموتريجين وعدم استخدامه مرة أخرى.

كثرة المنسجات اللمفاوية البلعمية المكونة للدم (انظر القسم 2: ما الذي يجب عليك معرفته قبل تناول لوكسول).

الآثار الجانبية الشائعة جدّاً

قد تؤثر على أكثر من شخص واحد من كل 10 أشخاص:

  •     صداع
  •     طفح جلدي.

الآثار الجانبية الشائعة

قد تؤثر على ما يصل إلى شخص واحد من كل 10 أشخاص:

  •     العدوانية أو التهيج
  •     الشعور بالنعاس أو الدوار
  •     الشعور بالدوخة
  •     الارتجاف أو الرعشة
  •     صعوبة في النوم (الأرق)
  •     الشعور بالتهيج
  •     الإسهال
  •     جفاف الفم
  •      الغثيان أو القيء
  •     الشعور بالإرهاق
  •     آلام في الظهر أو المفاصل، أو في أماكن أخرى.

الآثار الجانبية غير الشائعة

قد تؤثر على ما يصل إلى شخص واحد من كل 100 شخص:

  •     الخرق وفقدان تناسق الحركة (ترنح المشية)
  •     ازدواج أو ضبابية الرؤية
  •     تساقط الشعر غير المعتاد أو ترققه (الصلع)
  •     طفح جلدي أو حروق من الشمس بعد التعرض للشمس أو الضوء الصناعي (حساسية للضوء).

الآثار الجانبية النادرة

قد تؤثر ما يصل إلى شخص واحد من كل 1000 شخص:

  •  رد فعل جلدي مهدد للحياة (متلازمة ستيفنز جونسون): (انظر أيضاً المعلومات المذكورة في بداية القسم 4)
  •  مجموعة من الأعراض التي تحدث معاً وتتضمن: الحمّى، الغثيان، القيء، الصداع، تصلب الرقبة والحساسية الشديدة للضوء الساطع. قد تنتج هذه الحالة بسبب التهاب الأغشية التي تغطي الدماغ والحبل الشوكي (التهاب السحايا). عادة ما تختفي هذه الأعراض بمجرد توقفك عن تناول العلاج ولكن إذا استمرت أو تفاقمت الأعراض يجب عليك التواصل مع طبيبك
  •   حركات للعين سريعة ولا يمكن السيطرة عليها (رأرأة)
  •   حكة في العينين المصحوبة بإفرازات وتقشر الجفنين (التهاب الملتحمة).

الآثار الجانبية النادرة جداً

قد تؤثر على ما يصل إلى شخص واحد من كل 10000 شخص:

  •   رد فعل جلدي مهدد للحياة (تقشر الأنسجة المتموتة البشروية التسممي): انظر أيضاً المعلومات الواردة في بداية القسم 4
  •   تفاعلات دوائية مع كثرة اليوزينيات و ظهور أعراض جهازية: (انظر أيضاً المعلومات المذكورة في بداية القسم 4)
  •   ارتفاع درجة الحرارة (الحمّى): (انظر أيضاً المعلومات المذكورة في بداية القسم 4)
  •   تورم حول الوجه (الوذمة) أو تورم غدد الرقبة، الإبط أو العانة (تضخم العقد اللمفية): (انظر أيضاً المعلومات المذكورة في بداية القسم 4)
  •   تغيرات في وظائف الكبد، والتي ستظهر في فحوصات الدم، أو فشل الكبد: (انظر أيضاً المعلومات المذكورة في بداية القسم 4)
  •  اضطراب خطير في تخثر الدم، والذي يمكن أن يسبب نزيف غير متوقع أو كدمات (تخثر الدم المنتشر داخل الأوعية): (انظر أيضاً المعلومات المذكورة في بداية القسم 4)   
  •  كثرة المنسجات اللمفاوية البلعمية المكونة للدم (انظر القسم 2: ما الذي يجب عليك معرفته قبل تناول لوكسول)
  • تغيرات قد تظهر في فحوصات الدم - تتضمن انخفاض عدد خلايا الدم الحمراء (فقر الدم)، انخفاض عدد خلايا الدم البيضاء (قلة الكريات البيض، قلة العدلات، ندرة المحببات)، انخفاض عدد الصفائح الدموية (نقص الصفيحات)، انخفاض في أعداد جميع أنواع هذه الخلايا (قلة الكريات الشاملة) واضطراب في نخاع العظم يسمى فقر الدم اللاتنسجّي
  •  هلوسات (’رؤية‘ أو ’سماع‘ أشياء غير موجودة في الواقع)
  •  ارتباك
  • الشعور ’بالتذبذب‘ أو عدم الثبات عند الحركة
  • حركات لا يمكن السيطرة عليها للجسم (تشنجات لاإرادية)، تشنجات عضلية لا يمكن السيطرة عليها تؤثر على العينين، الرأس والجذع (الكنع الرقصي) أو غيرها من حركات الجسم غير الاعتيادية مثل الترنح، الاهتزاز أو التصلب
  • غالباً ما يتزايد تكرار حدوث النوبات، لدى الأشخاص الذين يعانون بالفعل من الصرع
  • تتفاقم الأعراض لدى الأشخاص الذين يعانون بالفعل من مرض باركنسون
  • رد فعل يشبه الذئبة (قد تشمل الأعراض: آلام في الظهر أو في المفاصل والتي قد تكون مصحوبة أحياناً بالحمّى و/أو اعتلال الصحة العامة).

الآثار الجانبية الأخرى

حدثت آثار جانبية أخرى لدى عدد قليل من الأشخاص، لكن تكرارها الفعلي غير معروف:

  • هناك تقارير لحالات اضطرابات في العظام تتضمن حالات لين العظام وهشاشة العظام (ترقق العظم) والكسور. تحقق مع طبيبك أو الصيدلي إذا كنت تتناول دواء مضاد للصرع على المدى الطويل، إذا كان لديك تاريخ لمرض هشاشة العظام أو كنت تتناول الستيرويدات
  • التهاب الكلى (التهاب الكلية النبيبيّ الخلاليّ)، أو التهاب في كل من الكلية والعين (التهاب الكلية النبيبيّ الخلاليّ ومتلازمة التهاب القزحية)
  •  الكوابيس
  •  انخفاض المناعة بسبب انخفاض مستويات الأجسام المضادة التي تسمى الغلوبولينات المناعية في الدم والتي تساعد على الحماية من العدوى.

 

احفظ هذا الدواء بعيداً عن مرأى ومتناول الأطفال.

يحفظ عند درجة حرارة أقل من 30° مئوية.

يحفظ داخل العبوة الأصلية.

لا تستخدم هذا الدواء بعد تاريخ انتهاء الصلاحية المذكور على العبوة الخارجية بعد “EXP”. يشير تاريخ انتهاء الصلاحية إلى اليوم الأخير من ذلك الشهر.

لا تستخدم هذا الدواء إذا لاحظت أي علامات تلف واضحة عليه.

لا تتخلص من أي أدوية عن طريق مياه الصرف الصحي أو النفايات المنزلية. اسأل الصيدلي عن كيفية التخلص من الأدوية التي لم تعد بحاجة إليها. هذه الإجراءات ستساعد في الحفاظ على سلامة البيئة.

المادة الفعّالة هي لاموتريجين.

يحتوي كل قرص من لوكسول 25 ملغم أقراص على 25 ملغم لاموتريجين.

يحتوي كل قرص من لوكسول 50 ملغم أقراص على 50 ملغم لاموتريجين.

يحتوي كل قرص من لوكسول 100 ملغم أقراص على 100 ملغم لاموتريجين.

يحتوي كل قرص من لوكسول 200 ملغم أقراص على 200 ملغم لاموتريجين.

المواد الأخرى المستخدمة في التركيبة التصنيعية هي لاكتوز، جليكولات نشا الصوديوم، بوڤيدون، سيلليلوز بلوري مكروي، أكسيد الحديد الأصفر (في لوكسول 50 ملغم أقراص فقط)، صبغة FD&C صفراء رقم 6 (في لوكسول 100 ملغم أقراص فقط)، صبغة FD&C زرقاء رقم 2 (في لوكسول 200 ملغم أقراص فقط) وستيرات المغنيسيوم.

لوكسول 25 ملغم أقراص هي أقراص لونها أبيض دائرية الشكل، منقوش عليها "JPI062" على جهة واحدة في أشرطة شفافة من كلوريد متعدد الڤينيل/ثنائي كلوريد متعدد الڤينيلدين-ألومنيوم.

لوكسول 50 ملغم أقراص هي أقراص محدبة الوجهين لونها بيج دائرية الشكل، منقوش عليها "JPI063" على جهة واحدة في أشرطة شفافة من كلوريد متعدد الڤينيل/ثنائي كلوريد متعدد الڤينيلدين-ألومنيوم.

لوكسول 100 ملغم أقراص هي أقراص لونها خوخي دائرية الشكل مع خط كسر، منقوش عليها "JPI064" على جهة واحدة في أشرطة شفافة من كلوريد متعدد الڤينيل/ثنائي كلوريد متعدد الڤينيلدين-ألومنيوم.

لوكسول 200 ملغم أقراص هي أقراص لونها أزرق دائرية الشكل، منقوش عليها "JPI065" على جهة واحدة في أشرطة شفافة من كلوريد متعدد الڤينيل/ثنائي كلوريد متعدد الڤينيلدين-ألومنيوم.

