قرص sandoz

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قرص sandoz

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A primary care data and quality improvement program developed and managed by NPS MedicineWise with funding from the Australian Government Department of Health.

Independent peer-reviewed journal providing critical commentary on drugs and therapeutics for health professionals.

Providing health professionals with timely, independent evidence-based information on new drugs and medical tests and changes to listings on the Pharmaceutical Benefits Scheme and Medicare Benefits Schedule.

Helping the healthcare community and consumers start an important conversation about eliminating the use of unnecessary and sometimes harmful tests, treatments, and procedures.

Relevant, timely and evidence-based information for Australian health professionals and consumers.

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Brand name

Olanzapine Sandoz

Active ingredient

Olanzapine

Schedule

S4

Please read this leaflet carefully before you start using Olanzapine Sandoz.

This leaflet answers some common questions about Olanzapine Sandoz.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking this medicine against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

قرص sandoz

Keep this leaflet with the medicine.
You may need to read it again.

This medicine is used:

It contains the active ingredient olanzapine.

Olanzapine belongs to a group of medicines called antipsychotics.

It works by helping to correct chemical imbalances in the brain, which may cause mental illness.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.
Your doctor may have prescribed it for another reason.

This medicine is available only with a doctor’s prescription.

Olanzapine is not recommended for use in children under the age of 18 years as there is not enough information on its effects in this age group.

Do not take this medicine if you have an allergy to:

Some of the symptoms of an allergic reaction may include:

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.
If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

Tell your doctor if you are pregnant or plan to become pregnant.
Like most antipsychotic medicines, Olanzapine Sandoz is not recommended for use during pregnancy. If there is a need to consider this medicine during your pregnancy your doctor will discuss with you the risks and benefits of using it.

Tell your doctor if you are breast-feeding or plan to breast-feed.
It is recommended that you do not breast-feed while taking this medicine.

Tell your doctor if you suffer from lactose intolerance (because Olanzapine Sandoz tablets contain lactose).

Tell your doctor if you will be in a hot environment or do a lot of vigorous exercise.
Olanzapine Sandoz may make you sweat less, causing your body to overheat.

This medicine is not recommended for use in children under the age of 18 years.

If you have not told your doctor about any of the above, tell him/her before you start taking Olanzapine Sandoz.

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Olanzapine Sandoz may interfere with each other. These include:

These medicines may be affected by Olanzapine Sandoz or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Smoking may also affect Olanzapine Sandoz or may affect how it works.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

Follow all directions given to you by your doctor or pharmacist carefully.
They may differ from the information contained in this leaflet.

If you do not understand the instructions, ask your doctor or pharmacist for help.

Your doctor will tell you how many tablets you should take. The dose your doctor will prescribe for you will usually be in the range 5mg to 20mg per day.

Your doctor may increase or decrease your dose in order to find the appropriate dose for your condition.

A lower starting dose may be prescribed for elderly patients over the age of 65 years.

Ask your doctor or pharmacist if you are unsure of the correct dose for you.
They will tell you exactly how much to take.

Follow the instructions they give you.
If you take the wrong dose, Olanzapine Sandoz may not work as well and your condition may not improve.

Swallow the tablets whole with a full glass of water.

Olanzapine Sandoz tablets should be taken once a day as advised by your doctor.

Take your medicine at about the same time each day.
Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

Olanzapine Sandoz can be taken with or without food.

Continue taking your medicine for as long as your doctor tells you. Do not stop taking Olanzapine Sandoz just because you feel better. It is important that you do NOT stop taking Olanzapine Sandoz unless your doctor tells you.

This medicine helps to control your condition, but does not cure it. It is important to keep taking your medicine even if you feel well.

Take your dose as soon as you remember, and continue to take it as you would normally.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose that you missed.
This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

Immediately telephone your doctor or the Poisons Information Centre (telephone Australia 13 11 26 or New Zealand 0800 POISON or 0800 764766) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much Olanzapine Sandoz. Do this even if there are no signs of discomfort or poisoning.
You may need urgent medical attention.

Symptoms of an overdose may include a fast heartbeat, agitation/aggression, difficulty speaking, uncontrollable movements and sedation.

It is important that you remember to take Olanzapine Sandoz daily and at the dose prescribed by your doctor.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking Olanzapine Sandoz.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

If you become pregnant while taking this medicine, tell your doctor immediately.

Keep all of your doctor’s appointments so that your progress can be checked.

Tell your doctor if you are female and your monthly periods are absent for six months or more.

