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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)

What Saxenda® is

Saxenda® is a weight loss medicine that contains the active substance liraglutide. It is similar to a natural occurring hormone called GLP-1 that is released from the intestine after a meal. Saxenda® works by acting on receptors in the brain that control your appetite, causing you to feel fuller and less hungry. This may help you eat less food and reduce your body weight.

 

What Saxenda® is used for

Saxenda® is used for weight loss in addition to diet and exercise in adults aged 18 and above who have:

•                 a BMI of 30 or greater (obese) or

•                 a BMI of 27 and less than 30 (overweight) and weight-related health problems (such as diabetes, high blood pressure, abnormal levels of fats in the blood or breathing problems during sleep called ‘obstructive sleep apnoea’).

BMI (Body Mass Index) is a measure of your weight in relation to your height.

 

You should only continue using Saxenda® if you have lost at least 5% of your initial body weight after 12 weeks on the 3 mg/day dose (see section 3 How to use Saxenda®). Consult your doctor before you continue.

 

Saxenda can be used in adolescents from the age of 12 to below 18 years with obesity as diagnosed by your doctor.

 

Consult with your doctor for the use of Saxenda in adolescents aged 12 to below 18 years.

 

Diet and exercise

Your doctor will start you on a diet and exercise programme. Stay on this programme while you are using Saxenda®.


Do not use Saxenda®

–                if you are allergic to liraglutide or any of the other ingredients of this medicine (listed in section 6 Contents of the pack and other information).

 

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Saxenda®.

The use of Saxenda® is not recommended if you have severe heart failure.

There is little experience with this medicine in patients of 75 years and older. It is not recommended if you are 75 years or older.

There is little experience with this medicine in patients with kidney problems. If you have kidney disease or are on dialysis, consult your doctor.

There is little experience with this medicine in patients with liver problems. If you have liver problems, consult your doctor.

This medicine is not recommended if you have a severe stomach or gut problem which results in delayed stomach emptying (called gastroparesis), or if you have an inflammatory bowel disease.

 

People with diabetes

If you have diabetes, do not use Saxenda® as a replacement for insulin.

 

Inflammation of the pancreas

Talk to your doctor if you have or have had a disease of the pancreas.

 

Gallbladder Problems:

Saxenda may cause gallbladder problems including gallstones. Some gallbladder problems need surgery. Call your healthcare provider if you have any of the following symptoms:

 

·         pain in your upper stomach (abdomen)

·         fever

·         yellowing of your skin or eyes (jaundice)

·         Clay-colored stools

 

Inflamed gall bladder and gallstones

If you lose substantial weight, you are at a risk of gallstones and thereby inflamed gall bladder. Stop taking Saxenda® and contact a doctor immediately if you experience severe pain in your upper abdomen, usually worst on the right side under the ribs. The pain may be felt through to your back or right shoulder. See section 4 Possible side effects.

 

Thyroid disease

If you have thyroid disease, including thyroid nodules and enlargement of the thyroid gland, consult your doctor.

 

Heart rate

Talk to your doctor if you have palpitations (you feel aware of your heartbeat) or if you have feelings of a racing heartbeat while at rest during Saxenda® treatment.

 

Kidney Problems (Kidney Failure):

Saxenda® may cause diarrhea, nausea and vomiting leading to loss of fluids (dehydration). Dehydration may cause kidney failure which can lead to the need for dialysis. This can happen in people who have never had kidney problems before. Drinking plenty of fluids may reduce your chance of dehydration. Call your healthcare provider right away if you have nausea, vomiting, or diarrhea that does not go away, or if you cannot drink liquids by mouth.

 

Loss of fluid and dehydration

When starting treatment with Saxenda®, you may lose body fluid or become dehydrated. This may be due to feeling sick (nausea), being sick (vomiting) and diarrhoea. It is important to avoid dehydration by drinking plenty of fluids. Talk to your doctor, pharmacist or nurse if you have any questions or concerns. See section 4 Possible side effects.

 

Depression or thoughts of suicide:

You should pay attention to any mental changes, especially sudden changes in your mood, behaviors, thoughts, or feelings.

Call your health care provider right away if you have any mental changes that are new, worse, or worry you.

 

 

Children and adolescents

Saxenda® should not be used in children under 12 years of age or in adolescents with a body weight below or equal to 60 kg. This is because the effects of this medicine have not been studied in these sub groups.

 

Other medicines and Saxenda®

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

In particular, tell your doctor, pharmacist or nurse if:

•                 you are taking medicines for diabetes called ‘sulfonylurea’ (such as glimepiride or glibenclamide) or if you are taking insulin – you may get low blood sugar (hypoglycaemia) when you use these medicines with Saxenda®. Your doctor may adjust the dose of your diabetes medicine to prevent you from getting low blood sugar. See section 4 Possible side effects for the warning signs of low blood sugar. If you adjust your insulin dose your doctor may recommend you to monitor your blood sugar more frequently.

•                 you are taking warfarin or other medicines by mouth that reduce your blood clotting (anticoagulants). More frequent blood testing to determine the ability of your blood to clot may be required.

 

Pregnancy and breast-feeding

 

Do not use Saxenda® if you are pregnant, think that you might be pregnant or are planning to have a baby. This is because it is not known if Saxenda® may affect the baby.

Do not breast-feed if you are using Saxenda®. This is because it is not known if Saxenda® passes into breast milk.

 

Driving and using machines

Saxenda® is unlikely to affect your ability to drive and use machines. If you need any further information, talk to your doctor, pharmacist or nurse.


Always use Saxenda® exactly as your doctor has told you. Check with your doctor, pharmacist or nurse if you are not sure.

Your doctor will start you on a diet and exercise programme. Stay on this programme while you are using Saxenda®.

 

How much to inject

Your treatment will start at a low dose which will be gradually increased over the first five weeks of treatment.

•                 When you first start using Saxenda®, the starting dose is 0.6 mg once a day, for at least one week.

•                 You should increase your dose by 0.6 mg each week until you reach the recommended dose of

3.0 mg once a day.

 

Your doctor will tell you how much Saxenda® to use each week. Usually, you will be told to follow the table below.

 

Week

Dose injected

Week 1

0.6 mg once a day

Week 2

1.2 mg once a day

Week 3

1.8 mg once a day

Week 4

2.4 mg once a day

Week 5 onwards

3.0 mg once a day

 

Once you reach the recommended dose of 3.0 mg in week 5 of treatment, keep using this dose until your treatment period ends. Do not increase your dose further.

Your doctor will assess your treatment on a regular basis.

 

How and when to use Saxenda®

•                 Before you use the pen for the first time, your doctor or nurse will show you how to use the pen.

•                 You can use Saxenda® at any time of the day, with or without food and drink.

•                 Use Saxenda® at about the same time each day – choose a time of the day that works best for you.

 

Where to inject

Saxenda® is given as an injection under the skin (subcutaneous injection).

•                 The best places to inject are the front of your waist (abdomen), the front of your thighs or your upper arm.

•                 Do not inject into a vein or muscle.

Detailed instructions for use are provided on the other side of this leaflet.

 

People with diabetes

 

Tell your doctor if you have diabetes. Your doctor may adjust the dose of your diabetes medicines to prevent you from getting low blood sugar.

•                 Do not mix Saxenda® up with other medicines that you inject (e.g. insulins).

•                 Do not use Saxenda® in combination with other medicines that contain GLP-1 receptor agonists (such as exenatide or lixisenatide).

 

If you use more Saxenda® than you should

If you use more Saxenda® than you should, talk to a doctor or go to a hospital straight away. Take the medicine pack with you. You may need medical treatment. The following effects may happen:

•                 feeling sick (nausea)

•                 being sick (vomiting).

•                 low blood sugar (hypoglycaemia). Please refer to ‘Common side effects’ for warning signs of low blood sugar.

 

If you forget to use Saxenda®

•                 If you forget a dose and remember it within 12 hours from when you usually take the dose, inject it as soon as you remember.

•                 However, if more than 12 hours have passed since you should have used Saxenda®, skip the missed dose and inject your next dose the following day at the usual time.

•                 Do not use a double dose or increase the dose on the following day to make up for the missed dose.

 

If you stop using Saxenda®

Do not stop using Saxenda® without talking to your doctor.

 

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

 


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

 

Serious side effects

 
 

Risk of thyroid C-cell tumors

Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Saxenda causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.

Saxenda is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with use of Saxenda and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Saxenda.

 

 

 

 

 

 

  

 

 

 

 

 

Some severe allergic reactions (anaphylaxis) have been reported rarely in patients using Saxenda®. You should see your doctor straight away if you get symptoms such as breathing problems, swelling of face and throat and a fast heartbeat.

Cases of inflammation of the pancreas (pancreatitis) have been reported uncommonly in patients using Saxenda®. Pancreatitis is a serious, potentially life-threatening medical condition.

Stop taking Saxenda® and contact a doctor immediately if you notice any of the following serious side effects:

•                 Severe and persistent pain in the abdomen (stomach area) which might reach through to your back, as well as nausea and vomiting, as it could be a sign of an inflamed pancreas (pancreatitis).

 

Other side effects

Very common: may affect more than 1 in 10 people

•                 Feeling sick (nausea), being sick (vomiting), diarrhoea, constipation, headache – these usually go away after a few days or weeks.

 

Common: may affect up to 1 in 10 people

•                 Problems affecting the stomach and intestines, such as indigestion (dyspepsia), inflammation in the lining of the stomach (gastritis), stomach discomfort, upper stomach pain, heartburn, feeling bloated, wind (flatulence), belching and dry mouth

•                 Feeling weak or tired

•                 Changed sense of taste

•                 Dizziness

•                 Difficulty sleeping (insomnia). This usually occurs the first 3 months of treatment

•                 Gallstones

•                 Rash

•                 Injection site reactions (such as bruising, pain, irritation, itching and rash)

•                 Low blood sugar (hypoglycaemia). The warning signs of low blood sugar may come on suddenly and can include: cold sweat, cool pale skin, headache, fast heartbeat, feeling sick, feeling very hungry, changes in vision, feeling sleepy, feeling weak, being nervous, being anxious, confusion, difficulty concentrating and shaking (tremor). Your doctor will tell you how to treat low blood sugar and what to do if you notice these warning signs

•                 Increase of pancreatic enzymes, such as lipase and amylase.

 

Uncommon: may affect up to 1 in 100 people

•                 Loss of fluids (dehydration). This is more likely to occur at the start of treatment and may be due to being sick (vomiting), feeling sick (nausea) and diarrhoea

•                 Delay in the emptying of the stomach

•                 Inflamed gall bladder

•                 Allergic reactions including skin rash

•                 Feeling generally unwell

•                 Faster pulse.

