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نشرة الممارس الصحي | نشرة معلومات المريض بالعربية | نشرة معلومات المريض بالانجليزية | صور الدواء | بيانات الدواء |
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How does Marlon work?
Marlon belongs to a group of medicines known as anti-dementia medicines.
Memory loss in Alzheimer’s disease is due to a disturbance of message signals in the brain. The brain contains so-called N-methyl-D-aspartate (NMDA)-receptors that are involved in transmitting nerve signals important in learning and memory. Marlon belongs to a group of medicines called NMDA-receptor antagonists. Marlon acts on these NMDA-receptors improving the transmission of nerve signals and the memory.
What is Marlon used for?
Marlon is used for the treatment of patients with moderate to severe Alzheimer’s disease.
Do not take Marlon:
● If you are allergic (hypersensitive) to memantine hydrochloride or any of the other ingredients of Marlon tablets (see section 6).
Take special care with Marlon
● If you have a history of epileptic seizures
● If you have recently experienced a myocardial infarction (heart attack), or if you are suffering from congestive heart failure or from an uncontrolled hypertension (high blood pressure).
● In these situations the treatment should be carefully supervised, and the clinical benefit of Marlon reassessed by your doctor on a regular basis.
● If you suffer from renal impairment (kidney problems), your doctor should closely monitor your kidney function and if necessary adapt the memantine doses accordingly.
The use of medicinal products called amantadine (for the treatment of Parkinson’s disease), ketamine (a substance generally used as an anaesthetic), dextromethorphan (generally used to treat cough) and other NMDA-antagonists at the same time should be avoided.
Children and adolescents
Marlon is not recommended for children and adolescents under the age of 18 years.
Using other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
In particular, Marlon may change the effects of the following medicines and their dose may need to be adjusted by your doctor:
● amantadine, ketamine, dextromethorphan
● dantrolene, baclofen
● cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine
● hydrochlorothiazide (or any combination with hydrochlorothiazide)
● anticholinergics (substances generally used to treat movement disorders or intestinal cramps)
● anticonvulsants (substances used to prevent and relieve seizures)
● barbiturates (substances generally used to induce sleep)
● dopaminergic agonists (substances such as L-dopa, bromocriptine)
● neuroleptics (substances used in the treatment of mental disorders)
● oral anticoagulants
If you go into hospital, let your doctor know that you are taking Marlon.
Taking Marlon with food and drink
You should inform your doctor if you have recently changed or intend to change your diet substantially (e.g. from normal diet to strict vegetarian diet) or if you are suffering from states of renal tubulary acidosis (RTA, an excess of acid-forming substances in the blood due to renal dysfunction (poor kidney function)) or severe infections of the urinary tract (structure that carries urine), as your doctor may need to adjust the dose of your medicine.
Pregnancy and breast-feeding
● Ask your doctor or pharmacist for advice before taking any medicine.
● Tell your doctor if you are pregnant or planning to become pregnant. The use of memantine in pregnant women is not recommended.
● Women taking Marlon should not breast-feed.
Driving and using machines
Your doctor will tell you whether your illness allows you to drive and to use machines safely.
Also, Marlon may change your reactivity, making driving or operating machinery inappropriate.
Always take Marlon exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.
The recommended dose of Marlon for adults and elderly patients is 20 mg once a day. In order to reduce the risk of side effects this dose is achieved gradually by the following daily treatment scheme:
Dosage
week 1 | Half Marlon 10 mg tablet |
week 2 | one 10 mg tablet |
week 3 | one and a half 10 mg tablets |
week 4 and beyond
| two 10 mg tablets or one tablet of Marlon 20mg once a day |
The usual starting dose is half a tablet once a day (1x 5 mg) for the first week. This is increased to one tablet once a day (1x 10 mg) in the second week and to 1 and a half tablets once a day in the third week. From the fourth week on, the usual dose is 2 tablets once a day (1x 20 mg).
Dosage in patients with impaired kidney function
If you have impaired kidney function, your doctor will decide upon a dose that suits your condition. In this case, monitoring of your kidney function should be performed by your doctor at specified intervals.
Administration
Marlonshould be administered orally once a day. To benefit from your medicine you should take it regularly every day at the same time of the day. The tablets should be swallowed with some water. The tablets can be taken with or without food.
