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نشرة الممارس الصحي نشرة معلومات المريض بالعربية نشرة معلومات المريض بالانجليزية صور الدواء بيانات الدواء
  SFDA PIL (Patient Information Leaflet (PIL) are under review by Saudi Food and Drug Authority)

Flukas is one of a group of medicines called “antifungals”. The active substance is fluconazole.
Flukas is used to treat infections caused by fungi and may also be used to stop you from getting candidal infection. The most common cause of fungal infections is a yeast called Candida.

Adults

You might be given this medicine by your doctor to treat the following types of fungal infections:
- Cryptococcal meningitis – a fungal infection in the brain
- Coccidioidomycosis – a disease of the bronchopulmonary system
- Infections caused by Candida and found in the blood stream, body organs (e.g. heart, lungs) or urinary tract
- Mucosal thrush - infection affecting the lining of the mouth, throat and denture sore mouth

You might also be given Flukas to:
- stop cryptococcal meningitis from coming back
- stop mucosal thrush from coming back
- stop you from getting an infection caused by Candida (if your immune system is weak and not working properly)

Children and adolescents (0 to 17 years old)

You might be given this medicine by your doctor to treat the following types of fungal infections:
- Mucosal thrush - infection affecting the lining of the mouth, throat
- Infections caused by Candida and found in the blood stream, body organs (e.g. heart, lungs) or urinary tract
- Cryptococcal meningitis – a fungal infection in the brain

You might also be given Flukas to:

- stop you from getting an infection caused by Candida (if your immune system is weak and not working properly)
- stop cryptococcal meningitis from coming back


Do not take Flukas
- if you are allergic to fluconazole, to other medicines you have taken to treat fungal infections or to any of the other ingredients of this medicine (listed in section 6). The symptoms may include itching, reddening of the skin or difficulty in breathing
- if you are taking astemizole, terfenadine (antihistamine medicines for allergies)
- if you are taking cisapride (used for stomach upsets)
- if you are taking pimozide (used for treating mental illness)
- if you are taking quinidine (used for treating heart arrhythmia)
- if you are taking erythromycin (an antibiotic for treating infections)

Warnings and precautions
Talk to your doctor or nurse before taking Flukas
- if you have liver or kidney problems
- if you suffer from heart disease, including heart rhythm problems
- if you have abnormal levels of potassium, calcium or magnesium in your blood
- if you develop severe skin reactions (itching, reddening of the skin or difficulty in breathing)
- if you develop signs of ‘adrenal insufficiency’ where the adrenal glands do not produce adequate amounts of certain steroid hormones such as cortisol (chronic, or long lasting fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain)

Other medicines and Flukas
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Tell your doctor immediately if you are taking astemizole, terfenadine (an antihistamine for treating allergies) or cisapride (used for stomach upsets) or pimozide (used for treating mental illness) or quinidine (used for treating heart arrhythmia) or erythromycin (an antibiotic for treating infections) as these should not be taken with Flukas (see section: “Do not take Flukas if you”).

There are some medicines that may interact with Flukas. Make sure your doctor knows if you are taking any of the following medicines:

- rifampicin or rifabutin (antibiotics for infections)
- alfentanil, fentanyl (used as anaesthetic)
- amitriptyline, nortriptyline (used as anti-depressant)
- amphotericin B, voriconazole (anti-fungal)
- medicines that thin the blood to prevent blood clots (warfarin or similar medicines)
- benzodiazepines (midazolam, triazolam or similar medicines) used to help you sleep or for anxiety
- carbamazepine, phenytoin (used for treating fits)
- nifedipine, isradipine, amlodipine, felodipine and losartan (for hypertension - high blood pressure)
- olaparib (used for treating ovarian cancer)
- ciclosporin, everolimus, sirolimus or tacrolimus (to prevent transplant rejection)
- cyclosphosphamide, vinca alkaloids (vincristine, vinblastine or similar medicines) used for treating cancer
- halofantrine (used for treating malaria)
- statins (atorvastatin, simvastatin and fluvastatin or similar medicines) used for reducing high cholesterol levels
- methadone (used for pain)
- celecoxib, flurbiprofen, naproxen, ibuprofen, lornoxicam, meloxicam, diclofenac (Non-Steroidal Anti-Inflammatory Drugs (NSAID))
- oral contraceptives
- prednisone (steroid)
- zidovudine, also known as AZT; saquinavir (used in HIV-infected patients)
- medicines for diabetes such as chlorpropamide, glibenclamide, glipizide or tolbutamide
- theophylline (used to control asthma)
- vitamin A (nutritional supplement)
- ivacaftor (used for treating cystic fibrosis)
- amiodarone (used for treating uneven heartbeats ‘arrhythmias’)
- hydrochlorothiazide (a diuretic)

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.
You should not take Flukas while you are pregnant unless your doctor has told you to.
You can continue breast-feeding after taking a single dose of 150 mg Flukas.
You should not breast-feed if you are taking a repeated dose of Flukas.

Driving and using machines
When driving vehicles or using machines it should be taken into account that occasionally dizziness or fits may occur.

Flukas contains sodium
Flukas contains 0.154 mmol sodium per ml. To be taken into consideration by patients on a controlled sodium diet.


This medicine will be given by your doctor or nurse as a slow injection (infusion) into your vein. Flukas is supplied as a solution. It will not be diluted further. There is more information for healthcare professionals in a section at the end of the leaflet.
The recommended doses of this medicine for different infections are below. Check with your doctor or nurse if you are not sure why you are being given Flukas.

Adults

ConditionDose
To treat cryptococcal meningitis400 mg on the first day then 200 mg to
400 mg once daily for 6 to 8 weeks or
longer if needed. Sometimes doses are
increased up to 800 mg
To stop cryptococcal meningitis from coming back200 mg once daily until you are told to
stop
To treat coccidioidomycosis200 mg to 400 mg once daily from
11 months for up to 24 months or longer
if needed. Sometimes doses are increased
up to 800 mg
To treat internal fungal infections caused by Candida800 mg on the first day then 400 mg once
daily until you are told to stop
To treat mucosal infections affecting the lining of mouth, throat and denture sore mouth200 mg to 400 mg on the first day then 100 mg to 200 mg once daily until you
are told to stop
To treat mucosal thrush – dose depends on where the infection is located50 mg to 400 mg once daily for 7 to 30 days until you are told to stop
To stop mucosal infections affecting the lining of mouth, throat from coming back.100 mg to 200 mg once daily, or 200 mg 3 times a week, while you are at risk of
getting an infection
To stop you from getting an infection caused by Candida (if your immune system is weak and not working properly)200 mg to 400 mg once daily while you are at risk of getting an infection

Adolescents from 12 to 17 years old
Follow the dose prescribed by your doctor (either adults or children posology).

Children to 11 years old
The maximum dose for children is 400 mg daily.
The dose will be based on the child’s weight in kilograms.

ConditionDaily dose
Mucosal thrush and throat infections caused by Candida – dose and duration depends on the severity of the infection and on where the infection is located3 mg per kg of body weight once daily (6 mg per kg of body weight might be given on the first day)
Cryptococcal meningitis or internal fungal infections caused by Candida6 mg to 12 mg per kg of body weight once daily
To stop cryptococcal meningitis from coming back6 mg per kg of body weight once daily
 
To stop children from getting an infection caused by Candida (if their immune system is not working properly)3 mg to 12 mg per kg of body weight once daily

 

Use in children 0 to 4 weeks of age

Use in children of 3 to 4 weeks of age:
• The same dose as above but given once every 2 days. The maximum dose is 12 mg per kg of body weight every 48 hours.

Use in children less than 2 weeks old:
• The same dose as above but given once every 3 days. The maximum dose is 12 mg per kg of body weight every 72 hours.

Elderly
The usual adult dose should be given unless you have kidney problems.

Patients with kidney problems
Your doctor may change your dose, depending on your kidney function.

If you take more Flukas than you should

If you are concerned that you may have been given too much Flukas, tell your doctor or nurse immediately. The symptoms of a possible overdose may include hearing, seeing, feeling and thinking things that are not real (hallucination and paranoid behaviour).

If you forget to take Flukas
As you will be given this medicine under close medical supervision, it is unlikely that a dose would be missed. However tell your doctor or pharmacist if you think that a dose has been forgotten.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.


Like all medicines, this medicine can cause side effects, although not everybody gets them.
A few people develop allergic reactions although serious allergic reactions are rare. If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. If you get any of the following symptoms, tell your doctor immediately.
- sudden wheezing, difficulty in breathing or tightness in the chest
- swelling of eyelids, face or lips
- itching all over the body reddening of the skin or itchy red spots
- skin rash
- severe skin reactions such as a rash that causes blistering (this can affect the mouth and tongue).

Flukas may affect your liver. The signs of liver problems include:
- tiredness
- loss of appetite
- vomiting
- yellowing of your skin or the whites of your eyes (jaundice)

If any of these happen, stop taking Flukas and tell your doctor immediately.

