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Julmentin is an antibiotic and works by killing bacteria that cause infections. It contains two different medicines called amoxicillin and clavulanic acid. Amoxicillin belongs to a group of medicines called “penicillins” that can sometimes be stopped from working (made inactive). The other active component (clavulanic acid) stops this from happening.
Julmentin is used in adults and children to treat the following infections:
· middle ear and sinus infections
· respiratory tract infections
· urinary tract infections
· skin and soft tissue infections including dental infections
· bone and joint infections.
Do not take Julmentin:
· • if you are allergic (hypersensitive) to amoxicillin, clavulanic acid, penicillin or any of the other ingredients of Julmentin (listed in section 6)
· • if you have ever had a severe allergic (hypersensitive) reaction to any other antibiotic. This can include a skin rash or swelling of the face or neck
· • if you have ever had liver problems or jaundice (yellowing of the skin) when taking an antibiotic.
Do not take Julmentin if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Julmentin.
Take special care with Julmentin
Talk to your doctor or pharmacist before taking this medicine if you:
· have glandular fever
· are being treated for liver or kidney problems
· are not passing water regularly.
If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking Julmentin.
In some cases, your doctor may investigate the type of bacteria that is causing your infection. Depending on the results, you may be given a different strength of Julmentin or a different medicine.
Conditions you need to look out for
Julmentin can make some existing conditions worse, or cause serious side effects. These include allergic reactions, convulsions (fits) and inflammation of the large intestine. You must look out for certain symptoms while you are taking Julmentin, to reduce the risk of any problems. See ‘Conditions you need to look out for’ in
Section 4.
Blood and urine tests
If you are having blood tests (such as red blood cell status tests or liver function tests) or urine tests (for glucose), let the doctor or nurse know that you are taking Julmentin. This is because Julmentin can affect the results of these types of tests.
Using other medicines
Please tell your doctor or pharmacist if you are using or have recently used any other medicines. This includes medicines that can be bought without a prescription and herbal medicines.
· If you are taking allopurinol (used for gout) with Julmentin, it may be more likely that you’ll have an allergic skin reaction.
· If you are taking probenecid (used for gout), your doctor may decide to adjust your dose of Julmentin.
· If medicines to help stop blood clots (such as warfarin) are taken with Julmentin then extra blood tests may be needed.
· Julmentin can affect how methotrexate (a medicine used to treat cancer or rheumatic diseases) works.
· Julmentin can affect how mycophenolate mofetil (a medicine used to prevent the rejection of transplanted organs) works.
Pregnancy, breast-feeding and fertility
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Driving and using machines
Julmentin can have side effects and the symptoms may make you unfit to drive.
Don’t drive or operate machinery unless you are feeling well.
Always take Julmentin exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.
Adults and children weighing 40 kg and over
Julmentin 375mg and Julmentin Forte 625mg tablets:
The usual dose is: 1 tablet three times a day.
Julmentin 2X 1000mg tablets:
Usual dose – 1 tablet two times a day.
Higher dose – 1 tablet three times a day.
Children weighing less than 40 kg
Children aged 6 years or less should preferably be treated with Julmentin oral suspension.
Ask your doctor or pharmacist for advice when giving Julmentin tablets to children weighing less than 40 kg. The tablets are not suitable for children weighing less than 25 kg.
Patients with kidney and liver problems
· If you have kidney problems the dose might be changed. A different strength or a different medicine may be chosen by your doctor.
· If you have liver problems you may have more frequent blood tests to check how your liver is working.
How to take Julmentin
· Swallow the tablets whole with a glass of water at the start of a meal or slightly before.
· Space the doses evenly during the day, at least 4 hours apart. Do not take 2 doses in 1 hour.
· Do not take Julmentin for more than 2 weeks. If you still feel unwell you should go back to see the doctor.
If you take more Julmentin than you should
If you have too much Julmentin, signs might include an upset stomach (feeling sick, being sick or diarrhoea) or convulsions. Talk to your doctor as soon as possible. Take the medicine carton to show the doctor.
If you forget to take Julmentin
If you forget to take a dose, take it as soon as you remember. You should not take the next dose too soon, but wait about 4 hours before taking the next dose. Do not take a double dose to make up for a forgotten dose.
If you stop taking Julmentin
Keep taking Julmentin until the treatment is finished, even if you feel better. You need every dose to help fight the infection. If some bacteria survive they can cause the infection to come back.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
Like all medicines, Julmentin can cause side effects, although not everybody gets them.
Conditions you need to look out for
Allergic reactions:
· skin rash
· inflammation of blood vessels (vasculitis) which may be visible as red or purple raised spots on the skin, but can affect other parts of the body
· fever, joint pain, swollen glands in the neck, armpit or groin
· swelling, sometimes of the face or mouth (angioedema), causing difficulty in breathing
· collapse.
Contact a doctor immediately if you get any of these symptoms. Stop taking Julmentin.
Inflammation of large intestine
Inflammation of the large intestine, causing watery diarrhoea usually with blood and mucus, stomach pain and/or fever.
Contact your doctor as soon as possible for advice if you get these symptoms.
Very common side effects
These may affect more than 1 in 10 people
· diarrhoea (in adults).
Common side effects
These may affect up to 1 in 10 people
· thrush (candida - a yeast infection of the vagina, mouth or skin folds)
· feeling sick (nausea), especially when taking high doses, if affected take Julmentin before food
· vomiting
· diarrhoea (in children).
Uncommon side effects
These may affect up to 1 in 100 people
· skin rash, itching
· raised itchy rash (hives)
· indigestion
· dizziness
· headache.
Uncommon side effects that may show up in your blood tests:
· increase in some substances (enzymes) produced by the liver.
Rare side effects
These may affect up to 1 in 1000 people
· skin rash, which may blister, and looks like small targets (central dark spots surrounded by a paler area, with a dark ring around the edge – erythema multiforme)
If you notice any of these symptoms contact a doctor urgently.
Rare side effects that may show up in your blood tests:
· low number of cells involved in blood clotting
· low number of white blood cells.
Frequency not known
Frequency cannot be estimated from the available data..
