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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)

1. What Olazine is and what it is used for?
Olazine belongs to a group of medicines called antipsychotics and is used to treat the following conditions:

  • Schizophrenia, a disease with symptoms such as hearing, seeing or sensing things which are not there, mistaken beliefs, unusual suspiciousness, and becoming withdrawn. People with this disease may also feel depressed, anxious or tense.
  • Moderate to severe manic episodes, a condition with symptoms of excitement or euphoria. Olazine has been shown to prevent recurrence of these symptoms in patients with bipolar disorder whose manic episode has responded to Olazine treatment

2. What you need to know before you take Olazine

Do not take Olazine:

  • If you are allergic (hypersensitive) to Olazine or any of the other ingredients of this medicine (listed in section 6). An allergic reaction may be recognised as a rash, itching, a swollen face, swollen lips or shortness of breath. If this has happened to you, tell your doctor.
  • If you have been previously diagnosed with eye problems such as certain kinds of glaucoma (increased pressure in the eye).

Warnings and precautions
Talk to your doctor or pharmacist before you take Olazine

  • The use of Olazine in elderly patients with dementia is not recommended as it may have serious side effects.
  • Medicines of this type may cause unusual movements mainly of the face or tongue. If this happens after you have been given Olazine tell your doctor.
  • Very rarely, medicines of this type cause a combination of fever, faster breathing, sweating, muscle stiffness and drowsiness or sleepiness. If this happens, contact your doctor at once.
  • Weight gain has been seen in patients taking Olazine. You and your doctor should check your weight regularly.
  • High blood sugar and high levels of fat (triglycerides and cholesterol) have been seen in patients taking Olazine. Your doctor should do blood tests to check blood sugar and certain fat levels before you start taking Olazine and regularly during treatment.
  • Tell the doctor if you or someone else in your family has a history of blood clots, as medicines like these have been associated with the formation of blood clots

If you suffer from any of the following illnesses tell your doctor as soon as possible:

  • Stroke or “mini” stroke (temporary symptoms of stroke)
  • Parkinson’s disease
  • Prostate problems
  • A blocked intestine (Paralytic ileus)
  • Liver or kidney disease
  • Blood disorders
  • Heart disease
  • Diabetes
  • Seizures
  • If you know that you may have salt depletion as a result of prolonged severe diarrhoea and vomiting (being sick) or usage of diuretics (water tablets).

If you suffer from dementia, you or your carer/relative should tell your doctor if you have ever had a stroke or “mini” stroke.
As a routine precaution, if you are over 65 years your blood pressure may be monitored by your doctor.

Children and adolescents
Olazine is not for patients who are under 18 years.

Other medicines and Olazine
Only take other medicines while you are on Olazine if your doctor tells you that you can. You might feel drowsy if Olazine is taken in combination with antidepressants or medicines taken for anxiety or to help you sleep (tranquillisers).

Tell your doctor if you are taking, have recently taken or might take any other medicines
In particular, tell your doctor if you are taking:

  • medicines for Parkinson’s disease
  • carbamazepine (an anti-epileptic and mood stabiliser), fluvoxamine (an antidepressant) or ciprofloxacin (an antibiotic)
  • it may be necessary to change your Olazine dose

OLAZINE with alcohol

Do not drink any alcohol if you have been given OLAZINE as together with alcohol it may make you feel drowsy.

Pregnancy, breast-feeding and fertility
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. You should not be given this medicine when breast-feeding, as small amounts of Olazine can pass into breast milk.
The following symptoms may occur in newborn babies, of mothers that have used Olazine in the last trimester (last three months of their pregnancy): shaking, muscle stiffness and/or weakness, sleepiness, agitation, breathing problems, and difficulty in feeding. If your baby develops any of these
symptoms you may need to contact your doctor.

Driving and using machines
There is a risk of feeling drowsy when you are given Olazine. If this happens do not drive or operate any tools or machines. Tell your doctor.

OLAZINE  contains lactose If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.


3. How to take Olazine
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.
Your doctor will tell you how many Olazine tablets to take and how long you should continue to take them. The daily dose of Olazine is between 5 and 20 mg. Consult your doctor if your symptoms return but do not stop taking Olazine unless your doctor tells you to.
You should take your Olazine tablets once a day following the advice of your doctor. Try to take your tablets at the same time each day. It does not matter whether you take them with or without food.
Olazine tablets break easily, so you should handle the tablets carefully. Do not handle the tablets with wet hands as the tablets may break up.

OLAZINE tablets are for oral use. You should swallow the OLAZINE tablets whole with water.

If you take more Olazine than you should
Patients who have taken more Olazine than they should, have
experienced the following symptoms: rapid beating of the
heart, agitation/aggressiveness, problems with speech, unusual
movements (especially of the face or tongue) and reduced level of consciousness. Other symptoms may be: acute confusion, seizures (epilepsy), coma, a combination of fever, faster breathing, sweating, muscle stiffness and drowsiness or sleepiness, slowing of the breathing rate, aspiration, high blood pressure or low blood pressure, abnormal rhythms of the heart. Contact your doctor or hospital straight away, if you experience any of the above symptoms. Show the doctor your pack of tablets.

If you forget to take Olazine
Take your tablets as soon as you remember. Do not take two doses in one day.

If you stop taking Olazine
Do not stop taking your tablets just because you feel better. It is important that you carry on taking Olazine for as long as your doctor tells you.
If you suddenly stop taking Olazine, symptoms such as sweating, unable to sleep, tremor, anxiety or nausea and vomiting might occur. Your doctor may suggest you to reduce the dose gradually before stopping treatment.

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


4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor immediately if you have:

  • Unusual movement (a common side effect that may affect up to 1 in 10 people) mainly of the face or tongue;
  • Blood clots in the veins (an uncommon side effect that may affect up to 1 in 100 people) especially in the legs (symptoms include swelling, pain, and redness in the leg), which may travel through blood vessels to the lungs causing chest pain and difficulty in breathing. If you notice any of these symptoms seek medical advice immediately.
  • A combination of fever, faster breathing, sweating, muscle stiffness and drowsiness or sleepiness (the frequency of this side effect cannot be estimated from the available data)

Very common side effects (may affect more than 1 in 10 people):

  • Weight gain
  • Sleepiness
  • Increases in the levels of prolactin in the blood
  • In the early stages of treatment, some people may feel dizzy or faint (with a slow heart rate), especially when getting up from a lying or sitting position. This will usually pass on its own but if it does not, tell your doctor.

Common side effects (may affect up to 1 in 10 people):

  • Changes in the levels of some blood cells , circulating fats and early in treatment, temporary increases in liver enzymes.
  • Increases in the level of sugars in the blood and urine.
  • Increases in levels of uric acid and creatine phosphokinase in the blood.
  • Feeling more hungry.
  • Dizziness.
  •  Restlessness.
  • Tremor.
  •  unusual movements(dyskinesias) .
  • Constipation.
  • Dry mouth.
  • Rash.
  • Loss of strength.
  • Extreme tiredness.
  • Water retention leading to swelling of the hands, ankles or feet.
  • Fever.
  • joint pain.
  • Sexual dysfunctions such as decreased libido in males and females or erectile dysfunction in males.

Uncommon side effects (may affect up to 1 in 100 people):

  • Include hypersensitivity (e.g. swelling in the mouth and throat, itching, rash)
  • Diabetes or the worsening of diabetes, occasionally associated with ketoacidosis (ketones in the blood and urine) or coma
  • Seizures, usually associated with a history of seizures (epilepsy)
  • Muscle stiffness or spasms (including eye movements)
  • Restless legs syndrome
  • Problems with speech
  • Stuttering
  • slow heart rate
  • Sensitivity to sunlight
  • Bleeding from the nose
  • Abdominal distension
  • Memory loss or forgetfulness
  • Urinary incontinence
  • Lack of ability to urinate
  • Hair loss
  • Absence or decrease in menstrual periods
  • Changes in breasts in males and females such as an abnormal production of breast milk or abnormal growth.

