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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)

Lomipat contains lacosamide. This belongs to a group of medicines called “antiepileptic medicines”.

These medicines are used to treat epilepsy.

•  You have been given this medicine to lower the number of fits (seizures) you have.


Do not take Lomipat

•        if you are allergic to lacosamide, or any of the other ingredients of this medicine (listed in section 6).

If you are not sure whether you are allergic, please discuss with your doctor.

•        if you have a certain type of heart beat problem called second- or third-degree AV block.

Do not take Lomipat if any of the above applies to you. If you are not sure, talk to your doctor or pharmacist before taking this medicine.

Warnings and precautions

Talk to your doctor before taking Lomipat if:

•        you have thoughts of harming or killing yourself. A small number of people being treated with antiepileptic medicinal products such as lacosamide have had thoughts of harming or killing themselves.

If you have any of these thoughts at any time, tell your doctor straight away.

•        you have a heart problem that affects the beat of your heart and you often have a particulary slow, fast or irregular heart beat (such as AV block, atrial fibrillation and atrial flutter).

•        you have severe heart disease such as heart failure or have had a heart attack.

•        you are often dizzy or fall over. Lomipat may make you dizzy - this could increase the risk of accidental injury or a fall. This means that you should take care until you are used to the effects of this medicine.

If any of the above apply to you (or you are not sure), talk to your doctor or pharmacist before taking Lomipat.

If you are taking Lomipat, talk to your doctor if you are experiencing a new type of seizure or worsening of existing seizures.

If you are taking Lomipat and you are experiencing symptoms of abnormal heartbeat (such as slow, rapid or irregular heartbeat, palpitations, shortness of breath, feeling lightheaded, fainting), seek medical advice immediately (see section 4).

Children under 4 years

Lomipat is not recommended for children aged under 4 years. This is because we do not yet know whether it will work and whether it is safe for children in this age group.

Other medicines and Lomipat

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

In particular, tell your doctor or pharmacist if you are taking any of the following medicines that affect your heart - this is because Lomipat can also affect your heart:

•  medicines to treat heart problems;

•  medicines which can increase the “PR interval” on a scan of the heart (ECG or electrocardiogram) such as medicines for epilepsy or pain called carbamazepine, lamotrigine or pregabalin;

•  medicines used to treat certain types of irregular heart beat or heart failure.

If any of the above apply to you (or you are not sure), talk to your doctor or pharmacist before taking Lomipat.

Also tell your doctor or pharmacist if you are taking any of the following medicines - this is because they may increase or decrease the effect of Lomipat on your body:

•  medicines for fungal infections called fluconazole, itraconazole or ketoconazole;

•  a medicine for HIV called ritonavir;

•  medicines used to treat bacterial infections called clarithromycin or rifampicin;

•  a herbal medicine used to treat mild anxiety and depression called St. John’s wort.

If any of the above apply to you (or you are not sure), talk to your doctor or pharmacist before taking Lomipat.

Lomipat with alcohol

As a safety precaution do not take Lomipat with alcohol.

Pregnancy and breast-feeding

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

It is not recommended to take Lomipat if you are pregnant or breast-feeding, as the effects of Lomipat on pregnancy and the unborn baby or the new-born child are not known. Also, it is not known whether Lomipat passes into breast milk. Seek advice immediately from your doctor if you get pregnant or are planning to become pregnant. They will help you decide if you should take Lomipat or not.

Do not stop treatment without talking to your doctor first as this could increase your fits (seizures). A worsening of your disease can also harm your baby.

Driving and using machines

Do not drive, cycle or use any tools or machines until you know how this medicine affects you. This is because Lomipat may make you feel dizzy or cause blurred vision.


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

Taking Lomipat

•  Take Lomipat twice each day - once in the morning and once in the evening.

•  Try to take it at about the same time each day.

•  Swallow the Lomipat tablet with a glass of water.

•  You may take Lomipat with or without food.

You will usually start by taking a low dose each day and your doctor will slowly increase this over a number of weeks. When you reach the dose that works for you, this is called the “maintenance dose”, you then take the same amount each day. Lomipat is used as a long term treatment. You should continue to take Lomipat until your doctor tells you to stop.

How much to take

Listed below are the normal recommended doses of Lomipat for different age groups and weights.

Your doctor may prescribe a different dose if you have problems with your kidneys or with your liver.

Adolescents and children weighing 50 kg or more and adults

When you take Lomipat on its own

The usual starting dose of Lomipat is 50 mg twice a day.

Your doctor may also prescribe a starting dose of 100 mg of Lomipat twice a day.

Your doctor may increase your twice daily dose every week by 50 mg. This will be until you reach a maintenance dose between 100 mg and 300 mg twice a day.

When you take Lomipat with other antiepileptic medicines The usual starting dose of Lomipat is 50 mg twice a day.

Your doctor may increase your twice daily dose every week by 50 mg. This will be until you reach a maintenance dose between 100 mg and 200 mg twice a day.

If you weigh 50 kg or more, your doctor may decide to start Lomipat treatment with a single “loading” dose of 200 mg. You would then start your ongoing maintenance dose 12 hours later.

Children and adolescent weighing less than 50 kg

The dose depends on their body weight. They usually start treatment with the syrup and only change to tablets if they are able to take tablets and get the correct dose with the different tablet strengths. The doctor will prescribe the formulation that is best suited to them.

If you take more Lomipat than you should

If you have taken more Lomipat than you should, contact your doctor immediately. Do not try to drive.

You may experience:

•  dizziness;

•  feeling sick (nausea) or being sick (vomiting);

•  fits (seizures), heart beat problems such a slow, fast or irregular heart beat, coma or a fall in blood pressure with rapid heartbeat and sweating.

If you forget to take Lomipat

•  If you have missed a dose within the first 6 hours of the scheduled dose, take it as soon as you remember.

•  If you have missed a dose beyond the first 6 hours of the scheduled dose, do not take the missed tablet anymore. Instead take Lomipat at the next time that you would normally take it.

•  Do not take a double dose to make up for a forgotten dose.

If you stop taking Lomipat

•  Do not stop taking Lomipat without talking to your doctor, as your epilepsy may come back again or become worse.

•  If your doctor decides to stop your treatment with Lomipat, they will tell you how to decrease the dose step by step.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.


4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Nervous system side effects such as dizziness may be higher after a single “loading” dose. Talk to your doctor or pharmacist if you get any of the following:

Very common: may affect more than 1 in 10 people

•         Headache;

•         Feeling dizzy or sick (nausea);

•         Double vision (diplopia).

Common: may affect up to 1 in 10 people

•         Short jerks of a muscle or group of muscles (myoclonic seizures);

•         Difficulties in coordinating your movements or walking;

•         Problems in keeping your balance, shaking (tremor), tingling (paresthesia) or muscle spasms, falling easily and getting bruises;

•         Troubles with your memory, thinking or finding words, confusion;

•         Rapid and uncontrollable movements of the eyes (nystagmus), blurred vision;

•         A spinning sensation (vertigo), feeling drunk;

•         Being sick (vomiting), dry mouth, constipation, indigestion, excessive gas in the stomach or bowel, diarrhoea;

•         Decreased feeling or sensitivity, difficulty in articulating words, disturbance in attention;

•         Noise in the ear such as buzzing, ringing or whistling;

•         Irritability, trouble sleeping, depression; • Sleepiness, tiredness or weakness (asthenia);

•         Itching, rash.

Uncommon: may affect up to 1 in 100 people

•         Slow heart rate, palpitations, irregular pulse or other changes in the electrical activity of your heart (conduction disorder);

•         Exaggerated feeling of wellbeing, seeing and/or hearing things which are not there;

•         Allergic reaction to medicine intake, hives;

•         Blood tests may show abnormal liver function, liver injury;

•         Thoughts of harming or killing yourself or attempting suicide: tell your doctor straight away; • Feeling angry or agitated;

•         Abnormal thinking or losing touch with reality;

•         Serious allergic reaction which causes swelling of the face, throat, hands, feet, ankles, or lower legs;

•         Fainting.

•         Abnormal involuntary movements (dyskinesia).

Not known: frequency cannot be estimated from available data

•         Abnormal rapid heartbeat (ventricular tachyarrhythmia);

•         A sore throat, high temperature and getting more infections than usual. Blood tests may show a severe decrease in a specific class of white blood cells (agranulocytosis);

•         A serious skin reaction which may include a high temperature and other flu-like symptoms, a rash on the face, extended rash, swollen glands (enlarged lymph nodes). Blood tests may show increased levels of liver enzymes and a type of white blood cell (eosinophilia);

•         A widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens–Johnson syndrome), and a more severe form causing skin peeling in more than 30 % of the body surface (toxic epidermal necrolysis);

•         Convulsion.

Additional side effects in children

Common: may affect up to 1 in 10 children

•         Runny nose (nasopharyngitis);

•         Fever (pyrexia);

•         Sore throat (pharyngitis);

•         Eating less than usual.

Uncommon: may affect up to 1 in 100 children

•         Feeling sleepy or lacking in energy (lethargy).

Not known: frequency cannot be estimated from available data

•         Changes in behaviour, not acting like themselves

 

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 (see details below)

Reporting of suspected adverse reactions
Saudi Arabia:

The National Pharmacovigilance and Drug Safety Centre (NPC) o SFDA Call Center: 19999

o E-mail:npc.drug@sfda.gov.sa o Website:https://ade.sfda.gov.sa/

•         Other GCC States:

Please contact the relevant competent authority.


•    Store below 30°C.

•    Keep out of reach of children.

•    Do not use this medicine after the expiry date which is stated on the pack after EXP. The expiry date refers to the last day of the month.

•    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.


Lomipat contains

The active substance is Lacosamide.

Lomipat 50:

Each Film coated tablet contains 50 mg of Lacosamide.

The other ingredients are: Cellulose, Microcrystalline, Low- substituted hydroxyl propyl cellulose, Crospovidone, Hydroxy propyl Cellulose, Silica, colloidal anhydrous, Magnesium Stearate.

Film coating composition: Polyvinyl Alcohol-Part.hydrolyzed, Talc, Titanium Dioxide, Macrogol/PEG, Lecithin (soya), Iron Oxide Red, FD&C Blue #2/Indigo Carmine Aluminum lake, Iron Oxide Black.

Clear coating composition: HPMC 2910/Hypromellose, Macrogol/PEG.

Lomipat 100:

Each Film coated tablet contains 100 mg of Lacosamide.