· Allergic reactions (see above)
· Inflammation of the large intestine (see above)
· Inflammation of the protective membrane surrounding the brain (aseptic meningitis)
· Serious skin reactions:
- a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals
(Stevens-Johnson syndrome), and a more severe form, causing extensive peeling of the skin (more than 30% of the body surface – toxic epidermal necrolysis)
- widespread red skin rash with small pus-containing blisters (bullous exfoliative dermatitis)
- a red, scaly rash with bumps under the skin and blisters (exanthemous pustulosis).
Contact a doctor immediately if you get any of these symptoms.
· inflammation of the liver (hepatitis)
· jaundice, caused by increases in the blood of bilirubin (a substance produced in the liver) which may make your skin and whites of the eyes appear yellow
· inflammation of tubes in the kidney
· blood takes longer to clot
· hyperactivity
· convulsions (in people taking high doses of Julmentin or who have kidney problems)
· black tongue which looks hairy
Side effects that may show up in your blood or urine tests:
· severe reduction in the number of white blood cells
· low number of red blood cells (haemolytic anaemia)
· crystals in urine.
If you get side effects, tell your doctor or pharmacist if any of the side effects become severe or troublesome, or if you notice any side effects not listed in this leaflet.
To report any side effect(s):
The National Pharmacovigilance and Drug Safety Center (NPC)
Fax: +966-11-205-7662
Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.
Toll free phone: 8002490000
E-mail: npc.drug@sfda.gov.sa
Website: www.sfda.gov.sa/npc
- Keep out of the reach and sight of children.
- Store below 30oC, in a dry place.
- Do not use Julmentin after the expiry date which is stated on the carton and on the blister.
- Do not use Julmentin if you notice any visible sign of deterioration.
- Medicines should not be disposed off via wastewater or household waste. Ask your pharmacist how to dispose off medicines no longer required. These measures will help to protect the environment.
What Julmentin contains
The active substance is Amoxicillin and clavulanic acid.
Julmentin
Tablets 375mg: Each tablet contains:
Active ingredients: Amoxicillin 250mg as amoxicillin trihydrate and clavulanic acid 125mg as potassium clavulanate.
Excipients: Colloidal silicon dioxide, crospovidone, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, ethylcellulose, titanium dioxide, polishing emulsion, polyvinylpyrrolidone, hydroxypropyl cellulose, talc, and triacetin.
Julmentin Forte Tablets 625mg: Each tablet contains:
Active ingredients: Amoxicillin 500mg as amoxicillin trihydrate and clavulanic acid 125mg as potassium clavulanate.
Excipients: Colloidal silicon dioxide, crospovidone, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, klucel EF, talc, triacetin, polyvinylpyrrolidone, titanium dioxide, polishing emulsion and ethyl cellulose.
Julmentin 2X Tablets 1000mg: Each tablet contains:
Active ingredients: Amoxicillin 875mg as amoxicillin trihydrate and clavulanic acid 125mg as potassium clavulanate.
Excipients: Colloidal silicon dioxide, crospovidone, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, hydroxypropyl cellulose, ethyl cellulose, polyvinylpyrrolidone, triacetin, titanium dioxide, talc and polishing emulsion.
Gulf Pharmaceutical Industries " Julphar".
إن جلمنتين عبارة عن مضاد حيوي ويعمل عن طريق قتل البكتيريا التي تسبب العدوى. ويحتوي على نوعين مختلفين من الدواء هما أموكسيسيلين وحمض كلافيولانيك. ينتمي أموكسيسيلين إلى مجموعة الأدوية التي يطلق عليها "البنسيلينات" والذي في بعض الأحيان قد يتعرض لمقاومة بكتيرية تفقده مفعوله (تكبح نشاطه). يقوم المكون الآخر النشط في هذا المستحضر وهو(حمض كلافيولانيك) بكبح هذه المقاومة.
يستخدم جلمنتين في الكبار والأطفال لعلاج أنواع العدوى التالية:
· عدوى الأذن الوسطى وعدوى الجيوب الأنفية
· عدوى الجهاز التنفسي
· عدوى المسالك البولية
· عدوى الجلد والأنسجة الرخوة بما في ذلك عدوى الأسنان
· عدوى العظام والمفاصل.
يجب عدم تناول جلمنتين في الحالات التالية:
· إذا كنت تعاني من الحساسية (فرط الحساسية) لأموكسيسيلين، حمض الكلافيولانيك، البنسيلين أو أي من المحتويات الأخرى في جلمنتين (المذكورة في الفقرة 6)
· إذا كنت قد تعرضت في أي وقت مضى لتفاعل تحسسي شديد (فرط الحساسية) لأي من المضادات الحيوية الأخرى. وقد يشمل ذلك حدوث طفح جلدي أو تورم في الوجه أو العنق
· إذا كنت قد عانيت في أي وقت مضى من مشاكل في الكبد أو يرقان (اصفرار الجلد) عند تناول أي من المضادات الحيوية.
يجب عدم تناول جلمنتين إذا كان أي من المذكور أعلاه ينطبق عليك. إذا لم تكن متأكداً من ذلك، الرجاء إخبار طبيبك المعالج أو الصيدلي الذي تتعامل معه قبل تناول جلمنتين.
تحذيرات خاصة قبل تناول جلمنتين
يرجى التأكد من طبيبك المعالج أو الصيدلي الذي تتعامل معه قبل تناول هذا الدواء إذا كنت:
· تعاني من حمى غدية
· تتلقى علاجاً لاضطرابات في الكبد أو الكلى
· تعاني من حالة تتمثل في عدم إدرار البول بصورة طبيعية.
في حال لم تكن متأكداً ما إذا كان أي من المذكور أعلاه ينطبق عليك، الرجاء التحدث إلى طبيبك المعالج أو الصيدلي الذي تتعامل معه قبل تناول جلمنتين.
في بعض الحالات، قد يقوم طبيبك المعالج بإجراء فحص مختبري لمعرفة نوع البكتيريا المسببة للعدوى. وبناءً على نتائج هذا الفحص، قد يعطى لك جلمنتين بقوة مختلفة أو قد يعطى لك دواء آخر.
الحالات التي تتطلب منك الانتباه
قد يسبب جلمنتين تفاقم بعض الحالات المرضية الكامنة، أو قد يسبب كذلك تأثيرات جانبية خطيرة. والتي تتضمن تفاعلات تحسسية، تشنجات (اختلاجات) والتهاب في الأمعاء الغليظة. يجب الانتباه لمثل هذه الأعراض التي قد تحدث بينما تتناول جلمنتين، للتقليل من خطر حدوث أية مشاكل. انظر " الحالات التي تتطلب منك الانتباه" في الفقرة 4.