حجم العبوة: 30 قرص.

مالك رخصة التسويق والشركة المصنعة

شركة الجزيرة للصناعات الدوائية
طريق الخرج
صندوق بريد 106229
الرياض 11666، المملكة العربية السعودية
هاتف: 8107023 (11-966) +، 2142472 (11-966) +
فاكس:  2078170 (11-966) +
البريد الإلكتروني: SAPV@hikma.com

 

للإبلاغ عن الآثار الجانبية

تحدث إلى الطبيب، الصيدلي، أو الممرض إذا عانيت من أية آثار جانبية. وذلك يشمل أي آثار جانبية لم يتم ذكرها في هذه النشرة. كما أنه يمكنك الإبلاغ عن هذه الآثار مباشرةً (انظر التفاصيل المذكورة أدناه). من خلال الإبلاغ عن الآثار الجانبية، يمكنك المساعدة بتوفير معلومات مهمة عن سلامة الدواء.

  •      المملكة العربية السعودية

المركز الوطني للتيقظ الدوائي

مركز الاتصال الموحد: 19999
البريد الإلكتروني: npc.drug@sfda.gov.sa

الموقع الإلكتروني: https://ade.sfda.gov.sa

  •      دول الخليج العربي الأخرى

الرجاء الاتصال بالجهات الوطنية في كل دولة.

تمت مراجعة هذه النشرة بتاريخ 01/2023، رقم النسخة: Un2.0.
 Read this leaflet carefully before you start using this product as it contains important information for you

Loxol 100 mg Tablets.

Each tablet contains 100 mg lamotrigine. Excipients with known effect: Lactose, sodium and FD & C yellow no.6 lake. For the full list of excipients, see section 6.1.

Tablets. Round peach tablets with break line, embossed with “JPI064” on one side. The score line is only there to help you break the tablet if you have difficulty swallowing it whole.

Epilepsy

Adults and adolescents aged 13 years and above

  •     Adjunctive or monotherapy treatment of partial seizures and generalised seizures, including tonic-clonic seizures.
  •    Seizures associated with Lennox-Gastaut syndrome. Loxol is given as adjunctive therapy but may be the initial antiepileptic drug (AED) to start with in Lennox-Gastaut syndrome.

Children and adolescents aged 2 to 12 years

  •     Adjunctive treatment of partial seizures and generalised seizures, including tonic-clonic seizures and the seizures associated with Lennox-Gastaut syndrome.
  •     Monotherapy of typical absence seizures.

Bipolar disorder

Adults aged 18 years and above

  •     Prevention of depressive episodes in patients with bipolar I disorder who experience predominantly depressive episodes (see section 5.1).

Loxol is not indicated for the acute treatment of manic or depressive episodes.


Posology

Loxol tablets should be swallowed whole, and should not be chewed or crushed. The score line is only there to help you break the tablet if you have difficulty swallowing it whole.

If the calculated dose of lamotrigine (for example for treatment of children with epilepsy or patients with hepatic impairment) does not equate to whole tablets, the dose to be administered is that equal to the lower number of whole tablets.

Restarting therapy

Prescribers should assess the need for escalation to maintenance dose when restarting Loxol in patients who have discontinued Loxol for any reason, since the risk of serious rash is associated with high initial doses and exceeding the recommended dose escalation for lamotrigine (see section 4.4). The greater the interval of time since the previous dose, the more consideration should be given to escalation to the maintenance dose. When the interval since discontinuing lamotrigine exceeds five half-lives (see section 5.2), Loxol should generally be escalated to the maintenance dose according to the appropriate schedule.

It is recommended that Loxol not be restarted in patients who have discontinued due to rash associated with prior treatment with lamotrigine unless the potential benefit clearly outweighs the risk.

Epilepsy

The recommended dose escalation and maintenance doses for adults and adolescents aged 13 years and above (Table 1) and for children and adolescents aged 2 to 12 years (Table 2) are given below. Because of a risk of rash the initial dose and subsequent dose escalation should not be exceeded (see section 4.4).

When concomitant AEDs are withdrawn or other AEDs/medicinal products are added on to treatment regimes containing lamotrigine, consideration should be given to the effect this may have on lamotrigine pharmacokinetics (see section 4.5).

 

Table 1: Adults and adolescents aged 13 years and above – recommended treatment regimen in epilepsy

Treatment regimen

Weeks 1 + 2

Weeks 3 + 4

Usual maintenance dose

Monotherapy:

25 mg/day (once a day)

50 mg/day (once a day)

100 - 200 mg/day (once a day or two divided doses)

To achieve maintenance, doses may be increased by maximum of 50 - 100 mg every one to two weeks until optimal response is achieved

500 mg/day has been required by some patients to achieve desired response

Adjunctive therapy WITH valproate (inhibitor of lamotrigine glucuronidation – see section 4.5):

This dosage regimen should be used with valproate regardless of any concomitant medicinal products

12.5 mg/day (given as 25 mg on alternate days)

25 mg/day (once a day)

100 - 200 mg/day

(once a day or two divided doses)

To achieve maintenance, doses may be increased by maximum of 25 - 50 mg every one to two weeks until optimal response is achieved

Adjunctive therapy WITHOUT valproate and WITH inducers of lamotrigine glucuronidation (see section 4.5):

This dosage regimen should be used without valproate but with:

phenytoin

carbamazepine

phenobarbitone

primidone

rifampicin

lopinavir/ritonavir

50 mg/day (once a day)

100 mg/day (two divided doses)

200 - 400 mg/day (two divided doses)

To achieve maintenance, doses may be increased by maximum of 100 mg every one to two weeks until optimal response is achieved

700 mg/day has been required by some patients to achieve desired response

Adjunctive therapy WITHOUT valproate and WITHOUT inducers of lamotrigine glucuronidation (see section 4.5):

This dosage regimen should be used with other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation

25 mg/day (once a day)

50 mg/day (once a day)

100 - 200 mg/day (once a day or two divided doses)

To achieve maintenance, doses may be increased by maximum of 50 - 100 mg every one to two weeks until optimal response is achieved

In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently not known (see section 4.5), the treatment regimen as recommended for lamotrigine with concurrent valproate should be used.

 

Table 2: Children and adolescents aged 2 to 12 years - recommended treatment regimen in epilepsy (total daily dose in mg/kg body weight/day)**

Treatment regimen

Weeks 1 + 2

Weeks 3 + 4

Usual maintenance dose

Monotherapy of typical absence seizures:

0.3 mg/kg/day (once a day or two divided doses)

0.6 mg/kg/day (once a day or two divided doses)

1 – 15 mg/kg/day (once a day or two divided doses)

To achieve maintenance, doses may be increased by maximum of 0.6 mg/kg/day every one to two weeks until optimal response is achieved, with a maximum maintenance dose of 200mg/day

Adjunctive therapy WITH valproate (inhibitor of lamotrigine glucuronidation – see section 4.5):

This dosage regimen should be used with valproate regardless of any other concomitant medicinal products

0.15 mg/kg/day* (once a day)

0.3 mg/kg/day (once a day)

1 - 5 mg/kg/day (once a day or two divided doses)

To achieve maintenance, doses may be increased by maximum of 0.3 mg/kg/day every one to two weeks until optimal response is achieved, with a maximum maintenance dose of 200 mg/day

Adjunctive therapy WITHOUT valproate and WITH inducers of lamotrigine glucuronidation (see section 4.5):

This dosage regimen should be used without valproate but with:

phenytoin

carbamazepine

phenobarbitone

primidone

rifampicin

lopinavir/ritonavir

0.6 mg/kg/day (two divided doses)

1.2 mg/kg/day (two divided doses)

5 - 15 mg/kg/day (once a day or two divided doses)

To achieve maintenance, doses may be increased by maximum of 1.2 mg/kg/day every one to two weeks until optimal response is achieved, with a maximum maintenance dose of 400 mg/day

Adjunctive therapy WITHOUT valproate and WITHOUT inducers of lamotrigine glucuronidation (see section 4.5):

This dosage regimen should be used with other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation

0.3 mg/kg/day (once a day or two divided doses)

0.6 mg/kg/day (once a day or two divided doses)

1 - 10 mg/kg/day (once a day or two divided doses)

To achieve maintenance, doses may be increased by maximum of 0.6 mg/kg/day every one to two weeks until optimal response is achieved, with a maximum of maintenance dose of 200 mg/day

In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently not known (see section 4.5), the treatment regimen as recommended for lamotrigine with concurrent valproate should be used.

* NOTE:- If the calculated daily dose in patients taking valproate is 1 mg or more but less than 2 mg, then lamotrigine 2 mg chewable/dispersible tablets may be taken on alternate days for the first two weeks. If the calculated daily dose in patients taking valproate is less than 1 mg, then lamotrigine should not be administered. DO NOT attempt to administer partial quantities of the chewable/dispersible tablets.

** If the calculated dose of lamotrigine cannot be achieved using whole tablets, the dose should be rounded down to the nearest whole tablet.

To ensure a therapeutic dose is maintained the weight of a child must be monitored and the dose reviewed as weight changes occur. It is likely that patients aged two to six years will require a maintenance dose at the higher end of the recommended range.

