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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)

Ondans tablets contain a medicine called ondansetron. This belongs to a group of medicines called anti-emetics.

Ondans tablets are 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 (adults only).

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


Do not take Ondans tablets if:

·       you are taking apomorphine (used to treat Parkinson’s disease).

·       you are allergic (hypersensitive) to ondans or any of the other ingredients in Ondans tablets (listed in Section 6).

·       you have ever had any allergic (hypersensitive) reaction with other anti-emetics (for example granisetron or dolasetron)

If you are not sure, talk to your doctor, nurse, or pharmacist before taking Ondans tablets.

 

Warnings and precautions

Check with your doctor, nurse, or pharmacist before taking Ondans tablets if:

·       you have ever had heart problems (e.g., congestive heart failure which causes shortness of breath and swollen ankles).

·       you have an uneven heartbeat (arrhythmias).

·       you are allergic to medicines similar to ondans, 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.

·       you are due to have surgery to the adenoids or tonsils.

 

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

 

Other medicines and Ondans

Please tell your doctor, nurse, or pharmacist if you are taking or have recently taken or might take

other medicines. This includes medicines that you buy without a prescription and herbal medicines. This is because Ondans can affect the way some medicines work. Also, some other medicines can affect the way Ondans 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 heartbeat.

·       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 Ondans tablets.

 

Pregnancy and breast-feeding

You should not use Ondans during the first trimester of pregnancy. This is because Ondans 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 taking Ondans. It is recommended that sexually active women of childbearing potential use effective contraception (methods resulting in less than 1% pregnancy rate) during treatment with Ondans.

Do not breastfeed if you are using Ondans. This is because small amounts can get into breast milk. Ask your doctor for advice.

 

 

Important information about some of the ingredients of Ondans tablets

This medicine contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, speak to your doctor before taking this medicine.

 


Always take Ondans tablets exactly as your doctor has told you. You should check with your doctor, nurse, or pharmacist if you are not sure. The dose you have been prescribed will depend on the treatment you are having.

 

To prevent nausea and vomiting from chemotherapy or radiotherapy

 

On the day of chemotherapy or radiotherapy

·       the usual adult dose is 8 mg taken one to two hours before treatment and another 8 mg twelve hours after.

 

On the following days

·       the usual adult dose is 8 mg twice a day

·       this may be given for up to 5 days.

 

Children aged over 6 months and adolescents

The doctor will decide the dose depending on the child’s size (body surface area) or weight. Look at the label for more information.

·       the usual dose for a child is up to 4 mg twice a day

·       this can be given for up to 5 days.

 

To prevent nausea and vomiting after an operation

The usual adult dose is 16 mg before your operation

 

Children aged over 1 month and adolescents:

It is recommended that Ondans is given as an injection.

 

Patients with moderate or severe liver problems

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

 

Ondans tablets should start to work within one or two hours of taking a dose.

 

If you are sick (vomit) within one hour of taking a dose

·       take the same dose again

·       otherwise, do not take more Ondans tablets than the label says.

If you continue to feel sick, tell your doctor or nurse.

 

If you take more Ondans tablets than you should

If you or your child take more Ondans than you should, talk to a doctor or go to a hospital straight away. Take the medicine pack with you.

If you forget to take Ondans tablets

If you miss a dose and feel sick or vomit:

·       take Ondans tablets as soon as possible, then

·       take your next tablet at the usual time (as shown on the label)

·       do not take a double dose to make up for a forgotten dose.

 

If you miss a dose but do not feel sick

·       take the next dose as shown on the label

·       do not take a double dose to make up for a forgotten dose.

 

 


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

 

Allergic reactions

If you have an allergic reaction, stop taking it and see a doctor 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 take Ondans tablets with a medicine called cisplatin, otherwise this side effect is uncommon).

 

Uncommon (may affect up to 1 in 100 people)

·       hiccups

·       low blood pressure, which can make you feel faint or dizzy

·       uneven heartbeat

·       chest pain

·       fits

·       unusual body movements or shaking.

 

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

·       feeling dizzy or lightheaded

·       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.

 

Not known (cannot be estimated from the available data)

·       Myocardial ischemia

signs include:

§  sudden chest pain or

§  chest tightness

 

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via The National Pharmacovigilance and Drug Safety Centre (NPC). By reporting side affects you can help provide more information on the safety of this medicine.

