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Zega® belongs to a group of medicines used to treat epilepsy, neuropathic pain and Generalized Anxiety Disorder (GAD) in adults.
Peripheral and central neuropathic pain: Zega® is used to treat long lasting pain caused by damage to the nerves. A variety of diseases can cause peripheral neuro- pathic pain, such as diabetes or shingles. Pain sensations may be described as hot, burning, throbbing, shooting, stabbing, sharp, cramping, aching, tingling, numbness, pins and needles. Peripheral and central neuropathic pain may also be associated with mood changes, sleep disturbance, fatigue (tiredness), and can have an impact on physical and social functioning and overall quality of life.
Epilepsy: Zega® is used to treat a certain form of epilepsy (partial seizures with or without secondary generalization) in adults. Your doctor will prescribe Zega® for you to help treat your epilepsy when your current treatment is not controlling your
condition. You should take Zega® in addition to your current treatment. Zega® is not intended to be used alone, but should always be used in combination with other anti-epileptic treatment.
Generalized Anxiety Disorder: Zega® is used to treat Generalized Anxiety Disorder (GAD). The symptoms of GAD are prolonged excessive anxiety and worry that are difficult to control. GAD can also cause restlessness or feeling keyed up or on edge, being easily fatigued (tired), having difficulty concentrating or mind going blank, feeling irritable, and having muscle tension or sleep disturbance. This is different to the stresses and strains of everyday life.
Do not take Zega®:
If you are allergic to pregabalin or any of the other ingredients of this medicine.
Warnings and Precautions
Talk to your doctor or pharmacist before taking Zega®.
· Some patients taking pregabalin have reported symptoms suggesting an allergic reaction. These symptoms include swelling of the face, lips, tongue, and throat, as well as diffuse skin rash. Should you experience any of these reactions, you should contact your physician immediately.
· Pregabalin has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall) in elderly patients. Therefore, you should be careful until you are used to any effect the medicine might have.
· Zega® may cause blurring or loss of vision, or other changes in eyesight, many of which are temporary. You should immediately tell your doctor if you experience any changes in your vision.
· Some patients with diabetes who gain weight while taking pregabalin may need an alteration in their diabetic medicines.
· Certain side effects may be more common, such as sleepiness, because patients with spinal cord injury may be taking other medicines to treat, for example, pain
or spasticity, that have similar side effects to pregabalin and the severity of these effects may be increased when taken together.
· There have been reports of heart failure in some patients when taking pregabalin;
these patients were mostly elderly with cardiovascular conditions. Before taking this medicine you should tell your doctor if you have a history of heart disease.
· There have been reports of kidney failure in some patients when taking pregabalin.
If while taking Zega® you notice decreased urination, you should tell your doctor as stopping the medicine may improve this.
· A small number of people being treated with anti-epileptics such as pregabalin
have had thoughts of harming or killing themselves. If at any time you have these thoughts, immediately contact your doctor.
· When Zega® is taken with other medicines that may cause constipation (such
as some types of pain medicines) it is possible that gastrointestinal problems may occur (e.g. constipation, blocked or paralysed bowel). Tell your doctor if you experi- ence constipation, especially if you are prone to this problem.
· Before taking this medicine you should tell your doctor if you have a history of
alcoholism or any drug abuse or dependence. Do not take more medicine than prescribed.
· There have been reports of convulsions when taking pregabalin or shortly
after stopping pregabalin. If you experience a convulsion, contact your doctor immediately.
· There have been reports of reduction in brain function (encephalopathy) in some
patients taking pregabalin when they have other conditions. Tell your doctor if you have a history of any serious medical conditions, including liver or kidney disease. Children and adolescents
The safety and efficacy in children and adolescents (under 18 years of age) has not been established and therefore, pregabalin should not be used in this age group.
Other medicines and Zega®
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Zega® and certain other medicines may influence each other (interaction). When taken with certain other medicines, Zega® may potentiate the side effects seen with these medicines, including respiratory failure and coma. The degree of dizziness, sleepiness and decreased concentration may be increased if Zega® is taken together with medicinal products containing:
· Oxycodone – (used as a pain-killer).
· Lorazepam – (used for treating anxiety).
· Alcohol.
Zega® may be taken with oral contraceptives.
Zega® with food, drink and alcohol
Zega® capsules may be taken with or without food. It is advised not to drink alcohol while taking Zega®. Pregnancy and breast-feeding
Zega® should not be taken during pregnancy or when breast-feeding, unless you are told otherwise by your doctor. Effective contraception must be used by women of child-bearing potential. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Driving and using machines
Zega® may produce dizziness, sleepiness and decreased concentration. You should not drive, operate complex machinery or engage in other potentially hazardous activities until you know whether this medicine affects your ability to perform these activities.
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 determine what dose is appropriate for you.
Zega® is for oral use only.
Peripheral and central neuropathic pain, epilepsy or Generalised Anxiety Disorder:
· Take the number of capsules as instructed by your doctor.
· The dose, which has been adjusted for you and your condition, will generally be between 150 mg and 600 mg each day.
· Your doctor will tell you to take Zega® either twice or three times a day. For twice a day take Zega® once in the morning and once in the evening, at about the same time each day. For three times a day take Zega® once in the morning, once in the afternoon and once in the evening, at about the same time each day.
If you have the impression that the effect of Zega® is too strong or too weak, talk to your doctor or pharmacist.
If you are an elderly patient (over 65 years of age), you should take Zega® normally except if you have problems with your kidneys.
Your doctor may prescribe a different dosing schedule and/or dose if you have problems with your kidneys.
Swallow the capsule whole with water.
Continue taking Zega® until your doctor tells you to stop.
If you take more Zega® than you should
Call your doctor or go to the nearest hospital emergency unit immediately. Take your box or bottle of Zega® capsules with you. You may feel sleepy, confused, agitated, or restless as a result of taking more Zega® than you should.
If you forget to take Zega®
It is important to take your Zega® capsules regularly at the same time each day. If you forget to take a dose, take it as soon as you remember unless it is time for your next dose. In that case, just carry on with the next dose as normal. Do not take a double dose to make up for a forgotten dose.
If you stop taking Zega®
Do not stop taking Zega® unless your doctor tells you to. If your treatment is stopped it should be done gradually over a minimum of 1 week.
After stopping long and short-term Zega® treatment, you need to know that you may experience certain side effects. These include, trouble sleeping, headache, nausea, feeling anxious, diarrhea, flu-like symptoms, convulsions, nervousness, depression, pain, sweating, and dizziness. These symptoms may occur more commonly or severely if you have been taking Zega® for a longer period of time.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Very common (may affect more than 1 in 10 people):
Dizziness, drowsiness, headache.
Common (may affect up to 1 in 10 people):
· Increased appetite.
· Feeling of elation, confusion, disorientation, decrease in sexual interest, irritability.
· Disturbance in attention, clumsiness, memory impairment, loss of memory, tremor, difficulty with speaking, tingling feeling, numbness, sedation, lethargy, insomnia, fatigue, feeling abnormal.
· Blurred vision, double vision.
· Vertigo, problems with balance, fall.
· Dry mouth, constipation, vomiting, flatulence, diarrhea, nausea, swollen abdomen.
· Difficulties with erection.
· Swelling of the body including extremities.
· Feeling drunk, abnormal style of walking.
· Weight gain.