Rare side effects (may affect up to 1 in 1000 people)

  • Lowering of normal body temperature
  • Abnormal rhythms of the heart
  • Sudden unexplained death
  • Inflammation of the pancreas causing severe stomach pain, fever and sickness
  • Liver disease appearing as yellowing of the skin and white parts of the eyes
  • Muscle disease presenting as unexplained aches and pains
  • Prolonged and/or painful erection.

Very rare side effects include serious allergic reactions such as

  • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). DRESS appears initially as flu-like symptoms with a rash on the face and then with an extended rash, high temperature, enlarged lymph nodes, increased levels of liver enzymes seen on blood tests and an increase in a type of white blood cells (eosinophilia).

While taking OLAZINE, elderly patients with dementia may suffer from stroke, pneumonia, urinary incontinence, falls, extreme tiredness, visual hallucinations, a rise in body temperature, redness of the skin and have trouble walking. Some fatal cases have been reported in this particular group of patients.

In patients with Parkinson's disease OLAZINE may worsen the symptoms.

Adverse events associated with the Combination of Olanzapine and Lithium or Valproate:

 • Manic or Mixed Episodes, Bipolar I Disorder (Adults)

 – dry mouth, weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, paresthesia

If you get any side effects, talk to your doctor or pharmacist. This includes anyside effects not listed in this leaflet


5. How to store Olazine

  • Keep this medicine out of the sight and reach of children.
  • Store below 30°C.
  • Store it in the original package in order to protect from light and moisture.
  • Do not use this medicine after the expiry date which is stated on the carton box & blister label after EXP. The expiry date refers to the last day of that month.
  • Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment

What Olazine tablets contain?
Active ingredient: Each film coated tablet contains Olanzapine 2.5mg, 5mg, 7.5mg, 10mg, 15mg or 20mg.
Other ingredients: Lactose Monohydrate, Low Substituted Hydroxypropyl
Cellulose, Microcrystalline Cellulose, Hydroxypropyl Cellulose, Magnesium
Stearate, Seal Coating (Hypromellose & Talc) and Film Coating (Opadry II White).


Olazine film coated tablets 2.5 mg : white to off white , circular film coated tablets ,embossed with “MC” on one side and “27” on the other side . Olazine film coated tablets 5 mg : white to off white , circular film coated tablets ,embossed with “MC” on one side and “7” on the other side . Olazine film coated tablets 7.5 mg : white to off white , circular film coated tablets ,embossed with “MC” on one side and “8” on the other side . Olazine film coated tablets 10 mg : white to off white , circular film coated tablets ,embossed with “MC” on one side and “93” on the other side . Olazine film coated tablets 15 mg : white to off white , oval film coated tablets ,embossed with “MC” on one side and “10” on the other side . Olazine film coated tablets 20 mg : white to off white , oval film coated tablets ,embossed with “MC57” on one side and plain on the other side . Pack: Packs contain (28) film coated tablets of OLAZINE 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg & 20 mg.

Marketing Authorisation Holder and Manufacturer
Medical and Cosmetic Products Company Ltd. (Riyadh Pharma)
P.O.Box 442, Riyadh 11411
Fax: +966 11 265 0505
Email: contact@riyadhpharma.com
For any information about this medicinal product, please contact the local representative of marketing authorisation holder:
Saudi Arabia
Marketing department
Riyadh
Tel: +966 11 265 0111
Email: marketing@riyadhpharma.com


This leaflet is revised in 3/2019
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

ينتمي أولازين إلى مجموعة من الأدوية تسمى مضادات الذهان، ويستخدم لعلاج الحالات التالية:

  • الفصام، وهو مرض يتميز بأعراض مثل سمع، ورؤية أو تحسس أشياء ليست موجودة، المعتقدات الخاطئة، وارتياب غير عادي، الانسحاب من الحياة العادية. الأشخاص الذين يعانون من هذا المرض قد يشعرون أيضا بالاكتئاب، القلق أو التوتر.
  • نوبات الهوس المعتدلة إلى الحادة، وهي حالة مع أعراض الإثارة أو النشوة. وقد تبين أن أولازين يمنع تكرار هذه الأعراض في المرضى الذين يعانون من الاضطراب ثنائي القطبية الذين قد استجابوا للعلاج بأولازين وقت نوبة جنون.

لا تتناول أولازين:

  • إذا كنت تعاني من حساسية (التحسس) لأولازين أو أي من المكونات الأخرى من هذا الدواء (المدرجة في المادة 6). قد يتم التعرف على الحساسية بشكل طفح جلدي، حكة، تورم الوجه، وتورم الشفتين أو ضيق في التنفس. إذا حدث هذا لك، أخبر طبيبك.
  • إذا كنت قد سبق أن تم تشخيصك بمشاكل في العين مثل أنواع معينة من الجلوكوما (زيادة الضغط في العين).

تحذيرات واحتياطات

تحدث إلى طبيبك أو الصيدلي قبل تناول أولازين

  • لا ينصح بتناول أولازين في المرضى المسنين المصابين بالخرف لأنه قد يكون له آثار جانبية خطيرة.
  • قد تسبب الأدوية من هذا النوع تحركات غير عادية بصورة رئيسية في الوجه أو اللسان. إذا حدث هذا بعد تعاطي أولازين أخبر طبيبك.
  • نادرا جدا، الأدوية من هذا النوع تسبب مزيج من الحمى وسرعة في التنفس، والتعرق، وتصلب العضلات والنعاس أو النوم. إذا حدث ذلك، اتصل بطبيبك على الفور.
  • تمت ملاحظة زيادة الوزن في المرضى الذين يتناولون أولازين. يجب عليك انت وطبيبك فحص وزنك بانتظام.
  • تمت ملاحظة ارتفاع سكر الدم ومستويات عالية من الدهون (الدهون الثلاثية والكوليسترول) في المرضى الذين يتناولون أولازين. طبيبك ينبغي أن يقوم باختبارات الدم للتأكد من نسبة سكر الدم ومستويات من دهون معينة قبل البدء بتناول أولازين وبانتظام خلال فترة العلاج.
  •  أخبر الطبيب إذا كنت أنت أو أي شخص آخر في عائلتك لديه تاريخ مرضي من الجلطات الدموية، فقد ارتبطت مثل هذه الأدوية مع تكوين جلطات الدم

إذا كنت تعاني من أي من الأمراض التالية أخبر طبيبك في أقرب وقت ممكن:

  • السكتة الدماغية أو سكتة دماغية "مصغرة" (أعراض مؤقتة للسكتة الدماغية)
  • مرض باركنسون
  • مشاكل البروستاتا
  • الأمعاء المسدودة (الشلل اللفائفي)
  • أمراض الكبد أو الكلى
  • مشاكل الدم
  • أمراض القلب
  • مرض السكري
  • نوبات
  • إذا كنت تعلم أنه قد يكون لديك فقدان للأملاح نتيجة للإسهال الشديد والقيء لفترة طويلة (المرض) أو استخدام مدرات البول (أقراص الماء)

إذا كنت تعاني من الخرف، ينبغي لك أو لمقدم الرعاية / قريبك إخبار الطبيب إذا كان لديك في أي وقت مضى سكتة دماغية أو سكتة دماغية"مصغرة".

كإجراء وقائي روتيني، إذا كنت أكثر من 65 عاما قد يراقب الطبيب ضغط الدم لديك .

الأطفال والمراهقين

أولازين ليس للمرضى الذين هم دون سن 18 عاما.

الأدوية الأخرى وأولازين

فقط تناول أي أدوية أخرى وأنت تتناول أولازين إذا طلب منك الطبيب ذلك. قد تشعر بالنعاس إذا تناولت أولازين بالاشتراك مع مضادات الاكتئاب أو أدوية تعالج القلق أو لمساعدتك على النوم (المهدئات).

أخبر طبيبك إذا كنت تتناول، قد تناولت مؤخرا أو قد تتناول أي أدوية أخرى

على وجه الخصوص، أخبر طبيبك فورا إذا كنت تتناول:

  • أدوية علاج مرض باركنسون
  • كاربامازيبين (المضادة للصرع ومنظم للمزاج)، فلوفوكسامين (مضاد للاكتئاب) أو سيبروفلوكساسين (مضاد حيوي)
  • قد يكون من الضروري تغيير جرعة أولازين الخاصة بك

أولازين مع الكحول

لا تشرب أي كحول إذا كنت قد تناولت أولازين حيث أن تناوله  مع الكحول قد يجعلك تشعر بالنعاس.