 

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

•                 Reduced kidney function

•                 Acute kidney failure. Signs may include reduction in urine volume, metallic taste in mouth and easily bruising.

 

Not known:

·        Bowel obstruction.

 

Reporting of side effects

If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, nurse or pharmacist.

 

To report any side effect(s):

The National Pharmacovigilance Centre (NPC):

·         Fax: +966-11-205-7662

·         SFDA Call Center: 19999

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

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

 


Keep this medicine out of the sight and reach of children. Do not use Saxenda® after the expiry date which is stated on the pen label and carton after ‘Expiry’. The expiry date refers to the last day of that month.

 

Before first use

Store in a refrigerator (2°C to 8°C). Do not freeze. Keep away from the freezer compartment.

 

Once you start using the pen

You can keep the pen for 1 month when stored at a temperature below 30°C or in a refrigerator (2°C to 8°C). Do not freeze. Keep away from the freezer compartment. When you are not using the pen, keep the pen cap on in order to protect it from light. Do not use this medicine if the solution is not clear and colourless or almost colourless.

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.


What Saxenda® contains

–                The active substance is liraglutide. 1 ml solution for injection contains 6 mg liraglutide. One pre-filled pen contains 18 mg liraglutide.

–                The other ingredients are disodium phosphate dihydrate, propylene glycol, phenol, hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injections.


What Saxenda® looks like and contents of the pack Saxenda® is supplied as a clear and colourless or almost colourless solution for injection in a pre-filled pen. Each pen contains 3 ml solution and is able to deliver doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg and 3.0 mg. Saxenda® is available in pack sizes containing 1, 3 or 5 pens. Not all pack sizes may be marketed. Needles are not included.

Novo Nordisk A/S

Novo Allé

DK-2880 Bagsværd

Denmark


Jan/2024
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

ما المقصود بالدواء ساكسِندا

ساكسِندا عبارة عن دواء لإنقاص الوزن يحتوي على المادة الفعالة ليراجلوتايد. تُشبه هذه المادة هرموناً طبيعياً يسمى جي إل بي -1 يُفرز من الأمعاء بعد تناول الطعام. يعمل ساكسِندا على المستقبلات الموجودة في الدماغ والتي تتحكم في الشهية، مما يسبب لك الشعور بالشبع ويقلل الرغبة في تناول الطعام. وقد يساعدك هذا على تقليل الحاجة إلى تناول الطعام وبالتالي إنقاص وزن الجسم.

 

دواعي استعمال ساكسِندا

يُستعمل ساكسِندا لإنقاص الوزن بالإضافة إلى اتباع حمية غذائية وممارسة الرياضة البالغين من عمر 18 سنة فما فوق والذين لديهم:

•        مؤشر كتلة جسم 30 أو أكثر (سمنة) أو

•        مؤشر كتلة الجسم 27 وأقل من 30 (وزن زائد) مع وجود مشاكل صحية مرتبطة بالوزن (مثل السكري وارتفاع ضغط الدم ومستويات الدهون غير الطبيعية في الدم أو مشاكل التنفس أثناء النوم تسمى "انقطاع النفس الانسدادي النومي").

مؤشر كتلة الجسم هو مقياس لوزن جسمك بالنسبة إلى طولك.

 

يجب أن تستمر فقط في استعمال ساكسِندا إذا كنت قد فقدت 5% على الأقل من وزن الجسم الأوّلي بعد 12  أسبوعاً من استخدام جرعة 3 ملجم/اليوم (انظر القسم 3 كيفية استخدام ساكسِندا). استشر طبيبك قبل الاستمرار.

 

يمكن استخدام ساكسِندا لدى المراهقين من سن 12 إلى أقل من 18 عامًا ويعانون من السمنة على حسب تشخيص طبيبك.

 

استشر طبيبك لاستخدام ساكسِندا في المراهقين الذين تتراوح أعمارهم بين 12 إلى أقل من 18 عامًا.

 

الحمية الغذائية وممارسة الرياضة

سيطلب منك الطبيب اتباع حمية غذائية وبرنامج رياضي معين. يجب الاستمرار في هذا البرنامج أثناء استخدام ساكسِندا.

 

يُحظر استعمال ساكسِندا في الحالات التالية

–        إذا كان لديك حساسية من مادة ليراجلوتايد أو أي من المكونات الأخرى لهذا الدواء (المدرجة في القسم 6 محتويات العبوة ومعلومات أخرى).

 

تحذيرات واحتياطات

استشر الطبيب أو الصيدلي أو الممرضة قبل استخدام ساكسِندا.

لا يُوصى باستعمال ساكسِندا إذا كنت تعاني من قصور شديد في القلب.

توجد تجارب قليلة متوفرة حول استعمال هذا الدواء مع المرضى في عُمر 75 سنة فما  فوق. ولذلك لا يوصى باستعماله إذا كنت تبلغ من العمر 75 سنة أو أكثر.

توجد تجارب قليلة متوفرة حول استعمال هذا الدواء في المرضى الذين يعانون من مشاكل في الكلى. فإذا كنت مصاباً بمرض في الكلى أو تقوم بإجراء غسيل للكلى، يجب عليك استشارة طبيبك.

توجد تجارب قليلة متوفرة حول استعمال هذا الدواء في المرضى الذين يعانون من مشاكل في الكبد. فإذا كنت تعاني من مشاكل في الكبد يجب عليك استشارة طبيبك.

لا يُنصح باستعمال هذا الدواء إذا كنت تعاني من مشكلة شديدة في المعدة أو الأمعاء تؤدي إلى إفراغ المعدة المتأخر (خزل المعدة)، أو إذا كنت مصاباً بمرض التهاب الأمعاء.

 

مرضى السكري

إذا كنت مريضاً بالسكري فلا تستعمل ساكسِندا كبديل للإنسولين.

 

التهاب البنكرياس

تحدث إلى طبيبك إذا كنت مصاباً بمرض في البنكرياس حالياً أو سابقاً.

 

مشاكل المرارة

قد يسبب ساكسِندا مشاكل في المرارة بما في ذلك حصوات المرارة وقد تحتاج بعض مشاكل المرارة إلى الجراحة. اتصل بطبيبك إذا كان لديك أي من الأعراض التالية:

 

• ألم في الجزء العلوي من معدتك (البطن)

• حمى

• اصفرار بشرتك أو عينيك (اليرقان)

• براز بلون الطين

 

التهاب المرارة وحصوات المرارة

إذا فقدت قدراً كبيراً من الوزن، فقد تكون معرضاً لخطر الإصابة بحصوات في المرارة، وبالتالي التهاب المرارة. يجب عليك التوقف عن استعمال ساكسِندا والاتصال بالطبيب فوراً إذا كنت تعاني من ألم شديد في الجزء العلوي من البطن، وعادة ما يكون بدرجة أسوأ عند الجانب الأيمن أسفل القفص الصدري. ويمكن الشعور بالألم في الظهر أو الكتف الأيمن. اطلع على قسم 4، الآثار الجانبية المحتملة.

 

مرض الغدة الدرقية

إذا كنت مصاباً بمرض الغدة الدرقية، بما في ذلك العقيدات الدرقية وتضخم الغدة الدرقية، يجب عليك استشارة طبيبك.

 

معدل ضربات القلب

تحدث إلى طبيبك إذا كنت تعاني من خفقان (تشعر بنبض قلبك بشكل واضح) أو إذا كنت تشعر بسرعة ضربات القلب أثناء الراحة خلال استعمال ساكسِندا.

 

مشاكل الكلى (الفشل الكلوي)

قد يسبب ساكسِندا الإسهال والغثيان والقيء مما يؤدي إلى فقدان السوائل (الجفاف). قد يؤدي الجفاف إلى فشل كلوي يمكن أن يؤدي إلى الحاجة إلى غسيل الكلى. يمكن أن يحدث هذا في الأشخاص الذين لم يسبق لهم أن عانوا من مشاكل في الكلى من قبل. قد يؤدي شرب الكثير من السوائل إلى تقليل فرصتك في الإصابة بالجفاف. اتصل بطبيبك على الفور إذا كنت تعاني من غثيان أو قيء أو إسهال لا يختفي ، أو إذا كنت لا تستطيع شرب السوائل عن طريق الفم.

 

فقدان سوائل الجسم والجفاف

عند بدء العلاج بساكسِندا، قد تفقد سوائل الجسم أو تُصاب بالجفاف. وقد يكون ذلك بسبب الشعور بالمرض (الغثيان والقيء والإسهال). ولذلك يجب الحرص على عدم الإصابة بالجفاف عن طريق شرب الكثير من السوائل. كما يجب التحدث مع الطبيب أو الصيدلي أو الممرضة إذا كانت لديك أي أسئلة أو مخاوف. اطلع على قسم 4، الآثار الجانبية المحتملة.

 

الاكتئاب أو أفكار الانتحار

يجب أن تنتبه لأي تغيرات عقلية ، خاصة التغيرات المفاجئة في مزاجك أو سلوكك أو أفكارك أو مشاعرك.

اتصل بطبيبك على الفور إذا كان لديك أي تغييرات عقلية تقلقك أو تغييرات عقلية جديدة .

 

الأطفال والمراهقون

ينبغي عدم استعمال ساكسِندا مع الأطفال  الذين تقل أعمارهم عن 12 سنة أو المراهقين الذين تقل أوزانهم عن 60 كجم. وذلك لأنه لم تُدرس آثار هذا الدواء على هذه الفئات العمرية.

 

الأدوية الأخرى وساكسِندا

يُرجى إخبار طبيبك أو الصيدلي أو الممرضة إذا كنت تتناول أدوية أخرى أو تناولت أي أدوية أخرى مؤخراً أو قد تتناول أدوية أخرى في المستقبل.

كما يُرجى إخبار طبيبك أو الصيدلي أو الممرضة إذا:

•        كنت تستعمل أدوية للسكري تسمى "سالفونيل يوريا" (مثل جليمبيرايد أو جليبنكلاميد) أو إذا كنت تتناول الإنسولين - فقد تتعرض لهبوط نسبة السكر في الدم عند استخدام هذه الأدوية مع ساكسِندا. وقد يقوم الطبيب بتعديل جرعة دواء السكري لمنعك من الإصابة بانخفاض نسبة السكر في الدم. راجع القسم 4 الآثار الجانبية المحتملة للعلامات التحذيرية لانخفاض نسبة السكر في الدم. إذا قمت بتعديل جرعة الإنسولين، فقد يوصي طبيبك بمراقبة نسبة السكر في الدم لديك بمعدل أكبر.

