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Provecta is a prescription medicine used to treat partial-onset seizures in people 1 month of age and older. It is not known if brivaracetam is safe and effective in children younger than 1 month of age.
Do not take Provecta
Do not take Provecta if you are allergic to brivaracetam or any of the ingredients in Provecta. See section 7 of this leaflet for a complete list of ingredients in Provecta.
Warnings and precautions
Before taking Provecta, tell your healthcare provider about all of your medical conditions, including if you:
- Have or had depression, mood problems, or suicidal thoughts or behavior.
- Have liver problems.
- Have abused or been dependent on prescription medicines, street drugs, or alcohol.
- Are pregnant or plan to become pregnant. It is not known if brivaracetam will harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking brivaracetam. You and your healthcare provider will have to decide if you should take brivaracetam while you are pregnant.
- Are breastfeeding or plan to breastfeed. It is not known if brivaracetam passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take brivaracetam.
Children and adolescents
It is not known if brivaracetam is safe and effective in children younger than 1 month of age.
Other medicines and Provecta
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Provecta may affect the way other medicines work, and other medicines may affect how Provecta works. Do not start a new medicine without first talking with your healthcare provider. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist each time you get a new medicine.
Pregnancy and breast-feeding
Before taking Provecta, tell your healthcare provider if you:
- Are pregnant or plan to become pregnant. It is not known if brivaracetam will harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking brivaracetam. You and your healthcare provider will have to decide if you should take brivaracetam while you are pregnant.
- Are breastfeeding or plan to breastfeed. It is not known if brivaracetam passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take brivaracetam.
Driving and using machines
Do not drive or operate machinery until you know how brivaracetam affects you. Brivaracetam may cause drowsiness, tiredness, dizziness, and problems with your balance and coordination.
Provecta contains sodium, sorbitol and methyl paraben
Provecta contains sodium. Each ml of Provecta 10 mg/ml Oral Solution contains 1.2 mg sodium. This medicine contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially “sodium-free”.
Provecta contains sorbitol. Each ml of Provecta 10 mg/ml Oral Solution contains 239.80 mg sorbitol.
- Sorbitol is a source of fructose. If your doctor has told you that you (or your child) have an intolerance to some sugars or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down fructose, talk to your doctor before you (or your child) take or receive this medicine.
- Sorbitol may cause gastrointestinal discomfort and mild laxative effect.
Provecta contains methyl paraben. Each ml of Provecta 10 mg/ml Oral Solution contains 1 mg methyl paraben, which may cause allergic reactions (possibly delayed).
Take Provecta exactly as your healthcare provider tells you.
Your healthcare provider will tell you how much Provecta to take and when to take it.
Your healthcare provider may change your dose if needed. Do not change your dose without talking to your healthcare provider.
Take Provecta with or without food.
If your healthcare provider has prescribed Provecta oral solution, be sure to use the provided oral syringes to help you measure the correct amount of Provecta oral solution. Do not use a household teaspoon or tablespoon. Ask your pharmacist for instructions on how to use the oral syringes the right way.
When using Provecta oral solution, no dilution is necessary. Provecta oral solution may also be administered using a nasogastric tube or gastrostomy tube.
Monotherapy or Adjunctive Therapy
The recommended dosage for patients 1 month of age and older is included in Table 1. In pediatric patients weighing less than 50 kg, the recommended dosing regimen is dependent upon body weight. When initiating treatment, gradual dose escalation is not required. Dosage should be adjusted based on clinical response and tolerability.
Table 1: Recommended Dosage for Patients 1 Month of Age and Older
Age and Body Weight | Initial Dosage | Minimum and Maximum Maintenance Dosage |
Adults (16 years and older) | 50 mg (5 ml) twice daily [100 mg (10 ml) per day] | 25 mg (2.5 ml) to 100 mg (10 ml) twice daily [50 mg (5 ml) to 200 mg (20 ml) per day] |
Pediatric patients weighing 50 kg or more | 25 mg (2.5 ml) to 50 mg (5 ml) twice daily [50 mg (5 ml) to 100 mg (10 ml) per day] | 25 mg (2.5 ml) to 100 mg (10 ml) twice daily [50 mg (5 ml) to 200 mg (20 ml) per day] |
Pediatric patients weighing 20 kg to less than 50 kg | 0.5 mg/kg (0.05 ml/kg) to 1 mg/kg (0.1 ml/kg) twice daily [1 mg/kg (0.1 ml/kg) to 2 mg/kg (0.2 ml/kg) per day] | 0.5 mg/kg (0.05 ml/kg) to 2 mg/kg (0.2 ml/kg) twice daily [1 mg/kg (0.1 ml/kg) to 4 mg/kg (0.4 ml/kg) per day] |
Pediatric patients weighing 11 kg to less than 20 kg | 0.5 mg/kg (0.05 ml/kg) to 1.25 mg/kg (0.125 ml/kg) twice daily [1 mg/kg (0.1 ml/kg) to 2.5 mg/kg (0.25 ml/kg) per day] | 0.5 mg/kg (0.05 ml/kg) to 2.5 mg/kg (0.25 ml/kg) twice daily [1 mg/kg (0.1 ml/kg) to 5 mg/kg (0.5 ml/kg) per day] |
Pediatric patients weighing less than 11 kg | 0.75 mg/kg (0.075 ml/kg) to 1.5 mg/kg (0.15 ml/kg) twice daily [1.5 mg/kg (0.15 ml/kg) to 3 mg/kg (0.3 ml/kg) per day] | 0.75 mg/kg (0.075 ml/kg) to 3 mg/kg (0.3 ml/kg) twice daily [1.5 mg/kg (0.15 ml/kg) to 6 mg/kg (0.6 ml/kg) per day] |
Brivaracetam Injection Dosage
Brivaracetam injection may be used when oral administration is temporarily not feasible. Brivaracetam injection should be administered intravenously at the same dosage and same frequency as brivaracetam tablets and oral solution.
Patients with Hepatic Impairment
The recommended dosage for patients with hepatic impairment is included in Table 2.
Table 2: Recommended Dosage for Patients with Hepatic Impairment
Age and Body Weight | Initial Dosage | Minimum and Maximum Maintenance Dosage |
Adults (16 years and older) | 25 mg (2.5 ml) twice daily [50 mg (5 ml) per day] | 75 mg (7.5 ml) twice daily [150 mg (15 ml) per day] |
Pediatric patients weighing 50 kg or more | ||
Pediatric patients weighing 20 kg to less than 50 kg | 0.5 mg/kg (0.05 ml/kg) twice daily [1 mg/kg (0.1 ml/kg) per day] | 1.5 mg/kg (0.15 ml/kg) twice daily [3 mg/kg (0.3 ml/kg) per day] |
Pediatric patients weighing 11 kg to less than 20 kg | 0.5 mg/kg (0.05 ml/kg) twice daily [1 mg/kg (0.1 ml/kg) per day] | 2 mg/kg (0.2 ml/kg) twice daily [4 mg/kg (0.4 ml/kg) per day] |
Pediatric patients weighing less than 11 kg | 0.75 mg/kg (0.075 ml/kg) twice daily [1.5 mg/kg (0.15 ml/kg) per day] | 2.25 mg/kg (0.225 ml/kg) twice daily [4.5 mg/kg (0.45 ml/kg) per day] |
Instructions for use for patients or carers:
Two oral syringes will be provided in the carton. Check with your doctor which one you should use.
- For volume between 0.5 ml and 5 ml, you should use the 5 ml oral syringe (blue graduation marks) provided in the carton to ensure accurate dosing.
- For volume above 5 ml and up to 10 ml, you should use the 10 ml oral syringe (black graduation marks) provided in the carton to ensure accurate dosing.
5 ml oral dosing syringe | 10 ml oral dosing syringe |
The 5 ml oral syringe has 2 overlapping blue graduation marks: in steps of 0.25 ml and in steps of 0.1 ml. | The 10 ml oral syringe has black graduation marks in steps of 0.25 ml. |
- Open the bottle: press the cap and turn it anti-clockwise (figure 1).
Follow these steps the first time you take Provecta:
- Take off the adaptor from the oral syringe (figure 2).
- Put the adaptor into the top of the bottle (figure 3). Make sure it is fixed well in place. You do not need to remove the adaptor after use.
Follow these steps each time you take Provecta:
- Put the oral syringe into the adaptor opening (figure 4).
- Turn the bottle upside down (figure 5).
Hold the bottle upside down in one hand and use the other hand to fill the oral syringe.
- Pull the plunger down to fill the oral syringe with a small amount of solution (figure 6).
- Then push the plunger up to remove any possible air bubbles (figure 7).
- Pull the plunger down to the millilitre (ml) dose marker on the oral syringe prescribed by your doctor (figure 8).
- Turn the bottle the right way up (figure 9).
- Take the oral syringe out of the adaptor (figure 10).
There are two ways in which you can choose to drink the medicine:
- Empty the contents of the syringe into water (or juice) by pushing the plunger to the bottom of the oral syringe (figure 11) – you will then need to drink all of the water (add just enough to make it easy to drink) or
- Drink the solution directly from the oral syringe without water – drink the whole contents of the syringe (figure 12).
