Search Results
| نشرة الممارس الصحي | نشرة معلومات المريض بالعربية | نشرة معلومات المريض بالانجليزية | صور الدواء | بيانات الدواء |
|---|
ERACID belongs to a group of medicines called macrolide antibiotics. Antibiotics stop the growth of bacteria (bugs) which cause infections. ERACID tablets are used to treat infections such as: □ Chest infections such as bronchitis and pneumonia □ Throat and sinus infections □ Skin and soft tissue infections □ Helicobacter pylori infection associated with duodenal ulcer. ERACID Tablets are indicated in adults and children 12 years and older
□ Know that you are allergic to clarithromycin, other macrolide antibiotics such as erythromycin or azithromycin, or any of the other ingredients in the tablets. □ Are taking medicines called ergot alkaloids (e.g. ergotamine or dihydroergotamine) or use ergotamine inhalers for migraine. □ Are taking medicines called terfenadine or astemizole (widely taken for hay fever or allergies) or cisapride or domperidone (for stomach disorders) or pimozide (for mental health problems) as combining these drugs can sometimes cause serious disturbances in heart rhythm. Consult your doctor for advice on alternative medicines. □ Are taking other medicines which are known to cause serious disturbances in heart rhythm. □ Are taking lovastatin or simvastatin (HMG-CoA reductase inhibitors, commonly known as statins, used to lower levels of cholesterol (a type of fat) in the blood). □ Are taking oral midazolam (a sedative). □ Are taking a medicine containing lomitapide □ Have abnormally low levels of potassium or magnesium in your blood (hypokalaemia or hypomagnesaemia). □ Have severe liver disease with kidney disease. □ Or someone in your family has a history of heart rhythm disorders (ventricular cardia arrhythmia, including torsades de pointes) or abnormality of electrocardiogram (ECG, electrical recording of the heart) called “long QT syndrome”. □ Are taking medicines called ticagrelor or ranolazine (for heart attack, chest pain or angina) □ Are taking colchicine (usually taken for gout) Take special care with ERACID: Talk to your doctor, pharmacist or nurse before taking ERACID Tablets: □ If you have heart problems (e.g. heart disease, heart failure, an unusually slow heart rate) □ If you have any liver or kidney problems □ If you have, or are prone to, fungal infections (e.g. thrush) □ If you are pregnant or breast feeding Children ERACID tablets are not suitable for use in children under 12 years of age. Taking other medicines with ERACID: You should not take ERACID tablets if you are taking any of the medicines listed in the section above “Do not take ERACID tablets if you;” Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines as your dose may need to be changed or you may need to have regular tests performed: □ Digoxin, quinidine or disopyramide (for heart problems). □ Ibrutinib (for cancer treatment) □ Warfarin, or any other anticoagulant e.g. dabigatran, rivaroxaban, apixaban (for blood thinning) □ Carbamazepine, valproate, phenobarbital or phenytoin (for epilepsy) □ Atorvastatin, rosuvastatin (HMG-CoA reductase inhibitors, commonly known as statins, and used to lower levels of cholesterol (a type of fat) in the blood). Statins can cause rhabdomyolysis (a condition which causes the breakdown of muscle tissue which can result in kidney damage) and signs of myopathy (muscle pain or muscle weakness) should be monitored. □ Nateglinide, pioglitazone, repaglinide, rosiglitazone or insulin (used to lower blood glucose levels) □ Gliclazide or glimepiride (sulphonylureas used in the treatment of type II diabetes) □ Theophylline (used in patients with breathing difficulties such as asthma) □ Triazolam, alprazolam or intravenous or oromucosal midazolam (sedatives) □ Cilostazol (for poor circulation) □ Methadone (used in the treatment of opioid addiction) □ Methylprednisolone (a corticosteroid) □ Vinblastine (for treatment of cancer) □ Ciclosporin, sirolimus and tacrolimus (immune suppressants) □ Etravirine, efavirenz, nevirapine, ritonavir, zidovudine, atazanavir, saquinavir (anti-viral drugs used in the treatment of HIV) □ Rifabutin, rifampicin, rifapentine, fluconazole, itraconazole (used in the treatment of certain bacterial infections) □ Tolterodine (for overactive bladder) □ Verapamil, amlodipine, diltiazem (for high blood pressure) □ Sildenafil, vardenafil and tadalafil (for impotence in adult males or for use in pulmonary arterial hypertension (highblood pressure in the blood vessels of the lung)) □ St John’s Wort (a herbal product used to treat depression) □ Quetiapine or other antipsychotic medicines. □ other macrolide medicines □ lincomycin and clindamycin (lincosamides – a type of antibiotic) Please tell your doctor if you are taking oral contraceptive pills and diarrhoea or vomiting occurs, as you may need to take extra contraceptive precautions such as using a condom. Pregnancy and breast-feeding: If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist before taking this medicine as the safety of ERACID tablets in pregnancy and breast-feeding is not known. Driving and using machines: ERACID tablets may make you feel dizzy or drowsy. If they affect you in this way do not drive, operate machinery or do anything that requires you to be alert.
Do not give these tablets to children under 12 years. Your doctor will prescribe another suitable medicine for your child. Always take ERACID tablets exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure. The recommended dose is; For chest infections, throat or sinus infections and skin and soft tissue infections: Usual dose of ERACID tablets for adults and children over 12 years is 250 mg twice daily for 6 to 14 days, e.g. one 250 mg tablet in the morning and one in the early evening. Your doctor may increase the dose to 500 mg twice daily in severe infections. ERACID tablets should be swallowed with at least half a glass of water. For the treatment of Helicobacter pylori infection associated with duodenal ulcers: There are a number of effective treatment combinations available to treat Helicobacter pylori in which ERACID tablets are taken together with one or two other drugs. These combinations include the following and are usually taken for 6 to 14 days: a) One ERACID 500 mg tablet taken twice a day together with amoxycillin, 1000 mg taken twice a day plus lansoprazole, 30 mg twice a day. b) One ERACID 500 mg tablet taken twice a day together with metronidazole, 400 mg taken twice a day plus lansoprazole, 30 mg twice a day. c) One ERACID 500 mg tablet taken twice a day together with amoxycillin, 1000 mg taken twice a day or metronidazole, 400 mg taken twice a day plus omeprazole, 40 mg a day. d) One ERACID 500 mg tablet taken twice a day together with amoxycillin, 1000 mg taken twice a day plus omeprazole, 20 mg taken once a day. The treatment combination which you receive may differ slightly from the above. Your doctor will decide which treatment combination is the most suitable for you. If you are unsure which tablets you should be taking or how long you should be taking them for, please consult your doctor for advice. If you take more ERACID than you should: If you accidentally take more tablets in one day than your doctor has told you to or if a child accidentally swallows some tablets, contact your doctor or nearest hospital emergency department immediately. An overdose of ERACID tablets is likely to cause vomiting and stomach pains. If you forget to take ERACID: If you forget to take a dose of your tablets, take one as soon as you remember. Do not take more tablets in one day than your doctor has told you to. If you stop taking ERACID: Do not stop taking your tablets, even if you feel better. It is important to take the tablets for as long as the doctor has told you to, otherwise the problem might come back. If you have any further questions on the use of this medicine, ask your doctor or pharmacistLike all medicines, ERACID can cause side effects although not everybody gets them. If you suffer from any of the following at any time during your treatment STOP TAKING your tablets and contact your doctor immediately: □ Severe or prolonged diarrhoea, which may have blood or mucus in it. Diarrhoea may occur over two months after treatment with clarithromycin, in which case you should still contact your doctor. □ A rash, difficulty breathing, fainting or swelling of the face, tongue, lips, eyes and throat.This is a sign that you may have developed an allergic reaction. □ Yellowing of the skin (jaundice), skin irritation, pale stools, dark urine, tender abdomen or loss of appetite. These are signs that your liver may have inflammation and not be working properly. □ Severe skin reactions such as painful blistering of the skin, mouth, lips, eyes and genitals (symptoms of a rare allergic reaction called Stevens-Johnson syndrome/toxic epidermal necrolysis). □ A red, scaly rash with bumps under the skin and blisters (symptoms of exanthematous pustulosis). The frequency of this side effect is not known (cannot be estimated from the available data). □ Rare allergic skin reactions which cause severe illness with ulceration of the mouth, lips and skin which causes severe illness with