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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)

Dansetron contains a medicine called ondansetron. This belongs to a group of medicines called anti-emetics.

Dansetron is used for:

  •  Preventing nausea and vomiting caused by chemotherapy (in adults and children) or radiotherapy for cancer (adults only)
  •   Preventing nausea and vomiting after surgery.

Ask your doctor, nurse or pharmacist if you would like any further explanation about these uses.


Do not use Dansetron If

  •  You are taking apomorphine (used to treat Parkinson’s disease)
  • You are allergic (hypersensitive) to ondansetron or any of the other ingredients in Dansetron (listed in section 6).

If you are not sure, talk to your doctor, nurse or pharmacist before having Dansetron.

Warnings and precautions

Check with your doctor, nurse or pharmacist before having Dansetron if:

  •  You have ever had heart problems (e.g. congestive heart failure which causes shortness of breath and swollen ankles)
  •  You have an uneven heart beat (arrhythmias)
  •  You are allergic to medicines similar to ondansetron, such as granisetron or palonosetron
  •  You have liver problems
  •  You have a blockage in your gut
  •  You have problems with the levels of salts in your blood, such as potassium, sodium and magnesium.

If you are not sure if any of the above apply to you, talk to your doctor, nurse or pharmacist before having Dansetron.

Other medicines and Dansetron

Please tell your doctor, nurse or pharmacist if you are taking, or have recently taken, or might take any other medicines. This includes medicines that you buy without a prescription and herbal medicines. This is because Dansetron can affect the way some medicines work. Also some other medicines can affect the way Dansetron works.

In particular, tell your doctor, nurse or pharmacist if you are taking any of the following medicines:

  • Carbamazepine or phenytoin used to treat epilepsy
  • Rifampicin used to treat infections such as tuberculosis (TB)
  • Antibiotics such as erythromycin or ketoconazole
  • Anti-arrhythmic medicines used to treat an uneven heart beat
  • Beta-blocker medicines used to treat certain heart or eye problems, anxiety or prevent migraines
  • Tramadol, a pain killer
  • Medicines that affect the heart (such as haloperidol or methadone)
  • Cancer medicines (especially anthracyclines and trastuzumab)
  • SSRIs (selective serotonin reuptake inhibitors) used to treat depression and/or anxiety including fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram
  • SNRIs (serotonin noradrenaline reuptake inhibitors) used to treat depression and/or anxiety including venlafaxine, duloxetine

If you are not sure if any of the above applies to you, talk to your doctor, nurse or pharmacist before having Dansetron.

Dansetron should not be given in the same syringe or infusion (drip) as any other medication.

Pregnancy and breast-feeding

Only use during the first trimester of pregnancy after discussion with your doctor of the potential benefits and risks to you and your unborn baby of the different treatment options. This is because ondansetron can slightly increase the risk of a baby being born with cleft lip and/or cleft palate (openings or splits in the upper lip and/or the roof of the mouth). If you are already pregnant, think you might be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before having ondansetron. If you are a woman of childbearing potential you may be advised to use effective contraception.

Ondansetron is not to be used for the treatment of nausea and vomiting in pregnancy.

If a woman becomes pregnant while using ondansetron, pregnancy will have to be closely monitored taking into account the risk of congenital malformations.

Physicians must inform women who clinically require ondansetron treatment about the potential risks of birth defects associated with use during pregnancy.

Do not breast-feed if you have ondansetron. This is because small amounts pass into the mother’s milk. Ask your doctor for advice.

Dansetron contains sodium

Dansetron contains sodium. Each ml of Dansetron 4 mg/2 ml and 8 mg/4 ml Solution for Injection contains 0.157 mmol (3.611 mg) sodium. This medicine contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially ‘sodium-free’.


Dansetron Injection is normally given by a nurse or doctor. The dose you have been prescribed will depend on the treatment you are having.

To prevent nausea and vomiting from chemotherapy or radiotherapy in adults

On the day of chemotherapy or radiotherapy

  • The usual adult dose is 8 mg given by a slow injection into your vein or muscle, just before your treatment, and another 8 mg twelve hours later. After chemotherapy, your medicine will usually be given by mouth as an 8 mg ondansetron tablet or 10 ml (8 mg) ondansetron syrup.

On the following days

  •  The usual adult dose is one 8 mg tablet or 10 ml (8 mg) syrup taken twice a day
  •  This may be given for up to 5 days.

If your chemotherapy or radiotherapy is likely to cause severe nausea and vomiting, you may be given more than the usual dose of Dansetron. Your doctor will decide this.

To prevent nausea and vomiting from chemotherapy in children aged over 6 months and adolescents  

The doctor will decide the dose depending on the child’s size (body surface area) or weight.

On the day of chemotherapy

  • The first dose is given by an injection into the vein, just before your child’s treatment. After chemotherapy, your child’s medicine will usually be given by mouth twelve hours later, as ondansetron syrup or a ondansetron tablet.

On the following days

  • 2.5 ml (2 mg) syrup twice a day for small children and those weighing 10 kg or less.
  • One 4 mg tablet or 5 ml (4 mg) syrup twice a day for larger children and those weighing more than 10 kg.
  • Two 4 mg tablets or 10 ml (8 mg) syrup twice a day for teenagers (or those with a large body surface area).
  • These doses can be given for up to five days.

To prevent and treat nausea and vomiting after an operation

 Adult:

  • The usual dose for adults is 4 mg given by a slow injection into your vein or an injection into your muscle. For prevention, this will be given just before your operation.

Children:

  • For children aged over 1 month and adolescents the doctor will decide the dose. The maximum dose is 4 mg given as a slow injection into the vein. For prevention, this will be given just before the operation.

Patients with moderate or severe liver problems

The total daily dose should not be more than 8 mg.

If you keep feeling or being sick

Dansetron should start to work soon after having the injection. If you continue to be sick or feel sick, tell your doctor or nurse.

If you used more Dansetron than you should

Your doctor or nurse will give you or your child Dansetron Injection so it is unlikely that you or your child will receive too much. If you think you or your child have been given too much or have missed a dose, tell your doctor or nurse.


Like all medicines, Dansetron can cause side effects, although not everybody gets them.

Allergic reactions

If you have an allergic reaction, tell your doctor or a member of the medical staff straight away. The signs may include:

  • Sudden wheezing and chest pain or chest tightness
  • Swelling of your eyelids, face, lips, mouth or tongue
  • Skin rash - red spots or lumps under your skin (hives) anywhere on your body
  • Collapse.

Other side effects include:

 Very common (may affect more than 1 in 10 people)

  • Headache.

Common (may affect up to 1 in 10 people)

  • A feeling of warmth or flushing
  • Constipation
  • Changes to liver function test results (if you have ondansetron with a medicine called cisplatin, otherwise this side effect is uncommon)
  • Irritation and redness at the site of injection.

Uncommon (may affect up to 1 in 100 people)

  • Hiccups
  • Low blood pressure, which can make you feel faint or dizzy
  • Uneven heart beat
  • Chest pain
  • Fits
  • Unusual body movements or shaking.

Rare (may affect up to 1 in 1,000 people)

  •  Feeling dizzy or light headed
  •  Blurred vision
  •  Disturbance in heart rhythm (sometimes causing a sudden loss of consciousness).

Very rare (may affect up to 1 in 10,000 people)

  •  Poor vision or temporary loss of eyesight, which usually comes back within 20 minutes.

Keep this medicine out of the sight and reach of children.

Store below 30°C.