 

 


 

·       Keep out of the reach and sight of children.

·       Do not use Ondans tablets after the expiry date which is stated on the pack after ‘EXP.’ The expiry date refers to the last day of that month.

·       Store below 30ºC.

·       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 ingredient is ondansetron. Each Ondans tablet contains ondansetron 4 mg or 8 mg (as hydrochloride dihydrate).

·       The other ingredients are Lactose NF Fast Flow-BMS 35957, Avicel PH 102, Starch 1500, and Magnesium Stearate.

·       Film-Coating: Opadry 20J22730 Yellow, Ethanol 96%, and Purified Water BP.


The Ondans 4 mg tablets are Pale yellow, round, biconvex, film-coated tablet, engraved with "91"on one side and plain on the other side. The Ondans 8 mg tablets are Pale yellow, round, biconvex, film-coated tablet, engraved with "92"on one side and plain on the other side. Ondans tablets come in: • White thermoformed PVC/PE/PVDC reel with hard tempered aluminum foil lid. • each unit carton contains 10 film-coated tablets.

SPIMACO

Al-Qassim pharmaceutical plant

Saudi Arabia.


August 2023.
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

أقراص اوندانس تحتوي على دواء يسمى اوندانسيترون. هذا الدواء ينتمي إلى مجموعة من الأدوية تسمي مضادات القئ.

 

تستخدم أقراص اوندانس في:

•       منع الغثيان والقيء الناجم عن العلاج الكيميائي (في البالغين والأطفال) أو العلاج الإشعاعي للسرطان (للبالغين فقط).

•       منع الغثيان والقيء بعد الجراحة (للبالغين فقط).

 

اسأل طبيبك، أو الممرضة أو الصيدلي إذا كنت تريد أي توضيح إضافي حول هذه الاستخدامات.

 

لا تتناول أقراص اوندانس إذا:

•       كنت تتناول ابومورفين (يستخدم لعلاج مرض شلل الرعاش).

•       كانت لديك حساسية (فرط حساسية) من اوندانس أو أي من المكونات الأخرى في أقراص اوندانس (المدرجة في الفقرة 6).

•       سبق أن عانيت من أي حساسية (فرط حساسية) مع مضادات القيء الأخرى (على سبيل المثال جرانيسترون أو دولاسترون)

إذا لم تكن متأكداً، تحدث إلى طبيبك أو الممرضة أو الصيدلي قبل تناول أقراص اوندانس.

 

التحذيرات والاحتياطات

تحقق مع طبيبك أو الممرضة أو الصيدلي قبل تناول أقراص اوندانس إذا:

•       كان لديك في أي وقت مضى مشاكل في القلب (مثل فشل القلب الاحتقاني الذي يسبب ضيق في التنفس وتورم الكاحلين)

•       كانت لديك دقات قلب غير منتظمة (اضطراب ضربات القلب)

•       كانت لديك حساسية من الأدوية المماثلة لاوندانس، مثل جرانيسيترون أو بالونوسيترون

•       كانت لديك مشاكل في الكبد

•       كان لديك انسداد في الأمعاء

•       كانت لديك مشاكل في مستويات الأملاح في الدم، مثل البوتاسيوم والصوديوم والماغنيسيوم.

•       إن كنت ستجري عملية إزالة اللوز أو اللحمية.

إذا لم تكن متأكداً مما إذا كان أي من أعلاه ينطبق عليك، تحدث إلى طبيبك أو الممرضة أو الصيدلي قبل تناول أقراص اوندانس.

 

الأدوية الأخرى واوندانس

فضلا أخبر طبيبك أو الممرضة أو الصيدلي إذا كنت تتناول، أو تناولت مؤخرا، أو قد تتناول أي أدوية أخرى. وهذا يشمل الأدوية التي تشتريها دون وصفه طبية، والأعشاب الطبية. وهذا لأن اوندانس من الممكن أن يؤثر على طريقة عمل بعض الأدوية.  أيضا بعض الأدوية الأخري من الممكن أن تؤثر على الطريقة التي يعمل بها اوندانس.