Talk to your doctor or mental health professional if you have thoughts or talk about death or suicide; or thoughts or talk about self-harm or doing harm to others.
These may be signs of changes or worsening in your mental illness.

Do not take Olanzapine Sandoz to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop taking your medicine or lower the dosage, even if you are feeling better, without checking with your doctor.
Your doctor may want you to gradually reduce the amount you are taking before stopping completely.

Be careful driving or operating machinery until you know how Olanzapine Sandoz affects you.
This medicine may cause drowsiness in some people. If you experience this symptom, do not drive, operate machinery or do anything else that could be dangerous.

Be careful when drinking alcohol while you are taking this medicine.
The effects of alcohol could be made worse while taking Olanzapine Sandoz. Your doctor may suggest you avoid alcohol while you are being treated with this medicine.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly.
Standing up slowly, especially when you get up from bed or chairs, will help your body get used to the change in position and blood pressure. If this problem continues or gets worse, talk to your doctor.

If outdoors, wear protective clothing and use at least a 30+ sunscreen.
Olanzapine Sandoz may cause your skin to be much more sensitive to sunlight than it is normally. Exposure to sunlight may cause a skin rash, itching, redness, or severe sunburn

If your skin does appear to be burning, tell your doctor.

Make sure you keep cool in hot weather and keep warm in cool weather. This medicine may affect the way your body reacts to temperature changes.

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Olanzapine Sandoz.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Side effects are likely to vary from patient to patient. Some side effects may be related to the dose of your medicine. Accordingly, it is important that you tell your doctor as soon as possible about any unwanted effects. Your doctor may then decide to adjust the dose of the medicine you are taking.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

Some people may feel dizzy in the early stages of treatment, especially when getting up from a lying or sitting position. This side effect usually passes after taking Olanzapine Sandoz for a few days.

Tell your doctor if you notice any of the above side effects and they worry you.

Tell your doctor as soon as possible if you notice any of the following:

Tell your doctor if your monthly periods are absent for six months or more.

The above list includes serious, uncommon side effects that may require medical attention.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. All of these side effects are very rare.

The following additional side effects may occur in some group of people taken olanzapine.

Elderly patients with dementia-related psychosis

may notice the following side effects:

Parkinson’s disease psychosis

Some patients with Parkinson’s disease may hallucinate (see, feel or hear things that are not there) or develop worsening symptoms of Parkinson’s Disease.

Patients with bipolar mania taking Olanzapine Sandoz in combination with lithium or valproate may notice the following side effects:

These are the more common side effects of Olanzapine Sandoz.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

Tell your doctor if you notice anything unusual or if you are concerned about any aspect of your health, even if you think the problems are not connected with this medicine and are not referred to in this leaflet.

Some of these side effects, such as changes to liver function, cholesterol or triglycerides can occur. These can only be found when your doctor does tests from time to time to check your progress.

Keep your medicine in the original container until it is time to take them.

If you take it out of its original container it may not keep well.

Keep your medicine in a cool dry place where the temperature stays below 25°C.

Do not store Olanzapine Sandoz or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car.

Heat and dampness can destroy some medicines.

Keep it where children cannot reach it.
A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Olanzapine Sandoz comes in four types of tablets:

Olanzapine Sandoz 2.5mg – white, round, film-coated tablet.

Olanzapine Sandoz 5mg – white, round, film-coated tablet with breaking notch on one side.

Olanzapine Sandoz 7.5mg – white, round, film-coated tablet.

Olanzapine Sandoz 10mg – white, round, film-coated tablet with breaking notch on one side.

Available in blisters of 28 tablets.

Active ingredients:

Inactive ingredients:

This medicine does not contain sucrose, gluten, tartrazine or any other azo dyes.

Olanzapine Sandoz is supplied in Australia by:

Sandoz Pty Ltd
ABN 60 075 449 553
54 Waterloo Road,
Macquarie Park, NSW 2113
Australia
Tel: 1800 726 369

Australian Register Number(s)

2.5mg tablets: AUST R 148450 (blisters)

5mg tablets: AUST R 148469 (blisters)

7.5mg tablets: AUST R 148474 (blisters)

10mg tablets: AUST R 148451 (blisters)

This leaflet was revised in October 2018.

Published by MIMS January 2019

Reasonable care is taken to provide accurate information at the time of creation. This information is not intended as a substitute for medical advice and should not be exclusively relied on to manage or diagnose a medical condition. NPS MedicineWise disclaims all liability (including for negligence) for any loss, damage or injury resulting from reliance on or use of this information. Read our full disclaimer. This website uses cookies. Read our privacy policy.