الحمل، الرضاعة الطبيعية والخصوبة

إذا كنتي حاملا أو تقومين بالرضاعة الطبيعية، تعتقدين أنك قد تكوني حاملا أو تخططين لإنجاب طفل، اسألي طبيبك للحصول على المشورة قبل تناول هذا الدواء.

لا ينبغي إعطاء هذا الدواء عند الرضاعة الطبيعية، كميات صغيرة من أولازين يمكن أن تنتقل إلى حليب الثدي.

قد تحدث الأعراض التالية في الأطفال حديثي الولادة، للأمهات اللاتي استخدمن أولازين في الثلث الأخير من الحمل (الشهور الثلاثة الأخيرة من الحمل): الرعشة، وتصلب العضلات و / أو ضعف، والنعاس، والتهيج، ومشاكل في التنفس، وصعوبة في الرضاعة. إذا تتطور لدى طفلك أي من هذه الأعراض قد تحتاجين إلى الاتصال بطبيبك.

القيادة واستخدام الآلات

هناك خطر من الشعور بالنعاس عند إعطاء أولازين. وإذا حدث ذلك لا تقود السيارة أو تشغل أي أدوات أو آلات. أخبر طبيبك.

يحتوي أولازين على اللاكتوز

إذا أخبرك طبيبك أن لديك عدم القدرة على تحمل بعض السكريات ، اتصل بطبيبك قبل تناول هذا المنتج الطبي.

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تناول دائما هذا الدواء تماما كما قال لك طبيبك. استشر طبيبك أو الصيدلي إذا لم تكن متأكدا.

طبيبك سوف يخبرك كم حبة أولازين يجب تناولها وإلى متى ينبغي عليك الاستمرار في تناولها. الجرعة اليومية من أولازين ما بين 5 و20 ملجم استشر طبيبك إذا عادت الأعراض الخاصة بك ولكن لا تتوقف عن تناول أولازين إلا إذا طلب منك الطبيب ذلك.

يجب أن تتناول أقراص أولازين مرة واحدة في اليوم متبعا لنصيحة الطبيب. حاول أن تأخذه الأقراص في نفس الوقت كل يوم. لا يهم ما إذا كنت تتناولهم مع او بدون الطعام.

أقراص أولازين تتكسر بسهولة، لذلك يجب التعامل مع الأقراص بعناية. لا تتعامل مع الأقراص بأيد مبتلة فالأقراص قد تتفتت.

أقراص أولازين للاستخدام الفموي. يجب ابتلاع أقراص أولازين بالكامل مع الماء.

إذا تناولت أولازين أكثر مما يجب

المرضى الذين تناولوا أولازين أكثر مما ينبغي، شوهدت لديهم الأعراض التالية: ضربات سريعة بالقلب، والإثارة / العدوانية، ومشاكل في الكلام، تحركات غير عادية (وخصوصا في الوجه أو اللسان) وانخفاض مستوى الوعي. قد تكون هناك أعراض أخرى: ارتباك حاد، والنوبات (الصرع)، والغيبوبة، مزيج من الحمى وسرعة في التنفس، والتعرق، وتصلب العضلات والنعاس أو النوم، وتباطؤ في معدل التنفس، والطموح، وارتفاع ضغط الدم أو انخفاض ضغط الدم، وإيقاعات غير طبيعية بالقلب. اتصل بطبيبك أو المستشفى على الفور، إذا كنت تواجه أي من الأعراض المذكورة أعلاه. اعرض على الطبيب علبتك من الأقراص.

إذا نسيت أن تتناول أولازين

تناول الأقراص الخاصة بك في أقرب وقت تتذكر فيه. لا تأخذ جرعتين في يوم واحد.

إذا توقفت عن تناول أولازين

لا تتوقف عن تناول الأقراص فقط لأنك تشعر بأنك أفضل. من المهم أن تستمر على تناول أولازين لطالما طلب منك الطبيب

إذا توقفت فجاه اخذ أولازين، أعراض مثل التعرق، عدم القدرة على النوم، ورعاش، والقلق أو الغثيان والقيء قد تحدث. قد يقترح الطبيب لكم الحد من الجرعة تدريجيا قبل وقف العلاج.

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

مثل جميع الأدوية، يمكن لهذا الدواء أن يسبب آثارا جانبية، وعلى الرغم من أنها لا تحدث للجميع.

أخبر طبيبك فورا إذا كان لديك:

  • حركة غير عادية (أحد الآثار الجانبية الشائعة التي قد تؤثر على ما يصل إلى 1 من كل 10 اشخاص) بشكل رئيسي في الوجه أو اللسان.
  • جلطات الدم في الأوردة (أثر جانبي غير متكرر قد يؤثر على ما يصل إلى 1 من كل 100 شخص) وخصوصا في الساقين (الأعراض تشمل تورم، ألم، واحمرار في الساق)، والتي قد تنتقل عبر الأوعية الدموية إلى الرئتين مما تسبب في ألم الصدر وصعوبة في التنفس. إذا لاحظت أي من هذه الأعراض اطلب المشورة الطبية فورا.
  • مزيج من الحمى وسرعة في التنفس، والتعرق، وتصلب العضلات والنعاس أو النوم (تكرار هذه الآثار الجانبية لا يمكن تقديرها من البيانات المتاحة)

الآثار الجانبية الشائعة جدا (قد تؤثر على أكثر من 1 من كل 10 اشخاص)

  • زيادة الوزن
  • النعاس
  • الزيادة في مستويات البرولاكتين في الدم
  • في المراحل المبكرة من العلاج ، قد يشعر بعض الأشخاص بالدوار أو الإغماء (مع معدل ضربات بطيء للقلب) ، خاصة عند الاستيقاظ من وضعية الاستلقاء أو الجلوس. هذا عادة ما ينتهي من تلقاء نفسه ولكن إذا لم يحدث ذلك ، أخبر طبيبك.

الآثار الجانبية الشائعة (قد يؤثر على ما يصل إلى 1 من كل 10 اشخاص)

  • تغيرات في مستويات بعض خلايا الدم ،الدهون المنتشرة ، عند العلاج المبكر تحدث زيادات مؤقتة في أنزيمات الكبد .
  • زيادة مستوى السكر في الدم والبول .
  • زيادة مستويات حمض اليوريك و فسفوكيناز الكرياتين في الدم .
  • شعور أكثر بالجوع .
  • دوخة .
  • عدم ارتياح .
  • رجفة .
  • حركات غير عادية (خلل حركي) .
  • الإمساك .
  • جفاف الفم .
  • الطفح .
  • فقدان القوة .
  • التعب الشديد .
  • احتباس الماء يؤدي إلى تورم في اليدين والكاحلين أو القدمين .
  • الحمى .
  • ألم المفصل .
  • الخلل الجنسي مثل انخفاض الرغبة الجنسية عند الذكور والإناث أو عدم القدرة على الانتصاب عند الذكور .

الآثار الجانبية غير شائعة (قد يؤثر على ما يصل إلى 1 من كل 100 شخص)

  • تشمل فرط الحساسية (مثل تورم في الفم والحلق والحكة والطفح الجلدي) .
  • مرض السكري أو تفاقم مرض السكري ، ترتبط أحيانًا بارتفاع الحموضة الكيتونية (الكيتونات في الدم والبول) أو الغيبوبة .
  • النوبات ، وعادة ما ترتبط مع تاريخ من النوبات (الصرع) .
  • تصلب العضلات أو التشنجات (بما في ذلك حركات العين) .
  • متلازمة تململ الساقين.
  • مشاكل في الكلام.
  • التلعثم.
  • بطء معدل ضربات القلب .
  • الحساسية لأشعة الشمس.
  • نزيف من الأنف.
  • انتفاخ في البطن.
  • فقدان الذاكرة أو النسيان .
  • سلس البول.
  • عدم القدرة على التبول .
  • تساقط الشعر .
  • غياب أو نقصان في فترات الحيض .
  • تغيرات في الثدي عند الذكور والإناث مثل الإنتاج غير الطبيعي لحليب الثدي أو نمو غير طبيعي.