· Muscle cramp, joint pain, back pain, pain in limb.
· Sore throat.
Uncommon (may affect up to 1 in 100 people):
· Loss of appetite, weight loss, low blood sugar, high blood sugar.
· Change in perception of self, restlessness, depression, agitation, mood swings, difficulty finding words, hallucinations, abnormal dreams, panic attacks, apathy, aggression, elevated mood, mental impairment, difficulty with thinking, increase in sexual interest, problems with sexual functioning including inability to achieve a sexual climax, delayed ejaculation.
· Changes in eyesight, unusual eye movement, changes in vision including tunnel vi-
sion, flashes of light, jerky movements, reduced reflexes, increased activity, dizziness on standing, sensitive skin, loss of taste, burning sensation, tremor on movement, decreased consciousness, loss of consciousness, fainting, increased sensitivity to noise, feeling unwell.
· Dry eyes, eye swelling, eye pain, weak eyes, watery eyes, eye irritation.
· Heart rhythm disturbances, increased heart rate, low blood pressure, high blood pressure, changes in heart beat, heart failure.
· Flushing, hot flushes.
· Difficulty breathing, dry nose, nasal congestion.
· Increased saliva production, heartburn, numb around mouth.
· Sweating, rash, chills, fever.
· Muscle twitching, joint swelling, muscle stiffness, pain including muscle pain, neck pain.
· Breast pain.
· Difficulty with or painful urination, incontinence.
· Weakness, thirst, chest tightness.
· Changes in blood and liver test results (blood creatinine phosphokinase increased, alanine amino transferase increased, aspartate aminotransferase increased, platelet count decreased, neutropaenia, increase in blood creatinine, decrease in blood potassium).
· Hypersensitivity, swollen face, itchiness, hives, runny nose, nose bleed, cough, snoring.
· Painful menstrual periods.
· Coldness of hands and feet.
Rare (may affect up to 1 in 1,000 people):
· Abnormal sense of smell, swinging vision, altered perception of depth, visual bright- ness, vision loss.
· Dilated pupils, cross eyes.
· Cold sweat, tightness of the throat, swollen tongue.
· Inflammation of the pancreas.
· Difficulty in swallowing.
· Slow or reduced movement of the body.
· Difficulty with writing properly.
· Increased fluid in the abdomen.
· Fluid in the lungs.
· Convulsions.
· Changes in the recording of electrical changes (ECG) in the heart which correspond to heart rhythm disturbances.
· Muscle damage.
· Breast discharge, abnormal breast growth, breast growth in males.
· Interrupted menstrual periods.
· Kidney failure, reduced urine volume, urinary retention.
· Decrease in white blood cell count.
· Inappropriate behaviour.
· Allergic reactions (which may include difficulty breathing, inflammation of the eyes (keratitis) and a serious skin reaction characterized by rash, blisters, peeling skin and pain).
If you experience swollen face or tongue or if your skin turns red and starts to blister or peel, you should seek immediate medical advice.
Certain side effects may be more common, such as sleepiness, because patients with spinal cord injury may be taking other medicines to treat, for example, pain or spastic- ity, that have similar side effects to pregabalin and the severity of these effects may be increased when taken together.
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.
Keep out of the reach and sight of children.
Do not use Zega® after the expiry date (EXP) which is stated on the blister and the carton.
The expiry date refers to the last day of that month.
Zega® capsules: Store below 30°C.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
The active substance is pregabalin (fine powder)..
The other ingredients are mannitol (fine powder), microcrystalline cellulose PH 102, povidone K30, croscarmellose sodium, magnesium stearate.
Pharma International Company Amman - Jordan
Tel: 00962-6-5158890 / 5157893
Fax: 00962-6-5154753
Email: marketing@pic-jo.com
ينتمي زيجا® إلى مجموعة من الأدوية تستعمل لعلاج الصرع، ألم الاعتلال العصبي و اضطراب القلق العام عند البالغين.
ألم الاعتلال العصبي الطرفي والمركزي: يستعمل زيجا® لعلاج الألم طويل الأمد الناتج عن تلف الأعصاب. قد تسبب أمراض مختلفة ألم الاعتلال العصبي الطرفي، مثل داء السكري أو الحلأ النطاقي. قد يوصف الإحساس بالألم كشعور بالحرارة، حرقة، نبض في العصب، ألم حاد يبدأ في مكان واحد وسرعان ما ينتقل إلى أماكن أخرى،
أو كالألم الناتج عن جرح بآلة حادة، ألم حاد، مغص، ألم مستمر، الإحساس بوخز خفيف، تنمل، تشوش الحس. ويمكن أيضا أن يرتبط ألم الاعتلال العصبي الطرفي والمركزي بتغيرات في المزاج، اضطراب النوم، شعور بالتعب، ويمكن أن يكون له تأثير على الوظائف الجسدية والاجتماعية ونمط الحياة بشكل عام.
الصرع: يستعمل زيجا® لعلاج شكل معين من الصرع )نوبات صرع جزئية مع أو بدون تعميم ثانوي( عند البالغين. سيصف لك الطبيب زيجا® للمساعدة في علاج حالة الصرع لديك عندما يكون العلاج الحالي لا يؤدي إلى تحسين حالتك. يجب أن تتناول زيجا® بالإضافة إلى العلاج الحالي. زيجا® غير مخصص للاستعمال لوحده، بل يجب دائما استعماله بالتزامن مع علاج آخر مضاد للصرع.
اضطراب القلق العام: يستعمل زيجا® لعلاج اضطراب القلق العام. تشمل أعراضه شعور بالقلق الشديد الذي يدوم لفترة طويلة ويصعب التحكم به. يمكن أيضاً أن يسبب شعور بعدم الراحة أو عصبية أو هياج، سرعة الشعور بالتعب، صعوبة في التركيز أو صعوبة القدرة على التذكر، سرعة الغضب، تشنج في العضلات أو اضطراب النوم، وذلك يختلف عن ضغوطات وتوترات الحياة اليومية.
الحالات التي يجب أن لا تأخذ فيها زيجا® كبسولات:
· إذا كنت تعاني من تحسس لبريجابالين أو لأي من المكونات الأخرى في هذا الدواء.
الاحتياطات والمحاذير
تحدث مع طبيبك أو الصيدلي قبل تناول زيجا®
· تم تسجيل أعراض تدل على حدوث تفاعل تحسسي لدى بعض المرضى الذين يتناولون بريجابالين. تتضمن هذه الأعراض تورم الوجه، الشفاه، اللسان، والحلق، بالإضافة إلى طفح جلدي منتشر. إذا عانيت من أي من هذه التفاعلات، يجب عليك الاتصال بطبيبك فوراً.
· ارتبط استعمال بريجابالين بالشعور بالدوار والنعاس، والذي من الممكن أن يزيد من حدوث الإصابات المفاجئة (السقوط) عند المرضى كبار السن. لذلك يجب أن تبقى حذرا لحين أن تعتاد على أي تأثير قد يسببه لك هذا الدواء.
· قد يسبب زيجا® ضبابية أوفقدان الرؤية، أو تغيرات أخرى في الرؤية، والعديد منها تكون مؤقتة. يجب عليك إخبار الطبيب فورا إذا حصل لديك أي تغيرات في الرؤية.
· قد يحتاج بعض المرضى الذين يعانون من داء السكري وزادت أوزانهم خلال فترة تناول بريجابالين إلى تغيير الأدوية التي يتناولونها لعلاج داء السكري.