The other ingredients are: Cellulose, Microcrystalline, Low- substituted hydroxyl propyl cellulose, Crospovidone, Hydroxy propyl Cellulose, Silica, colloidal anhydrous, Magnesium Stearate.

,Film           coating            composition:   Polyvinyl         Alcohol-Part.hydrolyzed,       Talc,    Titanium       Dioxide, Macrogol/PEG, Iron Oxide Yellow, Lecithin (soya).

Clear coating composition: HPMC 2910/Hypromellose, Macrogol/PEG.

Lomipat 150:

Each Film coated tablet contains 150 mg of Lacosamide.

,The  other  ingredients  are:  Cellulose,  Microcrystalline,  Low-  substituted  hydroxyl  propyl  cellulose, Crospovidone, Hydroxy propyl Cellulose, Silica, colloidal anhydrous, Magnesium Stearate.

Film           coating            composition:   Polyvinyl         Alcohol-Part.hydrolyzed,       Talc,    Titanium       Dioxide, Macrogol/PEG, Lecithin (soya), Iron Oxide Yellow, Iron Oxide Red, Iron Oxide Black.

Clear coating composition: HPMC 2910/Hypromellose, Macrogol/PEG.

Lomipat 200:

Each Film coated tablet contains 200 mg of Lacosamide.

The other ingredients are: Cellulose, Microcrystalline, Low- substituted hydroxyl propyl cellulose, Crospovidone, Hydroxy propyl Cellulose, Silica, colloidal anhydrous, Magnesium Stearate. Film       coating            composition:   Polyvinyl         Alcohol-Part.hydrolyzed,       Talc,    Titanium Dioxide, Macrogol/PEG, FD&C Blue #2/Indigo Carmine Aluminum lake, Lecithin (soya).

Clear coating composition: HPMC 2910/Hypromellose, Macrogol/PEG.


Lomipat 50: Pink colored, oval shaped, biconvex, film coated tablets, debossed with ‘J’ on one side and ‘12’ on the other side. Lomipat 100: Yellow coloured, oval shaped, biconvex, film coated tablets, debossed with ‘J’ on one side and ‘13’ on the other side. Lomipat 150: Salmon coloured, oval shaped, biconvex, film coated tablets, debossed with ‘J’ on one side and ‘14’ on the other side. Lomipat 200: Blue colored, oval shaped, biconvex, film coated tablets, debossed with ‘J’ on one side and ‘15’ on the other side. Lomipat is Supplied in Blister pack. Lomipat 50 - contains (3×10) tablets. Lomipat 100 - contains (3×10) tablets. Lomipat 150 - contains (3×10) tablets. Lomipat 200 - contains (3×10) tablets.

Saudi Amarox Industrial Company

Al Jamiah Street, Al Malaz District

Riyadh 12629, Saudi Arabia Tel & Fax: +966 11 226 8850
 

Manufacturer:

Hetero Labs Limited Unit V, India


May 2023, Version 1
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

يحتوي لوميبات أقراص على المادة الفعالة لاكوساميد. والذي ينتمي إلى مجموعة من الأدوية تسمى "الأدوية المضادة للصرع".

تستخدم هذه الأدوية لعلاج الصرع.

•          يتم وصف هذا الدواء لتقليل عدد النوبات (التشنجات) لديك.

ما هي دواعي استعمال لوميبات أقراص

•          يستخدم لوميبات في البالغين والمراهقين والأطفال من سن 4 سنوات فما فوق.

•          يتم استخدامها:

§         بمفرده وبالاشتراك مع أدوية أخرى مضادة للصرع لعلاج نوع معين من الصرع الذي يتصف بحدوث نوبة جزئية في البداية مع أو بدون تعميم ثانوي. في هذا النوع من الصرع ، تؤثر النوبات أولاً على جانب واحد فقط من الدماغ. ومع ذلك ، قد تنتشر بعد ذلك إلى مناطق أكبر على جانبي دماغك؛

§          بالاشتراك مع الأدوية الأخرى المضادة للصرع لعلاج نوبات الصرع الارتجاجية الأولية والمعممة (النوبات الرئيسية ، بما في ذلك فقدان الوعي) في المرضى الذين يعانون من الصرع المعمم مجهول السبب (نوع من الصرع الذي يعتقد أن له سبب وراثي).

لا تستخدم لوميبات أقراص

·         إذا كنت تعاني من حساسية تجاه لاكوساميد أو أي من المكونات الأخرى لهذا الدواء (المدرجة في القسم 6). إذا لم تكن متأكدًا مما إذا كنت تعاني من الحساسية ، فيرجى مناقشة الأمر مع طبيبك.

·         إذا كان لديك نوع معين من مشاكل ضربات القلب يسمى إحصار AV من الدرجة الثانية أو الثالثة.

لا تستخدم لوميبات إذا كان أي مما سبق ينطبق عليك. إذا لم تكن متأكدًا ، تحدث إلى طبيبك أو الصيدلي قبل تناول هذا الدواء.

 

التحذيرات والاحتياطات

تحدث إلى طبيبك أو الصيدلي أو الممرضة قبل تناول لوميبات أقراص في الحالات التالية:

·         إذا كان لديك أفكار بإيذاء نفسك أو قتلها. حيث كان لدى عدد قليل من الأشخاص الذين يعالجون بالمنتجات الطبية المضادة للصرع ، مثل لاكوساميد ، أفكار لإيذاء أنفسهم أو الانتحار. إذا كان لديك أي من هذه الأفكار في أي وقت ، أخبر طبيبك على الفور.

·         إذا كان لديك مشكلة في القلب تؤثر على ضربات قلبك وغالبًا ما يكون لديك ضربات قلب بطيئة أو سريعة أو غير منتظمة (مثل انسداد الأذين البطيني والرجفان الأذيني والرفرفة الأذينية).

·         إذا كنت تعاني من مرض قلبي شديد مثل قصور القلب أو أصبت مسبقاً بنوبة قلبية.

·         تناول لوميبات قد يصيبك بالدوار ، غالبًا ما تشعر بالدوار أو الوقوع. وهذا قد يزيد من خطر الإصابة العرضية أو السقوط. هذا يعني أنه يجب عليك توخي الحذر حتى تعتاد على تأثيرات هذا الدواء.

إذا كان أي مما سبق ينطبق عليك (أو لم تكن متأكدًا) ، تحدث إلى طبيبك أو الصيدلي قبل تناول لوميبات.

إذا كنت تتناول لوميبات ، فتحدث إلى طبيبك إذا كنت تعاني من نوع جديد من النوبات أو تفاقم النوبات الحالية.

إذا كنت تتناول لوميبات وتعاني من أعراض ضربات قلب غير طبيعية (مثل ضربات القلب البطيئة أو السريعة أو غير المنتظمة ، خفقان القلب ، ضيق التنفس ، الشعور بالدوار ، الإغماء) ، اطلب المشورة الطبية على الفور (انظر القسم 4).

الأطفال أقل من 4 سنوات

لا ينصح باستخدام لوميبات للأطفال الذين تقل أعمارهم عن 4 سنوات. هذا لأننا لا نعرف حتى الآن ما إذا كان سيعمل وما إذا كان آمنًا للأطفال في هذه الفئة العمرية.

الأدوية الأخرى و لوميبات أقراص

أخبر طبيبك أو الصيدلي إذا كنت تتناول أو تناولت مؤخرًا أو قد تتناول أي أدوية أخرى.

على وجه الخصوص ، أخبر طبيبك أو الصيدلي إذا كنت تتناول أيًا من الأدوية التالية التي تؤثر على قلبك - وذلك لأن لوميبات يمكن أن يؤثر أيضًا على قلبك:

·         أدوية لعلاج مشاكل القلب.

·         الأدوية التي يمكن أن تزيد "فترة PR" في فحص القلب (ECG أو مخطط كهربية القلب) مثل أدوية الصرع أو الألم الذي يسمى كاربامازيبين ، لاموتريجين أو بريجابالين.

·         الأدوية المستخدمة لعلاج أنواع معينة من عدم انتظام ضربات القلب أو قصور القلب.

·         إذا كان أي مما سبق ينطبق عليك (أو لم تكن متأكدًا) ، تحدث إلى طبيبك أو الصيدلي قبل تناول لوميبات.

·         أخبر طبيبك أو الصيدلي أيضًا إذا كنت تتناول أيًا من الأدوية التالية - هذا لأنها قد تزيد أو تقلل من تأثير لوميبات على جسمك:

·         أدوية للعدوى الفطرية تسمى فلوكونازول ، إيتراكونازول أو كيتوكونازول.

·         دواء لفيروس نقص المناعة البشرية يسمى ريتونافير.

·         الأدوية المستخدمة لعلاج الالتهابات البكتيرية تسمى كلاريثروميسين أو ريفامبيسين.

·         دواء عشبي يستخدم لعلاج القلق والاكتئاب الخفيف يسمى نبتة سانت جون.

إذا كان أي مما سبق ينطبق عليك (أو لم تكن متأكدًا) ، تحدث إلى طبيبك أو الصيدلي قبل تناول لوميبات.

تناول لوميبات مع الكحول

كإجراء وقائي ، لا تتناول لوميبات مع الكحول.

الحمل والرضاعة الطبيعية

إذا كنت حاملاً أو مرضعة ، تعتقدين أنك حامل أو تخططين لإنجاب طفل ، اسألي طبيبك أو الصيدلي للحصول على المشورة قبل تناول هذا الدواء.

لا ينصح بتناول لوميبات إذا كنت حاملاً أو مرضعة ، لأن آثار لوميبات على الحمل والجنين أو المولود الجديد غير معروفة. كما أنه من غير المعروف ما إذا كانت لوميبات ينتقل إلى حليب الأم. اطلب المشورة من طبيبك على الفور إذا كنت حاملاً أو تخططين للحمل. سوف يساعدونك في تحديد ما إذا كان يجب عليك تناول لوميبات أم لا.

لا تتوقف عن العلاج دون التحدث إلى طبيبك أولاً لأن هذا قد يزيد من نوباتك (النوبات). يمكن أن يؤدي تفاقم مرضك إلى الإضرار بطفلك أيضًا.