الآثار الجانبية النادرة (قد تؤثر على ما يصل إلى 1 من كل 1000 شخص)

  • خفض درجة حرارة الجسم الطبيعية .
  • إيقاعات القلب غير الطبيعية .
  • الموت المفاجئ غير المبرر .
  • التهاب البنكرياس الذي يسبب آلام شديدة في المعدة والحمى والمرض .
  • ظهور أمراض الكبد كصفرة الجلد والأجزاء البيضاء من العينين .
  • مرض عضلي يمثل آلامًا غير مبررة وآلام .
  • الانتصاب المطول و / أو المؤلم.

الآثار الجانبية النادرة جدا  تشمل الحساسية خطيرة مثل

  • التفاعل الدوائي مع فرط الكريات الحمضية مع أعراض جهازية((DRESS .  (DRESS )تظهر كأعراض شبيهة بالإنفلونزا مع ظهور طفح جلدي على الوجه ثم مع طفح جلدي ممتد ودرجة حرارة عالية وتضخم الغدد الليمفاوية وزيادة مستويات إنزيمات الكبد التي تظهر في اختبارات الدم وزيادة في نوع من خلايا الدم البيضاء (فرط الكريات الحمضية) .

أثناء  تناول أولازين، المرضى المسنين المصابين بالخرف قد يعانون من السكتة الدماغية، والالتهاب الرئوي، وسلس البول، السقوط، التعب الشديد، والهلوسة البصرية، وارتفاع في درجة حرارة الجسم، واحمرار الجلد وصعوبة في المشي. وقد تم الإبلاغ عن بعض حالات الوفاة في هذه المجموعة من المرضى.

في المرضى الذين يعانون من مرض باركنسون , أولازين قد تفاقم الأعراض.

الأثار الجانبية عند الجمع في العلاج بين أولانزابين وليثيوم أو فالبروات:

  • نوبات هوس أو نوبات مختلطة ، الاضطراب الثنائي القطب( للبالغين)

-          جفاف الفم ، زيادة الوزن ، زيادة الشهية ، الدوار ، آلام الظهر ، الإمساك ، اضطراب الكلام ، زيادة إفراز اللعاب ، فقدان الذاكرة ، تشوش الحس .

إذا كان لديك أي آثار جانبية، تحدث مع طبيبك أو الصيدلي. وهذا يشمل أي آثار جانبية غير المذكورة في هذه النشرة

  • يحفظ هذا الدواء بعيدا عن مرأى ومتناول الأطفال.
  • يحفظ في درجة حرارة أقل من 30 درجة مئوية.
  • يحفظ في العبوة الأصلية من أجل الحماية من الضوء والرطوبة.
  • لا تستخدم هذا الدواء بعد تاريخ انتهاء الصلاحية المذكور على العلبة الكرتون والشريط المدون بعد EXP. تاريخ انتهاء الصلاحية يشير إلى اليوم الأخير من ذلك الشهر.
  • لا تتخلص من أي أدوية عن طريق مياه الصرف الصحي أو النفايات المنزلية. اسأل الصيدلي عن كيفية التخلص الأدوية التي لم تعد تستخدم. سوف تساعد هذه التدابير حماية البيئة

المادة الفعالة: يحتوي كل قرص مغلف على أولانزابين 2.5 ملجم، 5 ملجم، 7.5 ملجم، 10 ملجم، 15 ملجم، أو 20 ملجم.

المواد الإضافية: لاكتوز مونوهيدريت، لو سبستيتيوتد هيدروكسي بروبايل سليلوز، مايكروكريستلين سليلوز، هيدروكسي بروبايل سليلوز، مغنيسيوم ستيريت، مواد مثبتة (هايبروميلوز وتالك) ومواد مغلفة (أوبادري II أبيض).

كيف يبدو أولازين  وماهي محتويات العبوة:

أقراص أولازين المغلفة 2.5 ملجم: أقراص دائرية مغلفة بيضاء الى ابيض داكن ، منقوش عليها "MC" على جانب و "27" على الجانب الآخر.

 

أقراص أولازين المغلفة 5 ملجم: أقراص دائرية مغلفة بيضاء الى ابيض داكن ، منقوش عليها "MC" على جانب و "7" على الجانب الآخر.

 

أقراص أولازين المغلفة 7.5 ملجم: أقراص دائرية مغلفة بيضاء الى ابيض داكن ، مغلفة بطبقة "MC" على جانب واحد و "8" على الجانب الآخر.

 

أقراص أولازين المغلفة 10 ملجم: أقراص دائرية مغلفة بيضاء الى ابيض داكن ، منقوش عليها "MC" على جانب و "93" على الجانب الآخر.

 

أقراص أولازين المغلفة 15 ملجم: أقراص بيضاوية مغلفة بيضاء الى ابيض داكن ، منقوش عليها "MC" على جانب ، و "10" على الجانب الآخر.

 

أقراص أولازين المغلفة 20 ملجم: أقراص بيضاوية مغلفة بيضاء الى ابيض داكن ، منقوش عليها "MC57" على جانب و مسطحة على الجانب الآخر.

 

العبوة: عبوات تحتوي على (28) قرص مغلف من أولازين 2.5 ملجم، 5 ملجم، 7.5 ملجم، 10 ملجم، 15 ملجم أو 20 ملجم.

اسم وعنوان مالك رخصة التسويق والمصنع

شركة المنتجات الطبية والتجميلية المحدودة ( الرياض فارما)

ص.ب. 442 الرياض 11411

فاكس: 966112650505+

البريد الإلكتروني: contact@riyadhpharma.com

لأية معلومات عن هذا المنتج الطبي، يرجى الاتصال على صاحب الترخيص والتسويق:

المملكة العربية السعودية

قسم التسويق

الرياض

تلفون: 966112650111+

البريد الإلكتروني: marketing@riyadhpharma.com

تمت مراجعة هذه النشرة في 3/2019
 Read this leaflet carefully before you start using this product as it contains important information for you

OLAZINE 15mg FILM COATED TABLET

Each tablet contains 15 mg olanzapine. Excipient with known effect: lactose monohydrate. For the full list of excipients, see section 6.1.

Film Coated Tablet Olazine film coated tablets 15 mg : white to off white , oval film coated tablets ,embossed with “MC” on one side and “10” on the other side .

Adults

Olanzapine is indicated for the treatment of schizophrenia.
Olanzapine is effective in maintaining the clinical improvement during continuation therapy in patients who have shown an initial treatment response.
Olanzapine is indicated for the treatment of moderate to severe manic episode.
In patients whose manic episode has responded to olanzapine treatment, olanzapine is indicated for the prevention of recurrence in patients with bipolar disorder (see section 5.1).


Adults

Schizophrenia: The recommended starting dose for olanzapine is 10 mg/day.
Manic episode: The starting dose is 15 mg as a single daily dose in monotherapy or 10 mg daily in combination therapy (see section 5.1).
Preventing recurrence in bipolar disorder: The recommended starting dose is 10 mg/day. For patients who have been receiving olanzapine for treatment of manic episode, continue therapy for preventing recurrence at the same dose. If a new manic, mixed, or depressive episode occurs, olanzapine treatment should be continued (with dose optimisation as needed), with supplementary therapy to treat mood symptoms, as clinically indicated.
During treatment for schizophrenia, manic episode and recurrence prevention in bipolar disorder, daily dosage may subsequently be adjusted on the basis of individual clinical status within the range 5- 20 mg/day. An increase to a dose greater than the recommended starting dose is advised only after appropriate clinical reassessment and should generally occur at intervals of not less than 24 hours.
Olanzapine can be given without regards for meals as absorption is not affected by food. Gradual tapering of the dose should be considered when discontinuing olanzapine.

Special populations

Elderly

A lower starting dose (5 mg/day) is not routinely indicated but should be considered for those 65 and over when clinical factors warrant (see section 4.4).

Renal and/or hepatic impairment

A lower starting dose (5 mg) should be considered for such patients. In cases of moderate hepatic insufficiency (cirrhosis, Child-Pugh class A or B), the starting dose should be 5 mg and only increased with caution.