· قد تكون بعض الآثار الجانبية أكثر شيوعا، مثل الشعور بالنعاس، حيث أن المرضى الذين يعانون من إصابات في الحبل الشوكي قد يتناولون أدوية أخرى لعلاج الحالات التالية، على سبيل المثال، الألم أو التشنج، والتي يكون لها آثار جانبية مشابهة لبريجابالين وقد تزداد حدة هذه الآثار عند تناول هذه الأدوية بشكل متزامن مع بريجابالين.
· تم تسجيل حدوث قصور في عضلة القلب عند بعض المرضى عند تناولهم بريجابالين، وكان معظمهم من كبار السن ويعانون من حالات قلبية وعائية. يجب إخبار الطبيب قبل تناول هذا الدواء إذا عانيت في السابق من مرض في القلب.
· تم تسجيل حدوث قصور في وظيفة الكلى عند بعض المرضى عند تناولهم بريجابالين. إذا لاحظت خلال تناولك زيجا® قلة كمية البول، يجب إخبار الطبيب حيث قد يساعد التوقف عن تناول هذا الدواء في تحسن الحالة.
· حصل لدى عدد قليل من الأشخاص الذين تم عالجهم بمضادات صرع مثل بريجابالين تفكير بإيذاء أو قتل أنفسهم. إذا حصل لديك هذه الأفكار في أي وقت، اتصل مع الطبيب فوراً.
· عند تناول زيجا® مع أدوية أخرى التي قد تسبب الإمساك )مثل بعض أنواع الأدوية التي تعالج الألم( فمن الممكن حصول مشاكل معدية معوية )مثل الإمساك، انسداد أو حصول عجز في حركة الأمعاء.( أخبر الطبيب إذا حصل لديك إمساك، خصوصا إذا كنت معرضاً للإصابة بهذه المشكلة.
· يجب أن تخبر طبيبك قبل تناول هذا الدواء إذا عانيت في السابق من إدمان على الكحول أو تعاطي المخدرات أو الإدمان على أدوية معينة. لا تتناول جرعة أكبر من الجرعة الموصوفة.
· تم تسجيل حدوث تشنجات خلال فترة تناول بريجابالين أو بعد فترة قصيرة من التوقف عن تناوله. إذا حصل لديك تشنجات، اتصل مع الطبيب فوراً.
· تم تسجيل حدوث قصور في وظيفة الدماغ )اعتلال دماغي( عند بعض المرضى الذين يتناولون بريجابالين ويعانون من حالات أخرى. أخبر طبيبك إذا عانيت في السابق من أي حالات طبية خطيرة، بما في ذلك مرض
في الكبد أو الكلى.
الأطفال والمراهقون
لم تثبت سالمة وفعالية استعمال هذا الدواء للأطفال والمراهقين )الأقل من 18 عاما(، لذلك يجب عدم استعمال
بريجابالين لهذه الفئة العمرية.
تناول أدوية أخرى مع زيجا®
الرجاء إخبار طبيبك أو الصيدلي إذا كنت تتناول، تناولت مؤخراً أو من الممكن أن تتناول أي أدوية أخرى.
قد يتفاعل زيجا® مع بعض الأدوية الأخرى. عند تناول زيجا® بشكل متزامن مع الأدوية الأخرى، قد يحفز زيجا® حصول الآثار الجانبية التي تظهر مع هذه الأدوية، والتي تتضمن قصور الجهاز التنفسي وغيبوبة. قد تزداد درجة الشعور بالدوار، النعاس وانخفاض التركيز إذا تم تناول زيجا® بالتزامن مع مستحضرات دوائية تحتوي على:
· أوكسيكودون - )يستعمل كمسكن للألم.(
· لورازيبام - )يستعمل لعلاج القلق.(
· الكحول.
من الممكن تناول زيجا® بالتزامن مع موانع الحمل التي يتم تناولها عن طريق الفم.
تناول زيجا® مع الطعام، الشراب والكحول
يمكن تناول كبسولات زيجا® مع أو بدون تناول الطعام.
ينصح بعدم شرب الكحول خلال فترة تناول زيجا.®
الحمل و الرضاعة الطبيعية
يجب عدم تناول زيجا® خلال فترة الحمل أو الرضاعة الطبيعية، ما لم يخبرك طبيبك بغير ذلك. يجب استعمال وسائل فعالة لمنع الحمل من قبل النساء في سن الإنجاب. إذا كنت حامل أو مرضعة، تعتقدين أنك حامل أو تخططين للحمل، استشيري الطبيب أو الصيدلي قبل تناول هذا الدواء. لا يوصى بالرضاعة الطبيعية خلال فترة تناول زيجا® حيث أنه من غير المعروف إذا كان زيجا® يفرز في حليب الثدي. استشيري الطبيب أو الصيدلي قبل تناول هذا الدواء.
القيادة و استخدام الآلات
قد يسبب زيجا® شعور بالدوار، النعاس وقلة التركيز. يجب تجنب القيادة، تشغيل الآلات المعقدة أو المشاركة في أنشطة أخرى قد تكون خطيرة إلى أن تتأكد إذا كان هذا الدواء يؤثر على قدرتك على القيام بمثل هذه الأنشطة.
تناول هذا الدواء دائما كما أخبرك طبيبك. يجب عليك التحقق من طبيبك أو الصيدلي إذا لم تكن متأكدا من كيفية استخدام الدواء.
سيحدد الطبيب الجرعة المناسبة لك.يستعمل زيجا® عن طريق الفم فقط.
ألم الاعتلال العصبي الطرفي والمركزي، الصرع أو اضطراب القلق العام:
· تناول عدد الكبسولات حسب تعليمات الطبيب.
· الجرعة التي تم تعديلها لك بناء على حالتك، ستتراوح بشكل عام بين 150 ملغم و600 ملغم يومياً.
· سيخبرك الطبيب بأن تتناول زيجا® إما مرتين أو ثلاث مرات يومياً، في حالة تناوله مرتين يوميا تناول زيجا® مرة في الصباح ومرة في المساء، في نفس الوقت تقريبا من كل يوم. في حالة تناوله ثلاث مرات يوميا تناول زيجا® مرة في الصباح، ومرة في وقت الظهيرة ومرة في المساء، في نفس الوقت تقريبا من كل يوم.
إذا لاحظت بأن تأثير زيجا® قوي أو ضعيف جداً، تحدث مع طبيبك أو الصيدلي. إذا كنت من المرضى كبار السن )فوق 65 عاما(، يجب تناول زيجا® كالمعتاد إلا إذا كنت تعاني من مشاكل في الكلى.
قد يصف الطبيب نظام جرعة و/أو جرعة مختلفة إذا كنت تعاني من مشاكل في الكلى.
قم بتناول الكبسولة كاملة مع الماء.
استمر في تناول زيجا® إلى أن يخبرك الطبيب بالتوقف عن تناوله.
إذا تناولت زيجا® أكثر مما يجب
اتصل مع الطبيب أو اذهب إلى قسم الطوارئ في أقرب مستشفى فوراً. اصطحب معك عبوة كبسوالت زيجا.® قد تشعر بالنعاس، الارتباك، الهياج، أو الشعور بعدم الراحة نتيجة لتناول زيجا® أكثر مما يجب.