فحوصات الدم أو البول
إذا كنت ستخضع لفحوصات الدم (مثل فحوصات خلايا الدم الحمراء أو فحوصات وظائف الكبد) أو فحوصات البول (للكشف عن الجلوكوز)، فإنه يجب إخبار الطبيب أو الممرضة بأنك تتناول جلمنتين، وذلك لأن جلمنتين يمكن أن يؤثر على نتائج هذه الفحوصات .
تناول جلمنتين مع الأدوية الأخرى:
يرجى أن تخبر طبيبك المعالج أو الصيدلي الذي تتعامل معه إذا كنت تتناول أو تناولت مؤخراً أية أدوية أخرى، بما في ذلك الأدوية التي تصرف بدون وصفة طبية والأدوية العشبية.
· إذا كنت تتناول ألوبيورينول (دواء يستخدم لعلاج النقرس) بالتزامن مع جلمنتين، فإنه من المرجح حدوث تفاعل تحسسي في الجلد.
· إذا كنت تتناول بروبنسيد (دواء يستخدم لعلاج النقرس)، فقد يقرر طبيبك المعالج تعديل جرعة جلمنتين.
· إذا كنت تتناول الأدوية التي تمنع تكون الخثرات في الدم (على سبيل المثال الوارفارين) بالتزامن مع جلمنتين فقد يحتاج الطبيب إلى إجراء فحوصات دموية إضافية.
· قد يؤثر جلمنتين على آلية عمل ميثوتركسات (دواء يستخدم لعلاج السرطان أو الأمراض الروماتيزمية).
· كما قد يؤثر جلمنتين على آلية عمل مايكوفينولات موفيتل (دواء يستخدم لمنع رفض الجسم لعمليات زراعة الأعضاء).
الحمل، الرضاعة الطبيعية والخصوبة
إذا كنت حاملاً أو مرضعة، تعتقدين بأنك حاملاً أو تخططين لإنجاب طفلاً، فيرجى استشارة طبيبك المعالج أو الصيدلي الذي تتعاملين معه للحصول على النصيحة قبل تناول هذا الدواء .
القيادة واستخدام الآلات
قد يسبب جلمنتين تأثيرات جانبية والتي يمكن أن تعيق قدرتك على القيادة. يجب عدم القيادة أو تشغيل الآلات ما لم تكن بصحة جيدة.
يجب دائماً تناول جلمنتين تماماً كما أخبرك الطبيب. استشر طبيبك المعالج أو الصيدلي الذي تتعامل معه إذا لم تكن متأكداً.
البالغين والأطفال الذين تبلغ أوزانهم 40 كيلوغرام أو أكثر
أقراص جلمنتين 375 ملغم و أقراص جلمنتين فورت 625 ملغم:
الجرعة الاعتيادية هي: قرص واحد ثلاث مرات يومياً.
أقراص جلمنتين 2 إكس 1000 ملغم:
الجرعة الاعتيادية- قرص واحد مرتين يومياً.
الجرعة الأعلى- قرص واحد ثلاث مرات يومياً.
الأطفال الذين تقل أوزانهم عن 40 كيلوغرام
الأطفال بعمر 6 سنوات أو أقل يفضل علاجهم بإعطاء معلق جلمنتين الفموي.
استشر طبيبك أو الصيدلي قبل إعطاء جلمنتين أقراص للأطفال الذين تبلغ أوزانهم أقل من 40 كيلوغرام. إن الأقراص غير مناسبة للأطفال الذين تبلغ أوزانهم أقل من 25 كيلوغرام.
المرضى الذين يعانون من مشاكل في الكلى والكبد
· إذا كنت تعاني من مشاكل في الكلى فإنه يمكن تغيير الجرعة أو استخدام قوة مختلفة أو اختيار دواء مختلف من قبل طبيبك المعالج.
· إذا كنت تعاني من مشاكل في الكبد، فإنه قد يلزم إجراء فحوصات للدم بشكل دوري لمعرفة مدى كفاءة وظيفة الكبد.
كيفية إعطاء جلمنتين
· ابلع الأقراص كاملةً مع كوب من الماء عند بداية تناول الوجبة أو قبلها بفترة قليلة.
· قم بترك فترة متساوية بين كل جرعة وأخرى خلال اليوم، بحيث لا تقل عن 4 ساعات. لا تتناول جرعتين خلال ساعة واحدة.
· لا تتناول جلمنتين لأكثر من أسبوعين. إذا استمر شعورك بإعياء، يجب عليك الذهاب لرؤية الطبيب مرة أخرى.
إذا تناولت جلمنتين بجرعة أكبر من الاعتيادية على سبيل الخطأ
إذا كنت قد تناولت جلمنتين بجرعة أكبر مما ينبغي، فإن ذلك قد يؤدي إلى ظهور علامات تشمل اضطراب في المعدة (الشعور بالإعياء، وتوعك أو إسهال) أو تشنجات. يرجى إخبار طبيبك المعالج بهذا الأمر في أسرع وقت ممكن. خذ عبوة الدواء لإظهارها للطبيب المعالج.
إذا سهوت عن تناول جلمنتين
إذا سهوت عن تناول جرعة جلمنتين، فإنه يجب تناول هذه الجرعة في أسرع وقت ممكن حال تذكرها. أما الجرعة التالية فيجب عدم تناولها في الحال ولكن يجب الانتظار مدة 4 ساعات تقريباً قبل تناول الجرعة التالية. يجب عدم تناول جرعة مضاعفة لتعويض الجرعة التي سهوت عنها.
إذا توقفت عن تناول جلمنتين
استمر في تناول جلمنتين إلى تنتهي دورة العلاج المقررة، حتى لو تحسنت حالتك. حيث أنك بحاجة إلى كل جرعة من الجرعات الموصوفة لك للقضاء على العدوى. إذا لم يتم القضاء على كل البكتيريا المسببة للعدوى فقد تعاود العدوى مرة أخرى.
إذا كان لديك أي أسئلة أخرى حول استخدام هذا المستحضر، اسأل طبيبك المعالج أو الصيدلي الذي تتعامل معه.