rash, fever and inflammation of internal organs (DRESS). □ Muscle pain or weakness known as rhabdomyolysis (a condition which causes the breakdown of muscle tissue which can result in kidney damage). Other side effects Common side effects (may affect up to 1 in 10 people) include; □ Difficulty sleeping □ Changes in sense of taste □ Headache □ Widening of blood vessels □ Stomach problems such as feeling sick, vomiting, stomach pain, indigestion, diarrhoea □ Increased sweating Uncommon side effects (may include up to 1 in 100 people) include: □ High temperature □ Swelling, redness or itchiness of the skin □ Oral or vaginal ‘thrush’ (a fungal infection) □ Inflammation of the stomach and intestines □ Decrease of the levels of blood platelets (blood platelets help stop bleeding) □ Decrease in white blood cells (leukopenia) □ Decrease in neutrophils (neutropenia) □ Stiffness □ Chills □ Increase of eosinophils (white blood cells involved in immunity) □ Exaggerated immune response to a foreign agent □ Lack or loss of appetite □ Anxiety, nervousness □ Drowsiness, tiredness, dizziness or shaking □ Involuntary muscle movements □ Vertigo □ Ringing in the ears or hearing loss □ Chest pain or changes in heart rhythm such as palpitations or an irregular heartbeat □ Asthma: lung disease associated with tightening of air passages, making breathing difficult □ Nosebleed □ Blood clot that causes sudden blockage in a lung artery (pulmonary embolism) □ Inflammation of the lining of the gullet (oesophagus) and lining of the stomach □ Anal pain □ Bloating, constipation, wind, burping □ Dry mouth □ Situation where the bile (fluid made by the liver and stored in the gallbladder) cannot flow from the gallbladder to the duodenum (cholestasis) □ Inflammation of the skin characterized by the presence of the bullae which are filled with fluid, itchy and painful rash □ Muscle spasms, muscle pain or loss of muscle tissue. If your child suffers from myasthenia gravis (a condition in which the muscles become weak and tire easily), clarithromycin may worsen these symptoms. □ Raised abnormal kidney and liver function blood test and raised blood tests □ Feeling weak, tired and having no energy Not known side effects (frequency cannot be estimated from the available data): □ Inflammation of the colon □ Bacterial infection of the outer layers of the skin □ Reduction in the level of certain blood cells (which can make infections more likely or increase the risk of bruising or bleeding) □ Confusion, loss of bearings, hallucinations (seeing things), change in sense of reality or panicking, depression, abnormal dreams or nightmares and mania (feeling of elation or over-excitement) □ Convulsion (fits) □ Paraesthesia, more commonly known as ‘pins and needles’ □ Loss of taste or smell or inability to smell properly □ Type of heart rhythm disorder (Torsade de pointes, ventricular tachycardia) □ Loss of blood (haemorrhage) □ Inflammation of the pancreas □ Discolouration of the tongue or teeth □ Acne □ Change in the levels of products produced by the kidney, inflammation of the kidney or an inability of the kidney to function properly (you may notice tiredness, swelling or puffiness in the face, abdomen, thighs or ankles or problems with urination)
Like all medicines, ERACID can cause side effects although not everybody gets them. If you suffer from any of the following at any time during your treatment STOP TAKING your tablets and contact your doctor immediately: □ Severe or prolonged diarrhoea, which may have blood or mucus in it. Diarrhoea may occur over two months after treatment with clarithromycin, in which case you should still contact your doctor. □ A rash, difficulty breathing, fainting or swelling of the face, tongue, lips, eyes and throat.This is a sign that you may have developed an allergic reaction. □ Yellowing of the skin (jaundice), skin irritation, pale stools, dark urine, tender abdomen or loss of appetite. These are signs that your liver may have inflammation and not be working properly. □ Severe skin reactions such as painful blistering of the skin, mouth, lips, eyes and genitals (symptoms of a rare allergic reaction called Stevens-Johnson syndrome/toxic epidermal necrolysis). □ A red, scaly rash with bumps under the skin and blisters (symptoms of exanthematous pustulosis). The frequency of this side effect is not known (cannot be estimated from the available data). □ Rare allergic skin reactions which cause severe illness with ulceration of the mouth, lips and skin which causes severe illness with rash, fever and inflammation of internal organs (DRESS). □ Muscle pain or weakness known as rhabdomyolysis (a condition which causes the breakdown of muscle tissue which can result in kidney damage). Other side effects Common side effects (may affect up to 1 in 10 people) include; □ Difficulty sleeping □ Changes in sense of taste □ Headache □ Widening of blood vessels □ Stomach problems such as feeling sick, vomiting, stomach pain, indigestion, diarrhoea □ Increased sweating Uncommon side effects (may include up to 1 in 100 people) include: □ High temperature □ Swelling, redness or itchiness of the skin □ Oral or vaginal ‘thrush’ (a fungal infection) □ Inflammation of the stomach and intestines □ Decrease of the levels of blood platelets (blood platelets help stop bleeding) □ Decrease in white blood cells (leukopenia) □ Decrease in neutrophils (neutropenia) □ Stiffness □ Chills □ Increase of eosinophils (white blood cells involved in immunity) □ Exaggerated immune response to a foreign agent □ Lack or loss of appetite □ Anxiety, nervousness □ Drowsiness, tiredness, dizziness or shaking □ Involuntary muscle movements □ Vertigo □ Ringing in the ears or hearing loss □ Chest pain or changes in heart rhythm such as palpitations or an irregular heartbeat □ Asthma: lung disease associated with tightening of air passages, making breathing difficult □ Nosebleed □ Blood clot that causes sudden blockage in a lung artery (pulmonary embolism) □ Inflammation of the lining of the gullet (oesophagus) and lining of the stomach □ Anal pain □ Bloating, constipation, wind, burping □ Dry mouth □ Situation where the bile (fluid made by the liver and stored in the gallbladder) cannot flow from the gallbladder to the duodenum (cholestasis) □ Inflammation of the skin characterized by the presence of the bullae which are filled with fluid, itchy and painful rash □ Muscle spasms, muscle pain or loss of muscle tissue. If your child suffers from myasthenia gravis (a condition in which the muscles become weak and tire easily), clarithromycin may worsen these symptoms. □ Raised abnormal kidney and liver function blood test and raised blood tests □ Feeling weak, tired and having no energy Not known side effects (frequency cannot be estimated from the available data): □ Inflammation of the colon □ Bacterial infection of the outer layers of the skin □ Reduction in the level of certain blood cells (which can make infections more likely or increase the risk of bruising or bleeding) □ Confusion, loss of bearings, hallucinations (seeing things), change in sense of reality or panicking, depression, abnormal dreams or nightmares and mania (feeling of elation or over-excitement) □ Convulsion (fits) □ Paraesthesia, more commonly known as ‘pins and needles’ □ Loss of taste or smell or inability to smell properly □ Type of heart rhythm disorder (Torsade de pointes, ventricular tachycardia) □ Loss of blood (haemorrhage) □ Inflammation of the pancreas □ Discolouration of the tongue or teeth □ Acne □ Change in the levels of products produced by the kidney, inflammation of the kidney or an inability of the kidney to function properly (you may notice tiredness, swelling or puffiness in the face, abdomen, thighs or ankles or problems with urination)
□ Keep out of the reach and sight of children. □ Do not store above 30°C, protected from light. □ Do not use ERACID after the expiry date which is stated on the carton and on the blister, after (EXP).Date. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment
The active substance is Clarithromycin. Each Film Coated Tablet of ERACID 250 and 500 contains Clarithromycin 250 and 500 mg, respectively. □ The other ingredients are: sodium starch glycolate type A, anhydrous calcium hydrogen phosphate, maize starch, hydroxypropyl cellulose, colloidal anhydrous silica, magnesium stearate, purified talc, opadry - OY 8487 yellow, white beeswax
The Jordanian pharmaceutical manufacturing company. P.O. BOX 151, Um Al-Amad 16197, Jordan Saudi Arabia: To report any side effect(s): National Pharmacovigilance Center (NPC): Fax: +966-11-205-7662, SFDA Call center: 19999, E-mail: npc.drug@sfda.gov.sa, Website: https://ade.sfda.gov.sa
The Jordanian pharmaceutical manufacturing co.(P.L.C.|)
نتمي إیراسید إلى مجموعة من الأدویة التي تسمى مضادات الماكرولاید الحیویة والتي تعمل على وقف نمو البكتیریا التي تسبب العدوى . تستخدم أقراص إیراسید لعلاج الالتھابات التي تسببھا البكتیریا، والتي تشمل الاستخدامات التالیة: □ عدوى صدریة مثل التھاب الشعب الھوائیة والالتھاب الرئوي. □ التھابات الحلق والجیوب الأنفیة. □ التھابات الجلد و الأنسجة الرخوة. □ العدوى الناجمة عن الملویة البوابیة المرتبطة بقرحة الاثني عشر. تستخدم أقراص إیراسید للبالغین والأطفال بعمر ۱۲ ًعاما فما فوق.