القيادة واستخدام الآلات

لا تقم بالقيادة أو ركوب الدراجة أو استخدام أي أدوات أو آلات حتى تعرف كيف يؤثر هذا الدواء عليك. وذلك لأن لوميبات قد تجعلك تشعر بالدوار أو تسبب عدم وضوح الرؤية.

https://localhost:44358/Dashboard

احرص دائمًا على تناول هذا الدواء تمامًا كما أخبرك طبيبك أو الصيدلي. استشر طبيبك أو الصيدلي إذا لم تكن متأكدًا.

طريقة استخدام لوميبات

·         تناول أقراص لوميبات مرتين كل يوم - مرة في الصباح ومرة في المساء.

·         حاول تناوله في نفس الوقت تقريبًا كل يوم.

·         ابتلع قرص لوميبات مع كوب من الماء.

·         يمكنك تناول لوميبات أقراص مع الطعام أو بدونه.

ستبدأ عادة بتناول جرعة منخفضة كل يوم وسيقوم طبيبك بزيادة هذه الجرعة ببطء على مدى عدة أسابيع. عندما تصل إلى الجرعة التي تناسبك ، تسمى هذه "جرعة المداومة" ، فيجب أن تتناول نفس المقدار كل يوم. يعتبر لوميبات علاج طويل الأمد. يجب أن تستمر في تناول لوميبات حتى يخبرك طبيبك بالتوقف.

الجرعة

الجرعات العادية الموصى بها من لوميبات لمختلف الفئات العمرية والأوزان مدرجة أدناه. قد يصف لك طبيبك جرعة مختلفة إذا كنت تعاني من مشاكل في الكلى أو في الكبد.

المراهقون والأطفال الذين يزنون 50 كجم أو أكثر والبالغون

في حالة استخدام لوميبات أقراص بمفردها

جرعة البدء المعتادة من لوميبات هي 50 ملجم مرتين في اليوم.

قد يصف لك طبيبك أيضًا جرعة أولية من 100 ملجم من لوميبات مرتين في اليوم.

قد يزيد طبيبك جرعتك مرتين يوميًا كل أسبوع بمقدار 50 ملجم. سيستمر ذلك حتى تصل إلى جرعة مداومة بين 100 ملجم و 300 ملجم مرتين في اليوم.

في حالة استخدام لوميبات أقراص مع أدوية أخرى مضادة للصرع

جرعة البدء المعتادة من لوميبات هي 50 ملجم مرتين في اليوم.

قد يزيد طبيبك جرعتك مرتين يوميًا كل أسبوع بمقدار 50 ملجم. سيستمر ذلك حتى تصل إلى جرعة مداومة بين 100 ملجم و 200 ملجم مرتين في اليوم.

إذا كان وزنك 50 كجم أو أكثر ، فقد يقرر طبيبك بدء العلاج باستخدام لوميبات بجرعة تحميل " الجرعة الابتدائية الكبيرة " واحدة تبلغ 200 ملجم. ستبدأ بعد ذلك جرعة المداومة المستمرة بعد 12 ساعة.

الأطفال والمراهقون الذين يقل وزنهم عن 50 كجم

تعتمد الجرعة على وزن الجسم. عادة ما يتم بدء العلاج بالشراب ويتحولون إلى أقراص فقط إذا كانوا قادرين على تناول الأقراص والحصول على الجرعة المناسبة والتركيز المناسب من الأقراص. سيصف الطبيب التركيبة الأنسب لهم.

إذا تناولت جرعة زائدة من لوميبات أقراص

إذا كنت قد تناولت جرعة زائدة من لوميبات أكثر مما ينبغي ، فاتصل بطبيبك على الفور. لا تحاول القيادة.

قد تواجه:

•          الدوخة.

•          الشعور بالغثيان أو المرض (القيء)؛

•          نوبات ، مشاكل في ضربات القلب مثل ضربات القلب البطيئة أو السريعة أو غير المنتظمة ، الغيبوبة أو انخفاض ضغط الدم مع تسارع ضربات القلب والتعرق.

إذا نسيت أن تتناول لوميبات أقراص:

•          إذا فاتتك جرعة خلال الـ 6 ساعات الأولى من الجرعة المقررة ، فتناولها حالما تتذكرها.

•          إذا فاتتك جرعة بعد أول 6 ساعات من الجرعة المقررة ، لا تتناول القرص بعد الآن. بدلاً من ذلك ، تناول لوميبات في المرة القادمة التي تتناولها عادةً.

•          لا تتناول جرعة مضاعفة لتعويض الجرعة المنسية.

التوقف عن تناول لوميبات أقراص:

في حالة التوقف عن العلاج ، يجب إيقاف لوميبات أقراص تدريجيًا لتجنب زيادة النوبات. إذا قرر طبيبك إيقاف علاج لوميبات أقراص الخاص بك ، فسوف يرشدك بشأن الانسحاب التدريجي لجرعات لوميبات أقراص.

•          لا تتوقف عن تناول لوميبات دون التحدث إلى طبيبك ، لأن الصرع قد يعود مرة أخرى أو يزداد سوءًا.

•          إذا قرر طبيبك إيقاف علاجك باستخدام لوميبات ، فسوف يخبرك بكيفية تقليل الجرعة تدريجيا.

إذا كان لديك أي أسئلة أخرى حول استخدام هذا الدواء ، اسأل طبيبك أو الصيدلي.

مثل جميع الأدوية ، يمكن أن يسبب هذا الدواء آثارًا جانبية ، على الرغم من عدم حدوثها لدى الجميع.

قد تكون الآثار الجانبية للجهاز العصبي مثل الدوخة أعلى بعد جرعة واحدة من جرعة "تحميل".

تحدث إلى طبيبك أو الصيدلي إذا حصلت على أي مما يلي:

شائعة جدًا: قد تظهر لدى أكثر من شخص من كل 10 أشخاص

·         صداع الراس؛

·         الشعور بالدوار أو الغثيان.

·         ازدواج الرؤية.

شائعة: قد تظهر لدى ما يصل إلى شخص من كل 10 أشخاص

·         هزات قصيرة في العضلات أو مجموعة من العضلات (نوبات رمع عضلي).

·         صعوبات في تنسيق حركاتك أو مشي.

·         مشاكل في الحفاظ على توازنك ، اهتزاز (رعشة) ، وخز (تنمل) أو تشنجات عضلية ، السقوط بسهولة والتعرض للكدمات.

·         مشاكل في الذاكرة ، والتفكير أو إيجاد الكلمات ، والارتباك.

·         حركات العين السريعة التي لا يمكن السيطرة عليها (رأرأة) ، عدم وضوح الرؤية.

·         الإحساس بالدوار والشعور بالسُكر.

·         الغثيان (القيء) ، جفاف الفم ، الإمساك ، عسر الهضم ، الغازات الزائدة في المعدة أو الأمعاء ، الإسهال.

·         قلة الإحساس أو الحساسية ، صعوبة في نطق الكلمات ، اضطراب في الانتباه.

·         ضوضاء في الأذن مثل الطنين أو الرنين أو الصفير.

·         التهيج ، وصعوبة النوم ، والاكتئاب.

·         النعاس أو التعب أو الضعف (الوهن).

·         حكة ، طفح جلدي.

غير شائعة: قد تظهر لدى ما يصل إلى شخص من كل 100 شخص

·         بطء معدل ضربات القلب ، خفقان القلب ، عدم انتظام النبض أو تغيرات أخرى في النشاط الكهربائي لقلبك (اضطراب التوصيل).

·         المبالغة في الشعور بالراحة ، ورؤية و / أو سماع أشياء غير موجودة؛

·         رد فعل تحسسي تجاه تناول الأدوية ، والشرى.

·         قد تظهر اختبارات الدم وجود خلل في وظائف الكبد ، إصابة الكبد.

·         أفكار لإيذاء نفسك أو قتلها أو محاولة الانتحار: أخبر طبيبك على الفور؛

·         الشعور بالغضب أو الانفعال.

·         التفكير غير الطبيعي أو فقدان الاتصال بالواقع.

·         رد فعل تحسسي خطير يسبب تورم في الوجه أو الحلق أو اليدين أو القدمين أو الكاحلين أو أسفل الساقين.

·         إغماء.

·         حركات لا إرادية غير طبيعية (خلل في الحركة).

 

غير معروف: لا يمكن تقدير معدلاتها من البيانات المتاحة

·         عدم انتظام ضربات القلب (عدم انتظام ضربات القلب البطيني).

·         التهاب الحلق وارتفاع درجة الحرارة وزيادة الإصابة بالتهابات أكثر من المعتاد. قد تظهر اختبارات الدم انخفاضًا حادًا في فئة معينة من خلايا الدم البيضاء (ندرة المحببات)؛

·         رد فعل جلدي خطير قد يشمل ارتفاع في درجة الحرارة وأعراض أخرى تشبه أعراض الأنفلونزا ، وطفح جلدي على الوجه ، وطفح جلدي ممتد ، وتضخم الغدد (تضخم الغدد الليمفاوية). قد تظهر اختبارات الدم زيادة في مستويات إنزيمات الكبد ونوع من خلايا الدم البيضاء (فرط الحمضات)؛

·         طفح جلدي منتشر مع ظهور بثور وتقشر الجلد ، خاصة حول الفم والأنف والعينين والأعضاء التناسلية (متلازمة ستيفنز جونسون) ، وشكل أكثر حدة يسبب تقشر الجلد في أكثر من 30٪ من سطح الجسم (انحلال البشرة النخري السام).

·         تشنج.

أعراض جانبية إضافية عند الأطفال

شائعة: قد تظهر لدى ما يصل إلى طفل من كل 10 أطفال

·         سيلان الأنف (التهاب البلعوم الأنفي).

·         الحمى.

·         التهاب الحلق (التهاب البلعوم).

·         الأكل أقل من المعتاد.

غير شائعة: قد تظهر لدى ما يصل إلى طفل من كل 100 طفل

·         الشعور بالنعاس أو نقص الطاقة (الخمول).

غير معروف: لا يمكن تقدير معدلاتها من البيانات المتاحة

·         التغييرات في السلوك ، وعدم التصرف كالمعتاد.

الإبلاغ عن الآثار الجانبية:

إذا زادت حدة أي من هذه الأعراض الجانبية ، أو لاحظت ظهور أعراض جانبية غير ما تم ذكره في هذه النشرة ، يرجى إبلاغ الطبيب المعالج أو الصيدلي. وهذا يشمل أي آثار جانبية محتملة غير مدرجة في هذه النشرة. يمكنك أيضا الإبلاغ عن الآثار الجانبية مباشرة (انظر التفاصيل أدناه). بالإبلاغ عن الآثار الجانبية يمكنك المساعدة في توفير مزيد من المعلومات حول أمان هذا الدواء.