كما هو الحال مع جميع الأدوية، قد يسبب جلمنتين تأثيرات جانبية، بالرغم من أنها قد لا تحدث لكل شخص.
الحالات التي تتطلب منك الانتباه
تفاعلات تحسسية:
· طفح جلدي
· التهاب الأوعية الدموية الذي يظهر على شكل بقع حمراء أو بنفسجية مرتفعة عن سطح الجلد، ولكن قد يؤثر على الأجزاء الأخرى من الجسم
· حمى، ألم في المفاصل، تورم الغدد في منطقة العنق، تورم في الفخذين أو الإبطين
· تورم في بعض الأحيان يشمل الوجه أو الفم (وذمة وعائية)، مسببة صعوبة في التنفس
· تدهور عام في الصحة.
يرجى الاتصال بالطبيب المعالج مباشرةً في حال تعرضت لأي من هذه الأعراض. توقف عن تناول جلمنتين.
التهاب الأمعاء الغليظة
التهاب الأمعاء الغليظة، والذي قد يؤدي إلى إسهال مائي مصحوب عادةً بدم أو مخاط، ألم في المعدة و/أو حمى.
يرجى الاتصال بطبيبك في أسرع وقت ممكن للاستشارة في حال تعرضك لأي من هذه الأعراض.
تأثيرات جانبية شائعة جداً
قد تصيب أكثر من شخص واحد لكل 10 من الأشخاص
· إسهال (في الكبار).
تأثيرات جانبية شائعة
قد تصيب حتى شخص واحد لكل 10 من الأشخاص
· مرض القلاع (الكانديدا – عدوى الخميرة في المهبل، الفم أو الثنايا الجلدية)
· الشعور بإعياء (غثيان)، خصوصاً مع تناول جرعات عالية، وفي حال الإصابة بذلك ينصح بتناول جلمنتين قبل الطعام
· تقيؤ
· إسهال (في الأطفال).
تأثيرات جانبية غير شائعة
قد تصيب حتى شخص واحد لكل 100 من الأشخاص
· طفح جلدي، حكة
· طفح جلدي مصحوب بحكة (طفح جلدي على شكل خلايا النحل)
· عسر الهضم
· دوخة
· صداع.
تأثيرات جانبية غير شائعة قد تظهر عند إجراء فحوصات للدم:
· زيادة في بعض المواد (الإنزيمات) التي يتم إنتاجها بواسطة الكبد.
تأثيرات جانبية نادرة
قد تصيب حتى شخص واحد لكل 1000 من الأشخاص
· طفح جلدي، قد يتحول إلى بثور، ويبدو على هيئة أقراص دائرية صغيرة (بقع داكنة في المركز محاطة بمنطقة شاحبة اللون، مع وجود حلقة داكنة حول الأطراف – حمامي متعددة الأشكال)
إذا لاحظت أي من هذه الأعراض، اتصل بطبيبك المعالج على الفور.
تأثيرات جانبية نادرة قد تظهر عند إجراء فحوصات للدم:
· نقص عدد الخلايا المساهمة في عملية تخثر الدم
· نقص عدد خلايا الدم البيضاء.
غير معروفة التكرار
لا يمكن تحديد معدل تكرار حدوثها من البيانات المتوفرة.
· تفاعلات تحسسية (انظر أعلاه)
· التهاب الأمعاء الغليظة (انظر أعلاه)
· التهاب الغشاء الواقي المحيط بالدماغ (التهاب السحايا العقيم)
· تفاعلات جلدية خطيرة:
- طفح جلدي منتشر مع بثور وتقشر في الجلد، خصوصاً حول الفم، الأنف، العينين والأعضاء التناسلية (متلازمة ستيفنز-جونسون)، وقد يؤدي
النوع الأكثر خطورة من هذا المرض إلى حدوث تقشر في مساحات واسعة من الجلد (أكثر من 30٪ من سطح الجسم- انحلال البشرة السمي
التنخري).
- طفح جلدي منتشر أحمر اللون مع بثور صغيرة متقيحة (التهاب الجلد التقشري الفقاعي)
- طفح جلدي متقشر أحمر اللون مع نتوءات تحت الجلد وبثور (بثار طفحي متقيح على الجلد).
يرجى الاتصال بالطبيب المعالج مباشرةً إذا تعرضت لأي من هذه الأعراض.
· التهاب الكبد
· يرقان، ناتج عن زيادة البليروبين في الدم (مادة مفرزة من الكبد) وقد يؤدي إلى تلون الجلد وبياض العينين باللون الأصفر
· التهاب الأنابيب في الكلى
· طول الفترة اللازمة لتخثر الدم
· فرط النشاط
· تشنجات (في المرضى الذين يتناولون جرعات عالية من جلمنتين أو الذين يعانون من مشاكل في الكلى)
· أسوداد لون اللسان و يبدو كأنه مشعر
تأثيرات جانبية قد تظهر عند إجراء فحوصات للدم أو البول:
· نقص شديد في تعداد خلايا الدم البيضاء
· نقص عدد خلايا الدم الحمراء (فقر الدم الإنحلالي)
· ظهور البلورات في البول
إذا ظهرت أي من هذه الأعراض الجانبية، يرجى إخبار طبيبك المعالج أو الصيدلي الذي تتعامل معه إذا زادت حدة أي من هذه الأعراض أو لاحظت أعراض جانبية لم تذكر في هذه النشرة.
للإبلاغ عن حدوث أية تأثيرات جانبية:
المركز الوطني للتيقظ والسلامة الدوائية
رقم الفاكس: 7662-205-11-966+
يرجى الاتصال بالمركز الوطني للتيقظ والسلامة الدوائية على: 2038222-11-966+
وصلة هاتف:2340-2334-2354-2353-2356-2317
الهاتف المجاني: 8002490000
البريد الإلكتروني: npc.drug@sfda.gov.sa
الموقع الإلكتروني: www.sfda.gov.sa/npc
- يحفظ بعيداً عن متناول ومرأى الأطفال.
- يحفظ في درجة حرارة أقل من 30 ºم، في مكان جاف.
- لا تستخدم جلمنتين بعد تاريخ انتهاء الصلاحية المذكور على العبوة والشريط الداخلي.
- لا تستخدم جلمنتين إذا لاحظت وجود علامات تلف واضحة.