 

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

•       كاربامازبين أو الفينيتوين المستخدم لعلاج الصرع

•       الريفامبيسين والذي يستخدم لعلاج الالتهابات مثل الدرن (السل)

•       المضادات الحيوية مثل الاريثروميسين أو الكيتوكونازول

•       أدوية علاج اضطراب ضربات القلب المستخدمة لعلاج دقات القلب غير المنتظمة

•       أدوية مُحْصِرُ المُسْتَقْبِلاتِ البيتا المستخدمة لعلاج بعض مشاكل القلب أو العين، القلق أو منع الصداع النصفي

•       ترامادول، قاتل الألم

•       الأدوية التي تؤثر على القلب (مثل هالوبيريدول أو الميثادون)

•       أدوية السرطان (وبخاصة أنثراسيكلينيس وتراستوزوماب)

•       إس إس أرأي (مثبطات امتصاص السيروتونين) يستخدم لعلاج الاكتئاب أو القلق بما في ذلك فلوكستين، باروكسيتين، سيرترالين، فلوڨوكسامين، سيتالوبرام، اسيتالوبرام

•       إس إن أر أي (مثبطات امتصاص السيروتونين والنورادرينالين) تستخدم لعلاج الاكتئاب أو القلق بما في ذلك ڨينلافاكسين، دولوكسيتين

 

إذا لم تكن متأكداً مما إذا كان أي من أعلاه ينطبق عليك، تحدث إلى طبيبك أو الممرضة أو الصيدلي قبل تناول أقراص اوندانس.

 

الحمل والرضاعة الطبيعية

يجب عدم استخدام اوندانس خلال الأشهر الثلاثة الأولى من الحمل. وذلك لأن اوندانس يمكن أن يزيد بشكل طفيف من خطر ولادة طفل بالحنك المشقوق (فتحات أو انشقاقات في الشفة العليا و/أو سقف الفم). إذا كنتِ حاملا بالفعل، أو تعتقدين أنك قد تكونين حاملا أو تخططين لإنجاب طفل، فاسألي طبيبك أو الصيدلي للحصول على المشورة قبل تناول اوندانس. من الموصى به أن تستخدم النساء اللواتي لديهن إمكانية الإنجاب وسائل منع الحمل الفعالة (الطرق التي تؤدي إلى معدل حمل أقل من 1٪) أثناء استخدام اوندانس.

لا تقومين بالرضاعة الطبيعية إذا كنتي تستخدمين اوندانس. وهذا بسبب وصول كميات صغيرة إلى حليب الأم. اسألي طبيبك أو المولدة للحصول على المشورة.

 

معلومات هامة عن بعض مكونات أقراص اوندانس

هذا الدواء يحتوي على اللاكتوز. إذا أخبرك طبيبك بأن لديك عدم القدرة على تحمل تناول بعض السكريات، تحدث إلى طبيبك قبل تناول هذا الدواء.

 

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احرص دائمًا على تناول أقراص اوندانس كما أخبرك طبيبك تمامًا. يجب عليك مراجعة الطبيب أو الممرضة أو الصيدلي إذا كنت غير متأكد. تعتمد الجرعة التي وصفت لك على العلاج الذي تحصل عليه.

 

لمنع الغثيان والقيء من العلاج الكيميائي أو العلاج الإشعاعي

 

في يوم العلاج الكيميائي أو العلاج الإشعاعي

•       الجرعة المعتادة للبالغين هي 8 ملجم قبل ساعة أو ساعتين من العلاج، و8 ملجم أخري بعد 12 ساعة من العلاج. 

في الأيام التالية

•       الجرعة المعتادة للبالغين هي 8 ملجم مرتين يوميا

•       وقد يتم اعطاؤها لمدة تصل إلى 5 أيام.

 

الأطفال الذين تتراوح أعمارهم أكثر من 6 أشهر والمراهقين

 

سوف يقرر الطبيب الجرعة حسب الوزن أو الحجم (مساحة سطح الجسم) للطفل. انظر الملصق لمزيد من المعلومات 

•       الجرعة المعتادة للطفل تصل إلى 4 ملجم مرتين يوميا

•       وقد يتم اعطاؤها لمدة تصل إلى 5 أيام.

 

لمنع وعلاج الغثيان والقيء بعد العملية

 

الجرعة المعتادة للبالغين هي 16 ملجم قبل العملية الخاصة بك.

 

الأطفال الذين تزيد أعمارهم عن شهر واحد والمراهقين:

ينصح بإعطاء اوندانس على هيئة حقن.