Duration of treatment
Continue to take Marlonas long as it is of benefit to you. Your doctor should assess your treatment on a regular basis.
If you take more Marlonthan you should
- In general, taking too much Marlonshould not result in any harm to you. You may experience increased symptoms as described in section 4. “Possible side effects”.
- If you take a large overdose of Marlon, contact your doctor or get medical advice, as you may need medical attention.
If you forget to take Marlon
- If you find you have forgotten to take your dose of Marlon, wait and take your next dose at the usual time.
- Do not take a double dose to make up for a forgotten dose.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Like all medicines, Marlon can cause side effects, although not everybody gets them.
In general, the observed side effects are mild to moderate.
Common (affects 1 to 10 users in 100):
Headache, sleepiness, constipation, elevated liver function tests, dizziness, balance disorders, shortness of breath, high blood pressure and drug hypersensitivity
Uncommon (affects 1 to 10 users in 1,000):
Tiredness, fungal infections, confusion, hallucinations, vomiting, abnormal gait, heart failure and venous blood clotting (thrombosis/thromboembolism)
Very Rare (affects less than 1 user in 10,000):
Seizures
Not known (frequency cannot be estimated from the available data):
Inflammation of the pancreas, inflammation of the liver (hepatitis) and psychotic reactions
Alzheimer’s disease has been associated with depression, suicidal ideation and suicide. These events have been reported in patients treated with Marlon.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
● Keep out of the reach and sight of children.
● Do not use Marlon after the expiry date which is stated on the carton. The expiry date refers to the last day of that month.
● Store below 30°C
● Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
The active substance is memantine hydrochloride.
Each 10mg film-coated tablet contains 10 mg memantine hydrochloride.
Each 20mg film-coated tablet contains 20 mg memantine hydrochloride.
The other ingredients are:
Tablet core: Microcrystalline Cellulose (Avicel pH 102), Lactose NF Fast Flow, Croscarmellose Sodium Type A, Colloidal Silicon Dioxide
Tablet coating: Hydroxypropyl Methylcellulose, Titanium Dioxide pharma grade, Purified Talc, Polyethylene Glycol MW 6000, Purified Water (10mg) Iron Oxide Yellow, (20mg) Iron Oxide Red
Dammam Pharma
Saudi Arabia
Address: 1st industrial city, unit No.1, PO.BOX: 7137, Dammam 32234-4384
Phone: +966138216444
Fax: +966138216422
Email: regulatory-affairs@dammampharma.sa
كيف يعمل مارلون؟
ينتمى مارلون إلى مجموعة من الأدوية تعرف بمضادات الخرف.
يحدث فقدان الذاكرة فى مرض الزهايمر نتيجة إلى اضطراب إشارات الرسائل في الدماغ. يحتوي الدماغ على ما يسمى مستقبلات إن ميثيل دى أسبارتات NMDA)) التي تشارك في نقل الإشارات العصبية الهامة في التعلم والذاكرة.ينتمى مارلون إلى مجموعة من الأدوية التى تسمى مضادات مستقبلات (NMDA). يعمل مارلون على هذه المستقبلات مما يحسن من نقل الإشارات العصبية و يحسن الذاكرة.
فيم يستخدم مارلون؟
يستخدم مارلون لعلاج المرضى المصابين بمرض الزهايمر من الدرجة المتوسطة إلى الشديدة.
لا تتناول مارلون:
● إذا كان لديك حساسية زائدة تجاه ميمانتين هيدروكلورايد أو أى مكون آخر من مكونات أقراص مارلون (أنظر فقرة 6)
ينبغى توخى الحذرمع مارلون:
● إذا كان لديك تاريخ من نوبات الصرع.
● إذا كنت قد تعرضت مؤخرا لإحتشاء عضلة القلب (نوبة قلبية)، أو إذا كنت تعاني من فشل القلب الاحتقاني أو ارتفاع ضغط الدم غير المنضبط (ارتفاع ضغط الدم).
● وفي هذه الحالات ينبغي أن يكون العلاج تحت الإشراف بعناية فائقة، وإعادة تقييم الفائدة السريرية من مارلون من قبل الطبيب على أساس منتظم.
● إذا كنت تعاني من اختلال كلوي (مشاكل في الكليتين)، وينبغي أن يراقب طبيبك وظائف الكلى الخاصة بك عن كثب وإذا لزم الأمر تعديل جرعات ميمانتين وفقا لذلك.