- يجب عدم التخلص من الأدوية عبر المياه المبتذلة (مياه الصرف الصحي) أو النفايات المنزلية. اسأل الصيدلي الذي تتعامل معه عن كيفية التخلص من الأدوية التي لم تعد بحاجة إليها. ستساعد هذه الإجراءات على حماية البيئة.
ماهي محتويات جلمنتين
المادة الفعالة هي: أموكسيسيلين وحمض كلافيولانيك.
جلمنتين
أقراص 375 ملغم: يحتوي كل قرص على:
المواد الفعالة: أموكسيسيلين 250 ملغم على هيئة أموكسيسيلين ثلاثي الهيدرات وحمض كلافيولانيك 125 ملغم على هيئة كلافيولانات البوتاسيوم.
المواد غير الفعالة: ثنائي أكسيد السيليكون الغروي، كروس بوفيدون، كروس كارميلوز الصوديوم، استيارات المغنيسيوم، سليلوز دقيق البلورات، إثيل السليلوز، ثنائي أكسيد التيتانيوم، مستحلب للصقل، بولي فينيل بايروليدون، هيدروكسي بروبيل السليلوز، تلك، وتراي أسيتين.
جلمنتين فورت أقراص 625 ملغم: يحتوي كل قرص على:
المواد الفعالة: أموكسيسيلين 500 ملغم على هيئة أموكسيسيلين ثلاثي الهيدرات وحمض كلافيولانيك 125 ملغم على هيئة كلافيولانات البوتاسيوم.
المواد غير الفعالة: ثنائي أكسيد السيليكون الغروي، كروس بوفيدون، كروس كارميلوز الصوديوم، استيارات المغنيسيوم، سليلوز دقيق البلورات، كليوسيل إي إف، تلك، تراي أسيتين، بولي فينيل بايروليدون، ثنائي أكسيد التيتانيوم، مستحلب للصقل وإثيل السليلوز.
جلمنتين 2 إكس أقراص 1000 ملغم: يحتوي كل قرص على:
المواد الفعالة: أموكسيسيلين 875 ملغم على هيئة أموكسيسيلين ثلاثي الهيدرات وحمض كلافيولانيك 125 ملغم على هيئة كلافيولانات البوتاسيوم.
المواد غير الفعالة: ثنائي أكسيد السيليكون الغروي، كروس بوفيدون، كروس كارميلوز الصوديوم، استيارات المغنيسيوم، سليلوز دقيق البلورات، هيدروكسي بروبيل السليلوز، إثيل السليلوز، بولي فينيل بايروليدون، تراي أسيتين، ثنائي أكسيد التيتانيوم، تلك ومستحلب للصقل.
"الخليج للصناعات الدوائية " جلفار
Julmentin Forte is indicated for the treatment of the following infections in adults and children (see sections 4.2, 4.4 and 5.1):
§ Acute bacterial sinusitis (adequately diagnosed)
§ Acute otitis media
§ Acute exacerbations of chronic bronchitis (adequately diagnosed)
§ Community acquired pneumonia
§ Cystitis
§ Pyelonephritis
§ Skin and soft tissue infections in particular cellulitis, animal bites, severe dental abscess with spreading cellulitis.
§ Bone and joint infections, in particular osteomyelitis.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Doses are expressed throughout in terms of amoxicillin/clavulanic acid content except when doses are stated in terms of an individual component.
The dose of Julmentin Forte that is selected to treat an individual infection should take into account:
§ The expected pathogens and their likely susceptibility to antibacterial agents (see section 4.4)
§ The severity and the site of the infection
§ The age, weight and renal function of the patient as shown below.
The use of alternative presentations of Julmentin Forte (e.g. those that provide higher doses of amoxicillin and/or different ratios of amoxicillin to clavulanic acid) should be considered as necessary (see sections 4.4 and 5.1).
For adults and children ≥ 40 kg, this formulation of Julmentin Forte provides a total daily dose of 1500 mg amoxicillin/375 mg clavulanic acid, when administered as recommended below. For children < 40 kg, this formulation of Julmentin Forte provides a maximum daily dose of 2400 mg amoxicillin/600 mg clavulanic acid, when administered as recommended below. If it is considered that a higher daily dose of amoxicillin is required, it is recommended that another preparation of Julmentin Forte is selected in order to avoid administration of unnecessarily high daily doses of clavulanic acid (see sections 4.4 and 5.1).
The duration of therapy should be determined by the response of the patient. Some infections (e.g. osteomyelitis) require longer periods of treatment. Treatment should not be extended beyond 14 days without review (see section 4.4 regarding prolonged therapy).
Adults and children ≥ 40 kg
One 500 mg/125 mg dose taken three times a day.
Children < 40 kg
20 mg/5 mg/kg/day to 60 mg/15 mg/kg/day given in three divided doses.
Children may be treated with Julmentin Forte tablets, suspensions.
As the tablets cannot be divided, children weighing less than 25 kg must not be treated with Julmentin Forte tablets.
The table below presents the received dose (mg/kg body weight) in children weighing 25 kg to 40 kg upon administering a single 500/125 mg tablet.
Body weight [kg] | 40 | 35 | 30 | 25 | Single dose recommended [mg/kg body weight] (see above) |
Amoxicillin [mg/kg body weight] per single dose (1 film-coated tablet) | 12.5 | 14.3 | 16.7 | 20.0 | 6.67 – 20 |
Clavulanic acid [mg/kg body weight] per single dose (1 film-coated tablet) | 3.1 | 3.6 | 4.2 | 5.0 | 1.67 - 5 |
Children aged 6 years and below or weighing less than 25 kg should preferably be treated with Julmentin Forte suspension.
No clinical data are available on doses of amoxicillin/clavulanic acid. 4:1 formulations higher than 40 mg/10 mg/kg per day in children under 2 years.
Elderly
No dose adjustment is considered necessary.
Renal impairment
Dose adjustments are based on the maximum recommended level of amoxicillin.
No adjustment in dose is required in patients with creatinine clearance (CrCl) greater than
30 ml/min.