Other side effects:
Additionally, if any of the following side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Common side effects (may affect up to 1 in 10 people) are:
- headache
- stomach discomfort, diarrhoea, feeling sick, vomiting
- increases in blood tests of liver function
- rash

Uncommon side effects (may affect up to 1 in 100 people) are:
- reduction in red blood cells which can make skin pale and cause weakness or breathlessness
- decreased appetite
- inability to sleep, feeling drowsy
- fit, dizziness, sensation of spinning, tingling, pricking or numbness, changes in sense of taste
- constipation, difficult digestion, wind, dry mouth
- muscle pain
- liver damage and yellowing of the skin and eyes (jaundice)
- wheals, blistering (hives), itching, increased sweating
- tiredness, general feeling of being unwell, fever

Rare side effects (may affect up to 1 in 1,000 people) are:

- lower than normal white blood cells that help defend against infections and blood cells that help to stop bleeding
- red or purple discoloration of the skin which may be caused by low platelet count, other blood cell changes
- blood chemistry changes (high blood levels of cholesterol, fats)
- low blood potassium
- shaking
- abnormal electrocardiogram (ECG), change in heart rate or rhythm
- liver failure
- allergic reactions (sometimes severe), including widespread blistering rash and skin peeling, severe skin reactions, swelling of the lips or face
- hair loss

Frequency not known, but may occur (cannot be estimated from the available data):
- hypersensitivity reaction with skin rash, fever, swollen glands, increase in a type of white blood cell (eosinophilia) and inflammation of internal organs (liver, lungs, heart, kidneys and large intestine) (Drug Reaction or rash with Eosinophilia and Systemic Symptoms (DRESS))

Reporting of side effects
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, health care provider or pharmacist.


- Store below 30°C
- Keep this medicine out of the sight and reach of children.
- Do not use this medicine after the expiry date which is stated on the pack after EXP. The expiry date refers to the last day of that month.
Storage conditions:
- Do not freeze.
- Once opened the product should be used immediately. Any unused infusion should be discarded. This medicinal product is for single use only.
- Do not use this medicine if you notice visible particles or if the solution is unclear or discoloured.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how throw away medicines you no longer use. These measures will help protect the environment
Shelf life : 24 months


- The active substance is fluconazole. Each ml contains 2 mg of fluconazole.
1 vial with 50 ml solution for infusion contains 100 mg fluconazole.
- The other ingredients are: sodium chloride, water for injections and sodium hydroxide (for pH adjustment).


- Flukas is a clear, colourless solution with no visible particles. - It comes in glass vials.

For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Salehiya Trading Establishment
(Medical equipment & pharmaceuticals)
P.O.Box: 991, Riyadh 11421- Kingdom of Saudi Arabia
Tel: 00 966 1 46 46 955
Fax: 00 966 1 46 34 362


This leaflet was last revised in : 05/2018
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

إن فلوكاس ينتمي لمجموعة من الأدوية تسمى مضادات الفطريات. المادة الفعالة هي فلوكونازول.
يستخدم فلوكاس لعلاج العدوى التي تسببها الفطريات بما في ذلك الكانديدا. إن السبب الأكثر شيوعا في حدوث العدوى الفطرية هي
خميرة تسمى كانديدا.
الكبار
قد يتم إعطاؤك هذا الدواء من قبل طبيبك لعلاج أنواع العدوى الفطرية التالية:
-التهاب السحايا بالمستخفيات - Cryptococcal meningitis - التهاب فطري في الدماغ.
-مرض في الجهاز القصبي الرئوي - Coccidioidomycosis.
- العدوى التي تسببها المبيضات وجدت في مجرى الدم، وأعضاء الجسم (مثل القلب والرئتين) أو المسالك البولية
- القلاع المخاطي - العدوى التي تؤثر على بطانة الفم والحلق و تهيج الاسنان الاصطناعية
قد يتم إعطاؤك أيضًا فلوكاس إلى:
- وقف معاودة مرض التهاب السحايا بالمستخفيات
- وقف معاودة مرض التهاب الغشاء المخاطي
- يمنعك من حصول العدوى التي تسببها المبيضات(إذا كان جهازك المناعي ضعيفًا ولا يعمل بشكل صحيح)
 

الأطفال والمراهقون (من 0 إلى 17 سنة)
قد يتم إعطاؤك هذا الدواء من قبل طبيبك لعلاج أنواع العدوى الفطرية التالية:
- القلاع المخاطي - العدوى التي تصيب بطانة الفم والحنجرة
- العدوى التي تسببها المبيضات في مجرى الدم، وأعضاء الجسم (مثل القلب والرئتين) أو المسالك البولية
-التهاب السحايا بالمستخفيات - Cryptococcal meningitis - التهاب فطري في الدماغ.

إذا كنت تعاني من حساسية من فلوكونازول ، الأدوية الأخرى التي أخذتها لعلاج العدوى الفطرية أو لأي من المكونات الأخرى لهذا
الدواء (المذكورة في القسم 6). قد تشمل الأعراض حكة أو احمرار في الجلد أو صعوبة في التنفس

- إذا كنت تأخذ ترفينادين أو استرميزول (مضاد للهيستامين لعلاج الحساسية)
- إذا كنت تأخذ سيسابريد (لعلاج اضطرابات المعدة.)
- إذا كنت تأخذ بيموزيد (لعلاج الفصام العقلى.)
- إذا كنت تأخذ كينيدين (لعلاج خفقان القلب.)
- إذا كنت تتناول الاريثرومايسين (مضاد حيوي لمعالجة العدوى).

المحاذير والإحتياطات
تحدث إلى طبيبك أو الممرضة قبل تناول فلوكاس
- إذا كنت تعاني من مشاكل في الكبد أو الكلى
- إذا كنت تعاني من مرض القلب ، بما في ذلك مشاكل إيقاع القلب
- إذا كان لديك مستويات غير طبيعية من البوتاسيوم والكالسيوم والمغنيسيوم في الدم
- إذا كنت تصاب بتفاعلات جلدية شديدة (حكة ، احمرار في الجلد أو صعوبة في التنفس)
- إذا ظهرت عليك علامات "قصور الغدة الكظرية" حيث لا تنتج الغدد الكظرية كميات كافية من هرمونات معينة مثل
الكورتيزول ( التعب طويل الأمد أو المزمن، ضعف العضلات ، فقدان الشهية ، فقدان الوزن ، آلام في البطن)

الأدوية الأخرى و فلوكاس
أخبر طبيبك أو الصيدلي إذا كنت تأخذ، أو اخذت مؤخرا أو قد تأخذ أي أدوية أخرى.
اخبر طبيبك فورا إذا كنت تأخذ ترفينادين أو استرميزول (مضاد للهيستامين لعلاج الحساسية) أو سيسابريد (لعلاج
إضرابات المعدة) حيث إن هذه الأدوية يجب عدم أخذها مع فلوكاس.
هناك بعض الأدوية التي قد تتفاعل مع فلوكاس. تأكد من إن طبيبك يعلم انك تأخذ أي من الأدوية التالية:
- الأدوية المستخدمة في علاج ألعدوي(المضادات الحيوية) مثل ازيثرومايسين، ريفامبيسين، اريثرومايسين أو ريفابيوتين.
–الفنتانيل ، فنتانيل أو ميثادون (كمخدر) .
–اميتريبتيلين ، نورتريبتيلين (التي تستخدم كمضاد للاكتئاب). - امفوتريسين بي، فوريكونازول (المستخدم في علاج
العدوى الفطرية)
–وارفارين (أو إي أدوية مماثلة) الذي يرقق الدم لمنع تجلط الدم.
- بنزوديازيبينات (ميدازولام،تريازولام أو الأدوية المشابهة) المستخدمة في مساعدتك علي النوم أو لعلاج القلق.
–كاربيمازيبين أو فينيتوين (المستخدمان في السيطرة علي مرض الصرع)
- نيفيديبين، اسراديبين، أملوديبين، فيلوديبين واللوسارتان(لعلاج ارتفاع ضغط الدم)
- سيكلوسبورين ، ايفروليماس ، سيروليماس أو تاكروليماس (لمنع رفض الأعضاء التي يتم زرعها)
- سيكلوفوسفاميد ، أو قلويات فينكا( فينكريستين، فينبلاستين أو الأدوية المشابهة) المستخدمة في علاج السرطان.
–هالوفانترين (لعلاج الملاريا)
- الستاتين (أتورفاستاتين،سيمفاستاتين وفلوفاستاتين أو الأدوية المشابهة) المستخدمة للحد من ارتفاع مستويات الكولسترول.
– ميثادون (لعلاج الألأم)
- سيليكوكسيب ، فلوربايبروفين، نابروكسين ، ايبوبروفين، لورونوكسيكام، ميلوكسيكام. ديكلوفيناك (الأدوية الغير
استيرويدية المضادة للالتهاب)
- وسائل منع الحمل التي تؤخذ عن طريق الفم.
–بريدنيزولون (ستيرويد)
- ساكوينافير أو زيدوفيدوين المعروف باسم ازيدوثيميدين (لعلاج المرضى المصابين بفيروس نقص المناعة البشرية)
- أدوية لعلاج مرض السكر مثل كلوربروباميد ، جلينكلاميد، جليبيزايد أو تولبيوتاميد.
- ثيوفيلين (المستخدم في السيطرة علي الربو)
–فيتامين (أ) (مكملات غذائية)
- ريفكافتر (يستخدم لعلاج التليف الكيسي)
- الأميودارون (يستخدم لعلاج عدم انتظام ضربات القلب في عدم انتظام ضربات القلب)
-هيدروكلوروثيازيد (مدر للبول)
يرجى إخبار الطبيب أو الصيدلي إذا كنت تأخذ أو أخذت في الآونة الأخيرة أي أدوية أخري ، بما في ذلك الأدوية التي
اشتريتها من دون وصفة طبية.