 

المرضى الذين يعانون من مشاكل متوسطة أو حادة في الكبد

لا يجب أن تكون الجرعة اليومية الإجمالية أكثر من 8 ملجم.

 

يجب أن تبدأ فعالية أقراص اوندانس بالعمل في غضون ساعة أو ساعتين من تناول الجرعة.

 

إذا شعرت بالإعياء (القيء) في غضون ساعة واحدة من تناول الجرعة

•       تناول نفس الجرعة مرة أخرى

•       خلاف ذلك، لا تتناول أقراص اوندانس أكثر مما هو مذكور على الملصق.

إذا استمر شعورك بحالة الإعياء، أخبر طبيبك أو الممرضة.

 

إذا تناولت أقراص اوندانس أكثر مما يجب

إذا تناولت أو تناول طفلك جرعة زائدة من اوندانس، أخبر طبيبك أو قم بالتوجه إلى المستشفى مباشرة. قم بأخذ عبوة الدواء معك.

 

إذا نسيت تناول أقراص اوندانس

إذا نسيت تناول جرعة وشعرت بالإعياء أو القيء:

•       تناول أقراص اوندانس في أقرب وقت ممكن، ثم

•       تناول قرصك التالي في الوقت المعتاد (كما هو موضح في الملصق)

•       لا تتناول جرعة مضاعفة للتعويض عن الجرعة المنسية.

 

إذا نسيت تناول جرعة، ولكن لم تشعر بالإعياء

•       تناول الجرعة التالية كما هو موضح في الملصق

•       لا تتناول جرعة مضاعفة للتعويض عن الجرعة المنسية.

مثل جميع الأدوية من الممكن أن تسبب أقراص اوندانس أعراضا جانبية، على الرغم من أن الجميع لا يحصل عليها.

 

ردود الفعل التحسسية

إذا ظهر عليك رد فعل تحسسي، توقف عن تناول الدواء وقم بالتوجه لرؤية الطبيب على الفور.  وقد تشمل الأعراض:

•       صفير مفاجئ عند التنفس وألم في الصدر أو ضيق في الصدر

•       تورم في الجفون، الوجه، الشفاه، والفم أو اللسان

•       طفح جلدي-البقع الحمراء أو كتل تحت الجلد (الشري) في أي مكان في جسمك

•       انهيار.

 

وتشمل الأعراض الجانبية الأخرى:

 

شائعة جداً (قد تؤثر على أكثر من 1 في كل 10 أشخاص)

•       صداع.

 

شائعة (قد تؤثر على ما يصل إلى 1 في كل 10 أشخاص)

•       شعور بالحرارة أو الاحمرار

•       الإمساك

•       تغير في نتائج اختبار وظائف الكبد (إذا كنت تستخدم أقراص اوندانس مع دواء يسمى سيسبلاتين، خلاف هذا يعتبر هذا العرض الجانبي غير شائع)

غير شائعة (قد تؤثر على ما يصل إلى 1 في كل 100 شخص)

•       الفواق

•       انخفاض ضغط الدم، والذي يمكن أن يجعلك تشعر بالاغماء أو بالدوار

•       ضربات قلب غير متساوية

•       ألم في الصدر

•       نوبات

•       حركات جسم غير عادية أو اهتزاز.

 

نادرة (قد تؤثر على ما يصل إلى 1 في كل 1,000 شخص)

•       الشعور بالدوخة أو الدوار

•       عدم وضوح الرؤية

•       اضطراب في ضربات القلب (في بعض الأحيان تسبب فقدان مفاجئ للوعي)

 

نادرة جداً (قد تؤثر على ما يصل إلى 1 في كل 10,000 شخص)

•       ضعف البصر أو فقدان مؤقت للبصر، الذي عادة ما يأتي مرة أخرى في غضون 20 دقيقة.

غير معروف (لا يمكن تقديره من البيانات المتاحة)

•       نقص تروية عضلة القلب

تشمل العلامات:

§       ألم مفاجئ في الصدر أو

§       ضيق الصدر

 

الإبلاغ عن الأعراض الجانبية

إذا ظهرت عليك أي أعراض جانبية، قم بالتحدث مع طبيبك أو الصيدلي أو الممرضة. ويشمل ذلك أي أعراض جانبية محتملة غير المُدرجة في هذه النشرة. يمكنك أيضا الإبلاغ عن الأعراض الجانبية مباشرة عبر المركز الوطني للتيقظ والسلامة الدوائية. يمكنك من خلال الإبلاغ عن الأعراض الجانبية أن تساعد في توفير المزيد من المعلومات حول سلامة هذا الدواء.