- Close the bottle with the plastic screw cap (you do not need to remove the adaptor).
- Wash the oral syringe with water only (figure 13).
- Keep the bottle, the oral syringe, and the leaflet in the carton.
If you take more Provecta than you should
If you take too much Provecta, call your doctor or go to the nearest emergency room right away.
If you stop taking Provecta
Do not stop Provecta without first talking to a healthcare provider.
- Stopping Provecta suddenly can cause serious problems.
- Stopping a seizure medicine suddenly can cause seizures that will not stop (status epilepticus).
Brivaracetam may cause serious side effects, including:
- See “Serious side effects”
- Nervous system problems. Drowsiness, tiredness, and dizziness are common with brivaracetam, but can be severe. See “Driving and using machines” brivaracetam can also cause problems with balance and coordination.
- Mental (psychiatric) symptoms. Brivaracetam can cause mood and behavior changes such as aggression, agitation, anger, anxiety, apathy, mood swings, depression, hostility, and irritability. Irritability and anxiety are common with brivaracetam, and can be severe. People who take brivaracetam can also get psychotic symptoms such as hallucinations (seeing or hearing things that are really not there), delusions (false or strange thoughts or beliefs), and unusual behavior.
The most common side effects of brivaracetam in adults include:
- Sleepiness
- Dizziness
- Feeling tired
- Nausea and vomiting
Side effects of brivaracetam in children 1 month to less than 16 years of age are similar to those seen in adults.
These are not all the possible side effects of brivaracetam. For more information, ask your healthcare provider or pharmacist. Tell your healthcare provider about any side effect that bothers you or that does not go away. Call your doctor for medical advice about side effects.
Keep this medicine out of the sight and reach of children.
Store below 30°C. Avoid freeze.
Store in the original package.
Safely throw away any opened bottle of Provecta oral solution after 8 months of first opening the bottle, even if there is medicine left in the bottle.
When using Provecta oral solution, no dilution is necessary.
Do not use this medicine after the expiry date which is stated on the package after “EXP”. The expiry date refers to the last day of that month.
Do not use this medicine if you notice any visible signs of deterioration.
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.
The active substance is brivaracetam.
Each ml of Provecta 10 mg/ml Oral Solution contains 10 mg brivaracetam.
The other ingredients are glycerin, sodium carboxymethylcellulose, sorbitol, sucralose, tri-sodium citrate, citric acid, methyl paraben, raspberry flavor and purified water.
Marketing Authorization Holder and Manufacturer
Jazeera Pharmaceutical Industries
Al-Kharj Road
P.O. Box 106229
Riyadh 11666, Saudi Arabia
Tel: + (966-11) 8107023, + (966-11) 2142472
Fax: + (966-11) 2078170
e-mail: SAPV@hikma.com
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly (see details below). By reporting side effects, you can also help provide more information on the safety of this medicine.
- Saudi Arabia
The National Pharmacovigilance Centre (NPC)
SFDA Call Center: 19999
E-mail: npc.drug@sfda.gov.sa
Website: https://ade.sfda.gov.sa
- Other GCC States
Please contact the relevant competent authority.
بروفيكتا هو دواء بوصفة طبية ويستخدم لعلاج النوبات التي تبدأ بشكل جزئي لدى الأشخاص من عمر شهر واحد وأكبر. ليس معروفاً إذا ما كان بريفاراسيتام آمناً وفعّالاً لدى الأطفال الذين تقل أعمارهم عن شهر واحد.
لا تتناول بروفيكتا
لا تتناول بروفيكتا إذا كنت تعاني من تحسس من بريفاراسيتام أو أي من المكونات الموجودة في بروفيكتا. انظر القسم 7 من هذه النشرة لمعرفة قائمة كاملة بمكونات بروفيكتا.
الاحتياطات والتحذيرات
قبل تناول بروفيكتا، أخبر مقدم الرعاية الصحية عن جميع الحالات الطبية التي تعاني منها، بما في ذلك إذا كنت:
- تعاني أو عانيت سابقاً من الاكتئاب، مشاكل في الحالة المزاجية ،أو أفكار أو سلوكيات انتحارية.
- تعاني من مشاكل في الكبد.
- قد تعاطيت أو أدمنت أدوية موصوفة طبياً، مخدرات تباع في الشوارع، أو كحول.
- حاملاً أو تخططين لذلك. ليس معروفاً إذا ما كان بريفاراسيتام سيضر جنينكِ. أخبري مقدم الرعاية الصحية على الفور إذا أصبحت حاملاً أثناء تناول بريفاراسيتام. ستقررين أنتِ ومقدم الرعاية الصحية إذا ما كان يجب عليك تناول بريفاراسيتام في أثناء الحمل من عدمه.
- تُرضعين رضاعة طبيعية أو تخططين لذلك. من غير المعروف إذا ما كان بريفاراسيتام ينتقل إلى حليب الثدي. تحدثي إلى مقدم الرعاية الصحية بشأن أفضل طريقة لتغذية طفلك في أثناء تناولك بريفاراسيتام.
الأطفال والمراهقون
ليس معروفاً إذا ما كان بريفاراسيتام آمناً وفعّالاً للأطفال الذين تقل أعمارهم عن شهر واحد.
الأدوية الأخرى وبروفيكتا
أخبر مقدم الرعاية الصحية عن جميع الأدوية التي تتناولها، بما في ذلك الأدوية التي يتم صرفها بوصفة طبية وبدون وصفة طبية، الفيتامينات والمكملات العشبية. قد يؤثر بروفيكتا في طريقة عمل الأدوية الأخرى وقد تؤثر الأدوية الأخرى في طريقة عمل بروفيكتا. لا تبدأ في تناول دواء آخر دون التحدث مع مقدم الرعاية الصحية. كن على علم بالأدوية التي تتناولها. احتفظ بقائمة منها واعرضها على مقدم الرعاية الصحية والصيدلي في كل مرة تحصل على دواء جديد.
الحمل والرضاعة
قبل تناول بروفيكتا، أخبري مقدم الرعاية الصحية إذا كنتِ:
- حاملاً أو تخططين لذلك. ليس معروفاً إذا ما كان بريفاراسيتام سيضر جنينكِ. أخبري مقدم الرعاية الصحية على الفور إذا أصبحت حاملاً في أثناء تناول بريفاراسيتام. ستقررين أنتِ ومقدم الرعاية الصحية إذا ما كان يجب عليك تناول بريفاراسيتام في أثناء الحمل من عدمه.
- تُرضعين رضاعة طبيعية أو تخططين لذلك. من غير المعروف إذا ما كان بريفاراسيتام ينتقل إلى حليب الثدي. تحدثي إلى مقدم الرعاية الصحية بشأن أفضل طريقة لتغذية طفلك في أثناء تناولك بريفاراسيتام.
القيادة واستخدام الآلات
تجنب القيادة أو تشغيل الآلات حتى تعلم كيف يؤثر بريفاراسيتام عليك. قد يسبب بريفاراسيتام النعاس، التعب، الدوخة، ومشاكل في التنسيق الحركي والتوازن.
يحتوي بروفيكتا على الصوديوم، السوربيتول وميثيل البارابين
يحتوي بروفيكتا على الصوديوم. يحتوي كل مللتر من بروفيكتا 10 ملغم/ مللتر محلول فموي على 1.2 ملغم صوديوم. يحتوي هذا الدواء على أقل من 1 ملمول صوديوم (23 ملغم) لكل مللتر، وهذا يعني أنه "خالٍ من الصوديوم" بشكل أساسي.
يحتوي بروفيكتا على السوربيتول. يحتوي كل مللتر من بروفيكتا 10 ملغم/ مللتر محلول فموي على 239.80 ملغم سوربيتول.
- يعتبر السوربيتول مصدراً للفركتوز. إذا أخبرك طبيبك أنك (أو طفلك) لا تتحمل بعض السكريات أو إذا تم تشخيصك بأنك مصاب بعدم التحمل الوراثي للفركتوز، وهو اضطراب وراثي نادر لا يستطيع فيه جسم الإنسان تكسير الفركتوز، فتحدث إلى طبيبك قبل أن تتناول (أو يتناول طفلك) أو تتلقى هذا الدواء.
- قد يسبب السوربيتول اضطراباً معدياً معوياً وتأثيراً مُليناً بسيطاً.
يحتوي بروفيكتا على ميثيل البارابين. يحتوي كل مللتر من بروفيكتا 10 ملغم/مللتر محلول فموي على 1 ملغم ميثيل بارابين، الذي قد يسبب ردود فعل تحسسية (ربما تتأخر).
قم بتناول بروفيكتا كما وصفه لك مقدم الرعاية الصحية تماماً.
سيخبرك مقدم الرعاية الصحية بمقدار بروفيكتا الذي يجب أن تتناوله وفي أي وقت يجب تناوله.
قد يقوم مقدم الرعاية الصحية بتغيير جرعتك إذا لزم الأمر. لا تغير جرعتك دون استشارة مقدم الرعاية الصحية.
تناول بروفيكتا مع الطعام أو بدونه.