ينبغى تجنب استخدام أدوية تدعى أمانتادين (لعلاج مرض الشلل الرعاش)، و كيتامين (وهي مادة تستخدم عادة كمخدر)، ديكسترومثورفان (تستخدم عادة لعلاج السعال) وغيرها من مضادات NMDA في نفس الوقت.
لا ينصح مارلون للأطفال والمراهقين الذين تقل أعمارهم عن 18 عاما.
استخدام أدوية أخرى
يرجى إخبار الطبيب أو الصيدلي إذا كنت تتناول أو تناولت في الآونة الأخيرة أي أدوية أخرى، بما في ذلك الأدوية التي تم الحصول عليها دون وصفة طبية.
على وجه الخصوص، قد يغير مارلون من تأثير الأدوية التالية و قد يحتاج طبيبك إلى تعديل جرعاتها:
● أمانتادين و كيتامين و ديكستروميثورفان
● دانترولين و باكلوفين
● سايميتيدين و رادنتيدين و بركاينامايد و كينيدين وكينين و نيكوتين
● هايدروكلوروثيازايد (أو أى مركب يحتوى على هيدروكلوروثيازايد)
● مضادات الكولين (أدوية تستخدم عادة لعلاج اضطرابات الحركة أو تقلصات الأمعاء)
● مضادات التشنجات (أدوية تمنع أو تخفف التشنجات)
● باربيتورات (أدوية تستخدم عادة للحث على النوم)
● محفزات الدوبامين (أدوية مثل ل- دوبا و بروموكريبتين)
● مضادات الذهان (أدوية تستخدم لعلاج الأمراض العقلية)
● مضادات التجلط الفموية
إذا ذهبت إلى المستشفى، اعلم طبيبك أنك تتناول مارلون.
تناول مارلون مع الطعام و الشراب
يجب عليك إبلاغ الطبيب إذا كنت قد غيرت مؤخرا أو تنوي تغيير النظام الغذائي الخاص بك بشكل كبير (على سبيل المثال من النظام الغذائي العادي إلى نظام غذائي نباتي صارم) أو إذا كنت تعاني من حالات الحماض الأنبوبى الكلوي (RTA) وهو وجود فائض من المواد الحمضية المكونة في الدم بسبب الفشل الكلوي (فقر وظيفة الكلى) أو التهاب حاد في المسالك البولية (الهيكل الذي يحمل البول)، والطبيب قد يحتاج إلى تعديل جرعة الدواء.
الحمل و الرضاعة
● اسأل طبيبك أو الصيدلي للحصول على المشورة قبل تناول أي دواء.
● أخبرى طبيبك إذا كنتى حاملا أو تخططين للحمل. لا ينصح استخدام النساء الحوامل لميمانتين.
● لا ينبغى إرضاع طفلك طبيعيا إذا كنتى تتناولين مارلون.
القيادة واستخدام الآلات
طبيبك سوف يخبرك ما اذا كان مرضك يسمح لك بالقيادة واستخدام الآلات بأمان.
أيضا، قد يغير مارلون ردة فعلك، مما يجعل القيادة أو تشغيل الآلات غير لائق.
قم دائما بتناول أقراص مارلون تماما كما أخبرك الطبيب المعالج. إذا كنت غير واثق يجب عليك التحقق من خلال الطبيب أو الصيدلى.
الجرعة الموصى بها من مارلون للكبار والمرضى كبار السن هي 20 ملجم مرة واحدة يوميا. من أجل الحد من خطر الآثار الجانبية ويتم الوصول إلى هذه الجرعة تدريجيا بمخطط العلاج اليومي التالى:
الجرعة
نصف قرص مارلون 10 ملجم | الأسبوع الأول |
قرصمارلون 10 ملجم | الأسبوع الثانى |
قرص و نصف من مارلون 10 ملجم | الأسبوع الثالث |
قرصين مارلون 10 ملجم مرة يوميا أو قرص من مارلون 20 ملجم | الأسبوع الرابع و باقى فترة العلاج |
الجرعة المعتادة المبدئيةهي نصف قرص مرة واحدة يوميا (1 X5 ملجم) في الأسبوع الأول. يتم زيادة هذا إلى قرص واحد مرة واحدة يوميا (1 X10 ملجم) في الأسبوع الثاني وقرص ونصف مرة واحدة في اليوم في الأسبوع الثالث. من الأسبوع الرابع و باقى فترة العلاج، الجرعة المعتادة هي 2 حبة مرة واحدة يوميا (1 X20 ملجم).