Adults and children ≥ 40 kg
CrCl: 10-30 ml/min | 500 mg/125 mg twice daily |
CrCl < 10 ml /min | 500 mg/125 mg once daily |
Haemodialysis | 500 mg/125 mg every 24 hours, plus 500 mg/125 mg during dialysis, to be repeated at the end of dialysis (as serum concentrations of both amoxicillin and clavulanic acid are decreased) |
Children < 40 kg
CrCl: 10-30 ml/min | 15 mg/3.75 mg/kg twice daily (maximum 500 mg/125 mg twice daily). |
CrCl < 10 ml /min | 15 mg/3.75 mg/kg as a single daily dose (maximum 500 mg/125 mg). |
Haemodialysis | 15 mg/3.75 mg/kg per day once daily. Prior to haemodialysis 15 mg/3.75 mg/kg. In order to restore circulating drug levels, 15 mg/3.75 mg per kg should be administered after haemodialysis. |
Hepatic impairment
Dose with caution and monitor hepatic function at regular intervals (see sections 4.3 and 4.4).
Method of administration
Julmentin Forte is for oral use.
Administer at the start of a meal to minimise potential gastrointestinal intolerance and optimise absorption of amoxicillin/clavulanic acid.
Before initiating therapy with amoxicillin/clavulanic acid, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam agents (see sections 4.3 and 4.8).
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in atopic individuals. If an allergic reaction occurs, amoxicillin/clavulanic acid therapy must be discontinued and appropriate alternative therapy instituted.
In the case that an infection is proven to be due to an amoxicillin-susceptible organisms(s) then consideration should be given to switching from amoxicillin/clavulanic acid to amoxicillin in accordance with official guidance.
This presentation of Amoxicillin/clavulanic acid is not suitable for use when there is a high risk that the presumptive pathogens have reduced susceptibility or resistance to beta-lactam agents that is not mediated by beta-lactamases susceptible to inhibition by clavulanic acid. This presentation should not be used to treat penicillin-resistant S. pneumoniae.
Convulsions may occur in patients with impaired renal function or in those receiving high doses (see section 4.8).
Amoxicillin/clavulanic acid should be avoided if infectious mononucleosis is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of amoxicillin.
Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions.
Prolonged use may occasionally result in overgrowth of non-susceptible organisms.
The occurrence at the treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthemous pustulosis (AGEP) (see Section 4.8). This reaction requires Amoxicillin/clavulanic acid discontinuation and contra-indicates any subsequent administration of amoxicillin.
Amoxicillin/clavulanic acid should be used with caution in patients with evidence of hepatic impairment (see section 4.2).
Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been very rarely reported in children. In all populations, signs and symptoms usually occur during or shortly after treatment but in some cases may not become apparent until several weeks after treatment has ceased. These are usually reversible. Hepatic events may be severe and, in extremely rare circumstances, deaths have been reported. These have almost always occurred in patients with serious underlying disease or taking concomitant medications known to have the potential for hepatic effects (see section 4.8).
Antibiotic-associated colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life threatening (see section 4.8). Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of any antibiotics. Should antibiotic-associated colitis occur, amoxicillin/clavulanic acid should immediately be discontinued, a physician be consulted and an appropriate therapy initiated. Anti-peristaltic medicinal products are contra-indicated in this situation.
Periodic assessment of organ system functions, including renal, hepatic and haematopoietic function is advisable during prolonged therapy.
Prolongation of prothrombin time has been reported rarely in patients receiving amoxicillin/clavulanic acid. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation (see section 4.5 and 4.8).
In patients with renal impairment, the dose should be adjusted according to the degree of impairment (see section 4.2).
In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy. During the administration of high doses of amoxicillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria. In patients with bladder catheters, a regular check of patency should be maintained (see section 4.9).
During treatment with amoxicillin, enzymatic glucose oxidase methods should be used whenever testing for the presence of glucose in urine because false positive results may occur with non-enzymatic methods.
The presence of Clavulanic acid in Amoxicillin/clavulanic acid tablets may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test.
There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus EIA test in patients receiving amoxicillin/clavulanic acid who were subsequently found to be free of Aspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with Bio-Rad Laboratories Platelia Aspergillus EIA test have been reported. Therefore, positive test results in patients receiving amoxicillin/clavulanic acid should be interpreted cautiously and confirmed by other diagnostic methods.
Oral anticoagulants
Oral anticoagulants and penicillin antibiotics have been widely used in practice without reports of interaction. However, in the literature there are cases of increased international normalised ratio in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxicillin. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of amoxicillin. Moreover, adjustments in the dose of oral anticoagulants may be necessary (see sections 4.4 and 4.8).
Methotrexate
Penicillins may reduce the excretion of methotrexate causing a potential increase in toxicity.
Probenecid
Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use of probenecid may result in increased and prolonged blood levels of amoxicillin but not of clavulanic acid.
Mycophenolate mofetil
In patients receiving mycophenolate mofetil, reduction in pre-dose concentration of the active metabolite mycophenolic acid (MPA) of approximately 50% has been reported following commencement of oral amoxicillin plus clavulanic acid. The change in pre-dose level may not accurately represent changes in overall MPA exposure. Therefore, a change in the dose of mycophenolate mofetil should not normally be necessary in the absence of clinical evidence of graft dysfunction. However, close clinical monitoring should be performed during the combination and shortly after antibiotic treatment.
Pregnancy
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). Limited data on the use of amoxicillin/clavulanic acid during pregnancy in humans do not indicate an increased risk of congenital malformations. In a single study in women with preterm, premature rupture of the foetal membrane it was reported that prophylactic treatment with amoxicillin/clavulanic acid may be associated with an increased risk of necrotising enterocolitis in neonates. Use should be avoided during pregnancy, unless considered essential by the physician.
Breastfeeding
Both substances are excreted into breast milk (nothing is known of the effects of clavulanic acid on the breast-fed infant). Consequently, diarrhoea and fungus infection of the mucous membranes are possible in the breast-fed infant, so that breast-feeding might have to be discontinued. Amoxicillin/clavulanic acid should only be used during breast-feeding after benefit/risk assessment by the physician in charge.
No studies on the effects on the ability to drive and use machines have been performed. However, undesirable effects may occur (e.g. allergic reactions, dizziness, convulsions), which may influence the ability to drive and use machines (see section 4.8).
The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and vomiting.
The ADRs derived from clinical studies and post-marketing surveillance with Amoxicillin/clavulanic acid, sorted by MedDRA System Organ Class are listed below.
The following terminologies have been used in order to classify the occurrence of undesirable effects.