•       يحفظ بعيدا عن متناول ونظر الأطفال.

•       لا تستخدم أقراص اوندانس بعد انتهاء تاريخ الصلاحية المدون على العبوة بعد EXP. وتاريخ الإنتهاء يشير إلى أخر يوم في الشهر المذكور.

•       يحفظ في درجة حرارة أقل من 30 درجة مئوية.

•       لا تتخلص من أي أدوية عن طريق مياه الصرف الصحي أو النفايات المنزلية. اسأل الصيدلي عن كيفية التخلص من الأدوية التي لم تعد تستخدمها. ومن شأن هذه التدابير أن تساعد على حماية البيئة. 

  • المادة الفعالة هي اوندانسيترون. يحتوي كل قرص اوندانس على اوندانسيترون 4 ملجم أو 8 ملجم (على هيئة ثنائي هيدرات الهيدروكلوريد).
  • المكونات الأخرى هي لاكتوز NF سريع التدفق- BMS 35957، افيسل PH 102، نشا 1500، وستيرات الماغنيسيوم.
  • غلاف القرص: اوبادري 20J22730 اصفر، ايثانول 96%، وماء منقى.

أقراص اوندانس 4 ملجم ذات لون أصفر باهت، دائرية، محدبة الوجهين، مغلفة بطبقة رقيقة، محفورة ب "91" على جانب واحد وخالية من العلامات على الجانب الآخر.

 

أقراص اوندانس 8 ملجم ذات لون أصفر باهت، دائرية، محدبة الوجهين، مغلفة بطبقة رقيقة، محفورة ب "92" على جانب واحد وخالية من العلامات على الجانب الآخر.

 

تأتي أقراص اوندانس في:

  • شريط PVC/PE/PVDC حراري التكوين أبيض ملفوف بغطاء من رقائق الألومنيوم الصلب المخفف.
  • كل عبوة تحتوي على 10 أقراص مغلفة بطبقة رقيقة.

 

مالك الحقوق التسويقية والمصنع

الدوائية

مصنع الأدوية بالقصيم

المملكة العربية السعودية

أغسطس 2023.
 Read this leaflet carefully before you start using this product as it contains important information for you

Ondans® Film coated Tablets 4 mg. Ondans® Film coated Tablets 8 mg.

Each tablet contains ondansetron 4 mg or 8 mg (as hydrochloride dihydrate) *. * Ondansetron HClDihydrate is dispensed based on the potency and the difference is compensated with Lactose NF Fast Flow-BMS 35957. Excipients with known effect: Contains Lactose NF Fast Flow-BMS 35957 85 mg or 170 mg (see section 4.4). For the full list of excipients see section 6.1.

Film coated tablet. The 4mg tablets are Pale yellow, round, biconvex, film-coated tablet, engraved with "91"on one side and plain on the other side. The 8mg tablets are Pale yellow, round, biconvex, film-coated tablet, engraved with "92"on one side and plain on the other side.

Adults:

Ondans tablets are indicated for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy.

Ondans tablets are indicated for the prevention of post-operative nausea and vomiting (PONV). For treatment of established PONV, administration by injection is recommended.

Pediatric Population:

Ondans is indicated for the management of chemotherapy-induced nausea and vomiting (CINV) in children aged ≥6 months.

No studies have been conducted on the use of orally administered ondansetron in the prevention and treatment of PONV in children aged ≥1 month, administration by IV injection is recommended for this purpose.


Chemotherapy and radiotherapy induced nausea and vomiting.

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 ondansetron should be flexible in the range of 8-32 mg a day and selected as shown below. The selection of dose regimen should be determined by the severity of the emetogenic challenge.

Emetogenic Chemotherapy and Radiotherapy: Ondans can be given either by rectal, oral (tablets or syrup), intravenous or intramuscular administration.

For oral administration: 8 mg taken 1 to 2 hours before chemotherapy or radiation treatment, followed by 8 mg every 12 hours for a maximum of 5 days to protect against delayed or prolonged emesis.

For highly emetogenic chemotherapy: a single dose of up to 24 mg Ondans taken with 12 mg oral dexamethasone sodium phosphate, 1 to 2 hours before chemotherapy, may be used.