•        كنت تتناول الوارفارين أو أدوية أخرى تؤخذ عن طريق الفم وتقلل من تخثر الدم (مضادات التخثر). فقد تكون هناك حاجة لإجراء مزيد من الفحوصات الدموية لتحديد مستوى قدرة دمك على التخثر.

 

الحمل والرضاعة الطبيعية

يجب عدم استخدام ساكسِندا إذا كنتِ حاملاً أو قد تكوني حاملاً أو تخططين للحمل. لأنه من غير المعروف ما إذا كان ساكسِندا له تأثير على الجنين أم لا.

ويجب عليكِ عدم الرضاعة الطبيعية إذا كنتِ تستخدمين ساكسِندا. لأنه من غير المعروف ما إذا كان ساكسِندا ينتقل إلى لبن الأم أم لا.

 

القيادة واستخدام الآلات

من غير المحتمل أن يؤثر ساكسِندا على القيادة واستخدام الآلات. إذا كانت لديك أي استفسارات أخرى استشر طبيبك أو الصيدلي أو الممرضة.

 

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يجب استخدام ساكسِندا دوماً وفق إرشادات طبيبك. ويجب استشارة طبيبك أو الصيدلي أو الممرضة في حالة عدم التأكد من طريقة الاستخدام.

سيطلب منك الطبيب اتباع حمية غذائية وبرنامج رياضي معين. يجب الاستمرار في هذا البرنامج أثناء استخدام ساكسِندا.

 

مقدار الجرعة

يبدأ العلاج بأخذ جرعة منخفضة، ثم تزداد الجرعة تدريجياً خلال الأسابيع الخمس الأولى من العلاج.

•        عند البدء في استخدام ساكسِندا لأول مرة، تكون الجرعة المبدئية 0.6 ملجم مرة واحدة في اليوم لمدة أسبوع واحد على الأقل.

•        يجب زيادة الجرعة بمقدار 0.6 ملجم كل أسبوع حتى تصل إلى الجرعة الموصى بها والتي قدرها 3.0 ملجم، مرة واحدة في اليوم.

 

سيخبرك طبيبك بمقدار الجرعة التي تأخذها من ساكسِندا كل أسبوع. عادةً سيطلب منك طبيبك إتباع الجدول التالي.

 

الأسبوع

الجرعة المحقونة

الأسبوع الأول

0.6 ملجم مرة واحدة في اليوم

الأسبوع الثاني

1.2 ملجم مرة واحدة في اليوم

الأسبوع الثالث

1.8 ملجم مرة واحدة في اليوم

الأسبوع الرابع

2.4 ملجم مرة واحدة في اليوم

الأسبوع الخامس وما بعده

3.0 ملجم مرة واحدة في اليوم

 

عند الوصول إلى الجرعة الموصى بها 3.0 ملجم في الأسبوع الخامس، يجب الاستمرار في هذه الجرعة حتى نهاية مدة العلاج. فلا تأخذ جرعة زائدة عن هذه الجرعة.

سيقوم طبيبك بتقييم مدى فعالية علاجك بصفة منتظمة.

 

كيفية استخدام ساكسِندا ومواعيد أخذ الجرعة

•        قبل استخدام قلم الحقن المعبأ مسبقاَ لأول مرة، سوف يوضح لك الطبيب أو الممرضة كيفية استخدامه.

•        يمكن استخدام ساكسِندا في أي وقت من اليوم مع الطعام أو الشراب أو بدونهما.

•        ينبغي الحرص على استخدام ساكسِندا في وقت واحد محدد كل يوم - ينبغي اختيار الوقت الأنسب لك.

 

موضع الحقن

تؤخذ جرعة ساكسِندا كحقنة تحت الجلد.

•        أفضل أماكن للحقن هي الجزء الأمامي من الخصر (البطن) ومقدمة الفخذ والجزء العلوي من الذراعين.

•        لا يُحقن في الوريد أو العضل.

التعليمات المفصلة للاستخدام موضحة في الجانب الآخر من هذه النشرة.

 

مرضى السكري

يرجى إبلاغ طبيبك إذا كنت تعاني من داء السكري. فقد يقوم طبيبك بتعديل الجرعة التي تأخذها من أدوية السكري لوقايتك من انخفاض مستوى السكر في الدم.

•        لا تمزج ساكسِندا مع أدوية أخرى (مثل الإنسولين) في حقنة واحدة.

•        لا تستخدم ساكسِندا مع أدوية أخرى محتوية على ناهضات مستقبلات جي إل بي- 1 (مثل إكسيناتيد أو ليكيسيناتيد).

 

في حالة أخذ جرعة زائدة من ساكسِندا عن الجرعة الموصوفة

في حالة أخذ جرعة زائدة من ساكسِندا عن الجرعة الموصوفة، استشر طبيبك أو اذهب إلى المستشفى على الفور. ينبغي أخذ عبوة الدواء معك. فقد تحتاج إلى علاج طبي. وقد تحدث الآثار التالية:

•        شعور بالتوعك (غثيان)

•        التوعك (القيء).

•        انخفاض السكر في الدم (هبوط سكر الدم). ‏‫يُرجى الرجوع إلى "الآثار الجانبية الشائعة" للاطلاع على العلامات التحذيرية لانخفاض نسبة السكر في الدم.

 

في حالة نسيان جرعة ساكسِندا

•        في حالة نسيان الجرعة وتذكرها خلال 12 ساعة من موعدها المعتاد، خذ هذه الجرعة بمجرد تذكرها.

•        إذا انقضى أكثر من 12 ساعة من موعد جرعة ساكسِندا، اترك الجرعة المنسية وخذ الجرعة التالية في اليوم التالي في موعدها المحدد.

•        لا تأخذ جرعة مضاعَفة ولا تزد مقدار الجرعة الموصوفة لك في اليوم التالي لتعويض الجرعة الفائتة.

 

 

في حالة التوقف عن استخدام ساكسِندا

لا تتوقف عن استعمال ساكسِندا دون استشارة طبيبك.

 

إذا كانت لديك أي أسئلة أخرى بشأن استخدام هذا الدواء، استشر طبيبك أو الصيدلي أو الممرضة.

 

 

كما هو حال جميع الأدوية، يمكن أن يسبب هذا الدواء آثاراً جانبية، ولكن لا يُصاب بها الجميع.

 

الآثار الجانبية الخطيرة

 
 

 

خطورة الإصابة بسرطان الغدة الدرقية

- ليراجلوتايد يحدث سرطان الغدة الدرقية بالقوارض من خلال الدراسات الإكلينيكية التي أجريت عليهم، ومن غير المعروف أذا كان ساكسندا يسبب سرطان الغدة الدرقية، بما في ذلك سرطان الغدة الدرقية النخاعي، في البشر، حيث انه لا يمكن تحديد ذلك.

 

- يمنع استخدام ساكسندا للمرضى الذين يشمل تاريخهم الشخصي أو العائلي على سرطان الغدة الدرقية النخاعي أو المرضى الذين يعانون من متلازمة تكون الورم الصماوي المتعدد.

 

وردت تقارير عن حدوث تفاعلات تحسسية حادة (تأقٍ) في حالات نادرة من المرضى الذين استخدموا ساكسِندا. ولذلك يجب الذهاب إلى الطبيب على الفور عند حدوث أعراض مثل اضطرابات التنفس وتورم الوجه والحلق وتسرع في نبضات القلب.

وردت تقارير عن حالات التهاب البنكرياس بشكل غير شائع في المرضى الذين استخدموا ساكسِندا. يُعد التهاب البنكرياس حالة مرضية خطيرة ومهددة للحياة.

يجب التوقف عن استخدام ساكسِندا وإخبار طبيبك فوراً عند ملاحظة أي من الآثار الجانبية التالية:

•        ألم شديد متواصل في البطن (منطقة المعدة) قد تشعر به في الظهر، وغثيان وقيء، لأن هذه الأعراض قد تكون أعراضاً لالتهاب البنكرياس.

 

الآثار الجانبية الأخرى

شائعة جداً: يمكن أن تصيب أكثر من مريض واحد من بين 10 مرضى

•        شعور بالتوعك (غثيان)، توعك (قيء)، إسهال، إمساك، صداع - عادةً ما تزول هذه الأعراض بعد عدة أيام أو أسابيع قليلة.

 

شائعة: يمكن أن تصيب مريضاً واحداً من بين 10 مرضى

•        اضطرابات في المعدة والأمعاء، مثل عسر الهضم والتهاب بطانة المعدة (التهاب المعدة)، واضطراب المعدة، وألم في أعلى المعدة، وحرقة المعدة، وشعور بالانتفاخ، وريح وتجشؤ وجفاف الفم.

•        شعور بالضعف أو التعب

•        تغير في حاسة التذوق

•        دوار

•        صعوبة في النوم (أرق). عادةً ما تحدث هذه الأعراض في الأشهر الثلاث الأولى من العلاج

•        حصوات في المرارة

•         طفح جلدي

•        حساسية في موضع الحقن (تشمل كدمات، أو شعور بألم، أو تهيج، أو طفح جلدي)

•        انخفاض السكر في الدم (نقص جلوكوز الدم وقد تحدث العلامات التحذيرية لانخفاض مستوى السكر في الدم فجأة ويمكن أن تشمل: عرق بارد، شحوب وبرودة الجلد، صداع، تسرع في نبضات القلب، شعور بالتعب، شعور بالجوع الشديد، تغيرات في الرؤية، شعور بالنعاس، شعور بالضعف، شعور بالتوتر، قلق، ارتباك، صعوبة في التركيز، رعشة. ‏‫سيخبرك طبيبك بكيفية علاج انخفاض مستوى السكر في الدم وماذا تفعل عند ملاحظة هذه العلامات التحذيرية.

•        زيادة في إنزيمات البنكرياس، مثل الليباز والأميليز.

غير شائعة: يمكن أن تصيب مريضاً واحداً من بين 100 مريض

•        فقدان سوائل الجسم (جفاف). يزيد احتمال حدوث هذا العارض في بداية العلاج، وقد يحدث بسبب التوعك (القيء) والشعور بالتوعك (الغثيان) والإسهال

•        تأخر في إفراغ المعدة

•        التهاب المرارة

•        حساسية تشمل الطفح الجلدي

•        شعور بعدم الارتياح بشكل عام

•        زيادة سرعة نبض القلب.