Protect from light.

Store in the original package.

When Dansetron Injection is diluted in intravenous fluids:

  •  It must be stored at 2-8°C for not more than 24 hours before the start of administration.
  •  It does not need to be protected from light during infusion.

Do not use this medicine after the expiry date which is stated on the package after “EXP”. The expiry date refers to the last day of that month.

Do not use this medicine if you notice any visible signs of deterioration.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.


The active substance is ondansetron hydrochloride dihydrate.

Each 2 ml of Dansetron 4 mg/2 ml Solution for Injection contains 5.02 mg ondansetron hydrochloride dihydrate equivalent to 4 mg ondansetron anhydrous.

Each 4 ml of Dansetron 8 mg/4 ml Solution for Injection contains 10.04 mg ondansetron hydrochloride dihydrate equivalent to 8 mg ondansetron anhydrous.

The other ingredients are sodium chloride, citric acid monohydrate, trisodium citrate dihydrate and water for injection.


Dansetron 4 mg/2 ml Solution for Injection is a clear colorless solution in 2 ml clear ampoules with green one-point-cut (OPC). Pack size: 5 Ampoules (2 ml). Dansetron 8 mg/4 ml Solution for Injection is a clear colorless solution in 5 ml clear ampoules with blue one-point-cut (OPC). Pack size: 5 Ampoules (4 ml).

Marketing Authorization Holder
Hikma Pharmaceuticals
Bayader Wadi El Seer
Industrial Area
P.O. Box 182400
Amman 11118, Jordan
Tel: + (962-6) 5802900
Fax: + (962-6) 5817102
Website: www.hikma.com
Manufacturer
Hikma Farmaceutica (Portugal), S.A.
Estrada do Rio Da Mó,
n.°8, 8A e 8B, Fervença
2705-906 Terrugem
Sintra, Portugal
Tel: + (351-2) 19608410
Fax: + (351-2) 19615102


This leaflet was last revised in 03/2021; version number SA1.0.
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

يحتوي دانسترون على دواء يسمى أوندانسيترون. ينتمي هذا الدواء إلى مجموعة الأدوية التي تسمى مضادات القيء.

يستخدم دانسترون من أجل:

  •  منع الغثيان والقيء الناتجان عن العلاج الكيميائي (عند البالغين والأطفال) أو العلاج الإشعاعي لعلاج السرطان (عند البالغين فقط)
  •  منع الغثيان والقيء بعد العملية الجراحية.

إذا كنت تريد المزيد من التوضيح حول هذه الاستخدامات، اسأل طبيبك، الممرض أو الصيدلي.

لا تستخدم دانسترون إذا:

  • كنت تتناول آبومورفين (يستخدم لعلاج مرض الباركنسون)
  • كنت تعاني من الحساسية (فرط الحساسية) لأوندانسيترون أو لأي من المواد الأخرى المستخدمة في تركيبة دانسترون (المذكورة في القسم 6).

تحدث مع طبيبك، الممرض أو الصيدلي قبل القيام بأخذ دانسترون، إذا لم تكن متأكداً.

الاحتياطات والتحذيرات

تحقق مع طبيبك، الممرض أو الصيدلي قبل القيام بأخذ دانسترون إذا:

  • كنت تعاني من مشاكل في القلب في أي وقت (مثل فشل القلب الاحتقاني الذي يسبب ضيق النفس وتورم الكاحلين)
  • كنت تعاني من نبضات غير منتظمة للقلب (اضطرابات نظم القلب)
  • كنت تعاني من الحساسية للأدوية المشابهة لأوندانسيترون، مثل غرانيسيترون أو بالونوسيترون
  • كنت تعاني من مشاكل في الكبد
  • كنت تعاني من انسداد معوي
  • كنت تعاني من مشاكل في مستويات الأملاح في دمك، مثل البوتاسيوم، الصوديوم والمغنيسيوم.

تحدث إلى طبيبك، الممرض أو الصيدلي قبل القيام بأخذ دانسترون، إذا لم تكن متأكدا إذا كان أي مِما سبق ينطبق عليك.

الأدوية الأخرى ودانسترون

الرجاء إخبار طبيبك، الممرض أو الصيدلي إذا كنت تتناول، أو تناولت مؤخراً، أو قد تتناول أية أدوية أخرى. يتضمن هذا الأدوية التي تقوم بشرائها من غير وصفة طبية والأدوية العشبية. هذا لأن دانسترون قد يؤثر على طريقة عمل بعض الأدوية. أيضاً قد تؤثر بعض الأدوية على طريقة عمل دانسترون.

على وجه الخصوص، أخبر طبيبك، الممرض أو الصيدلي إذا كنت تتناول أي من الأدوية التالية:

  •  الكاربامازيبين أو الفينيتوين اللّذان يستخدمان لعلاج الصَّرْع
  • الريفامبيسين الذي يستخدم لعلاج العدوى مثل السل
  • المضادات الحيوية مثل إيريثروميسين أو كيتوكونازول
  • الأدوية المضادة لاضطراب نظم القلب التي تستخدم لعالج النبضات الغير منتظمة للقلب
  •  أدوية حاصرات البيتا المستخدمة لعلاج مشاكل معينة في القلب أو العين، القلق أو منع الشقيقة
  • الترامادول، مسكن للألم
  • الأدوية التي تؤثر على القلب (مثل هالوبيريدول أو ميثادون)
  •  أدوية علاج السرطان (خاصة الأَنثراسيكلين والتراستوزماب)
  •  مثبطات استرداد السيريتونين الانتقائية التي تستخدم لعلاج الاكتئاب و/أو القلق من ضمنها فلوكسيتين، باروكسيتين، سيرترالين، فلوفوكسامين، سيتالوبرام، إيسيتالوبرام
  • مثبطات استرداد السيريتونين والنورإيبينيفرين التي تستخدم لعلاج الاكتئاب و/أو القلق من ضمنها فانلافاكسين، دولوكستين.

تحدث إلى طبيبك، الممرض أو الصيدلي قبل القيام بأخذ دانسترون إذا لم تكن متأكدا إذا كان أي من ما سبق ينطبق عليك.

لا يجب القيام بإعطاء دانسترون في نفس الحقنة أو التسريب (التسييل) مع أي دواء آخر.

الحمل والرضاعة

لا تستخدمي هذا الدواء خلال الثلث الأول من الحمل إلا بعد مناقشة الفوائد والأخطار المحتملة لخيارات العلاج الأخرى عليك وعلى جنينك. هذا لأن أوندانسيترون يمكن أن يزيد قليلاً من خطورة ولادة الطفل بشفة مشقوقة و/أو حنك مشقوق (فتحات أو تفككات في الشفة العليا و/أو سقف الفم). قومي بطلب النصيحة من طبيبكِ أو الصيدلي قبل القيام بأخذ أوندانسيترون، إذا كنتِ حاملاً بالفعل، تعتقدين بأنك حاملاً أو تخططين لذلك. إذا كنتِ امرأة قادرة على الإنجاب قد تُنصحين باستخدام وسائل منع حمل فعالة.

يجب عدم استخدام أوندانسيترون لعلاج الغثيان والقيء خلال الحمل.

إذا أصبحت المرأة حاملاً أثناء استخدام أوندانسيترون، سيتم مراقبة الحمل بعناية مع الأخذ بعين الاعتبار خطورة التشوه الخلقي الجنيني.