□ إذا كنت تعاني من حساسیة لكلاریثرومایسین أو مضادات الماكرولاید الحیویة الأخرى مثل الإیریثرومایسین أو الأزیثرومایسین أو لأي من المكونات الأخرى الموجودة في الأقراص . □ إذا كنت تتناول أدویة تسمى ارغوت الألكالوید (مثل الإرغوتامین أو ثنائي ھیدروإرغوتامین) أو تستخدم جھاز استنشاق الإرغوتامین لمعالجة الصداع النصفي. □ إذا كنت تتناول أدویة تسمى تیرفینادین أو أستیمیزول (یتم تناولھا على نطاق واسع لحمى الكلأ أو الحساسیة) أو سیسابراید أو دومبیریدون (لاضطرابات المعدة) أو بیموزید (لمشاكل الصحة العقلیة) لأن الجمع بین استخدام ھذه الأدویة قد یسبب ًا اضطرابات خطیرة في نظم القلب. استشر أحیان طبیبك للحصول على المشورة بشأن الأدویة البدیلة. □ إذا كنت تتناول أدویة أخرى من المعروف أنھا تسبب اضطرابات خطیرة في نظم القلب. □ إذا كنت تتناول لوفاستاتین أو سیمفاستاتین (مثبطات اختزال CoA-HMG ،المعروفة باسم الستاتین، التي تستخدم لخفض مستویات الكولیسترول (نوع من الدھون) في الدم). □ إذا كنت تتناول میدازولام عن طریق الفم (مھدئ). □ إذا كنت تتناول دواء یحتوي على لومیتابید □ إذا كان لدیك مستویات منخفضة بشكل غیر طبیعي من البوتاسیوم أو المغنیزیوم في الدم (نقص بوتاسیوم الدم أو نقص مغنیزیوم الدم). □ لدیك مرض كبدي شدید مصحوب بمرض كلوي. □ أو أن أحد أفراد عائلتك لدیھ تاریخ من اضطرابات نظم القلب (عدم انتظام ضربات القلب البطیني، بما في ذلك تورساد دي بوانت) أو شذوذ في مخطط كھربیة القلب (ECG ،التخطیط الكھربائي للقلب) یسمى "متلازمة الزیادة في طول فترة QT." □ إذا كنت تتناول أدویة تسمى تیكاجریلور أو رانولازین (للنوبات القلبیة، ألم الصدر أوالذبحة الصدریة). كنت تتناول دواء كولشیسین (عادة ما یتم تناولھ لعلاج النقرس). الاحتیاطات عند استعمال إیراسید: تحدث إلى طبیبك أو الصیدلاني أو الممرض قبل تناول أقراص إیراسید: □ إذا كنت تعاني من مشاكل في القلب (مثل أمراض القلب ، قصور القلب، بطء معدل ضربات القلب بشكل غیر عادي). □ إذا كنت تعاني من مشاكل في الكبد أو الكلى □ إذا كان لدیك، أو كنت عرضة للإصابة بعدوى فطریة (مثل مرض القلاع). ً أو مرضعة. □ إذا كنت حاملا الأطفال أقراص إیراسید غیر مناسبة للاستخدام في الأطفال دون سن ۱۲ سنة من العمر. تناول إیراسید مع الأدویة الأخرى: ًا یجب ألا تتناول أقراص إیراسید إذا كنت تتناول أی من الأدویة المذكورة في القسم أعلاه "لا تتناول أقراص إیراسید إذا كنت ؛" أخبر طبیبك أو الصیدلي إذا كنت تتناول أو تناولت ً مؤخرا أو قد تتناول أي أدویة أخرى لأن جرعتك قد تحتاج إلى تغییر أو قد تحتاج إلى إجراء اختبارات منتظمة: □ دیجوكسین، كینیدین أو دیسوبیرامید (لمشاكل في القلب). □ إبروتینیب (لعلاج السرطان). □ الوارفارین، أو أي مضادات أخرى للتخثر مثل: دابیغاتران، ریفاروكسابان، أبیكسابان (لتسییل الدم). □ كاربامازیبین، فالبروات، فینوباربیتال أو فینیتوین (لعلاج الصرع). □ أتورفاستاتین ، روسوفاستاتین (مثبطات اختزال CoA-HMG ،المعروفة باسم الستاتین، وتستخدم لخفض مستویات الكولیسترول (نوع من الدھون) في الدم). یمكن أن تسبب الستاتینات انحلال الربیدات (وھي حالة تسبب انھیار الأنسجة العضلیة التي یمكن أن تؤدي إلى تلف الكلى) ویجب مراقبة علامات الاعتلال العضلي (ألم العضلات أو ضعف العضلات). □ ناتیجلینید، بیوجلیتازون، ریباجلینید، روزیجلیتازون أو أنسولین (یستخدم لخفض مستویات السكر في الدم) □ غلیكلازید أو غلیمیبیرید (سلفونیل یوریا المستخدم في علاج داء السكري من النوع الثاني) □ ثیوفیلین (یستخدم في المرضى الذین یعانون من صعوبات في التنفس مثل الربو). □ تریازولام، ألبرازولام أو میدازولام في الورید أو الفم المخاطي (مھدئات) □ سیلوستازول (لضعف الدورة الدمویة). □ المیثادون (المستخدم في علاج إدمان المواد الأفیونیة). □ میثیل بریدنیزولون (كورتیكوستیروید) □ فینبلاستین (لعلاج السرطان). □ سیكلوسبورین، سیرولیموس وتاكرولیموس (مثبطات المناعة) □ إیترافیرین، إیفافیرینز، نیفیرابین، ریتونافیر، زیدوفودین ، أتازانافیر، ساكوینافیر(الأدویة المضادة للفیروسات المستخدمة في علاج فیروس نقص المناعة البشریة) □ ریفابوتین، ریفامبیسین، ریفابنتین، فلوكونازول، إیتراكونازول (یستخدم في علاج بعض أنواع العدوى البكتیریة). □ تولتیرودین (لعلاج فرط نشاط المثانة)
□ فیرابامیل، أملودیبین، دیلتیازیم (لارتفاع ضغط الدم). □ سیلدینافیل، فاردینافیل وتادالافیل (للعجز الجنسي عند الذكور البالغین أو للإستعمال في إرتفاع ضغط الدم الشریاني الرئوي (إرتفاع ضغط الدم في الأوعیة الدمویة في الرئة)) □ نبتة سانت جون (منتج عشبي یستخدم لعلاج الاكتئاب) □ كیتیابین أو أدویة أخرى مضادة للذھان. □ أدویة الماكرولید الأخرى □ لینكومایسین وكلیندامایسین (لینكوزامیدات - نوع من المضادات الحیویة) یرجى إخبار طبیبك إذا كنت تتناول حبوب منع الحمل ویحدث الإسھال أو القيء ، حیث قد تحتاج إلى اتخاذ احتیاطات إضافیة لمنع الحمل مثل استخدام الواقي الذكري. الحمل والرضاعة: ً أو مرضعة ، أو تعتقدین أنك حامل أو إذا كنت حاملا تخططین لإنجاب طفل ، استشیري طبیبك أو الصیدلي قبل تناول ھذا الدواء لأن مأمونیة أقراص إیراسید غیر معروفة أثناء الحمل والرضاعة. تأثیر المستحضر على القیادة واستخدام الآلات: قد تجعلك أقراص إیراسید تشعر بالدوار أو النعاس. إذا أثروا علیك بھذه الطریقة فلا تقود السیارة أو تشغل الآلات أو تفعل أي شيء یتطلب منك أن تكون ً متیقظا. ۳ .طریقة
لا تعط ھذه الأقراص للأطفال دون سن ۱۲ ً عاما. ًا لطفلك. ً سیصف طبیبك دواء آخر مناسب تناول أقراص إیراسید ً دائم ً ا تماما كما أخبرك طبیبك. ً استشر طبیبك أو الصیدلي إذا لم تكن متأكدا. الجرعة الموصى بھا ھي؛ لالتھابات الصدر والحنجرة والجیوب الأنفیة والتھابات الجلد والأنسجة الرخوة: الجرعة المعتادة من أقراص إیراسید للبالغین ًا والأطفال فوق ۱۲ ً عاما ھي ۲٥۰ ملغم مرتین یومی لمدة ٦ إلى ۱٤ ً یوما ، على سبیل المثال قرص واحد ۲٥۰ ملغم في الصباح والآخر في بدایة المساء. قد یقوم طبیبك بزیادة الجرعة إلى ٥۰۰ ملغم مرتین ًا في حالات العدوى الشدیدة. یومی یجب ابتلاع أقراص إیراسید مع نصف كوب من الماء على الأقل. لعلاج عدوى الملویة البوابیة المصاحبة لقرحة الاثني عشر: ھناك عدد من تركیبات العلاج الفعالة المتاحة لعلاج ھیلیكوباكتر بیلوري حیث یتم تناول أقراص إیراسید مع دواء أو دواءین آخرین. تشمل ھذه المجموعات ما یلي وعادة ما یتم تناولھا لمدة ٦ إلى ۱٤ ً یوما: أ) قرص واحد من إیراسید ٥۰۰ ملغم مرتین في الیوم مع أموكسیسیلین ۱۰۰۰ ملغم مرتین في الیوم بالإضافة إلى لانسوبرازول ۳۰ ملغم مرتین في الیوم. ب) قرص واحد من إیراسید ٥۰۰ ملغم مرتین في الیوم مع میترونیدازول ٤۰۰ ملغم مرتین في الیوم بالإضافة إلى لانسوبرازول ۳۰ ملغم مرتین في الیوم. ج) قرص واحد من إیراسید ٥۰۰ ملغم مرتین في الیوم مع أموكسیسیلین ۱۰۰۰ ملغم مرتین في الیوم أو میترونیدازول ٤۰۰ ملغم مرتین في الیوم بالإضافة إلى أومیبرازول ٤۰ ملغم في الیوم. د) قرص واحد من إیراسید ٥۰۰ ملغم مرتین في الیوم مع أموكسیسیلین ۱۰۰۰ ملغم مرتین في الیوم بالإضافة إلى أومیبرازول ۲۰ ملغم مرة واحدة في الیوم. ً عما سبق. قد تختلف تركیبة العلاج التي تتلقاھا قلیلا سیقرر طبیبك تركیبة العلاج الأنسب لك. إذا لم تكن ً متأكدا من الأقراص التي یجب أن تتناولھا أو كم من الوقت یجب أن تتناولھا ، فیرجى استشارة طبیبك للحصول على المشورة. ً كما أخبرك طبیبك. یجب ً تناول إیراسید تماما دائما علیك مراجعة طبیبك أو الصیدلي إذا كنت غیر متأكد. الجرعة الزائدة من إیراسید: إذا تناولت أقراص إیراسید أكثر من التي وصفھا لك الطبیب في الیوم الواحد عن طریق الخطأ أو إذا تناول طفلك بعض الأقراص عن طریق الخطأ فإنھ یجب علیك الاتصال بالطبیب أو أقرب قسم طوارئ ً. من المحتمل أن تتسبب الجرعة الزائدة من مباشرة إیراسید بتقیؤ وآلام في المعدة . نسیان تناول جرعة إیراسید: إذا نسیت تناول أقراص الدواء الخاصة بك ، فإنھ یجب علیك تناولھا في أقرب وقت ممكن من تذكرھا. لا تتناول أقراص أكثر من التي وصفھا لك الطبیب في الیوم الواحد. التوقف عن تناول إیراسید: لا تتوقف عن تناول أقراص الدواء الخاصة بك حتى لو شعرت بتحسن. من المھم تناول الأقراص للمدة التي حددھا لك الطبیب، و إلا فإن المشكلة من الممكن أن تعود مرة أخرى .