إذا نسيت تناول زيجا® من المهم تناول كبسولات زيجا® بانتظام في نفس الوقت من كل يوم. إذا نسيت تناول جرعة، تناولها حال تذكرك ما لم يحين موعد الجرعة التالية. في هذه الحالة، فقط استمر في تناول الجرعة التالية كالمعتاد. لا تتناول جرعة مضاعفة لتعويض الجرعة التي نسيتها.
إذا توقفت عن تناول زيجا®
لا تتوقف عن تناول زيجا® ما لم يخبرك الطبيب بذلك. إذا تم ايقاف العلاج يجب أن يتم ذلك تدريجيا خلال فترة لا تقل عن أسبوع واحد. بعد التوقف عن تناول زيجا® سواء تم تناوله لفترة طويلة أو قصيرة، فإنك تحتاج إلى معرفة بأنه قد يحصل لديك آثار جانبية معينة، تتضمن، اضطراب النوم، صداع، شعور بالغثيان، شعور بالقلق، إسهال، أعراض تشبه الانفلونزا، تشنجات، الشعور بالعصبية، اكتئاب، ألم، تعرق و شعور بالدوار. قد تحدث هذه الأعراض بشكل أكثر شيوعا أو قد تكون حادة أكثر إذا تناولت زيجا® لفترة أطول.
إذا كان لديك أية أسئلة أخرى عن استخدام هذا الدواء، اسأل طبيبك أو الصيدلي.
مثل جميع الأدوية، يمكن لهذا الدواء أن يتسبب في آثار جانبية، على الرغم من أنها لا تحصل عند الجميع.
شائعة جداً (قد تؤثر على أكثر من شخص واحد من كل 10 أشخاص):
شعور بالدوار، النعاس، صداع.
شائعة (قد تؤثر على واحد أو أقل من كل 10 أشخاص):
· زيادة الشهية.
· الشعور بالزهو، ارتباك، اضطراب، انخفاض في الرغبة الجنسية، سرعة الغضب.
· اضطراب في الانتباه، حركات لا إرادية غير متناسقة، ضعف الذاكرة، رعاش، صعوبة في الكلام، الاحساس بوخز خفيف، تنمل، تسكين، وسن، أرق، شعور بالتعب، شعور بأنك لست على ما يرام.
· ضبابية و ازدواجية الرؤية.
· رنح، مشاكل في التوازن، التعرض للسقوط.
· جفاف الفم، إمساك، قيء، انتفاخ البطن، إسهال، شعور بالغثيان، تورم البطن.
· صعوبة حدوث الانتصاب.
· تورم في الجسم بما في ذلك الأطراف.
· شعور بالثمالة، طريقة مشي غير طبيعية.
· ازدياد الوزن.
· تقلصات عضلية، ألم في المفاصل، في الظهر و الأطراف.
· التهاب الحلق.
غير شائعة (قد تؤثر على واحد أو أقل من كل 100 شخص):
· فقدان الشهية، نقص الوزن، انخفاض مستوى السكر في الدم، ارتفاع مستوى السكر في الدم.
· تغير النظرة إلى الذات، شعور بعدم الراحة، اكتئاب، هياج، تقلبات في المزاج، صعوبة في إيجاد الكلمات،
هلوسات، أحلام غير طبيعية، نوبات هلع، خمول، عدوانية، الشعور بالنشوة، ضعف عقلي، صعوبة في التفكير، زيادة الرغبة الجنسية، مشاكل في الوظائف الجنسية تتضمن عدم القدرة على تحقيق الذروة الجنسية، تأخر في القذف.
· تغيرات في الرؤية، حركات غير طبيعية في العين، تغيرات في الرؤية تتضمن فقدان الرؤية الطرفية، رؤية ومضات ضوئية، حركات غير متوازنة، قلة ردود الفعل، ازدياد النشاط، شعور بالدوار عند الوقوف، حساسية الجلد، فقدان حاسة التذوق، شعور بالحرقة، رعاش عند الحركة، انخفاض الوعي، فقدان الوعي، إغماء، زيادة الحساسية للإزعاج، شعور بأنك لست على ما يرام.
· جفاف، تورم، ضعف، تدمع، تهيج العيون.
· اضطرابات نظمية نبضات القلب، ازدياد معدل نبضات القلب، انخفاض ضغط الدم، ارتفاع ضغط الدم، تغيرات في نبضات القلب، قصور وظيفة عضلة القلب.
·احمرار الوجه، احمرار الوجه المصحوب بارتفاع درجة الحرارة.
· صعوبة في التنفس، جفاف الأنف، احتقان الانف.
· ازدياد إفراز اللعاب، شعور بالحرقة، تنمل حول الفم.
· تعرق، طفح، قشعريرة، حمى.
· نفضان في العضلات، تورم المفاصل، تصلب العضلات، ألم يشمل ألم في العضلات، ألم في الرقبة.
· ألم في الثدي.
· صعوبة التبول أو ألم عند التبول، سلس بولي.
·شعور بالضعف، العطش، ضيق في الصدر.
· تغيرات في نتائج فحوصات الدم و وظائف الكبد (ارتفاع مستوى كرياتينين كاينيز في الدم، ارتفاع مستوى ألانين
أمينوترانسفيريز، ارتفاع مستوى أسبارتيت أمينوترانسفيريز، انخفاض تعداد الصفيحات الدموية، قلة العدلات،
ارتفاع مستوى الكرياتينين في الدم، انخفاض مستوى البوتاسيوم في الدم.(
·فرط التحسس، تورم الوجه، حكة، شرى، سيلان الأنف، نزيف في الأنف، سعال، شخير.
· دورة شهرية مؤلمة.
· برودة الأيدي والاقدام.
نادرة (قد تؤثر على واحد أو أقل من كل 1000 شخص):
· إحساس غير طبيعي بالروائح، تذبذب الرؤية، تغير في عمق الرؤية، سطوع الرؤية، فقدان البصر.
· توسع حدقة العين، حول.
· عرق بارد، تضيق في الحلق، تورم اللسان.
· التهاب البنكرياس.
· صعوبة في البلع.
·بطء أو قلة حركة الجسم.
· زيادة السوائل في منطقة البطن.
· تراكم السوائل في الرئتين.
· تشنجات.
· تغيرات في تسجيل التخطيط الكهربائي للقلب التي تدل على وجود اضطرابات في نظمية نبضات القلب.
· تلف العضلات.
· خروج إفرازات من الثدي، نمو غير طبيعي للثدي، نمو الثدي عند الرجال.
· انقطاع الدورة الشهرية.
· قصور وظيفة الكلى، انخفاض حجم البول، احتباس البول.
· انخفاض عدد خلايا الدم البيضاء.
· تصرفات غير مناسبة.
· تفاعلات تحسس (التي قد تتضمن صعوبة في التنفس، التهاب العيون )التهاب القرنية( وتفاعل تحسسي خطير في
الجلد يتميز بظهور طفح، تنفط، تقشر الجلد و ألم.)
إذا عانيت من تورم الوجه أو اللسان أو إذا أصبح لون الجلد أحمر وبدأ ظهور التنفطات أو التقشير، يجب الحصول على استشارة طبية فورية.