If epileptic control is achieved with adjunctive treatment, concomitant AEDs may be withdrawn and patients continued on lamotrigine monotherapy.

Children below 2 years

There are limited data on the efficacy and safety of lamotrigine for adjunctive therapy of partial seizures in children aged 1 month to 2 years (see section 4.4). There are no data in children below 1 month of age. Thus, Loxol is not recommended for use in children below 2 years of age. If, based on clinical need, a decision to treat is nevertheless taken, see sections 4.4, 5.1 and 5.2.

Bipolar disorder

The recommended dose escalation and maintenance doses for adults of 18 years of age and above are given in the tables below. The transition regimen involves escalating the dose of lamotrigine to a maintenance stabilisation dose over six weeks (Table 3) after which other psychotropic medicinal products and/or AEDs can be withdrawn, if clinically indicated (Table 4). The dose adjustments following addition of other psychotropic medicinal products and/or AEDs are also provided below (Table 5). Because of the risk of rash the initial dose and subsequent dose escalation should not be exceeded (see section 4.4).

 

Table 3: Adults aged 18 years and above - recommended dose escalation to the maintenance total daily stabilisation dose in treatment of bipolar disorder

Treatment Regimen

Weeks 1 + 2

Weeks 3 + 4

Week 5

Target Stabilisation Dose (Week 6)*

Monotherapy with lamotrigine OR adjunctive therapy WITHOUT valproate and WITHOUT inducers of lamotrigine glucuronidation (see section 4.5):

This dosage regimen should be used with other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation

25 mg/day

(once a day)

50 mg/day

(once a day or two divided doses)

100 mg/day

(once a day or two divided doses)

200 mg/day - usual target dose for optimal response

(once a day or two divided doses)

Doses in the range 100 - 400 mg/day used in clinical trials

Adjunctive therapy WITH valproate (inhibitor of lamotrigine glucuronidation – see section 4.5):

This dosage regimen should be used with valproate regardless of any concomitant medicinal products

12.5 mg/day

(given as 25 mg on alternate days)

25 mg/day

(once a day)

50 mg/day

(once a day or two divided doses)

100 mg/day - usual target dose for optimal response

(once a day or two divided doses)

Maximum dose of 200 mg/day can be used depending on clinical response

Adjunctive therapy WITHOUT valproate and WITH inducers of lamotrigine glucuronidation (see section 4.5):

This dosage regimen should be used without valproate but with:

phenytoin

carbamazepine

phenobarbitone

primidone

rifampicin

lopinavir/ritonavir

50 mg/day (once a day)

100 mg/day (two divided doses)

200 mg/day (two divided doses)

300 mg/day in week 6, if necessary increasing to usual target dose of 400 mg/day in week 7, to achieve optimal response (two divided doses)

In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently not known (see section 4.5), the dose escalation as recommended for lamotrigine with concurrent valproate, should be used.

*The Target stabilisation dose will alter depending on clinical response.

 

Table 4: Adults aged 18 years and above - maintenance stabilisation total daily dose following withdrawal of concomitant medicinal products in treatment of bipolar disorder

Once the target daily maintenance stabilisation dose has been achieved, other medicinal products may be withdrawn as shown below.

Treatment Regimen

Current lamotrigine stabilisation dose (prior to withdrawal)

Week 1 (beginning with withdrawal)

Week 2

Week 3 onwards *

Withdrawal of valproate (inhibitor of lamotrigine glucuronidation – see section 4.5), depending on original dose of lamotrigine:

When valproate is withdrawn, double the stabilisation dose, not exceeding an increase of more than 100 mg/week

100 mg/day

200 mg/day

Maintain this dose (200 mg/day)

(two divided doses)

200 mg/day

300 mg/day

400 mg/day

Maintain this dose (400 mg/day)

Withdrawal of inducers of lamotrigine glucuronidation (see section 4.5), depending on original dose of lamotrigine:

This dosage regimen should be used when the following are withdrawn:

phenytoin

carbamazepine

phenobarbitone

primidone

rifampicin

lopinavir/ritonavir

400 mg/day

400 mg/day

300 mg/day

200 mg/day

300 mg/day

300 mg/day

225 mg/day

150 mg/day

200 mg/day

200 mg/day

150 mg/day

100 mg/day

Withdrawal of medicinal products that do NOT significantly inhibit or induce lamotrigine glucuronidation (see section 4.5):

This dosage regimen should be used when other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation are withdrawn

Maintain target dose achieved in dose escalation (200 mg/day; two divided doses)

(dose range 100 - 400 mg/day)

In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently not known (see section 4.5), the treatment regimen recommended for lamotrigine is to initially maintain the current dose and adjust the lamotrigine treatment based on clinical response.

*Dose may be increased to 400 mg/day as needed.

 

Table 5: Adults aged 18 years and above - adjustment of lamotrigine daily dosing following the addition of other medicinal products in treatment of bipolar disorder

There is no clinical experience in adjusting the lamotrigine daily dose following the addition of other medicinal products. However, based on interaction studies with other medicinal products, the following recommendations can be made:

Treatment Regimen

Current lamotrigine stabilisation dose (prior to addition)

Week 1 (beginning with addition)

Week 2

Week 3 onwards

Addition of valproate (inhibitor of lamotrigine glucuronidation – see section 4.5), depending on original dose of lamotrigine:

This dosage regimen should be used when valproate is added regardless of any concomitant medicinal products

200 mg/day

100 mg/day

Maintain this dose (100 mg/day)

300 mg/day

150 mg/day

Maintain this dose (150 mg/day)

400 mg/day

200 mg/day

Maintain this dose (200 mg/day)

Addition of inducers of lamotrigine glucuronidation in patients NOT taking valproate (see section 4.5), depending on original dose of lamotrigine:

This dosage regimen should be used when the following are added without valproate:

phenytoin

carbamazepine

phenobarbitone

primidone

rifampicin

lopinavir/ritonavir

200 mg/day

200 mg/day

300 mg/day

400 mg/day

150 mg/day

150 mg/day

225 mg/day

300 mg/day

100 mg/day

100 mg/day

150 mg/day

200 mg/day

Addition of medicinal products that do NOT significantly inhibit or induce lamotrigine glucuronidation (see section 4.5):

This dosage regimen should be used when other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation are added

Maintain target dose achieved in dose escalation (200 mg/day; dose range 100-400 mg/day)

In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently not known (see section 4.5), the treatment regimen as recommended for lamotrigine with concurrent valproate, should be used.

 

Discontinuation of Loxol in patients with bipolar disorder

In clinical trials, there was no increase in the incidence, severity or type of adverse reactions following abrupt termination of lamotrigine versus placebo. Therefore, patients may terminate Loxol without a step-wise reduction of dose.

Children and adolescents below 18 years

Lamotrigine is not recommended for use in children below 18 years of age because a randomised withdrawal study demonstrated no significant efficacy and showed increased reporting of suicidality (see section 4.4 and 5.1).

General dosing recommendations for Loxol in special patient populations

Women taking hormonal contraceptives

The use of an ethinyloestradiol/levonorgestrel (30 μg/150 μg) combination increases the clearance of lamotrigine by approximately two-fold, resulting in decreased lamotrigine levels. Following titration, higher maintenance doses of lamotrigine (by as much as two-fold) may be needed to attain a maximal therapeutic response. During the pill-free week, a two-fold increase in lamotrigine levels has been observed. Dose-related adverse events cannot be excluded. Therefore, consideration should be given to using contraception without a pill-free week, as first-line therapy (for example, continuous hormonal contraceptives or non-hormonal methods; see sections 4.4 and 4.5).

Starting hormonal contraceptives in patients already taking maintenance doses of lamotrigine and NOT taking inducers of lamotrigine glucuronidation

The maintenance dose of lamotrigine will in most cases need to be increased by as much as two-fold (see sections 4.4 and 4.5). It is recommended that from the time that the hormonal contraceptive is started, the lamotrigine dose is increased by 50 to 100 mg/day every week, according to the individual clinical response. Dose increases should not exceed this rate, unless the clinical response supports larger increases. Measurement of serum lamotrigine concentrations before and after starting hormonal contraceptives may be considered, as confirmation that the baseline concentration of lamotrigine is being maintained. If necessary, the dose should be adapted. In women taking a hormonal contraceptive that includes one week of inactive treatment ("pill-free week"), serum lamotrigine level monitoring should be conducted during week 3 of active treatment, i.e. on days 15 to 21 of the pill cycle. Therefore, consideration should be given to using contraception without a pill-free week, as first-line therapy (for example, continuous hormonal contraceptives or non-hormonal methods; see sections 4.4 and 4.5).

Stopping hormonal contraceptives in patients already taking maintenance doses of lamotrigine and NOT taking inducers of lamotrigine glucuronidation

The maintenance dose of lamotrigine will in most cases need to be decreased by as much as 50% (see sections 4.4 and 4.5). It is recommended to gradually decrease the daily dose of lamotrigine by 50-100 mg each week (at a rate not exceeding 25% of the total daily dose per week) over a period of 3 weeks, unless the clinical response indicates otherwise. Measurement of serum lamotrigine concentrations before and after stopping hormonal contraceptives may be considered, as confirmation that the baseline concentration of lamotrigine is being maintained. In women who wish to stop taking a hormonal contraceptive that includes one week of inactive treatment ("pill-free week"), serum lamotrigine level monitoring should be conducted during week 3 of active treatment, i.e. on days 15 to 21 of the pill cycle. Samples for assessment of lamotrigine levels after permanently stopping the contraceptive pill should not be collected during the first week after stopping the pill. 