إذا وصف لك مقدم الرعاية الصحية بروفيكتا المحلول الفموي، فتأكد من استخدام المحاقن الفموية المتوفرة لمساعدتك في قياس المقدار الصحيح من بروفيكتا المحلول الفموي. لا تستخدم ملعقة صغيرة أو ملعقة كبيرة المستخدمة في المنزل. اطلب من الصيدلي الحصول على تعليمات حول كيفية استخدام المحاقن الفموية بالطريقة الصحيحة.
لا داعي للتخفيف عند استخدام بروفيكتا المحلول الفموي. يمكن أيضاً إعطاء بروفيكتا المحلول الفموي باستخدام أنبوب أنفي معدي أو أنبوب معدي.
العلاج الأحادي أو العلاج المساعد
يتم تضمين الجرعة الموصى بها للمرضى بعمر شهر واحد فأكثر في الجدول 1. في المرضى الأطفال الذين يقل وزنهم عن 50 كغم، يعتمد نظام تحديد الجرعات الموصى به على وزن الجسم. لا تلزم الزيادة التدريجية للجرعة عند بدء العلاج. يجب تعديل الجرعة بناءً على الاستجابة السريرية ومدى التحمل.
الجدول 1: الجرعة الموصى بها للمرضى بعمر شهر واحد فأكثر
العمر ووزن الجسم | الجرعة الأولية | الحد الأدنى والحد الأقصى لجرعة المداومة |
للبالغين (بعمر 16 سنة فأكثر) | 50 ملغم (5 مللتر) مرتان يومياً [100 ملغم (10 مللتر) يومياً] | 25 ملغم (2.5 مللتر) إلى 100 ملغم (10 مللتر) مرتين يومياً [50 ملغم (5 مللتر) إلى 200 ملغم (20 مللتر) يومياً] |
المرضى الأطفال الذين تبلغ أوزانهم 50 كغم أو أكثر | 25 ملغم (2.5 مللتر) إلى 50 ملغم (5 مللتر) مرتين يومياً [50 ملغم (5 مللتر) إلى 100 ملغم (10 مللتر) يومياً] | 25 ملغم (2.5 مللتر) إلى 100 ملغم (10 مللتر) مرتين يومياً [50 ملغم (5 مللتر) إلى 200 ملغم (20 مللتر) يومياً] |
المرضى الأطفال الذين تبلغ أوزانهم 20 كغم إلى أقل من 50 كغم | 0.5 ملغم/كغم (0.05 مللتر/كغم) إلى 1 ملغم/كغم (0.1 مللتر/كغم) مرتين يومياً [1 ملغم/كغم (0.1 مللتر/كغم) إلى 2 ملغم/كغم (0.2 مللتر/كغم) يومياً] | 0.5 ملغم/كغم (0.05 مللتر/كغم) إلى 2 ملغم/كغم (0.2 مللتر/كغم) مرتين يومياً [1 ملغم/كغم (0.1 مللتر/كغم) إلى 4 ملغم/كغم (0.4 مللتر/كغم) يومياً] |
المرضى الأطفال الذين تبلغ أوزانهم 11 كغم إلى أقل من 20 كغم | 0.5 ملغم/كغم (0.05 مللتر/كغم) إلى 1.25 ملغم/كغم (0.125 مللتر/كغم) مرتين يومياً [1 ملغم/كغم (0.1 مللتر/كغم) إلى 2.5 ملغم/كغم (0.25 مللتر/كغم) يومياً] | 0.5 ملغم/كغم (0.05 مللتر/كغم) إلى 2.5 ملغم/كغم (0.25 مللتر/كغم) مرتين يومياً [1 ملغم/كغم (0.1 مللتر/كغم) إلى 5 ملغم/كغم (0.5 مللتر/كغم) يومياً] |
المرضى الأطفال الذين تقل أوزانهم عن 11 كغم | 0.75 ملغم/كغم (0.075 مللتر/كغم) إلى 1.5 ملغم/كغم (0.15 مللتر/كغم) مرتين يومياً [1.5 ملغم/كغم (0.15 مللتر/كغم) إلى 3 ملغم/كغم (0.3 مللتر/كغم) يوميًا] | 0.75 ملغم/كغم (0.075 مللتر/كغم) إلى 3 ملغم/كغم (0.3 مللتر/كغم) مرتين يومياً [1.5 ملغم/كغم (0.15 مللتر/كغم) إلى 6 ملغم/كغم (0.6 مللتر/كغم) يومياً] |
جرعة بريفاراسيتام للحقن
يمكن إعطاء بريفاراسيتام للحقن عندما يتعذر التناول عن طريق الفم مؤقتاً. يجب إعطاء بريفاراسيتام للحقن في الوريد بالجرعة ذاتها وبمعدل التكرار ذاته اللذين يتم بهما تناول بريفاراسيتام أقراص والمحلول الفموي.
مرضى القصور الكبدي
يتم تضمين الجرعة الموصى بها لمرضى القصور الكبدي في الجدول 2.
الجدول 2: الجرعة الموصى بها لمرضى القصور الكبدي
العمر ووزن الجسم | الجرعة الأولية | الحد الأقصى لجرعة المداومة |
للبالغين (بعمر 16 سنة فأكثر) | 25 ملغم (2.5 مللتر) مرتان يومياً [50 ملغم (5 مللتر) يومياً] | 75 ملغم (7.5 مللتر) مرتان يومياً (150 ملغم يومياً) |
المرضى الأطفال الذين تبلغ أوزانهم 50 كغم أو أكثر | ||
المرضى الأطفال الذين تبلغ أوزانهم 20 كغم إلى أقل من 50 كغم | 0.5 ملغم/كغم (0.05 مللتر/كغم) مرتان يومياً [1 ملغم/كغم (0.1 مللتر/كغم) يومياً] | 1.5 ملغم/كغم (0.15 مللتر/كغم) مرتان يومياً [3 ملغم/كغم (0.3 مللتر/كغم) يومياً] |
المرضى الأطفال الذين تبلغ أوزانهم 11 كغم إلى أقل من 20 كغم | 0.5 ملغم/كغم (0.05 مللتر/كغم) مرتان يومياً [1 ملغم/كغم (0.1 مللتر/كغم) يومياً] | 2 ملغم/كغم (0.2 مللتر/كغم) مرتان يومياً [4 ملغم/كغم (0.4 مللتر/كغم) يومياً] |
المرضى الأطفال الذين تقل أوزانهم عن 11 كغم | 0.75 ملغم/كغم (0.075 مللتر/كغم) مرتان يومياً [1.5 ملغم/كغم (0.15 مللتر/كغم) يومياً] | 2.25 ملغم/كغم (0.225 مللتر/كغم) مرتان يومياً [4.5 ملغم/كغم (0.45 مللتر/كغم) يومياً] |
تعليمات للاستخدام للمرضى أو مقدمي الرعاية:
ستتوفر محقنتان فمويتان مع العلبة الكرتونية. تحقق من طبيبك أيهما يجب استخدامها.
- للحجم الذي يتراوح بين 0.5 مللتر و5 مللتر، يتعين استخدام المحقنة الفموية بحجم 5 مللتر (علامات التدرج الزرقاء) المتوفرة مع العلبة الكرتونية لضمان دقة إعطاء الجرعات.
- للحجم الذي يزيد عن 5 مللتر ويصل إلى 10 مللتر، يتعين استخدام المحقنة الفموية بحجم 10 مللتر (علامات التدرج السوداء) المتوفرة مع العبوة لضمان دقة إعطاء الجرعات.
محقنة جرعات فموية بحجم 5 مللتر | محقنة جرعات فموية بحجم 10 مللتر |
تحتوي المحقنة الفموية بحجم 5 مللتر على علامتي تدرج متداخلتين باللون الأزرق: عند الدرجة 0.25 مللتر والدرجة 0.1 مللتر. | تحتوي المحقنة الفموية بحجم 10 مللتر على علامات تدرج سوداء بدرجات مقدارها 0.25 مللتر. |
- افتح القنينة: اضغط على الغطاء وأدره عكس اتجاه عقارب الساعة (الشكل 1).
اتبع هذه الخطوات في المرة الأولى التي تتناول فيها بروفيكتا:
- انزع المحول من المحقنة الفموية (الشكل 2).
- ضع المحول في الجزء العلوي من القنينة (الشكل 3). تأكد من تثبيته جيداً في مكانه. لا تحتاج إلى إزالة المحول بعد استخدامه.
اتبع هذه الخطوات في كل مرة تتناول فيها بروفيكتا:
- ضع المحقنة الفموية في فتحة المحول (الشكل 4).
- اقلب القنينة رأساً على عقب (الشكل 5).
امسك القنينة مقلوبة في إحدى يديك واستخدم اليد الأخرى لملء المحقنة الفموية.
- اسحب المكبس لأسفل لملء المحقنة الفموية بكمية صغيرة من المحلول (الشكل 6).
- ثم ادفع المكبس لأعلى لإزالة أي فقاعات قد تكون موجودة (الشكل 7).
- اسحب المكبس لأسفل إلى علامة جرعة المليلتر (مللتر) على المحقنة الفموية التي وصفها طبيبك (الشكل 8).