 

نادرة: يمكن أن تصيب مريضاً واحداً من بين 1000 مريض

•        قصور وظائف الكلى

•        فشل كلوي حاد. يمكن أن تشمل الأعراض نقص كمية البول وطعم معدني في الفم وحدوث كدمات بسهولة.

 

غير معروفة (لا يمكن تقدير معدل انتشارها من البيانات المتاحة)

•         انسداد معوي

 

 

الإبلاغ عن الآثار الجانبية

في حال تفاقم أي من الآثار الجانبية أو إذا لاحظت ظهور آثار جانبية غير مذكورة في هذه النشرة، يُرجى إخبار طبيبك أو الممرضة أو الصيدلي.

المركز الوطني للتيقظ والسلامة الدوائية:

·    فاكس: +966-11-205-7662

·    للاتصال بالمركز الموحد للهيئة العامة للغذاء والدواء 19999

·    بريد الالكتروني: npc.drug@sfda.gov.sa

·    الموقع  الالكتروني: https://ade.sfda.gov.sa

 

يُحفظ هذا الدواء بعيداً عن متناول ومرأى الأطفال. لا تستخدم ساكسِندا بعد تاريخ انتهاء الصلاحية الذي يظهر على ملصق قلم الحقن والعبوة الخارجية بعد كلمة "Expiry". يشير تاريخ الانتهاء إلى آخر يوم في ذلك الشهر.

 

قبل الاستخدام لأول مرة

يُخزن الدواء في الثلاجة (عند درجة حرارة 2 إلى 8 درجات مئوية) يُراعى عدم التجميد. ويُحفظ بعيداً عن وحدة التجميد.

 

بعد البدء في استخدام قلم الحقن

يمكنك الاحتفاظ بالقلم لمدة شهر واحد في حالة حفظه في درجة حرارة أقل من 30 درجة مئوية أو في الثلاجة (عند درجة حرارة 2 إلى 8 درجات مئوية). يُراعى عدم التجميد. ويُحفظ بعيداً عن وحدة التجميد. وعند عدم استخدام القلم يرجى تغطيته بالغطاء لحمايته من الضوء. كما يرجى عدم استخدام هذا الدواء إذا كان المحلول غير صافٍ وغير عديم اللون أو غير عديم اللون تقريباً.

لا تلقِ أي أدوية في الفضلات السائلة أو الفضلات المنزلية. اسأل الصيدلي بشأن كيفية التخلص من الأدوية التي لم تعد تستعملها. هذه الإجراءات ستساعد على حماية البيئة.

محتويات ساكسِندا

–        المادة الفعَّالة هي ليراجلوتايد. يحتوي كل 1 مل من محلول الحقن على 6 ملجم من مادة ليراجلوتايد. ويحتوي كل قلم حقن معبأ مسبقاً على 18 ملجم من مادة ليراجلوتايد.

–        المكونات الأخرى هي ثنائي هيدرات فوسفات ثنائي الصوديوم، وبروبيلين جلايكول، فينول، وحمض هيدروكلوريك وهيدروكسيد صوديوم (لتعديل درجة الحموضة)، وماء للحقن.

 

شكل ساكسِندا ومحتويات العبوة

يأتي ساكسِندا في شكل محلول صافٍ عديم اللون أو عديم اللون تقريباً للحقن في قلم معبأ مسبقاً. يحتوي كل قلم على 3 مل المحلول ويعطي جرعات 0.6 ملجم و1.2 ملجم و1.8 ملجم و2.4 ملجم و3.0 ملجم. ويأتي ساكسِندا في عبوات بها قلم واحد أو 3 أقلام أو 5 أقلام. لا تتوفر جميع أحجام العبوات في بعض الأسواق. الإبر غير مرفقة.

Novo Nordisk A/S

Novo Allé

DK-2880 Bagsværd

Denmark

يناير/2024
 Read this leaflet carefully before you start using this product as it contains important information for you

Saxenda 6 mg/ml solution for injection in pre-filled pen Warning: Risk of thyroid C-cell tumors Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Saxenda® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined. Saxenda® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with use of Saxenda® and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Saxenda®

1 ml of solution contains 6 mg of liraglutide*. One pre-filled pen contains 18 mg liraglutide in 3 ml. *human glucagon-like peptide-1 (GLP-1) analogue produced by recombinant DNA technology in Saccharomyces cerevisiae. For the full list of excipients, see section 6.1.

Solution for injection. Clear and colourless or almost colourless, isotonic solution; pH=8.15.

Adults

 

Saxenda is indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adult patients with an initial Body Mass Index (BMI) of

•                 30 kg/m² (obesity), or

•                 27 kg/m² to <30 kg/m² (overweight) in the presence of at least one weight-related comorbidity such as dysglycaemia (prediabetes or type 2 diabetes mellitus), hypertension, dyslipidaemia or obstructive sleep apnoea.

 

Treatment with Saxenda should be discontinued after 12 weeks on the 3.0 mg/day dose if patients have not lost at least 5% of their initial body weight.

 

Adolescents

 

Saxenda can be used as an adjunct to a healthy nutrition and physical activity counselling for weight management in adolescent patients from the age of 12 years and above with:

 

•                 body weight above 60 kg and

•                 obesity (BMI corresponding to ≥30 kg/m2 for adults by international cut-off points)*.

 

*IOTF BMI cut-off points for obesity by sex between 12–18 years (see table 1):

 

Table 1 IOTF BMI cut-off points for obesity by sex between 12–18 years

Age (years)

Body mass index 30 kg/m2

Males

Females

12

26.02

26.67

12.5

26.43

27.24

13

26.84

27.76

13.5

27.25

28.20

14

27.63

28.57

14.5

27.98

28.87

15

28.30

29.11

15.5

28.60

29.29

16

28.88

29.43

16.5

29.14

29.56

17

29.41

29.69

17.5

29.70

29.84

18

30.00

30.00


Posology

 

The starting dose is 0.6 mg once daily. The dose should be increased to 3.0 mg once daily in increments of 0.6 mg with at least one week intervals to improve gastro-intestinal tolerability (see table 2). If escalation to the next dose step is not tolerated for two consecutive weeks, consider discontinuing treatment. Daily doses higher than 3.0 mg are not recommended.

 

Table 2 Dose escalation schedule

 

Dose

Weeks

 

Dose escalation 4 weeks

0.6 mg

1

1.2 mg

1

1.8 mg

1

2.4 mg

1

Maintenance dose

3.0 mg

 

Missed doses

 

If a dose is missed within 12 hours from when it is usually taken, the patient should take the dose as soon as possible. If there is less than 12 hours to the next dose, the patient should not take the missed dose and resume the once-daily regimen with the next scheduled dose. An extra dose or increase in dose should not be taken to make up for the missed dose.

 

Patients with type 2 diabetes mellitus

 

Saxenda should not be used in combination with another GLP-1 receptor agonist.

 

When initiating Saxenda, it should be considered to reduce the dose of concomitantly administered insulin or insulin secretagogues (such as sulfonylureas) to reduce the risk of hypoglycaemia. Blood glucose self-monitoring is necessary to adjust the dose of insulin or insulin-secretagogues (see section 4.4).

 

Special populations

 

Elderly (≥65 years old)

No dose adjustment is required based on age. Therapeutic experience in patients ≥75 years of age is limited and use in these patients is not recommended (see sections 4.4 and 5.2).

 

Renal impairment

No dose adjustment is required for patients with mild or moderate renal impairment (creatinine clearance ≥30 ml/min). Saxenda is not recommended for use in patients with severe renal impairment (creatinine clearance <30 ml/min) including patients with end-stage renal disease (see sections 4.4, 4.8 and 5.2).

 

Hepatic impairment

No dose adjustment is recommended for patients with mild or moderate hepatic impairment. Saxenda is not recommended for use in patients with severe hepatic impairment and should be used cautiously in patients with mild or moderate hepatic impairment (see sections 4.4 and 5.2).

 

Paediatric population

 

For adolescents from the age of 12 to below 18 years old a similar dose escalation schedule as for adults should be applied (see table 2). The dose should be increased until 3.0 mg (maintenance dose) or maximum tolerated dose has been reached. Daily doses higher than 3.0 mg are not recommended. The safety and efficacy of Saxenda in children and adolescents below 12 years of age have not been established (see section 5.1).

 

Method of administration

 

Saxenda is for subcutaneous use only. It must not be administered intravenously or intramuscularly.

 

Saxenda is administered once daily at any time, independent of meals. It should be injected in the abdomen, thigh or upper arm. The injection site and timing can be changed without dose adjustment. However, it is preferable that Saxenda is injected around the same time of the day, when the most convenient time of the day has been chosen.

 

For further instructions on administration, see section 6.6.

 


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

Traceability

 

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

 

Patients with heart failure

 

There is no clinical experience in patients with congestive heart failure New York Heart Association (NYHA) class IV, and liraglutide is therefore not recommended for use in these patients.

 

Special populations

 

The safety and efficacy of liraglutide for weight management have not been established in patients:

–                aged 75 years or more,

–                treated with other products for weight management,

 

–                with obesity secondary to endocrinological or eating disorders or to treatment with medicinal products that may cause weight gain,

–                with severe renal impairment,

–                with severe hepatic impairment.

Use in these patients is not recommended (see section 4.2).

As liraglutide for weight management was not investigated in subjects with mild or moderate hepatic impairment, it should be used with caution in these patients (see sections 4.2 and 5.2).

 

There is limited experience in patients with inflammatory bowel disease and diabetic gastroparesis. Use of liraglutide is not recommended in these patients since it is associated with transient gastrointestinal adverse reactions, including nausea, vomiting and diarrhoea.

 

Pancreatitis

 

Acute pancreatitis has been observed with the use of GLP-1 receptor agonists. Patients should be informed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, liraglutide should be discontinued; if acute pancreatitis is confirmed, liraglutide should not be restarted.

 

Acute Gallbladder Disease

 

In Saxenda clinical trials, 2.2% of Saxenda-treated patients reported adverse events of cholelithiasis versus 0.8% of placebo-treated patients. The incidence of cholecystitis was 0.8% in Saxenda-treated patients versus 0.4% in placebo-treated patients. The majority of Saxenda-treated patients with adverse events of cholelithiasis and cholecystitis required cholecystectomy. Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in Saxenda-treated patients than in placebo-treated patients even after accounting for the degree of weight loss. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated. Cholelithiasis and cholecystitis may lead to hospitalisation and cholecystectomy. Patients should be informed of the characteristic symptoms of cholelithiasis and cholecystitis.