الحمل والرضاعة الطبيعية والخصوبة
اخبري طبيبك إذا كنتى حاملا. أو تحاولين إن تصبحين حاملا أو خلال فترة الرضاعة الطبيعية ، اسألي طبيبك أو الصيدلي
للحصول على المشورة قبل تناول هذا الدواء.

يجب عليك عدم تناول فلوكاس أثناء الحمل إلا إذا أخبرك الطبيب بذلك.
يمكنك الاستمرار في الرضاعة الطبيعية بعد تناول جرعة واحدة من 150 ملغ فلوكاس .
يجب عليك التوقف عن الرضاعة الطبيعية إذا كنت تأخذين جرعة متكررة من فلوكاس .
 

القيادة واستخدام الآلات
عند قيادة المركبات أو استخدام الآلات يجب أن يؤخذ بعين الاعتبار أنه قد يحدث دوخة أو نوبات في بعض الأحيان.
 

فلوكاس يحتوي على الصوديوم
تحتوي فلوكاس على 0.154 ملي مول صوديوم لكل مل. ليأخذ بعين الاعتبار من قبل المرضى على نظام غذائي الصوديوم التي
تسيطر عليها.

https://localhost:44358/Dashboard

سيعطى هذا الدواء من قبل الطبيب أو الممرضة كحقن بطيء (ضخ) في الوريد. يتم توفير فلوكاس كمحلول دون حاجة إلى
تخفيف. هناك المزيد من المعلومات لأخصائيي الرعاية الصحية في قسم في نهاية النشرة.
الجرعات الموصى بها من هذا الدواء لأنواع العدوى المختلفة المبينة أدناه. استشر طبيبك أو الممرضة إذا لم تكن متأكداً من سبب
حصولك على فلوكاس .

المرضجرعة
لعلاج التهاب السحايا بالمستخفيات400 ملغ في اليوم الأول ثم 200 ملغ
400 ملغ مرة واحدة يوميا لمدة 6 إلى 8 أسابيع أو
أطول إذا لزم الأمر. أحيانا الجرعات هي
زيادة تصل إلى 800 ملغ
لوقف التهاب السحايا بالمستخفيات من العودة200 ملغ مرة واحدة يوميا حتى يتم إخبارك بذلك
توقف
لعلاج داء الكرواني200 ملغ إلى 400 ملغ مرة واحدة يوميًا من
11 شهرًا لمدة تصل إلى 24 شهرًا أو أكثر
إذا لزم الأمر. في بعض الأحيان يتم زيادة الجرعات
تصل إلى 800 ملغ
لعلاج الالتهابات الفطرية الداخلية التي تسببها المبيضات800ملغ في اليوم الأول ثم 400 ملغ مرة واحدة يوميا حتى يطلب منك التوقف
لعلاج العدوى المخاطية التي تؤثر على بطانة الفم والحلق والتهابات الأسنان الصناعيةمن 200 ملغ إلى 400 ملغ في اليوم الأول 100 ملغ إلى 200 ملغ مرة واحدة يوميا حتى يطلب منك التوقف
لعلاج مرض القلاع الغشاء المخاطي - تعتمد الجرعة على موضع العدوى50 ملغ إلى 400 ملغ مرة واحدة يوميا لمدة 7 إلى
العدوى 30 يومًا حتى يطلب منك التوقف
لوقف العدوى المخاطية التي تؤثر على بطانة الفم والحلق من العودة100 ملغ إلى 200 ملغ مرة واحدة يوميا،ً أو 200 ملغ 3 مرات في الأسبوع، بينما أنت في خطر حصول العدوى
لمنع حصول العدوى التي تسببها  لمبيضات(إذا كان جهازك المناعي ضعيفًا و لا تعمل بشكل صحيح)200 ملغ إلى 400 ملغ مرة واحدة يوميا بينما أنت معرض لخطر الإصابة

 

المراهقون من سن 12 إلى 17 عامًا
اتبع الجرعة الموصوفة من قبل طبيبك .
 

الأطفال حتى سن 11 سنة
الحد الأقصى لجرعة الأطفال هو 400 ملغ يوميا.

تعتمد الجرعة على وزن الطفل بالكيلوغرام.

  
التهاب الغشاء المخاطي والالتهابات التي تسببها  لمبيضات- الجرعة والمدة يعتمد على شدة العدوى وعلى مكانها3 ملغ لكل كيلوغرام من وزن الجسم مرة واحدة يوميا (يمكن زيادة الجرعة ال- 6 ملغ لكل كيلوغرام من العدوى وعلى مكانها وزن الجسم خلال اليوم الأول)
Cryptococcal meningitis أو الالتهابات الفطرية الداخلية تسببها المبيضات6 ملغ إلى 12 ملغ لكل كيلوغرام من وزن الجسم مرة واحدة يوميا.
لوقف التهاب السحايا بالمستخفيات من العودة6 مجم لكل كيلوغرام من وزن الجسم مرة واحدة يوميا
لمنع الأطفال من الحصول على العدوى التي تسببها لمبيضات(إذا كان نظام المناعة لديهم لا يعمل بصورة صحيحة)3 ملغ إلى 12 ملغ لكل كيلوغرام من وزن الجسم مرة واحدة يوميا

استخدام في الأطفال من عمر 0 إلى 4 أسابيع من العمر

يستخدم في الأطفال من 3 إلى 4 أسابيع من العمر:
• نفس الجرعة المذكورة أعلاه ولكنها تعطى مرة كل يومين. الجرعة القصوى هي 12 ملغ لكل كيلوغرام من وزن الجسم كل 48 ساعة.
استخدم في الأطفال أقل من أسبوعين:
• نفس الجرعة المذكورة أعلاه ولكن تعطى مرة واحدة كل 3 أيام. الجرعة القصوى هي 12 ملغ لكل كيلوغرام من وزن الجسم كل 72 ساعة.

كبار السن
يجب أن تعطى جرعة البالغين المعتادة إلا إذا كان لديك مشاكل في الكلى.

المرضى الذين يعانون من مشاكل في الكلى
قد يقوم طبيبك بتغيير الجرعة، اعتمادا على وظائف الكلى.

عند تناول جرعة أكبر من مطلوب
إذا كنت تشعر بالقلق من أنك قد أعطيت الكثير من فلوكاس ، أخبر طبيبك أو الممرضة على الفور. قد تشمل أعراضجرعة زائدة
محتملة الاستماع ورؤية والشعور والتفكير بأشياء ليست حقيقية (هلوسة وسلوك بجنون العظمة).

إذا نسيت أن تأخذ فلوكاس
بما أنك ستحصل على هذا الدواء تحت إشراف طبي دقيق ، فمن غير المحتمل أن يتم تفويت جرعة ما. لكن أخبر طبيبك أو الصيدلي
إذا كنت تعتقد أن الجرعة قد نسيت.
إذا كان لديك أي أسئلة أخرى حول استخدام هذا الدواء ، اسأل طبيبك أو الصيدلي أو الممرضة.

مثل جميع الأدوية ، يمكن أن يسبب هذا الدواء آثارًا جانبية ، على الرغم من عدم حصول الجميع عليها.
وهناك عدد قليل من الناس لديهم ردود فعل تحسسية على الرغم من أن نوبات الحساسية الخطيرة نادرة . إذا حصلت على أي آثار
جانبية ، تحدث إلى طبيبك أو الصيدلي. يتضمن ذلك أي آثار جانبية محتملة غير مدرجة في هذه النشرة. إذا حصلت على أي من
الأعراض التالية ، أخبر طبيبك على الفور.
- أزيز مفاجئ ، صعوبة في التنفس أو ضيق في الصدر
- تورم الجفون أو الوجه أو الشفتين
- حكة في جميع أنحاء الجسم احمرار الجلد أو بقع حمراء حاك
- الطفح الجلدي
- تفاعلات جلدية شديدة مثل الطفح الجلدي الذي يسبب تقرحات (يمكن أن يؤثر ذلك على الفم واللسان).