- اقلب القنينة بالطريقة الصحيحة (الشكل 9).
- انزع المحقنة الفموية من المحول (الشكل 10).
توجد طريقتان تستطيع شرب الدواء من خلالهما:
- أفرغ محتويات المحقنة في الماء (أو العصير) عن طريق دفع المكبس إلى آخر المحقنة الفموية (الشكل 11) - ستحتاج بعد ذلك إلى شرب الماء بالكامل (أضف ما يكفي لتسهيل الشرب فقط) أو
- اشرب المحلول مباشرة من المحقنة الفموية بدون ماء - اشرب كامل محتويات المحقنة (الشكل 12).
- أغلق القنينة باستخدام الغطاء اللولبي البلاستيكي (لا تحتاج إلى إزالة المحول).
- اغسل المحقنة الفموية بالماء فقط (الشكل 13).
- احتفظ بالقنينة، المحقنة الفموية، والنشرة في العلبة الكرتونية.
إذا كنت تتناول بروفيكتا أكثر من اللازم
إذا تناولت جرعة زائدة من بروفيكتا، اتصل بالطبيب أو توجه إلى أقرب غرفة طوارئ على الفور.
إذا توقفت عن تناول بروفيكتا
لا تتوقف عن تناول بروفيكتا دون استشارة مقدم الرعاية الصحية أولاً.
- يمكن أن يسبب التوقف عن تناول بروفيكتا فجأة مشاكل خطيرة.
- قد يؤدي التوقف عن تناول دواء النوبات فجأة إلى حدوث نوبات لن تتوقف (حالة صرعية).
يمكن أن يسبب بريفاراسيتام آثاراً جانبية خطيرة تشمل:
- انظر "الآثار الجانبية الخطيرة".
- مشاكل بالجهاز العصبي. يشيع النعاس، التعب، والدوخة مع استخدام بريفاراسيتام، ولكن قد تكون شديدة. انظر "القيادة واستخدام الآلات" يمكن أن يسبب بريفاراسيتام مشاكل في التنسيق الحركي والتوازن.
- الأعراض (النفسية) العقلية. قد يسبب بريفاراسيتام تغيرات في المزاج والسلوك مثل العدوانية، التهيج، الغضب، القلق، اللامبالاة، تقلبات المزاج، الاكتئاب، العدائية وسرعة الانفعال. تشيع سرعة الانفعال والقلق مع تناول بريفاراسيتام، وقد تكون شديدة. يمكن للأشخاص الذين يتناولون بريفاراسيتام أيضاً أن يصابوا بأعراض ذهانية مثل الهلوسة (رؤية أو سماع أشياء غير موجودة)، الأوهام (أفكار أو معتقدات خاطئة أو غريبة)، والسلوك غير المعتاد.
تشمل الآثار الجانبية الأكثر شيوعاً لبريفاراسيتام لدى البالغين ما يلي:
- نعاس
- دوخة
- شعور بالإرهاق
- غثيان وقيء
تتشابه الآثار الجانبية لبريفاراسيتام التي تظهر لدى الأطفال من سن شهر إلى أقل من 16 سنة مع تلك التي تظهر لدى البالغين.
هذه ليست جميع الآثار الجانبية المحتملة لبريفاراسيتام للحصول على مزيد من المعلومات، اسأل مقدم الرعاية الصحية أو الصيدلي. أخبر مقدم الرعاية الصحية إذا كنت تعاني من أي أثر جانبي يزعجك أو لا يزول. اتصل على طبيبك للحصول على استشارة طبية بشأن الآثار الجانبية.
احفظ هذا الدواء بعيداً عن مرأى ومتناول الأطفال.
يحفظ عند درجة حرارة أقل من 30° مئوية. تجنب التجميد.
يحفظ داخل العبوة الأصلية.
تخلص بشكل آمن من أي قنينة مفتوحة بعد 8 أشهر من فتح القنينة لأول مرة، حتى لو تبقى دواء في القنينة.
عند الاستخدام، لا حاجة لأي تخفيف.
لا تستخدم هذا الدواء بعد تاريخ انتهاء الصلاحية المذكور على العبوة الخارجية بعد "EXP". يشير تاريخ انتهاء الصلاحية إلى اليوم الأخير من ذلك الشهر.
لا تستخدم هذا الدواء إذا لاحظت أي علامات تلف واضحة عليه.
لا تتخلص من أي أدوية عن طريق مياه الصرف الصحي أو النفايات المنزلية. اسأل الصيدلي عن كيفية التخلص من الأدوية التي لم تعد بحاجة إليها. هذه الإجراءات ستساعد في الحفاظ على سلامة البيئة.
المادة الفعالة هي بريفاراسيتام.
يحتوي كل مللتر من بروفيكتا 10 ملغم/مللتر محلول فموي على 10 ملغم بريفاراسيتام.
المواد الأخرى المستخدمة في التركيبة التصنيعية هي جليسيرين، كاربوكسي ميثيل سيلليلوز الصوديوم، سوربيتول، سكرالوز، سيترات ثلاثي الصوديوم، حمض السيتريك، ميثيل بارابين، نكهة التوت وماء منقّى.
بروفيكتا 10 ملغم/مللتر محلول فموي هو سائل لزج قليلاً، صافٍ عديم اللون مائل إلى الصفرة، في قنينات كهرمانية زجاجية بحجم 150 مللتر مع أغطية مقاومة لعبث الأطفال، محقنة فموية بحجم 5 مللتر (عليها علامتي تدريج متداخلتين باللون الأزرق: بتدرج 0.25 مللتر وبتدرج 0.1 مللتر) مع محول ومحقنة فموية 10 مللتر (عليها علامات تدرج سوداء بتدرج 0.25 مللتر) مع محول.
حجم العبوة: قنينة واحدة (150 مللتر).
مالك رخصة التسويق والشركة المصنعة
شركة الجزيرة للصناعات الدوائية
طريق الخرج
صندوق بريد 106229
الرياض 11666، المملكة العربية السعودية
هاتف: 8107023 (11-966) +، 2142472 (11-966) +
فاكس: 2078170 (11-966) +
البريد الإلكتروني: SAPV@hikma.com
للإبلاغ عن الآثار الجانبية
تحدث إلى الطبيب، الصيدلي، أو الممرض إذا عانيت من أية آثار جانبية. وذلك يشمل أي آثار جانبية لم يتم ذكرها في هذه النشرة. كما أنه يمكنك الإبلاغ عن هذه الآثار مباشرةً (انظر التفاصيل المذكورة أدناه). من خلال الإبلاغ عن الآثار الجانبية، يمكنك المساعدة بتوفير معلومات مهمة عن سلامة الدواء.
- المملكة العربية السعودية
المركز الوطني للتيقظ الدوائي
مركز الاتصال الموحد: 19999
البريد الإلكتروني: npc.drug@sfda.gov.sa
الموقع الإلكتروني: https://ade.sfda.gov.sa
- دول الخليج العربي الأخرى
الرجاء الاتصال بالجهات الوطنية في كل دولة.
Provecta is indicated for the treatment of partial-onset seizures in patients 1 month of age and older.
Dosage Information
Monotherapy or Adjunctive Therapy
The recommended dosage for patients 1 month of age and older is included in Table 1. In pediatric patients weighing less than 50 kg, the recommended dosing regimen is dependent upon body weight. When initiating treatment, gradual dose escalation is not required. Dosage should be adjusted based on clinical response and tolerability.
Table 1: Recommended Dosage for Patients 1 Month of Age and Older
Age and Body Weight | Initial Dosage | Minimum and Maximum Maintenance Dosage |
Adults (16 years and older) | 50 mg (5 ml) twice daily [100 mg (10 ml) per day] | 25 mg (2.5 ml) to 100 mg (10 ml) twice daily [50 mg (5 ml) to 200 mg (20 ml) per day] |
Pediatric patients weighing 50 kg or more | 25 mg (2.5 ml) to 50 mg (5 ml) twice daily [50 mg (5 ml) to 100 mg (10 ml) per day] | 25 mg (2.5 ml) to 100 mg (10 ml) twice daily [50 mg (5 ml) to 200 mg (20 ml) per day] |
Pediatric patients weighing 20 kg to less than 50 kg | 0.5 mg/kg (0.05 ml/kg) to 1 mg/kg (0.1 ml/kg) twice daily [1 mg/kg (0.1 ml/kg) to 2 mg/kg (0.2 ml/kg) per day] | 0.5 mg/kg (0.05 ml/kg) to 2 mg/kg (0.2 ml/kg) twice daily [1 mg/kg (0.1 ml/kg) to 4 mg/kg (0.4 ml/kg) per day] |
Pediatric patients weighing 11 kg to less than 20 kg | 0.5 mg/kg (0.05 ml/kg) to 1.25 mg/kg (0.125 ml/kg) twice daily [1 mg/kg (0.1 ml/kg) to 2.5 mg/kg (0.25 ml/kg) per day] | 0.5 mg/kg (0.05 ml/kg) to 2.5 mg/kg (0.25 ml/kg) twice daily [1 mg/kg (0.1 ml/kg) to 5 mg/kg (0.5 ml/kg) per day] |
Pediatric patients weighing less than 11 kg | 0.75 mg/kg (0.075 ml/kg) to 1.5 mg/kg (0.15 ml/kg) twice daily [1.5 mg/kg (0.15 ml/kg) to 3 mg/kg (0.3 ml/kg) per day] | 0.75 mg/kg (0.075 ml/kg) to 3 mg/kg (0.3 ml/kg) twice daily [1.5 mg/kg (0.15 ml/kg) to 6 mg/kg (0.6 ml/kg) per day] |
Brivaracetam Injection Dosage
Brivaracetam injection may be used when oral administration is temporarily not feasible [see Dosage and Administration (2.3)]. Brivaracetam injection should be administered intravenously at the same dosage and same frequency as brivaracetam tablets and oral solution.