الجرعة في المرضى الذين يعانون من خلل فى وظائف الكلى
إذا كان لديك خلل فى وظائف الكلى، و سوف يقرر الطبيبالجرعة التي تناسب حالتك. في هذه الحالة، يجب القيام بمراقبة وظيفة الكلى الخاصة بك من قبل الطبيب على فترات زمنية محددة.
التناول
ينبغي أن تتناولمارلون عن طريق الفم مرة واحدة يوميا. للاستفادة من الدواء يجب أن تتناوله بانتظام كل يوم في نفس الوقت من اليوم. يجب ابتلاع الأقراص مع بعض الماء. يمكن تناول الأقراص مع أو بدون الطعام.
مدة العلاج
استمر في تناول مارلون طالما أنهيفيدك. يجب على طبيبك أن يقيم علاجك بشكل منتظم.
إذا تتناولت من مارلون أكثرمما يجب
- بشكل عام، لا ينبغي أن يؤدي تناول الكثير من مارلون إلى أي ضرر لك. قد تواجه أعراض متزايدة كما هو موضح في الفقرة 4. "الأعراض الجانبية المحتملة".
- إذا تناولت جرعة زائدة كبيرة من مارلون ، اتصل بطبيبك أو احصل على المشورة الطبية، كما قد تحتاج إلى عناية طبية.
إذا كنت قد نسيت أن تتناولمارلون
- إذا وجدت أنك قد نسيت أن تتناول جرعة من مارلون ، ننتظر وخذ الجرعة التالية في الوقت المعتاد.
- لا تأخذ جرعة مضاعفة لتعويض الجرعة المنسية.
إذا كان لديك أي أسئلة أخرى عن استخدام هذا الدواء، اسأل طبيبك أو الصيدلي.
مثل جميع الأدوية، مارلون قد يسبب أعراض جانبية، وإن لم تكن تحدث لكل من يتناول هذا الدواء.
بشكل عام، الآثار الجانبية الملحوظة خفيفة إلى متوسطة.
شائعة (تؤثر 1-10 مستخدمين في 100):
الصداع، والنعاس، والإمساك، ارتفاع فى تحاليل وظائف الكبد، والدوخة، واضطرابات في التوازن، وضيق في التنفس، وارتفاع ضغط الدم وفرط الحساسية للدواء.
غير شائعة (تؤثر 1-10 مستخدمين في 1000):
التعب، والعدوى الفطرية، والارتباك، والهلوسة، والتقيؤ، ومشية غير طبيعية، وفشل القلب وتجلط الدم الوريدي (الجلطة / الجلطات الدموية).
نادرة جدا (تؤثر فى أقل من 1 مستخدم فى 10000):
النوبات.
غير معروف (لا يمكن تقدير تردد من البيانات المتاحة):
التهاب البنكرياس، التهاب الكبد (التهاب الكبد) وردود الفعل الذهانية
ارتبط مرض الزهايمر بالإكتئاب، التفكير في الإنتحار والإنتحار. وقد تم الإبلاغ عن هذه الأحداث في المرضى الذين تناولوا مارلون.
إذا لاحظت أن أيا من هذه الأعراض الجانبية أصبح جسيما، أو إذا لاحظت ظهور أى أعراض جانبية لم ترد فى هذه النشرة فإنه يرجى أن تخبر طبيبك المعالج أو الصيدلى الذى تتعامل معه بشأنها.
● يحفظ الدواء بعيدا عن متناول ونظر الأطفال.
● لا تستعمل مارلون بعد انتهاء تاريخ الصلاحية المدون على العبوة. وتاريخ الإنتهاء يشير إلى أخر يوم فى الشهر المذكور.
● يحفظ في درجة حرارة أقل من 30 درجة مئوية.
● يجب عدم التخلص من الأدوية في مياه المجاري أو قمامة المنزل. اسأل الصيدلي كيف تتخلص من الأدوية التي لم تعد بحاجتها. لأن هذه الاعتبارات ستعمل على حماية البيئة.