قد يؤثر  Flukas على الكبد. تشمل علامات مشاكل الكبد ما يلي:

- تعب
- فقدان الشهية
- قيء
- اصفرار بشرتك أو بياض عينيك (اليرقان)

إذا حدث أي من هذه الأعراض، فتوقف عن تناول Flukas وأخبر طبيبك على الفور.

الآثار الجانبية الأخرى:
بالإضافة إلى ذلك ، إذا كان أي من الآثار الجانبية التالية خطيرة ، أو إذا لاحظت أي آثار جانبية غير مدرجة في هذه النشرة ، يرجى إخبار طبيبك أو الصيدلي.

الآثار الجانبية الشائعة (قد تؤثر على 1 من كل 10 أشخاص) هي:
- صداع
- إضطراب المعدة ، والإسهال ، والشعور بالغثيان ، والتقيؤ
- إرتفاع نتائج اختبارات الدم من وظائف الكبد
- طفح جلدي

الآثار الجانبية غير الشائعة (قد تؤثر على 1 من كل 100 شخص) هي:
- انخفاض في خلايا الدم الحمراء التي يمكن أن تجعل البشرة شاحبة وتسبب ضعف أو ضيق في التنفس
- قلة الشهية
- عدم القدرة على النوم ، والشعور بالنعاس
- نوبة ، والدوخة ، والإحساس بالغزل ، والوخز ، وخز أو خدر ، والتغيرات في معنى الذوق
- الإمساك ، صعوبة في الهضم ، ريح ، جفاف الفم
- ألم عضلي
- تلف الكبد واصفرار الجلد والعينين (اليرقان)
- التقرحات ، الحويصلات (خلايا النحل) ، الحكة ، زيادة التعرق
- التعب والشعور العام بالفتور والحمى

الآثار الجانبية النادرة (قد تؤثر على 1 من كل 1000 شخص) هي:
- إنخفاض خلايا الدم البيضاء الطبيعية التي تساعد في الحماية من العدوى وخلايا الدم التي تساعد على وقف النزيف
- تلون الجلد بالأحمر أو الأرجواني من الجلد وهذا قد يكون ناتجًا عن انخفاض عدد الصفائح الدموية وغيرها خلايا الدم الأخرى
- تغيرات كيمياء الدم (إرتفاع مستويات الدم من الكوليسترول والدهون)
- انخفاض البوتاسيوم في الدم
- رعشة
- رسم القلب الكهربائي غير الطبيعي (ECG) ، تغير في معدل أو إيقاع ضربات القلب 
- تفاعلات حساسية (أحيانًا شديدة) ، بما في ذلك الطفح الجلدي المنتشر على نطاق واسع وتقشر الجلد ، والتفاعلات الجلدية الشديدة ، وتورم الشفاه أو الوجه.
- تساقط الشعر.

التردد غير معروف ، ولكن قد يحدث (لا يمكن تقديره من البيانات المتاحة):

- تفاعل فرط الحساسية مع الطفح الجلدي ، والحمى ، وتورم الغدد ، وزيادة في نوع من خلايا الدم البيضاء (فرط الحمضات) والتهاب الأعضاء الداخلية (الكبد والرئتين والقلب والكليتين والأمعاء الغليظة، التفاعلات الدوائية أو الطفح الجلدي مع فرط الحمضات والأعراض الجهازية DRESS)

الإبلاغ عن الآثار الجانبية
إذا كانت أي من الآثار الجانبية خطيرة، أو إذا لاحظت أي آثار جانبية غير مدرجة في هذه النشرة ، يرجى إخبار طبيبك أو مقدم
الرعاية الصحية أو الصيدلاني .

ابق هذا الدواء بعيدا عن متناول الأطفال.
- يحفظ في درجة حرارة لا تتجاوز 30 درجة مئوية
لا تستخدم هذا الدواء بعد تاريخ انتهاء الصلاحية المذكور في العبوة بعد EXP يشير تاريخ انتهاء الصلاحية إلى آخر يوم في ذلك الشهر.
آخر يوم في ذلك الشهر.
شروط التخزين:
- لا تضع هذا الدواء في مجمد الثلاجة.
- بمجرد فتح المنتج يجب استخدامه على الفور. يجب التخلص من أي محلول غير مستخدم. هذا المنتج الطبي
للاستخدام الفردي فقط.
- لا تستخدم هذا الدواء إذا لاحظت وجود جسيمات مرئية أو إذا كان المحلول غير شفافٌ أو متغير اللون.
لا تتخلص من أي أدوية عن طريق مياه الصرف الصحي أو النفايات المنزلية. اسأل الصيدلي عن كيفية التخلص من الأدوية
التي لم تعد تستخدمها. هذه التدابير سوف تساعد في حماية البيئة.
مدة الصلاحية : 24 شهر

- المادة الفعالة هي فلوكونازول .كل مل يحتوي على 2 ملغ من فلوكونازول.
قارورة مع محلول 50 مل للتسريب يحتوي على 100 ملغ فلوكونازول.
- المكونات الأخرى هي: كلوريد الصوديوم ، الماء للحقن وهيدروكسيد الصوديوم (لضبط الرقم الهيدروجيني)

فلوكاس هو محلول شفاف، عديم اللون، و بدون جزيئات مرئية معبأ في قوارير زجاجية.

للحصول على أي معلومات حول هذا المنتج الطبي ، يرجى الاتصال بالممثل المحلي لصاحب الترخيص التسويقي:
مؤسسة الصالحية للتجارة

(المعدات الطبية والمستحضرات الطبية)
صندوق البريد: 991 ، الرياض 11421 - المملكة العربية السعودية
Tel: 00 966 1 46 46 955
الفاكس: 362 34 46 1 966 00

05/2018
 Read this leaflet carefully before you start using this product as it contains important information for you

Flukas 100, solution for infusion

Each ml contains 2 mg of fluconazole. Excipient: each ml also contains 4.5 mg sodium chloride. For a full list of excipients, see section 6.1

Solution for infusion Clear, colourless solution with no visible particles.

Flukas 100 is indicated in the following fungal infections (see section 5.1).

Flukas 100 is indicated in adults for the treatment of:
• Cryptococcal meningitis (see section 4.4).
• Coccidioidomycosis (see section 4.4).Invasive candidiasis.
Mucosal candidiasis including oropharyngeal, oesophageal candidiasis, candiduria and chronic mucocutaneous candidiasis.
• Chronic oral atrophic candidiasis (denture sore mouth) if dental hygiene topical treatment are insufficient.

Flukas 100 is indicated in adults for the prophylaxis of:
• Relapse of crytopcoccal meningitis in patients with high risk of recurrence.
• Relapse of oropharyngeal or oesophageal candidiasis in patients infected with HIV who are at high risk of experiencing relapse.
• Prophylaxis of candidal infections in patients with prolonged neutropenia (such as patients with haematological malignancies receiving chemotherapy or patients receiving Hematopoietic Stem Cell Transplantation (see section 5.1).

Flukas 100 is indicated in term newborn infants, infants, toddlers, children and adolescents aged from 0 to 17 years old:

Flukas 100 is used for the treatment of mucosal candidiasis (oropharyngeal, oesophageal), invasive candidiasis, cryptococcal meningitis and the prophylaxis of candidal infections in immunocompromised patients.

Flukas 100 can be used as maintenance therapy to prevent relapse of cryptococcal meningitis in children with high risk of reoccurrence (see section 4.4). Therapy may be instituted before the results of the cultures and other laboratory studies are known; however, once these results become available, anti-infective therapy should be adjusted accordingly.

Consideration should be given to official guidance on the appropriate use of antifungals.


The dose should be based on the nature and severity of the fungal infection. Treatment of infections requiring multiple dosing should be continued until clinical parameters or laboratory tests indicate that active fungal infection has subsided. An inadequate period of treatment may lead to recurrence of active infection.

Adults:

Special populations

Elderly

Dosage should be adjusted based on the renal function (see “Renal impairment”).

Renal impairment

Flukas 100 is predominantly excreted in the urine as unchanged active substance. No adjustments in single dose therapy are necessary. In patients (including paediatric population) with impaired renal function who will receive multiple doses of fluconazole, an initial dose of 50 mg to 400 mg should be given, based on the recommended daily dose for the indication. After this initial loading dose, the daily dose (according to indication) should be based on the following table:

Patients on regular dialysis should receive 100% of the recommended dose after each dialysis; on non-dialysis days, patients should receive a reduced dose according to their creatinine clearance

Hepatic impairment

Limited data are available in patients with hepatic impairment, therefore fluconazole should be administered with caution to patients with liver dysfunction (see sections 4.4 and 4.8).

Paediatric population:

A maximum dose of 400 mg daily should not be exceeded in paediatric population. As with similar infections in adults, the duration of treatment is based on the clinical and mycological response.

Flukas100 is administered as a single daily dose.