Smokers

The starting dose and dose range need not be routinely altered for non-smokers relative to smokers. The metabolism of olanzapine may be induced by smoking. Clinical monitoring is recommended and an increase of olanzapine dose may be considered if necessary (see section 4.5).

When more than one factor is present which might result in slower metabolism (female gender, geriatric age, non-smoking status), consideration should be given to decreasing the starting dose. Dose escalation, when indicated, should be conservative in such patients.

In cases where dose increments of 2.5 mg are considered necessary, OLAZINEcoated tablets should be used.

(See sections 4.5 and 5.2.)

Paediatric population

Olanzapine is not recommended for use in children and adolescents below 18 years of age due to a lack of data on safety and efficacy. A greater magnitude of weight gain, lipid and prolactin alterations has been reported in short-term studies of adolescent patients than in studies of adult patients (see sections 4.4, 4.8, 5.1 and 5.2).


Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Patients with known risk for narrow-angle glaucoma.

During antipsychotic treatment, improvement in the patient's clinical condition may take several days to some weeks. Patients should be closely monitored during this period.

Dementia-related psychosis and/or behavioural disturbances
Olanzapine is not approved for the treatment of dementia-related psychosis and/or behavioural disturbances and is not recommended for use in this particular group of patients because of an increase in mortality and the risk of cerebrovascular accident. In placebo-controlled clinical trials (6-12 weeks duration) of elderly patients (mean age 78 years) with dementia-related psychosis and/or disturbed behaviours, there was a 2- fold increase in the incidence of death in olanzapine-treated patients compared to patients treated with placebo (3.5% vs. 1.5%, respectively). The higher incidence of death was not associated with olanzapine dose (mean daily dose 4.4 mg) or duration of treatment. Risk factors that may predispose this patient population to increased mortality include age > 65 years, dysphagia, sedation, malnutrition and dehydration, pulmonary conditions (e.g., pneumonia, with or without aspiration), or concomitant use of benzodiazepines. However, the incidence of death was higher in olanzapine-treated than in placebo-treated patients independent of these risk factors
In the same clinical trials, cerebrovascular adverse events (CVAE e.g., stroke, transient ischemic attack), including fatalities, were reported. There was a 3-fold increase in CVAE in patients treated with olanzapine compared to patients treated with placebo (1.3% vs. 0.4%, respectively). All olanzapine- and placebotreated patients who experienced a cerebrovascular event had pre-existing risk factors. Age > 75 years and vascular/mixed type dementia were identified as risk factors for CVAE in association with olanzapine treatment. The efficacy of olanzapine was not established in these trials.

Parkinson's disease
The use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with Parkinson's disease is not recommended. In clinical trials, worsening of Parkinsonian symptomatology and hallucinations were reported very commonly and more frequently than with placebo (see section 4.8), and olanzapine was not more effective than placebo in the treatment of psychotic symptoms. In these trials, patients were initially required to be stable on the lowest effective dose of anti- Parkinsonian medicinal products (dopamine agonist) and to remain on the same anti-Parkinsonian medicinal products and dosages throughout the study. Olanzapine was started at 2.5 mg/day and titrated to a maximum of 15 mg/day based
on investigator judgement.

Neuroleptic Malignant Syndrome (NMS)
NMS is a potentially life-threatening condition associated with antipsychotic medicinal products. Rare cases reported as NMS have also been received in association with olanzapine. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all antipsychotic medicines, including olanzapine must be discontinued.

Hyperglycaemia and diabetes
Hyperglycaemia and/or development or exacerbation of diabetes occasionally associated with ketoacidosis or coma has been reported rarely, including some fatal cases (see section 4.8). In some cases, a prior increase in body weight has been reported which may be a predisposing factor.
Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines. Patients treated with any antipsychotic agents, including olanzapine, should be observed for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia, and weakness) and patients with diabetes mellitus or with risk factors for diabetes mellitus should be monitored regularly for worsening of glucose control. Weight should be monitored regularly, e.g. at baseline, 4, 8 and 12 weeks after starting olanzapine treatment and quarterly thereafter.

Lipid alterations
Undesirable alterations in lipids have been observed in olanzapine-treated patients in placebocontrolled clinical trials (see section 4.8). Lipid alterations should be managed as clinically appropriate, particularly in dyslipidemic patients and in patients with risk factors for the development of lipids disorders. Patients treated with any antipsychotic agents, including olanzapine, should be monitored regularly for lipids in accordance with utilised antipsychotic guidelines, e.g. at baseline, 12 weeks after starting olanzapine treatment and every 5 years thereafter.

Anticholinergic activity
While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials revealed a low incidence of related events. However, as clinical experience with olanzapine in patients with concomitant illness is limited, caution is advised when prescribing for patients with prostatic hypertrophy, or paralytic ileus and related conditions.

Hepatic function
Transient, asymptomatic elevations of hepatic aminotransferases, ALT, AST have been seen commonly, especially in early treatment. Caution should be exercised and follow-up organised in patients with elevated ALT and/or AST, in patients with signs and symptoms of hepatic impairment, in patients with pre-existing conditions associated with limited hepatic functional reserve, and in patients who are being treated with potentially hepatotoxic medicines. In cases where hepatitis (including hepatocellular, cholestatic or mixed liver injury) has been diagnosed, olanzapine treatment should be discontinued.

Neutropenia
Caution should be exercised in patients with low leukocyte and/or neutrophil counts for any reason, in patients receiving medicines known to cause neutropenia, in patients with a history of drug-induced bone marrow depression/toxicity, in patients with bone marrow depression caused by concomitant illness, radiation therapy or chemotherapy and in patients with hypereosinophilic conditions or with myeloproliferative disease. Neutropenia has been reported commonly when olanzapine and valproate are used concomitantly (see section 4.8).

Discontinuation of treatment
Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting have been reported very rarely (< 0.01%) when olanzapine is stopped abruptly.

QT interval
In clinical trials, clinically meaningful QTc prolongations (Fridericia QT correction [QTcF] ≥ 500 milliseconds [msec] at any time post baseline in patients with baseline QTcF < 500 msec) were uncommon (0.1% to 1%) in patients treated with olanzapine, with no significant differences in associated cardiac events compared to placebo. However, as with other antipsychotics, caution should be exercised when olanzapine is prescribed with medicines known to increase QTc interval, especially in the elderly, in patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalaemia or hypomagnesaemia.

Thromboembolism
Temporal association of olanzapine treatment and venous thromboembolism has been reported uncommonly (≥ 0.1% and < 1%) . A causal relationship between the occurrence of venous thromboembolism and treatment with olanzapine has not been established. However, since patients with schizophrenia often present with acquired risk factors for venous thromboembolism all possible risk factors of VTE e.g. immobilisation of patients, should be identified and preventive measures undertaken.

General CNS activity
Given the primary CNS effects of olanzapine, caution should be used when it is taken in combination with other centrally acting medicines and alcohol. As it exhibits in vitro dopamine antagonism, olanzapine may antagonize the effects of direct and indirect dopamine agonists.

Seizures
Olanzapine should be used cautiously in patients who have a history of seizures or are subject to factors which may lower the seizure threshold. Seizures have been reported to occur rarely in patients when treated with olanzapine. In most of these cases, a history of seizures or risk factors for seizures were reported.

Tardive Dyskinesia
In comparator studies of one year or less duration, olanzapine was associated with a statistically significant lower incidence of treatment emergent dyskinesia. However the risk of tardive dyskinesia increases with long term exposure, and therefore if signs or symptoms of tardive dyskinesia appear in a patient on olanzapine, a dose reduction or discontinuation should be considered. These symptoms can temporally deteriorate or even arise after discontinuation of treatment.

Postural hypotension
Postural hypotension was infrequently observed in the elderly in olanzapine clinical trials. As with other antipsychotics, it is recommended that blood pressure is measured periodically in patients over 65 years.

Sudden cardiac death
In postmarketing reports with olanzapine, the event of sudden cardiac death has been reported in patients with olanzapine. In a retrospective observational cohort study, the risk of presumed sudden cardiac death in patients treated with olanzapine was approximately twice the risk in patients not using antipsychotics. In the study, the risk of olanzapine was comparable to the risk of atypical antipsychotics included in a pooled analysis.