PO Box 1147 Strawberry Hills NSW 2012

Level 7, 418A Elizabeth St, Surry Hills NSW 2010

ABN: 61 082 034 393

We are always looking for ways to improve our website

Get medicines information:

Report a problem with medicines, medical devices or vaccines:

An independent peer-reviewed journal providing critical commentary on drugs and therapeutics.

Timely, independent, evidence-based information on new drugs and medical tests, and changes to the PBS and MBS.

Medicine Finder

Find information on medicines by brand name or active ingredient

Receive Email Updates

قرص sandoz

Latest news, evidence and CPD opportunities

Information for consumers on prescription, over-the-counter and complementary medicines.

Provides consumers with a way to report and discuss adverse experiences with medicines

Keep track of medicines and access important health info any time and anywhere, especially in emergencies.

Medicine Finder

Find information on medicines by brand name or active ingredient

Receive Email Updates

Latest news, evidence and CPD opportunities

A primary care data and quality improvement program developed and managed by NPS MedicineWise with funding from the Australian Government Department of Health.

Independent peer-reviewed journal providing critical commentary on drugs and therapeutics for health professionals.

Helping the healthcare community and consumers start an important conversation about eliminating the use of unnecessary and sometimes harmful tests, treatments, and procedures.

Relevant, timely and evidence-based information for Australian health professionals and consumers.

Medicine Finder

Find information on medicines by brand name or active ingredient

Receive Email Updates

Latest news, evidence and CPD opportunities

20 years of helping Australians make better decisions about medicines, medical tests and other health technologies

Medicine Finder

Find information on medicines by brand name or active ingredient

Receive Email Updates

Latest news, evidence and CPD opportunities

All fields are required

Brand name

Anastrozole Sandoz Tablets

Active ingredient

Anastrozole

Schedule

S4

Please read this leaflet carefully before you start using Anastrozole Sandoz.

This leaflet answers some common questions about Anastrozole Sandoz. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risk of you taking Anastrozole Sandoz against the benefits it is expected to have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

قرص sandoz

You may want to read it again.

The name of your medicine is Anastrozole Sandoz. It contains the active ingredient anastrozole.

Anastrozole Sandoz is used to treat breast cancer in women who are postmenopausal (i.e. women who no longer have their menstrual periods).

Ask your doctor if you have any questions about why Anastrozole Sandoz was prescribed for you.

Your doctor may have prescribed Anastrozole Sandoz for another reason.

Anastrozole Sandoz belongs to a group of medicines called non-steroidal aromatase inhibitors.

Anastrozole Sandoz is a non-steroidal aromatase inhibitor, which reduces the amount of oestrogen (female sex hormone) made by the body in postmenopausal women. In some types of breast cancer, oestrogen can help the cancer cells grow. By blocking oestrogen, Anastrozole Sandoz may slow or stop the growth of cancer.

Anastrozole Sandoz should only be taken by postmenopausal women.

Anastrozole Sandoz is not recommended for use in men, children or women who are not postmenopausal.

There is no evidence that Anastrozole Sandoz is addictive.

Do not take Anastrozole Sandoz if:

Anastrozole is not recommended for use in children or in premenopausal women as safety and efficacy have not been established in these groups of patients.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Tell your doctor if you have allergies to:

Tell your doctor if you plan on becoming pregnant or will be breastfeeding while you are using Anastrozole Sandoz.

Tell your doctor if you have or have had any medical conditions, especially the following medical conditions:

Tell your doctor if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

In particular, tell your doctor if you take any of the following:

These medicines may be affected by Anastrozole Sandoz, or may affect how well it works. You may need to use different amounts of your medicine, or you may need to take different medicines. Your doctor will advise you.

The usual dose is one tablet every day.

Take Anastrozole Sandoz at about the same time each day.

Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

Swallow Anastrozole Sandoz tablets whole, with a glass of water.

It does not matter if you take Anastrozole Sandoz before, with or after food.

Continue taking Anastrozole Sandoz for as long as your doctor or pharmacist tells you.

Anastrozole Sandoz helps to control your condition, but does not cure it. Therefore you must take Anastrozole Sandoz every day. Do not stop taking it unless your doctor tells you to – even if you feel better.