Starting lamotrigine in patients already taking hormonal contraceptives

Dose escalation should follow the normal dose recommendation described in the tables.

Starting and stopping hormonal contraceptives in patients already taking maintenance doses of lamotrigine and TAKING inducers of lamotrigine glucuronidation

Adjustment to the recommended maintenance dose of lamotrigine may not be required.

Use with atazanavir/ritonavir

No adjustments to the recommended dose escalation of lamotrigine should be necessary when lamotrigine is added to the existing atazanavir/ritonavir therapy.

In patients already taking maintenance doses of lamotrigine and not taking glucuronidation inducers, the lamotrigine dose may need to be increased if atazanavir/ritonavir is added, or decreased if atazanavir/ritonavir is discontinued. Plasma lamotrigine monitoring should be conducted before and during 2 weeks after starting or stopping atazanavir/ritonavir, in order to see if lamotrigine dose adjustment is needed (see section 4.5).

Use with lopinavir/ritonavir

No adjustments to the recommended dose escalation of lamotrigine should be necessary when lamotrigine is added to the existing lopinavir/ritonavir therapy.

In patients already taking maintenance doses of lamotrigine and not taking glucuronidation inducers, the lamotrigine dose may need to be increased if lopinavir/ritonavir is added, or decreased if lopinavir/ritonavir is discontinued. Plasma lamotrigine monitoring should be conducted before and during 2 weeks after starting or stopping lopinavir/ritonavir, in order to see if lamotrigine dose adjustment is needed (see section 4.5).

Elderly (above 65 years)

No dosage adjustment from the recommended schedule is required. The pharmacokinetics of lamotrigine in this age group do not differ significantly from a non-elderly adult population (see section 5.2).

Renal impairment

Caution should be exercised when administering Loxol to patients with renal failure. For patients with end-stage renal failure, initial doses of lamotrigine should be based on patients' concomitant medicinal products; reduced maintenance doses may be effective for patients with significant renal functional impairment (see sections 4.4 and 5.2).

Hepatic impairment

Initial, escalation and maintenance doses should generally be reduced by approximately 50% in patients with moderate (Child-Pugh grade B) and 75% in severe (Child-Pugh grade C) hepatic impairment. Escalation and maintenance doses should be adjusted according to clinical response (see section 5.2).

Method of administration

For oral use.


Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Skin rash

There have been reports of adverse skin reactions, which have generally occurred within the first eight weeks after initiation of lamotrigine treatment. The majority of rashes are mild and self-limiting, however serious rashes requiring hospitalisation and discontinuation of lamotrigine have also been reported. These have included potentially life-threatening rashes such as Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS); also known as hypersensitivity syndrome (HSS) (see section 4.8).

In adults enrolled in studies utilizing the current lamotrigine dosing recommendations the incidence of serious skin rashes is approximately 1 in 500 in epilepsy patients. Approximately half of these cases have been reported as Stevens–Johnson syndrome (1 in 1000). In clinical trials in patients with bipolar disorder, the incidence of serious rash is approximately 1 in 1000.

The risk of serious skin rashes in children is higher than in adults. Available data from a number of studies suggest the incidence of rashes associated with hospitalisation in children is from 1 in 300 to 1 in 100.

In children, the initial presentation of a rash can be mistaken for an infection, physicians should consider the possibility of a reaction to lamotrigine treatment in children that develop symptoms of rash and fever during the first eight weeks of therapy.

Additionally the overall risk of rash appears to be strongly associated with:

  •     High initial doses of lamotrigine and exceeding the recommended dose escalation of lamotrigine therapy (see section 4.2)
  •     Concomitant use of valproate (see section 4.2).

Caution is also required when treating patients with a history of allergy or rash to other AEDs as the frequency of non-serious rash after treatment with lamotrigine was approximately three times higher in these patients than in those without such history.

All patients (adults and children) who develop a rash should be promptly evaluated and Loxol withdrawn immediately unless the rash is clearly not related to lamotrigine treatment. It is recommended that Loxol not be restarted in patients who have discontinued due to rash associated with prior treatment with lamotrigine unless the potential benefit clearly outweighs the risk. If the patient has developed SJS, TEN or DRESS with the use of lamotrigine, treatment with lamotrigine must not be re-started in this patient at any time.

Rash has also been reported as part of DRESS; also known as hypersensitivity syndrome. This condition is associated with a variable pattern of systemic symptoms including fever, lymphadenopathy, facial oedema, abnormalities of the blood, liver, kidney and aseptic meningitis (see section 4.8). The syndrome shows a wide spectrum of clinical severity and may, rarely, lead to disseminated intravascular coagulation and multiorgan failure. It is important to note that early manifestations of hypersensitivity (for example fever, lymphadenopathy) may be present even though rash is not evident. If such signs and symptoms are present the patient should be evaluated immediately, and Loxol discontinued if an alternative aetiology cannot be established.

Aseptic meningitis was reversible on withdrawal of the drug in most cases, but recurred in a number of cases on re-exposure to lamotrigine. Re-exposure resulted in a rapid return of symptoms that were frequently more severe. Lamotrigine should not be restarted in patients who have discontinued due to aseptic meningitis associated with prior treatment of lamotrigine.

There have also been reports of photosensitivity reactions associated with lamotrigine use (see section 4.8). In several cases, the reaction occurred with a high dose (400 mg or more), upon dose escalation or rapid up-titration. If lamotrigine-associated photosensitivity is suspected in a patient showing signs of photosensitivity (such as an exaggerated sunburn), treatment discontinuation should be considered. If continued treatment with lamotrigine is considered clinically justified, the patient should be advised to avoid exposure to sunlight and artificial UV light and take protective measures (e.g. use of protective clothing and sunscreens).

Haemophagocytic lymphohistiocytosis (HLH)

HLH has been reported in patients taking lamotrigine (see section 4.8). HLH is characterised by signs and symptoms, like fever, rash, neurological symptoms, hepatosplenomegaly, lymphadenopathy, cytopenias, high serum ferritin, hypertriglyceridaemia and abnormalities of liver function and coagulation. Symptoms occur generally within 4 weeks of treatment initiation, HLH can be life threatening.

Patients should be informed of the symptoms associated with HLH and should be advised to seek medical attention immediately if they experience these symptoms while on lamotrigine therapy.

Immediately evaluate patients who develop these signs and symptoms and consider a diagnosis of HLH. Lamotrigine should be promptly discontinued unless an alternative aetiology can be established.

Clinical worsening and suicide risk

Suicidal ideation and behaviour have been reported in patients treated with AEDs in several indications. A meta-analysis of randomised placebo-controlled trials of AEDs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for lamotrigine.

Therefore, patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

In patients with bipolar disorder, worsening of depressive symptoms and/or the emergence of suicidality may occur whether or not they are taking medications for bipolar disorder, including Loxol. Therefore, patients receiving Loxol for bipolar disorder should be closely monitored for clinical worsening (including development of new symptoms) and suicidality, especially at the beginning of a course of treatment, or at the time of dose changes. Certain patients, such as those with a history of suicidal behaviour or thoughts, young adults, and those patients exhibiting a significant degree of suicidal ideation prior to commencement of treatment, may be at a greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment.

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients who experience clinical worsening (including development of new symptoms) and/or the emergence of suicidal ideation/behaviour, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.

Hormonal contraceptives

Effects of hormonal contraceptives on lamotrigine efficacy

The use of an ethinyloestradiol/levonorgestrel (30 μg/150 μg) combination increases the clearance of lamotrigine by approximately two-fold resulting in decreased lamotrigine levels (see section 4.5). A decrease in lamotrigine levels has been associated with loss of seizure control. Following titration, higher maintenance doses of lamotrigine (by as much as two-fold) will be needed in most cases to attain a maximal therapeutic response. When stopping hormonal contraceptives, the clearance of lamotrigine may be halved. Increases in lamotrigine concentrations may be associated with dose-related adverse events. Patients should be monitored with respect to this.

In women not already taking an inducer of lamotrigine glucuronidation and taking a hormonal contraceptive that includes one week of inactive treatment (for example "pill-free week"), gradual transient increases in lamotrigine levels will occur during the week of inactive treatment (see section 4.2). Variations in lamotrigine levels of this order may be associated with adverse effects. Therefore, consideration should be given to using contraception without a pill-free week, as first-line therapy (for example, continuous hormonal contraceptives or non-hormonal methods).

The interaction between other oral contraceptive or HRT treatments and lamotrigine have not been studied, though they may similarly affect lamotrigine pharmacokinetic parameters.

Effects of lamotrigine on hormonal contraceptive efficacy

An interaction study in 16 healthy volunteers has shown that when lamotrigine and a hormonal contraceptive (ethinyloestradiol/levonorgestrel combination) are administered in combination, there is a modest increase in levonorgestrel clearance and changes in serum FSH and LH (see section 4.5). The impact of these changes on ovarian ovulatory activity is unknown. However, the possibility of these changes resulting in decreased contraceptive efficacy in some patients taking hormonal preparations with lamotrigine cannot be excluded. Therefore patients should be instructed to promptly report changes in their menstrual pattern, i.e. breakthrough bleeding.