Paediatric population
Olanzapine is not indicated for use in the treatment of children and adolescents. Studies in patients aged 13-17 years showed various adverse reactions, including weight gain, changes in metabolic parameters and increases in prolactin levels. Long-term outcomes associated with these events have not been studied and remain unknown (see sections 4.8 and 5.1).

Lactose
Olanzapine Film-coated tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
 


Interaction studies have only been performed in adults.

Potential interactions affecting olanzapine

Since olanzapine is metabolised by CYP1A2, substances that can specifically induce or inhibit this isoenzyme may affect the pharmacokinetics of olanzapine.

Induction of CYP1A2

The metabolism of olanzapine may be induced by smoking and carbamazepine, which may lead to reduced olanzapine concentrations. Only slight to moderate increase in olanzapine clearance has been observed. The clinical consequences are likely to be limited, but clinical monitoring is recommended and an increase of olanzapine dose may be considered if necessary (see section 4.2).

Inhibition of CYP1A2

Fluvoxamine, a specific CYP1A2 inhibitor, has been shown to significantly inhibit the metabolism of olanzapine. The mean increase in olanzapine Cmax following fluvoxamine was 54% in female non-smokers and 77% in male smokers. The mean increase in olanzapine AUC was 52% and 108%, respectively. A lower starting dose of olanzapine should be considered in patients who are using fluvoxamine or any other CYP1A2 inhibitors, such as ciprofloxacin. A decrease in the dose of olanzapine should be considered if treatment with an inhibitor of CYP1A2 is initiated.

Decreased bioavailability

Activated charcoal reduces the bioavailability of oral olanzapine by 50 to 60% and should be taken at least 2 hours before or after olanzapine.

Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have not been found to significantly affect the pharmacokinetics of olanzapine.

Potential for olanzapine to affect other medicinal products

Olanzapine may antagonise the effects of direct and indirect dopamine agonists.

Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e.g., 1A2, 2D6, 2C9, 2C19, 3A4). Thus, no particular interaction is expected, as verified through in vivo studies, where no inhibition of metabolism of the following active substances was found: tricyclic antidepressant (representing mostly CYP2D6 pathway), warfarin (CYP2C9), theophylline (CYP1A2), or diazepam (CYP3A4 and 2C19).

Olanzapine showed no interaction when co-administered with lithium or biperiden.

Therapeutic monitoring of valproate plasma levels did not indicate that valproate dosage adjustment is required after the introduction of concomitant olanzapine.

General CNS activity

Caution should be exercised in patients who consume alcohol or receive medicinal products that can cause central nervous system depression.

The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with Parkinson's disease and dementia is not recommended (see section 4.4).

QTc interval

Caution should be used if olanzapine is being administered concomitantly with medicinal products known to increase QTc interval (see section 4.4).


Pregnancy

There are no adequate and well-controlled studies in pregnant women. Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during treatment with olanzapine. Nevertheless, because human experience is limited, olanzapine should be used in pregnancy only if the potential benefit justifies the potential risk to the foetus.
Neonates exposed to antipsychotics (including olanzapine) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonis, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully.

Breast-feeding
In a study in breast-feeding, healthy women, olanzapine was excreted in breast milk. Mean infant exposure (mg/kg) at steady state was estimated to be 1.8% of the maternal olanzapine dose (mg/kg). Patients should be advised not to breast-feed an infant if they are taking olanzapine.

Fertility
Effects on fertility are unknown (see section 5.3 for preclinical information)


No studies on the effects on the ability to drive and use machines have been performed. Because olanzapine may cause somnolence and dizziness, patients should be cautioned about operating machinery, including motor vehicles.


Summary of the safety profile

Adults

The most frequently (seen in ≥ 1% of patients) reported adverse reactions associated with the use of olanzapine in clinical trials were somnolence, weight gain, eosinophilia, elevated prolactin, cholesterol, glucose and triglyceride levels (see section 4.4), glucosuria, increased appetite, dizziness, akathisia, parkinsonism (see section 4.4), dyskinesia, orthostatic hypotension, anticholinergic effects, transient asymptomatic elevations of hepatic aminotransferases (see section 4.4), rash, asthenia, fatigue and oedema.

 Tabulated list of adverse reactions

The following table lists the adverse reactions and laboratory investigations observed from spontaneous reporting and in clinical trials. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The frequency terms listed are defined as follows: 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 data available).

 

Very common

Common

Uncommon

Rare

Not known

Blood and the lymphatic system disorders

 
 

Eosinophilia

Leukopenia10

Neutropenia10

 

Thrombocytopenia11

 

Immune system disorders

 
  

Hypersensitivity11

  

Metabolism and nutrition disorders

 

Weight gain1

Elevated cholesterol levels2,3

Elevated glucose levels4

Elevated triglyceride levels2,5

Glucosuria

Increased appetite

Development or exacerbation of diabetes occasionally associated with ketoacidosis or coma, including some fatal cases (see section 4.4)11

Hypothermia12

 

Nervous system disorders

 

Somnolence

Dizziness

Akathisia6

Parkinsonism6

Dyskinesia6

Seizures where in most cases a history of seizures or risk factors for seizures were reported 11

Dystonia (including oculogyration) 11

Tardive dyskinesia11

Amnesia 9

Dysarthria

Stuttering11

Restless Legs Syndrome

Neuroleptic malignant syndrome (see section 4.4) 12

Discontinuation symptoms7, 12

 

Cardiac disorders

 
  

Bradycardia

QTc prolongation (see section 4.4)

Ventricular tachycardia/ fibrillation, sudden death (see section 4.4) 11

 

Vascular disorders

 

Orthostatic hypotension10

 

Thromboembolism (including pulmonary embolism and deep vein thrombosis) (see section 4.4)

  

Respiratory, thoracic and mediastinal disorders

  

Epistaxis9

  

Gastrointestinal disorders

 
 

Mild, transient anticholinergic effects including constipation and dry mouth

Abdominal distension9

Pancreatitis11

 

Hepatobiliary disorders

 
 

Transient, asymptomatic elevations of hepatic aminotransferases (ALT, AST), especially in early treatment (see section 4.4)

 

Hepatitis (including hepatocellular, cholestatic or mixed liver injury) 11

 

Skin and subcutaneous tissue disorders

 
 

Rash

Photosensitivity reaction

Alopecia

 

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Musculoskeletal and connective tissue disorders

 
 

Arthralgia9

 

Rhabdomyolysis11

 

Renal and urinary disorders

 
  

Urinary incontinence, urinary retention

Urinary hesitation11

  

Pregnancy, puerperium and perinatal conditions

    

Drug withdrawal syndrome neonatal (see section 4.6)

Reproductive system and breast disorders

 
 

Erectile dysfunction in males

Decreased libido in males and females

Amenorrhea

Breast enlargement

Galactorrhea in females

Gynaecomastia/breast enlargement in males

Priapism12

 

General disorders and administration site conditions

 
 

Asthenia

Fatigue

Oedema

Pyrexia10

   

Investigations

 

Elevated plasma prolactin levels8

Increased alkaline phosphatase10

High creatine phosphokinase11

High Gamma Glutamyltransferase10

High uric acid 10

Increased total bilirubin

  

 

1Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories. Following short-term treatment (median duration 47 days), weight gain ≥ 7% of baseline body weight was very common (22.2%); ≥ 15% was common (4.2%); and ≥ 25% was uncommon (0.8%). Patients gaining ≥ 7%, ≥ 15% and ≥ 25% of their baseline body weight with long-term exposure (at least 48 weeks) were very common (64.4%, 31.7% and 12.3% respectively).

2Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline.

3Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high (≥ 6.2 mmol/l). Changes in total fasting cholesterol levels from borderline at baseline (≥ 5.17 - < 6.2 mmol/l) to high (≥ 6.2 mmol/l) were very common.

4Observed for fasting normal levels at baseline (< 5.56 mmol/l) which increased to high (≥ 7 mmol/l). Changes in fasting glucose from borderline at baseline (≥ 5.56 - < 7 mmol/l) to high (≥ 7 mmol/l) were very common.