يجب على الطبيب الممارس إبلاغ النساء اللواتي يتطلب علاجهم سريرياً بالأوندانسيترون بمخاطر التشوهات الخلقية المحتملة المصاحبة للاستخدام خلال الحمل.

لا ترضعي طفلك إذا قمتِ بأخذ أوندانسيترون. هذا لأن كميات قليلة منه تنتقل إلى حليب الأم. قومي بطلب النصيحة من طبيبكِ.

يحتوي دانسترون على الصوديوم

يحتوي دانسترون على الصوديوم. يحتوي كل مللتر من دانسترون 4 ملغم/2 مللتر و8 ملغم/4 مللتر محلول للحقن على 0.157 ملمول (3.611 ملغم) صوديوم. يحتوي هذا الدواء على أقل من 1 ملمول صوديوم (23 ملغم) لكل مللتر، فيمكن اعتباره أنه ’خالٍ من الصوديوم‘ بشكل أساسي.

https://localhost:44358/Dashboard

يعطى دانسترون بطبيعة الحال من قبل الممرض أو الطبيب. تعتمد الجرعة الموصوفة لك على العلاج المقدم لك.

لمنع الغثيان والقيء الناتجان من العلاج الكيميائي أو العلاج الإشعاعي عند البالغين

في يوم موعد أخذ العلاج الكيميائي أو العلاج الإشعاعي

  • الجرعة المعتادة للبالغين هي 8 ملغم تعطى عن طريق الحقن البطيء في الوريد أو العضل لديك، قبل علاجك بالضبط، ثم تعطى جرعة 8 ملغم أخرى بعد 12 ساعة. بعد العلاج الكيميائي، سيتم إعطاؤك دواؤك عن طريق الفم على شكل قرص أوندانسيترون 8 ملغم أو شراب أوندانسيترون 10 مللتر (8 ملغم).

في الأيام التالية

  • الجرعة المعتادة للبالغين هي قرص واحد 8 ملغم أو شراب 10 مللتر (8 ملغم) مرتين في اليوم
  • قد تعطى هذه الجرعة لمدة تصل إلى 5 أيام.

قد يتم إعطاؤك أكثر من الجرعة المعتادة من دانسترون، إذا كان العلاج الكيميائي أو العلاج الإشعاعي يسبب بالعادة غثيان وقيء شديدان. سوف يقوم طبيبك بتقرير ذلك.

لمنع الغثيان والقيء الناتجان من العلاج الكيميائي عند الأطفال الذين يتعدى عمرهم 6 أشهر والمراهقين

سوف يقرر الطبيب الجرعة بالاعتماد على حجم الطفل (مساحة سطح الجسم) أو الوزن.

في يوم موعد أخذ العلاج الكيميائي

  • تعطى الجرعة الأولى عن طريق الحقن في الوريد، قبل العلاج الكيميائي لطفلك بالضبط. سيتم إعطاء طفلك الدواء عن طريق الفم بعد العلاج الكيميائي بـ 12 ساعة، على شكل شراب أو أقراص أوندانسيترون.

في الأيام التالية

  • تعطى جرعة 2.5 مللتر (2 ملغم) شراب مرتين في اليوم للأطفال الصغار وهؤلاء الذين يزنون 10 كغم أو أقل.
  • يعطى قرص واحد 4 ملغم أو 5 مللتر (4 ملغم) شراب مرتين في اليوم للأطفال الأكبر حجما والذين يزيد وزنهم عن 10 كغم.
  • يعطى قرصين 4 ملغم أو 10 مللتر (8 ملغم) شراب مرتين في اليوم للمراهقين (أو الذين مساحة سطح جسمهم كبيرة).
  • يمكن أن تعطى هذه الجرعات لمدة تصل إلى 5 أيام.

لمنع وعلاج الغثيان والقيء الناتجان بعد العملية الجراحية

البالغين:

  •  الجرعة المعتادة للبالغين هي 4 ملغم تعطى عن طريق الحقن البطيء في الوريد أو الحقن في العضل لديك. سوف تعطى هذه جرعة لك قبل عمليتك بالضبط، لمنع الغثيان والقيء.

الأطفال:

  •  سيقرر الطبيب جرعة الأطفال فوق عمر الشهر والمراهقين. الحد الأعلى للجرعة هو 4 ملغم تعطى عن طريق الحقن البطيء في الوريد. لمنع الغثيان والقيء، تعطى هذه جرعة قبل العملية مباشرة.

المرضى الذين يعانون من مشاكل متوسطة أو شديدة في الكبد

يجب ألا تتجاوز الجرعة الكلية اليومية 8 ملغم.

إذا كنت لا تزال تشعر أو مصاب بالإعياء  

يجب أن يبدأ مفعول دانسترون بعد أخذ الحقنة بفترة وجيزة. أخبر طبيبك أو الممرض، إذا كنت لا تزال مصاب أو تشعر بالإعياء. 

إذا استخدمت دانسترون أكثر من اللازم

سوف يقوم طبيبك أو الممرض بإعطاء دانسترون لك أو لطفلك فمن غير المحتمل تلقيك أو تلقي طفلك جرعة زائدة. أخبر طبيبك أو الممرض، إذا كنت تعتقد أنه قد تم إعطاؤك أو إعطاء طفلك جرعة زائدة أو أنه قد تم نسيان جرعة منه.

مثل جميع الأدوية، قد يسبب دانسترون آثاراً جانبيةً، إلا أنه ليس بالضرورة أن تحدث لدى جميع مستخدمي هذا الدواء.

ردود الفعل التحسسية

أخبر طبيبك أو أي عضو من الهيئة الطبية على الفور إذا كان لديك رد فعل تحسسي. قد تشمل الأعراض:

  •  صفير مفاجىء وألم في الصدر أو ضيق في الصدر
  •   تورم الجفون، الوجه، الشفاه، الفم أو اللسان
  •  طفح جلدي - بقع حمراء أو كتل تحت الجلد (الشرى) في أي مكان في جسمك
  •  هبوط.

آثار جانبية أخرى:

شائعة جدًا (قد تؤثر على أكثر من شخص من كل 10 أشخاص)

  • صداع.

شائعة (قد تؤثر على ما يصل إلى شخص واحد من كل 10 أشخاص)

  •  الشعور بالدفء أو التورّد
  •   الإمساك
  •   تغيّر في نتائج اختبار وظائف الكبد (إذا أخذت أوندانسيترون للحقن مع دواء يسمى سيسبلاتين، غير ذلك، تعتبر من الآثار الجانبية الغير شائعة)
  •   تهيج واحمرار عند موضع الحقن.

غير شائعة (قد تؤثر على ما يصل إلى شخص من كل 100 شخص)

  •   الفواق
  •   انخفاض ضغط الدم، الذي بإمكانه أن يؤدي إلى شعورك بالإغماء أو الدوخة
  •   نبضات قلب غير منتظمة
  •   ألم في الصدر
  •   نوبات تشنجية
  •  حركات غير اعتيادية للجسم أو الرجفان.

النادرة (قد تؤثر على ما يصل إلى شخص من بين كل 1000 شخص)

  •  الشعور بالدوخة أو الدوار
  •  تغيم الرؤية
  •   اضطرابات في نظم القلب (مما قد يؤدي في بعض الأحيان إلى فقدان وعي مفاجىء).

نادرة جدًا (قد تؤثر على ما يصل إلى شخص من بين كل 10000 شخص)

  •  رؤية سيئة أو فقدان مؤقت للبصر، الذي يعود خلال 20 دقيقة في العادة.

احفظ هذا الدواء بعيداً عن مرأى ومتناول الأطفال.