مثل جمیع الأدویة، یمكن أن یسبب إیراسید ً آثارا جانبیة على الرغم من عدم حدوثھا لدى الجمیع. إذا كنت تعاني من أي مما یلي في أي وقت أثناء العلاج توقف عن تناول الأقراص الخاصة بك واتصل بطبیبك على الفور: □ إسھال شدید أو طویل الأمد قد یحتوي على دم أو مخاط. قد یحدث الإسھال على مدى شھرین بعد العلاج بكلاریثرومیسین، وفي ھذه الحالة لا یزال یتعین علیك الاتصال بطبیبك. □ طفح جلدي، صعوبة في التنفس، إغماء أو إنتفاخ في الوجھ، اللسان، الشفتین، العینین والحلق، ھذه علامة على احتمال إصابتك برد فعل تحسسي. □ اصفرار الجلد (الیرقان)، تھیج الجلد، شحوب البراز، البول الداكن، رقة البطن أو فقدان الشھیة. ھذه ًا بالتھاب ولا علامات على أن الكبد قد یكون مصاب یعمل بشكل صحیح. تفاعلات جلدیة شدیدة مثل تقرحات مؤلمة في الجلد ، الفم، الشفتین، العینین والأعضاء التناسلیة (أعراض رد فعل تحسسي نادر یسمى متلازمة ستیفنز جونسون / انحلال البشرة النخري السام). □ طفح جلدي أحمر متقشر مع نتوءات تحت الجلد وبثور (أعراض بثور طفیلي). تواتر ھذا التأثیر الجانبي غیر معروف (لا یمكن تقدیره من البیانات المتاحة). □ ردود فعل جلدیة تحسسیة نادرة تسبب مرضا وخیما مع تقرح في الفم والشفتین والجلد مما یؤدي إلى مرض شدید مصحوب بطفح جلدي وحمى والتھاب في الأعضاء الداخلیة (DRESS.( □ آلام أو ضعف في العضلات یعرف باسم انحلال الربیدات (حالة تؤدي إلى انھیار الأنسجة العضلیة التي یمكن أن تؤدي إلى تلف الكلى). أعراض جانبیة أخرى تشمل الآثار الجانبیة الشائعة (قد تؤثر على ما یصل إلى شخص واحد من كل ۱۰ أشخاص)؛ □ صعوبة النوم □ تغیرات في حاسة التذوق □ صداع □ اتساع الأوعیة الدمویة □ مشاكل في المعدة مثل الشعور بالغثیان، قيء، آلام في المعدة، عسر ھضم، إسھال □ زیادة التعرق تشمل الآثار الجانبیة غیر الشائعة (قد تشمل على ما یصل إلى شخص واحد من كل ۱۰۰ شخص) ما یلي: □ ارتفاع في درجة الحرارة □ انتفاخ، احمرارأو حكة في الجلد □ مرض القلاع الفموي أو المھبلي (عدوى فطریة). □ إلتھاب المعدة والأمعاء □ انخفاض في نسبة الصفیحات الدمویة (الصفائح الدمویة تساعد في وقف النزیف). □ نقص في خلایا الدم البیضاء (قلة الكریات البیض).
□ انخفاض في العدلات (قلة العدلات) □ تصلب □ قشعریرة □ زیادة الحمضات (خلایا الدم البیضاء التي تدخل في المناعة). □ استجابة مناعیة مبالغ فیھا لعامل خارجي □ قلة الشھیة أو فقدانھا □ قلق، عصبیة □ نعاس، إرھاق، دوار أو إرتجاف □ حركات عضلیة لا إرادیة □ دوار □ رنین في الأذنین أو فقدان السمع □ ألم في الصدر أو تغیرات في نظم القلب مثل خفقان القلب أو عدم انتظام ضربات القلب □ الربو: مرض رئوي یترافق مع ضیق في الممرات ً الھوائیة، مما یجعل التنفس صعبا □ نزیف في الأنف □ جلطة دمویة تسبب انسداد مفاجئ في الشریان الرئوي (انسداد رئوي). □ التھاب بطانة المريء (المريء) وبطانة المعدة □ ألم في الشرج □ انتفاخ، إمساك، ریاح، تجشؤ □ جفاف الفم □ حالة حیث لا یمكن أن تتدفق العصارة الصفراویة (السائل الذي ینتجھ الكبد ویخزن في المرارة) من المرارة إلى الاثني عشر (ركود صفراوي) □ التھاب في الجلد یتمیز بوجود فقاعات ملیئة بالسوائل وطفح جلدي مؤلم ومثیر للحكة □ تشنجات عضلیة، آلام عضلیة أو فقدان أنسجة عضلیة. إذا كان طفلك یعاني من الوھن العضلي الوبیل (حالة تصبح فیھا العضلات ضعیفة وتتعب بسھولة)، قد یؤدي الكلاریثرومیسین إلى تفاقم ھذه الأعراض. □ إرتفاع غیر طبیعي في إختبارات الدم في وظائف الكلى والكبد وإرتفاع إختبارات الدم □ الشعور بالضعف، التعب وانعدام الطاقة أعراض جانبیة غیر معروفة (لا یمكن تقدیر تكرار حدوثھا من البیانات المتاحة): □ التھاب القولون □ عدوى بكتیریة تصیب طبقات الجلد الخارجیة □ انخفاض في مستوى بعض خلایا الدم (مما قد یزید من احتمالیة حدوث الالتھابات أو یزید من خطر حدوث كدمات أو نزیف) □ ارتباك، فقدان القدرة على التحمل، ھلوسة (رؤیة الأشیاء)، تغیر في الإحساس بالواقع أو الذعر، اكتئاب، أحلام غیر طبیعیة أو كوابیس وھوس (شعور بالبھجة أو الإثارة المفرطة) □ تشنج (نوبات) □ مذل، المعروف أكثر باسم "دبابیس وإبر" □ فقدان حاسة التذوق أو الشم أو عدم القدرة على الشم بشكل صحیح □ نوع من اضطراب ضربات القلب (تورساد دي بوانت، تسرع القلب البطیني) □ فقدان الدم (نزیف) □ التھاب البنكریاس □ تغیر لون اللسان أو الأسنان □ حب الشباب □ تغیر في مستویات المنتجات التي تفرزھا الكلى، التھاب الكلى أو عدم قدرة الكلى على العمل بشكل صحیح (قد تلاحظ إرھاق، انتفاخ أو انتفاخ في الوجھ، البطن، الفخذین أو الكاحلین أو مشاكل في التبول)
□ یحفظ بعیدا □ لا یحفظ بدرجة حرارة أعلى من ۳۰°م، یحفظ ً عن الضوء. بعیدا □ لا ینبغي استعمال إیراسید بعد تاریخ انتھاء الصلاحیة الموجود على العلبة وعلى شریط الدواء . لا ینبغي التخلص من الأدویة من خلال میاه الصرف الصحي أو المنزلي. اسأل الصیدلاني عن كیفیة التخلص من الأدویة التي لم تعد مطلوبة. سوف تساعد ھذه الاجراءات على حمایة البیئة .
□ المادة الفعالة ھي كلاریثرومایسین. كل قرص مغلف من إیراسید ۲٥۰ و ٥۰۰ یحتوي على ۲٥۰ و ٥۰۰ ملغم من كلاریثرومایسین على التوالي . □ المكونات الأخرى ھي: جلایكولات نشا الصودیوم نوع أ، فوسفات الكالسیوم اللامائیة الھیدروجینیة، نشا الذرة، ھیدروكسي بروبیل سیلیلوز، سیلیكا غرویة لامائیة ، ستیارات المغنیزیوم، تالك منقى، أوبادراي ۸٤۸۷ – OY الأصفر، شمع العسل الأبیض
□ أقراص إیراسید ۲٥۰ ھي أقراص مغلفة صفراء اللون، دائریة، مسطحة، ثنائیة التحدب منقوش علیھا ’ 250 ERACID ‘ من جانب واحد و الجانب الأخر جلي (غیر منقوش). □ أقراص إیراسید ٥۰۰ ھي أقراص مغلفة صفراء اللون، مستطیلة، محززة، ثنائیة التحدب منقوش علیھا ’ 500 ER ‘ من جانب واحد. □ علب تحتوي على ۱٤ قرص من أقراص إیراسید ۲٥۰ المحفوظة في أشرطة. □ علب تحتوي على ۱٤ قرص من أقراص إیراسید ٥۰۰ المحفوظة في أشرطة.
الشركة الأردنیة لإنتاج الأدویة. ص.ب. ۱٥۱- أم العمد ۱٦۱۹۷- الأردن. المملكة العربیة السعودیة: للإبلاغ عن الأعراض الجانبیة: المركزالوطني للتیقظ: فاكس: ۰۰۹٦٦۱۱۲۰٥۷٦٦۲، مركز اتصال الھیئة العامة للغذاء والدواء ،۱۹۹۹۹:(SFDA) ،npc.drug@sfda.gov.sa :الإلكتروني البرید https://ade.sfda.gov.sa :الإلكتروني ا
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Eracid 500 mg Tablets are indicated in adults and children 12 years and older. Clarithromycin is indicated for treatment of infections caused by susceptible organisms.
Indications include:
Lower respiratory tract infections for example, acute and chronic bronchitis, and pneumonia (see section 4.4 and 5.1 regarding Sensitivity Testing).
Upper respiratory tract infections for example, sinusitis and pharyngitis. Clarithromycin is appropriate for initial therapy in community acquired respiratory infections and has been shown to be active in vitro against common and atypical respiratory pathogens as listed in the microbiology section.
Clarithromycin is also indicated in skin and soft tissue infections of mild to moderate severity (e.g. folliculitis, cellulitis, erysipelas).
Clarithromycin in the presence of acid suppression effected by omeprazole or lansoprazole is also indicated for the eradication of H. pylori in patients with duodenal ulcers. See Dosage and Administration section.
Clarithromycin is usually active against the following organisms in vitro:
Gram-positive Bacteria: Staphylococcus aureus (methicillin susceptible); Streptococcus pyogenes (Group A beta-haemolytic streptococci); alphahaemolytic streptococci (viridans group); Streptococcus (Diplococcus) pneumoniae; Streptococcus agalactiae; Listeria monocytogenes.
Gram-negative Bacteria: Haemophilus influenzae; Haemophilus parainfluenzae; Moraxella (Branhamella) catarrhalis; Neisseria gonorrhoeae; Legionella pneumophila; Bordetella pertussis; Helicobacter pylori; Campylobacter jejuni. Mycoplasma:
Mycoplasma pneumoniae; Ureaplasma urealyticum.