Dihydrofolate reductase

Lamotrigine has a slight inhibitory effect on dihydrofolic acid reductase, hence there is a possibility of interference with folate metabolism during long-term therapy (see section 4.6). However, during prolonged human dosing, lamotrigine did not induce significant changes in the haemoglobin concentration, mean corpuscular volume, or serum or red blood cell folate concentrations up to 1 year or red blood cell folate concentrations for up to 5 years.

Renal failure

In single dose studies in subjects with end stage renal failure, plasma concentrations of lamotrigine were not significantly altered. However, accumulation of the glucuronide metabolite is to be expected; caution should therefore be exercised in treating patients with renal failure.

Patients taking other preparations containing lamotrigine

Loxol should not be administered to patients currently being treated with any other preparation containing lamotrigine without consulting a doctor.

Brugada-type ECG and other cardiac rhythm and conduction abnormalities

Arrhythmogenic ST-T abnormality and typical Brugada ECG pattern have been reported in patients treated with lamotrigine.

Based on in vitro findings, lamotrigine could potentially slow ventricular conduction (widen QRS) and induce proarrhythmia at therapeutically relevant concentrations in patients with heart disease. Lamotrigine behaves like a weak class IB antiarrhythmic agent with associated potential risks for serious or fatal cardiac events. Concomitant use of other sodium channel blockers may further increase the risks (see section 5.3). At therapeutic doses up to 400 mg/day, lamotrigine did not slow ventricular conduction (widen QRS) or cause QT prolongation in healthy individuals in a thorough QT study. The use of lamotrigine should be carefully considered in patients with clinically important structural or functional heart disease such as Brugada syndrome or other cardiac channelopathies, heart failure, ischemic heart disease, heart block or ventricular arrhythmias. If lamotrigine is clinically justified in these patients, consultation with a cardiologist before initiating lamotrigine should be considered.

Loxol contains lactose, sodium and FD & C yellow no.6 lake

Loxol contains lactose. Each tablet of Loxol 100 mg Tablets contains 54 mg lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Loxol contains sodium. Each tablet of Loxol 100 mg Tablets contains 2.2188 mg sodium. This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

Loxol contains FD & C yellow no.6 lake. Each tablet of Loxol 100 mg Tablets contains 0.4 mg FD & C yellow no.6 lake, which may cause allergic reactions. 

Development in children

There are no data on the effect of lamotrigine on growth, sexual maturation and cognitive, emotional and behavioural developments in children.

Precautions relating to epilepsy

As with other AEDs, abrupt withdrawal of Loxol may provoke rebound seizures. Unless safety concerns (for example rash) require an abrupt withdrawal, the dose of Loxol should be gradually decreased over a period of two weeks.

There are reports in the literature that severe convulsive seizures including status epilepticus may lead to rhabdomyolysis, multiorgan dysfunction and disseminated intravascular coagulation, sometimes with fatal outcome. Similar cases have occurred in association with the use of lamotrigine.

A clinically significant worsening of seizure frequency instead of an improvement may be observed. In patients with more than one seizure type, the observed benefit of control for one seizure type should be weighed against any observed worsening in another seizure type.

Myoclonic seizures may be worsened by lamotrigine.

There is a suggestion in the data that responses in combination with enzyme inducers is less than in combination with non-enzyme inducing antiepileptic agents. The reason is unclear.

In children taking lamotrigine for the treatment of typical absence seizures, efficacy may not be maintained in all patients.

Precautions relating to bipolar disorder

Children and adolescents below 18 years

Treatment with antidepressants is associated with an increased risk of suicidal thinking and behaviour in children and adolescents with major depressive disorder and other psychiatric disorders.


Interaction studies have only been performed in adults.

Uridine 5'-diphospho (UDP)-glucuronyl transferases (UGTs) have been identified as the enzymes responsible for metabolism of lamotrigine. Drugs that induce or inhibit glucuronidation may, therefore, affect the apparent clearance of lamotrigine. Strong or moderate inducers of the cytochrome P450 3A4 (CYP3A4) enzyme, which are also known to induce UGTs, may also enhance the metabolism of lamotrigine. There is no evidence that lamotrigine causes clinically significant induction or inhibition of cytochrome P450 enzymes. Lamotrigine may induce its own metabolism but the effect is modest and unlikely to have significant clinical consequences.

Those drugs that have been demonstrated to have a clinically relevant impact on lamotrigine concentration are outlined in Table 6. Specific dosing guidance for these drugs is provided in Section 4.2. In addition, this table lists those drugs which have been shown to have little or no effect on the concentration of lamotrigine. Coadministration of such drugs would generally not be expected to result in any clinical impact. However, consideration should be given to patients whose epilepsy is especially sensitive to fluctuations in concentrations of lamotrigine.

 

Table 6: Effects of medicinal products on the concentration of lamotrigine

Medicinal products that increase the concentration of lamotrigine

Medicinal products that decrease the concentration ion of lamotrigine

Medicinal products have little or no effect on the concentration of lamotrigine

Valproate

Atazanavir/ritonavir*

Aripiprazole

 

Carbamazepine

Buproprion

 

Ethinyloestradiol/levonorgestrel combination*

Felbamate

 

Lopinavir/ritonavir

Gabapentin

 

Phenobarbitone

Lacosamide

 

Phenytoin

Levetiracetam

 

Primidone

Lithium

 

Rifampicin

Olanzapine

  

Oxcarbazepine

  

Paracetamol

  

Perampanel

  

Pregabalin

  

Topiramate

  

Zonisamide

*For dosing guidance (see section 4.2) plus for women taking hormonal contraceptives also see Hormonal Contraceptives in section 4.4.

 

Interactions involving antiepileptic drugs

Valproate, which inhibits the glucuronidation of lamotrigine, reduces the metabolism of lamotrigine and increases the mean half-life of lamotrigine nearly two-fold. In patients receiving concomitant therapy with valproate, the appropriate treatment regimen should be used (see section 4.2).

Certain AEDs (such as phenytoin, carbamazepine, phenobarbitone and primidone) which induce cytochrome P450 enzymes also induce UGTs and, therefore, enhance the metabolism of lamotrigine. In patients receiving concomitant therapy with phenytoin, carbamazepine, pheonbarbitone or primidone, the appropriate treatment regimen should be used (see section 4.2).

There have been reports of central nervous system events including dizziness, ataxia, diplopia, blurred vision and nausea in patients taking carbamazepine following the introduction of lamotrigine. These events usually resolve when the dose of carbamazepine is reduced. A similar effect was seen during a study of lamotrigine and oxcarbazepine in healthy adult volunteers, but dose reduction was not investigated.

There are reports in the literature of decreased lamotrigine levels when lamotrigine was given in combination with oxcarbazepine. However, in a prospective study in healthy adult volunteers using doses of 200 mg lamotrigine and 1200 mg oxcarbazepine, oxcarbazepine did not alter the metabolism of lamotrigine and lamotrigine did not alter the metabolism of oxcarbazepine. Therefore, in patients receiving concomitant therapy with oxcarbazepine, the treatment regimen for lamotrigine adjunctive therapy without valproate and without inducers of lamotrigine glucuronidation should be used (see section 4.2).

In a study of healthy volunteers, coadministration of felbamate (1200 mg twice daily) with lamotrigine (100 mg twice daily for 10 days) appeared to have no clinically relevant effects on the pharmacokinetics of lamotrigine.

Based on a retrospective analysis of plasma levels in patients who received lamotrigine both with and without gabapentin, gabapentin does not appear to change the apparent clearance of lamotrigine.

Potential interactions between levetiracetam and lamotrigine were assessed by evaluating serum concentrations of both agents during placebo-controlled clinical trials. These data indicate that lamotrigine does not influence the pharmacokinetics of levetiracetam and that levetiracetam does not influence the pharmacokinetics of lamotrigine.

Steady-state trough plasma concentrations of lamotrigine were not affected by concomitant pregabalin (200 mg, 3 times daily) administration. There are no pharmacokinetic interactions between lamotrigine and pregabalin.

Topiramate resulted in no change in plasma concentrations of lamotrigine. Administration of lamotrigine resulted in a 15% increase in topiramate concentrations.

In a study of patients with epilepsy, coadministration of zonisamide (200 to 400 mg/day) with lamotrigine (150 to 500 mg/day) for 35 days had no significant effect on the pharmacokinetics of lamotrigine.

Plasma concentrations of lamotrigine were not affected by concomitant lacosamide (200, 400, or 600 mg/day) in placebo-controlled clinical trials in patients with partial-onset seizures.

In a pooled analysis of data from three placebo-controlled clinical trials investigating adjunctive perampanel in patients with partial-onset and primary generalised tonic-clonic seizures, the highest perampanel dose evaluated (12 mg/day) increased lamotrigine clearance by less than 10%.

Although changes in the plasma concentrations of other AEDs have been reported, controlled studies have shown no evidence that lamotrigine affects the plasma concentrations of concomitant AEDs. Evidence from in vitro studies indicates that lamotrigine does not displace other AEDs from protein binding sites.