 

Thyroid disease

 

In clinical trials in type 2 diabetes, thyroid adverse events, such as goitre, have been reported in particular in patients with pre-existing thyroid disease. Liraglutide should therefore be used with caution in patients with thyroid disease.

 

Heart rate

 

An increase in heart rate was observed with liraglutide in clinical trials (see section 5.1). Heart rate should be monitored at regular intervals consistent with usual clinical practice. Patients should be informed of the symptoms of increased heart rate (palpitations or feelings of a racing heartbeat while at rest). For patients who experience a clinically relevant sustained increase in resting heart rate, treatment with liraglutide should be discontinued.

 

Renal Impairment

 

In patients treated with GLP-1 receptor agonists, including Saxenda, there have been reports of acute renal failure and worsening of chronic renal failure, sometimes requiring hemodialysis. Some of these events were reported in patients without known underlying renal disease. A majority of the reported events occurred in patients who had experienced nausea, vomiting, and/or diarrhea leading to volume depletion. Some of the reported events occurred in patients receiving one or more medications known to affect renal function or volume status. Altered renal function has been reversed in many of the reported cases with supportive treatment and discontinuation of potentially causative agents, including liraglutide. Use caution when initiating or escalating doses of Saxenda in patients with renal impairment.

 

Dehydration

 

Signs and symptoms of dehydration, including renal impairment and acute renal failure, have been reported in patients treated with GLP-1 receptor agonists. Patients treated with liraglutide should be advised of the potential risk of dehydration in relation to gastrointestinal side effects and take precautions to avoid fluid depletion.

 

Hypoglycaemia in patients with type 2 diabetes mellitus

 

Patients with type 2 diabetes mellitus receiving liraglutide in combination with insulin and/or sulfonylurea may have an increased risk of hypoglycaemia. The risk of hypoglycaemia may be lowered by a reduction in the dose of insulin and/or sulfonylurea.

 

Hyperglycaemia in insulin treated patients with diabetes mellitus

 

In patients with diabetes mellitus Saxenda must not be used as a substitute for insulin. Diabetic ketoacidosis has been reported in insulin-dependent patients after rapid discontinuation or dose reduction of insulin (see section 4.2).

 

Suicidal Behavior and Ideation 

 

In Saxenda clinical trials, 9 (0.3%) of 3384 Saxenda-treated patients and 2 (0.1%) of the 1941 placebo-treated patients reported suicidal ideation; one of these Saxenda-treated patients attempted suicide. Patients treated with Saxenda should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue Saxenda in patients who experience suicidal thoughts or behaviors. Avoid Saxenda in patients with a history of suicidal attempts or active suicidal ideation.

 

 

Excipients

 

Saxenda contains less than 1 mmol sodium (23 mg) per dose, therefore the medicinal product is essentially ‘sodium-free’.


In vitro, liraglutide has shown very low potential to be involved in pharmacokinetic interactions with other active substances related to cytochrome P450 (CYP) and plasma protein binding.

 

The small delay of gastric emptying with liraglutide may influence absorption of concomitantly administered oral medicinal products. Interaction studies did not show any clinically relevant delay of absorption and therefore no dose adjustment is required.

 

Interaction studies have been performed with 1.8 mg liraglutide. The effect on rate of gastric emptying was equivalent between liraglutide 1.8 mg and 3.0 mg, (paracetamol AUC0-300 min). Few patients treated with liraglutide reported at least one episode of severe diarrhoea. Diarrhoea may affect the absorption of concomitant oral medicinal products.

 

Warfarin and other coumarin derivatives

 

No interaction study has been performed. A clinically relevant interaction with active substances with poor solubility or narrow therapeutic index such as warfarin cannot be excluded. Upon initiation of liraglutide treatment in patients on warfarin or other coumarin derivatives, more frequent monitoring of International Normalised Ratio (INR) is recommended.

 

Paracetamol (Acetaminophen)

 

Liraglutide did not change the overall exposure of paracetamol following a single dose of 1,000 mg. Paracetamol Cmax was decreased by 31% and median tmax was delayed up to 15 min. No dose adjustment for concomitant use of paracetamol is required.

 

Atorvastatin

 

Liraglutide did not change the overall exposure of atorvastatin following single dose administration of atorvastatin 40 mg. Therefore, no dose adjustment of atorvastatin is required when given with liraglutide. Atorvastatin Cmax was decreased by 38% and median tmax was delayed from 1 h to 3 h with liraglutide.

 

Griseofulvin

 

Liraglutide did not change the overall exposure of griseofulvin following administration of a single dose of griseofulvin 500 mg. Griseofulvin Cmax increased by 37% while median tmax did not change. Dose adjustments of griseofulvin and other compounds with low solubility and high permeability are not required.

 

Digoxin

 

A single dose administration of digoxin 1 mg with liraglutide resulted in a reduction of digoxin AUC by 16%; Cmax decreased by 31%. Digoxin median tmax was delayed from 1 h to 1.5 h. No dose adjustment of digoxin is required based on these results.

 

Lisinopril

 

A single dose administration of lisinopril 20 mg with liraglutide resulted in a reduction of lisinopril AUC by 15%; Cmax decreased by 27%. Lisinopril median tmax was delayed from 6 h to 8 h with liraglutide. No dose adjustment of lisinopril is required based on these results.

 

Oral contraceptives

 

Liraglutide lowered ethinylestradiol and levonorgestrel Cmax by 12% and 13%, respectively, following administration of a single dose of an oral contraceptive product. tmax was delayed by 1.5 h with liraglutide for both compounds. There was no clinically relevant effect on the overall exposure of either ethinylestradiol or levonorgestrel. The contraceptive effect is therefore anticipated to be unaffected when co-administered with liraglutide.


 Pregnancy

 

There are limited data from the use of liraglutide in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown.

 

Liraglutide should not be used during pregnancy. If a patient wishes to become pregnant or pregnancy occurs, treatment with liraglutide should be discontinued.

 

Breast-feeding

 

It is not known whether liraglutide is excreted in human milk. Animal studies have shown that the transfer of liraglutide and metabolites of close structural relationship into milk is low. Non-clinical studies have shown a treatment-related reduction of neonatal growth in suckling rat pups (see section 5.3). Because of lack of experience, Saxenda should not be used during breast-feeding.

 

Fertility

 

Apart from a slight decrease in the number of live implants, animal studies did not indicate harmful effects with respect to fertility (see section 5.3).


Saxenda has no or negligible influence on the ability to drive and use machines. However, dizziness can be experienced mainly during the first 3 months of treatment with Saxenda. Driving or use of machines should be exercised with caution if dizziness occurs.


Summary of the safety profile:

 

Saxenda was evaluated for safety in 5 double-blind, placebo controlled trials that enrolled 5,813 adult patients with overweight or obesity with at least one weight-related comorbidity. Overall, gastrointestinal reactions were the most frequently reported adverse reactions during treatment (67.9%) (see section ‘Description of selected adverse reactions’).

 

Tabulated list of adverse reactions

 

Table 3 lists adverse reactions reported in adults. Adverse reactions are listed by system organ class and frequency. Frequency categories are defined as: 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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

 

Table 3 Adverse reactions reported in adults

MedDRA system organ classes

Very common

Common

Uncommon

Rare

Immune system disorders

 

 

 

Anaphylactic reaction

Metabolism and nutrition disorders

 

Hypoglycaemia*

Dehydration

 

Psychiatric disorders

 

Insomnia**

 

 

Nervous system disorders

Headache

Dizziness Dysgeusia

 

 

Cardiac disorders

 

 

Tachycardia

 

Gastrointestinal disorders

Nausea Vomiting Diarrhoea Constipation

Dry mouth Dyspepsia Gastritis

Gastro-oesophageal reflux disease Abdominal pain upper

Flatulence Eructation Abdominal

distension

Pancreatitis*** Delayed gastric emptying****

 

Hepatobiliary disorders

 

Cholelithiasis***

Cholecystitis***

 

Skin and

subcutaneous tissue disorders

 

Rash

Urticaria

 

Renal and urinary disorders

 

 

 

Acute renal failure Renal

impairment

General disorders and administration site conditions

 

Injection site reactions Asthenia

Fatigue

Malaise

 

Investigations

 

Increased lipase Increased amylase

 

 

*Hypoglycaemia (based on self-reported symptoms by patients and not confirmed by blood glucose measurements) reported in patients without type 2 diabetes mellitus treated with Saxenda in combination with diet and exercise. Please see section ‘Description of selected adverse reactions’ for further information.

**Insomnia was mainly seen during the first 3 months of treatment.

***See section 4.4.

****From controlled phase 2, 3a and 3b clinical trials. Description of selected adverse reactions:

Hypoglycaemia in patients without type 2 diabetes mellitus

 

In clinical trials in overweight or obese patients without type 2 diabetes mellitus treated with Saxenda in combination with diet and exercise, no severe hypoglycaemic events (requiring third party assistance) were reported. Symptoms of hypoglycaemic events were reported by 1.6 % of patients treated with Saxenda and 1.1% of patients treated with placebo; however, these events were not confirmed by blood glucose measurements. The majority of events were mild.

 

Hypoglycaemia in patients with type 2 diabetes mellitus

 

In a clinical trial in overweight or obese patients with type 2 diabetes mellitus treated with Saxenda in combination with diet and exercise, severe hypoglycaemia (requiring third party assistance) was reported by 0.7% of patients treated with Saxenda and only in patients concomitantly treated with sulfonylurea. Also, in these patients documented symptomatic hypoglycaemia was reported by 43.6% of patients treated with Saxenda and in 27.3% of patients treated with placebo. Among patients not concomitantly treated with sulfonylurea, 15.7% of patients treated with Saxenda and 7.6% of patients treated with placebo reported documented symptomatic hypoglycaemic events (defined as plasma glucose ≤3.9 mmol/L accompanied by symptoms).

 

Hypoglycaemia in patients with type 2 diabetes mellitus treated with insulin

 

In a clinical trial in overweight or obese patients with type 2 diabetes mellitus treated with insulin and liraglutide 3.0 mg/day in combination with diet and exercise and up to 2 OADs, severe hypoglycaemia (requiring third party assistance) was reported by 1.5% of patients treated with liraglutide 3.0 mg/day. In this trial, documented symptomatic hypoglycaemia (defined as plasma glucose ≤3.9 mmol/L accompanied by symptoms) was reported by 47.2% of patients treated with liraglutide 3.0 mg/day and by 51.8% of patients treated with placebo. Among patients concomitantly treated with sulfonylurea, 60.9% of patients treated with liraglutide 3.0 mg/day and 60.0% of patients treated with placebo reported documented symptomatic hypoglycaemic events.