Other Organisms: Chlamydia trachomatis; Mycobacterium avium; Mycobacterium leprae.
Anaerobes: Macrolide-susceptible Bacteroides fragilis; Clostridium perfringens; Peptococcus species; Peptostreptococcus species; Propionibacterium acnes.
Clarithromycin has bactericidal activity against several bacterial strains. The organisms include Haemophilus influenzae; Streptococcus pneumoniae; Streptococcus pyogenes; Streptococcus agalactiae; Moraxella (Branhamella) catarrhalis; Neisseria gonorrhoeae; H. pylori and Campylobacter spp.
The activity of clarithromycin against H. pylori is greater at neutral pH than at acid pH.
Patients with respiratory tract/skin and soft tissue infections.
Adults: The usual dose is 250 mg twice daily although this may be increased to 500mg twice daily in severe infections. The usual duration of treatment is 6 to 14 days.
Children older than 12 years: As for adults.
Children younger than 12 years:
Use of Eracid 500mg Tablets are not recommended for children younger than 12 years.
Clarithromycin may be given without regard to meals as food does not affect the extent of bioavailability.
Eradication of H. pylori in patients with duodenal ulcers (Adults)
The usual duration of treatment is 6 to 14 days.
Triple Therapy
Clarithromycin (500mg) twice daily and lansoprazole 30mg twice daily should be given with amoxycillin 1000mg twice daily.
Triple Therapy
Clarithromycin (500mg) twice daily and lansoprazole 30mg twice daily should be given with metronidazole 400mg twice daily.
Triple Therapy
Clarithromycin (500mg) twice daily and omeprazole 40mg daily should be given with amoxycillin 1000mg twice daily or metronidazole 400mg twice daily.
Triple Therapy
Clarithromycin (500mg) twice daily and omeprazole 20mg daily should be given with amoxycillin 1000mg twice daily.
Elderly: As for adults.
Renal impairment:
In patients with renal impairment with creatinine clearance less than 30 mL/min, the dosage of clarithromycin should be reduced by one-half, i.e. 250 mg once daily, or 250 mg twice daily in more severe infections. Treatment should not be continued beyond 14 days in these patients
Use of any antimicrobial therapy, such as clarithromycin, to treat H. pylori infection may select for drug-resistant organisms. The physician should not prescribe clarithromycin to pregnant women without carefully weighing the benefits against risk, particularly during the first three months of pregnancy.
Clarithromycin is principally metabolised by the liver. Therefore, caution should be exercised in administering this antibiotic to patients with impaired hepatic function. Caution should also be exercised when administering clarithromycin to patients with moderate to severe renal impairment.
Hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been reported with clarithromycin.
This hepatic dysfunction may be severe and is usually reversible. Cases of fatal hepatic failure have been reported. Some patients may have had preexisting hepatic disease or may have been taking other hepatotoxic medicinal products. Patients should be advised to stop treatment and contact their doctor if signs and symptoms of hepatic disease develop, such as anorexia, jaundice, dark urine, pruritus, or tender abdomen. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including macrolides, and may range in severity from mild to life-threatening.
Clostridioides difficile- associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents including clarithromycin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, which may lead to overgrowth of C. difficile. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. Therefore, discontinuation of clarithromycin therapy should be considered regardless of the indication. Microbial testing should be performed and adequate treatment initiated. Drugs inhibiting peristalsis should be avoided. There have been post-marketing reports of colchicine toxicity with concomitant use of clarithromycin and colchicine, especially in the elderly, some of which occurred in patients with renal insufficiency. Deaths have been reported in some such patients. Concomitant administration of clarithromycin and colchicine is contraindicated.
Caution is advised regarding concomitant administration of clarithromycin and triazolobenzodiazepines, such as triazolam, and intravenous or oromucosal midazolam.
Cardiovascular Events: Prolongation of the QT interval, reflecting effects on cardiac repolarisation imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in patients treated with macrolides including clarithromycin. Due to increased risk of QT prolongation and ventricular arrhythmias (including torsades de pointes), the use of clarithromycin is contraindicated in patients taking any of astemizole, cisapride, domperidone, pimozide and terfenadine; in patients who have electrolyte disturbances such as hypomagnesaemia or hypokalaemia; and in patients with a history of QT prolongation or ventricular cardiac arrhythmia. Furthermore, clarithromycin should be used with caution in the following:
• Patients with coronary artery disease, severe cardiac insufficiency, conduction disturbances or clinically relevant bradycardia;
• Patients concomitantly taking other medicinal products associated with QT prolongation other than those which are contraindicated
Epidemiological studies investigating the risk of adverse cardiovascular outcomes with macrolides have shown variable results.
Some observational studies have identified a rare short-term risk of arrhythmia, myocardial infarction and cardiovascular mortality associated with macrolides including clarithromycin. Consideration of these findings should be balanced with treatment benefits when prescribing clarithromycin.
Pneumonia: In view of the emerging resistance of Streptococcus pneumoniae to macrolides, it is important that sensitivity testing be performed when prescribing clarithromycin for community-acquired pneumonia. In hospital-acquired pneumonia, clarithromycin should be used in combination with additional appropriate antibiotics.
Skin and soft tissue infections of mild to moderate severity: These infections are most often caused by Staphylococcus aureus and Streptococcus pyogenes, both of which may be resistant to macrolides. Therefore, it is important that sensitivity testing be performed.
In cases where beta–lactam antibiotics cannot be used (e.g. allergy), other antibiotics, such as clindamycin, may be the drug of first choice. Currently, macrolides are only considered to play a role in some skin and soft tissue infections, such as those caused by Corynebacterium minutissimum, acne vulgaris, and erysipelas and in situations where penicillin treatment cannot be used.
In the event of severe acute hypersensitivity reactions, such as anaphylaxis, severe cutaneous adverse reactions (SCAR) (e.g. Acute generalised exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome, toxic epidermal necrolysis and drug rash with eosinophilia and systemic symptoms (DRESS)), clarithromycin therapy should be discontinued immediately and appropriate treatment should be urgently initiated. Clarithromycin should be used with caution when administered concurrently with medications that induce the cytochrome CYP3A4 enzyme.
HMG-CoA Reductase Inhibitors (statins): Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated.
Caution should be exercised when prescribing clarithromycin with other statins. Rhabdomyolysis has been reported in patients taking clarithromycin and statins. Patients should be monitored for signs and symptoms of myopathy.
In situations where the concomitant use of clarithromycin with statins cannot be avoided, it is recommended to prescribe the lowest registered dose of the statin. Use of a statin that is not dependent on CYP3A metabolism (e.g. fluvastatin) can be considered.
Oral hypoglycaemic agents/Insulin: The concomitant use of clarithromycin and oral hypoglycaemic agents (such as sulphonylauriad) and/or insulin can result in significant hypoglycaemia. Careful monitoring of glucose is recommended.
Oral anticoagulants: There is a risk of serious haemorrhage and significant elevations in International Normalized Ratio (INR) and prothrombin time when clarithromycin is co-administered with warfarin. INR and prothrombin times should be frequently monitored while patients are receiving clarithromycin and oral anticoagulants concurrently.
Caution should be exercised when clarithromycin is co-administered with direct acting oral anticoagulants such as dabigatran, rivaroxaban and apixaban, particularly to patients at high risk of bleeding.
Long-term use may, as with other antibiotics, result in colonisation with increased numbers of non-susceptible bacteria and fungi. If superinfections occur, appropriate therapy should be instituted. Attention should also be paid to the possibility of cross resistance between clarithromycin and other macrolide drugs, as well as lincomycin and clindamycin
Astemizole, cisapride, domperidone, pimozide, and terfenadine:
Elevated cisapride levels have been reported in patients receiving clarithromycin and cisapride concomitantly. This may result in QT prolongation and cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation and torsades de pointes. Similar effects have been observed in patients taking clarithromycin and pimozide concomitantly.
Macrolides have been reported to alter the metabolism of terfenadine resulting in increased levels of terfenadine which has occasionally been associated with cardiac arrhythmias, such as QT prolongation, ventricular tachycardia, ventricular fibrillation and torsades de pointes.
In one study in 14 healthy volunteers, the concomitant administration of clarithromycin and terfenadine resulted in 2- to 3-fold increase in the serum level of the acid metabolite of terfenadine and in prolongation of the QT interval which did not lead to any clinically detectable effect. Similar effects have been observed with concomitant administration of astemizole and other macrolides.
Ergot alkaloids:
Post-marketing reports indicate that co-administration of clarithromycin with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm, and ischaemia of the extremities and other tissues including the central nervous system. Concomitant administration of clarithromycin and ergot alkaloids is contraindicated.
Oral Midazolam
When midazolam was co-administered with clarithromycin tablets (500 mg twice daily), midazolam AUC was increased 7-fold after oral administration of midazolam. Concomitant administration of oral midazolam and clarithromycin is contraindicated.
HMG-CoA Reductase Inhibitors (statins)
Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated as these statins are extensively metabolized by CYP3A4 and concomitant treatment with clarithromycin increases their plasma concentration, which increases the risk of myopathy, including rhabdomyolysis.
Reports of rhabdomyolysis have been received for patients taking clarithromycin concomitantly with these statins. If treatment with clarithromycin cannot be avoided, therapy with lovastatin or simvastatin must be suspended during the course of treatment.
Caution should be exercised when prescribing clarithromycin with statins. In situations where the concomitant use of clarithromycin with statins cannot be avoided, it is recommended to prescribe the lowest registered dose of the statin. Use of a statin that is not dependent on CYP3A metabolism (e.g. fluvastatin) can be considered. Patients should be monitored for signs and symptoms of myopathy.
Effects of Other Medicinal Products on Clarithromycin
Drugs that are inducers of CYP3A (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, St John’s wort) may induce the metabolism of clarithromycin. This may result in sub-therapeutic levels of clarithromycin leading to reduced efficacy.