The clinical study experience with brivaracetam injection is up to 4 consecutive days of treatment.
Administration Instructions for Provecta Oral Solution
Brivaracetam can be initiated with either intravenous or oral administration.
Provecta oral solution may be taken with or without food.
A calibrated measuring device is recommended to measure and deliver the prescribed dose accurately. A household teaspoon or tablespoon is not an adequate measuring device.
When using Provecta oral solution, no dilution is necessary. Provecta oral solution may also be administered using a nasogastric tube or gastrostomy tube. Discard any unused Provecta oral solution remaining after 5 months of first opening the bottle.
Discontinuation of Provecta
Avoid abrupt withdrawal from Provecta in order to minimize the risk of increased seizure frequency and status epilepticus [see 4.4. Special warnings and precautions for use and 5.1. Pharmacodynamic properties].
Patients with Hepatic Impairment
The recommended dosage for patients with hepatic impairment is included in Table 2 [see 5.1. Pharmacodynamic properties].
Table 2: Recommended Dosage for Patients with Hepatic Impairment
Age and Body Weight | Initial Dosage | Minimum and Maximum Maintenance Dosage |
Adults (16 years and older) | 25 mg (2.5 ml) twice daily [50 mg (5 ml) per day] | 75 mg (7.5 ml) twice daily [150 mg (15 ml) per day] |
Pediatric patients weighing 50 kg or more | ||
Pediatric patients weighing 20 kg to less than 50 kg | 0.5 mg/kg (0.05 ml/kg) twice daily [1 mg/kg (0.1 ml/kg) per day] | 1.5 mg/kg (0.15 ml/kg) twice daily [3 mg/kg (0.3 ml/kg) per day] |
Pediatric patients weighing 11 kg to less than 20 kg | 0.5 mg/kg (0.05 ml/kg) twice daily [1 mg/kg (0.1 ml/kg) per day] | 2 mg/kg (0.2 ml/kg) twice daily [4 mg/kg (0.4 ml/kg) per day] |
Pediatric patients weighing less than 11 kg | 0.75 mg/kg (0.075 ml/kg) twice daily [1.5 mg/kg (0.15 ml/kg) per day] | 2.25 mg/kg (0.225 ml/kg) twice daily [4.5 mg/kg (0.45 ml/kg) per day] |
Co-administration with Rifampin
Increase the Provecta dosage in patients on concomitant rifampin by up to 100% (i.e., double the dosage) [see 4.5. Interaction with other medicinal products and other forms of interaction and 5.1. Pharmacodynamic properties].
Pediatric Use
Safety and effectiveness of brivaracetam have been established in pediatric patients 1 month to less than 16 years of age. Use of brivaracetam in these age groups is supported by evidence from adequate and well-controlled studies of brivaracetam in adults with partial-onset seizures, pharmacokinetic data from adult and pediatric patients, and safety data in pediatric patients 2 months to less than 16 years of age [see 4.2. Posology and method of administration, 4.4. Special warnings and precautions for use, 4.8. Undesirable effects and 5.1. Pharmacodynamic properties].
Safety and effectiveness in pediatric patients below the age of 1 month have not been established.
Geriatric Use
There were insufficient numbers of patients 65 years of age and older in the double-blind, placebo- controlled epilepsy trials (n=38) to allow adequate assessment of the effectiveness of brivaracetam in this population. In general, dose selection for an elderly patient should be judicious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see 5.1. Pharmacodynamic properties].
Renal Impairment
Dose adjustments are not required for patients with impaired renal function. There are no data in patients with end-stage renal disease undergoing dialysis, and use of brivaracetam is not recommended in this patient population [see 5.1. Pharmacodynamic properties].
Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including Provecta, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Pooled analyses of 199 placebo-controlled clinical trials (mono-and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed. Table 3 shows absolute and relative risk by indication for all evaluated AEDs.
Table 3: Risk of Suicidal Thoughts or Behaviors by Indication for Antiepileptic Drugs in the Pooled Analysis
Indication | Placebo Patients with Events Per 1000 Patients | Drug Patient with Events Per 1000 Patients | Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients | Risk Difference: Additional Drug Patients with Events Per 1000 Patients |
Epilepsy | 1.0 | 3.4 | 3.5 | 2.4 |
Psychiatric | 5.7 | 8.5 | 1.5 | 2.9 |
Other | 1.0 | 1.8 | 1.9 | 0.9 |
Total | 2.4 | 4.3 | 1.8 | 1.9 |
The relative risk for suicidal thoughts or behavior was higher in clinical trials in patients with epilepsy than in clinical trials in patients with psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing Provecta or any other AED must balance the risk of suicidal thoughts or behaviors with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Neurological Adverse Reactions
Provecta causes somnolence, fatigue, dizziness, and disturbance in coordination. Patients should be monitored for these signs and symptoms and advised not to drive or operate machinery until they have gained sufficient experience on Provecta to gauge whether it adversely affects their ability to drive or operate machinery.
Somnolence and Fatigue
Brivaracetam causes dose-dependent increases in somnolence and fatigue-related adverse reactions (fatigue, asthenia, malaise, hypersomnia, sedation, and lethargy) [see 4.8. Undesirable effects)]. In the Phase 3 controlled adjunctive epilepsy trials, these events were reported in 25% of patients randomized to receive brivaracetam at least 50 mg/day (20% at 50 mg/day, 26% at 100 mg/day, and 27% at 200 mg/day) compared to 14% of patients who received placebo. The risk is greatest early in treatment but can occur at any time.
Dizziness and Disturbance in Gait and Coordination
Brivaracetam causes adverse reactions related to dizziness and disturbance in gait and coordination (dizziness, vertigo, balance disorder, ataxia, nystagmus, gait disturbance, and abnormal coordination) [see 4.8. Undesirable effects]. In the Phase 3 controlled adjunctive epilepsy trials, these events were reported in 16% of patients randomized to receive brivaracetam at least 50 mg/day compared to 10% of patients who received placebo. The risk is greatest early in treatment but can occur at any time.
Psychiatric Adverse Reactions
Brivaracetam causes psychiatric adverse reactions. In the Phase 3 controlled adjunctive epilepsy trials, psychiatric adverse reactions were reported in approximately 13% of patients who received brivaracetam (at least 50 mg/day) compared to 8% of patients who received placebo. Psychiatric events included both non-psychotic symptoms (irritability, anxiety, nervousness, aggression, belligerence, anger, agitation, restlessness, depression, depressed mood, tearfulness, apathy, altered mood, mood swings, affect lability, psychomotor hyperactivity, abnormal behavior, and adjustment disorder) and psychotic symptoms (psychotic disorder along with hallucination, paranoia, acute psychosis, and psychotic behavior). A total of 1.7% of adult patients treated with brivaracetam discontinued treatment because of psychiatric reactions compared to 1.3% of patients who received placebo.
Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults [see 4.8. Undesirable effects and 4.2. Posology and method of administration].
Hypersensitivity: Bronchospasm and Angioedema
Brivaracetam can cause hypersensitivity reactions. Bronchospasm and angioedema have been reported in patients taking brivaracetam. If a patient develops hypersensitivity reactions after treatment with brivaracetam, the drug should be discontinued. Brivaracetam is contraindicated in patients with a prior hypersensitivity reaction to brivaracetam or any of the inactive ingredients [see 4.3. Contraindications].
Withdrawal of Antiepileptic Drugs
As with most antiepileptic drugs, brivaracetam should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus [see 4.2. Posology and method of administration and 5.1. Pharmacodynamic properties]. But if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered.
Drug abuse and dependence
Abuse
In a human abuse potential study, single doses of brivaracetam at therapeutic and supratherapeutic doses were compared to alprazolam (C-IV) (1.5 mg and 3 mg). Brivaracetam at the recommended single dose (50 mg) caused fewer sedative and euphoric effects than alprazolam; however, brivaracetam at supratherapeutic single doses (200 mg and 1000 mg) was similar to alprazolam on other measures of abuse.
Dependence
There was no evidence of physical dependence potential or a withdrawal syndrome with brivaracetam in a pooled review of placebo-controlled adjunctive therapy studies.
Provecta contains sodium, sorbitol and methyl paraben
Provecta contains sodium. Each ml of Provecta 10 mg/ml Oral Solution contains 1.2 mg sodium. This medicine contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially “sodium-free”.