يحفظ عند درجة حرارة أقل من 30° مئوية.

احمه من الضوء.

يحفظ داخل العبوة الأصلية.

عند تخفيف دانسترون للحقن في السوائل الوريدية:

  • يجب أن يحفظ عند درجة حرارة 2-8° مئوية لمدة لا تزيد عن 24 ساعة قبل بدأ الإعطاء.
  • لا يحتاج للحماية من الضوء أثناء التسريب.

لا تستخدم هذا الدواء بعد تاريخ انتهاء الصلاحية المذكور على العبوة الخارجية بعد "EXP". يشير تاريخ انتهاء الصلاحية إلى اليوم الأخير من ذلك الشهر.

لا تستخدم هذا الدواء إذا لاحظت أي علامات تلف واضحة عليه.

لا تتخلص من الأدوية عن طريق مياه الصرف الصحي أو النفايات المنزلية. اسأل الصيدلي عن كيفية التخلص من الأدوية التي لم تعد بحاجة إليها. اتبع هذه الإجراءات للحفاظ على سلامة البيئة.

المادة الفعالة هي هيدروكلوريد الأوندانسيترون ثنائي الماء.

يحتوي كل 2 مللتر من دانسترون 4 ملغم/2 مللتر محلول للحقن على 5.02 ملغم هيدروكلوريد الأوندانسيترون ثنائي الماء يكافئ 4 ملغم أوندانسيترون لامائي.

يحتوي كل 4 مللتر من دانسترون 8 ملغم/4 مللتر محلول للحقن على 10.04 ملغم هيدروكلوريد الأوندانسيترون ثنائي الماء يكافئ 8 ملغم أوندانسيترون لامائي.

المواد الأخرى المستخدمة في التركيبة التصنيعية هي كلوريد الصوديوم، حمض السيتريك أحادي الماء، سیترات ثلاثي الصوديوم ثنائي الماء وماء معد للحقن.

دانسترون 4 ملغم/2 مللتر محلول للحقن هو محلول صافي عديم اللون في أمبولات شفافة بحجم 2 مللتر مع نقطة كسر واحدة خضراء اللون.

حجم العبوة: 5 أمبولات (2 مللتر).

دانسترون 8 ملغم/4 مللتر محلول للحقن هو محلول صافي عديم اللون في أمبولات شفافة بحجم 5 مللتر مع نقطة كسر واحدة زرقاء اللون.

حجم العبوة: 5 أمبولات (4 مللتر).

اسم وعنوان مالك رخصة التسويق
شركة أدوية الحكمة
بيادر وادي السير
المنطقة الصناعية
صندوق بريد 182400
عمان 11118، الأردن
هاتف: 5802900 (6-962) +
فاكس: 5817102 (6-962) +
الموقع الإلكتروني: www.hikma.com

الشركة المصنعة

شركة أدوية الحكمة (البرتغال)
إسترادا دو ريو دا مو،

مبنى رقم 8, 8A e 8B، فارفانسا
2705-906 تيروجيم

سنترا، البرتغال
هاتف: 19608410 (2-351) +
فاكس: 19615102 (2-351) +

تمت مراجعة هذه النشرة بتاريخ 03/2021؛ رقم النسخة SA1.0.
 Read this leaflet carefully before you start using this product as it contains important information for you

Dansetron 4 mg/2 ml Solution for Injection

Each 2 ml contains 5.02 mg ondansetron hydrochloride dihydrate equivalent to 4 mg ondansetron anhydrous. Excipient(s) with known effect: Sodium. For a full list of excipients, see section 6.1.

Solution for injection. Clear colorless solution.

Adults:

Dansetron is indicated for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy. Dansetron is indicated for the prevention and treatment of post-operative nausea and vomiting (PONV).

 

Paediatric Population:

Dansetron is indicated for the management of chemotherapy-induced nausea and vomiting (CINV) in children aged ≥ 6 months, and for the prevention and treatment of PONV in children aged ≥ 1 month.


Posology

Chemotherapy and Radiotherapy induced nausea and vomiting (CINV and RINV)

Adults:

The emetogenic potential of cancer treatment varies according to the doses and combinations of chemotherapy and radiotherapy regimens used. The route of administration and dose of Dansetron should be flexible in the range of 8-32 mg a day and selected as shown below.

  •  Emetogenic chemotherapy and radiotherapy: Ondansetron can be given either by intravenous administration.

 

For most patients receiving emetogenic chemotherapy or radiotherapy, the recommended intravenous (IV) dose of ondansetron is 8 mg and should be administered as a slow intravenous injection (in not less than 30 seconds) or intramuscular injection, immediately before treatment, followed by 8 mg orally twelve hourly.

 

To protect against delayed or prolonged emesis after the first 24 hours, oral or rectal treatment with ondansetron should be continued for up to 5 days after a course of treatment.

  •   Highly emetogenic chemotherapy: For patients receiving highly emetogenic chemotherapy, e.g. high- dose cisplatin, ondansetron can be given either by oral, rectal, intravenous or intramuscular administration. Ondansetron has been shown to be equally effective in the following dose schedules over the first 24 hours of chemotherapy:

  -    A single dose of 8 mg by slow intravenous injection (in not less than 30 seconds) or intramuscular injection immediately before chemotherapy.

 

-     A dose of 8 mg by slow intravenous injection (in not less than 30 seconds) or intramuscular injection immediately before chemotherapy, followed by two further intravenous injection (in not less than 30 seconds) or intramuscular doses of 8 mg four hours apart, or by a constant infusion of 1 mg/hour for up to 24 hours.

 

-    A maximum initial intravenous dose of 16 mg diluted in 50-100 ml of saline or other compatible infusion fluid (see section 6.6) and infused over not less than 15 minutes immediately before chemotherapy. The initial dose of ondansetron may be followed by two additional 8 mg intravenous doses (in not less than 30 seconds) or intramuscular doses four hours apart.

 

A single dose greater than 16 mg must not be given due to dose dependent increase of QT- prolongation risk (see sections 4.4, 4.8 and 5.1).

 

The selection of dose regimen should be determined by the severity of the emetogenic challenge. The efficacy of ondansetron in highly emetogenic chemotherapy may be enhanced by the addition of a single intravenous dose of dexamethasone sodium phosphate, 20 mg administered prior to chemotherapy.

 

To protect against delayed or prolonged emesis after the first 24 hours, oral or rectal treatment with ondansetron should be continued for up to 5 days after a course of treatment.

 

Paediatric Population:

  •  CINV in children and adolescents (aged 6 months to 17 years)

The dose for CINV can be calculated based on body surface area (BSA) or weight – see below. In paediatric clinical studies, ondansetron was given by IV infusion diluted in 25 to 50 ml of saline or other compatible infusion fluid and infused over not less than 15 minutes.

 

Weight-based dosing results in higher total daily doses compared to BSA-based dosing (sections 4.4.and 5.1).

 

Dansetron injection should be diluted in 5% glucose or 0.9% sodium chloride or other compatible infusion fluid (see section 6.6) and infused intravenously over not less than 15 minutes.

 

There are no data from controlled clinical trials on the use of ondansetron in the prevention of delayed or prolonged CINV. There are no data from controlled clinical trials on the use of ondansetron for radiotherapy-induced nausea and vomiting in children.

 

Dosing by BSA:

Dansetron should be administered immediately before chemotherapy as a single intravenous dose of 5 mg/m2. The single intravenous dose must not exceed 8 mg.