 

Gastrointestinal adverse reactions

 

Most episodes of gastrointestinal events were mild to moderate, transient and the majority did not lead to discontinuation of therapy. The reactions usually occurred during the first weeks of treatment and diminished within a few days or weeks on continued treatment.

 

Patients ≥65 years of age may experience more gastrointestinal effects when treated with Saxenda.

 

Patients with mild or moderate renal impairment (creatinine clearance ≥30 ml/min) may experience more gastrointestinal effects when treated with Saxenda.

 

Acute renal failure

 

In patients treated with GLP-1 receptor agonists, there have been reports of acute renal failure. A majority of the reported events occurred in patients who had experienced nausea, vomiting or diarrhoea leading to volume depletion (see section 4.4).

 

Allergic reactions

 

Few cases of anaphylactic reactions with symptoms such as hypotension, palpitations, dyspnoea and oedema have been reported with marketed use of liraglutide. Anaphylactic reactions may potentially be life threatening. If an anaphylactic reaction is suspected, liraglutide should be discontinued and treatment should not be restarted (see section 4.3).

 

Injection site reactions

 

Injection site reactions have been reported in patients treated with Saxenda. These reactions were usually mild and transitory and the majority disappeared during continued treatment.

 

Tachycardia

 

In clinical trials, tachycardia was reported in 0.6% of patients treated with Saxenda and in 0.1% of patients treated with placebo. The majority of events were mild or moderate. Events were isolated and the majority resolved during continued treatment with Saxenda.

 

 

 

Post-marketing experience:

The following adverse reactions have been reported during post-approval use of liraglutide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

 

·         Gastrointestinal Disorders:

Acute pancreatitis, hemorrhagic and necrotizing pancreatitis, sometimes resulting in death, ileus.

 

·         General Disorders and Administration Site Conditions:

Allergic reactions: rash and pruritus.

 

·         Hepatobiliary Disorders:

Hyperbilirubinemia, cholestasis and hepatitis.

 

Paediatric population

 

In a clinical trial conducted in adolescents of 12 years to less than 18 years with obesity, 125 patients were exposed to Saxenda for 56 weeks.

Overall, the frequency, type and severity of adverse reactions in the adolescents with obesity were comparable to that observed in the adult population. Vomiting occurred with a 2-fold higher frequency in adolescents compared to adults.

 

No effects on growth or pubertal development were found. 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.

To report any side effect(s):

The National Pharmacovigilance Centre (NPC):

·         Fax: +966-11-205-7662

·         SFDA Call Center: 19999

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

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

 

 


From clinical trials and post-marketing use of liraglutide overdoses have been reported up to 72 mg (24 times the recommended dose for weight management). Events reported included severe nausea severe vomiting and severe hypoglycaemia .

In the event of overdose, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms. The patient should be observed for clinical signs of dehydration and blood glucose should be monitored.


Pharmacotherapeutic group: Drugs used in diabetes, glucagon-like peptide-1 (GLP-1) analogues. ATC code: A10BJ02

 

Mechanism of action

 

Liraglutide is an acylated human glucagon-like peptide-1 (GLP-1) analogue with 97% amino acid sequence homology to endogenous human GLP-1. Liraglutide binds to and activates the GLP-1 receptor (GLP-1R).

 

GLP-1 is a physiological regulator of appetite and food intake, but the exact mechanism of action is not entirely clear. In animal studies, peripheral administration of liraglutide led to uptake in specific brain regions involved in regulation of appetite, where liraglutide, via specific activation of the GLP- 1R, increased key satiety and decreased key hunger signals, thereby leading to lower body weight.

 

GLP-1 receptors are also expressed in specific locations in the heart, vasculature, immune system and kidneys. In mouse models of atherosclerosis, liraglutide prevented aortic plaque progression and reduced inflammation in the plaque. In addition, liraglutide had a beneficial effect on plasma lipids. Liraglutide did not reduce the plaque size of already established plaques.

 

Pharmacodynamic effects

 

Liraglutide lowers body weight in humans mainly through loss of fat mass with relative reductions in visceral fat being greater than for subcutaneous fat loss. Liraglutide regulates appetite by increasing feelings of fullness and satiety, while lowering feelings of hunger and prospective food consumption, thereby leading to reduced food intake. Liraglutide does not increase energy expenditure compared to placebo.

 

Liraglutide stimulates insulin secretion and lowers glucagon secretion in a glucose-dependent manner which results in a lowering of fasting and post-prandial glucose. The glucose-lowering effect is more pronounced in patients with prediabetes and diabetes compared to patients with normoglycaemia.

Clinical trials suggest that liraglutide improves and sustains beta-cell function, according to HOMA-B and the proinsulin-to-insulin ratio.

 

Clinical efficacy and safety

 

The efficacy and safety of liraglutide for weight management in conjunction with reduced calorie intake and increased physical activity were studied in four phase 3 randomised, double-blind, placebo- controlled trials which included a total of 5,358 adult patients.

 

•                 Trial 1 (SCALE Obesity & Pre-Diabetes - 1839): A total of 3,731 patients with obesity (BMI

≥30 kg/m²) or with overweight (BMI ≥27 kg/m²) with dyslipidaemia and/or hypertension were

stratified according to prediabetes status at screening and BMI at baseline (≥30 kg/m² or

<30 kg/m²). All 3,731 patients were randomised to 56 weeks of treatment and the 2,254 patients with prediabetes at screening were randomised to 160 weeks of treatment. Both treatment periods were followed by a 12-week off drug/placebo observational follow-up period. Lifestyle intervention in the form of an energy-restricted diet and exercise counselling was background therapy for all patients.

The 56-week part of trial 1 assessed body weight loss in all the 3,731 randomised patients (2,590 completers).

The 160-week part of trial 1 assessed time to onset of type 2 diabetes in the 2,254 randomised patients with prediabetes (1,128 completers).

•                 Trial 2 (SCALE Diabetes - 1922): A 56-week trial assessing body weight loss in 846 randomised (628 completers) obese and overweight patients with insufficiently controlled type 2 diabetes mellitus (HbA1c range 7–10%). The background treatment at trial start was either diet and exercise alone, metformin, a sulfonylurea, a glitazone as single agents or any combination hereof.

•                 Trial 3 (SCALE Sleep Apnoea - 3970): A 32-week trial assessing sleep apnoea severity and body weight loss in 359 randomised (276 completers) obese patients with moderate or severe obstructive sleep apnoea.

•                 Trial 4 (SCALE Maintenance - 1923): A 56-week trial assessing body weight maintenance and weight loss in 422 randomised (305 completers) obese and overweight patients with hypertension or dyslipidaemia after a preceding weight loss of ≥5% induced by a low-calorie diet.

 

Body weight

 

Superior weight loss was achieved with liraglutide compared to placebo in obese/overweight patients in all groups studied. Across the trial populations, greater proportions of the patients achieved ≥5% and >10% weight loss with liraglutide than with placebo (tables 4–5). In the 160-weeks part of trial 1, the weight loss occurred mainly in the first year and was sustained throughout 160 weeks. In trial 4, more patients maintained the weight loss achieved prior to treatment initiation with liraglutide than with placebo (81.4% and 48.9%, respectively). Specific data on weight loss, responders, time course and cumulative distribution of weight change (%) for trials 1–4 are presented in tables 4–7 and figures 1, 2 and 3.

 

Weight loss response after 12 weeks with liraglutide (3.0 mg) treatment

 

Early responders were defined as patients who achieved ≥5% weight loss after 12 weeks on treatment dose of liraglutide (4 weeks of dose escalation and 12 weeks on treatment dose). In the 56-week part of trial 1, 67.5% achieved ≥5% weight loss after 12 weeks. In trial 2, 50.4% achieved ≥5% weight loss after 12 weeks. With continued treatment with liraglutide, 86.2% of these early responders are predicted to achieve a weight loss of ≥5% and 51% are predicted to achieve a weight loss of ≥10% after 1 year of treatment. The predicted mean weight loss in early responders who complete 1 year of treatment is 11.2% of their baseline body weight (9.7% for males and 11.6% for females). For patients who have achieved a weight loss of <5% after 12 weeks on treatment dose of liraglutide, the proportion of patients not reaching a weight loss of ≥10% after 1 year is 93.4%.

 

Glycaemic control

 

Treatment with liraglutide significantly improved glycaemic parameters across sub-populations with normoglycaemia, prediabetes and type 2 diabetes mellitus. In the 56-week part of trial 1, fewer patients treated with liraglutide had developed type 2 diabetes mellitus compared to patients treated with placebo (0.2% vs. 1.1%). More patients with prediabetes at baseline had reversed their prediabetes compared to patients treated with placebo (69.2% vs. 32.7%). In the 160-week part of trial 1, the primary efficacy endpoint was the proportion of patients with onset of type 2 diabetes mellitus evaluated as time to onset. At week 160, while on treatment, 3% treated with Saxenda and 11% treated with placebo were diagnosed with type 2 diabetes mellitus. The estimated time to onset of type 2 diabetes mellitus for patients treated with liraglutide 3.0 mg was 2.7 times longer (with a 95% confidence interval of [1.9, 3.9]), and the hazard ratio for risk of developing type 2 diabetes mellitus was 0.2 for liraglutide versus placebo.

 

Cardiometabolic risk factors

 

Treatment with liraglutide significantly improved systolic blood pressure and waist circumference compared with placebo (tables 4, 5 and 6).

 

Apnoea-Hypopnoea Index (AHI)

 

Treatment with liraglutide significantly reduced the severity of obstructive sleep apnoea as assessed by change from baseline in the AHI compared with placebo (table 7).