Provecta contains sorbitol. Each ml of Provecta 10 mg/ml Oral Solution contains 239.80 mg sorbitol.
- Sorbitol is a source of fructose. If your doctor has told you that you (or your child) have an intolerance to some sugars or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down fructose, talk to your doctor before you (or your child) take or receive this medicine.
- Sorbitol may cause gastrointestinal discomfort and mild laxative effect.
Provecta contains methyl paraben. Each ml of Provecta 10 mg/ml Oral Solution contains 1 mg methyl paraben, which may cause allergic reactions (possibly delayed).
Rifampin
Co-administration with rifampin decreases brivaracetam plasma concentrations likely because of CYP2C19 induction [see 5.1. Pharmacodynamic properties]. Prescribers should increase the brivaracetam dose by up to 100% (i.e., double the dosage) in patients while receiving concomitant treatment with rifampin [see 4.2. Posology and method of administration].
Carbamazepine
Co-administration with carbamazepine may increase exposure to carbamazepine-epoxide, the active metabolite of carbamazepine. Though available data did not reveal any safety concerns, if tolerability issues arise when co-administered, carbamazepine dose reduction should be considered [see 5.1. Pharmacodynamic properties].
Phenytoin
Because brivaracetam can increase plasma concentrations of phenytoin, phenytoin levels should be monitored in patients when concomitant brivaracetam is added to or discontinued from ongoing phenytoin therapy [see 5.1. Pharmacodynamic properties].
Levetiracetam
Brivaracetam provided no added therapeutic benefit to levetiracetam when the two drugs were co- administered [see 5.1. Pharmacodynamic properties].
Pregnancy
Risk Summary
Available data from the North American Antiepileptic Drug (NAAED) pregnancy registry, a prospective cohort study, case reports, and a case series are insufficient to identify a risk of major birth defects, miscarriage or other maternal or fetal outcomes associated with brivaracetam use during pregnancy. In animal studies, brivaracetam produced evidence of developmental toxicity (increased embryofetal mortality and decreased fetal body weights in rabbits; decreased growth, delayed sexual maturation, and long-term neurobehavioral changes in rat offspring) at maternal plasma exposures greater than clinical exposures [see Data].
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data
Animal Data
Oral administration of brivaracetam (0, 150, 300, or 600 mg/kg/day) to pregnant rats during the period of organogenesis did not produce any significant maternal or embryofetal toxicity. The highest dose tested was associated with maternal plasma exposures (AUC) approximately 30 times exposures in humans at the maximum recommended dose (MRD) of 200 mg/day.
Oral administration of brivaracetam (0, 30, 60, 120, or 240 mg/kg/day) to pregnant rabbits during the period of organogenesis resulted in embryofetal mortality and decreased fetal body weights at the highest dose tested, which was also maternally toxic.
The highest no-effect dose (120 mg/kg/day) was associated with maternal plasma exposures approximately 4 times human exposures at the MRD.
When brivaracetam (0, 150, 300, or 600 mg/kg/day) was orally administered to rats throughout pregnancy and lactation, decreased growth, delayed sexual maturation (female), and long-term neurobehavioral changes were observed in the offspring at the highest dose. The highest no-effect dose (300 mg/kg/day) was associated with maternal plasma exposures approximately 7 times human exposures at the MRD.
Brivaracetam was shown to readily cross the placenta in pregnant rats after a single oral (5 mg/kg) dose of 14C-brivaracetam.
From 1 hour post dose, radioactivity levels in fetuses, amniotic fluid, and placenta were similar to those measured in maternal blood.
Lactation
Risk Summary
Data from published literature indicate that brivaracetam is present in human milk. There is insufficient information on the effects of brivaracetam on the breastfed infant or on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for brivaracetam and any potential adverse effects on the breastfed infant from brivaracetam or from the underlying maternal condition.
Data
Animal Data
Following a single oral (5 mg/kg) dose of 14C-brivaracetam to lactating rats, radioactivity was secreted in milk and rapidly reached levels similar to those in plasma.
Provecta causes somnolence, fatigue, dizziness, and disturbance in coordination. Patients should be monitored for these signs and symptoms and advised not to drive or operate machinery until they have gained sufficient experience on Provecta to gauge whether it adversely affects their ability to drive or operate machinery.
The following serious adverse reactions are described elsewhere in labeling:
- Suicidal Behavior and Ideation [see 4.4. Special warnings and precautions for use)]
- Neurological Adverse Reactions [see 4.4. Special warnings and precautions for use]
- Psychiatric Adverse Reactions [see 4.4. Special warnings and precautions for use Hypersensitivity: Bronchospasm and Angioedema [see 4.4. Special warnings and precautions for use]
- Withdrawal of Antiepileptic Drugs [see 4.4. Special warnings and precautions for use]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In all controlled and uncontrolled trials performed in adult epilepsy patients, brivaracetam was administered as adjunctive therapy to 2437 patients. Of these patients, 1929 were treated for at least 6 months, 1500 for at least 12 months, 1056 for at least 24 months, and 758 for at least 36 months. A total of 1558 patients (1099 patients treated with brivaracetam and 459 patients treated with placebo) constituted the safety population in the pooled analysis of Phase 3 placebo-controlled studies in patients with partial-onset seizures (Studies 1, 2, and 3) [see 5.1. Pharmacodynamic properties)]. The adverse reactions presented in Table 4 are based on this safety population; the median length of treatment in these studies was 12 weeks. Of the patients in those studies, approximately 51% were male, 74% were Caucasian, and the mean age was 38 years.
In the Phase 3 controlled epilepsy studies, adverse events occurred in 68% of patients treated with brivaracetam and 62% treated with placebo. The most common adverse reactions occurring at a frequency of at least 5% in patients treated with brivaracetam doses of at least 50 mg/day and greater than placebo were somnolence and sedation (16%), dizziness (12%), fatigue (9%), and nausea and vomiting symptoms (5%).
The discontinuation rates due to adverse events were 5%, 8%, and 7% for patients randomized to receive brivaracetam at the recommended doses of 50 mg, 100 mg, and 200 mg/day, respectively, compared to 4% in patients randomized to receive placebo.
Table 4 lists adverse reactions for brivaracetam that occurred at least 2% more frequently for brivaracetam doses of at least 50 mg/day than placebo.
Table 4: Adverse Reactions in Pooled Placebo-Controlled Adjunctive Therapy Studies in Adult Patients with Partial-Onset Seizures (Brivaracetam 50 mg/day, 100 mg/day, and 200 mg/day)
Adverse Reactions | Brivaracetam (N=803) % | Placebo (N=459) % |
Gastrointestinal disorders | ||
Nausea/vomiting symptoms | 5 | 3 |
Constipation | 2 | 0 |
Nervous system disorders | ||
Somnolence and sedation | 16 | 8 |
Dizziness | 12 | 7 |
Fatigue | 9 | 4 |
Cerebellar coordination and balance disturbances* |
3 |
1 |
Psychiatric disorders | ||
Irritability | 3 | 1 |
*Cerebellar coordination and balance disturbances includes ataxia, balance disorder, coordination abnormal, and nystagmus.
There was no apparent dose-dependent increase in adverse reactions listed in Table 4 with the exception of somnolence and sedation.
Pediatric Patients
Safety of brivaracetam was evaluated in two open-label, safety and pharmacokinetic trials in pediatric patients 2 months to less than 16 years of age. Across studies of pediatric patients with partial onset seizures, 186 patients received brivaracetam oral solution or tablet, of whom 123 received brivaracetam for at least 12 months. Adverse reactions reported in clinical studies of pediatric patients were generally similar to those seen in adult patients. Decreased appetite was also observed in these pediatric trials.
Hematologic Abnormalities
Brivaracetam can cause hematologic abnormalities. In the Phase 3 controlled adjunctive epilepsy studies, a total of 1.8% of brivaracetam-treated patients and 1.1% of placebo-treated patients had at least one clinically significant decreased white blood cell count (<3.0 x 109/L), and 0.3% of brivaracetam -treated patients and 0% of placebo-treated patients had at least one clinically significant decreased neutrophil count (<1.0 x 109/L).
Adverse Reactions with brivaracetam Injection
Adverse reactions with brivaracetam injection administered to adults and pediatric patients 2 months to 16 years of age were generally similar to those observed with brivaracetam tablets. Other adverse events that occurred in at least 3% of adult patients who received brivaracetam injection included dysgeusia, euphoric mood, feeling drunk, and infusion site pain.
Comparison by Sex
There were no significant differences by sex in the incidence of adverse reactions.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:
- Saudi Arabia
The National Pharmacovigilance Centre (NPC)
SFDA Call Center: 19999
E-mail: npc.drug@sfda.gov.sa
Website: https://ade.sfda.gov.sa
- Other GCC States
Please contact the relevant competent authority.
There is limited clinical experience with brivaracetam overdose in humans. Somnolence and dizziness were reported in a patient taking a single dose of 1400 mg (14 times the highest recommended single dose) of brivaracetam. The following adverse reactions were reported with brivaracetam overdose: vertigo, balance disorder, fatigue, nausea, diplopia, anxiety, and bradycardia. In general, the adverse reactions associated with brivaracetam overdose were consistent with the known adverse reactions.