للإبلاغ عن الأعراض الجانبية

-          المملكة العربية السعودية

-          المركز الوطني للتيقظ والسلامة الدوائية

o      الاتصال على المركز الوطني للتيقظ والسلامة الدوائية 19999

o      البريد الإلكتروني : npc.drug@sfda.gov.sa

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

 

دول مجلس التعاون الخليجي الأخرى:

 يرجى الاتصال بالسلطة الصحية المختصة.

•          يحفظ في درجة حرارة أقل من 30 درجة مئوية.

•          احفظ هذا الدواء بعيدًا عن رؤية ومتناول أيدي الأطفال.

•          لا تستخدم هذا الدواء بعد تاريخ انتهاء الصلاحية المذكور على العبوة بعد EXP. يشير تاريخ انتهاء الصلاحية إلى اليوم الأخير من الشهر.

•          لا تتخلص من الأدوية في مياه الصرف الصحي أو النفايات المنزلية. اسأل الصيدلي عن كيفية التخلص من الأدوية التي لم تعد بحاجة إليها. ستساعد هذه الإجراءات في حماية البيئة.

المادة الفعالة هي لاكوساميد.

لوميبات أقراص 50 ملجم:

يحتوي كل قرص مغلف بطبقة رقيقة على 50 ملجم لاكوساميد.

الصواغات الأخرى هي: السليلوز دقيق التبلور ، هيدروكسيل بروبيل سليلوز low-substituted ، كروسبوفيدون ، هيدروكسي بروبيل سليلوز ، السيليكا الغروية لا مائية ، ستيرات الماغنيسيوم.

الصواغات الأخرى لطبقة الكسوة الخارجية: كحول البولي فينيل المتحلل جزئيًا ، التلك ، ثاني أكسيد التيتانيوم ، ماكروغول / PEG ، ليسيثين (فول الصويا) ، أكسيد الحديد الأحمر ، صبغة زرقاء FD&C Blue #2/Indigo Carmine Aluminum lake ، أكسيد الحديد الأسود.

الصواغات الأخرى لطبقة الكسوة الخارجية الشفافة: HPMC 2910 / هيبروميلوز ، ماكروغول / PEG.

لوميبات أقراص 100 ملجم:

يحتوي كل قرص مغلف بطبقة رقيقة على 100 ملغج لاكوساميد.

الصواغات الأخرى هي: السليلوز دقيق التبلور ، هيدروكسيل بروبيل سليلوز low-substituted ، كروسبوفيدون ، هيدروكسي بروبيل سليلوز ، السيليكا الغروية لا مائية ، ستيرات الماغنيسيوم.

الصواغات الأخرى لطبقة الكسوة الخارجية: كحول البولي فينيل المتحلل جزئيًا ، التلك ، ثاني أكسيد التيتانيوم ، ماكروغول / PEG ، ليسيثين (فول الصويا) ، أكسيد الحديد الأصفر.

الصواغات الأخرى لطبقة الكسوة الخارجية الشفافة: HPMC 2910 / هيبروميلوز ، ماكروغول / PEG.

لوميبات أقراص 150 ملجم:

يحتوي كل قرص مغلف بطبقة رقيقة على 150 ملجم لاكوساميد.

الصواغات الأخرى هي: السليلوز دقيق التبلور ، هيدروكسيل بروبيل سليلوز low-substituted ، كروسبوفيدون ، هيدروكسي بروبيل سليلوز ، السيليكا الغروية لا مائية ، ستيرات الماغنيسيوم.

الصواغات الأخرى لطبقة الكسوة الخارجية: كحول البولي فينيل المتحلل جزئيًا ، التلك ، ثاني أكسيد التيتانيوم ، ماكروغول / PEG ، ليسيثين (فول الصويا) ، أكسيد الحديد الأصفر ، أكسيد الحديد الأحمر ، أكسيد الحديد الأسود.

الصواغات الأخرى لطبقة الكسوة الخارجية الشفافة: HPMC 2910 / هيبروميلوز ، ماكروغول / PEG.

لوميبات أقراص 200 ملجم:

يحتوي كل قرص مغلف بطبقة رقيقة على 200 ملجم لاكوساميد.

الصواغات الأخرى هي: السليلوز دقيق التبلور ، هيدروكسيل بروبيل سليلوز low-substituted ، كروسبوفيدون ، هيدروكسي بروبيل سليلوز ، السيليكا الغروية لا مائية ، ستيرات الماغنيسيوم.

الصواغات الأخرى لطبقة الكسوة الخارجية: كحول البولي فينيل المتحلل جزئيًا ، التلك ، ثاني أكسيد التيتانيوم ، ماكروغول / PEG ، ليسيثين (فول الصويا) ، صبغة زرقاء FD&C Blue #2/Indigo Carmine Aluminum lake.

الصواغات الأخرى لطبقة الكسوة الخارجية الشفافة: HPMC 2910 / هيبروميلوز ، ماكروغول / PEG.

ما هو شكل لوميبات أقراص؟

عبوة زجاجية ملونة باللون الداكن سعة 200 مل مملوءة بسائل شفاف عديم اللون بنكهة العنب مع سداداه من EPE

لوميبات أقراص 50 ملجم:

أقراص بيضاوية الشكل ذات لون وردي ، محدبة من الجانبين ، مغلفة بطبقة رقيقة خارجية ، مدموغ عليها حرف "J" على جانب واحد و "12" على الجانب الآخر.

لوميبات أقراص 100 ملجم:

أقراص بيضاوية الشكل ذات لون أصفر ، محدبة من الجانبين ، مغلفة بطبقة رقيقة خارجية ، مدموغ عليها حرف "J" على جانب واحد و "13" على الجانب الآخر.

لوميبات أقراص 150 ملجم:

أقراص بيضاوية الشكل ذات اللون السلموني ، محدبة من الجانبين ، مغلفة بطبقة رقيقة خارجية ، مدموغ عليها حرف "J" على جانب واحد و "14" على الجانب الآخر.

لوميبات أقراص 200 ملجم:

أقراص بيضاوية الشكل ذات لون أزرق ، محدبة من الجانبين ، مغلفة بطبقة رقيقة خارجية ، مدموغ عليها حرف "J" على جانب واحد و "15" على الجانب الآخر.

كيفية توفير لوميبات أقراص؟

يتم توفير لوميبات أقراص في علبة تحتوي على شرائط.

لوميبات أقراص 50 ملجم: يحتوي على ) 3×10) أقراص

لوميبات أقراص 100 ملجم: يحتوي على ) 3×10) أقراص

لوميبات أقراص 150 ملجم: يحتوي على ) 3×10) أقراص

لوميبات أقراص 200 ملجم: يحتوي على ) 3×10) أقراص

صاحب حق التسويق:

شركة أماروكس السعودية للصناعة

شارع الجامعة – الملز – الرياض 12629

المملكة العربية السعودية.

تليفون: + 966 226 8850

مايو 2023، نسخة 1
 Read this leaflet carefully before you start using this product as it contains important information for you

Lomipat (Lacosamide Tablets 50mg, 100mg, 150mg and 200mg)

Lomipat 50 Each Film coated tablet contains 50 mg of Lacosamide. Lomipat 100 Each Film coated tablet contains 100 mg of Lacosamide. Lomipat 150 Each Film coated tablet contains 150 mg of Lacosamide. Lomipat 200 Each Film coated tablet contains 200 mg of Lacosamide.

Film Coated Tablet Lomipat 50 Pink coloured, oval shaped, biconvex, film coated tablets, debossed with ‘J’ on one side and ‘12’ on the other side. Lomipat 100 Yellow coloured, oval shaped, biconvex, film coated tablets, debossed with ‘J’ on one side and ‘13’ on the other side. Lomipat 150 Salmon coloured, oval shaped, biconvex, film coated tablets, debossed with ‘J’ on one side and ‘14’ on the other side. Lomipat 200 Blue coloured, oval shaped, biconvex, film coated tablets, debossed with ‘J’ on one side and ‘15’ on the other side.

Lomipat is indicated as monotherapy in the treatment of partial-onset seizures with or without secondary generalisation in adults, adolescents and children from 4 years of age with epilepsy.

Lomipat is indicated as adjunctive therapy

•                   in the treatment of partial-onset seizures with or without secondary generalisation in adults, adolescents and children from 4 years of age with epilepsy.

in the treatment of primary generalised tonic-clonic seizures in adults, adolescents and children from 4 years of age with idiopathic generalised epilepsy.


Posology 

Lacosamide must be taken twice a day (usually once in the morning and once in the evening).

Lacosamide may be taken with or without food.

If a dose is missed, the patient should be instructed to take the missed dose immediately, and then to take the next dose of lacosamide at the regularly scheduled time. If the patient notices the missed dose within 6 hours of the next one, he/she should be instructed to wait to take the next dose of lacosamide at the regularly scheduled time. Patients should not take a double dose.

Adolescents and children weighing 50 kg or more, and adults 

The following table summarises the recommended posology for adolescents and children weighing 50 kg or more, and for adults. More details are provided in the table below.

 

Monotherapy

Adjunctive therapy

Starting dose

Single loading dose (if applicable)

100 mg/day or 200 mg/day

100 mg/day

200 mg

200 mg

Titration (incremental steps)

50 mg twice a day (100 mg/day) at weekly intervals

50 mg twice a day (100 mg/day) at weekly intervals

Maximum recommended dose

up to 600 mg/day

up to 400 mg/day

Monotherapy (in the treatment of partial-onset seizures) 

The recommended starting dose is 50 mg twice a day which should be increased to an initial therapeutic dose of 100 mg twice a day after one week.

Lacosamide can also be initiated at the dose of 100 mg twice a day based on the physician's assessment of required seizure reduction versus potential side effects. Depending on response and tolerability, the maintenance dose can be further increased at weekly intervals by 50 mg twice a day (100 mg/day), up to a maximum recommended daily dose of 300 mg twice a day (600 mg/day).

In patients having reached a dose greater than 400 mg/day and who need an additional antiepileptic medicinal product, the posology that is recommended for adjunctive therapy below should be followed.

Adjunctive therapy (in the treatment of partial-onset seizures or in the treatment of primary generalised tonic-clonic seizures) 

The recommended starting dose is 50 mg twice a day which should be increased to an initial therapeutic dose of 100 mg twice a day after one week. Depending on response and tolerability, the maintenance dose can be further increased at weekly intervals by 50 mg twice a day (100 mg/day), up to a maximum recommended daily dose of 400 mg (200 mg twice a day).