For paediatric patients with impaired renal function, see dosing in “Renal impairment”. The pharmacokinetics of fluconazole has not been studied in paediatric population with renal insufficiency (for “Term newborn infants” who often exhibit primarily renal immaturity please see below).

Infants, toddlers and children (from 28 days to 11 years old)

Adolescents (from 12 to 17 years old):

Depending on the weight and pubertal development, the prescriber would need to assess which posology (adults or children) is the most appropriate. Clinical data indicate that children have a higher fluconazole clearance than observed for adults. A dose of 100, 200 and 400 mg in adults corresponds to a 3, 6 and 12 mg/kg dose in children to obtain a comparable systemic exposure.

Term newborn infants (0 to 27 days):

Neonates excrete fluconazole slowly. There are few pharmacokinetic data to support this posology in term newborn infants (see section 5.2).

Method of administration

Intravenous infusion should be administrated at a rate not exceeding 10 ml/minute. Flukas100 is formulated in sodium chloride 9 mg/ml (0.9%) solution for infusion, each 200 mg (50 ml bottle) containing 15 mmol each of Na+ and C1-.

Because Flukas100 is available as a dilute sodium chloride solution, in patients requiring sodium or fluid restriction, consideration should be given to the rate of fluid administration.

For instruction on handling of the product, see section 6.6.


Hypersensitivity to the active substance to related azole substances, or to any of the excipients (see section 6.1). Coadministration of terfenadine is contraindicated in patients receiving Flukas100 at multiple doses of 400 mg per day or higher based upon results of a multiple dose interaction study. Coadministration of other medicinal products known to prolong the QT interval and which are metabolised via the cytochrome P450 (CYP) 3A4 such as cisapride, astemizole, pimozide, quinidine and erythromycin are contraindicated in patients receiving fluconazole (see sections 4.4 and 4.5).

Tinea capitis

Fluconazole has been studied for treatment of tinea capitisin children. It was shown not to be superior to griseofulvin and the overall success rate was less than 20%. Therefore, Flukas 100 should not be used for tinea capitis.

Cryptococcosis

The evidence for efficacy of fluconazole in the treatment of cryptococcosis of other sites (e.g. pulmonary and cutaneous cryptococcosis) is limited, which prevents dosing recommendations.

Deep endemic mycoses

The evidence for efficacy of fluconazole in the treatment of other forms of endemic mycoses such as paracoccidioidomycosis, lymphocutaneous sporotrichosisand histoplasmosisis limited, which prevents specific dosing recommendations.

Renal system

Flukas100 should be administered with caution to patients with renal dysfunction (see section 4.2).

Hepatobiliary system

Flukas100 should be administered with caution to patients with liver dysfunction. Flukas100 has been associated with rare cases of serious hepatic toxicity including fatalities, primarily in patients with serious underlying medical conditions. In cases of fluconazole associated hepatotoxicity, no obvious relationship to total daily dose, duration of therapy, sex or age of patient has been observed. Fluconazole hepatotoxicity has usually been reversible on discontinuation of therapy.

Patients who develop abnormal liver function tests during fluconazole therapy must be monitored closely for the development of more serious hepatic injury.

The patient should be informed of suggestive symptoms of serious hepatic effect (important asthenia, anorexia, persistent nausea, vomiting and jaundice). Treatment of fluconazole should be immediately discontinued and the patient should consult a physician.

Cardiovascular system

Some azoles, including fluconazole, have been associated with prolongation of the QT interval on the electrocardiogram. During post-marketing surveillance, there have been very rare cases of QT prolongation and torsades de pointesin patients taking Flukas100. These reports included seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities and concomitant treatment that may have been contributory.
Flukas100 should be administered with caution to patients with these potentially proarrhythmic conditions. Coadministration of other medicinal products known to prolong the QT interval and which are metabolised via the cytochrome P450 (CYP) 3A4 are contraindicated (see sections 4.3 and 4.5).

Halofantrine

Halofantrine has been shown to prolong QTc interval at the recommended therapeutic dose and is a substrate of CYP3A4. The concomitant use of fluconazole and halofantrine is therefore not recommended (see section 4.5).

Dermatological reactions

Patients have rarely developed exfoliative cutaneous reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, during treatment with fluconazole. AIDS patients are more prone to the development of severe cutaneous reactions to many medicinal products. If a rash, which is considered attributable to fluconazole, develops in a patient treated for a superficial fungal infection, further therapy with this medicinal product should be discontinued. If patients with invasive/systemic fungal infections develop rashes, they should be monitored closely and fluconazole discontinued if bullous lesions or erythemamultiforme develop.

Hypersensitivity

In rare cases anaphylaxis has been reported (see section 4.3).

Cytochrome P450

Fluconazole is a potent CYP2C9 inhibitor and a moderate CYP3A4 inhibitor. Fluconazole is also an inhibitor of CYP2C19. Flukas100 treated patients who are concomitantly treated with medicinal products with a narrow therapeutic window metabolised through CYP2C9, CYP2C19 and CYP3A4, should be monitored (see section 4.5).

Terfenadine

The coadministration of fluconazole at doses lower than 400 mg per day with terfenadine should be carefully monitored (see sections 4.3 and 4.5).

Excipients

This medicinal product contains 0.154 mmol sodium per ml. To be taken into consideration by patients on a controlled sodium diet


Concomitant use of the following other medicinal products is contraindicated: Cisapride: There have been reports of cardiac events including torsades de pointes in patients to whom fluconazole and cisapride were coadministered. A controlled study found that concomitant fluconazole 200 mg once daily and cisapride 20 mg four times a day yielded a significant increase in cisapride plasma levels and prolongation of QTc interval. Concomitant treatment with fluconazole and cisapride is contraindicated (see section 4.3).

Terfenadine: Because of the occurrence of serious cardiac dysrhythmias secondary to prolongation of the QTc interval in patients receiving azole antifungals in conjunction with terfenadine, interaction studies have been performed. One study at a 200 mg daily dose of fluconazole failed to demonstrate a prolongation in QTc interval. Another study at a 400 mg and 800 mg daily dose of fluconazole demonstrated that fluconazole taken in doses of 400 mg per day or greater significantly increases plasma levels of terfenadine when taken concomitantly. The combined use of fluconazole at doses of 400 mg or greater with terfenadine is contraindicated (see section 4.3). The coadministration of fluconazole at doses lower than 400 mg per day with terfenadine should be carefully monitored.

Astemizole: Concomitant administration of fluconazole with astemizole may decrease the clearance of astemizole. Resulting increased plasma concentrations of astemizole can lead to QT prolongation and rare occurrences of torsades de pointes. Coadministration of fluconazole and astemizole is contraindicated (see section 4.3).

Pimozide: Although not studied in vitro or in vivo, concomitant administration of fluconazole with pimozide may result in inhibition of pimozide metabolism. Increased pimozide plasma concentrations can lead to QT prolongation and rare occurrences of torsades de pointes. Coadministration of fluconazole and pimozide is contraindicated (see section 4.3).
 

Quinidine: Although not studied in vitro or in vivo, concomitant administration of fluconazole with quinidine may result in inhibition of quinidine metabolism. Use of quinidine has been associated with QT prolongation and rare occurrences of torsades de pointes. Coadministration of fluconazole and quinidine is contraindicated (see section 4.3).

Erythromycin: Concomitant use of fluconazole and erythromycin has the potential to increase the risk of cardiotoxicity (prolonged QT interval, torsades de pointes) and consequently sudden heart death. Coadministration of fluconazole and erythromycin is contraindicated (see section 4.3).

Concomitant use of the following other medicinal products cannot be recommended:

Halofantrine: Fluconazole can increase halofantrine plasma concentration due to an inhibitory effect on CYP3A4. Concomitant use of fluconazole and halofantrine has the potential to increase the risk of cardiotoxicity (prolonged QT interval, torsades de pointes) and consequently sudden heart death. This combination should be avoided (see section 4.4).

Concomitant use that should be used with caution:

Amiodarone: Concomitant administration of fluconazole with amiodarone may increase QT prolongation. Caution must be exercised if the concomitant use of fluconazole and amiodarone is necessary, notably with high dose fluconazole (800 mg).

Concomitant use of the following other medicinal products lead to precautions and dose adjustments:

The effect of other medicinal products on fluconazole

Rifampicin: Concomitant administration of fluconazole and rifampicin resulted in a 25% decrease in the AUC and a 20% shorter half-life of fluconazole. In patients receiving concomitant rifampicin, an increase of the fluconazole dose should be considered.

Interaction studies have shown that when oral fluconazole is coadministered with food, cimetidine, antacids or following total body irradiation for bone marrow transplantation, no clinically significant impairment of fluconazole absorption occurs.

Hydrochlorothiazide: In a pharmacokinetic interaction study, coadministration of multiple-dose hydrochlorothiazide to healthy volunteers receiving fluconazole increased plasma concentration of fluconazole by 40%. An effect of this magnitude should not necessitate a change in the fluconazole dose regimen in subjects receiving concomitant diuretics.