المادة الفعالة هى ميمانتين هيدروكلورايد.
يحتوى كل قرص من مارلون 10 ملجم مغلف بطبقة رقيقة على 10 ملجم من ميمانتين هيدروكلورايد.
يحتوى كل قرص من مارلون 20 ملجم مغلف بطبقة رقيقة على 20 ملجم من ميمانتين هيدروكلورايد.
المكونات الأخرى:
لب القرص: ميكروكريستالين السليلوز (أفسيل بى إتش 102)، لاكتوز NF تدفق سريع، كروزكارميللوز صوديوم نوع A، ثاني أكسيد السيليكون الغرواني
طلاء القرص: هيدروكسي بروبيل ميثيل سيلليولوز، ثاني أكسيد التيتانيوم فارما الصف، و تلك منقى ، والبولي إيثلين جلايكول MW 6000، والمياه النقية (10 ملجم) أكسيد الحديد الأصفر، (20 ملجم) أكسيد الحديد الأحمر
مارلون أقراص مغلفة بطبقة رقيقة
قرص مارلون10ملجم هو قرص أصفر، على شكل كبسولة ، قرص ثنائي التحدب مغلف بطبقة رقيقة،محفور برقم " T225" على جانب و خط فاصل للكسر على الجانب الآخر.
قرص مارلون20ملجم هو قرص بمبي، على شكل كبسولة ، قرص ثنائي التحدب مغلف بطبقة رقيقة،محفور برقم "T226" على جانب وجلي السطح على الجانب الآخر.
تتوفر أقراص مارلون فى عبوة تحتوى كل عبوة على 30 قرص مغلف بطبقة رقيقة.
الدمام فارما
العنوان: المدينة الصناعية الأولى , وحدة رقم 1 , صندوق بريد: 7137 , الدمام 32234 – 4384
تليفون: 966138216444+
فاكس: 966138216422+
regulatory-affairs@dammampharma.saالبريد الإلكتروني:
Treatment of patients with moderate to severe Alzheimer's disease.
Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer's dementia. Therapy should only be started if a caregiver is available who will regularly monitor the intake of the medicinal product by the patient. Diagnosis should be made according to current guidelines. The tolerance and dosing of memantine should be reassessed on a regular basis, preferably within three months after start of treatment. Thereafter, the clinical benefit of memantine and the patient's tolerance of treatment should be reassessed on a regular basis according to current clinical guidelines. Maintenance treatment can be continued for as long as a therapeutic benefit is favourable and the patient tolerates treatment with memantine. Discontinuation of memantine should be considered when evidence of a therapeutic effect is no longer present or if the patient does not tolerate treatment.
Marlon tablets should be administered once a day and should be taken at the same time every day.
The film-coated tablets can be taken with or without food.
Adults:
Dose titration
Treatment Initiation Pack:
The recommended starting dose is 5 mg per day, which is stepwise increased over the first 4 weeks of treatment reaching the recommended maintenance dose as follows:
Week 1 (day 1-7):
The patient should take one 5 mg film-coated tablet per day for 7 days.
Week 2 (day 8-14):
The patient should take one 10 mg film-coated tablet per day for 7 days.
Week 3 (day 15-21):
The patient should take one 15 mg film-coated tablet per day for 7 days.
Week 4 (day 22-28):
The patient should take one 20 mg film-coated tablet per day for 7 days.
The maximum daily dose is 20 mg per day.
Tablet packs of 10 mg and 20 mg
The maximum daily dose is 20 mg daily. In order to reduce the risk of undesirable effects the maintenance dose is achieved by upward titration of 5 mg per week over the first 3 weeks as follows:
Week 1 (day 1-7):
The patient should take half a 10 mg film-coated tablet
Week 2 (day 8-14):
The patient should take one 10 mg film-coated tablet
Week 3 (day 15-21):
The patient should take one and a half 10 mg film-coated tablets
From Week 4 on:
The patient should take one 20 mg film-coated tablet/two 10 mg film-coated tablets
Maintenance dose
The recommended maintenance dose is 20 mg per day.
Elderly: On the basis of the clinical studies, the recommended dose for patients over the age of 65 years is 20 mg per day (one 20 mg film-coated tablet/two 10 mg film-coated tablets) as described above.