Initiation of lacosamide treatment with a loading dose (initial monotherapy or conversion to monotherapy in the treatment of partial-onset seizures or adjunctive therapy in the treatment of partial-onset seizures or adjunctive therapy in the treatment of primary generalised tonic-clonic seizures) Lacosamide treatment may also be initiated with a single loading dose of 200 mg, followed approximately 12 hours later by a 100 mg twice a day (200 mg/day) maintenance dose regimen. Subsequent dose adjustments should be performed according to individual response and tolerability as described above. A loading dose may be initiated in patients in situations when the physician determines that rapid attainment of lacosamide steady state plasma concentration and therapeutic effect is warranted. It should be administered under medical supervision with consideration of the potential for increased incidence of serious cardiac arrhythmia and central nervous system adverse reactions (see section 4.8). Administration of a loading dose has not been studied in acute conditions such as status epilepticus.

Discontinuation 

In accordance with current clinical practice, if lacosamide has to be discontinued, it is recommended this be done gradually (e.g. taper the daily dose by 200 mg/week).

In patients who develop serious cardiac arrhythmia, clinical benefit/risk assessment should be performed and if needed lacosamide should be discontinued.

Special populations 

Elderly (over 65 years of age) 

No dose reduction is necessary in elderly patients. Age associated decreased renal clearance with an increase in AUC levels should be considered in elderly patients (see following paragraph 'renal impairment' and section 5.2). There is limited clinical data in the elderly patients with epilepsy, particularly at doses greater than 400 mg/day (see sections 4.4, 4.8, and 5.1).

Renal impairment 

No dose adjustment is necessary in mildly and moderately renally impaired adult and paediatric patients (CLCR > 30 ml/min). In paediatric patients weighing 50 kg or more and in adult patients with mild or moderate renal impairment a loading dose of 200 mg may be considered, but further dose titration (> 200 mg daily) should be performed with caution. In paediatric patients weighing 50 kg or more and in adult patients with severe renal impairment (CLCR ≤ 30 ml/min) or with end-stage renal disease, a maximum dose of 250 mg/day is recommended and the dose titration should be performed with caution. If a loading dose is indicated, an initial dose of 100 mg followed by a 50 mg twice daily regimen for the first week should be used. In paediatric patients weighing less than 50 kg with severe renal impairment (CLCR ≤ 30 ml/min) and in those with end-stage renal disease, a reduction of 25 % of the maximum dose is recommended. For all patients requiring haemodialysis a supplement of up to 50 % of the divided daily dose directly after the end of haemodialysis is recommended. Treatment of patients with end-stage renal disease should be made with caution as there is little clinical experience and accumulation of a metabolite (with no known pharmacological activity).

Hepatic impairment 

A maximum dose of 300 mg/day is recommended for paediatric patients weighing 50 kg or more and for adult patients with mild to moderate hepatic impairment.

The dose titration in these patients should be performed with caution considering co-existing renal impairment. In adolescents and adults weighing 50 kg or more, a loading dose of 200 mg may be considered, but further dose titration (> 200 mg daily) should be performed with caution. Based on data in adults, in paediatric patients weighing less than 50 kg with mild to moderate hepatic impairment, a reduction of 25 % of the maximum dose should be applied. The pharmacokinetics of lacosamide has not been evaluated in severely hepatic impaired patients (see section 5.2). Lacosamide should be administered to adult and paediatric patients with severe hepatic impairment only when the expected therapeutic benefits are anticipated to outweigh the possible risks. The dose may need to be adjusted while carefully observing disease activity and potential side effects in the patient.

Paediatric population 

The physician should prescribe the most appropriate formulation and strength according to weight and dose.

Adolescents and children weighing 50 kg or more 

Dosage in adolescents and children weighing 50 kg or more is the same as in adults (see above).

Children (from 4 years of age) and adolescents weighing less than 50 kg 

The dose is determined based on body weight. It is therefore recommended to initiate treatment with the syrup and switch to tablets, if desired.

Monotherapy (in the treatment of partial-onset seizures) 

The recommended starting dose is 2 mg/kg/day which should be increased to an initial therapeutic dose of 4 mg/kg/day after one week.

Depending on response and tolerability, the maintenance dose can be further increased by 2 mg/kg/day every week. The dose should be gradually increased until the optimum response is obtained. In children weighing less than 40 kg, a maximum dose of up to 12 mg/kg/day is recommended. In children weighing from 40 to under 50 kg, a maximum dose of 10 mg/kg/day is recommended.

The following table summarises the recommended posology in monotherapy for children and adolescents weighing less than 50 kg.

Starting dose

Single loading dose

2 mg/kg/day

Not recommended

Titration (incremental steps)

2 mg/kg/day every week

Maximum recommended dose in patients < 40 kg

up to 12 mg/kg/day

Maximum recommended dose in patients ≥ 40 kg to <

50 kg

 up to 10 mg/kg/day

Adjunctive therapy (in the treatment of partial-onset seizures or in the treatment of primary generalised tonic-clonic seizures) 

The recommended starting dose is 2 mg/kg/day which should be increased to an initial therapeutic dose of 4 mg/kg/day after one week.

Depending on response and tolerability, the maintenance dose can be further increased by 2 mg/kg/day every week. The dose should be gradually adjusted until the optimum response is obtained. In children weighing less than 20 kg, due to an increased clearance compared to adults, a maximum dose of up to 12 mg/kg/day is recommended. In children weighing from 20 to under 30 kg, a maximum dose of 10 mg/kg/day is recommended and in children weighing from 30 to under 50 kg, a maximum dose of 8 mg/kg/day is recommended, although in open-label studies (see sections 4.8 and 5.2), a dose up to 12 mg/kg/day has been used by a small number of these children.

The following table summarises the recommended posology in adjunctive therapy for children and adolescents weighing less than 50 kg.

Starting dose

Single loading dose

2 mg/kg/day

Not recommended

Titration (incremental steps)

2 mg/kg/day every week

Maximum recommended dose in patients

up to 12 mg/kg/day

< 20 kg

 

Maximum recommended dose in patients

≥20 kg to < 30 kg

up to 10 mg/kg/day

Maximum recommended dose in patients

≥30 kg to < 50 kg

up to 8 mg/kg/day

Loading dose 

Administration of a loading dose has not been studied in children. Use of a loading dose is not recommended in adolescents and children weighing less than 50 kg.

Children less than 4 years 

The safety and efficacy of lacosamide in children aged below 4 years have not yet been established. No data are available.

Method of administration 

Lacosamide film-coated tablets are for oral use. Lacosamide may be taken with or without food.


Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Known second- or third-degree atrioventricular (AV) block.

Suicidal ideation and behaviour 

Suicidal ideation and behaviour have been reported in patients treated with antiepileptic medicinal products in several indications. A meta-analysis of randomised placebo-controlled studies of antiepileptic medicinal products 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 lacosamide.

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 (see section

4.8).

Cardiac rhythm and conduction 

Dose-related prolongations in PR interval with lacosamide have been observed in clinical studies. Lacosamide should be used with caution in patients with underlying proarrhythmic conditions such as patients with known cardiac conduction problems or severe cardiac disease (e.g. myocardial ischaemia/infarction, heart failure, structural heart disease or cardiac sodium channelopathies) or patients treated with medicinal products affecting cardiac conduction, including antiarrhythmics and sodium channel blocking antiepileptic medicinal products (see section 4.5), as well as in elderly patients.

In these patients it should be considered to perform an ECG before a lacosamide dose increase above 400 mg/day and after lacosamide is titrated to steady-state.

In the placebo-controlled studies of lacosamide in epilepsy patients, atrial fibrillation or flutter were not reported; however, both have been reported in open-label epilepsy studies and in postmarketing experience.

In post-marketing experience, AV block (including second degree or higher AV block) has been reported. In patients with proarrhythmic conditions, ventricular tachyarrhythmia has been reported. In rare cases, these events have led to asystole, cardiac arrest and death in patients with underlying proarrhythmic conditions.

Patients should be made aware of the symptoms of cardiac arrhythmia (e.g. slow, rapid or irregular pulse, palpitations, shortness of breath, feeling lightheaded, fainting). Patients should be counselled to seek immediate medical advice if these symptoms occur.

Dizziness 

Treatment with lacosamide has been associated with dizziness which could increase the occurrence of accidental injury or falls. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicine (see section 4.8).

Potential for new onset or worsening of myoclonic seizures 

New onset or worsening of myoclonic seizures has been reported in both adult and paediatric patients with PGTCS, in particular during titration. 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.

Potential for electro-clinical worsening in specific paediatric epilepsy syndromes 

The safety and efficacy of lacosamide in paediatric patients with epilepsy syndromes in which focal and generalised seizures may coexist have not been determined.


Lacosamide should be used with caution in patients treated with medicinal products known to be associated with PR prolongation (including sodium channel blocking antiepileptic medicinal products) and in patients treated with antiarrhythmics. However, subgroup analysis in clinical studies did not identify an increased magnitude of PR prolongation in patients with concomitant administration of carbamazepine or lamotrigine. In vitro data 

Data generally suggest that lacosamide has a low interaction potential. In vitro studies indicate

that the enzymes CYP1A2, CYP2B6, and CYP2C9 are not induced and that CYP1A1, CYP1A2,

CYP2A6, CYP2B6, CYP2C8, CYP2C9,

CYP2D6, and CYP2E1 are not inhibited by lacosamide at plasma concentrations observed in clinical studies. An in vitro study indicated that lacosamide is not transported by P-glycoprotein in the intestine. In vitro data show that CYP2C9, CYP2C19 and CYP3A4 are capable of

catalysing the formation of the O-desmethyl metabolite. In vivo data 

Lacosamide does not inhibit or induce CYP2C19 and CYP3A4 to a clinically relevant extent. Lacosamide did not affect the AUC of midazolam (metabolised by CYP3A4, lacosamide given 200 mg twice a day), but Cmax of midazolam was slightly increased (30 %). Lacosamide did not affect the pharmacokinetics of omeprazole (metabolised by CYP2C19 and CYP3A4, lacosamide given 300 mg twice a day).

The CYP2C19 inhibitor omeprazole (40 mg once daily) did not give rise to a clinically significant change in lacosamide exposure. Thus, moderate inhibitors of CYP2C19 are unlikely to affect systemic lacosamide exposure to a clinically relevant extent.