The effect of fluconazole on other medicinal products

Fluconazole is a moderate inhibitor of cytochrome P450 (CYP) isoenzymes 2C9 and 3A4. Fluconazole is also a strong inhibitor of the isozyme CYP2C19. In addition to the observed/documented interactions mentioned below, there is a risk of increased plasma concentration of other compounds metabolised by CYP2C9, CYP2C19 and CYP3A4 coadministered with fluconazole. Therefore, caution should be exercised when using these combinations and the patients should be carefully monitored. The enzyme inhibiting effect of fluconazole persists 4-5 days after discontinuation of fluconazole treatment due to the long half-life of fluconazole (see section 4.3).

Alfentanil: During concomitant treatment with fluconazole (400 mg) and intravenous alfentanil (20 μg/kg) in healthy volunteers the alfentanil AUC 10 increased 2-fold, probably through inhibition of CYP3A4.

Dose adjustment of alfentanil may be necessary.

Amitriptyline, nortriptyline: Fluconazole increases the effect of amitriptyline and nortriptyline. 5-nortriptyline and/or S-amitriptyline may be measured at initiation of the combination therapy and after one week. Dose of amitriptyline/nortriptyline should be adjusted, if necessary.

Amphotericin B: Concurrent administration of fluconazole and amphotericin B in infected normal and immunosuppressed mice showed the following results: a small additive antifungal effect in systemic infection with C. albicans, no interaction in intracranial infection with Cryptococcus neoformans, and antagonism of the two medicinal products in systemic infection with Aspergillus fumigatus. The clinical significance of results obtained in these studies is unknown.

Anticoagulants: In post-marketing experience, as with other azole antifungals, bleeding events (bruising, epistaxis, gastrointestinal bleeding, hematuria, and melena) have been reported, in association with increases in prothrombin time in patients receiving fluconazole concurrently with warfarin. During concomitant treatment with fluconazole and warfarin the prothrombin time was prolonged up to 2-fold, probably due to an inhibition of the warfarin metabolism through CYP2C9. In patients receiving coumarin-type or indanedione anticoagulants concurrently with fluconazole the prothrombin time should be carefully monitored. Dose adjustment of the anticoagulant may be necessary.

Benzodiazepines (short acting), i.e. midazolam, triazolam: Following oral administration of midazolam, fluconazole resulted in substantial increases in midazolam concentrations and psychomotor effects. Concomitant intake of fluconazole 200 mg and midazolam 7.5 mg orally increased the midazolam AUC and half-life 3.7-fold and 2.2-fold, respectively. Fluconazole 200 mg daily given concurrently with triazolam 0.25 mg orally increased the triazolam AUC and half-life 4.4-fold and 2.3-fold, respectively. Potentiated and prolonged effects of triazolam have been observed at concomitant treatment with fluconazole. If concomitant benzodiazepine therapy is necessary in patients being treated with fluconazole, consideration should be given to decreasing the benzodiazepine dose, and the patients should be appropriately monitored.

Carbamazepine: Fluconazole inhibits the metabolism of carbamazepine and an increase in serum carbamazepine of 30% has been observed. There is a risk of developing carbamazepine toxicity. Dose adjustment of carbamazepine may be necessary depending on concentration measurements/effect.

Calcium channel blockers: Certain calcium channel antagonists (nifedipine, isradipine, amlodipine, verapamil and felodipine) are metabolised by CYP3A4. Fluconazole has the potential to increase the systemic exposure of the calcium channel antagonists. Frequent monitoring for adverse events is recommended.

Celecoxib: During concomitant treatment with fluconazole (200 mg daily) and celecoxib (200 mg) the celecoxib Cmax and AUC increased by 68% and 134%, respectively. Half of the celecoxib dose may be necessary when combined with fluconazole.

Cyclophosphamide: Combination therapy with cyclophosphamide and fluconazole results in an increase in serum bilirubin and serum creatinine. The combination may be used while taking increased consideration to the risk of increased serum bilirubin and serum creatinine.

Fentanyl: One fatal case of fentanyl intoxication due to possible fentanyl fluconazole interaction was reported. Furthermore, it was shown in healthy volunteers that fluconazole delayed the elimination of fentanyl significantly. Elevated fentanyl concentration may lead to respiratory depression. Patients should be monitored closely for the potential risk of respiratory depression. Dosage adjustment of fentanyl may be necessary.

HMG CoA reductase inhibitors: The risk of myopathy and rhabdomyolysis increases when fluconazole is coadministered with HMG-CoA reductase inhibitors metabolised through CYP3A4, such as atorvastatin and simvastatin, or through CYP2C9, such as fluvastatin. If concomitant therapy is necessary, the patient should be observed for symptoms of myopathy and rhabdomyolysis and creatine kinase should be monitored. HMG-CoA reductase inhibitors should be discontinued if a marked increase in creatine kinase is observed or myopathy/rhabdomyolysis is diagnosed or suspected.

Olaparib: Moderate inhibitors of CYP3A4 such as fluconazole increase olaparib plasma concentrations; concomitant use is not recommended. If the combination cannot be avoided, limit the dose of olaparib to 200 mg twice daily.

Immunosuppresors (i.e. ciclosporin, everolimus, sirolimus and tacrolimus):

Ciclosporin: Fluconazole significantly increases the concentration and AUC of ciclosporin. During concomitant treatment with fluconazole 200 mg daily and ciclosporin (2.7 mg/kg/day) there was a 1.8-fold increase in ciclosporin AUC. This combination may be used by reducing the dose of ciclosporin depending on ciclosporin concentration.

Everolimus: Although not studied in vivo or in vitro, fluconazole may increase serum concentrations of everolimus through inhibition of CYP3A4.

Sirolimus: Fluconazole increases plasma concentrations of sirolimus presumably by inhibiting the metabolism of sirolimus via CYP3A4 and P-glycoprotein. This combination may be used with a dose adjustment of sirolimus depending on the effect/concentration measurements.

Tacrolimus: Fluconazole may increase the serum concentrations of orally administered tacrolimus up to 5 times due to inhibition of tacrolimus metabolism through CYP3A4 in the intestines. No significant pharmacokinetic changes have been observed when tacrolimus is given intravenously. Increased tacrolimus levels have been associated with nephrotoxicity. Dose of orally administered tacrolimus should be decreased depending on tacrolimus concentration.

Losartan: Fluconazole inhibits the metabolism of losartan to its active metabolite (E-31 74) which is responsible for most of the angiotensin II-receptor antagonism which occurs during treatment with losartan. Patients should have their blood pressure monitored continuously.

Methadone: Fluconazole may enhance the serum concentration of methadone. Dose adjustment of methadone may be necessary.

Non-steroidal anti-inflammatory drugs: The Cmax and AUC of flurbiprofen was increased by 23% and 81%, respectively, when coadministered with fluconazole compared to administration of flurbiprofen alone. Similarly, the Cmax and AUC of the pharmacologically active isomer [S-(+)-ibuprofen] was increased by 15% and 82%, respectively, when fluconazole was coadministered with racemic ibuprofen (400 mg) compared to administration of racemic ibuprofen alone.

Although not specifically studied, fluconazole has the potential to increase the systemic exposure of other NSAIDs that are metabolised by CYP2C9 (e.g. naproxen, lornoxicam, meloxicam, diclofenac). Frequent monitoring for adverse events and toxicity related to NSAIDs is recommended. Adjustment of dose of NSAIDs may be needed.

Phenytoin: Fluconazole inhibits the hepatic metabolism of phenytoin. Concomitant repeated administration of 200 mg fluconazole and 250 mg phenytoin intravenously, caused an increase of the phenytoin AUC24 by 75% and Cmin by 128%. With coadministration, serum phenytoin concentration levels should be monitored in order to avoid phenytoin toxicity.

Prednisone: There was a case report that a liver-transplanted patient treated with prednisone developed acute adrenal cortex insufficiency when a three month therapy with fluconazole was discontinued. The discontinuation of fluconazole presumably caused an enhanced CYP3A4 activity which led to increased metabolism of prednisone. Patients on long-term treatment with fluconazole and prednisone should be carefully monitored for adrenal cortex insufficiency when fluconazole is discontinued.

Rifabutin: Fluconazole increases serum concentrations of rifabutin, leading to increase in the AUC of rifabutin up to 80%. There have been reports of uveitis in patients to whom fluconazole and rifabutin were coadministered. In combination therapy, symptoms of rifabutin toxicity should be taken into consideration.

Saquinavir: Fluconazole increases the AUC and Cmax of saquinavir with approximately 50% and 55% respectively, due to inhibition of saquinavir's hepatic metabolism by CYP3A4 and inhibition of P-glycoprotein. Interaction with saquinavir/ritonavir has not been studied and might be more marked. Dose adjustment of saquinavir may be necessary.