 

Oral dosing can commence 12 hours later and may be continued for up to 5 days (Table 1).

 

The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32 mg.

 

Table 1: BSA-based dosing for CINV (aged ≥ 6 months to 17 years)

BSA

Day 1 (a,b)

Days 2-6 (b)

< 0.6 m2

5 mg/m2 IV plus

2 mg syrup after 12 hrs

2 mg syrup every 12 hrs

≥ 0.6 m2 to ≤ 1.2 m2

5 mg/m2 IV plus

4 mg syrup or tablet after 12 hrs

4 mg syrup or tablet every 12 hrs

> 1.2 m2

5 mg/m2 or 8 mg IV plus 8 mg syrup or tablet after 12 hours

8 mg syrup or tablet every 12 hours

a The intravenous dose must not exceed 8 mg.

b The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32 mg

 

Dosing by bodyweight:

Weight-based dosing results in higher total daily doses compared to BSA-based dosing (sections 4.4. and 5.1).

 

Dansetron should be administered immediately before chemotherapy as a single intravenous dose of 0.15 mg/kg. The single intravenous dose must not exceed 8 mg. Two further intravenous doses may be given in 4-hourly intervals.

 

Oral dosing can commence 12 hours later and may be continued for up to 5 days (Table 2).

 

The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32 mg.

 

Table 2: Weight-based dosing for CINV (aged ≥ 6 months to 17 years)

Weight

Day 1 (a,b)

Days 2-6 (b)

≤ 10 kg

Up to 3 doses of 0.15 mg/kg IV every 4 hrs

2 mg syrup every 12 hrs

> 10 kg

Up to 3 doses of 0.15 mg/kg IV every 4 hrs

4 mg syrup or tablet every 12 hrs

a The intravenous dose must not exceed 8 mg.

b The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32 mg.

 

Elderly:

In patients 65 to 74 years of age, the dose schedule for adults can be followed. All intravenous doses should be diluted in 50-100 ml of saline or other compatible infusion fluid (see section 6.6) and infused over 15 minutes.

 

In patients 75 years of age or older, the initial intravenous dose of Dansetron should not exceed 8 mg. All intravenous doses should be diluted in 50-100 ml of saline or other compatible infusion fluid (see section 6.6) and infused over 15 minutes. The initial dose of 8 mg may be followed by two further intravenous doses of 8 mg, infused over 15 minutes and given no less than four hours apart (see section 5.2).

 

Patients with Renal Impairment:

No alteration of daily dosage or frequency of dosing, or route of administration are required.

 

Patients with Hepatic Impairment:

Clearance of ondansetron is significantly reduced and serum half-life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients a total daily dose of 8 mg should not be exceeded and therefore parenteral or oral administration is recommended.

 

Patients with Poor Sparteine/Debrisoquine Metabolism:

The elimination half-life of ondansetron is not altered in subjects classified as poor metabolisers of sparteine and debrisoquine. Consequently in such patients repeat dosing will give drug exposure levels no different from those of the general population. No alteration of daily dosage or frequency of dosing is required.

 

Post-Operative Nausea and Vomiting (PONV):

Adults:

For the prevention of PONV, ondasetron can be administered orally or by intravenous or intramuscular injection.

 

The recommended dose is as a single dose of 4 mg given by intramuscular or slow intravenous injection at induction of anaesthesia.

 

For treatment of established PONV, A single dose of 4 mg given by intramuscular or slow intravenous injection is recommended.

 

Paediatric population:

  •  PONV in children and adolescents (aged 1 month to 17 years)

For prevention of PONV in paediatric patients having surgery performed under general anaesthesia, a single dose of Dansetron may be administered by slow intravenous injection (not less than 30 seconds) at a dose of 0.1 mg/kg up to a maximum of 4 mg either prior to, at or after induction of anaesthesia.

 

For the treatment of PONV after surgery in paediatric patients having surgery performed under general anaesthesia, a single dose of Dansetron may be administered by slow intravenous injection (not less than 30 seconds) at a dose of 0.1 mg/kg up to a maximum of 4 mg.

 

There are no data on the use of ondansetron in the treatment of PONV in children below 2 years of age.

 

Elderly:

There is limited experience in the use of ondansetron in the prevention and treatment of PONV in the elderly, however ondansetron is well tolerated in patients over 65 years receiving chemotherapy.

 

Patients with Renal Impairment:

No alteration of daily dosage or frequency of dosing, or route of administration are required.

 

Patients with Hepatic Impairment:

Clearance of ondansetron is significantly reduced and serum half-life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients a total daily dose of 8 mg should not be exceeded and therefore parenteral or oral administration is recommended.

 

Patients with poor Sparteine/Debrisoquine Metabolism:

The elimination half-life of ondansetron is not altered in subjects classified as poor metabolisers of sparteine and debrisoquine. Consequently in such patients repeat dosing will give drug exposure levels no different from those of the general population. No alteration of daily dosage or frequency of dosing are required.


Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Concomitant use with apomorphine is contraindicated (see section 4.5 interactions).

Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5HT3 receptor antagonists.

 

Respiratory events should be treated symptomatically and clinicians should pay particular attention to them as precursors of hypersensitivity reactions.

 

Ondansetron prolongs the QT interval in a dose-dependent manner (see section 5.1). In addition, post- marketing cases of Torsade de Pointes have been reported in patients using ondansetron. Avoid ondansetron in patients with congenital long QT syndrome. Ondansetron should be administered with caution to patients who have or may develop prolongation of QTc, including patients with electrolyte abnormalities, congestive heart failure, bradyarrhythmias or patients taking other medicinal products that lead to QT prolongation or electrolyte abnormalities.

 

Hypokalaemia and hypomagnesaemia should be corrected prior to ondansetron administration.

 

There have been post-marketing reports describing patients with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following the concomitant use of ondansetron and other serotonergic drugs (including selective serotonin reuptake inhibitors (SSRI) and serotonin noradrenaline reuptake inhibitors (SNRIs) (see section 4.5)). If concomitant treatment with ondansetron and other serotonergic drugs is clinically warranted, appropriate observation of the patient is advised.

 

As ondansetron is known to increase large bowel transit time, patients with signs of sub-acute intestinal obstruction should be monitored following administration.

 

In patients with adenotonsillar surgery prevention of nausea and vomiting with ondansetron may mask occult bleeding. Therefore, such patients should be followed carefully after ondansetron.

 

Dansetron contain sodium

Dansetron contain sodium. Each ml contains 0.157 mmol (3.611 mg) sodium. This medicine contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially ‘sodium-free’.

 

Paediatric Population:

Paediatric patients receiving ondansetron with hepatotoxic chemotherapeutic agents should be monitored closely for impaired hepatic function.

 

CINV:

When calculating the dose on an mg/kg basis and administering three doses at 4-hour intervals, the total daily dose will be higher than if one single dose of 5 mg/m2 followed by an oral dose is given. The comparative efficacy of these two different dosing regimens has not been investigated in clinical trials. Cross-trial comparison indicates similar efficacy for both regimens (section 5.1).

 


There is no evidence that ondansetron either induces or inhibits the metabolism of other drugs commonly co-administered with it. Specific studies have shown that there are no interactions when ondansetron is administered with alcohol, temazepam, furosemide, alfentanil, tramadol, morphine, lidocaine, thiopental, or propofol.