Furthermore, it might be necessary to monitor the plasma levels of the CYP3A inducer, which could be increased owing to the inhibition of CYP3A by clarithromycin (see also the relevant product information for the CYP3A4 inducer administered).
Concomitant administration of rifabutin and clarithromycin resulted in an increase in rifabutin, and decrease in clarithromycin serum levels together with an increased risk of uveitis.
The following drugs are known or suspected to affect circulating concentrations of clarithromycin; clarithromycin dosage adjustment or consideration of alternative treatments may be required.
Efavirenz, nevirapine, rifampicin, rifabutin and rifapentine Strong inducers of the cytochrome P450 metabolism system such as efavirenz, nevirapine, rifampicin, rifabutin, and rifapentine may accelerate the metabolism of clarithromycin and thus lower the plasma levels of clarithromycin, while increasing those of 14-OH-clarithromycin, a metabolite that is also microbiologically active.
Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers.
Etravirine
Clarithromycin exposure was decreased by etravirine; however, concentrations of the active metabolite, 14-OH-clarithromycin, were increased. Because 14-OHclarithromycin has reduced activity against Mycobacterium avium complex (MAC), overall activity against this pathogen may be altered; therefore alternatives to clarithromycin should be considered for the treatment of MAC.
Fluconazole
Concomitant administration of fluconazole 200 mg daily and clarithromycin 500 mg twice daily to 21 healthy volunteers led to increases in the mean steady-state minimum clarithromycin concentration (Cmin) and area under the curve (AUC) of 33% and 18% respectively.
Steady state concentrations of the active metabolite 14- OH-clarithromycin were not significantly affected by concomitant administration of fluconazole. No clarithromycin dose adjustment is necessary.
Ritonavir
Ritonavir A pharmacokinetic study demonstrated that the concomitant administration of ritonavir 200 mg every eight hours and clarithromycin 500 mg every 12 hours resulted in a marked inhibition of the metabolism of clarithromycin. The clarithromycin Cmax increased by 31%, Cmin increased 182% and AUC increased by 77% with concomitant administration of ritonavir. An essentially complete inhibition of the formation of 14-OH-clarithromycin was noted. Because of the large therapeutic window for clarithromycin, no dosage reduction should be necessary in patients with normal renal function. However, for patients with renal impairment, the following dosage adjustments should be considered: For patients with CLCR 30 to 60 mL/min the dose of clarithromycin should be reduced by 50%. For patients with CLCR<30 mL/min the dose of clarithromycin should be decreased by 75%. Doses of clarithromycin greater than 1 g/day should not be co-administered with ritonavir. Similar dose adjustments should be considered in patients with reduced renal function when ritonavir is used as a pharmacokinetic enhancer with other HIV protease inhibitors including atazanavir and saquinavir (see section below, Bi-directional drug interactions).
Effect of Clarithromycin on Other Medicinal Products
CYP3A-based interactions Co-administration of clarithromycin, which is known to inhibit CYP3A, and a drug primarily metabolised by CYP3A may be associated with elevations in drug concentrations that could increase or prolong both therapeutic and adverse effects of the concomitant drug.
The use of clarithromycin is contraindicated in patients receiving the CYP3A substrates astemizole, cisapride, domperidone, pimozide and terfenadine due to the risk of QT prolongation and cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, and torsades de pointes.
The use of clarithromycin is also contraindicated with ergot alkaloids, oral midazolam, HMG CoA reductase inhibitors metabolised mainly by CYP3A4 (e.g. lovastatin and simvastatin), colchicine, ticagrelor and ranolazine.
Concomitant administration of clarithromycin with lomitapide is contraindicated due to the potential for markedly increased transaminases.
Caution is required if clarithromycin is co-administered with other drugs known to be CYP3A enzyme substrates, especially if the CYP3A substrate has a narrow safety margin (e.g. carbamazepine) and/or the substrate is extensively metabolised by this enzyme. Dosage adjustments may be considered, and when possible, serum concentrations of drugs primarily metabolised by CYP3A should be monitored closely in patients concurrently receiving clarithromycin.
Drugs or drug classes that are known or suspected to be metabolised by the same CYP3A isozyme include (but this list is not comprehensive) alprazolam, carbamazepine, cilostazole, ciclosporin, disopyramide, ibrutinib, methadone, methylprednisolone, midazolam (intravenous), omeprazole, oral anticoagulants (e.g. warfarin, rivaroxaban, apixaban), atypical antipsychotics (e.g. quetiapine), quinidine, rifabutin, sildenafil, sirolimus, tacrolimus, triazolam and vinblastine. Drugs interacting by similar mechanisms through other isozymes within the cytochrome P450 system include phenytoin, theophylline and valproate. Antiarrhythmics There have been post-marketing reports of torsades de pointes occurring with the concurrent use of clarithromycin and quinidine or disopyramide. Electrocardiograms should be monitored for QT prolongation during co-administration of clarithromycin with these drugs.
Serum levels of quinidine and disopyramide should be monitored during clarithromycin therapy. There have been post marketing reports of hypoglycemia with the concomitant administration of clarithromycin and disopyramide.
Therefore blood glucose levels should be monitored during concomitant administration of clarithromycin and disopyramide.
Oral hypoglycemic agents/Insulin
With certain hypoglycemic drugs such as nateglinide, and repaglinide, inhibition of CYP3A enzyme by clarithromycin may be involved and could cause hypoglycaemia when used concomitantly. Careful monitoring of glucose is recommended.
Omeprazole
Clarithromycin (500 mg every 8 hours) was given in combination with omeprazole (40 mg daily) to healthy adult subjects. The steady-state plasma concentrations of omeprazole were increased (Cmax, AUC0-24, and t1/2 increased by 30%, 89%, and 34%, respectively), by the concomitant administration of clarithromycin. The mean 24-hour gastric pH value was 5.2 when omeprazole was administered alone and 5.7 when omeprazole was co-administered with clarithromycin.
Direct acting oral anticoagulants (DOACs)
The DOAC dabigatran is a substrate for the efflux transporter P-gp. Rivaroxaban and apixaban are metabolised via CYP3A4 and are also substrates for P-gp. Caution should be exercised when clarithromycin is co-administered with these agents particularly to patients at high risk of bleeding.
Sildenafil, tadalafil and vardenafil
Each of these phosphodiesterase inhibitors is metabolised, at least in part, by CYP3A, and CYP3A may be inhibited by concomitantly administered clarithromycin. Coadministration of clarithromycin with sildenafil, tadalafil or vardenafil would likely result in increased phosphodiesterase inhibitor exposure. Reduction of sildenafil, tadalafil and vardenafil dosages should be considered when these drugs are coadministered with clarithromycin.
Theophylline, carbamazepine
Results of clinical studies indicate that there was a modest but statistically significant (p≤ 0.05) increase of circulating theophylline or carbamazepine levels when either of these drugs were administered concomitantly with clarithromycin. Dose reduction may need to be considered.
Tolterodine
The primary route of metabolism for tolterodine is via the 2D6 isoform of cytochrome P450 (CYP2D6). However, in a subset of the population devoid of CYP2D6, the identified pathway of metabolism is via CYP3A. In this population subset, inhibition of CYP3A results in significantly higher serum concentrations of tolterodine. A reduction in tolterodine dosage may be necessary in the presence of CYP3A inhibitors, such as clarithromycin in the CYP2D6 poor metaboliser population.
Triazolobenzodiazepines (e.g., alprazolam, midazolam, triazolam)
When midazolam was co-administered with clarithromycin tablets (500 mg twice daily), midazolam AUC was increased 2.7-fold after intravenous administration of midazolam. If intravenous midazolam is co-administered with clarithromycin, the patient must be closely monitored to allow dose adjustment. Drug delivery of midazolam via oromucosal route, which could bypass pre-systemic elimination of the drug, will likely result in a similar interaction to that observed after intravenous midazolam rather than oral administration.
The same precautions should also apply to other benzodiazepines that are metabolised by CYP3A, including triazolam and alprazolam. For benzodiazepines which are not dependent on CYP3A for their elimination (temazepam, nitrazepam, lorazepam), a clinically important interaction with clarithromycin is unlikely. There have been post-marketing reports of drug interactions and central nervous system (CNS) effects (e.g., somnolence and confusion) with the concomitant use of clarithromycin and triazolam. Monitoring the patient for increased CNS pharmacological effects is suggested.
Other drug interactions
Colchicine
Colchicine is a substrate for both CYP3A and the efflux transporter, P-glycoprotein (Pgp). Clarithromycin and other macrolides are known to inhibit CYP3A and Pgp. When clarithromycin and colchicine are administered together, inhibition of Pgp and/or CYP3A by clarithromycin may lead to increased exposure to colchicine.
Digoxin
Digoxin is thought to be a substrate for the efflux transporter, P-glycoprotein (Pgp). Clarithromycin is known to inhibit Pgp. When clarithromycin and digoxin are administered together, inhibition of Pgp by clarithromycin may lead to increased exposure to digoxin.
Elevated digoxin serum concentrations in patients receiving clarithromycin and digoxin concomitantly have also been reported in post marketing surveillance.
Some patients have shown clinical signs consistent with digoxin toxicity, including potentially fatal arrhythmias. Serum digoxin concentrations should be carefully monitored while patients are receiving digoxin and clarithromycin simultaneously.
Zidovudine
Simultaneous oral administration of clarithromycin tablets and zidovudine to HIV infected adult patients may result in decreased steady-state zidovudine concentrations. Because clarithromycin appears to interfere with the absorption of simultaneously administered oral zidovudine, this interaction can be largely avoided by staggering the doses of clarithromycin and zidovudine to allow for a 4-hour interval between each medication. This interaction does not appear to occur in paediatric HIV-infected patients taking clarithromycin suspension with zidovudine or dideoxyinosine.