قد تكون بعض الآثار الجانبية أكثر شيوعاً، مثل الشعور بالنعاس، وذلك ألن المرضى الذين يعانون من إصابة في الحبل الشوكي قد يتناولون أدوية أخرى لعلاج الحالات التالية، على سبيل المثال، الألم أو التشنج، والتي يكون لها آثار جانبية مشابهة لبريجابالين وقد تزداد حدة هذه الآثار عند تناول هذه الأدوية بشكل متزامن مع بريجابالين.
إذا حصل لديك أي آثار جانبية، تحدث مع طبيبك أو الصيدلي. هذا يتضمن أي آثار جانبية غير مذكورة في هذه النشرة.
يحفظ بعيدا عن متناول الأطفال و نظرهم.
لا تستخدم أقراص زيجا® بعد تاريخ انتهاء الصلاحية المذكور على الشريط و العلبة الخارجية.
تاريخ الانتهاء يشير إلى اليوم الأخير من ذلك الشهر.
زيجا® كبسولات: يحفظ بدرجة حرارة دون 30 °م.
يجب أن لا يتم التخلص من الأدوية عن طريق مياه الصرف الصحي أو النفايات المنزلية. اسأل الصيدلي عن كيفية
التخلص من الأدوية التي لم تعد مطلوبة. وسوف تساعد هذه التدابير في حماية البيئة.
المادة الفعالة هي بريجابالين. المكونات الأخرى هي مانيتول، ميكروكريستالين سيليلوز، بوفيدون، كروسكارميلوز صوديوم، ستيرات المغنيسيوم.
زيجا® 75 ملغم كبسولات
كبسولات جيلاتينية صلبة حجم 3 ذات غطاء غير شفاف ذو لون أحمر مطبوع عليهPhI و جسمها غير شفاف
أبيض اللون مطبوع عليه mg 75 .Zega
حجم العبوة:
14 كبسولة7, كبسولات لكل شريط. شريطين/عبوة.
الشركة الدولية للدواء
عمان - الأردن
5158890-6-00962 / 5157893 :الهاتف
5154753-6-00962 :فاكس
البريد الإلكتروني: marketing@pic-jo.com
Neuropathic pain
Zega® is indicated for the treatment of peripheral and central neuropathic pain in adults.
Epilepsy
Zega® is indicated as adjunctive therapy in adults with partial seizures with or without secondary generalisation.
Generalised Anxiety Disorder
Zega® is indicated for the treatment of Generalised Anxiety Disorder (GAD) in adults.
Posology
The dose range is 150 to 600 mg per day given in either two or three divided doses.
Neuropathic pain
Pregabalin treatment can be started at a dose of 150 mg per day given as two or three divided doses. Based on individual patient response and tolerability, the dose may be increased to 300 mg per day after an interval of 3 to 7 days, and if needed, to a maximum dose of 600 mg per day after an additional 7-day interval.
Epilepsy
Pregabalin treatment can be started with a dose of 150 mg per day given as two or three divided doses. Based on individual patient response and tolerability, the dose may be increased to 300 mg per day after 1 week. The maximum dose of 600 mg per day may be achieved after an additional week.
Generalised Anxiety Disorder
The dose range is 150 to 600 mg per day given as two or three divided doses. The need for treatment should be reassessed regularly.
Pregabalin treatment can be started with a dose of 150 mg per day. Based on individual patient response and tolerability, the dose may be increased to 300 mg per day after 1 week. Following an additional week the dose may be increased to 450 mg per day. The maximum dose of 600 mg per day may be achieved after an additional week.
Discontinuation of pregabalin
In accordance with current clinical practice, if pregabalin has to be discontinued it is recommended this should be done gradually over a minimum of 1 week independent of the indication (see sections 4.4 and 4.8).
Patients with renal impairment
Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. As pregabalin clearance is directly proportional to creatinine clearance (see section 5.2), dose reduction in patients with compromised renal function must be individualised according to creatinine clearance (CLcr), as indicated in Table 1 determined using the following formula:
| creatinine clearance = (((140 - age in years) x (wt in kg)) x 1.23) / (serum creatinine in micromol/l) |
Pregabalin is removed effectively from plasma by haemodialysis (50% of drug in 4 hours). For patients receiving haemodialysis, the pregabalin daily dose should be adjusted based on renal function. In addition to the daily dose, a supplementary dose should be given immediately following every 4-hour haemodialysis treatment (see Table 1).
Table 1. Pregabalin dose adjustment based on renal function
Creatinine clearance (CLcr) (ml/min) | Total pregabalin daily dose * | Dose regimen | |
| Starting dose (mg/day) | Maximum dose (mg/day) |
|
≥ 60 | 150 | 600 | BID or TID |
≥ 30 - < 60 | 75 | 300 | BID or TID |
≥ 15 - < 30 | 25 – 50 | 150 | Once Daily or BID |
< 15 | 25 | 75 | Once Daily |
Supplementary dosage following haemodialysis (mg) | |||
| 25 | 100 | Single dose+ |
TID = Three divided doses BID = Two divided doses
* Total daily dose (mg/day) should be divided as indicated by dose regimen to provide mg/dose
+ Supplementary dose is a single additional dose
Patients with hepatic impairment
No dose adjustment is required for patients with hepatic impairment (see section 5.2).
Paediatric population
The safety and efficacy of Zega® in children below the age of 12 years and in adolescents (12-17 years of age) have not been established. Currently available data are described in section 4.8, 5.1 and 5.2 but no recommendation on a posology can be made.
Elderly (over 65 years of age) population
Elderly patients may require a dose reduction of pregabalin due to a decreased renal function (see patients with renal impairment).
Method of administration
Zega® may be taken with or without food.
Zega® is for oral use only.
Diabetic patients
In accordance with current clinical practice, some diabetic patients who gain weight on pregabalin treatment may need to adjust hypoglycaemic medicinal products.
Hypersensitivity reactions
There have been reports in the postmarketing experience of hypersensitivity reactions, including cases of angioedema. Pregabalin should be discontinued immediately if symptoms of angioedema, such as facial, perioral, or upper airway swelling occur.
Dizziness, somnolence, loss of consciousness, confusion, and mental impairment
Pregabalin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall) in the elderly population. There have also been postmarketing reports of loss of consciousness, confusion and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicinal product.
Vision-related effects
In controlled trials, a higher proportion of patients treated with pregabalin reported blurred vision than did patients treated with placebo which resolved in a majority of cases with continued dosing. In the clinical studies where ophthalmologic testing was conducted, the incidence of visual acuity reduction and visual field changes was greater in pregabalin-treated patients than in placebo-treated patients; the incidence of fundoscopic changes was greater in placebo-treated patients (see section 5.1).
In the postmarketing experience, visual adverse reactions have also been reported, including loss of vision, visual blurring or other changes of visual acuity, many of which were transient. Discontinuation of pregabalin may result in resolution or improvement of these visual symptoms.
Renal failure
Cases of renal failure have been reported and in some cases discontinuation of pregabalin did show reversibility of this adverse reaction.
Withdrawal of concomitant anti-epileptic medicinal products
There are insufficient data for the withdrawal of concomitant anti-epileptic medicinal products, once seizure control with pregabalin in the add-on situation has been reached, in order to reach monotherapy on pregabalin.
Withdrawal symptoms
After discontinuation of short-term and long-term treatment with pregabalin, withdrawal symptoms have been observed in some patients. The following events have been mentioned: insomnia, headache, nausea, anxiety, diarrhoea, flu syndrome, nervousness, depression, pain, convulsion, hyperhidrosis and dizziness, suggestive of physical dependence. The patient should be informed about this at the start of the treatment.