There is no specific antidote for overdose with brivaracetam. In the event of overdose, standard medical practice for the management of any overdose should be used. An adequate airway, oxygenation, and ventilation should be ensured; monitoring of cardiac rate and rhythm and vital signs is recommended. A certified poison control center should be contacted for updated information on the management of overdose with brivaracetam. There are no data on the removal of brivaracetam using hemodialysis, but because less than 10% of brivaracetam is excreted in urine, hemodialysis is not expected to enhance brivaracetam clearance.
Pharmacotherapeutic group: Antiepileptics, Other antiepileptics, ATC code: N03AX23.
Mechanism of Action
The precise mechanism by which brivaracetam exerts its anticonvulsant activity is not known. Brivaracetam displays a high and selective affinity for synaptic vesicle protein 2A (SV2A) in the brain, which may contribute to the anticonvulsant effect.
Pharmacodynamics
Interactions with Alcohol
In a pharmacokinetic and pharmacodynamic interaction study in healthy subjects, co-administration of brivaracetam (single dose 200 mg [2 times greater than the highest recommended single dose]) and ethanol (continuous intravenous infusion to achieve a blood alcohol concentration of 60 mg/100 ml during 5 hours) increased the effects of alcohol on psychomotor function, attention, and memory. Co- administration of brivaracetam and ethanol caused a larger decrease from baseline in saccadic peak velocity, smooth pursuit, adaptive tracking performance, and Visual Analog Scale (VAS) alertness, and a larger increase from baseline in body sway and in saccadic reaction time compared with brivaracetam alone or ethanol alone. The immediate word recall scores were generally lower for brivaracetam when co-administered with ethanol.
Cardiac Electrophysiology
At a dose 4 times the maximum recommended dose, brivaracetam did not prolong the QT interval to a clinically relevant extent.
Clinical studies
The effectiveness of brivaracetam in partial-onset seizures with or without secondary generalization was established in 3 fixed-dose, randomized, double-blind, placebo-controlled, multicenter studies (Studies 1, 2, and 3), which included 1550 patients. Patients enrolled had partial-onset seizures that were not adequately controlled with 1 to 2 concomitant antiepileptic drugs (AEDs). In each of these studies, 72% to 86% of patients were taking 2 or more concomitant AEDs with or without vagal nerve stimulation. The median baseline seizure frequency across the 3 studies was 9 seizures per 28 days. Patients had a mean duration of epilepsy of approximately 23 years.
All trials had an 8-week baseline period, during which patients were required to have at least 8 partial- onset seizures. The baseline period was followed by a 12-week treatment period. There was no titration period in these studies. Study 1 compared doses of brivaracetam 50 mg/day and 100 mg/day with placebo. Study 2 compared a dose of brivaracetam 50 mg/day with placebo. Study 3 compared doses of brivaracetam 100 mg/day and 200 mg/day with placebo. brivaracetam was administered in equally divided twice daily doses. Upon termination of brivaracetam treatment, patients were down-titrated over a 1-, 2-, and 4-week duration for patients receiving 25, 50, and 100 mg twice daily brivaracetam, respectively.
The primary efficacy outcome in Study 1 and Study 2 was the percent reduction in 7-day partial-onset seizure frequency over placebo, while the primary outcome for Study 3 was the percent reduction in 28- day partial-onset seizure frequency over placebo. The criteria for statistical significance for all 3 studies was p<0.05. Table 6 presents the primary efficacy outcome of the percent change in seizure frequency over placebo, based upon each study’s protocol-defined 7-and 28-day seizure frequency efficacy outcome.
Table 6: Percent Reduction in Partial-Onset Seizure Frequency over Placebo (Studies 1, 2, and 3)
| Percent Reduction Over Placebo (%) |
STUDY 1a | |
Placebo (n=100) | ------ |
50 mg/day (n=99) | 9.5 |
100 mg/day (n=100) | 17.0 |
STUDY 2a | |
Placebo (n=96) | ------ |
50 mg/day (n=101) | 16.9* |
STUDY 3b | |
Placebo (n=259) | ------ |
100 mg/day (n=252) | 25.2* |
200 mg/day (n= 249) | 25.7* |
* Statistically significant based on testing procedure with alpha = 0.05
a Based upon 7-day seizure frequency
b Based upon 28-day seizure frequency
Figure 1 presents the percentage of patients by category of reduction from baseline in partial-onset seizure frequency per 28 days for all pooled patients in the 3 pivotal studies. Patients in whom the seizure frequency increased are shown at left as “worse.” Patients with an improvement in percent reduction from baseline partial-onset seizure frequency are shown in the 4 right-most categories.
Figure 1: Proportion of Patients by Category of Seizure Response for Brivaracetam and Placebo Across all Three Double-Blind Trials
Treatment with Levetiracetam
In Studies 1 and 2, which evaluated brivaracetam dosages of 50 mg and 100 mg daily, approximately 20% of the patients were on concomitant levetiracetam. Although the numbers of patients were limited, brivaracetam provided no added benefit when it was added to levetiracetam.
Although patients on concomitant levetiracetam were excluded from Study 3, which evaluated 100 and 200 mg daily, approximately 54% of patients in this study had prior exposure to levetiracetam.
Brivaracetam tablets, oral solution, and injection can be used interchangeably. Brivaracetam exhibits linear and time-independent pharmacokinetics at the approved doses.
The pharmacokinetics of brivaracetam are similar when used as monotherapy or as adjunctive therapy for the treatment of partial-onset seizures.
Absorption
Brivaracetam is highly permeable and is rapidly and almost completely absorbed after oral administration. Pharmacokinetics is dose-proportional from 10 to 600 mg (a range that extends beyond the minimum and maximum single-administration dose levels described in Dosage and Administration [see 4.2. Posology and method of administration]). The median Tmax for tablets taken without food is 1 hour (range 0.25 to 3 hours). Co-administration with a high-fat meal slowed absorption, but the extent of absorption remained unchanged. Specifically, when a 50 mg tablet was administered with a high-fat meal, Cmax (maximum brivaracetam plasma concentration during a dose interval, an exposure metric) was decreased by 37% and Tmax was delayed by 3 hours, but AUC (area under the brivaracetam plasma concentration versus time curve, an exposure metric) was essentially unchanged (decreased by 5%).
Distribution
Brivaracetam is weakly bound to plasma proteins (≤20%). The volume of distribution is 0.5 L/kg, a value close to that of the total body water. Brivaracetam is rapidly and evenly distributed in most tissues.
Elimination
Metabolism
Brivaracetam is primarily metabolized by hydrolysis of the amide moiety to form the corresponding carboxylic acid metabolite, and secondarily by hydroxylation on the propyl side chain to form the hydroxy metabolite. The hydrolysis reaction is mediated by hepatic and extra-hepatic amidase. The hydroxylation pathway is mediated primarily by CYP2C19. In human subjects possessing genetic variations in CYP2C19, production of the hydroxy metabolite is decreased 2-fold or 10-fold, while the blood level of brivaracetam itself is increased by 22% or 42%, respectively, in individuals with one or both mutated alleles. CYP2C19 poor metabolizers and patients using inhibitors of CYP2C19 may require dose reduction. An additional hydroxy acid metabolite is created by hydrolysis of the amide moiety on the hydroxy metabolite or hydroxylation of the propyl side chain on the carboxylic acid metabolite (mainly by CYP2C9). None of the 3 metabolites are pharmacologically active.
Excretion
Brivaracetam is eliminated primarily by metabolism and by excretion in the urine. More than 95% of the dose, including metabolites, is excreted in the urine within 72 hours after intake. Fecal excretion accounts for less than 1% of the dose. Less than 10% of the dose is excreted unchanged in the urine. Thirty-four percent of the dose is excreted as the carboxylic acid metabolite in urine. The terminal plasma half-life (t1/2) is approximately 9 hours.
Specific Populations
Age
Pediatric Patients (2 months to less than 16 years): An open-label, single-arm, multicenter, pharmacokinetic study with a 3week evaluation period and fixed 3-step up-titration using brivaracetam oral solution was conducted in 99 pediatric patients 2 months to less than 16 years of age. In those patients, plasma concentrations were shown to be dose-proportional. The pediatric pharmacokinetic profile for brivaracetam was determined in a population pharmacokinetic analysis using sparse plasma concentration data obtained in three open-label studies in 255 adult and pediatric patients with epilepsy 2 months to 22 years of age that received intravenous, oral solution, or oral tablet formulations.
A weight-based dosing regimen is necessary to achieve brivaracetam exposures in pediatric patients 1 month to less than 16 years of age that are similar to those observed in adults treated at effective doses of brivaracetam [see 4.2. Posology and method of administration]. The estimated plasma clearance was 1.09 L/h, 1.81 L/h, and 3.11 L/h for pediatric patients weighing 11 kg, 20 kg, and 50 kg, respectively. In comparison, plasma clearance was estimated at 3.58 L/h in adult patients (70 kg body weight).