 

Table 4 Trial 1: Changes from baseline in body weight, glycaemia and cardiometabolic parameters at week 56

                                                                           Saxenda (N=2437)

Placebo (N=1225)

Saxenda vs. placebo

Body weight

 

 

Baseline, kg (SD)                                                       106.3 (21.2)

106.3 (21.7)

-

Mean change at week 56, % (95% CI)                         -8.0

-2.6

-5.4** (-5.8; -5.0)

Mean change at week 56, kg (95% CI)                        -8.4

-2.8

-5.6** (-6.0; -5.1)

Proportion of patients losing ≥5% body                   63.5

weight at week 56, % (95% CI)                 

26.6

4.8** (4.1; 5.6)

 

Proportion of patients losing >10% body                 32.8

  weight at week 56, % (95% CI)            

10.1

4.3** (3.5; 5.3)

Glycaemia and cardiometabolic factors

Baseline

Change

Baseline

Change

 

HbA1c, %

5.6

-0.3

5.6

-0.1

-0.23** (-0.25; -0.21)

FPG, mmol/L

5.3

-0.4

5.3

-0.01

-0.38** (-0.42; -0.35)

Systolic blood pressure, mmHg

123.0

-4.3

123.3

-1.5

-2.8** (-3.6; -2.1)

Diastolic blood pressure, mmHg

78.7

-2.7

78.9

-1.8

-0.9* (-1.4; -0.4)

Waist circumference, cm

115.0

-8.2

114.5

-4.0

-4.2** (-4.7; -3.7)

 

 

Full Analysis Set. For body weight, HbA1c, FPG, blood pressure and waist circumference, baseline values are means, changes from baseline at week 56 are estimated means (least-squares) and treatment contrasts at week 56 are estimated treatment differences. For the proportions of patients losing ≥5/>10% body weight, estimated odds ratios are presented. Missing post-baseline values were imputed using the last observation carried forward.

* p<0.05. ** p<0.0001. CI=confidence interval. FPG=fasting plasma glucose. SD=standard deviation.

 

Table 5 Trial 1: Changes from baseline in body weight, glycaemia and cardiometabolic parameters at week 160

 

 

Saxenda (N=1472)

Placebo (N=738)

Saxenda vs. placebo

Body weight

 

 

 

Baseline, kg (SD)

107.6 (21.6)

108.0 (21.8)

 

Mean change at week 160, % (95% CI)

-6.2

-1.8

-4.3** (-4.9; -3.7)

Mean change at week 160, kg (95% CI)

-6.5

-2.0

-4.6** (-5.3; -3.9)

Proportion of patients losing ≥5% body

 

49.6

 

23.4

 

3.2** (2.6; 3.9)

weight at week 160, % (95% CI)

 

 

 

 

 

Proportion of patients losing >10% body

 

 

 

 

 

weight at week 160, % (95% CI)

24.4

 

9.5

 

3.1** (2.3; 4.1)

Glycaemia and cardiometabolic factors

Baseline

Change

Baseline

Change

 

HbA1c, %

5.8

-0.4

5.7

-0.1

-0.21** (-0.24; -0.18)

FPG, mmol/L

5.5

-0.4

5.5

0.04

-0.4** (-0.5; -0.4)

Systolic blood pressure, mmHg

124.8

-3.2

125.0

-0.4

-2.8** (-3.8; -1.8)

Diastolic blood pressure, mmHg

79.4

-2.4

79.8

-1.7

-0.6 (-1.3; 0.1)

Waist circumference, cm

116.6

-6.9

116.7

-3.4

-3.5** (-4.2; -2.8)

Full Analysis Set. For body weight, HbA1c, FPG, blood pressure and waist circumference, baseline values are means, changes from baseline at week 160 are estimated means (least-squares) and treatment contrasts at week 160 are estimated treatment differences. For the proportions of patients losing ≥5/>10% body weight, estimated odds ratios are presented. Missing post-baseline values were imputed using the last observation carried forward.

** p<0.0001. CI=confidence interval. FPG=fasting plasma glucose. SD=standard deviation.

 

 

Figure 2 Cumulative distribution of weight change (%) after 56 weeks of treatment in trial 1

 Table 6 Trial 2: Changes from baseline in body weight, glycaemia and cardiometabolic parameters at week 56

 

Saxenda (N=412)

Placebo (N=211)

Saxenda vs. placebo

Body weight

 

 

 

Baseline, kg (SD)

105.6 (21.9)

106.7 (21.2)

-

Mean change at week 56, % (95% CI)

-5.9

-2.0

-4.0** (-4.8; -3.1)

Mean change at week 56, kg (95% CI)

-6.2

-2.2

-4.1** (-5.0; -3.1)

Proportion of patients losing ≥5% body    49.8

weight at week 56, % (95% CI)    

13.5

6.4** (4.1; 10.0)

Proportion of patients losing >10% body  22.9

    weight at week 56, % (95% CI) 

4.2

6.8** (3.4; 13.8)

Glycaemia and cardiometabolic factors

 

Baseline

 

Change

 

Baseline

 

Change

 

HbA1c, %

7.9

-1.3

7.9

-0.4

-0.9** (-1.1; -0.8)

FPG, mmol/L

8.8

-1.9

8.6

-0.1

-1.8** (-2.1; -1.4)

Systolic blood pressure, mmHg

128.9

-3.0

129.2

-0.4

-2.6* (-4.6; -0.6)

Diastolic blood pressure, mmHg

79.0

-1.0

79.3

-0.6

-0.4 (-1.7; 1.0)

Waist circumference, cm

118.1

-6.0

117.3

-2.8

-3.2** (-4.2; -2.2)

 

Full Analysis Set. For body weight, HbA1c, FPG, blood pressure and waist circumference, baseline values are means, changes from baseline at week 56 are estimated means (least-squares) and treatment contrasts at week 56 are estimated treatment differences. For the proportions of patients losing ≥5/>10% body weight, estimated odds ratios are presented. Missing post-baseline values were imputed using the last observation carried forward.

* p<0.05. ** p<0.0001. CI=confidence interval. FPG=fasting plasma glucose. SD=standard deviation.

Table 7 Trial 3: Changes from baseline in body weight and Apnoea-Hypopnoea Index at week 32

                                                                              Saxenda (N=180)

Placebo (N=179)

Saxenda vs. placebo

Body weight

 

 

Baseline, kg (SD)                                                      116.5 (23.0)

118.7 (25.4)

-

Mean change at week 32, % (95% CI)                        -5.7

-1.6

-4.2** (-5.2; -3.1)

Mean change at week 32, kg (95% CI)                       -6.8

-1.8

-4.9** (-6.2; -3.7)

Proportion of patients losing ≥5% body                  46.4

weight at week 32, % (95% CI)                

18.1

3.9** (2.4; 6.4)

Proportion of patients losing >10% body              22.4

weight at week 32 % (95% CI)

1.5

19.0** (5.7; 63.1)

                                                                               Baseline      Change

Baseline     Change

 

Apnoea-Hypopnoea Index, events/hour        49.0           -12.2            49.3            -6.1             -6.1* (-11.0; -1.2)

 

Full Analysis Set. Baseline values are means, changes from baseline at week 32 are estimated means (least- squares) and treatment contrasts at week 32 are estimated treatment differences (95% CI). For the proportions of patients losing ≥5/>10% body weight, estimated odds ratios are presented. Missing post-baseline values were imputed using the last observation carried forward. * p<0.05. ** p<0.0001. CI=confidence interval. SD=standard deviation.

 

Table 8 Trial 4: Changes from baseline in body weight at week 56                                          

 

 

Saxenda (N=207)

Placebo (N=206)

Saxenda vs. placebo

Baseline, kg (SD)

100.7 (20.8)

98.9 (21.2)

-

Mean change at week 56, % (95% CI)

-6.3

-0.2

-6.1** (-7.5; -4.6)

Mean change at week 56, kg (95% CI)

-6.0

-0.2

-5.9** (-7.3; -4.4)

Proportion of patients losing ≥5% body

weight at week 56, % (95% CI)

50.7

21.3

3.8** (2.4; 6.0)

Proportion of patients losing >10% body

weight at week 56, % (95% CI)

27.4

6.8

5.1** (2.7; 9.7)

Full Analysis Set. Baseline values are means, changes from baseline at week 56 are estimated means (least- squares) and treatment contrasts at week 56 are estimated treatment differences. For the proportions of patients losing ≥5/>10% body weight, estimated odds ratios are presented. Missing post-baseline values were imputed using the last observation carried forward. ** p<0.0001. CI=confidence interval. SD=standard deviation.

Figure 3 Change from randomisation (week 0) in body weight (%) by time in trial 4

 

Before week 0 patients were only treated with low-calorie diet and exercise. At week 0 patients were randomised to receive either Saxenda or placebo.

 

Immunogenicity

 

Consistent with the potentially immunogenic properties of protein and peptide pharmaceuticals, patients may develop anti-liraglutide antibodies following treatment with liraglutide. In clinical trials, 2.5% of patients treated with liraglutide developed anti-liraglutide antibodies. Antibody formation has not been associated with reduced efficacy of liraglutide.

 

Cardiovascular evaluation

 

Major adverse cardiovascular events (MACE) were adjudicated by an external independent group of experts and defined as non-fatal myocardial infarction, non-fatal stroke and cardiovascular death. In all the long-term clinical trials with Saxenda, there were 6 MACE for patients treated with liraglutide and 10 MACE for placebo-treated patients. The hazard ratio and 95% CI is 0.33 [0.12; 0.90] for liraglutide versus placebo. A mean increase in heart rate from baseline of 2.5 beats per minute (ranging across trials from 1.6 to 3.6 beats per minute) has been observed with liraglutide in clinical phase 3 trials. The heart rate peaked after approximately 6 weeks. The long-term clinical impact of this mean increase in heart rate has not been established. The change in heart rate was reversible upon discontinuation of liraglutide (see section 4.4).

 

The Liraglutide Effect and Action in Diabetes Evaluation of Cardiovascular Outcomes Results (LEADER) trial included 9,340 patients with insufficiently controlled type 2 diabetes. The vast majority of these had established cardiovascular disease. Patients were randomly allocated to either liraglutide on a daily dose of up to 1.8 mg (4,668) or placebo (4,672), both on a background of standard of care.

 

The duration of exposure was between 3.5 and 5 years. The mean age was 64 years and the mean BMI was 32.5 kg/m². Mean baseline HbA1c was 8.7 and had improved after 3 years by 1.2 % in patients assigned to liraglutide and by 0.8 % in patients assigned to placebo. The primary endpoint was the time from randomisation to first occurrence of any major adverse cardiovascular events (MACE): cardiovascular death, non-fatal myocardial infarction or non-fatal stroke.

 

Liraglutide significantly reduced the rate of major adverse cardiovascular events (primary endpoint events, MACE) vs. placebo (3.41 vs. 3.90 per 100 patient years of observation in the liraglutide and placebo groups, respectively) with a risk reduction of 13%, HR 0.87, [0.78, 0.97] [95% CI]) (p=0.005)

(see figure 4).