Children and adolescents under the age of 18 years: Marlon is not recommended for use in children below 18 years due to a lack of data on safety and efficacy.
Renal impairment: In patients with mildly impaired renal function (creatinine clearance 50 - 80 ml/min) no dosage adjustment is required. In patients with moderate renal impairment (creatinine clearance 30 - 49 ml/min) daily dose should be 10 mg If tolerated well after at least 7 days of treatment, the dose could be increased up to 20 mg/day according to standard titration scheme. In patients with severe renal impairment (creatinine clearance 5 - 29 ml/min) daily dose should be 10 mg per day.
Hepatic impairment: In patients with mild or moderate hepatic impaired function (Child-Pugh A and Child-Pugh B) no dosage adjustment is needed. No data on the use of memantine in patients with severe hepatic impairment are available. Administration of Marlon is not recommended in patients with severe hepatic impairment.
Caution is recommended in patients with epilepsy, former history of convulsions or patients with predisposing factors for epilepsy.
Concomitant use of N-methyl-D-aspartate (NMDA)-antagonists such as amantadine, ketamine or dextromethorphan should be avoided. These compounds act at the same receptor system as memantine, and therefore adverse drug reactions (mainly CNS-related) may be more frequent or more pronounced (see also section 4.5).
Some factors that may raise urine pH (see section 5.2 “Elimination”) may necessitate careful monitoring of the patient. These factors include drastic changes in diet, e.g. from a carnivore to a vegetarian diet, or a massive ingestion of alkalising gastric buffers. Also, urine pH may be elevated by states of renal tubulary acidosis (RTA) or severe infections of the urinary tract with Proteus bacteria.
In most clinical trials, patients with recent myocardial infarction, uncompensated congestive heart failure (NYHA III-IV), or uncontrolled hypertension were excluded. As a consequence, only limited data are available and patients with these conditions should be closely supervised.
Due to the pharmacological effects and the mechanism of action of memantine the following interactions may occur:
• The mode of action suggests that the effects of L-dopa, dopaminergic agonists, and anticholinergics may be enhanced by concomitant treatment with NMDA-antagonists such as memantine. The effects of barbiturates and neuroleptics may be reduced. Concomitant administration of memantine with the antispasmodic agents, dantrolene or baclofen, can modify their effects and a dosage adjustment may be necessary.
• Concomitant use of memantine and amantadine should be avoided, owing to the risk of pharmacotoxic psychosis. Both compounds are chemically related NMDA-antagonists. The same may be true for ketamine and dextromethorphan (see also section 4.4). There is one published case report on a possible risk also for the combination of memantine and phenytoin.
• Other active substances such as such as cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine that use the same renal cationic transport system as amantadine may also possibly interact with memantine leading to a potential risk of increased plasma levels.
• There may be a possibility of reduced serum level of hydrochlorothiazide (HCT) when memantine is co-administered with HCT or any combination with HCT.
• In post-marketing experience isolated cases with international normalized ratio (INR) increases have been reported in patients concomitantly treated with warfarin. Although no causal relationship has been established, close monitoring of prothrombin time or INR is advisable for patients concomitantly treated with oral anticoagulants.
In single dose PK studies in young healthy subjects no relevant drug-drug interaction of memantine with glyburide/metformin or donepezil was observed.
In a clinical study in young healthy volunteers no relevant effect of memantine on the pharmacokinetics of galantamine was observed.
Memantine did not inhibit CYP 1A2, 2A6, 2C9, 2D6, 2E1, 3A, flavin-containing monooxygenase, epoxide hydrolase or sulphation in vitro.
Pregnancy Category: C
Pregnancy: For memantine, no clinical data on exposed pregnancies are available. Animal studies indicate a potential for reducing intrauterine growth at exposure levels that are identical or slightly higher than at human exposure (see section 5.3). The potential risk for humans is unknown. Memantine should not be used during pregnancy unless clearly necessary.
Lactation: It is not known whether memantine is excreted in human breast milk but, taking into consideration the lipophilicity of the substance, this probably occurs. Women taking memantine should not breast-feed.
Moderate to severe Alzheimer's disease usually causes impairment of driving performance and compromises the ability to use machinery. Furthermore, Marlon has minor or moderate influence on the ability to drive and use machines, such that outpatients should take special care.