 

Ondansetron is metabolised by multiple hepatic cytochrome P-450 enzymes: CYP3A4, CYP2D6 and CYP1A2. Due to the multiplicity of metabolic enzymes capable of metabolising ondansetron, enzyme inhibition or reduced activity of one enzyme (e.g. CYP2D6 genetic deficiency) is normally compensated by other enzymes and should result in little or no significant change in overall ondansetron clearance or dose requirement.

 

Caution should be exercised when ondansetron is coadministered with drugs that prolong the QT interval and/or cause electrolyte abnormalities. (See section 4.4).

 

Use of ondansetron with QT prolonging drugs may result in additional QT prolongation. Concomitant use of ondansetron with cardiotoxic drugs (e.g. anthracyclines (such as doxorubicin, daunorubicin) or trastuzumab), antibiotics (such as erythromycin), antifungals (such as ketoconazole), antiarrhythmics (such as amiodarone) and beta blockers (such as atenolol or timolol) may increase the risk of arrhythmias. (See section 4.4).

 

Serotonergic Drugs (e.g. SSRIs and SNRIs): There have been post-marketing reports describing patients with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following the concomitant use of ondansetron and other serotonergic drugs (including SSRIs and SNRIs) (See section 4.4).

 

Apomorphine: Based on reports of profound hypotension and loss of consciousness when ondansetron was administered with apomorphine hydrochloride, concomitant use with apomorphine is contraindicated.

 

Phenytoin, Carbamazepine and Rifampicin: In patients treated with potent inducers of CYP3A4 (i.e. phenytoin, carbamazepine, and rifampicin), the oral clearance of ondansetron was increased and ondansetron blood concentrations were decreased.

 

Tramadol: Data from small studies indicate that ondansetron may reduce the analgesic effect of tramadol.

 


Women of childbearing potential

Women of childbearing potential should consider the use of contraception.

 

Pregnancy

Based on human experience from epidemiological studies, ondansetron is suspected to cause orofacial malformations when administered during the first trimester of pregnancy.

 

In one cohort study including 1.8 million pregnancies, first trimester ondansetron use was associated with an increased risk of oral clefts (3 additional cases per 10 000 women treated; adjusted relative risk, 1.24, (95% CI 1.03-1.48)).

 

The available epidemiological studies on cardiac malformations show conflicting results.

 

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

 

Ondansetron should not be used during the first trimester of pregnancy.

 

Breast-feeding

Tests have shown that ondansetron passes into the milk of lactating animals. It is therefore recommended that mothers receiving Dansetron should not breast-feed their babies.

 

Fertility

There is no information on the effects of ondansetron on human fertility.


In psychomotor testing ondansetron does not impair performance nor cause sedation. No detrimental effects on such activities are predicted from the pharmacology of ondansetron.


Tabulated list of adverse reactions

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000) and very rare (<1/10,000). Very common, common and uncommon events were generally determined from clinical trial data. The incidence in placebo was taken into account. Rare and very rare events were generally determined from post-marketing spontaneous data.

 

The following frequencies are estimated at the standard recommended doses of ondansetron. The adverse event profiles in children and adolescents were comparable to that seen in adults.

Immune system disorders

Rare:

Immediate hypersensitivity reactions sometimes severe, including anaphylaxis.

Nervous system disorders

Very common:

Headache.

Uncommon:

Seizures, movement disorders (including extrapyramidal reactions such as dystonic reactions, oculogyric crisis and dyskinesia) (1).

Rare:

Dizziness predominantly during rapid IV administration.

Eye disorders

Rare:

Transient visual disturbances (e.g. blurred vision) predominantly during IV administration.

Very rare:

Transient blindness predominantly during intravenous administration (2).

Cardiac disorders

Uncommon:

Arrhythmias, chest pain with or without ST segment depression, bradycardia.

Rare:

QTc prolongation (including Torsade de Pointes).

Vascular disorders

Common:

Sensation of warmth or flushing.

Uncommon:

Hypotension.

Respiratory, thoracic and mediastinal disorders

Uncommon:

Hiccups.

Gastrointestinal disorders

Common:

Constipation.

Hepatobiliary disorders

Uncommon:

Asymptomatic increases in liver function tests (3).

General disorders and administration site conditions

Common:

Local IV injection site reactions.

1. Observed without definitive evidence of persistent clinical sequelae.

2. The majority of the blindness cases reported resolved within 20 minutes. Most patients had received chemotherapeutic agents, which included cisplatin. Some cases of transient blindness were reported as cortical in origin.

3. These events were observed commonly in patients receiving chemotherapy with cisplatin.

 

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

  • Saudi Arabia

The National Pharmacovigilance Centre (NPC)

SFDA Call Center: 19999

E-mail: npc.drug@sfda.gov.sa

Website: https://ade.sfda.gov.sa

  •  Other GCC States

Please contact the relevant competent authority.


Symptoms and Signs

There is limited experience of ondansetron overdose. In the majority of cases, symptoms were similar to those already reported in patients receiving recommended doses (see section 4.8). Manifestations that have been reported include visual disturbances, severe constipation, hypotension and a vasovagal episode with transient second-degree AV block.

 

Ondansetron prolongs the QT interval in a dose-dependent fashion. ECG monitoring is recommended in cases of overdose.

 

Paediatric population

Paediatric cases consistent with serotonin syndrome have been reported after inadvertent oral overdoses of ondansetron (exceeded estimated ingestion of 4 mg/kg) in infants and children aged 12 months to 2 years.

 

Management

There is no specific antidote for ondansetron, therefore in all cases of suspected overdose, symptomatic and supportive therapy should be given as appropriate.

 

Further management should be as clinically indicated or as recommended by the national poisons centre, where available.

 

The use of ipecacuanha to treat overdose with ondansetron is not recommended, as patients are unlikely to respond due to the anti-emetic action of ondansetron itself.

 

 


Mechanism of Action

Ondansetron is a potent, highly selective 5HT3 receptor-antagonist. Its precise mode of action in the control of nausea and vomiting is not known. Chemotherapeutic agents and radiotherapy may cause release of 5HT in the small intestine initiating a vomiting reflex by activating vagal afferents via 5HT3 receptors. Ondansetron blocks the initiation of this reflex. Activation of vagal afferents may also cause a release of 5HT in the area postrema, located on the floor of the fourth ventricle, and this may also promote emesis through a central mechanism. Thus, the effect of ondansetron in the management of the nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy is probably due to antagonism of 5HT3 receptors on neurons located both in the peripheral and central nervous system.

 

The mechanisms of action in post-operative nausea and vomiting are not known but there may be common pathways with cytotoxic induced nausea and vomiting.

 

Ondansetron does not alter plasma prolactin concentrations.

 

Clinical safety and efficacy

The role of ondansetron in opiate-induced emesis is not yet established.

 

QT Prolongation

The effect of ondansetron on the QTc interval was evaluated in a double blind, randomised, placebo and positive (moxifloxacin) controlled, crossover study in 58 healthy adult men and women.

 

Ondansetron doses included 8 mg and 32 mg infused intravenously over 15 minutes. At the highest tested dose of 32 mg, the maximum mean (upper limit of 90% CI) difference in QTcF from placebo after baseline-correction was 19.6 (21.5) msec. At the lower tested dose of 8 mg, the maximum mean (upper limit of 90% CI) difference in QTcF from placebo after baseline-correction was 5.8 (7.8) msec.

 

In this study, there were no QTcF measurements greater than 480 msec and no QTcF prolongation was greater than 60 msec. No significant changes were seen in the measured electrocardiographic PR or QRS intervals.