Sulfonylureas: Fluconazole has been shown to prolong the serum half-life of concomitantly administered oral sulfonylureas (e.g., chlorpropamide, glibenclamide, glipizide, tolbutamide) in healthy volunteers. Frequent monitoring of blood glucose and appropriate reduction of sulfonylurea dose is recommended during coadministration.

Theophylline: In a placebo controlled interaction study, the administration of fluconazole 200 mg for 14 days resulted in an 18% decrease in the mean plasma clearance rate of theophylline. Patients who are receiving high dose theophylline or who are otherwise at increased risk for theophylline toxicity should be observed for signs of theophylline toxicity while receiving fluconazole. Therapy should be modified if signs of toxicity develop.

Vinca alkaloids: Although not studied, fluconazole may increase the plasma levels of the vinca alkaloids (e.g. vincristine and vinblastine) and lead to neurotoxicity, which is possibly due to an inhibitory effect on CYP3A4.

Vitamin A: Based on a case-report in one patient receiving combination therapy with all-trans-retinoid acid (an acid form of vitamin A) and fluconazole, CNS related undesirable effects have developed in the form of pseudotumour cerebri, which disappeared after discontinuation of fluconazole treatment. This combination may be used but the incidence of CNS related undesirable effects should be borne in mind.
Voriconazole: (CYP2C9, CYP2C19 and CYP3A4 inhibitor): Coadministration of oral voriconazole (400 mg Q12h for 1 day, then 200 mg Q12h for 2.5 days) and oral fluconazole (400 mg on day 1, then 200 mg Q24h for 4 days) to 8 healthy male subjects resulted in an increase in Cmax and AUC of voriconazole by an average of 57% (90% CI: 20%, 107%) and 79% (90% CI: 40%, 128%), respectively. The reduced dose and/or frequency of voriconazole and fluconazole that would eliminate this effect have not been established. Monitoring for voriconazole associated adverse events is recommended if voriconazole is used sequentially after fluconazole.

Zidovudine: Fluconazole increases Cmax and AUC of zidovudine by 84% and 74%, respectively, due to an approx. 45% decrease in oral zidovudine clearance. The half-life of zidovudine was likewise prolonged by approximately 128% following combination therapy with fluconazole. Patients receiving this combination should be monitored for the development of zidovudine-related adverse reactions. Dose reduction of zidovudine may be considered.

Azithromycin: An open-label, randomized, three-way crossover study in 18 healthy subjects assessed the effect of a single 1200 mg oral dose of azithromycin on the pharmacokinetics of a single 800 mg oral dose of fluconazole as well as the effects of fluconazole on the pharmacokinetics of azithromycin. There was no significant pharmacokinetic interaction between fluconazole and azithromycin.

Oral contraceptives: Two pharmacokinetic studies with a combined oral contraceptive have been performed using multiple doses of fluconazole. There were no relevant effects on hormone level in the 50 mg fluconazole study, while at 200 mg daily, the AUCs of ethinyl estradiol and levonorgestrel were increased 40% and 24%, respectively. Thus, multiple dose use of fluconazole at these doses is unlikely to have an effect on the efficacy of the combined oral contraceptive.

Ivacaftor: Co-administration with ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, increased ivacaftor exposure by 3-fold and hydroxymethyl-ivacaftor (M1) exposure by 1.9-fold. A reduction of the ivacaftor dose to 150 mg once daily is recommended for patients taking concomitant moderate CYP3A inhibitors, such as fluconazole and erythromycin.


Pregnancy

An observational study has suggested an increased risk of spontaneous abortion in women treated with fluconazole during the first trimester.

There have been reports of multiple congenital abnormalities (including brachycephalia, ears dysplasia, giant anterior fontanelle, femoral bowing and radio-humeral synostosis) in infants whose mothers were treated for at least three or more months with high doses (400-800 mg daily) of fluconazole for coccidioidomycosis. The relationship between fluconazole use and these events is unclear.

Studies in animals have shown reproductive toxicity (see section 5.3).

Fluconazole in standard doses and short-term treatments should not be used in pregnancy unless clearly necessary.

Fluconazole in high dose and/or in prolonged regimens should not be used during pregnancy except for potentially life-threatening infections.

Breast-feeding

Fluconazole passes into breast milk to reach concentrations similar to those in plasma (see section 5.2). Breast-feeding may be maintained after a single dose of 150 mg fluconazole. Breast-feeding is not recommended after repeated use or after high dose fluconazole. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for fluconazole and any potential adverse effects on the breast-fed child from fluconazole or from the underlying maternal condition.

Fertility

Fluconazole did not affect the fertility of male or female rats (see section 5.3).


No studies have been performed on the effects of Flukas 100 on the ability to drive or use machines.

Patients should be warned about the potential for dizziness or seizures (see section 4.8) while taking Flukas 100 and should be advised not to drive or operate machines if any of these symptoms occur.


The most frequently (>1/10) reported adverse reactions are headache, abdominal pain, diarrhoea, nausea, vomiting, alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased and rash. The following adverse reactions have been observed and reported during treatment with Flukas with the following frequencies: 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).

* including Fixed Drug Eruption

Paediatric Population The pattern and incidence of adverse reactions and laboratory abnormalities recorded during paediatric clinical trials are comparable to those seen in adults.


There have been reports of overdose with Flukas 100 and hallucination and paranoid behaviour have been concomitantly reported.

In the event of overdose, symptomatic treatment (with supportive measures and gastric lavage if necessary) may be adequate.

Fluconazole is largely excreted in the urine; forced volume diuresis would probably increase the elimination rate. A three-hour haemodialysis session decreases plasma levels by approximately 50%.


ATC classification

Pharmacotherapeutic group: Antimycotics for systemic use, triazole derivatives,

ATC code: J02AC01.

Mode of action

Fluconazole is a triazole antifungal agent. Its primary mode of action is the inhibition of fungal cytochrome P-450-mediated 14 alpha-lanosterol demethylation, an essential step in fungal ergosterol biosynthesis. The accumulation of 14 alpha-methyl sterols correlates with the subsequent loss of ergosterol in the fungal cell membrane and may be responsible for the antifungal activity of fluconazole. Fluconazole has been shown tobe more selective for fungal cytochrome P-450 enzymes than for various mammalian cytochrome P-450 enzyme systems. Fluconazole 50 mg daily given up to 28 days has been shown not to effect testosteroneplasma concentrations in males or steroid concentration in females of child-bearing age. Fluconazole 200 mg to400 mg daily has no clinically significant effect on endogenous steroid levels or on ACTH stimulated response in healthy male volunteers. Interaction studies with antipyrine indicate that single or multiple doses of fluconazole 50 mg do not affect its metabolism.

Susceptibility in vitro

In vitro, fluconazole displays antifungal activity against most clinically common Candida species (including C. albicans, C. parapsilosis, C. tropicalis). C. glabrata shows a wide range of susceptibility while C. krusei is resistant to fluconazole. Fluconazole also exhibits activity in vitro against Cryptococcus neoformans and Cryptococcus gattii as well as the endemic moulds Blastomyces dermatiditis, Coccidioides immitis, Histoplasma capsulatum and Paracoccidioides brasiliensis.

PK/PD relationship

In animal studies, there is a correlation between MIC values and efficacy against experimental mycoses due to Candidaspp. In clinical studies, there is an almost 1:1 linear relationship between the AUC and the dose of fluconazole. There is also a direct though imperfect relationship between the AUC or dose and a successful clinical response of oral candidosis and to a lesser extent candidaemia to treatment. Similarly cure is less likely for infections caused by strains with a higher fluconazole MIC.

Mechanism(s) of resistance

Candidaspp have developed a number of resistance mechanisms to azole antifungal agents. Fungal strains which have developed one or more of these resistance mechanisms are known to exhibit high minimum inhibitory concentrations (MICs) to fluconazole which impacts adversely efficacy in vivo and clinically. There have been reports of superinfection with Candidaspecies other than C. albicans, which are often inherently not susceptible to fluconazole (e.g. Candida krusei). Such cases may require alternative antifungal therapy.

Breakpoints (according to EUCAST)

Based on analyses of pharmacokinetic/pharmacodynamic (PK/PD) data, susceptibility in vitro and clinical response EUCAST-AFST (European Committee on Antimicrobial susceptibility Testing-subcommittee on Antifungal Susceptibility Testing) has determined breakpoints for fluconazole for Candidaspecies (EUCAST Fluconazole rational document (2007)-version 2). These have been divided into non-species related breakpoints; which have been determined mainly on the basis of PK/PD data and are independent of MIC distributions of specific species, and species related breakpoints for those species most frequently associated with human infection. These breakpoints are given in the table below:

S = Susceptible, R = Resistant

A. = Non-species related breakpoints have been determined mainly on the basis of PK/PD data and are independent of MIC distributions of specific species. They are for use only for organisms that do not have specific breakpoints. --= Susceptibility testing not recommended as the species is a poor target for therapy with the medicinal product.