Interactions involving other psychoactive agents

The pharmacokinetics of lithium after 2 g of anhydrous lithium gluconate given twice daily for six days to 20 healthy subjects were not altered by co-administration of 100 mg/day lamotrigine.

Multiple oral doses of bupropion had no statistically significant effects on the single dose pharmacokinetics of lamotrigine in 12 subjects and had only a slight increase in the AUC of lamotrigine glucuronide.

In a study in healthy adult volunteers, 15 mg olanzapine reduced the AUC and Cmax of lamotrigine by an average of 24% and 20%, respectively. Lamotrigine at 200 mg did not affect the pharmacokinetics of olanzapine.

Multiple oral doses of lamotrigine 400 mg daily had no clinically significant effect on the single dose pharmacokinetics of 2 mg risperidone in 14 healthy adult volunteers. Following the co-administration of risperidone 2 mg with lamotrigine, 12 out of the 14 volunteers reported somnolence compared to 1 out of 20 when risperidone was given alone, and none when lamotrigine was administered alone.

In a study of 18 adult patients with bipolar I disorder, receiving an established regimen of lamotrigine (100-400 mg/day), doses of aripiprazole were increased from 10 mg/day to a target of 30 mg/day over a 7 day period and continued once daily for a further 7 days. An average reduction of approximately 10% in Cmax and AUC of lamotrigine was observed.

In vitro experiments indicated that the formation of lamotrigine's primary metabolite, the 2-N-glucuronide, was minimally inhibited by co-incubation with amitriptyline, bupropion, clonazepam, haloperidol or lorazepam. These experiments also suggested that metabolism of lamotrigine was unlikely to be inhibited by clozapine, fluoxetine, phenelzine, risperidone, sertraline or trazodone. In addition, a study of bufuralol metabolism using human liver microsome preparations suggested that lamotrigine would not reduce the clearance of medicinal products metabolised predominantly by CYP2D6.

Interactions involving hormonal contraceptives

Effect of hormonal contraceptives on lamotrigine pharmacokinetics

In a study of 16 female volunteers, dosing with 30 μg ethinyloestradiol/150 μg levonorgestrel in a combined oral contraceptive pill caused an approximately two-fold increase in lamotrigine oral clearance, resulting in an average 52% and 39% reduction in lamotrigine AUC and Cmax, respectively. Serum lamotrigine concentrations increased during the course of the week of inactive treatment (including the "pill-free" week), with pre-dose concentrations at the end of the week of inactive treatment being, on average, approximately two-fold higher than during co-therapy (see section 4.4). No adjustments to the recommended dose escalation guidelines for lamotrigine should be necessary solely based on the use of hormonal contraceptives, but the maintenance dose of lamotrigine will need to be increased or decreased in most cases when starting or stopping hormonal contraceptives (see section 4.2).

Effect of lamotrigine on hormonal contraceptive pharmacokinetics

In a study of 16 female volunteers, a steady state dose of 300 mg lamotrigine had no effect on the pharmacokinetics of the ethinyloestradiol component of a combined oral contraceptive pill. A modest increase in oral clearance of the levonorgestrel component was observed, resulting in an average 19% and 12% reduction in levonorgestrel AUC and Cmax, respectively. Measurement of serum FSH, LH and oestradiol during the study indicated some loss of suppression of ovarian hormonal activity in some women, although measurement of serum progesterone indicated that there was no hormonal evidence of ovulation in any of the 16 subjects. The impact of the modest increase in levonorgestrel clearance, and the changes in serum FSH and LH, on ovarian ovulatory activity is unknown (see section 4.4). The effects of doses of lamotrigine other than 300 mg/day have not been studied and studies with other female hormonal preparations have not been conducted.

Interactions involving other medicinal products

In a study in 10 male volunteers, rifampicin increased lamotrigine clearance and decreased lamotrigine half-life due to induction of the hepatic enzymes responsible for glucuronidation. In patients receiving concomitant therapy with rifampicin, the appropriate treatment regimen should be used (see section 4.2).

In a study in healthy volunteers, lopinavir/ritonavir approximately halved the plasma concentrations of lamotrigine, probably by induction of glucuronidation. In patients receiving concomitant therapy with lopinavir/ritonavir, the appropriate treatment regimen should be used (see section 4.2).

In a study in healthy adult volunteers, atazanavir/ritonavir (300 mg/100 mg) administered for 9 days reduced the plasma AUC and Cmax of lamotrigine (single 100 mg dose) by an average of 32% and 6%, respectively. In patients receiving concomitant therapy with atazanavir/ritonavir, the appropriate treatment regimen should be used (see section 4.2).

In a study in healthy adult volunteers, paracetamol 1g (four times daily) reduced the plasma AUC and Cmin of lamotrigine by an average of 20% and 25%, respectively.

Data from in vitro assessment demonstrate that lamotrigine, but not the N(2)-glucuronide metabolite, is an inhibitor of Organic Transporter 2 (OCT 2) at potentially clinically relevant concentrations. These data demonstrate that lamotrigine is an inhibitor of OCT 2, with an IC50 value of 53.8 µM. Co-administration of lamotrigine with renally excreted medicinal products, which are substrates of OCT 2 (e.g. metformin, gabapentin and varenicline), may result in increased plasma levels of these medicinal products.

The clinical significance of this has not been clearly defined, however care should be taken in patients co-administered with these medicinal products.


Risk related to antiepileptic drugs in general

Specialist advice should be given to women who are of childbearing potential. The antiepileptic treatment should be reviewed when a woman is planning to become pregnant. In women being treated for epilepsy, sudden discontinuation of AED therapy should be avoided as this may lead to breakthrough seizures that could have serious consequences for the woman and the unborn child. Monotherapy should be preferred whenever possible because therapy with multiple AEDs could be associated with a higher risk of congenital malformations than monotherapy, depending on the associated antiepileptics. 

Risk related to lamotrigine

Pregnancy

A large amount of data on pregnant women exposed to lamotrigine monotherapy during the first trimester of pregnancy (more than 8700) do not suggest a substantial increase in the risk for major congenital malformations, including oral clefts. Animal studies have shown developmental toxicity (see section 5.3).

If therapy with Loxol is considered necessary during pregnancy, the lowest possible therapeutic dose is recommended.

Lamotrigine has a slight inhibitory effect on dihydrofolic acid reductase and could therefore theoretically lead to an increased risk of embryofoetal damage by reducing folic acid levels. Intake of folic acid when planning pregnancy and during early pregnancy may be considered.

Physiological changes during pregnancy may affect lamotrigine levels and/or therapeutic effect. There have been reports of decreased lamotrigine plasma levels during pregnancy with a potential risk of loss of seizure control. After birth lamotrigine levels may increase rapidly with a risk of dose-related adverse events. Therefore lamotrigine serum concentrations should be monitored before, during and after pregnancy, as well as shortly after birth. If necessary, the dose should be adapted to maintain the lamotrigine serum concentration at the same level as before pregnancy, or adapted according to clinical response. In addition, dose-related undesirable effects should be monitored after birth.

Lactation

Lamotrigine has been reported to pass into breast milk in highly variable concentrations, resulting in total lamotrigine levels in infants of up to approximately 50% of the mothers’. Therefore, in some breast-fed infants, serum concentrations of lamotrigine may reach levels at which pharmacological effects occur.

The potential benefits of breast-feeding should be weighed against the potential risk of adverse effects occurring in the infant. Should a woman decide to breast-feed while on therapy with lamotrigine, the infant should be monitored for adverse effects, such as sedation, rash and poor weight gain. 

Fertility

Animal experiments did not reveal impairment of fertility by lamotrigine (see section 5.3).


As there is individual variation in response to all AED therapy, patients taking Loxol to treat epilepsy should consult their physician on the specific issues of driving and epilepsy.

No studies on the effects on the ability to drive and use machines have been performed. Two volunteer studies have demonstrated that the effect of lamotrigine on fine visual motor co-ordination, eye movements, body sway and subjective sedative effects did not differ from placebo. In clinical trials with lamotrigine adverse reactions of a neurological character such as dizziness and diplopia have been reported. Therefore, patients should see how Loxol therapy affects them before driving or operating machinery.


The undesirable effects for epilepsy and bipolar disorder indications are based on available data from controlled clinical studies and other clinical experience and are listed in the table below.

Frequency categories are derived from controlled clinical studies (epilepsy monotherapy (identified by) and bipolar disorder (identified by §)). Where frequency categories differ between clinical trial data from epilepsy and bipolar disorder the most conservative frequency is shown. However, where no controlled clinical trial data are available, frequency categories have been obtained from other clinical experience.

The following convention has been utilised for the classification of undesirable effects:- Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000), not known (cannot be estimated from the available data).