 

Paediatric population

CINV

The efficacy of ondansetron in the control of emesis and nausea induced by cancer chemotherapy was assessed in a double-blind randomised trial in 415 patients aged 1 to 18 years (S3AB3006). On the days of chemotherapy, patients received either ondansetron 5 mg/m2 intravenous and ondansetron 4 mg orally after 8 to 12 hours or ondansetron 0.45 mg/kg intravenous and placebo orally after 8 to 12 hours. Post-chemotherapy both groups received 4 mg ondansetron syrup twice daily for 3 days. Complete control of emesis on worst day of chemotherapy was 49% (5 mg/m2 intravenous and ondansetron 4 mg orally) and 41% (0.45 mg/kg intravenous and placebo orally). Post-chemotherapy both groups received 4 mg ondansetron syrup twice daily for 3 days. There was no difference in the overall incidence or nature of adverse events between the two treatment groups.

 

A double-blind randomised placebo-controlled trial (S3AB4003) in 438 patients aged 1 to 17 years demonstrated complete control of emesis on worst day of chemotherapy in:

  •  73% of patients when ondansetron was administered intravenously at a dose of 5 mg/m2 intravenous together with 2 to 4 mg dexamethasone orally.
  •   71% of patients when ondansetron was administered as syrup at a dose of 8 mg together with 2 to 4 mg dexamethasone orally on the days of chemotherapy.

 

Post-chemotherapy both groups received 4 mg ondansetron syrup twice daily for 2 days. There was no difference in the overall incidence or nature of adverse events between the two treatment groups.

 

The efficacy of ondansetron in 75 children aged 6 to 48 months was investigated in an open-label, non-comparative, single-arm study (S3A40320). All children received three 0.15 mg/kg doses of intravenous ondansetron, administered 30 minutes before the start of chemotherapy and then at 4 and 8 hours after the first dose. Complete control of emesis was achieved in 56% of patients.

 

Another open-label, non-comparative, single-arm study (S3A239) investigated the efficacy of one intravenous dose of 0.15 mg/kg ondansetron followed by two oral ondansetron doses of 4 mg for children aged < 12 years and 8 mg for children aged ≥ 12 years (total no. of children n = 28). Complete control of emesis was achieved in 42% of patients.

 

PONV

The efficacy of a single dose of ondansetron in the prevention of post-operative nausea and vomiting was investigated in a randomised, double-blind, placebo-controlled study in 670 children aged 1 to 24 months (post-conceptual age ≥44 weeks, weight ≥ 3 kg). Included subjects were scheduled to undergo elective surgery under general anaesthesia and had an ASA status ≤ III. A single dose of ondansetron 0.1 mg/kg was administered within five minutes following induction of anaesthesia. The proportion of subjects who experienced at least one emetic episode during the 24-hour assessment period (ITT) was greater for patients on placebo than those receiving ondansetron (28% vs. 11%, p <0.0001).

 

Four double-blind, placebo-controlled studies have been performed in 1469 male and female patients (2 to 12 years of age) undergoing general anaesthesia. Patients were randomised to either single intravenous doses of ondansetron (0.1 mg/kg for paediatric patients weighing 40 kg or less, 4 mg for paediatric patients weighing more than 40 kg; number of patients = 735) or placebo (number of patients = 734). Study drug was administered over at least 30 seconds, immediately prior to or following anaesthesia induction. Ondansetron was significantly more effective than placebo in preventing nausea and vomiting. The results of these studies are summarised in Table 3.

 

Table 3: Prevention and treatment of PONV in Paediatric Patients – Treatment response over 24 hours

Study

Endpoint

Ondansetron %

Placebo %

p value

S3A380

CR

68

39

≤0.001

S3GT09

CR

61

35

≤0.001

S3A381

CR

53

17

≤0.001

S3GT11

no nausea

64

51

0.004

S3GT11

no emesis

60

47

0.004

CR = no emetic episodes, rescue or withdrawal


Following oral administration, ondansetron is passively and completely absorbed from the gastrointestinal tract and undergoes first pass metabolism. Peak plasma concentrations of about 30 ng/mL are attained approximately 1.5 hours after an 8 mg dose. For doses above 8 mg the increase in ondansetron systemic exposure with dose is greater than proportional; this may reflect some reduction in first pass metabolism at higher oral doses. Mean bioavailability in healthy male subjects, following the oral administration of a single 8 mg tablet, is approximately 55 to 60%. Bioavailability, following oral administration, is slightly enhanced by the presence of food but unaffected by antacids. Studies in healthy elderly volunteers have shown slight, but clinically insignificant, age-related increases in both oral bioavailability (65%) and half-life (5 hours) of ondansetron.

 

The disposition of ondansetron following oral, intramuscular and intravenous dosing in adults is similar with a terminal half-life of about 3 hours and steady state volume of distribution of about 140 l. Equivalent systemic exposure is achieved after intramuscular and intravenous administration of ondansetron.

 

A 4 mg intravenous infusion of ondansetron given over 5 minutes results in peak plasma concentrations of about 65 ng/ml. Following intramuscular administration of ondansetron, peak plasma concentrations of about 25 ng/ml are attained within 10 minutes of injection.

 

Following administration of ondansetron suppository, plasma ondansetron concentrations become detectable between 15 and 60 minutes after dosing. Concentrations rise in an essentially linear fashion, until peak concentrations of 20-30 ng/ml are attained, typically 6 hours after dosing. Plasma concentrations then fall, but at a slower rate than observed following oral dosing due to continued absorption of ondansetron. The absolute bioavailability of ondansetron from the suppository is approximately 60% and is not affected by gender. The half-life of the elimination phase following suppository administration is determined by the rate of ondansetron absorption, not systemic clearance and is approximately 6 hours. Females show a small, clinically insignificant, increase in half-life in comparison with males.

 

Distribution

Ondansetron is not highly protein bound (70-76%).

 

Biotransformation and Elimination

Ondansetron is cleared from the systemic circulation predominantly by hepatic metabolism through multiple enzymatic pathways. Less than 5% of the absorbed dose is excreted unchanged in the urine. The absence of the enzyme CYP2D6 (the debrisoquine polymorphism) has no effect on ondansetron's pharmacokinetics. The pharmacokinetic properties of ondansetron are unchanged on repeat dosing.

 

Special Patient Populations

Gender

Gender differences were shown in the disposition of ondansetron, with females having a greater rate and extent of absorption following an oral dose and reduced systemic clearance and volume of distribution (adjusted for weight).

 

Children and Adolescents (aged 1 month to 17 years)

In paediatric patients aged 1 to 4 months (n = 19) undergoing surgery, weight normalised clearance was approximately 30% slower than in patients aged 5 to 24 months (n = 22) but comparable to the patients aged 3 to 12 years. The half-life in the patient population aged 1 to 4 month was reported to average 6.7 hours compared to 2.9 hours for patients in the 5 to 24 month and 3 to 12 year age range. The differences in pharmacokinetic parameters in the 1 to 4 month patient population can be explained in part by the higher percentage of total body water in neonates and infants and a higher volume of distribution for water soluble drugs like ondansetron.

 

In paediatric patients aged 3 to 12 years undergoing elective surgery with general anaesthesia, the absolute values for both the clearance and volume of distribution of ondansetron were reduced in comparison to values with adult patients. Both parameters increased in a linear fashion with weight and by 12 years of age, the values were approaching those of young adults. When clearance and volume of distribution values were normalised by body weight, the values for these parameters were similar between the different age group populations. Use of weight-based dosing compensates for age- related changes and is effective in normalising systemic exposure in paediatric patients.