Caution is recommended in concomitant treatment with strong inhibitors of CYP2C9 (e.g. fluconazole) and CYP3A4 (e.g. itraconazole, ketoconazole, ritonavir, clarithromycin), which may lead to increased systemic exposure of lacosamide. Such interactions have not been established in vivo, but are possible based on in vitro data.

Strong enzyme inducers such as rifampicin or St John's wort (Hypericum perforatum) may moderately reduce the systemic exposure of lacosamide. Therefore, starting or ending treatment with these enzyme inducers should be done with caution.

Antiepileptic medicinal products 

In interaction studies lacosamide did not significantly affect the plasma concentrations of carbamazepine and valproic acid. Lacosamide plasma concentrations were not affected by carbamazepine and by valproic acid. Population pharmacokinetic analyses in different age groups estimated that concomitant treatment with other antiepileptic medicinal products known to be enzyme inducers (carbamazepine, phenytoin, phenobarbital, in various doses) decreased the overall systemic exposure of lacosamide by 25 % in adults and 17 % in paediatric patients.

Oral contraceptives 

In an interaction study there was no clinically relevant interaction between lacosamide and the oral contraceptives ethinylestradiol and levonorgestrel. Progesterone concentrations were not affected when the medicinal products were co-administered.

Others 

Interaction studies showed that lacosamide had no effect on the pharmacokinetics of digoxin. There was no clinically relevant interaction between lacosamide and metformin.

Co-administration of warfarin with lacosamide does not result in a clinically relevant change in the pharmacokinetics and pharmacodynamics of warfarin. Although no pharmacokinetic data on the interaction of lacosamide with alcohol are available, a pharmacodynamic effect cannot be excluded.

Lacosamide has a low protein binding of less than 15 %. Therefore, clinically relevant interactions with other medicinal products through competition for protein binding sites are considered unlikely.


Pregnancy 

Risk related to epilepsy and antiepileptic medicinal products in general 

For all antiepileptic medicinal products, it has been shown that in the offspring of treated women with epilepsy, the prevalence of malformations is two to three times greater than the rate of approximately 3 % in the general population. In the treated population, an increase in malformations has been noted with polytherapy, however, the extent to which the treatment and/or the illness is responsible has not been elucidated.

Moreover, effective antiepileptic therapy must not be interrupted, since the aggravation of the illness is detrimental to both the mother and the foetus.

Risk related to lacosamide 

There are no adequate data from the use of lacosamide in pregnant women. Studies in animals did not indicate any teratogenic effects in rats or rabbits, but embryotoxicity was observed in rats and rabbits at maternal toxic doses (see section 5.3). The potential risk for humans is unknown. Lacosamide should not be used during pregnancy unless clearly necessary (if the benefit to the mother clearly outweighs the potential risk to the foetus). If women decide to become pregnant, the use of this product should be carefully re-evaluated.

Breastfeeding 

It is unknown whether lacosamide is excreted in human breast milk. A risk to the newborns/infants cannot be excluded. Animal studies have shown excretion of lacosamide in breast milk. For precautionary measures, breast- feeding should be discontinued during treatment with lacosamide.

Fertility 

No adverse reactions on male or female fertility or reproduction were observed in rats at doses producing plasma exposures (AUC) up to approximately 2 times the plasma AUC in humans at the maximum recommended human dose (MRHD).


Lacosamide has minor to moderate influence on the ability to drive and use machines.

Lacosamide treatment has been associated with dizziness or blurred vision.

Accordingly, patients should be advised not to drive or to operate other potentially hazardous machinery until they are familiar with the effects of lacosamide on their ability to perform such activities.


Summary of safety profile 

Based on the analysis of pooled placebo-controlled clinical studies in adjunctive therapy in 1,308 patients with partial-onset seizures, a total of 61.9 % of patients randomised to lacosamide and 35.2 % of patients randomised to placebo reported at least 1 adverse reaction. The most frequently reported adverse reactions (≥ 10 %) with lacosamide treatment were dizziness, headache, nausea and diplopia. They were usually mild to moderate in intensity. Some were dose-related and could be alleviated by reducing the dose. Incidence and severity of central nervous system (CNS) and gastrointestinal (GI) adverse reactions usually decreased over time. In all of these controlled studies, the discontinuation rate due to adverse reactions was 12.2 % for patients randomised to lacosamide and 1.6 % for patients randomised to placebo. The most common adverse reaction resulting in discontinuation of lacosamide therapy was dizziness.

Incidence of CNS adverse reactions such as dizziness may be higher after a loading dose.

Based on the analysis of data from a non-inferiority monotherapy clinical study comparing lacosamide to carbamazepine controlled release (CR), the most frequently reported adverse reactions (≥ 10 %) for lacosamide were headache and dizziness. The discontinuation rate due to adverse reactions was 10.6 % for patients treated with lacosamide and 15.6 % for patients treated with carbamazepine CR.

The safety profile of lacosamide reported in a study conducted in patients aged 4 years and older with idiopathic generalised epilepsy with primary generalised tonic- clonic seizures (PGTCS) was consistent with the safety profile reported from the pooled placebo-controlled clinical studies in partial-onset seizures. Additional adverse reactions reported in PGTCS patients were myoclonic epilepsy (2.5 % in the lacosamide-group and 0 % in the placebo-group) and ataxia (3.3 % in the lacosamide- group and 0 % in the placebo-group). The most frequently reported adverse reactions were dizziness and somnolence. The most common adverse reactions resulting in discontinuation of lacosamide therapy were dizziness and suicidal ideation. The discontinuation rate due to adverse reactions was 9.1 % in the lacosamide group and 4.1 % in the placebo group.

Tabulated list of adverse reactions 

The table below shows the frequencies of adverse reactions which have been reported in clinical studies and post-marketing experience. The frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) and not known (frequency cannot be estimated from available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

System organ class

Very common

Common

Uncommon

Not known

Blood and lymphatic disorders

 

 

 

Agranulocytosis(1)

Immune            system

disorders

 

 

Drug hypersensitivity(1)

Drug reaction with eosinophilia and systemic symptoms

(DRESS) (1,2)

Psychiatric disorders

 

Depression 

Confusional state 

Insomnia(1)

Aggression

Agitation(1)

Euphoric mood(1)

Psychotic disorder(1)

Suicide attempt (1)

Suicidal ideation

Hallucination (1)

 

Nervous            system

disorders

 Dizziness Headache

Myoclonic

seizures(3)

Ataxia 

Balance disorder 

Syncope(2)

Coordination abnormal

Dyskinesia

Convulsion

 

 

 

Memory

impairment 

Cognitive disorder

Somnolence 

Tremor 

Nystagmus 

Hypoesthesia 

Dysarthria  Disturbance attention 

Paraesthesia

 

in

 

 

Eye disorders

Diplopia

Vision blurred

 

 

 

Ear     and     labyrinth

disorders

 

Vertigo

Tinnitus

 

 

 

Cardiac disorders

 

 

 

Atrioventricular block(1,2)

Bradycardia(1,2)

Atrial Fibrillation (1,2)

Atrial Flutter (1,2)

Ventricular tachyarrhythmia (1)

Gastrointestinal disorders

Nausea

Vomiting

Constipation 

Flatulence 

Dyspepsia 

Dry mouth 

Diarrhoea

 

 

 

Hepatobiliary disorders

 

 

Liver      function      test

abnormal(2)

 

 

 

 

Hepatic enzyme increased (> 2x ULN)

(1)

 

Skin    and subcutaneous tissue

disorders

 

 

Pruritus

Rash(1)

Angioedema(1)

Urticaria(1)

Stevens-Johnson syndrome(1)

Toxic          epidermal

necrolysis(1)

Musculoskeletal and connective tissue

disorders

 

 

Muscle spasms

 

 

General disorders and administration site conditions

 

 

Gait disturbance 

Asthenia 

Fatigue 

Irritability 

Feeling drunk

 

 

Injury, poisoning and procedural complications

 

Fall                 Skin

laceration

Contusion

 

 

(1)   Adverse reactions reported in post marketing experience.

(2)   See Description of selected adverse reactions.

(3)   Reported in PGTCS studies.

Description of selected adverse reactions 

The use of lacosamide is associated with dose-related increase in the PR interval. Adverse reactions associated with PR interval prolongation (e.g. atrioventricular block, syncope, bradycardia) may occur.

In adjunctive clinical studies in epilepsy patients, the incidence rate of reported first-degree AV Block is uncommon, 0.7 %, 0 %, 0.5 % and 0 % for lacosamide 200 mg, 400 mg, 600 mg or placebo, respectively. No second- or higher degree AV Block was seen in these studies. However, cases with second- and third- degree AV Block associated with lacosamide treatment have been reported in post-marketing experience. In the monotherapy clinical study comparing lacosamide to carbamazepine CR, the extent of increase in PR interval was comparable between lacosamide and carbamazepine.

The incidence rate for syncope reported in pooled adjunctive therapy clinical studies is uncommon and did not differ between lacosamide (n=944) treated epilepsy patients (0.1 %) and placebo (n=364) treated epilepsy patients (0.3 %). In the monotherapy clinical study comparing lacosamide to carbamazepine CR, syncope was reported in 7/444 (1.6 %) lacosamide patients and in 1/442 (0.2 %) carbamazepine CR patients.

Atrial fibrillation or flutter were not reported in short term clinical studies; however, both have been reported in open-label epilepsy studies and in post-marketing experience.

Laboratory abnormalities 

Abnormalities in liver function tests have been observed in placebo-controlled studies with lacosamide in adult patients with partial-onset seizures who were taking 1 to 3 concomitant antiepileptic medicinal products. Elevations of ALT to ≥ 3x ULN occurred in 0.7 % (7/935) of Lacosamide patients and 0 % (0/356) of placebo patients.

Multiorgan hypersensitivity reactions 

Multiorgan hypersensitivity reactions (also known as Drug Reaction with Eosinophilia and Systemic Symptoms, DRESS) have been reported in patients treated with some antiepileptic medicinal products. These reactions are variable in expression, but typically present with fever and rash and can be associated with involvement of different organ systems. If multiorgan hypersensitivity reaction is suspected, lacosamide should be discontinued.