Take your dose as soon as you remember, and continue to take it as you would normally.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

Immediately telephone your doctor, or the Poisons Information Centre (telephone Australia 13 11 26 or New Zealand 0800 POISON or 0800 764766) or go to Accident and Emergency at your nearest hospital, if you think you or anyone else has taken too much Anastrozole Sandoz. Do this even if there are no signs of discomfort or poisoning.

Be careful driving or operating machinery until you know how Anastrozole Sandoz affects you.

This medicine may occasionally cause some people to feel weak or sleepy.

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Anastrozole Sandoz.

This medicine helps most postmenopausal women with breast cancer, but it may have unwanted side effects in a few people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. Side effects may happen at the start of treatment or they may happen after you have been taking your medicine for some time. You may need medical attention if you get some of the side effects.

If you get any side effects do not stop taking this medicine without first talking to your doctor or pharmacist.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

These are the more common side effects of the medicine. Mostly, these are mild to moderate in nature.

Uncommon side effects can include vaginal bleeding, loss of appetite, vomiting, feeling sleepy and an increase in cholesterol levels or changes in blood tests of liver function. These side effects are generally mild to moderate and often resolve themselves over time.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are rare.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell.

Other side effects not listed above may also occur in some people.

Keep Anastrozole Sandoz in the original packaging until you need to take it.

Store below 30°C. Keep out of the reach of children.

Return any unused or out of date medicine to your pharmacist.

Anastrozole Sandoz 1mg: white, round, biconvex film coated tablet without breaking notch and embossment ‘A1’ on one side. Available in PVC/Al blisters of 30 tablets.

Active Ingredient Each Anastrozole Sandoz 1mg tablet contains 1mg anastrozole.

Inactive Ingredients Each Anastrozole Sandoz 1mg tablet also contains:

Anastrozole Sandoz is supplied in Australia by:Sandoz Pty LtdABN 60 075 449 55354 Waterloo Road,Macquarie Park,NSW 2113, AUSTRALIATel: 1800 634 500

This leaflet was prepared in May 2015.

Australian Register Number: Anastrozole Sandoz 1mg tablet: AUST R 142746 (blisters)

PO Box 1147 Strawberry Hills NSW 2012

Level 7, 418A Elizabeth St, Surry Hills NSW 2010

ABN: 61 082 034 393

We are always looking for ways to improve our website

Get medicines information:

Report a problem with medicines, medical devices or vaccines:

انواع ساده و کمپلکس صرع فوکال و جنرالیزه(Absenceو گراندمال) و انواع دیگر صرع ( میوکلونیک ، آتونیک)
مانیای حاد .
روفیلاکسی میگرن

E.C . Tab : 200 mg
Syrup : 200 mg/5 ml
E.C Tab (SR) : 500 mg
(Inj : 100 mg/ml (3 , 5 ml
Cap :300 mg
Powder for inj : 400 mg
Valproic Acid Tab : 250 , 500 mg

D – مطالعات کافی درباره مصرف داروی این گروه شواهدی مبنی بر وجود خطر برای جنین انسان وجود دارد ولی در بعضی از موارد منافع دارو ممکن است استفاده از آن را اجتناب ناپذیر نماید. و در مقابل منافع دارو خطرات احتمالی دارو را باید پذیرفت

از نظر مصرف در حاملگی در گروه Dاست . ممکن است در مادرانی که طی سه ماه اول حاملگی اسید والپروییک مصرف می کنن ، بروز نقص لوله عصبی افزایش یابد . مرکزکنترل و پیشگیری بیماری ها (CDC) خطر بروز اپسانیا بیفیدا در کودکان مادرانی که والپروات مصرف می کنند ، حدود 1 تا 2 درصد برآورده می کند . این میزان مشابه میزان زنان غیر صرعی است که کودکان مبتلا به نقص لوله عصبی ( آنانسفالی و اسپانیابیفیدا ) دارند . همچنین به تک نگار Phenytoinمراجعه کنید . غلظت اسید والپروییک در شیر 1تا10 درصد غلظت سرمی آن است . مشخص نیست این امر چه اثری بر شیرخوار دارد . یک مورد پورپورای ترومبوسیتوپنیک و آنمی در شیرخواری که مادرش از والپروات استفاده می کرد ، رخ داده است . کودک با قطع شیردهی و بهبود یافت . در تجویز به مادر شیرده احتیاط کنید