 

Population pharmacokinetic analysis was performed on 428 subjects (cancer patients, surgery patients and healthy volunteers) aged 1 month to 44 years following intravenous administration of ondansetron. Based on this analysis, systemic exposure (AUC) of ondansetron following oral or IV dosing in children and adolescents was comparable to adults, with the exception of infants aged 1 to 4 months. Volume was related to age and was lower in adults than in infants and children. Clearance was related to weight but not to age with the exception of infants aged 1 to 4 months. It is difficult to conclude whether there was an additional reduction in clearance related to age in infants 1 to 4 months or simply inherent variability due to the low number of subjects studied in this age group. Since patients less than 6 months of age will only receive a single dose in PONV a decreased clearance is not likely to be clinically relevant.

 

Elderly

Early Phase I studies in healthy elderly volunteers showed a slight age-related decrease in clearance, and an increase in half-life of ondansetron. However, wide inter-subject variability resulted in considerable overlap in pharmacokinetic parameters between young (< 65 years of age) and elderly subjects (≥ 65 years of age) and there were no overall differences in safety or efficacy observed between young and elderly cancer patients enrolled in CINV clinical trials to support a different dosing recommendation for the elderly.

 

Based on more recent ondansetron plasma concentrations and exposure-response modelling, a greater effect on QTcF is predicted in patients ≥ 75 years of age compared to young adults. Specific dosing information is provided for patients over 65 years of age and over 75 years of age for IV dosing (see section 4.2).

 

Renal Impairment

In patients with renal impairment (creatinine clearance 15-60 ml/min), both systemic clearance and volume of distribution are reduced following IV administration of ondansetron, resulting in a slight, but clinically insignificant, increase in elimination half-life (5.4 hours). A study in patients with severe renal impairment who required regular haemodialysis (studied between dialyses) showed ondansetron's pharmacokinetics to be essentially unchanged following intravenous administration.

 

Hepatic Impairment

Following oral, intravenous or intramuscular dosing in patients with severe hepatic impairment, ondansetron's systemic clearance is markedly reduced with prolonged elimination half-lives (15 to 32 hours) and an oral bioavailability approaching 100% due to reduced pre-systemic metabolism. The pharmacokinetics of ondansetron following administration as a suppository have not been evaluated in patients with hepatic impairment.

 


Embryo-fetal development studies in rats and rabbits, did not show evidence of harm to the fetus when ondansetron was administered during the period of organogenesisat approximately 6 and 24 times respectively the maximum recommended human oral dose of 24 mg/day, based on body surface area. In a pre- and postnatal developmental toxicity study, there were no effects upon the pregnant rats and the pre- and postnatal development of their offspring, including reproductive performance at approximately 6 times the maximum recommended human oral dose of 24 mg/day based on body surface area.


-    Sodium chloride

-    Citric acid monohydrate

-    Trisodium citrate dihydrate

-    Water for injection


Dansetron injection should not be administered in the same syringe or infusion as any other medication. Ondansetron injection should only be mixed with those infusion solutions that are recommended.

 


Unopened: 3 years. After dilution: It must be stored at 2-8°C for not more than 24 hours before the start of administration.

Store below 30°C.

 

Protect from light.

 

Store in the original package.


2 ml clear ampoules with green one-point-cut (OPC).

 

Pack size: 5 Ampoules (2 ml).


Dansetron injection should not be autoclaved.

 

Compatibility with intravenous fluids

Dansetron injection should only be mixed with those infusion solutions which are recommended, at a concentration higher than 0.8 mg/ml:

  • Sodium Chloride Intravenous Infusion 0.9% w/v
  • Glucose Intravenous Infusion 5% w/v
  • Ringers Intravenous Infusion
  • Potassium Chloride 0.3% w/v and Sodium Chloride 0.9% w/v Intravenous Infusion
  • Potassium Chloride 0.3% w/v and Glucose 5% w/v Intravenous Infusion

 

In keeping with good pharmaceutical practice dilutions of Dansetron injection in intravenous fluids should be prepared at the time of infusion or stored at 2-8°C for no more than 24 hours before the start of administration.

 

Compatibility studies have been undertaken in polyvinyl chloride infusion bags and polyvinyl chloride administration sets. It is considered that adequate stability would also be conferred by the use of polyethylene infusion bags or Type 1 glass bottles. Dilutions of Dansetron in sodium chloride 0.9%w/v or in glucose 5%w/v have been demonstrated to be stable in polypropylene containers. It is considered that Dansetron injection diluted with other compatible infusion fluids would be stable in polypropylene containers.

 

Compatibility with other drugs: 

Ondansetron may be administered by intravenous infusion at 1 mg/hour, e.g. from an infusion bag or syringe pump. The following drugs may be administered via the Y-site of the ondansetron giving set for ondansetron concentrations of 16 to 160 micrograms/ml (e.g. 8 mg/500 ml and 8 mg/50 ml respectively).

 

Cisplatin: Concentrations up to 0.48 mg/ml (e.g. 240 mg in 500 mL) administered over one to eight hours.

 

5-Fluorouracil: Concentrations up to 0.8 mg/ml (e.g. 2.4 g in 3 litres or 400 mg in 500 ml) administered at a rate of at least 20 ml per hour (500 mL per 24 hours). Higher concentrations of 5-fluorouracil may cause precipitation of ondansetron. The 5-fluorouracil infusion may contain up to 0.045% w/v magnesium chloride in addition to other excipients shown to be compatible.

 

Carboplatin: Concentrations in the range 0.18 mg/ml to 9.9 mg/ml (e.g. 90 mg in 500 ml to 990 mg in 100 ml), administered over ten minutes to one hour.

 

Etoposide: Concentrations in the range 0.14 mg/ml to 0.25 mg/ml (e.g. 72 mg in 500 ml to 250 mg in 1 litre), administered over thirty minutes to one hour.

 

Ceftazidime: Doses in the range 250 mg to 2000 mg reconstituted with Water for Injections BP as recommended by the manufacturer (e.g. 2.5 ml for 250 mg and 10 ml for 2 g ceftazidime) and given as an intravenous bolus injection over approximately five minutes.

 

Cyclophosphamide: Doses in the range 100 mg to 1 g, reconstituted with Water for Injections BP, 5 ml per 100 mg cyclophosphamide, as recommended by the manufacturer and given as an intravenous bolus injection over approximately five minutes.

 

Doxorubicin: Doses in the range 10-100 mg reconstituted with Water for Injections BP, 5 ml per 10 mg doxorubicin, as recommended by the manufacturer and given as an intravenous bolus injection over approximately 5 minutes.

 

Dexamethasone: Dexamethasone sodium phosphate 20 mg may be administered as a slow intravenous injection over 2-5 minutes via the Y-site of an infusion set delivering 8 or 16 mg of ondansetron diluted in 50-100 ml of a compatible infusion fluid over approximately 15 minutes. Compatibility between dexamethasone sodium phosphate and ondansetron has been demonstrated supporting administration of these drugs through the same giving set resulting in concentrations in line of 32 microgram - 2.5 mg/ml for dexamethasone sodium phosphate and 8 microgram - 1 mg/ml for ondansetron.


Hikma Pharmaceuticals Bayader Wadi El Seer Industrial Area P.O. Box 182400 Amman 11118, Jordan Tel: + (962-6) 5802900 Fax: + (962-6) 5817102 Website: www.hikma.com

25 April 2021
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