Paediatric population 

The safety profile of lacosamide in placebo-controlled (see study details in section 5.1) and in open-label studies (n=408) in adjunctive therapy in children from 4 years of age with partialonset seizures was consistent with the safety profile observed in adults although the frequency of some adverse reactions (somnolence, vomiting and convulsion) was increased and additional adverse reactions (nasopharyngitis, pyrexia, pharyngitis, decreased appetite, lethargy and abnormal behaviour) have been reported in paediatric patients: nasopharyngitis (15.7 %), vomiting (14.7 %), somnolence (14.0 %), dizziness (13.5 %), pyrexia (13.0 %), convulsion (7.8 %), decreased appetite (5.9 %), pharyngitis (4.7 %), lethargy (2.7 %) and abnormal behaviour (1.7 %). A total of 67.8 % of patients randomised to lacosamide and 58.1 % of patients randomised to placebo reported at least 1 adverse reaction.

Behavioural, cognition and emotional functioning were measured by the questionnaires Achenbach CBCL and BRIEF that were applied at baseline and throughout the studies and were mainly stable during the course of the studies.

Elderly population 

In the monotherapy study comparing lacosamide to carbamazepine CR, the types of adverse reactions related to lacosamide in elderly patients (≥ 65 years of age) appear to be similar to that observed in patients less than 65 years of age. However, a higher incidence (≥ 5 % difference) of fall, diarrhoea and tremor has been reported in elderly patients compared to younger adult patients. The most frequent cardiac-related adverse reaction reported in elderly compared to the younger adult population was first-degree AV block. This was reported with lacosamide in 4.8 % (3/62) in elderly patients versus 1.6 % (6/382) in younger adult patients. The discontinuation rate due to adverse events observed with lacosamide was 21.0 % (13/62) in elderly patients versus 9.2 % (35/382) in younger adult patients. These differences between elderly and younger adult patients were similar to those observed in the active comparator group.

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 (see details below) 

Reporting of suspected adverse reactions 

Saudi Arabia:

The National Pharmacovigilance and Drug Safety Centre (NPC)

 o SFDA Call Center: 19999
o E-mail:npc.drug@sfda.gov.sa 
o Website:https://ade.sfda.gov.sa/              

Other GCC States:

Please contact the relevant competent authority.


Symptoms 

Symptoms observed after an accidental or intentional overdose of lacosamide are primarily associated with CNS and gastrointestinal system.

 The types of adverse reactions experienced by patients exposed to doses above 400 mg up to 800 mg were not clinically different from those of patients administered recommended doses of lacosamide.

Reactions reported after an intake of more than 800 mg are dizziness, nausea, vomiting, seizures (generalised tonic-clonic seizures, status epilepticus). Cardiac conduction disorders, shock and coma have also been observed. Fatalities have been reported in patients following an intake of acute single overdose of several grams of lacosamide.

Management 

There is no specific antidote for overdose with lacosamide. Treatment of lacosamide overdose should include general supportive measures and may include haemodialysis if necessary (see section 5.2).

 


Pharmacotherapeutic group: antiepileptics, other antiepileptics, ATC code: N03AX18

Mechanism of action 

The active substance, lacosamide (R-2-acetamido-N-benzyl-3-methoxypropionamide) is a functionalised amino acid.

The precise mechanism by which lacosamide exerts its antiepileptic effect in humans remains to be fully elucidated. In vitro electrophysiological studies have shown that lacosamide selectively enhances slow inactivation of voltage- gated sodium channels, resulting in stabilization of hyperexcitable neuronal membranes.

Pharmacodynamic effects 

Lacosamide protected against seizures in a broad range of animal models of partial and primary generalised seizures and delayed kindling development. In non-clinical experiments lacosamide in combination with levetiracetam, carbamazepine, phenytoin, valproate, lamotrigine, topiramate or gabapentin showed synergistic or additive anticonvulsant effects.

 

Clinical efficacy and safety (partial-onset seizures)  Adult population 

Monotherapy 

Efficacy of lacosamide as monotherapy was established in a double-blind, parallel group, noninferiority comparison to carbamazepine CR in 886 patients 16 years of age or older with newly or recently diagnosed epilepsy. The patients had to present with unprovoked partial-onset seizures with or without secondary generalisation. The patients were randomised to carbamazepine CR or lacosamide, provided as tablets, in a 1:1 ratio. The dose was based on dose-response and ranged from 400 to 1,200 mg/day for carbamazepine CR and from 200 to 600 mg/day for lacosamide. The duration of the treatment was up to 121 weeks depending on the response.

The estimated 6-month seizure freedom rates were 89.8 % for lacosamide-treated patients and 91.1 % for carbamazepine CR treated patients using the Kaplan-Meier survival analysis method.

The adjusted absolute difference between treatments was - 1.3 % (95 % CI: -5.5, 2.8). The Kaplan-Meier estimates of 12-month seizure freedom rates were 77.8 % for lacosamide-treated patients and 82.7 % for carbamazepine CR treated patients.

The 6-month seizure freedom rates in elderly patients of 65 and above (62 patients in lacosamide, 57 patients in carbamazepine CR) were similar between both treatment groups. The rates were also similar to those observed in the overall population. In the elderly population, the maintenance lacosamide dose was 200 mg/day in 55 patients (88.7 %), 400 mg/day in 6 patients (9.7 %) and the dose was escalated to over 400 mg/day in 1 patient (1.6 %).

Conversion to monotherapy 

The efficacy and safety of lacosamide in conversion to monotherapy has been assessed in a historical-controlled, multicentre, double-blind, randomised trial. In this study, 425 patients aged 16 to 70 years with uncontrolled partial-onset seizures taking stable doses of 1 or 2 marketed antiepileptic medicinal products were randomised to be converted to lacosamide monotherapy (either 400 mg/day or 300 mg/day in a 3:1 ratio). In treated patients who completed titration and started withdrawing antiepileptic medicinal products (284 and 99 respectively), monotherapy was maintained in 71.5 % and 70.7 % of patients respectively for 57-105 days (median 71 days), over the targeted observation period of 70 days.

Adjunctive therapy 

The efficacy of lacosamide as adjunctive therapy at recommended doses (200 mg/day, 400 mg/day) was established in 3 multicenter, randomised, placebo-controlled clinical studies with a 12-week maintenance period. Lacosamide 600 mg/day was also shown to be effective in controlled adjunctive therapy studies, although the efficacy was similar to 400 mg/day and patients were less likely to tolerate this dose because of CNS- and gastrointestinal-related adverse reactions. Thus, the 600 mg/day dose is not recommended. The maximum recommended dose is 400 mg/day. These studies, involving 1,308 patients with a history of an average of 23 years of partial-onset seizures, were designed to evaluate the efficacy and safety of lacosamide when administered concomitantly with 1-3 antiepileptic medicinal products in patients with uncontrolled partial-onset seizures with or without secondary generalisation. Overall the proportion of subjects with a 50 % reduction in seizure frequency was 23 %, 34 %, and 40 % for placebo, lacosamide 200 mg/day and lacosamide 400 mg/day.

The pharmacokinetics and safety of a single loading dose of intravenous lacosamide were determined in a multicenter, open-label study designed to assess the safety and tolerability of rapid initiation of lacosamide using a single intravenous loading dose (including 200 mg) followed by twice daily oral dosing (equivalent to the intravenous dose) as adjunctive therapy in adult subjects 16 to 60 years of age with partial-onset seizures.

Paediatric population 

Partial-onset seizures have a similar clinical expression in children from 4 years of age and in adults. The efficacy of lacosamide in children aged 4 years and older has been extrapolated from data of adolescents and adults with partial-onset seizures, for whom a similar response was expected provided the paediatric dose adaptations are established (see section 4.2) and safety has been demonstrated (see section 4.8).

The efficacy supported by the extrapolation principle stated above was confirmed by a doubleblind, randomised, placebo-controlled study. The study consisted of an 8- week baseline period followed by a 6-week titration period. Eligible patients on a stable dose regimen of 1 to ≤ 3 antiepileptic medicinal products, who still experienced at least 2 partial-onset seizures during the 4 weeks prior to screening with seizure-free phase no longer than 21 days in the 8-week period prior to entry into the baseline period, were randomised to receive either placebo (n=172) or lacosamide (n=171).

Dosing was initiated at a dose of 2 mg/kg/day in subjects weighing less than 50 kg or 100 mg/day in subjects weighing 50 kg or more in 2 divided doses. During the titration period, lacosamide doses were adjusted in 1or 2 mg/kg/day increments in subjects weighing less than 50 kg or 50 or 100 mg/day in subjects weighing 50 kg or more at weekly intervals to achieve the target maintenance period dose range.

Subjects must have achieved the minimum target dose for their body weight category for the final 3 days of the titration period to be eligible for entry into the 10-week maintenance period. Subjects were to remain on stable lacosamide dose throughout the maintenance period or were withdrawn and entered in the blinded taper period. Statistically significant (p=0.0003) and clinically relevant reduction in partial-onset seizure frequency per 28 days from baseline to the maintenance period was observed between the lacosamide and the placebo group. The percent reduction over placebo based on analysis of covariance was 31.72 % (95 % CI: 16.342, 44.277). Overall, the proportion of subjects with at least a 50 % reduction in partial-onset seizure frequency per 28 days from baseline to the maintenance period was 52.9 % in the lacosamide group compared with 33.3 % in the placebo group.

The quality of life assessed by the Pediatric Quality of Life Inventory indicated that subjects in both lacosamide and placebo groups had a similar and stable health-related quality of life during the entire treatment period.

Clinical efficacy and safety (primary generalized tonic-clonic seizures) 

The efficacy of lacosamide as adjunctive therapy in patients 4 years of age and older with idiopathic generalized epilepsy experiencing primary generalized tonic-clonic seizures (PGTCS) was established in a 24-week double-blind, randomized, placebo-controlled, parallel-group, multi-center study. The study consisted of a 12-week historical baseline period, a 4-week prospective baseline period and a 24-week treatment period (which included a 6-week titration period and an 18-week maintenance period). Eligible patients on a stable dose of 1 to 3 antiepileptic drugs experiencing at least 3 documented PGTCS during the 16-week combined baseline period were randomized 1 to 1 to receive lacosamide or placebo (patients in the full analysis set: lacosamide n=118, placebo n=121; of them 8 patients in the ≥ 4 to < 12 years age group and 16 patients in the ≥ 12 to < 18 years range were treated with lacosamide and 9 and 16

patients, respectively with placebo).