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

The recommended dose for oral administration is 8 mg to be taken twice daily.

Pediatric Population:

CINV in children aged ≥ 6 months and adolescents

The dose for CINV can be calculated based on body surface area (BSA) or weight – see below. In pediatric 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 (see section 4.4).

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

Dosing by BSA:

Ondans 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 Chemotherapy - Children aged ≥ 6 months and adolescents

BSA

Day 1 (a,b)

Days 2-6 (b)

< 0.6 m2

5 mg/m2 IV plus

2 mg syrup after 12 hours

2 mg syrup every 12 hours

≥ 0.6 m2 to ≤ 1.2 m2

5 mg/m2 IV plus

4 mg syrup or tablet after 12 hours

4 mg syrup or tablet every 12 hours

> 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 (see sections 4.4. and 5.1).

Ondans 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 Chemotherapy - Children aged ≥6 months and adolescents

Weight

Day 1 (a,b)

Days 2-6 (b)

≤ 10 kg

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

2 mg syrup every 12 hours

> 10 kg

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

4 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.

Elderly:

No alteration of oral dose or frequency of administration is required.

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 Ondans 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.

Patients with Poor Sparteine/Debrisoquine Metabolism:

The elimination half-life of ondansetron is not altered in subjects classified as poor metabolizers 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: Ondans can be administered orally or by intravenous or intramuscular injection.

For oral administration: 16 mg taken one hour prior to anesthesia.

For the treatment of established PONV: Intravenous or intramuscular administration is recommended.

Pediatric population:

PONV in children aged ≥ 1 month and adolescents

Oral formulation:

No studies have been conducted on the use of orally administered ondansetron in the prevention or treatment of post-operative nausea and vomiting; slow IV injection (not less than 30 seconds) is recommended for this purpose.

Injection:

For prevention of PONV in pediatric patients having surgery performed under general anesthesia, a single dose of ondansetron 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 anesthesia.

For the treatment of PONV after surgery in pediatric patients having surgery performed under general anesthesia, a single dose of Ondans 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 Ondans in the treatment of PONV in children below 2 years of age.

Elderly:

There is limited experience in the use of Ondans in the prevention and treatment of post-operative nausea and vomiting in the elderly, however Ondans 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 Ondans 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.

Patients with poor Sparteine/Debrisoquine Metabolism:

The elimination half-life of ondansetron is not altered in subjects classified as poor metabolizers 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.


• Hypersensitivity to the ondansetron or to any of the excipients listed in section 6.1. • Hypersensitivity to other selective 5-HT3 receptor antagonists (e.g., granisetron, dolasetron). • Concomitant use with apomorphine is contraindicated (see section 4.5 Interactions with other medicinal products).

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.

Hypokalemia 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)). 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 subacute 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.

Patients with rare hereditary problems of galactose intolerance, Lapp lactase-deficiency or glucose- galactose malabsorption should not take this medicine.

Since there is little experience to date of the use of ondansetron in cardiac patients, caution should be exercised if ondansetron is co-administered with anesthetics to patients with arrhythmias or cardiac conduction disorders or to patients who are being treated with antiarrhythmic agents or beta-blockers.

Very rarely and predominantly with intravenous ondansetron, transient ECG changes including QT interval prolongation have been reported. Caution is advised if patients have received cardiotoxic agents and in patients with a history of prolonged QT syndrome.

 

Pediatric Population:

Pediatric 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 (see section 5.1).


There is no evidence that ondansetron either induces or inhibits the metabolism of other drugs commonly coadministered 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 metabolized by multiple hepatic cytochrome P-450 enzymes: CYP3A4, CYP2D6 and CYP1A2. Due to the multiplicity of metabolic enzymes capable of metabolizing 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

It is recommended that sexually active women of childbearing potential use effective contraception (methods resulting in less than 1% pregnancy rate) during treatment with ondansetron.

 

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 Ondans 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


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.

 

There may be cross-sensitivity with other selective 5-HT3- antagonists.

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 IV administration (2).

Cardiac disorders

Uncommon:

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

Rare:

QTc prolongation (including Torsade de Pointes).

Not known

Myocardial Ischemia (see section 4.4).

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).

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 authorization 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 the national reporting system.