IE = There is insufficient evidence that the species in question is a good target for therapy with the medicinal product.


The pharmacokinetic properties of fluconazole are similar following administration by the intravenous or oral route.

Absorption

After oral administration fluconazole is well absorbed, and plasma levels (and systemic bioavailability) are over 90% of the levels achieved after intravenous administration. Oral absorption is not affected by concomitant food intake. Peak plasma concentrations in the fasting state occur between 0.5 and 1.5 hours post-dose. Plasma concentrations are proportional to dose. Ninety percent steady state levels are reached by day 4-5 with multiple once daily dosing. Administration of a loading dose (on day 1) of twice the usual daily dose enables plasma levels to approximate to 90% steady-state levels by day 2.

Distribution

The apparent volume of distribution approximates to total body water. Plasma protein binding is low (11-12%). Fluconazole achieves good penetration in all body fluids studied. The levels of fluconazole in saliva and sputum are similar to plasma levels. In patients with fungal meningitis, fluconazole levels in the CSF are approximately 80% the corresponding plasma levels.

High skin concentration of fluconazole, above serum concentrations, are achieved in the stratum corneum, epidermis-dermis and eccrine sweat. Fluconazole accumulates in the stratum corneum. At a dose of 50 mg once daily, the concentration of fluconazole after 12 days was 73 μg/g and 7 days after cessation of treatment the concentration was still 5.8 μg/g. At the 150 mg once-a-week dose, the concentration of fluconazole in stratum corneum on day 7 was 23.4 μg/g and 7 days after the second dose was still 7.1 μg/g.

Concentration of fluconazole in nails after 4 months of 150 mg once-a-week dosing was4.05 μg/g in healthy and 1.8 μg/g in diseased nails; and, fluconazole was still measurable in nail samples 6 months after the end of therapy.

Biotransformation

Fluconazole is metabolised only to a minor extent. Of a radioactive dose, only 11% isexcreted in a changed form in the urine. Fluconazole is a selective inhibitor of the isozymes CYP2C9 and CYP3A4 (see section 4.5). Fluconazole is also an inhibitor of the isozyme CYP2C19.

Excretion

Plasma elimination half-life for fluconazole is approximately 30 hours. The major route of excretion is renal, with approximately 80% of the administered dose appearing in the urine as unchanged medicinal product. Fluconazole clearance is proportional to creatinine clearance. There is no evidence of circulating metabolites. The long plasma elimination half-life provides the basis for single dose therapy for vaginal candidiasis, once daily and once weekly dosing for other indications.

Pharmacokinetics in renal impairment

In patients with severe renal insufficiency, (GFR< 20 ml/min) half life increased from 30 to 98 hours. Consequently, reduction of the dose is needed. Fluconazole is removed by haemodialysis and to a lesser extent by peritoneal dialysis. After three hours of haemodialysis session, around 50% of fluconazole is eliminated from blood.

Pharmacokinetics during lactation

A pharmacokinetic study in ten lactating women, who had temporarily or permanently stopped breast-feeding their infants, evaluated fluconazole concentrations in plasma and breast milk for 48 hours following a single 150 mg dose of fluconazole. Fluconazole was detected in breast milk at an average concentration of approximately 98% of those in maternal plasma. The mean peak breast milk concentration was 2.61 mg/L at 5.2 hours post-dose. The estimated daily infant dose of fluconazole from breast milk (assuming mean milk consumption of 150 ml/kg/day) based on the mean peak milk concentration is 0.39 mg/kg/day, which is approximately 40% of the recommended neonatal dose (<2 weeks of age) or 13% of the recommended infant dose for mucosal candidiasis.

Pharmacokinetics in children

Pharmacokinetic data were assessed for 113 paediatric patients from 5 studies; 2 single-dose studies, 2 multiple-dosestudies, and a study in premature neonates. Data from one study were not interpretable due to changes in formulation pathway through the study. Additional data were available from a compassionate use study.

After administration of 2-8 mg/kg fluconazole to children between the ages of 9 months to 15 years, an AUC of about 38 μg•h/ml was found per 1 mg/kg dose units. The average fluconazole plasma elimination half-life varied between 15 and 18 hours and the distribution volume was approximately 880 ml/kg after multiple doses. A higher fluconazole plasma elimination half-life of approximately 24 hours was found after a single dose.This is comparable with the fluconazole plasma elimination half-life after a single administration of 3 mg/kg i.v. to children of 11 days-11 months old. The distribution volume in this age group was about 950 ml/kg.

Experience with fluconazole in neonates is limited to pharmacokinetic studies in premature newborns. The mean age at first dose was 24 hours (range 9-36 hours) and mean birth weight was 0.9 kg (range 0.75-1.10 kg) for 12 pre-term neonates of average gestation around 28 weeks. Seven patients completed the protocol; a maximum of five 6 mg/kg intravenous infusions of fluconazole were administered every 72 hours. The mean half-life (hours) was 74 (range 44-185) on day 1 which decreased, with time to a mean of 53 (range 30-131) on day 7 and 47 (range 27-68) on day13.

The area under the curve (microgram.h/ml) was 271 (range 173-385) on day 1 and increased with a mean of 490 (range 292-734) on day 7 and decreased with a mean of 360 (range 167-
566) on day 13. The volume of distribution (ml/kg) was 1183 (range 1070-1470) on day 1 and increased, with time, to a mean of 1184 (range 510-2130) on day 7 and 1328 (range 1040-1680) on day 13.

Pharmacokinetics in elderly

A pharmacokinetic study was conducted in 22 subjects, 65 years of age or older receiving a single 50 mg oral dose of fluconazole. Ten of these patients were concomitantly receiving diuretics. The Cmaxwas 1.54 μg/ml and occurred at 1.3 hours post-dose. The mean AUC was 76.4 ± 20.3 μg•h/ml, and the mean terminal half-life was 46.2 hours.

These pharmacokinetic parameter values are higher than analogous values reported for normalyoung male volunteers.

Coadministation of diuretics did not significantly alter AUC or Cmax. In addition, creatinine clearance (74 ml/min), the percent of medicinal product recovered unchanged in urine (0-24 hr, 22%) and the fluconazole renal clearance estimates (0.124 ml/min/kg) for the elderly were generally lower than those of younger volunteers. Thus, the alteration of fluconazole disposition in the elderly appears to be related to reduced renal function characteristics of this group.


Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the human exposure indicating little relevance to clinical use.

Carcinogenesis

Fluconazole showed no evidence of carcinogenic potential in mice and rats treated orally for 24 months at doses of 2.5, 5, or 10 mg/kg/day (approximately 2-7 times the recommended human dose). Male rats treated with 5 and 10 mg/kg/day had an increased incidence of hepatocellular adenomas.

Reproductive toxicity

Fluconazole did not affect the fertility of male or female rats treated orally with daily doses of 5, 10, or 20 mg/kg or with parenteral doses of 5, 25, or 75 mg/kg. There were no foetal effects at 5 or 10 mg/kg; increases in foetal anatomical variants (supernumerary ribs, renal pelvis dilation) and delays in ossification were observed at 25 and 50 mg/kg and higher doses. At doses ranging from 80 mg/kg to 320 mg/kg embryolethality in rats was increased and foetal abnormalities included wavy ribs, cleft palate, and abnormal cranio-facial ossification.

The onset of parturition was slightly delayed at 20 mg/kg orally and dystocia and prolongation of parturition were observed in a few dams at 20 mg/kg and 40 mg/kg intravenously. The disturbances in parturition were reflected by a slight increase in the number of still-born pups and decrease of neonatal survival at these dose levels. These effects on parturation are consistent with the species specific oestrogen-lowering property produced by high doses of fluconazole. Such a hormone change has not been observed in women treated with fluconazole (see section 5.1).


Sodium chloride

Hydrochloride acid or sodium hydroxide for pH

adjustment Water for injection


This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.


24 months

Store the product in a temperature not exceeding 30°C.


Type I glass vial


Fluconazole intravenous infusion is compatible with the following administration fluids:
a) Dextrose 5% and 20%
b) Ringer's solution
c) Hartmann's solution
d) Potassium chloride in dextrose
e) Sodium bicarbonate 4.2% and 5%

f) Aminosyn 3.5%
g) Sodium chloride 4.5 mg/ml
h) Dialaflex (interperitoneal dialysis Soln 6.36%)
Fluconazole may be infused through an existing line with one of the above listed fluids. Although no specific incompatibilities have been noted, mixing with any other medicinal products prior to infusion is not recommended.

The solution for infusion is for single use only.

The dilution is to be made under aseptic conditions. The solution is to be inspected visually for particulate matter and discoloration prior to administration. The solution should only be used if the solution is clear and free from particles.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.


Les Laboratoires « MédiS »; Route de Tunis km 7 – BP 206 – 8000 Nabeul, Tunisie.

DATE OF REVISION OF THE TEXT: 05/2018
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