Convulsions, including status epilepticus and grand mal convulsions, may occur during pregabalin use or shortly after discontinuing pregabalin.
Concerning discontinuation of long-term treatment of pregabalin, data suggest that the incidence and severity of withdrawal symptoms may be dose-related.
Congestive heart failure
There have been postmarketing reports of congestive heart failure in some patients receiving pregabalin. These reactions are mostly seen in elderly cardiovascular compromised patients during pregabalin treatment for a neuropathic indication. Pregabalin should be used with caution in these patients. Discontinuation of pregabalin may resolve the reaction.
Treatment of central neuropathic pain due to spinal cord injury
In the treatment of central neuropathic pain due to spinal cord injury the incidence of adverse reactions in general, central nervous system adverse reactions and especially somnolence was increased. This may be attributed to an additive effect due to concomitant medicinal products (e.g. anti-spasticity agents) needed for this condition. This should be considered when prescribing pregabalin in this condition.
Suicidal ideation and behaviour
Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomised placebo controlled studies of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for pregabalin.
Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.
Reduced lower gastrointestinal tract function
There are postmarketing reports of events related to reduced lower gastrointestinal tract function (e.g. intestinal obstruction, paralytic ileus, constipation) when pregabalin was co- administered with medications that have the potential to produce constipation, such as opioid analgesics. When pregabalin and opioids will be used in combination, measures to prevent constipation may be considered (especially in female patients and elderly).
Misuse, abuse potential or dependence
Cases of misuse, abuse and dependence have been reported. Caution should be exercised in patients with a history of substance abuse and the patient should be monitored for symptoms of pregabalin misuse, abuse or dependence (development of tolerance, dose escalation, drug-seeking behaviour have been reported).
Encephalopathy
Cases of encephalopathy have been reported, mostly in patients with underlying conditions that may precipitate encephalopathy.
Since pregabalin is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (< 2% of a dose recovered in urine as metabolites), does not inhibit drug metabolism in vitro, and is not bound to plasma proteins, it is unlikely to produce, or be subject to, pharmacokinetic interactions.
In vivo studies and population pharmacokinetic analysis
Accordingly, in in vivo studies no clinically relevant pharmacokinetic interactions were observed between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol. Population pharmacokinetic analysis indicated that oral antidiabetics, diuretics, insulin, phenobarbital, tiagabine and topiramate had no clinically significant effect on pregabalin clearance.
Oral contraceptives, norethisterone and/or ethinyl oestradiol
Co-administration of pregabalin with the oral contraceptives norethisterone and/or ethinyl oestradiol does not influence the steady-state pharmacokinetics of either substance.
Central nervous system influencing medical products
Pregabalin may potentiate the effects of ethanol and lorazepam. In controlled clinical trials, multiple oral doses of pregabalin co-administered with oxycodone, lorazepam, or ethanol did not result in clinically important effects on respiration. In the postmarketing experience, there are reports of respiratory failure and coma in patients taking pregabalin and other central nervous system (CNS) depressant medicinal products. Pregabalin appears to be additive in the impairment of cognitive and gross motor function caused by oxycodone.
Interactions and the elderly
No specific pharmacodynamic interaction studies were conducted in elderly volunteers. Interaction studies have only been performed in adults.
Women of childbearing potential / Contraception in males and females
As the potential risk for humans is unknown, effective contraception must be used in women of child bearing potential.
Pregnancy
There are no adequate data from the use of pregabalin in pregnant women.
Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown.
Zega® should not be used during pregnancy unless clearly necessary (if the benefit to the mother clearly outweighs the potential risk to the foetus).
Breast-feeding
Pregabalin is excreted into human milk (see section 5.2). The effect of pregabalin on newborns/infants is unknown.A decision must be made whether to discontinue breast-feeding or to discontinue pregabalin therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility
There are no clinical data on the effects of pregabalin on female fertility.
In a clinical trial to assess the effect of pregabalin on sperm motility, healthy male subjects were exposed to pregabalin at a dose of 600 mg/day. After 3 months of treatment, there were no effects on sperm motility.
A fertilty study in female rats has shown adverse reproductive effects. Fertility studies in male rats have shown adverse reproductive and developmental effects. The clinical relevance of these findings is unknown (see section 5.3).
Zega® may have minor or moderate influence on the ability to drive and use machines. Zega® may cause dizziness and somnolence and therefore may influence the ability to drive or use machines. Patients are advised not to drive, operate complex machinery or engage in other potentially hazardous activities until it is known whether this medicinal product affects their ability to perform these activities.
The pregabalin clinical programme involved over 8900 patients exposed to pregabalin, of whom over 5600 were in double-blind placebo-controlled trials. The most commonly reported adverse reactions were dizziness and somnolence. Adverse reactions were usually mild to moderate in intensity. In all controlled studies, the discontinuation rate due to adverse reactions was 12% for patients receiving pregabalin and 5% for patients receiving placebo. The most common adverse reactions resulting in discontinuation from pregabalin treatment groups were dizziness and somnolence.
In table 2 below all adverse reactions, which occurred at an incidence greater than placebo and in more than one patient, are listed by class and frequency (very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
The adverse reactions listed may also be associated with the underlying disease and / or concomitant medicinal products.
In the treatment of central neuropathic pain due to spinal cord injury the incidence of adverse reactions in general, CNS adverse reactions and especially somnolence was increased (see section 4.4).
Additional reactions reported from postmarketing experience are included in italics in the list below.