§ 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)
Infections and infestations | |
Mucocutaneous candidosis | Common |
Overgrowth of non-susceptible organisms | Not known |
Blood and lymphatic system disorders | |
Reversible leucopenia (including neutropenia) | Rare |
Thrombocytopenia | Rare |
Reversible agranulocytosis | Not known |
Haemolytic anaemia | Not known |
Prolongation of bleeding time and prothrombin time1 | Not known |
Immune system disorders10 | |
Angioneurotic oedema | Not known |
Anaphylaxis | Not known |
Serum sickness-like syndrome | Not known |
Hypersensitivity vasculitis | Not known |
Nervous system disorders | |
Dizziness | Uncommon |
Headache | Uncommon |
Reversible hyperactivity | Not known |
Convulsions2 | Not known |
Aeseptic meningitis | Not known |
Gastrointestinal disorders | |
Diarrhoea | Very common |
Nausea3 | Common |
Vomiting | Common |
Indigestion | Uncommon |
Antibiotic-associated colitis4 | Not known |
Black hairy tongue | Not known |
Hepatobiliary disorders | |
Rises in AST and/or ALT5 | Uncommon |
Hepatitis6 | Not known |
Cholestatic jaundice6 | Not known |
Skin and subcutaneous tissue disorders7 | |
Skin rash | Uncommon |
Pruritus | Uncommon |
Urticaria | Uncommon |
Erythema multiforme | Rare |
Stevens-Johnson syndrome | Not known |
Toxic epidermal necrolysis | Not known |
Bullous exfoliative-dermatitis | Not known |
Acute generalised exanthemous pustulosis (AGEP)9 | Not known |
Renal and urinary disorders | |
Interstitial nephritis | Not known |
Crystalluria8 | Not known |
1 See section 4.4 2 See section 4.4 3 Nausea is more often associated with higher oral doses. If gastrointestinal reactions are evident, they may be reduced by taking Amoxicillin/clavulanic acid at the start of a meal. 4 Including pseudomembranous colitis and haemorrhagic colitis (see section 4.4) 5 A moderate rise in AST and/or ALT has been noted in patients treated with beta-lactam class antibiotics, but the significance of these findings is unknown. 6 These events have been noted with other penicillins and cephalosporins (see section 4.4). 7 If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued (see section 4.4). 8 See section 4.9 9 See section 4.4 10 See sections 4.3 and 4.4 | |
To report any side effect(s):
The National Pharmacovigilance and Drug Safety Center (NPC)
Fax: +966-11-205-7662
Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.
Toll free phone: 8002490000
E-mail: npc.drug@sfda.gov.sa
Website: www.sfda.gov.sa/npc
Symptoms and signs of overdose
Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see section 4.4).
Convulsions may occur in patients with impaired renal function or in those receiving high doses.
Amoxicillin has been reported to precipitate in bladder catheters, predominantly after intravenous administration of large doses. A regular check of patency should be maintained (see section 4.4).
Treatment of intoxication
Gastrointestinal symptoms may be treated symptomatically, with attention to the water/electrolyte balance.
Amoxicillin/clavulanic acid can be removed from the circulation by haemodialysis.
Pharmacotherapeutic group: Combinations of penicillins, incl. beta-lactamase inhibitors; ATC code: J01CR02.
Mechanism of action
Amoxicillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBPs) in the biosynthetic pathway of bacterial peptidoglycan, which is an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, which is usually followed by cell lysis and death.
Amoxicillin is susceptible to degradation by beta-lactamases produced by resistant bacteria and therefore the spectrum of activity of amoxicillin alone does not include organisms which produce these enzymes.
Clavulanic acid is a beta-lactam structurally related to penicillins. It inactivates some beta-lactamase enzymes thereby preventing inactivation of amoxicillin. Clavulanic acid alone does not exert a clinically useful antibacterial effect.
Pharmacokinetic/pharmacodynamic relationship
The time above the minimum inhibitory concentration (T>MIC) is considered to be the major determinant of efficacy for amoxicillin.
Mechanisms of resistance
The two main mechanisms of resistance to amoxicillin/clavulanic acid are:
§ Inactivation by those bacterial beta-lactamases that are not themselves inhibited by clavulanic acid, including class B, C and D.
§ Alteration of PBPs, which reduce the affinity of the antibacterial agent for the target.
Impermeability of bacteria or efflux pump mechanisms may cause or contribute to bacterial resistance, particularly in Gram-negative bacteria.
Breakpoints
MIC breakpoints for amoxicillin/clavulanic acid are those of the European Committee on Antimicrobial Susceptibility Testing (EUCAST)
Organism | Susceptibility Breakpoints (μg/ml) | ||
| Susceptible | Intermediate | Resistant |
Haemophilus influenzae1 | ≤ 1 | - | > 1 |
Moraxella catarrhalis1 | ≤ 1 | - | > 1 |
Staphylococcus aureus 2 | ≤ 2 | - | > 2 |
Coagulase-negative staphylococci 2 | ≤ 0.25 |
| > 0.25 |
Enterococcus1 | ≤ 4 | 8 | > 8 |
Streptococcus A, B, C, G5 | ≤ 0.25 | - | > 0.25 |
Streptococcus pneumoniae3 | ≤ 0.5 | 1-2 | > 2 |
Enterobacteriaceae1,4 | - | - | > 8 |
Gram-negative Anaerobes1 | ≤ 4 | 8 | > 8 |
Gram-positive Anaerobes1 | ≤ 4 | 8 | > 8 |
Non-species related breakpoints1 | ≤ 2 | 4-8 | > 8 |
1 The reported values are for Amoxicillin concentrations. For susceptibility testing purposes, the concentration of Clavulanic acid is fixed at 2 mg/l. 2 The reported values are Oxacillin concentrations. 3 Breakpoint values in the table are based on Ampicillin breakpoints. 4 The resistant breakpoint of R>8 mg/l ensures that all isolates with resistance mechanisms are reported resistant. 5 Breakpoint values in the table are based on Benzylpenicillin breakpoints. | |||
The prevalence of resistance may vary geographically and with time for selected species, and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.