 

System Organ Class

Adverse Event

Frequency

Blood and lymphatic system disorders

Haematological abnormalities1 including neutropenia, leucopenia, anaemia, thrombocytopenia, pancytopenia, aplastic anaemia, agranulocytosis

Haemophagocytic lymphohistiocytosis (see section 4.4)

 

Lymphadenopathy1

Very rare

 

Very rare

 

Not known

Immune System Disorders

Hypersensitivity syndrome2

Hypogammaglobulinaemia

Very rare

Unknown

Psychiatric Disorders

Aggression, irritability

Confusion, hallucinations, tics

Nightmares

Common

Very rare

Not known

Nervous System Disorders

Headache§

 

Somnolence†§, dizziness†§, tremor, insomnia agitation§

 

Ataxia

 

Nystagmus, aseptic meningitis (see section 4.4)

 

Unsteadiness, movement disorders, worsening of Parkinson's disease 3, extrapyramidal effects, choreoathetosis, increase in seizure frequency

Very common

Common

 

Uncommon

 

Rare

 

Very rare

Eye disorders

Diplopia, blurred vision

Conjunctivitis

Uncommon

Rare

Gastrointestinal disorders

Nausea, vomiting, diarrhoea, dry mouth§

Common

Hepatobiliary disorders

Hepatic failure, hepatic dysfunction4, increased liver function tests

Very rare

Skin and subcutaneous tissue disorders

Skin rash5†§

 

Alopecia, photosensitivity reaction

 

Stevens–Johnson Syndrome§

Toxic epidermal necrolysis

Drug Reaction with Eosinophilia and Systemic2 Symptoms

Very common

Uncommon

 

Rare

Very rare

Very rare

Musculoskeletal and connective tissue disorders

Arthralgia§

Lupus-like reactions

Common

Very rare

Renal and urinary disorders

Tubulointerstitial nephritis, tubulointerstitial nephritis and uveitis syndrome

Not known

General disorders and administration site conditions

Tiredness, pain§, back pain§

Common

 

Description of selected adverse reactions

Haematological abnormalities and lymphadenopathy may or may not be associated with the Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / hypersensitivity syndrome (see Special warnings and precautions for use and Immune system disorders).

Rash has also been reported as part of this syndrome, also known as DRESS. This condition is associated with a variable pattern of systemic symptoms including fever, lymphadenopathy, facial oedema, and abnormalities of the blood, liver and kidney. The syndrome shows a wide spectrum of clinical severity and may, rarely, lead to disseminated intravascular coagulation and multiorgan failure. It is important to note that early manifestations of hypersensitivity (for example fever, lymphadenopathy) may be present even though rash is not evident. If such signs and symptoms are present, the patient should be evaluated immediately, and lamotrigine discontinued if an alternative aetiology cannot be established (see section 4.4).

These effects have been reported during other clinical experience.

There have been reports that lamotrigine may worsen parkinsonian symptoms in patients with pre-existing Parkinson's disease, and isolated reports of extrapyramidal effects and choreoathetosis in patients without this underlying condition.

Hepatic dysfunction usually occurs in association with hypersensitivity reactions but isolated cases have been reported without overt signs of hypersensitivity.

In clinical trials in adults, skin rashes occurred in up to 8-12% of patients taking lamotrigine and in 5-6% of patients taking placebo. The skin rashes led to the withdrawal of lamotrigine treatment in 2% of patients. The rash, usually maculopapular in appearance, generally appears within eight weeks of starting treatment and resolves on withdrawal of lamotrigine (see section 4.4).

Serious potentially life-threatening skin rashes, including Stevens–Johnson syndrome and toxic epidermal necrolysis (Lyell's Syndrome) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have been reported. Although the majority recover on withdrawal of lamotrigine treatment, some patients experience irreversible scarring and there have been rare cases of associated death (see section 4.4).

The overall risk of rash, appears to be strongly associated with:

  •     High initial doses of lamotrigine and exceeding the recommended dose escalation of lamotrigine therapy (see section 4.2)
  •     Concomitant use of valproate (see section 4.2).

There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in patients on long-term therapy with lamotrigine. The mechanism by which lamotrigine affects bone metabolism has not been identified

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

  •     Saudi Arabia

The National Pharmacovigilance Centre (NPC)

SFDA Call Center: 19999

E-mail: npc.drug@sfda.gov.sa

Website: https://ade.sfda.gov.sa

  •     Other GCC States

Please contact the relevant competent authority.


Symptoms and signs

Acute ingestion of doses in excess of 10 to 20 times the maximum therapeutic dose has been reported, including fatal cases. Overdose has resulted in symptoms including nystagmus, ataxia, impaired consciousness, grand mal convulsion and coma. QRS broadening (intraventricular conduction delay) and QT prolongation have also been observed in overdose patients Broadening of QRS duration to more than 100 msec may be associated with more severe toxicity.

Treatment

In the event of overdose, the patient should be admitted to hospital and given appropriate supportive therapy. Therapy aimed at decreasing absorption (activated charcoal) should be performed if indicated. Further management should be as clinically indicated, taking into account potential effects on cardiac conduction (see section 4.4). There is no experience with haemodialysis as treatment of overdose. In six volunteers with kidney failure, 20% of the lamotrigine was removed from the body during a 4 hour haemodialysis session (see section 5.2).


Pharmacotherapeutic group: other antiepileptics, ATC code: N03AX09.

Mechanism of action

The results of pharmacological studies suggest that lamotrigine is a use- and voltage-dependent blocker of voltage gated sodium channels. It inhibits sustained repetitive firing of neurones and inhibits release of glutamate (the neurotransmitter which plays a key role in the generation of epileptic seizures). These effects are likely to contribute to the anticonvulsant properties of lamotrigine.

In contrast, the mechanisms by which lamotrigine exerts its therapeutic action in bipolar disorder have not been established, although interaction with voltage gated sodium channels is likely to be important.

Pharmacodynamic effects

In tests designed to evaluate the central nervous system effects of medicinal products, the results obtained using doses of 240 mg lamotrigine administered to healthy volunteers did not differ from placebo, whereas both 1000 mg phenytoin and 10 mg diazepam each significantly impaired fine visual motor co-ordination and eye movements, increased body sway and produced subjective sedative effects.

In another study, single oral doses of 600 mg carbamazepine significantly impaired fine visual motor co-ordination and eye movements, while increasing both body sway and heart rate, whereas results with lamotrigine at doses of 150 mg and 300 mg did not differ from placebo.

Study of the effect of lamotrigine on cardiac conduction

A study in healthy adult volunteers evaluated the effect of repeat doses of lamotrigine (up to 400 mg/day) on cardiac conduction, as assessed by 12 lead ECG. There was no clinically significant effect of lamotrigine on QT interval compared to placebo.

Clinical efficacy and safety

Prevention of mood episodes in patients with bipolar disorder

The efficacy of lamotrigine in the prevention of mood episodes in patients with bipolar I disorder has been evaluated in two studies.

Study SCAB2003 was a multicentre, double blind, double dummy, placebo and lithium-controlled, randomised fixed dose evaluation of the long term prevention of relapse and recurrence of depression and/or mania in patients with bipolar I disorder who had recently or were currently experiencing a major depressive episode. Once stabilised using lamotrigine monotherapy or adjunctive therapy, patients were randomly assigned into one of five treatment groups: lamotrigine (50, 200, 400 mg/day), lithium (serum levels of 0.8 to 1.1 mMol/L) or placebo for a maximum of 76 weeks (18 months). The primary endpoint was "Time to Intervention for a Mood Episode (TIME)", where the interventions were additional pharmacotherapy or electroconvulsive therapy (ECT). Study SCAB2006 had a similar design as study SCAB2003, but differed from study SCAB2003 in evaluating a flexible dose of lamotrigine (100 to 400 mg/day) and including patients with bipolar I disorder who had recently or were currently experiencing a manic episode. The results are shown in Table 7.

 

Table 7: Summary of results from studies investigating the efficacy of lamotrigine in the prevention of mood episodes in patients with bipolar I disorder

'Proportion' of patients being event free at week 76

 

Study SCAB2003

Bipolar I

Study SCAB2006

Bipolar I

Inclusion criterion

Major depressive episode

Major manic episode

 

Lamotrigine

Lithium

Placebo

Lamotrigine

Lithium

Placebo

Intervention free

0.22

0.21

0.12

0.17

0.24

0.04

p-value Log rank test

0.004

0.006

-

0.023

0.006

-

Depression free

0.51

0.46

0.41

0.82

0.71

0.40

p-value Log rank test

0.047

0.209

-

0.015

0.167

-

Free of mania

0.70

0.86

0.67

0.53

0.64

0.37

p-value Log rank test

0.339

0.026

-

0.280

0.006

-

 

In supportive analyses of time to first depressive episode and time to first manic/hypomanic or mixed episode, the lamotrigine-treated patients had significantly longer times to first depressive episode than placebo patients, and the treatment difference with respect to time to manic/hypomanic or mixed episodes was not statistically significant.

The efficacy of lamotrigine in combination with mood stabilisers has not been adequately studied.

Paediatric population

Children aged 1 to 24 months

The efficacy and safety of adjunctive therapy in partial seizures in patients aged 1 to 24 months has been evaluated in a small double-blind placebo-controlled withdrawal study. Treatment was initiated in 177 subjects, with a dose titration schedule similar to that of children aged 2 to 12 years. Lamotrigine 2 mg tablets are the lowest strength available, therefore the standard dosing schedule was adapted in some cases during the titration phase (for example, by administering a 2 mg tablet on alternate days when the calculated dose was less than 2 mg). Serum levels were measured at the end of week 2 of titration and the subsequent dose either reduced or not increased if the concentration exceeded 0.41 µg/ml, the expected concentration in adults at this time point. Dose reductions of up to 90% were required in some patients at the end of week 2. Thirty-eight responders (> 40% decrease in seizure frequency) were randomised to placebo or continuation of lamotrigine. The proportion of subjects with treatment failure was 84% (16/19 subjects) in the placebo arm and 58% (11/19 subjects) in the lamotrigine arm. The difference was not statistically significant: 26.3%, CI95% -2.6% <> 50.2%, p=0.07.