This interaction is unlikely when clarithromycin is administered via intravenous infusion. Phenytoin and Valproate There have been spontaneous or published reports of interactions of CYP3A inhibitors, including clarithromycin with drugs not thought to be metabolised by CYP3A (e.g. phenytoin and valproate). Serum level determinations are recommended for these drugs when administered concomitantly with clarithromycin. Increased serum levels have been reported.
Bi-directional drug interactions
Atazanavir
Both clarithromycin and atazanavir are substrates and inhibitors of CYP3A, and there is evidence of a bi-directional drug interaction. Co-administration of clarithromycin (500 mg twice daily) with atazanavir (400 mg once daily) resulted in a 2-fold increase in exposure to clarithromycin and a 70% decrease in exposure to 14-OHclarithromycin, with a 28% increase in the AUC of atazanavir.
Because of the large therapeutic window for clarithromycin, no dosage reduction should be necessary in patients with normal renal function. For patients with moderate renal function (creatinine clearance 30 to 60 mL/min), the dose of clarithromycin should be decreased by 50%. For patients with creatinine clearance <30 mL/min, the dose of clarithromycin should be decreased by 75% using an appropriate clarithromycin formulation. Doses of clarithromycin greater than 1000 mg per day should not be coadministered with protease inhibitors.
Calcium Channel Blockers
Caution is advised regarding the concomitant administration of clarithromycin and calcium channel blockers metabolized by CYP3A4 (e.g. verapamil, amlodipine, diltiazem) due to the risk of hypotension. Plasma concentrations of clarithromycin as well as calcium channel blockers may increase due to the interaction. Hypotension, bradyarrhythmias and lactic acidosis have been observed in patients taking clarithromycin and verapamil concomitantly.
Itraconazole
Both clarithromycin and itraconazole are substrates and inhibitors of CYP3A, leading to a bidirectional drug interaction. Clarithromycin may increase the plasma levels of itraconazole, while itraconazole may increase the plasma levels of clarithromycin.
Patients taking itraconazole and clarithromycin concomitantly should be monitored closely for signs or symptoms of increased or prolonged pharmacologic effect.
Saquinavir
Both clarithromycin and saquinavir are substrates and inhibitors of CYP3A, and there is evidence of a bi-directional drug interaction. Concomitant administration of clarithromycin (500 mg twice daily) and saquinavir (soft gelatin capsules, 1200 mg three times daily) to 12 healthy volunteers resulted in steady-state AUC and Cmax values of saquinavir which were 177% and 187% higher than those seen with saquinavir alone. Clarithromycin AUC and Cmax values were approximately 40% higher than those seen with clarithromycin alone. No dose adjustment is required when the two drugs are co-administered for a limited time at the doses/formulations studied. Observations from drug interaction studies using the soft gelatin capsule formulation may not be representative of the effects seen using the saquinavir hard gelatin capsule. Observations from drug interaction studies performed with saquinavir alone may not be representative of the effects seen with saquinavir/ritonavir therapy.
When saquinavir is co-administered with ritonavir, consideration should be given to the potential effects of ritonavir on clarithromycin.
Patients taking oral contraceptives should be warned that if diarrhoea, vomiting or breakthrough bleeding occur there is a possibility of contraceptive failure.
Pregnancy
The safety of clarithromycin for use during pregnancy has not been established. Based on variable results obtained from animal studies and experience in humans, the possibility of adverse effects on embryofoetal development cannot be excluded. Some observational studies evaluating exposure to clarithromycin during the first and second trimester have reported an increased risk of miscarriage compared to no antibiotic use or other antibiotic use during the same period.
The available epidemiological studies on the risk of major congenital malformations with use of macrolides including clarithromycin during pregnancy provide conflicting results.
Therefore, use during pregnancy is not advised without carefully weighing the benefits against risks.
Breast-feeding
The safety of clarithromycin for using during breast-feeding of infants has not been established. Clarithromycin is excreted into human breast milk in small amounts. It has been estimated that an exclusively breastfed infant would receive about 1.7% of the maternal weight-adjusted dose of clarithromycin.
Fertility
In the rat, fertility studies have not shown any evidence of harmful effects.
There are no data on the effect of clarithromycin on the ability to drive or use machines. The potential for dizziness, vertigo, confusion and disorientation, which may occur with the medication, should be taken into account before patients drive or use machines.
a. Summary of the safety profile
The most frequent and common adverse reactions related to Clarithromycin therapy for both adult and paediatric populations are abdominal pain, diarrhoea, nausea, vomiting and taste perversion. These adverse reactions are usually mild in intensity and are consistent with the known safety profile of macrolide antibiotics (see section b of section 4.8).
There was no significant difference in the incidence of these gastrointestinal adverse reactions during clinical trials between the patient population with or without pre-existing mycobacterial infections.
b. Tabulated summary of adverse reactions
The following table displays adverse reactions reported in clinical trials and from post-marketing experience with Clarithromycin immediate-release tablets, granules for oral suspension, powder for solution for injection, extended-release tablets and modified-release tablets.
The reactions considered at least possibly related to Clarithromycin are displayed by system organ class and frequency using the following convention: very common (≥1/10), common (≥ 1/100 to < 1/10), uncommon (≥1/1,000 to < 1/100) and not known (adverse reactions from post-marketing experience; cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness when the seriousness could be assessed.
System Organ Class | Very common (≥1/10 | Common ≥ 1/100 to < 1/10 | Uncommon ≥1/1,000 to < 1/100 | Not Known (*cannot be estimated from the available data) |
Infections and infestations | Cellulitis1, candidiasis, gastroenteritis2,infection3, vaginal infection | Pseudomembranous colitis, erysipelas | ||
Blood and lymphatic system | Leukopenia, neutropenia4, thrombocythemia3, eosinophilia4 | Agranulocytosis, thrombocytopenia | ||
Immune system disorders | Anaphylactoid reaction1, hypersensitivity | Anaphylactic reaction, angioedema | ||
Metabolism and nutrition disorders | Anorexia, decreased appetite | |||
Psychiatric disorders | Insomnia | Anxiety, nervousness3, | Psychotic disorder, confusional state, depersonalisation, depression, disorientation, hallucination, abnormal dreams, mania | |
Nervous system disorders | Dysgeusia, headache, taste perversion | Loss of consciousness1, dyskinesia1, dizziness, somnolence, tremor | Convulsion, ageusia, parosmia, anosmia, paraesthesia | |
Ear and labyrinth disorders | Vertigo, hearing impaired, tinnitus | Deafness | ||
Cardiac disorders | Cardiac arrest1, atrial fibrillation1, electrocardiogram QT prolonged, extrasystoles1, palpitations | Torsades de pointes, ventricular tachycardia, ventricular fibrillation | ||
Vascular disorders | Vasodilation1 | Haemorrhage | ||
Respiratory, thoracic and mediastinal disorder | Asthma1, epistaxis2, pulmonary embolism1 | |||
Gastrointestinal disorders | Diarrhoea, vomiting, dyspepsia, nausea, abdominal pain | Oesophagitis1, gastrooesophageal reflux disease2, gastritis, proctalgia2, stomatitis, glossitis, abdominal distension4, constipation, dry mouth, eructation, flatulence | Pancreatitis acute, tongue discolouration, tooth discolouration | |
Hepatobiliary disorders | Liver function test abnormal | Cholestasis4, hepatitis4, alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyltransferase increased4 | Hepatic failure, jaundice hepatocellular | |
Skin and subcutaneous tissue disorders | Rash, hyperhidrosis | Dermatitis bullous1, pruritus, urticaria, rash maculo-papular3 | Severe cutaneous adverse reactions (SCAR) (e.g. Acute generalised exanthematous pustulosis (AGEP),StevensJohnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS)), acne | |
Musculoskeletal and connective tissue disorders | Muscle spasms3, musculoskeletal stiffness1, myalgia2 | Rhabdomyolysis2, **, myopathy | ||
Renal and urinary disorders | Blood creatinine increased1, blood urea increased1 | Renal failure, nephritis interstitial | ||
General disorders and administration site conditions | Injection site phlebitis1 | Injection site pain1, injection site inflammation1 | Malaise4, pyrexia3, asthenia, chest pain4, chills4, fatigue4 | |
Investigations | Albumin globulin ratio abnormal1, blood alkaline phosphatase increased4, blood lactate dehydrogenase increased4 | International normalised ratio increased, prothrombin time prolonged, urine colour abnormal |
1 ADRs reported only for the Powder for Concentrate for Solution for Infusion formulation
2 ADRs reported only for the Extended-Release Tablets formulation
3 ADRs reported only for the Granules for Oral Suspension formulation
4 ADRs reported only for the Immediate-Release Tablets formulation
5, 6 See section c)
* Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Patient exposure is estimated to be greater than 1 billion patient treatment days for clarithromycin.
c. Description of selected adverse reactions
Injection site phlebitis, injection site pain, vessel puncture site pain, and injection site inflammation are specific to the Clarithromycin intravenous formulation.
In some of the reports of rhabdomyolysis, clarithromycin was administered concomitantly with statins, fibrates, colchicine or allopurinol.
There have been post-marketing reports of drug interactions and central nervous system (CNS) effects (e.g. somnolence and confusion) with the concomitant use of clarithromycin and triazolam. Monitoring the patient for increased CNS pharmacological effects is suggested.
There have been rare reports of clarithromycin ER tablets in the stool, many of which have occurred in patients with anatomic (including ileostomy or colostomy) or functional gastrointestinal disorders with shortened GI transit times. In several reports, tablet residues have occurred in the context of diarrhoea. It is recommended that patients who experience tablet residue in the stool and no improvement in their condition should be switched to a different clarithromycin formulation (e.g. suspension) or another antibiotic.
Special population: Adverse Reactions in Immunocompromised Patients (see section e).
d. Paediatric populations
Clinical trials have been conducted using Clarithromycin paediatric suspension in children 6 months to 12 years of age. Therefore, children under 12 years of age should use Clarithromycin paediatric suspension.