Commonly susceptible species |
Aerobic Gram-positive micro-organisms Enterococcus faecalis Gardnerella vaginalis Staphylococcus aureus (methicillin-susceptible)£ Coagulase-negative staphylococci (methicillin-susceptible) Streptococcus agalactiae Streptococcus pneumoniae1 Streptococcus pyogenes and other beta-haemolytic streptococci Streptococcus viridans group Aerobic Gram-negative micro-organisms Capnocytophaga spp. Eikenella corrodens Haemophilus influenzae2 Moraxella catarrhalis Pasteurella multocida Anaerobic micro-organisms Bacteroides fragilis Fusobacterium nucleatum Prevotella spp. |
Species for which acquired resistance may be a problem |
Aerobic Gram-positive micro-organisms Enterococcus faecium $ Aerobic Gram-negative micro-organisms Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Proteus vulgaris |
Inherently resistant organisms |
Aerobic Gram-negative micro-organisms Acinetobacter sp. Citrobacter freundii Enterobacter sp. Legionella pneumophila Morganella morganii Providencia spp. Pseudomonas sp. Serratia sp. Stenotrophomonas maltophilia Other micro-organisms Chlamydophila pneumoniae Chlamydophila psittaci Coxiella burnetti Mycoplasma pneumoniae |
$ Natural intermediate susceptibility in the absence of acquired mechanism of resistance. £All methicillin-resistant staphylococci are resistant to amoxicillin/clavulanic acid 1Streptococcus pneumoniae that are resistant to penicillin should not be treated with this presentation of amoxicillin/clavulanic acid (see sections 4.2 and 4.4). 2 Strains with decreased susceptibility have been reported in some countries in the EU with a frequency higher than 10%. |
Absorption
Amoxicillin and clavulanic acid, are fully dissociated in aqueous solution at physiological pH. Both components are rapidly and well absorbed by the oral route of administration. Absorption of amoxicillin/clavulanic acid is optimised when taken at the start of a meal. Following oral administration, amoxicillin and clavulanic acid are approximately 70% bioavailable. The plasma profiles of both components are similar and the time to peak plasma concentration (Tmax) in each case is approximately one hour.
The pharmacokinetic results for a study, in which amoxicillin/clavulanic acid (500 mg/125 mg tablets three times daily) was administered in the fasting state to groups of healthy volunteers are presented below.
Mean (± SD) pharmacokinetic parameters | |||||
Active substance(s) administered | Dose | Cmax | Tmax * | AUC (0-24h) | T 1/2 |
(mg) | (μg/ml) | (h) | ((μg.h/ml) | (h) | |
Amoxicillin | |||||
AMX/CA 500/125 mg | 500 | 7.19 ± 2.26 | 1.5 (1.0-2.5) | 53.5 ± 8.87 | 1.15 ± 0.20 |
Clavulanic acid | |||||
AMX/CA 500 mg/125 mg | 125 | 2.40 ± 0.83 | 1.5 (1.0-2.0) | 15.72 ± 3.86 | 0.98 ± 0.12 |
AMX – amoxicillin, CA – clavulanic acid * Median (range) | |||||
Amoxicillin and clavulanic acid serum concentrations achieved with amoxicillin/clavulanic acid are similar to those produced by the oral administration of equivalent doses of amoxicillin or clavulanic acid alone.
Distribution
About 25% of total plasma clavulanic acid and 18% of total plasma amoxicillin is bound to protein. The apparent volume of distribution is around 0.3-0.4 l/kg for amoxicillin and around 0.2 l/kg for clavulanic acid.
Following intravenous administration, both amoxicillin and clavulanic acid have been found in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids, bile and pus. Amoxicillin does not adequately distribute into the cerebrospinal fluid.
From animal studies there is no evidence for significant tissue retention of drug-derived material for either component. Amoxicillin, like most penicillins, can be detected in breast milk. Trace quantities of clavulanic acid can also be detected in breast milk (see section 4.6).
Both amoxicillin and clavulanic acid have been shown to cross the placental barrier (see section 4.6).
Biotransformation
Amoxicillin is partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to up to 10 to 25% of the initial dose. Clavulanic acid is extensively metabolized in man and eliminated in urine and faeces and as carbon dioxide in expired air.
Elimination
The major route of elimination for amoxicillin is via the kidney, whereas for clavulanic acid it is by both renal and non-renal mechanisms.
Amoxicillin/clavulanic acid has a mean elimination half-life of approximately one hour and a mean total clearance of approximately 25 l/h in healthy subjects. Approximately 60 to 70% of the amoxicillin and approximately 40 to 65% of the clavulanic acid are excreted unchanged in urine during the first 6 h after administration of single amoxicillin/clavulanic acid 250 mg/125 mg or 500 mg/125 mg tablets. Various studies have found the urinary excretion to be 50-85% for amoxicillin and between 27-60% for clavulanic acid over a 24 hour period. In the case of clavulanic acid, the largest amount of drug is excreted during the first 2 hours after administration.
Concomitant use of probenecid delays amoxicillin excretion but does not delay renal excretion of clavulanic acid (see section 4.5).
Age
The elimination half-life of amoxicillin is similar for children aged around 3 months to 2 years and older children and adults. For very young children (including preterm newborns) in the first week of life the interval of administration should not exceed twice daily administration due to immaturity of the renal pathway of elimination. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Gender
Following oral administration of amoxicillin/clavulanic acid to healthy males and female subjects, gender has no significant impact on the pharmacokinetics of either amoxicillin or clavulanic acid.
Renal impairment
The total serum clearance of amoxicillin/clavulanic acid decreases proportionately with decreasing renal function. The reduction in drug clearance is more pronounced for amoxicillin than for clavulanic acid, as a higher proportion of amoxicillin is excreted via the renal route. Doses in renal impairment must therefore prevent undue accumulation of amoxicillin while maintaining adequate levels of clavulanic acid (see section 4.2).
Hepatic impairment
Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals.
Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, genotoxicity and toxicity to reproduction.
Repeat dose toxicity studies performed in dogs with amoxicillin/clavulanic acid demonstrate gastric irritancy and vomiting, and discoloured tongue.
Carcinogenicity studies have not been conducted with amoxicillin/clavulanic acid or its components.
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Not applicable.
Store below 30 ºC, in a dry place.
4 x 5 tablets in Alu-Alu blister strips, packed in a printed carton along with a leaflet.
3 x 5 tablets in Alu-Alu blister strips, packed in a printed carton along with a leaflet.
None.