Geriatric Population: In a study in elderly subjects (65 to 79 years old; creatinine clearance 53 to 98 ml/min/1.73 m²) receiving brivaracetam 200 mg twice daily (2 times the highest recommended dosage), the plasma half-life of brivaracetam was 7.9 hours and 9.3 hours in the 65 to 75 and >75 years groups, respectively. The steady-state plasma clearance of brivaracetam was slightly lower (0.76 ml/min/kg) than in young healthy controls (0.83 ml/min/kg).
Sex
There were no differences observed in the pharmacokinetics of brivaracetam between male and female subjects.
Race/Ethnicity
A population pharmacokinetic analysis comparing Caucasian and non-Caucasian patients showed no significant pharmacokinetic difference.
Renal Impairment
A study in adult subjects with severe renal impairment (creatinine clearance <30 ml/min/1.73m² and not requiring dialysis) revealed that the plasma AUC of brivaracetam was moderately increased (21%) relative to healthy controls, while the AUCs of the acid, hydroxy, and hydroxyacid metabolites were increased 3- fold, 4-fold, and 21-fold, respectively. The renal clearance of these inactive metabolites was decreased 10-fold. Brivaracetam has not been studied in patients undergoing hemodialysis [see 4.2. Posology and method of administration].
Hepatic Impairment
A pharmacokinetic study in adult subjects with hepatic cirrhosis, Child-Pugh grades A, B, and C, showed 50%, 57%, and 59% increases in brivaracetam exposure, respectively, compared to matched healthy controls. The effect of hepatic impairment on brivaracetam pharmacokinetics in pediatric patients is expected to be comparable to the effect observed in adults [see 4.2. Posology and method of administration].
Drug Interaction Studies
In Vitro Assessment of Drug Interactions
Drug-Metabolizing Enzyme Inhibition
Brivaracetam did not inhibit CYP1A2, 2A6, 2B6, 2C8, 2C9, 2D6, or 3A4. Brivaracetam weakly inhibited CYP2C19 and would not be expected to cause significant inhibition of CYP2C19 in humans. Brivaracetam was an inhibitor of epoxide hydrolase, (IC50 = 8.2 μM), suggesting that brivaracetam can inhibit the enzyme in vivo.
Drug-Metabolizing Enzyme Induction
Brivaracetam at concentrations up to 10 μM caused little or no change of mRNA expression of CYP1A2, 2B6, 2C9, 2C19, 3A4, and epoxide hydrolase. It is unlikely that brivaracetam will induce these enzymes in vivo.
Transporters
Brivaracetam was not a substrate of P-gp, MRP1, or MRP2. Brivaracetam did not inhibit or weakly inhibit BCRP, BSEP, MATE1, MATE2/K, MRP2, OAT1, OAT3, OCT1, OCT2, OATP1B1, OATP1B3, or P-gp, suggesting that brivaracetam is unlikely to inhibit these transporters in vivo.
In Vivo Assessment of Drug Interactions
Drug Interaction Studies with Antiepileptic Drugs (AEDs)
Potential interactions between brivaracetam (25 mg twice daily to 100 mg twice daily) and other AEDs were investigated in a pooled analysis of plasma drug concentrations from all Phase 2 and 3 studies and in a population exposure-response analysis of placebo-controlled, Phase 3 studies in adjunctive therapy in the treatment of partial-onset seizures. None of the interactions require changes in the dose of brivaracetam. Interactions with carbamazepine and phenytoin can be clinically important [see 4.5. Interaction with other medicinal products and other forms of interaction]. The interactions are summarized in Table 5.
Table 5: Drug Interactions Between Brivaracetam and Concomitant Antiepileptic
Concomitant AED | Influence of AED on brivaracetam | Influence of brivaracetam on AED |
Carbamazepine | 26% decrease in plasma concentration | None for carbamazepine Increase of carbamazepine-epoxide metabolite* [see 4.5. Interaction with other medicinal products and other forms of interaction] |
Lacosamide | No data | None |
Lamotrigine | None | None |
Levetiracetam | None | None |
Oxcarbazepine | None | None on the active monohydroxy metabolite derivative (MHD) |
Phenobarbital | 19% decrease in plasma concentration | None |
Phenytoin | 21% decrease in plasma concentration | Up to 20% increase in plasma concentration [see 4.5. Interaction with other medicinal products and other forms of interaction]** |
Pregabalin | No data | None |
Topiramate | None | None |
Valproic acid | None | None |
Zonisamide | No data | None |
*Brivaracetam is a re versible inhibitor of epoxide hydrolase resulting in an increased concentration of carbamazepine e poxide, an active metabolite of carbamazepine. The carbamazepine epoxide plasma concentration increased up to 198% at a brivaracetam dose of 100 mg twice daily.
**At a supratherapeutic dose of 400 mg/day brivaracetam, there was a 20% increase in phe nytoin plasma concentration.
Drug Interaction Studies with Other Drugs
Effect of Other Drugs on Brivaracetam
Co-administration with CYP inhibitors or transporter inhibitors is unlikely to significantly affect brivaracetam exposure.
Co-administration with rifampin decreases brivaracetam plasma concentrations by 45%, an effect that is probably the result of CYP2C19 induction [see 4.2. Posology and method of administration and 4.5. Interaction with other medicinal products and other forms of interaction]
Oral Contraceptives
Co-administration of brivaracetam 200 mg twice daily (twice the recommended maximum daily dosage) with an oral contraceptive containing ethinylestradiol (0.03 mg) and levonorgestrel (0.15 mg) reduced estrogen and progestin AUCs by 27% and 23%, respectively, without impact on suppression of ovulation. However, co-administration of brivaracetam 50 mg twice daily with an oral contraceptive containing ethinylestradiol (0.03 mg) and levonorgestrel (0.15 mg) did not significantly influence the pharmacokinetics of either substance. The interaction is not expected to be of clinical significance.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
In a carcinogenicity study in mice, oral administration of brivaracetam (0, 400, 550, or 700 mg/kg/day) for 104 weeks increased the incidence of liver tumors (hepatocellular adenoma and carcinoma) in male mice at the two highest doses tested. At the dose (400 mg/kg) not associated with an increase in liver tumors, plasma exposures (AUC) were approximately equal to those in humans at the maximum recommended dose (MRD) of 200 mg/day. Oral administration (0, 150, 230, 450, or 700 mg/kg/day) to rats for 104 weeks resulted in an increased incidence of thymus tumors (benign thymoma) in female rats at the highest dose tested. At the highest dose not associated with an increase in thymus tumors, plasma exposures were approximately 9 times those in humans at the MRD.
Mutagenesis
Brivaracetam was negative for genotoxicity in in vitro (Ames, mouse lymphoma, and CHO chromosomal aberration) and in vivo (rat bone marrow micronucleus) assays.
Impairment of Fertility
Oral administration of brivaracetam (0, 100, 200, or 400 mg/kg/day) to male and female rats prior to and throughout mating and early gestation produced no adverse effects on fertility. The highest dose tested was associated with plasma exposures approximately 6 (males) and 13 (females) times those in humans at the MRD.
Juvenile Animal Toxicity Data
The potential adverse effects of brivaracetam on postnatal growth and development were investigated in juvenile rats and dogs. Oral administration (0, 150, 300, or 600 mg/kg/day) to rats during the neonatal and juvenile periods of development (approximately equivalent to neonatal through adolescent development in humans) resulted in increased mortality, decreased body weight gain, delayed male sexual maturation, and adverse neurobehavioral effects at the highest dose tested and decreased brain size and weight at all doses. Therefore, a no-effect dose was not established; the lowest dose tested in juvenile rats was associated with plasma exposures (AUC) approximately 2 times those in children and adolescents at the recommended maintenance dose. In dogs, oral administration (0, 15, 30, or 100 mg/kg/day) throughout the neonatal and juvenile periods of development induced liver changes similar to those observed in adult animals at the highest dose but produced no adverse effects on growth, bone density or strength, neurological testing, or neuropathology evaluation. The overall no-effect dose (30 mg/kg/day) and the no-effect dose for adverse effects on developmental parameters (100 mg/kg/day) were associated with plasma exposures approximately equal to and 4 times, respectively, those in children and adolescents at the recommended maintenance dose.
- Glycerin
- Sodium carboxymethylcellulose
- Sorbitol
- Sucralose
- Tri-sodium citrate
- Citric acid
- Methyl paraben
- Raspberry flavor
- Purified water
Not applicable.
Store below 30°C. Avoid freeze.
Store in the original package.
150 ml amber glass bottles with child resistant caps (CRCs), 5 ml oral syringe (has 2 overlapping blue graduation marks: in steps of 0.25 ml and in steps of 0.1 ml) with an adaptor and 10 ml oral syringe (has black graduation marks in steps of 0.25 ml) with an adaptor.
Pack size: 1 Bottle (150 ml).
A calibrated measuring device is recommended to measure and deliver the prescribed dose accurately (Two oral syringes will be provided in the carton). A household teaspoon or tablespoon is not an adequate measuring device.
When using Provecta oral solution, no dilution is necessary. Provecta oral solution may also be administered using a nasogastric tube or gastrostomy tube. Discard any unused Provecta oral solution remaining after 5 months of first opening the bottle.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