Table 2. Pregabalin Adverse Drug Reactions
System Organ Class | Adverse drug reactions |
Infections and infestations | |
Common | Nasopharyngitis |
Blood and lymphatic system disorders | |
Uncommon | Neutropaenia |
Immune system disorders | |
Uncommon | Hypersensitivity |
Rare | Angioedema, allergic reaction |
Metabolism and nutrition disorders | |
Common | Appetite increased |
Uncommon | Anorexia, hypoglycaemia |
Psychiatric disorders | |
Common | Euphoric mood, confusion, irritability, disorientation, insomnia, libido decreased |
Uncommon | Hallucination, panic attack, restlessness, agitation, depression, depressed mood, elevated mood, aggression, mood swings, depersonalisation, word finding difficulty, abnormal dreams, libido increased, anorgasmia, apathy |
Rare | Disinhibition |
Nervous system disorders | |
Very Common | Dizziness, somnolence, headache |
Common | Ataxia, coordination abnormal, tremor, dysarthria, amnesia, memory impairment, disturbance in attention, paraesthesia, hypoaesthesia, sedation, balance disorder, lethargy |
Uncommon | Syncope, stupor, myoclonus, loss of consciousness, psychomotor hyperactivity, dyskinesia, dizziness postural, intention tremor, nystagmus, cognitive disorder, mental impairment, speech disorder, hyporeflexia, hyperaesthesia, burning sensation, ageusia, malaise |
Rare | Convulsions, parosmia, hypokinesia, dysgraphia |
Eye disorders | |
Common | Vision blurred, diplopia |
Uncommon | Peripheral vision loss, visual disturbance, eye swelling, visual field defect, visual acuity reduced, eye pain, asthenopia, photopsia, dry eye, lacrimation increased, eye irritation |
Rare | Vision loss, keratitis, oscillopsia, altered visual depth perception, mydriasis, strabismus, visual brightness |
Ear and labyrinth disorders | |
Common | Vertigo |
Uncommon | Hyperacusis |
Cardiac disorders | |
Uncommon | Tachycardia, atrioventricular block first degree, sinus bradycardia, congestive heart failure |
Rare | QT prolongation, sinus tachycardia, sinus arrhythmia |
Vascular disorders | |
Uncommon | Hypotension, hypertension, hot flushes, flushing, peripheral coldness |
Respiratory, thoracic and mediastinal disorders | |
Uncommon | Dyspnoea, epistaxis, cough, nasal congestion, rhinitis, snoring, nasal dryness |
Rare | Pulmonary oedema, throat tightness, |
Gastrointestinal disorders | |
Common | Vomiting, nausea, constipation, diarrhoea, flatulence, abdominal distension, dry mouth |
Uncommon | Gastrooesophageal reflux disease, salivary hypersecretion, hypoaesthesia oral |
Rare | Ascites, pancreatitis, swollen tongue, dysphagia |
Skin and subcutaneous tissue disorders | |
Uncommon | Rash papular, urticaria, hyperhidrosis, pruritus |
Rare | Stevens Johnson syndrome, cold sweat |
Musculoskeletal and connective tissue disorders | |
Common | Muscle cramp, arthralgia, back pain, pain in limb, cervical spasm |
Uncommon | Joint swelling, myalgia, muscle twitching, neck pain, muscle stiffness |
Rare | Rhabdomyolysis |
Renal and urinary disorders | |
Uncommon | Urinary incontinence, dysuria |
Rare | Renal failure, oliguria, urinary retention |
Reproductive system and breast disorders | |
Common | Erectile dysfunction |
Uncommon | Sexual dysfunction, ejaculation delayed, dysmenorrhoea, breast pain |
Rare | Amenorrhoea, breast discharge, breast enlargement, gynaecomastia |
General disorders and administration site conditions | |
Common | Oedema peripheral, oedema, gait abnormal, fall, feeling drunk, feeling abnormal, fatigue |
Uncommon | Generalised oedema, face oedema, chest tightness, pain, pyrexia, thirst, chills, asthenia |
Investigations | |
Common | Weight increased |
Uncommon | Blood creatine phosphokinase increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood glucose increased, platelet count decreased, blood creatinine increased, blood potassium decreased, weight decreased |
Rare | White blood cell count decreased |
After discontinuation of short-term and long-term treatment with pregabalin withdrawal symptoms have been observed in some patients. The following reactions have been mentioned: insomnia, headache, nausea, anxiety, diarrhea, flu syndrome, convulsions, nervousness, depression, pain, hyperhidrosis and dizziness, suggestive of physical dependence. The patient should be informed about this at the start of the treatment.
Concerning discontinuation of long-term treatment of pregabalin, data suggest that the incidence and severity of withdrawal symptoms may be dose-related.
Paediatric population
The pregabalin safety profile observed in two paediatric studies (pharmacokinetic and tolerability study, n=65; 1 year open label follow on safety study, n=54) was similar to that observed in the adult studies (see sections 4.2, 5.1 and 5.2).
In the postmarketing experience, the most commonly reported adverse reactions observed when pregabalin was taken in overdose included somnolence, confusional state, agitation, and restlessness.
In rare occasions, cases of coma have been reported.
Treatment of pregabalin overdose should include general supportive measures and may include haemodialysis if necessary (see section 4.2 Table 1).
Pharmacotherapeutic group: Anti-epileptics, other anti-epileptics ATC code: N03AX16
The active substance, pregabalin, is a gamma-aminobutyric acid analogue [(S)-3- (aminomethyl)-5-methylhexanoic acid].
Mechanism of action
Pregabalin binds to an auxiliary subunit (α2-δ protein) of voltage-gated calcium channels in the central nervous system,
Clinical efficacy and safety
Neuropathic pain
Efficacy has been shown in trials in diabetic neuropathy, post herpetic neuralgia and spinal cord injury. Efficacy has not been studied in other models of neuropathic pain.
Pregabalin has been studied in 10 controlled clinical trials of up to 13 weeks with twice a day dosing (BID) and up to 8 weeks with three times a day (TID) dosing. Overall, the safety and efficacy profiles for BID and TID dosing regimens were similar.
In clinical trials up to 12 weeks for both peripheral and central neuropathic pain, a reduction in pain was seen by week 1 and was maintained throughout the treatment period.
In controlled clinical trials in peripheral neuropathic pain 35% of the pregabalin treated patients and 18% of the patients on placebo had a 50% improvement in pain score. For patients not experiencing somnolence, such an improvement was observed in 33% of patients treated with pregabalin and 18% of patients on placebo. For patients who experienced somnolence the responder rates were 48% on pregabalin and 16% on placebo.
In the controlled clinical trial in central neuropathic pain 22% of the pregabalin treated patients and 7% of the patients on placebo had a 50% improvement in pain score.
Epilepsy
Adjunctive Treatment
Pregabalin has been studied in 3 controlled clinical trials of 12 week duration with either BID or TID dosing. Overall, the safety and efficacy profiles for BID and TID dosing regimens were similar.
A reduction in seizure frequency was observed by Week 1.
Paediatric population
The efficacy and safety of pregabalin as adjunctive treatment for epilepsy in paediatric patients below the age of 12 and adolescents has not been established. The adverse events observed in a pharmacokinetic and tolerability study that enrolled patients from 3 months to 16 years of age (n=65) were similar to those observed in adults. Results of a 1 year open label safety study in 54 paediatric patients from 3 months to 16 years of age with epilepsy indicate that the adverse events of pyrexia and upper respiratory infections were observed more frequently than in adult studies (see sections 4.2, 4.8 and 5.2).
Monotherapy (newly diagnosed patients)
Pregabalin has been studied in 1 controlled clinical trial of 56 week duration with BID dosing. Pregabalin did not achieve non-inferiority to lamotrigine based on the 6-month seizure freedom endpoint. Pregabalin and lamotrigine were similarly safe and well tolerated.
Generalised Anxiety Disorder
Pregabalin has been studied in 6 controlled trials of 4-6 week duration, an elderly study of 8 week duration and a long-term relapse prevention study with a double blind relapse prevention phase of 6 months duration.
Relief of the symptoms of GAD as reflected by the Hamilton Anxiety Rating Scale (HAM-A) was observed by Week 1.
In controlled clinical trials (4-8 week duration) 52% of the pregabalin treated patients and 38% of the patients on placebo had at least a 50% improvement in HAM-A total score from baseline to endpoint.
In controlled trials, a higher proportion of patients treated with pregabalin reported blurred vision than did patients treated with placebo which resolved in a majority of cases with
continued dosing. Ophthamologic testing (including visual acuity testing, formal visual field testing and dilated funduscopic examination) was conducted in over 3600 patients within controlled clinical trials. In these patients, visual acuity was reduced in 6.5% of patients treated with pregabalin, and 4.8% of placebo-treated patients. Visual field changes were detected in 12.4% of pregabalin-treated, and 11.7% of placebo-treated patients. Funduscopic changes were observed in 1.7% of pregabalin-treated and 2.1% of placebo-treated patients.
Pregabalin steady-state pharmacokinetics are similar in healthy volunteers, patients with epilepsy receiving anti-epileptic drugs and patients with chronic pain.