Frequency, type and severity of adverse reactions in children are expected to be the same as in adults.
e. Other special populations
Immunocompromised patients
In AIDS and other immunocompromised patients treated with the higher doses of Clarithromycin over long periods of time for mycobacterial infections, it was often difficult to distinguish adverse events possibly associated with Clarithromycin administration from underlying signs of Human Immunodeficiency Virus (HIV) disease or intercurrent illness.
In adult patients, the most frequently reported adverse reactions by patients treated with total daily doses of 1000 mg and 2000mg of Clarithromycin were: nausea, vomiting, taste perversion, abdominal pain, diarrhoea, rash, flatulence, headache, constipation, hearing disturbance, and Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvate Transaminase (SGPT) elevations. Additional low-frequency events included dyspnoea, insomnia and dry mouth. The incidences were comparable for patients treated with 1000mg and 2000mg, but were generally about 3 to 4 times as frequent for those patients who received total daily doses of 4000mg of Clarithromycin.
In these immunocompromised patients, evaluations of laboratory values were made by analysing those values outside the seriously abnormal level (i.e. the extreme high or low limit) for the specified test. On the basis of these criteria, about 2% to 3% of those patients who received 1000mg or 2000mg of Clarithromycin daily had seriously abnormal elevated levels of SGOT and SGPT, and abnormally low white blood cell and platelet counts. A lower percentage of patients in these two dosage groups also had elevated Blood Urea Nitrogen levels. Slightly higher incidences of abnormal values were noted for patients who received 4000mg daily for all parameters except White Blood Cell.
To report any side effect (s):
Saudi Arabia: To report any side effect(s):
National Pharmacovigilance Center (NPC):
· Fax: +966-11-205-7662,
· SFDA Call center: 19999,
· E-mail: npc.drug@sfda.gov.sa,
Website: https://ade.sfda.gov.sa
Reports indicate that the ingestion of large amounts of Clarithromycin can be expected to produce gastro-intestinal symptoms. One patient who had a history of bipolar disorder ingested 8 grams of Clarithromycin and showed altered mental status, paranoid behaviour, hypokalaemia and hypoxaemia.
Adverse reactions accompanying overdosage should be treated by the prompt elimination of unabsorbed drug and supportive measures. As with other macrolides, Clarithromycin serum levels are not expected to be appreciably affected by haemodialysis or peritoneal dialysis
Pharmacotherapeutic group: Antibacterial for systemic use, macrolide
ATC code: J01FA09.
Mechanism of action:
Clarithromycin is an antibiotic belonging to the macrolide antibiotic group. It exerts its antibacterial action by selectively binding to the 50s ribosomal subunit of susceptible bacteria preventing translocation of activated amino acids.
It inhibits the intracellular protein synthesis of susceptible bacteria. The 14-hydroxy metabolite of clarithromycin, a product of parent drug metabolism also has antimicrobial activity.
The metabolite is less active than the parent compound for most organisms, including mycobacterium spp. An exception is Haemophilus influenza where the 14-hydroxy metabolite is twofold more active than the parent compound.
Clarithromycin is usually active against the following organisms in vitro:-
Gram-positive Bacteria: Staphylococcus aureus (methicillin susceptible); Streptococcus pyogenes (Group A beta-hemolytic streptococci); alpha- hemolytic streptococci (viridans group); Streptococcus (Diplococcus) pneumoniae; Streptococcus agalactiae; Listeria monocytogenes.
Gram-negative Bacteria: Haemophilus influenzae; Haemophilus parainfluenzae;Moraxella (Branhamella) catarrhalis; Neisseria gonorrhoeae; Legionella pneumophila; Bordetella pertussis; Helicobacter pylori; Campylobacter jejuni.
Mycoplasma: Mycoplasma pneumoniae; Ureaplasma urealyticum.
Other Organisms: Chlamydia trachomatis; Mycobacterium avium; Mycobacterium leprae.
Anaerobes: Macrolide-susceptible Bacteroides fragilis; Clostridium perfringens; Peptococcus species; Peptostreptococcus species; Propionibacterium acnes.
Clarithromycin has bactericidal activity against several bacterial strains. The organisms include Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae, H. pylori and Campylobacter spp
Breakpoints
The following breakpoints for clarithromycin, separating susceptible organisms from resistant organisms, have been established by the European Committee for Antimicrobial Susceptibility Testing (EUCAST).
Breakpoints (MIC, mg/L) | ||
Microorganism | Susceptible (≤) | Resistant (>) |
Streptococcus spp. | 1 mg/ L | 2 mg/L |
Streptococcus A, B, C and G | 0.25 mg/ L | 0.5 mg/ L |
Streptococcus pneumonia | 0.25 mg/ L | 0.5 mg/ L |
Viridans group streptococcus | IE | IE |
Haemophilus spp. | 1 mg/ L | 32 mg/ L |
Moraxella catarrhalis | 0.25 mg/ L | 0.5 mg/ L1 |
Helicobacter pylori | 0.25 mg/ L1 | 0.5 mg/ L |
1 The breakpoints are based on epidemiological cut-off values (ECOFFs), which distinguish wild-type isolates from those with reduces susceptibility.
“IE" indicates that there is insufficient evidence that the species in question is a good target for therapy with the drug.
H. pylori is associated with acid peptic disease including duodenal ulcer and gastric ulcer in which about 95% and 80% of patients respectively are infected with the agent. H. pylori is also implicated as a major contribution factor in the development of gastric and ulcer recurrence in such patients.
Clarithromycin has been used in small numbers of patients in other treatment regimens. Possible kinetic interactions have not been fully investigated. These regimens include:
Clarithromycin plus tinidazole and omeprazole; Clarithromycin plus tetracycline, bismuth subsalicylate and ranitidine; Clarithromycin plus ranitidine alone.
Clinical studies using various different H. pylori eradication regimens have shown that eradication of H. pylori prevents ulcer recurrence.
Clarithromycin is rapidly and well absorbed from the gastro-intestinal tract after oral administration of Clarithromycin tablets. The microbiologically active metabolite 14-hydroxyClarithromycin is formed by first pass metabolism. Clarithromycin may be given without regard to meals as food does not affect the extent of bioavailability of Clarithromycin tablets. Food does slightly delay the onset of absorption of Clarithromycin and formation of the 14-hydroxymetabolite. The pharmacokinetics of Clarithromycin are non linear; however, steady-state is attained within 2 days of dosing. At 250 mg b.i.d. 15-20% of unchanged drug is excreted in the urine. With 500 mg b.i.d. daily dosing urinary excretion is greater (approximately 36%). The 14-hydroxyClarithromycin is the major urinary metabolite and accounts for 10-15% of the dose. Most of the remainder of the dose is eliminated in the faeces, primarily via the bile. 5-10% of the parent drug is recovered from the faeces.
When Clarithromycin 500 mg is given three times daily, the Clarithromycin plasma concentrations are increased with respect to the 500 mg twice daily dosage.
ERACID provides tissue concentrations that are several times higher than the circulating drug levels. Increased levels have been found in both tonsillar and lung tissue. Clarithromycin is 80% bound to plasma proteins at therapeutic levels.
ERACID also penetrates the gastric mucus. Levels of Clarithromycin in gastric mucus and gastric tissue are higher when Clarithromycin is co-administered with omeprazole than when Clarithromycin is administered alone.
In acute mouse and rat studies, the median lethal dose was greater than the highest feasible dose for administration (5g/kg).
In repeated dose studies, toxicity was related to dose, duration of treatment and species. Dogs were more sensitive than primates or rats. The major clinical signs at toxic doses included emesis, weakness, reduced food consumption and weight gain, salivation, dehydration and hyperactivity.
In all species the liver was the primary target organ at toxic doses. Hepatotoxicity was detectable by early elevations of liver function tests. Discontinuation of the drug generally resulted in a return to or toward normal results. Other tissues less commonly affected included the stomach, thymus and other lymphoid tissues and the kidneys. At near therapeutic doses, conjunctival injection and lacrimation occurred only in dogs. At a massive dose of 400mg/kg/day, some dogs and monkeys developed corneal opacities and/or oedema.
Fertility, Reproduction and Teratogenicity
Studies performed in rats at oral doses up to 500 mg/kg/day (highest dose associated with overt renal toxicity) demonstrated no evidence for clarithromycin-related adverse effects on male fertility. This dose corresponds to a human equivalent dose (HED) of approximately 5 times the maximum recommended human dose (MRHD) on a mg/m2 basis for a 60-kg individual.
Fertility and reproduction studies in female rats have shown that a daily dosage of 150 mg/kg/day (highest dose tested) caused no adverse effects on the oestrus cycle, fertility, parturition and number and viability of offspring. Oral teratogenicity studies in rats (Wistar and Spraque-Dawley), rabbits (New Zealand White) and cynomolgous monkeys failed to demonstrate any teratogenicity from clarithromycin at the highest doses tested up to 1.5, 2.4 and 1.5 times the MRHD on a mg/m2 basis in the respective species.
However, a similar study in Sprague-Dawley rats indicated a low (6%) incidence of cardiovascular abnormalities which appeared to be due to spontaneous expression of genetic changes.
Two mouse studies revealed a variable incidence (3-30%) of cleft palate at ~5 times the MRHD on a mg/m2 basis for a 60-kg individual. Embryonic loss was seen in monkeys but only at dose levels which were clearly toxic to the mothers.
q Sodium Starch Glycolate (Type A)
q Anhydrous Calcium Hydrogen Phosphate
q Maize Starch
q Hydroxypropyl Cellulose
q Colloidal Anhydrous Silica
q Magnesium Stearate
q Purified Talc
q Opadry-OY 8487 Yellow
None known.
Do not store above 30°C, protected from light.
Boxes of 14 tablets in PVC/aluminium foil blisters.
No special requirments