5Observed for fasting normal levels at baseline (< 1.69 mmol/l) which increased to high (≥ 2.26 mmol/l). Changes in fasting triglycerides from borderline at baseline (≥ 1.69 mmol/l - < 2.26 mmol/l) to high (≥ 2.26 mmol/l) were very common.

6In clinical trials, the incidence of Parkinsonism and dystonia in olanzapine-treated patients was numerically higher, but not statistically significantly different from placebo. Olanzapine-treated patients had a lower incidence of Parkinsonism, akathisia and dystonia compared with titrated doses of haloperidol. In the absence of detailed information on the pre-existing history of individual acute and tardive extrapyramidal movement disorders, it cannot be concluded at present that olanzapine produces less tardive dyskinesia and/or other tardive extrapyramidal syndromes.

7Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been reported when olanzapine is stopped abruptly.

8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of normal range in approximately 30% of olanzapine-treated patients with normal baseline prolactin value. In the majority of these patients the elevations were generally mild, and remained below two times the upper limit of normal range.

9 Adverse event identified from clinical trials in the Olanzapine Integrated Database.

10 As assessed by measured values from clinical trials in the Olanzapine Integrated Database.

11 Adverse event identified from spontaneous post-marketing reporting with frequency determined utilising the Olanzapine Integrated Database.

12 Adverse event identified from spontaneous post-marketing reporting with frequency estimated at the upper limit of the 95% confidence interval utilising the Olanzapine Integrated Database.

 

Long-term exposure (at least 48 weeks)

The proportion of patients who had adverse, clinically significant changes in weight gain, glucose, total/LDL/HDL cholesterol or triglycerides increased over time. In adult patients who completed 9-12 months of therapy, the rate of increase in mean blood glucose slowed after approximately 6 months.

 

Additional information on special populations

In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher incidence of death and cerebrovascular adverse reactions compared to placebo (see section 4.4). Very common adverse reactions associated with the use of olanzapine in this patient group were abnormal gait and falls. Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and urinary incontinence were observed commonly.

In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with Parkinson's disease, worsening of Parkinsonian symptomatology and hallucinations were reported very commonly and more frequently than with placebo.

In one clinical trial in patients with bipolar mania, valproate combination therapy with olanzapine resulted in an incidence of neutropenia of 4.1%; a potential contributing factor could be high plasma valproate levels. Olanzapine administered with lithium or valproate resulted in increased levels (≥  10%) of tremor, dry mouth (32% for olanzapine combination vs 9% for placebo), increased appetite (24% vs 8%), increased salivation (6% vs 2%) , weight gain(26% vs 7%), dizziness (14% vs 7%), back pain (8% vs 4%), constipation (8% vs 4%). Speech disorder  (7% vs 1%) was also reported commonly, amnesia (5% vs 2%), and paresthesia (5% vs 2%).

Long-term olanzapine treatment (up to 12 months) for recurrence prevention in patients with bipolar disorder was associated with an increase of ≥7% from baseline body weight in 39.9% of patients.

 

Paediatric population

Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years. Although no clinical studies designed to compare adolescents to adults have been conducted, data from the adolescent trials were compared to those of the adult trials.

The following table summarises the adverse reactions reported with a greater frequency in adolescent patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-term clinical trials in adolescent patients. Clinically significant weight gain (≥ 7%) appears to occur more frequently in the adolescent population compared to adults with comparable exposures. The magnitude of weight gain and the proportion of adolescent patients who had clinically significant weight gain were greater with long-term exposure (at least 24 weeks) than with short-term exposure.

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The frequency terms listed are defined as follows: Very common (≥ 1/10), common (≥ 1/100 to < 1/10).

 

Metabolism and nutrition disorders

Very common: Weight gain13, elevated triglyceride levels14, increased appetite.

Common: Elevated cholesterol levels15.

Nervous system disorders

Very common: Sedation (including: hypersomnia, lethargy, somnolence).

Gastrointestinal disorders

Common: Dry mouth.

Hepatobiliary disorders

Very common: Elevations of hepatic aminotransferases (ALT/AST; see section 4.4).

Investigations

Very common: Decreased total bilirubin, increased GGT, elevated plasma prolactin levels16.

 

13Following short-term treatment (median duration 22 days), weight gain ≥ 7% of baseline body weight (kg) was very common (40.6%); ≥ 15% of baseline body weight was common (7.1%) and ≥ 25% was common (2.5%). With long-term exposure (at least 24 weeks), 89.4% gained ≥ 7%, 55.3% gained ≥ 15% and 29.1% gained ≥ 25% of their baseline body weight.

14Observed for fasting normal levels at baseline (< 1.016 mmol/l) which increased to high (≥ 1.467 mmol/l) and changes in fasting triglycerides from borderline at baseline (≥ 1.016 mmol/l - < 1.467 mmol/l) to high (≥ 1.467 mmol/l).

15Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/l) to high (≥ 5.17 mmol/l) were observed commonly. Changes in total fasting cholesterol levels from borderline at baseline (≥ 4.39 - < 5.17 mmol/l) to high (≥ 5.17 mmol/l) were very common.

16Elevated plasma prolactin levels were reported in 47.4% of adolescent patients.

 

To report any side effects

-       National Pharmacovigilance and Drug Safety Center (NPC)

o   Fax: +966-11-205-7662

o   To call the executive management of vigilance and crisis management: +966-11-2038222 ext.: 2353 – 2356 – 2317 – 2354 – 2334 – 2340

o   Toll-free: 8002490000

o   E-mail: npc.drug@sfda.gov.sa

o   Website: www.sfda.gov.sa/npc


Signs and symptoms

Very common symptoms in overdose (>10% incidence) include tachycardia, agitation/aggressiveness, dysarthria, various extrapyramidal symptoms, and reduced level of consciousness ranging from sedation to coma.

Other medically significant sequelae of overdose include delirium, convulsion, coma, possible neuroleptic malignant syndrome, respiratory depression, aspiration, hypertension or hypotension, cardiac arrhythmias (< 2% of overdose cases) and cardiopulmonary arrest. Fatal outcomes have been reported for acute overdoses as low as 450 mg but survival has also been reported following acute overdose of approximately 2 g of oral olanzapine.

Management

There is no specific antidote for olanzapine. Induction of emesis is not recommended. Standard procedures for management of overdose may be indicated (i.e. gastric lavage, administration of activated charcoal).

The concomitant administration of activated charcoal was shown to reduce the oral bioavailability of olanzapine by 50 to 60%.

Symptomatic treatment and monitoring of vital organ function should be instituted according to clinical presentation, including treatment of hypotension and circulatory collapse and support of respiratory function. Do not use epinephrine, dopamine, or other sympathomimetic agents with betaagonist activity since beta stimulation may worsen hypotension. Cardiovascular monitoring is necessary to detect possible arrhythmias. Close medical supervision and monitoring should continue until the patient recovers.


Pharmacotherapeutic group: Antipsychotics, diazepines, oxazepines and thiazepines, ATC code: N05A H03.

Pharmacodynamic effects

Olanzapine is an antipsychotic, antimanic and mood stabilising agent that demonstrates a broad pharmacologic profile across a number of receptor systems.

In preclinical studies, olanzapine exhibited a range of receptor affinities (Ki < 100 nM) for serotonin 5 HT2A/2C, 5 HT3, 5 HT6; dopamine D1, D2, D3, D4, D5; cholinergic muscarinic receptors M1-M5; α1 adrenergic; and histamine H1 receptors. Animal behavioural studies with olanzapine indicated 5HT, dopamine, and cholinergic antagonism, consistent with the receptor-binding profile. Olanzapine demonstrated a greater in vitro affinity for serotonin 5HT2 than dopamine D2 receptors and greater 5 HT2 than D2 activity in vivo models. Electrophysiological studies demonstrated that olanzapine selectively reduced the firing of mesolimbic (A10) dopaminergic neurons, while having little effect on the striatal (A9) pathways involved in motor function. Olanzapine reduced a conditioned avoidance response, a test indicative of antipsychotic activity, at doses below those producing catalepsy, an effect indicative of motor side-effects. Unlike some other antipsychotic agents, olanzapine increases responding in an “anxiolytic” test.