In clinical trials in mild to severe dementia, involving 1,784 patients treated with Marlon and 1,595 patients treated with placebo, the overall incidence rate of adverse events with Marlon did not differ from those with placebo; the adverse events were usually mild to moderate in severity. The most frequently occurring adverse events with a higher incidence in the Marlon group than in the placebo group were dizziness (6.3% vs 5.6%, respectively), headache (5.2% vs 3.9%), constipation (4.6% vs 2.6%), somnolence (3.4% vs 2.2%) and hypertension (4.1% vs 2.8% ). The following Adverse Drug Reactions listed in the Table below have been accumulated in clinical studies with Marlon and since its introduction in the market. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Adverse reactions are ranked according to system organ class, using the following convention: very common (≥1/10), common (≥1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).
1 Hallucinations have mainly been observed in patients with severe Alzheimer's disease. 2 Isolated cases reported in post-marketing experience. Alzheimer's disease has been associated with depression, suicidal ideation and suicide. In post-marketing experience these events have been reported in patients treated with Marlon.
To report any side effect(s):
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Only limited experience with overdose is available from clinical studies and post-marketing experience.
Symptoms: Relatively large overdoses (200 mg and 105 mg/day for 3 days, respectively) have been associated with either only symptoms of tiredness, weakness and/or diarrhoea or no symptoms. In the overdose cases below 140 mg or unknown dose the patients revealed symptoms from central nervous system (confusion, drowsiness, somnolence, vertigo, agitation, aggression, hallucination, and gait disturbance) and/or of gastrointestinal origin (vomiting and diarrhoea).
In the most extreme case of overdosage, the patient survived the oral intake of a total of 2000 mg memantine with effects on the central nervous system (coma for 10 days, and later diplopia and agitation). The patient received symptomatic treatment and plasmapheresis. The patient recovered without permanent sequelae.
In another case of a large overdose, the patient also survived and recovered. The patient had received 400 mg memantine orally. The patient experienced central nervous system symptoms such as restlessness, psychosis, visual hallucinations, proconvulsiveness, somnolence, stupor, and unconsciousness.
Treatment: In the event of overdosage, treatment should be symptomatic. No specific antidote for intoxication or overdose is available. Standard clinical procedures to remove active substance material, e.g. gastric lavage, carbo medicinalis (interruption of potential entero-hepatic recirculation), acidification of urine, forced diuresis should be used as appropriate.
In case of signs and symptoms of general CNS overstimulation, careful symptomatic clinical treatment should be considered.
Pharmacotherapeutic group: Anti-dementia drugs, ATC code: N06DX01.
There is increasing evidence that malfunctioning of glutamatergic neurotransmission, in particular at NMDA-receptors, contributes to both expression of symptoms and disease progression in neurodegenerative dementia.
Memantine is a voltage-dependent, moderate-affinity uncompetitive NMDA-receptor antagonist. It modulates the effects of pathologically elevated tonic levels of glutamate that may lead to neuronal dysfunction.
Clinical studies: A pivotal monotherapy study in a population of patients suffering from moderate to severe Alzheimer's disease (mini mental state examination (MMSE) total scores at baseline of 3 - 14) included a total of 252 outpatients. The study showed beneficial effects of memantine treatment in comparison to placebo at 6 months (observed cases analysis for the clinician's interview based impression of change (CIBIC-plus): p=0.025; Alzheimer's disease cooperative study - activities of daily living (ADCS-ADLsev): p=0.003; severe impairment battery (SIB): p=0.002).
A pivotal monotherapy study of memantine in the treatment of mild to moderate Alzheimer's disease (MMSE total scores at baseline of 10 to 22) included 403 patients. Memantine-treated patients showed a statistically significantly better effect than placebo-treated patients on the primary endpoints: Alzheimer's disease assessment scale (ADAS-cog) (p=0.003) and CIBIC-plus (p=0.004) at week 24 (last observation carried forward (LOCF)). In another monotherapy study in mild to moderate Alzheimer's disease a total of 470 patients (MMSE total scores at baseline of 11-23) were randomised. In the prospectively defined primary analysis statistical significance was not reached at the primary efficacy endpoint at week 24.