Figure 4 Kaplan Meier plot of time to first MACE – FAS population

 

Paediatric population

 

The European Medicines Agency has deferred the obligation to submit the results of studies with Saxenda in one or more subsets of the paediatric population in the treatment of obesity (see section 4.2 for information on paediatric use).

 

In a double-blind trial comparing the efficacy and safety of Saxenda versus placebo on weight loss in adolescent patients aged 12 years and above with obesity, Saxenda was superior to placebo in weight reduction (evaluated as BMI Standard Deviation Score) after 56 weeks of treatment (table 9).

A greater proportion of the patients achieved ≥5% and ≥10% reductions in BMI with liraglutide than with placebo, as well as greater reductions in mean BMI and body weight (table 9). After 26 weeks of off-trial product follow-up period, weight regain was observed with liraglutide vs placebo (table 9).

 

Table 9       Trial 4180: Changes from baseline in body weight and BMI at week 56 and change in BMI SDS from week 56 to week 82

                                                                                                     Saxenda (N=125)

Placebo (N=126)

Saxenda vs. placebo

BMI SDS

 

 

 

Baseline, BMI SDS (SD)

3.14 (0.65)

3.20 (0.77)

 

Mean change at week 56 (95% CI)

-0.23

0.00

-0.22* (-0.37; -0.08)

week 56, BMI SDS (SD)

2.88 (0.94)

3.14 (0.98)

 

Mean change from week 56 to week 82, BMI SDS (95% CI)

0.22

0.07

0.15** (0.07; 0.23)

Body weight

Baseline, kg (SD)

99.3 (19.7)

102.2 (21.6)

-

Mean change at week 56, % (95% CI)

-2.65

2.37

-5.01** (-7.63; -2.39)

Mean change at week 56, kg (95% CI)

-2.26

2.25

-4.50** (-7.17; -1.84)

BMI

 

 

 

Baseline, kg/m2 (SD)

35.3 (5.1)

35.8 (5.7)

-

Mean change at week 56, kg/m2 (95%

-1.39

0.19

-1.58** (-2.47; -0.69)

CI)

 

 

 

Proportion of patients with ≥5%

 

 

 

reduction in baseline BMI at week 56,

43.25

18.73

3.31** (1.78; 6.16)

% (95% CI)

 

 

 

 

Proportion of patients with ≥10%

reduction in baseline BMI at week 56,                                    26.08                            8.11                          4.00** (1.81; 8.83)                           

% (95% CI)

Full Analysis Set. For BMI SDS, body weight and BMI, baseline values are means, changes from baseline at week 56 are estimated means (least-squares) and treatment contrasts at week 56 are estimated treatment differences. For BMI SDS, value at week 56 are means, changes from week 56 to week 82 are estimated means (least-squares) and treatment contrasts at week 82 are estimated treatment differences. For the proportions of patients losing ≥5%/≥10% baseline BMI, estimated odds ratios are presented. Missing observations were imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach.

*p<0.01, **p<0.001. CI=confidence interval. SD=standard deviation.

 

Based on tolerability, 103 patients (82.4%) escalated and remained on dose of 3.0 mg, 11 patients (8.8%) escalated and remained on dose of 2.4 mg, 4 patients (3.2%) escalated and remained on dose of

1.8 mg, 4 patients (3.2%) escalated and remained on dose of 1.2 mg and 3 patients (2.4%) remained on dose of 0.6 mg.

 

A 16-week double-blind, 36 week open-label study was conducted to evaluate the efficacy and safety of Saxenda in paediatric patients with Prader-Willi Syndrome and obesity. The study included 32 patients between 12 to <18 years of age (part A) and 24 patients between 6 to <12 years of age (part B). Patients were randomized 2:1 to receive Saxenda or placebo. Patients with a body weight less than 45 kg started dose escalation at a lower dose; 0.3 mg instead of 0.6 mg and were escalated to a maximum dose of 2.4 mg.

The estimated treatment difference in mean BMI SDS at 16 weeks (part A: -0.20 vs -0.13, part B: -0.50 vs -0.44) and 52 weeks (part A: -0.31 vs -0.17, part B: -0.73 vs -0.67) were similar with Saxenda and placebo. 

No additional safety concerns were seen in the trial.


Absorption

 

The absorption of liraglutide following subcutaneous administration was slow, reaching maximum concentration approximately 11 hours post dosing. The average liraglutide steady state concentration (AUCτ/24) reached approximately 31 nmol/L in obese (BMI 30–40 kg/m2) patients following administration of 3 mg liraglutide. Liraglutide exposure increased proportionally with dose. Absolute bioavailability of liraglutide following subcutaneous administration is approximately 55%.

 

Distribution

 

The mean apparent volume of distribution after subcutaneous administration is 20–25 L (for a person weighing approximately 100 kg). Liraglutide is extensively bound to plasma protein (>98%).

 

Biotransformation

 

During 24 hours following administration of a single [3H]-liraglutide dose to healthy subjects, the major component in plasma was intact liraglutide. Two minor plasma metabolites were detected (£9% and £5% of total plasma radioactivity exposure).

 

Elimination

 

Liraglutide is endogenously metabolised in a similar manner to large proteins without a specific organ as major route of elimination. Following a [3H]-liraglutide dose, intact liraglutide was not detected in urine or faeces. Only a minor part of the administered radioactivity was excreted as liraglutide-related metabolites in urine or faeces (6% and 5%, respectively). The urine and faeces radioactivity was mainly excreted during the first 6–8 days and corresponded to three minor metabolites, respectively.

 

The mean clearance following subcutaneous administration of liraglutide is approximately 0.9–1.4 L/h with an elimination half-life of approximately 13 hours.

 

Special populations

 

Elderly

 

Age had no clinically relevant effect on the pharmacokinetics of liraglutide based on the results from a population pharmacokinetic analysis of data from overweight and obese patients (18 to 82 years). No dosage adjustment is required based on age.

 

Gender

 

Based on the results of population pharmacokinetic analysis, females have 24% lower weight adjusted clearance of liraglutide compared to males. Based on the exposure response data, no dose adjustment is necessary based on gender.

 

Ethnic origin

 

Ethnic origin had no clinically relevant effect on the pharmacokinetics of liraglutide based on the results of population pharmacokinetic analysis which included overweight and obese patients of White, Black, Asian and Hispanic/non-Hispanic groups.

 

Body weight

 

The exposure of liraglutide decreases with an increase in baseline body weight. The 3.0 mg daily dose of liraglutide provided adequate systemic exposures over the body weight range of 60–234 kg evaluated for exposure response in the clinical trials. Liraglutide exposure was not studied in patients with body weight >234 kg.

 

Hepatic impairment

 

The pharmacokinetics of liraglutide was evaluated in patients with varying degree of hepatic impairment in a single-dose trial (0.75 mg). Liraglutide exposure was decreased by 13–23% in patients with mild to moderate hepatic impairment compared to healthy subjects. Exposure was significantly lower (44%) in patients with severe hepatic impairment (Child Pugh score >9).

 

Renal impairment

 

Liraglutide exposure was reduced in patients with renal impairment compared to individuals with normal renal function in a single-dose trial (0.75 mg). Liraglutide exposure was lowered by 33%, 14%, 27% and 26%, respectively, in patients with mild (creatinine clearance, CrCl 50–80 ml/min), moderate (CrCl 30–50 ml/min) and severe (CrCl <30 ml/min) renal impairment and in end-stage renal disease requiring dialysis.

 

Paediatric population

 

Pharmacokinetic properties for liraglutide 3.0 mg were assessed in clinical studies for adolescent patients with obesity aged 12 to less than 18 years (134 patients, body weight 62-178 kg). The liraglutide exposure in adolescents (age 12 to less than 18 years) was similar to that in adults with obesity.

 

Pharmacokinetic properties were also assessed in a clinical pharmacology study in the paediatric population with obesity aged 7-11 years (13 patients, body weight 54-87 kg) respectively.

Exposure associated with 3.0 mg liraglutide was found to be comparable between the children aged 7 to 11, adolescents and adult patients, after correction for body weight.


Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeat-dose toxicity or genotoxicity.

 

Non-lethal thyroid C-cell tumours were seen in two-year carcinogenicity studies in rats and mice. In rats, a no observed adverse effect level (NOAEL) was not observed. These tumours were not seen in monkeys treated for 20 months. These findings in rodents are caused by a non-genotoxic, specific GLP-1 receptor-mediated mechanism to which rodents are particularly sensitive. The relevance for humans is likely to be low but cannot be completely excluded. No other treatment-related tumours have been found.

 

Animal studies did not indicate direct harmful effects with respect to fertility but slightly increased early embryonic deaths at the highest dose. Dosing with liraglutide during mid-gestation caused a reduction in maternal weight and foetal growth with equivocal effects on ribs in rats and skeletal variation in the rabbit. Neonatal growth was reduced in rats while exposed to liraglutide and persisted in the post-weaning period in the high dose group. It is unknown whether the reduced pup growth is caused by reduced pup milk intake due to a direct GLP-1 effect or reduced maternal milk production due to decreased caloric intake.

 


Disodium phosphate dihydrate

Propylene glycol

Phenol

Hydrochloric acid (for pH adjustment)

Sodium hydroxide (for pH adjustment)

Water for injections

 


Substances added to Saxenda may cause degradation of liraglutide. In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.


30 months After first use: 1 month

Store in a refrigerator (2°C–8°C). Do not freeze.

Store away from the freezer compartment.

 

After first use: Store below 30°C or store in a refrigerator (2°C–8°C).

Keep the cap on the pen in order to protect from light.


Cartridge (type 1 glass) with a plunger (bromobutyl) and a laminate rubber sheet (bromobutyl/polyisoprene) contained in a pre-filled multidose disposable pen made of polypropylene, polyacetal, polycarbonate and acrylonitrile butadiene styrene.

 

Each pen contains 3 ml solution and is able to deliver doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg and

3.0 mg.

 

Pack sizes of 1, 3 or 5 pre-filled pens. Not all pack sizes may be marketed.


The solution should not be used if it does not appear clear and colourless or almost colourless.

 

Saxenda should not be used if it has been frozen.

 

The pen is designed to be used with NovoFine or NovoTwist disposable needles up to a length of 8 mm and as thin as 32G.

 

Needles are not included.

 

The patient should be advised to discard the injection needle after each injection and store the pen without an injection needle attached. This prevents contamination, infection and leakage. It also ensures that the dosing is accurate.

 

Any unused medicinal product or waste material should be disposed in accordance with local requirements.

 


Novo Nordisk A/S Novo Allé DK-2880 Bagsværd Denmark

Jan/2024
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