Patients were titrated up to the target maintenance period dose of 12 mg/kg/day in patients weighing less than 30 kg, 8 mg/kg/day in patients weighing from 30 to less than 50 kg or 400 mg/day in patients weighing 50 kg or more.

Efficacy variable

Parameter

Placebo 

N=121

Lacosamide

N=118

Time to second PGTCS

 

 

Median (days)

77.0

-

95 % CI

49.0, 128.0

-

Lacosamide – Placebo

 

 

Hazard Ratio

0.540

 

95 % CI

0.377, 0.774

 

p-value

< 0.001

 

Seizure freedom

 

 

Stratified Kaplan-Meier estimate (%)

17.2

31.3

95 % CI

10.4, 24.0

22.8, 39.9

Lacosamide – Placebo

14.1

 

95 % CI

3.2, 25.1

 

p-value

0.011

 

Note: For the lacosamide group, the median time to second PGTCS could not be estimated by Kaplan-Meier methods because 50% of patients did not experience a second PGTCS by Day 166.

The findings in the paediatric subgroup were consistent with the results of the overall population for the primary, secondary and other efficacy endpoints.


Absorption 

Lacosamide is rapidly and completely absorbed after oral administration. The oral bioavailability of lacosamide tablets is approximately 100 %. Following oral administration, the plasma concentration of unchanged lacosamide increases rapidly and reaches Cmax about 0.5 to 4 hours post-dose. Lacosamide tablets and oral syrup are bioequivalent. Food does not affect the rate and extent of absorption.

Distribution 

The volume of distribution is approximately 0.6 L/kg. Lacosamide is less than 15 % bound to plasma proteins.

Biotransformation 

95 % of the dose is excreted in the urine as lacosamide and metabolites. The metabolism of lacosamide has not been completely characterised.

The major compounds excreted in urine are unchanged lacosamide (approximately 40 % of the dose) and its O-desmethyl metabolite less than 30 %.

A polar fraction proposed to be serine derivatives accounted for approximately 20 % in urine, but was detected only in small amounts (0-2 %) in human plasma of some subjects. Small amounts (0.5-2 %) of additional metabolites were found in the urine.

In vitro data show that CYP2C9, CYP2C19 and CYP3A4 are capable of catalysing the formation of the O-desmethyl metabolite but the main contributing isoenzyme has not been confirmed in vivo. No clinically relevant difference in lacosamide exposure was observed comparing its pharmacokinetics in extensive metabolisers (EMs, with a functional CYP2C19) and poor metabolisers (PMs, lacking a functional CYP2C19).

Furthermore an interaction study with omeprazole (CYP2C19-inhibitor) demonstrated no clinically relevant changes in lacosamide plasma concentrations indicating that the importance of this pathway is minor. The plasma concentration of O-desmethyl-lacosamide is approximately 15 % of the concentration of lacosamide in plasma. This major metabolite has no known pharmacological activity.

Elimination 

Lacosamide is primarily eliminated from the systemic circulation by renal excretion and biotransformation. After oral and intravenous administration of radiolabeled lacosamide, approximately 95 % of radioactivity administered was recovered in the urine and less than 0.5 % in the faeces. The elimination half-life of lacosamide is approximately 13 hours. The pharmacokinetics is dose-proportional and constant over time, with low intra- and inter-subject variability. Following twice daily dosing, steady state plasma concentrations are achieved after a

3 day period. The plasma concentration increases with an accumulation factor of approximately

2.

A single loading dose of 200 mg approximates steady-state concentrations comparable to 100 mg twice daily oral administration.

Pharmacokinetics in special patient groups 

Gender 

Clinical studies indicate that gender does not have a clinically significant influence on the plasma concentrations of lacosamide.

Renal impairment 

The AUC of lacosamide was increased by approximately 30 % in mildly and moderately and 60 % in severely renal impaired patients and patients with end-stage renal disease requiring haemodialysis compared to healthy subjects, whereas Cmax was unaffected.

Lacosamide is effectively removed from plasma by haemodialysis. Following a 4-hour haemodialysis treatment, AUC of lacosamide is reduced by approximately 50 %. Therefore, dosage supplementation following haemodialysis is recommended (see section 4.2). The exposure of the O-desmethyl metabolite was several-fold increased in patients with moderate and severe renal impairment. In absence of haemodialysis in patients with end-stage renal disease, the levels were increased and continuously rising during the 24-hour sampling. It is unknown whether the increased metabolite exposure in end-stage renal disease subjects could give rise to adverse effects but no pharmacological activity of the metabolite has been identified.

Hepatic impairment 

Subjects with moderate hepatic impairment (Child-Pugh B) showed higher plasma concentrations of lacosamide (approximately 50 % higher AUCnorm). The higher exposure was partly due to a reduced renal function in the studied subjects. The decrease in non-renal clearance in the patients of the study was estimated to give a 20 % increase in the AUC of lacosamide. The pharmacokinetics of lacosamide has not been evaluated in severe hepatic impairment (see section

4.2).

Elderly (over 65 years of age) 

In a study in elderly men and women including 4 patients > 75 years of age, AUC was about 30 and 50 % increased compared to young men, respectively. This is partly related to lower body weight. The body weight normalized difference is 26 and 23 %, respectively. An increased variability in exposure was also observed. The renal clearance of lacosamide was only slightly reduced in elderly subjects in this study.

A general dose reduction is not considered to be necessary unless indicated due to reduced renal function (see section 4.2).

Paediatric population 

The paediatric pharmacokinetic profile of lacosamide was determined in a population pharmacokinetic analysis using sparse plasma concentration data obtained in one placebocontrolled randomised study and three open-label studies in 414 children with epilepsy aged 6 months to 17 years. The administered lacosamide doses ranged from 2 to 17.8 mg/kg/day in twice daily intake, with a maximum of 600 mg/day for children weighing 50 kg or more. The typical plasma clearance was estimated to be 1.04 L/h, 1.32 L/h and 1.86 L/h for children weighing 20 kg, 30 kg and 50 kg respectively. In comparison, plasma clearance was estimated at 1.92 L/h in adults (70 kg body weight).

Population pharmacokinetic analysis using sparse pharmacokinetic samples from PGTCS study showed a similar exposure in patients with PGTCS and in patients with partial-onset seizures.


In the toxicity studies, the plasma concentrations of lacosamide obtained were similar or only marginally higher than those observed in patients, which leaves low or non- existing margins to human exposure.

A safety pharmacology study with intravenous administration of lacosamide in anesthetised dogs showed transient increases in PR interval and QRS complex duration and decreases in blood pressure most likely due to a cardiodepressant action. These transient changes started in the same concentration range as after maximum recommended clinical dosing. In anesthetised dogs and Cynomolgus monkeys, at intravenous doses of 15-60 mg/kg, slowing of atrial and ventricular conductivity, atrioventricular block and atrioventricular dissociation were seen.

In the repeated dose toxicity studies, mild reversible liver changes were observed in rats starting at about 3 times the clinical exposure. These changes included an increased organ weight, hypertrophy of hepatocytes, increases in serum concentrations of liver enzymes and increases in total cholesterol and triglycerides. Apart from the hypertrophy of hepatocytes, no other histopathologic changes were observed.

In reproductive and developmental toxicity studies in rodents and rabbits, no teratogenic effects but an increase in numbers of stillborn pups and pup deaths in the peripartum period, and slightly reduced live litter sizes and pup body weights were observed at maternal toxic doses in rats corresponding to systemic exposure levels similar to the expected clinical exposure. Since higher exposure levels could not be tested in animals due to maternal toxicity, data are insufficient to fully characterise the embryofetotoxic and teratogenic potential of lacosamide.

Studies in rats revealed that lacosamide and/or its metabolites readily crossed the placental barrier.

In juvenile rats and dogs, the types of toxicity do not differ qualitatively from those observed in adult animals. In juvenile rats, a reduced body weight was observed at systemic exposure levels similar to the expected clinical exposure. In juvenile dogs, transient and dose-related CNS clinical signs started to be observed at systemic exposure levels below the expected clinical exposure.


Lomipat 50:

Cellulose, Microcrystalline, Low- substituted hydroxyl propyl cellulose, Crospovidone, Hydroxy propyl Cellulose, Silica, colloidal anhydrous, Magnesium Stearate.

Film coating composition: Polyvinyl Alcohol-Part.hydrolyzed, Talc, Titanium Dioxide, Macrogol/PEG, Lecithin (soya), Iron Oxide Red, FD&C Blue #2/Indigo Carmine Aluminum lake, Iron Oxide Black.

Clear coating composition: HPMC 2910/Hypromellose, Macrogol/PEG.
 

Lomipat 100:  

Cellulose, Microcrystalline, Low- substituted hydroxyl propyl cellulose, Crospovidone, Hydroxy propyl Cellulose, Silica, colloidal anhydrous, Magnesium Stearate.

,Film coating composition: Polyvinyl Alcohol-Part.hydrolyzed, Talc, Titanium Dioxide, Macrogol/PEG, Iron Oxide Yellow, Lecithin (soya).

Clear coating composition: HPMC 2910/Hypromellose, Macrogol/PEG.
 

Lomipat 150:

Cellulose, Microcrystalline, Low- substituted hydroxyl propyl cellulose, Crospovidone, Hydroxy propyl Cellulose, Silica, colloidal anhydrous, Magnesium Stearate.

Film coating composition: Polyvinyl Alcohol-Part.hydrolyzed, Talc, Titanium Dioxide, Macrogol/PEG, Lecithin (soya), Iron Oxide Yellow, Iron Oxide Red, Iron Oxide Black.

Clear coating composition: HPMC 2910/Hypromellose, Macrogol/PEG.
 

Lomipat 200:  

Cellulose, Microcrystalline, Low- substituted hydroxyl propyl cellulose, Crospovidone, Hydroxy propyl Cellulose, Silica, colloidal anhydrous, Magnesium Stearate.

Film coating composition: Polyvinyl Alcohol-Part.hydrolyzed, Talc, Titanium Dioxide, Macrogol/PEG, FD&C Blue #2/Indigo Carmine Aluminum lake, Lecithin (soya).

Clear coating composition: HPMC 2910/Hypromellose, Macrogol/PEG.


NA


24 months

Store below 30ºC.


  Alu-PVC/PVdc blister 


NA


Saudi Amarox Industrial Company, Aljameah Street, Malaz quarter, Riyadh 11441, Saudi Arabia Tel: +966 11 477 2215 Manufacture: Hetero Labs Limited, Unit V, Telangana, India

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