A total of 256 subjects between 1 to 24 months of age have been exposed to lamotrigine in the dose range 1 to 15 mg/kg/day for up to 72 weeks. The safety profile of lamotrigine in children aged 1 month to 2 years was similar to that in older children except that clinically significant worsening of seizures (>=50%) was reported more often in children under 2 years of age (26%) as compared to older children (14%).

Lennox Gastaut syndrome

There are no data for monotherapy in seizures associated with Lennox Gastaut syndrome.

Prevention of mood episodes in children (10-12 years of age) and adolescents (13-17 years of age)

A multicentre, parallel group, placebo-controlled, double-blind, randomised withdrawal study, evaluated the efficacy and safety of lamotrigine IR as add-on maintenance therapy to delay mood episodes in male and female children and adolescents (age 10-17 years) who had been diagnosed with bipolar I disorder and who had remitted or improved from a bipolar episode while treated with lamotrigine in combinations with concomitant antipsychotic or other mood-stabilising drugs. The result of the primary efficacy analysis (time to occurrence of a bipolar event – TOBE) did not reach statistical significance (p=0.0717), thus efficacy was not shown. In addition, safety results showed increased reporting of suicidal behaviours in lamotrigine treated patients: 5% (4 patients) in the lamotrigine arm compared to 0 in placebo (see section 4.2).


Absorption

Lamotrigine is rapidly and completely absorbed from the gut with no significant first-pass metabolism. Peak plasma concentrations occur approximately 2.5 hours after oral administration of lamotrigine. Time to maximum concentration is slightly delayed after food but the extent of absorption is unaffected. There is considerable inter-individual variation in steady state maximum concentrations but within an individual, concentrations rarely vary. 

Distribution

Binding to plasma proteins is about 55%; it is very unlikely that displacement from plasma proteins would result in toxicity.

The volume of distribution is 0.92 to 1.22 L/kg. 

Biotransformation

UDP-glucuronyl transferases have been identified as the enzymes responsible for metabolism of lamotrigine.

Lamotrigine induces its own metabolism to a modest extent depending on dose. However, there is no evidence that lamotrigine affects the pharmacokinetics of other AEDs and data suggest that interactions between lamotrigine and medicinal products metabolised by cytochrome P450 enzymes are unlikely to occur. 

Elimination

The apparent plasma clearance in healthy subjects is approximately 30 ml/min. Clearance of lamotrigine is primarily metabolic with subsequent elimination of glucuronide-conjugated material in urine. Less than 10% is excreted unchanged in the urine. Only about 2% of lamotrigine-related material is excreted in faeces. Clearance and half-life are independent of dose. The apparent plasma half-life in healthy subjects is estimated to be approximately 33 hours (range 14 to 103 hours). In a study of subjects with Gilbert's Syndrome, mean apparent clearance was reduced by 32% compared with normal controls but the values are within the range for the general population.

The half-life of lamotrigine is greatly affected by concomitant medicinal products. Mean half-life is reduced to approximately 14 hours when given with glucuronidation-inducing medicinal products such as carbamazepine and phenytoin and is increased to a mean of approximately 70 hours when co-administered with valproate alone (see section 4.2).

Linearity

The pharmacokinetics of lamotrigine are linear up to 450 mg, the highest single dose tested. 

Special patient populations

Children

Clearance adjusted for body weight is higher in children than in adults with the highest values in children under five years. The half-life of lamotrigine is generally shorter in children than in adults with a mean value of approximately 7 hours when given with enzyme-inducing medicinal products such as carbamazepine and phenytoin and increasing to mean values of 45 to 50 hours when co-administered with valproate alone (see section 4.2). 

Infants aged 2 to 26 months

In 143 paediatric patients aged 2 to 26 months, weighing 3 to 16 kg, clearance was reduced compared to older children with the same body weight, receiving similar oral doses per kg body weight as children older than 2 years. The mean half-life was estimated at 23 hours in infants younger than 26 months on enzyme-inducing therapy, 136 hours when co-administered with valproate and 38 hours in subjects treated without enzyme inducers/inhibitors. The inter-individual variability for oral clearance was high in the group of paediatric patients of 2 to 26 months (47%). The predicted serum concentration levels in children of 2 to 26 months were in general in the same range as those in older children, though higher Cmax levels are likely to be observed in some children with a body weight below 10 kg.

Elderly

Results of a population pharmacokinetic analysis including both young and elderly patients with epilepsy, enrolled in the same trials, indicated that the clearance of lamotrigine did not change to a clinically relevant extent. After single doses apparent clearance decreased by 12% from 35 ml/min at age 20 to 31 ml/min at 70 years. The decrease after 48 weeks of treatment was 10% from 41 to 37 ml/min between the young and elderly groups. In addition, pharmacokinetics of lamotrigine was studied in 12 healthy elderly subjects following a 150 mg single dose. The mean clearance in the elderly (0.39 ml/min/kg) lies within the range of the mean clearance values (0.31 to 0.65 ml/min/kg) obtained in nine studies with non-elderly adults after single doses of 30 to 450 mg.

Renal impairment

Twelve volunteers with chronic renal failure, and another six individuals undergoing haemodialysis were each given a single 100 mg dose of lamotrigine. Mean clearances were 0.42 ml/min/kg (chronic renal failure), 0.33 ml/min/kg (between haemodialysis) and 1.57 ml/min/kg (during haemodialysis), compared with 0.58 ml/min/kg in healthy volunteers. Mean plasma half-lives were 42.9 hours (chronic renal failure), 57.4 hours (between haemodialysis) and 13.0 hours (during haemodialysis), compared with 26.2 hours in healthy volunteers. On average, approximately 20% (range = 5.6 to 35.1) of the amount of lamotrigine present in the body was eliminated during a 4-hour haemodialysis session. For this patient population, initial doses of lamotrigine should be based on the patient's concomitant medicinal products; reduced maintenance doses may be effective for patients with significant renal functional impairment (see sections 4.2 and 4.4). 

Hepatic impairment

A single dose pharmacokinetic study was performed in 24 subjects with various degrees of hepatic impairment and 12 healthy subjects as controls. The median apparent clearance of lamotrigine was 0.31, 0.24 or 0.10 ml/min/kg in patients with Grade A, B, or C (Child-Pugh Classification) hepatic impairment, respectively, compared with 0.34 ml/min/kg in the healthy controls. Initial, escalation and maintenance doses should generally be reduced in patients with moderate or severe hepatic impairment (see section 4.2).


Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.

In reproductive and developmental toxicity studies in rodents and rabbits, no teratogenic effects but reduced foetal weight and retarded skeletal ossification were observed, at exposure levels below or similar to the expected clinical exposure. Since higher exposure levels could not be tested in animals due to the severity of maternal toxicity, the teratogenic potential of lamotrigine has not been characterised above clinical exposure.

In rats, enhanced foetal as well as post-natal mortality was observed when lamotrigine was administered during late gestation and through the early post-natal period. These effects were observed below the expected clinical exposure.

In juvenile rats, an effect on learning in the Biel maze test, a slight delay in balanopreputial separation and vaginal patency and a decreased postnatal body weight gain in F1 animals were observed at exposures less than the therapeutic exposures in human adults, based on body surface area.

Animal experiments did not reveal impairment of fertility by lamotrigine. Lamotrigine reduced foetal folic acid levels in rats. Folic acid deficiency is assumed to be associated with an enhanced risk of congenital malformations in animals as well as in humans.

Lamotrigine caused a dose-related inhibition of the hERG channel tail current in human embryonic kidney cells. The IC50 was approximately nine-times above the maximum therapeutic free concentration. Lamotrigine did not cause QT prolongation in animals at exposures up to approximately two-times the maximum therapeutic free concentration. In a clinical study, there was no clinically significant effect of lamotrigine on QT interval in healthy adult volunteers (see section 5.1).

In vitro studies show that lamotrigine exhibits Class IB antiarrhythmic activity at therapeutically relevant concentrations. It inhibits human cardiac sodium channels with rapid onset and offset kinetics and strong voltage dependence, consistent with other Class IB antiarrhythmic agents. At therapeutic doses, lamotrigine did not slow ventricular conduction (widen QRS) in healthy individuals in a thorough QT study; however, in patients with clinically important structural or functional heart disease lamotrigine could potentially slow ventricular conduction (widen QRS) and induce proarrhythmia (see section 4.4).


-     Lactose

-     Sodium starch glycolate

-     Povidone

-     Microcrystalline cellulose

-     FD & C yellow no.6 lake

-     Magnesium stearate


Not applicable.


36 months.

Store below 30°C.

Store in the original package.


Clear PVC/PVDC-aluminum blisters.

Pack size: 30 Tablets.


No special requirements for disposal.


Jazeera Pharmaceutical Industries Al-Kharj Road P.O. BOX 106229 Riyadh 11666, Saudi Arabia Tel: + (966-11) 8107023, + (966-11) 2142472 Fax: + (966-11) 2078170 e-mail: SAPV@hikma.com

26 January 2023
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