To report any side effect(s):

For Saudi Arabia:

- The National Pharmacovigilance and Drug Safety Centre (NPC)

Fax: +966-11-205-7662

SFDA Call Center: 19999

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

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

For UAE:

Pharmacovigilance & Medical Device section
P.O.Box: 1853 

Tel: 80011111

Email: pv@mohap.gov.ae

Drug Department

Ministry of Health & Prevention,

Dubai, UAE

For OMAN:

Department of Pharmacovigilance & Drug Information

Directorate General of Pharmaceutical Affairs & Drug Control

Ministry of Health, Sultanate of Oman

Phone Nos. 0096822357687 / 0096822357686

Fax: 0096822358489

Email: dg-padc@moh.gov.om

Website: www.moh.gov.om


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.

Treatment

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.

In a pharmaco-psychological study in volunteers, ondansetron has not shown a sedative effect.

Ondansetron does not alter plasma prolactin concentrations.

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, randomized, 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.

Pediatric population:

CINV

The efficacy of ondansetron in the control of emesis and nausea induced by cancer chemotherapy was assessed in a double-blind randomized 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 randomized 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 randomized, 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 anesthesia and had an ASA status ≤ III. A single dose of ondansetron 0.1 mg/kg was administered within five minutes following induction of anesthesia. 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 anesthesia. Patients were randomized to either single intravenous doses of ondansetron (0.1 mg/kg for pediatric patients weighing 40 kg or less, 4 mg for pediatric 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 anesthesia induction. Ondansetron was significantly more effective than placebo in preventing nausea and vomiting. The results of these studies are summarized in Table 3.

Table 3: Prevention and treatment of PONV in Pediatric 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.

 

Gender differences were shown in the disposition of ondansetron given as a single dose. The extent and rate of ondansetron's absorption is greater in women than men. Slower clearance in women, a smaller apparent volume of distribution (adjusted for weight), and higher absolute bioavailability resulted in higher plasma ondansetron levels. These higher plasma levels may in part be explained by differences in body weight between men and women. It is not known

whether these gender-related differences were clinically important.)

 

The disposition of ondansetron following oral, intramuscular (IM) and intravenous (IV) dosing is similar with a terminal half-life of about 3 hours and steady state volume of distribution of about 140 L. Equivalent systemic exposures is achieved after IM and IV administration of ondansetron.

A 4mg 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.

Ondansetron is not highly protein bound (70-76%). 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 pediatric patients aged 1 to 4 months (n=19) undergoing surgery, weight normalized 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 pediatric patients aged 3 to 12 years undergoing elective surgery with general anesthesia, 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 normalized 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 normalizing systemic exposure in pediatric 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 intravenous dosing.

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 hemodialysis (studied between dialyses) showed ondansetron's pharmacokinetics to be essentially unchanged following IV 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 (15-32 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.


Non-clinical data revealed no special hazard for humans based on conventional studies of repeated-dose toxicity, genotoxicity, and carcinogenic potential.

Ondansetron and its metabolites accumulate in the milk of rats with a milk: plasma ratio of 5.2:1.

A study in cloned human cardiac ion channels has shown ondansetron has the potential to affect cardiac repolarization via blockade of HERG potassium channels. A dose-dependent prolongation of the QT interval was observed in a thorough QT study with healthy volunteers (see section 5.1).

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 organogenesis at 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 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.


Name of Ingredients

Ondans 8mg Unit Dose

(mg)

Ondans 4mg Unit Dose

(mg)

Lactose NF Fast Flow-BMS 35957

170.000

85.000

Avicel PH 102

62.000

31.000

Starch 1500

12.800

6.400

Magnesium Stearate

1.200

0.600

Film-Coating

Opadry 20J22730 Yellow ****

7.000

3.500

Ethanol 96% **

63.000

31.500

Purified Water BP ***

7.000

3.500

 

** Ethanol 96% is a process solvent which is evaporated during process.

*** Purified Water BP is a process solvent which is evaporated during process.

**** 50% excess coating material taken to compensate losses during coating.


Not Applicable.


24 Months (2 years)

Store below 30ºC.


White thermoformed PVC/PE/PVDC reel with hard tempered aluminum foil lid. 

Each unit carton contains 10 film-coated tablets


No special requirements.


SPIMACO Al-Qassim Pharmaceutical Plant Saudi Arabia

August 2023
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