Absorption
Pregabalin is rapidly absorbed when administered in the fasted state, with peak plasma concentrations occurring within 1 hour following both single and multiple dose administration. Pregabalin oral bioavailability is estimated to be ≥ 90% and is independent of dose. Following repeated administration, steady state is achieved within 24 to 48 hours. The rate of pregabalin absorption is decreased when given with food resulting in a decrease in Cmax by approximately 25-30% and a delay in tmax to approximately 2.5 hours. However, administration of pregabalin with food has no clinically significant effect on the extent of pregabalin absorption.
Distribution
In preclinical studies, pregabalin has been shown to cross the blood brain barrier in mice, rats, and monkeys. Pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats. In humans, the apparent volume of distribution of pregabalin following oral administration is approximately 0.56 l/kg. Pregabalin is not bound to plasma proteins.
Biotransformation
Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabelled pregabalin, approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The N-methylated derivative of pregabalin, the major metabolite of pregabalin found in urine, accounted for 0.9% of the dose. In preclinical studies, there was no indication of racemisation of pregabalin S-enantiomer to the R-enantiomer.
Elimination
Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug.
Pregabalin mean elimination half-life is 6.3 hours. Pregabalin plasma clearance and renal clearance are directly proportional to creatinine clearance (see section 5.2 Renal impairment). Dose adjustment in patients with reduced renal function or undergoing haemodialysis is necessary (see section 4.2 Table 1).
Linearity / non-linearity
Pregabalin pharmacokinetics are linear over the recommended daily dose range. Inter-subject pharmacokinetic variability for pregabalin is low (< 20%). Multiple dose pharmacokinetics are
predictable from single-dose data. Therefore, there is no need for routine monitoring of plasma concentrations of pregabalin.
Gender
Clinical trials indicate that gender does not have a clinically significant influence on the plasma concentrations of pregabalin.
Renal impairment
Pregabalin clearance is directly proportional to creatinine clearance. In addition, pregabalin is effectively removed from plasma by haemodialysis (following a 4 hour haemodialysis treatment plasma pregabalin concentrations are reduced by approximately 50%). Because renal elimination is the major elimination pathway, dose reduction in patients with renal impairment and dose supplementation following haemodialysis is necessary (see section 4.2 Table 1).
Hepatic impairment
No specific pharmacokinetic studies were carried out in patients with impaired liver function. Since pregabalin does not undergo significant metabolism and is excreted predominantly as unchanged drug in the urine, impaired liver function would not be expected to significantly alter pregabalin plasma concentrations.
Paediatric population
Pregabalin pharmacokinetics were evaluated in paediatric patients with epilepsy (age groups: 1 to 23 months, 2 to 6 years, 7 to 11 years and 12 to 16 years) at dose levels of 2.5, 5, 10 and 15 mg/kg/day in a pharmacokinetic and tolerability study.
After oral administration of pregabalin in paediatric patients in the fasted state, in general, time to reach peak plasma concentration was similar across the entire age group and occurred 0.5 hours to 2 hours postdose.
Pregabalin Cmax and AUC parameters increased in a linear manner with increasing dose within each age group. The AUC was lower by 30% in paediatric patients below a weight of
30 kg due to an increased body weight adjusted clearance of 43% for these patients in comparison to patients weighing ≥30 kg.
Pregabalin terminal half-life averaged about 3 to 4 hours in paediatric patients up to 6 years of age, and 4 to 6 hours in those 7 years of age and older.
Population pharmacokinetic analysis showed that creatinine clearance was a significant covariate of pregabalin oral clearance, body weight was a significant covariate of pregabalin apparent oral volume of distribution, and these relationships were similar in paediatric and adult patients.
Pregabalin pharmacokinetics in patients younger than 3 months old have not been studied (see sections 4.2, 4.8 and 5.1).
Elderly (over 65 years of age)
Pregabalin clearance tends to decrease with increasing age. This decrease in pregabalin oral clearance is consistent with decreases in creatinine clearance associated with increasing age.
Reduction of pregabalin dose may be required in patients who have age related compromised renal function (see section 4.2 Table 1).
Breast-feeding mothers
The pharmacokinetics of 150 mg pregabalin given every 12 hours (300 mg daily dose) was evaluated in 10 lactating women who were at least 12 weeks postpartum. Lactation had little to no influence on pregabalin pharmacokinetics. Pregabalin was excreted into breast milk with average steady-state concentrations approximately 76% of those in maternal plasma. The estimated infant dose from breast milk (assuming mean milk consumption of 150 ml/kg/day) of women receiving 300 mg/day or the maximum dose of 600 mg/day would be 0.31 or 0.62 mg/kg/day, respectively. These estimated doses are approximately 7% of the total daily maternal dose on a mg/kg basis.
In conventional safety pharmacology studies in animals, pregabalin was well-tolerated at clinically relevant doses. In repeated dose toxicity studies in rats and monkeys CNS effects were observed, including hypoactivity, hyperactivity and ataxia. An increased incidence of retinal atrophy commonly observed in aged albino rats was seen after long-term exposure to pregabalin at exposures ≥ 5 times the mean human exposure at the maximum recommended clinical dose.
Pregabalin was not teratogenic in mice, rats or rabbits. Foetal toxicity in rats and rabbits occurred only at exposures sufficiently above human exposure. In prenatal/postnatal toxicity studies, pregabalin induced offspring developmental toxicity in rats at exposures > 2 times the maximum recommended human exposure.
Adverse effects on fertility in male and female rats were only observed at exposures sufficiently in excess of therapeutic exposure. Adverse effects on male reproductive organs and sperm parameters were reversible and occurred only at exposures sufficiently in excess of therapeutic exposure or were associated with spontaneous degenerative processes in male reproductive organs in the rat. Therefore the effects were considered of little or no clinical relevance.
Pregabalin is not genotoxic based on results of a battery of in vitro and in vivo tests.
Two-year carcinogenicity studies with pregabalin were conducted in rats and mice. No tumours were observed in rats at exposures up to 24 times the mean human exposure at the maximum recommended clinical dose of 600 mg/day. In mice, no increased incidence of tumours was found at exposures similar to the mean human exposure, but an increased incidence of haemangiosarcoma was observed at higher exposures. The non-genotoxic mechanism of pregabalin-induced tumour formation in mice involves platelet changes and associated endothelial cell proliferation. These platelet changes were not present in rats or in humans based on short-term and limited long-term clinical data. There is no evidence to suggest an associated risk to humans.
In juvenile rats the types of toxicity do not differ qualitatively from those observed in adult rats. However, juvenile rats are more sensitive. At therapeutic exposures, there was evidence of CNS clinical signs of hyperactivity and bruxism and some changes in growth (transient body weight gain suppression). Effects on the oestrus cycle were observed at 5-fold the human therapeutic exposure. Reduced acoustic startle response was observed in juvenile rats 1-2 weeks after exposure at >2 times the human therapeutic exposure. Nine weeks after exposure, this effect was no longer observable.
mannitol (fine powder), microcrystalline cellulose PH 102, povidone K30, croscarmellose sodium, magnesium stearate.
Not applicable.
Store below 30°C.
Zega® 75 mg Capsules
Size three hard gelatin capsule with red opaque cap printed PhI and white opaque body
printed Zega 75 mg.
Pack size:
14 capsules, 7 Capsules/Blister. 2 blisters/pack.
No special requirements.