In a single oral dose (10 mg) Positron Emission Tomography (PET) study in healthy volunteers, olanzapine produced a higher 5 HT2A than dopamine D2 receptor occupancy. In addition, a Single Photon Emission Computed Tomography SPECT imaging study in schizophrenic patients revealed that olanzapine- responsive patients had lower striatal D2 occupancy than some other antipsychotic- and risperidone- responsive patients, while being comparable to clozapine-responsive patients.

Clinical efficacy

In two of two placebo and two of three comparator controlled trials with over 2,900 schizophrenic patients presenting with both positive and negative symptoms, olanzapine was associated with statistically significantly greater improvements in negative as well as positive symptoms.

In a multinational, double-blind, comparative study of schizophrenia, schizoaffective, and related disorders which included 1,481 patients with varying degrees of associated depressive symptoms (baseline mean of

16.6 on the Montgomery-Asberg Depression Rating Scale), a prospective secondary analysis of baseline to endpoint mood score change demonstrated a statistically significant improvement (p= 0.001) favouring olanzapine (-6.0) versus haloperidol (-3.1).

In patients with a manic or mixed episode of bipolar disorder, olanzapine demonstrated superior efficacy to placebo and valproate semisodium (divalproex) in reduction of manic symptoms over 3 weeks. Olanzapine also demonstrated comparable efficacy results to haloperidol in terms of the proportion of patients in symptomatic remission from mania and depression at 6 and 12 weeks. In a co-therapy study of patients treated with lithium or valproate for a minimum of 2 weeks, the addition of olanzapine 10 mg (co-therapy with lithium or valproate) resulted in a greater reduction in symptoms of mania than lithium or valproate monotherapy after 6 weeks.

In a 12-month recurrence prevention study in manic episode patients who achieved remission on olanzapine and were then randomised to olanzapine or placebo, olanzapine demonstrated statistically significant superiority over placebo on the primary endpoint of bipolar recurrence. Olanzapine also showed a statistically significant advantage over placebo in terms of preventing either recurrence into mania or recurrence into depression.

In a second 12-month recurrence prevention study in manic episode patients who achieved remission with a combination of olanzapine and lithium and were then randomised to olanzapine or lithium alone, olanzapine was statistically non-inferior to lithium on the primary endpoint of bipolar recurrence (olanzapine 30.0%, lithium 38.3%; p = 0.055).

In an 18-month co-therapy study in manic or mixed episode patients stabilised with olanzapine plus a mood stabiliser (lithium or valproate), long-term olanzapine co-therapy with lithium or valproate was not statistically significantly superior to lithium or valproate alone in delaying bipolar recurrence, defined according to syndromic (diagnostic) criteria.

Paediatric population

The experience in adolescents (ages 13 to 17 years) is limited to short term efficacy data in schizophrenia (6 weeks) and mania associated with bipolar I disorder (3 weeks), involving less than 200 adolescents.Olanzapine was used as a flexible dose starting with 2.5 and ranging up to 20 mg/day. During treatment with olanzapine, adolescents gained significantly more weight compared with adults. The magnitude of changes in fasting total cholesterol, LDL cholesterol, triglycerides, and prolactin (see sections 4.4 and 4.8) were greater in adolescents than in adults. There are no data on maintenance of effect and limited data on long term safety (see sections 4.4 and 4.8).). Information on long term safety is primarily limited to open-label, uncontrolled data.


Absorption

Olanzapine is well absorbed after oral administration, reaching peak plasma concentrations within 5 to 8 hours. The absorption is not affected by food. Absolute oral bioavailability relative to intravenous administration has not been determined.

Distribution

The plasma protein binding of olanzapine was about 93% over the concentration range of about 7 to about 1000 ng/ml. Olanzapine is bound predominantly to albumin and α1-acid-glycoprotein.

Biotransformation

Olanzapine is metabolised in the liver by conjugative and oxidative pathways. The major circulating metabolite is the 10-N-glucuronide, which does not pass the blood brain barrier. Cytochromes P450-CYP1A2 and P450-CYP2D6 contribute to the formation of the N-desmethyl and 2-hydroxymethyl metabolites; both exhibited significantly less in vivopharmacological activity than olanzapine in animal studies. The predominant pharmacologic activity is from the parent, olanzapine.

Elimination

After oral administration, the mean terminal elimination half-life of olanzapine in healthy subjects varied on the basis of age and gender.

In healthy elderly (65 and over) versus non-elderly subjects, the mean elimination half-life was prolonged (51.8 versus 33.8 hours) and the clearance was reduced (17.5 versus 18.2 l/hr). The pharmacokinetic variability observed in the elderly is within the range for the non-elderly. In 44 patients with schizophrenia >65 years of age, dosing from 5 to 20 mg/day was not associated with any distinguishing profile of adverse events.

In female versus male subjects, the mean elimination half-life was somewhat prolonged (36.7 versus 32.3 hours) and the clearance was reduced (18.9 versus 27.3 l/hr). However, olanzapine (5-20 mg) demonstrated a comparable safety profile in female (n = 467) as in male patients (n = 869).

Renal impairment

In renally impaired patients (creatinine clearance <10ml/min) versus healthy subjects, there was no significant difference in mean elimination half-life (37.7 versus 32.4 hours) or clearance (21.2 versus 25.0 l/hr). A mass balance study showed that approximately 57% of radiolabelled olanzapine appeared in urine, principally as metabolites.

 Hepatic impairment

A small study of the effect of impaired liver function in 6 subjects with clinically significant (Childs Pugh Classification A (n = 5) and B (n = 1)) cirrhosis revealed little effect on the pharmacokinetics of orally administered olanzapine (2.5 – 7.5 mg single dose): Subjects with mild to moderate hepatic dysfunction had slightly increased systemic clearance and faster elimination half-time compared to subjects with no hepatic dysfunction (n = 3). There were more smokers among subjects with cirrhosis (4/6; 67 %) than among subjects with no hepatic dysfunction (0/3; 0 %).

Smoking

In non-smoking versus smoking subjects (males and females), the mean elimination half-life was prolonged (38.6 versus 30.4 hours) and the clearance was reduced (18.6 versus 27.7 l/hr).

The plasma clearance of olanzapine is lower in elderly versus young subjects, in females versus males, and in non-smokers versus smokers. However, the magnitude of the impact of age, gender, or smoking on olanzapine clearance and half-life is small in comparison to the overall variability between individuals.

In a study of Caucasians, Japanese, and Chinese subjects, there were no differences in the pharmacokinetic parameters among the three populations.

Paediatric population

Adolescents (ages 13 to 17 years): The pharmacokinetics of olanzapine are similar between adolescents and adults. In clinical studies, the average olanzapine exposure was approximately 27% higher in adolescents. Demographic differences between the adolescents and adults include a lower average body weight and fewer adolescents were smokers. Such factors possibly contribute to the higher average exposure observed in adolescents.


In long-term animal studies with neuroleptic drugs, including sulpiride, an increased incidence of various endocrine tumours (some of which have occasionally been malignant) has been seen in some but not all strains of rats and mice studied. The significance of these findings to man is not known; there is no current evidence of an association between neuroleptic use and tumour risk in man.

 


Lactose monohydrate

Low Substituted Hydroxypropyl Cellulose

Microcrystalline Cellulose

Hydroxypropyl Cellulose

Magnesium Stearate

Seal Coating (Hypromellose & Talc)

Film Coating (Opadry II White)


Not Applicable


Blister pack: 3 years

Store below 30°C.

Store it in the original package in order to protect from light and moisture.


Olazaine film coated Tablets are packed in Alu /Alu Blister as 7 tablets per blister and 28 tablets per pack.


Not applicable.


Marketing Authorisation Holder and Manufacturer Medical and Cosmetic Products Company Ltd. (Riyadh Pharma) P.O.Box 442, Riyadh 11411 Fax: +966 11 265 0505 Email: contact@riyadhpharma.com For any information about this medicinal product, please contact the local representative of marketing authorisation holder: Saudi Arabia Marketing department Riyadh Tel: +966 11 265 0111 Email: marketing@riyadhpharma.com

3/2019
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