A meta-analysis of patients with moderate to severe Alzheimer's disease (MMSE total scores < 20) from the six phase III, placebo-controlled, 6-month studies (including monotherapy studies and studies with patients on a stable dose of acetylcholinesterase inhibitors) showed that there was a statistically significant effect in favour of memantine treatment for the cognitive, global, and functional domains. When patients were identified with concurrent worsening in all three domains, results showed a statistically significant effect of memantine in preventing worsening, as twice as many placebo-treated patients as memantine-treated patients showed worsening in all three domains (21% vs. 11%, p<0.0001).
Absorption: Memantine has an absolute bioavailability of approximately 100%. Tmax is between 3 and 8 hours. There is no indication that food influences the absorption of memantine.
Distribution: Daily doses of 20 mg lead to steady-state plasma concentrations of memantine ranging from 70 to 150 ng/ml (0.5 - 1 µmol) with large interindividual variations. When daily doses of 5 to 30 mg were administered, a mean cerebrospinal fluid (CSF)/serum ratio of 0.52 was calculated. The volume of distribution is around 10 l/kg. About 45% of memantine is bound to plasma-proteins.
Biotransformation: In man, about 80% of the circulating memantine-related material is present as the parent compound. Main human metabolites are N-3,5-dimethyl-gludantan, the isomeric mixture of 4- and 6-hydroxy-memantine, and 1-nitroso-3,5-dimethyl-adamantane. None of these metabolites exhibit NMDA-antagonistic activity. No cytochrome P 450 catalysed metabolism has been detected in vitro.
In a study using orally administered 14C-memantine, a mean of 84% of the dose was recovered within 20 days, more than 99% being excreted renally.
Elimination: Memantine is eliminated in a monoexponential manner with a terminal t½ of 60 to 100 hours. In volunteers with normal kidney function, total clearance (Cltot) amounts to 170 ml/min/1.73 m² and part of total renal clearance is achieved by tubular secretion.
Renal handling also involves tubular reabsorption, probably mediated by cation transport proteins. The renal elimination rate of memantine under alkaline urine conditions may be reduced by a factor of 7 to 9 (see section 4.4). Alkalisation of urine may result from drastic changes in diet, e.g. from a carnivore to a vegetarian diet, or from the massive ingestion of alkalising gastric buffers.
Linearity: Studies in volunteers have demonstrated linear pharmacokinetics in the dose range of 10 to 40 mg.
Pharmacokinetic/pharmacodynamic relationship: At a dose of memantine of 20 mg per day the cerebrospinal fluid (CSF) levels match the ki-value (ki = inhibition constant) of memantine, which is 0.5 µmol in human frontal cortex.
In short term studies in rats memantine like other NMDA-antagonists have induced neuronal vacuolisation and necrosis (Olney lesions) only after doses leading to very high peak serum concentrations. Ataxia and other preclinical signs have preceded the vacuolisation and necrosis. As the effects have neither been observed in long term studies in rodents nor in non-rodents, the clinical relevance of these findings is unknown.
Ocular changes were inconsistently observed in repeat dose toxicity studies in rodents and dogs, but not in monkeys. Specific ophthalmoscopic examinations in clinical studies with memantine did not disclose any ocular changes.
Phospholipidosis in pulmonary macrophages due to accumulation of memantine in lysosomes was observed in rodents. This effect is known from other drugs with cationic amphiphilic properties. There is a possible relationship between this accumulation and the vacuolisation observed in lungs. This effect was only observed at high doses in rodents. The clinical relevance of these findings is unknown.
No genotoxicity has been observed following testing of memantine in standard assays. There was no evidence of any carcinogenicity in life long studies in mice and rats. Memantine was not teratogenic in rats and rabbits, even at maternally toxic doses, and no adverse effects of memantine were noted on fertility. In rats, foetal growth reduction was noted at exposure levels that are identical or slightly higher than at human exposure.
Tablet core: Microcrystalline Cellulose (Avicel pH 102), Lactose NF Fast Flow, Croscarmellose Sodium Type A, Colloidal Silicon Dioxide Tablet coating: Hydroxypropyl Methylcellulose, Titanium Dioxide pharma grade, Purified Talc, Polyethylene Glycol MW 6000, Purified Water (10mg) Iron Oxide Yellow, (20mg) Iron Oxide Red |
Not applicable.
Store below 30°C.
White Opaque PVC/PE/PVDC with hard tempered aluminum foil lid.
Each pack contains 30 film coated tablets
No Special Requirements.
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