سدیم والپروات آثار خود را از طریق مهار کانال های سدیم وابسته به ولتاژ و نیز افزایش میزان GABA در مغز اعمال می کند.
سدیم والپروات به سرعت و به طور کامل از دستگاه گوارش جذب می شود. در صورتی که این دارو همراه یا بعد از غذا مصرف شود سرعت جذب آن، بدون تغییر میزان جذب کلی ،کاهش می یابد.
پلاسما در حدود 90 درصد است. سدیم والپروات به طور عمده ای در کبد متابولیزه می شود. قسمت اعظم متابولیسم این دارو از راه گلوکورونیداسیون و مابقی آن از طریق بتا- اکسیداسیون و امگا – اکسیداسیون در میتوکندری ها صورت می گیرد که برخی از متابولیت های حاصل نیز دارای فعالیت فارماکولیژیکی هستند . نیمه عمر والپروات تقریبا 15ساعت است که ممکن است در بیماران مبتلا به نارسایی کبدی ، بیماران مسن و کودکان زیر 2 سال طولانی تر و در بیمارانی که تحت درمان با سایر داروهای ضد صرع نیز هستند کوتاه تر باشد . این دارو به شکل متابولیت از طریق ادرار دفع می شودقرص sandoz

گزارش شده است که در 6 کودک صرعی ، تجویز هم زمان آسپیرین ، کسر آزاد و نیمه عمر اسید والپروپیک را افزایش داده است .این امر حاکی از آن است که ممکن است سالیسیلات ها علاوه بر جابه جا کردن اسید والپروییک از محل اتصال آن به پروتئین ، متابولیسم آن را نیز مهار می کند . به علاهو سالیسیلات ها با افزایش خطر بروز سندرم ری در کودکان همراه هستند وترکیب با داروی هپاتوتوکسیک دیگری نظیر والپروات کاملا نامطلوب است . والپروات و آسپیرین ، هر دو برعملکرد پلاکت ها اثر می گذراند . ناپروکسن نیز جابه جایی جزیی در اسید والپروییک متصل به پروتئین ایجاد می کند : ولی این اثر احتمالا چندان قابل توجه نیست تا آثار کلینیکی داشته باشد . ممکن است داروهای ضد افسردگی با کاهش استانه تشنج به صورت آنتاگونیست فعالیت ضد صرعی والپروات (و همچنین سایر داروهای ضد صرع ) عمل می کنند . ضد صرع ها : فنوباربیتال می تواند کلیرانس و متابولیسم والپروات را افزایش دهد : والپروات نیز متابولیسم را مهار می کند کاربامازپین و فنی تویین داروهای القاء کننده آنزیم هستند و طبق انتظار متابولیسم والپروات را افزایش می دهند . ولی اثر والپروات برروی هر دودارو پیچیده است . برای مطالعه به تک نگار های Carbamazepineو Phenytoinمراجعه کنید . به دنبال تجویز هم زمان والپروات با لاموتریژین ممکن است غلظت سرمی والپرووات کاهش یابد ، در حالی که ممکن است غلظت لاموتریژین زیاد شود . دوز لاموتریژین را کاهش دهید . والپروات متابولیسم اتوسوکسماید را مهار می کند . غلظت سرمی هر دودارو را به خصوص در صورت مصرف هم زمان سایر داروهای ضد صرع کنترل کنید . آنتی سایکوتیک ها با کاهش آستانه تشنج به صورت آنتاگونیست فعالیت ضد صرع والپروات عمل می کنند . کلسترامین ممکن است جذب والپرووات را کاهش دهد . مشاهده شده است که تجویز اسید والپروییک با آنتی اسید هیدروکسید آلومینیوم و منیزیوم به طور مشخص فراهم زیستی آن را در فرد سالم افزایش می دهد . مصرف هم زمان دارو با الکل موجب کاهش اثر والپروییک اسید و تشدید عوارض جانبی مغزی آن می شد . مصرف الکل در این بیماران باید قطع شود

والپروات را به بیماران مبتلا یا دارای سابقه اختلال یا بیماری کبدی ، دارای سابقه فامیلی ابتلا به اختلال بسیار شدید کبدی و دارای حساسیت مفرط به دارو تجویز نکنید . کودکان کمتر از 3 سال و افراد مبتلا به بیماری های متابولیک ارثی، آسیب ارگانیک مغزی ، اختلالات تشنجی شدید همراه با عقب ماندگی ذهنی بیشتر در خطر مسمومیت کبدی هستند . در این افراد با احتیاط کامل تجویز کنید . در صورت امکان از تجویز با سایر داروهای ضد صرع که آن ها نیز ممکن است موجب آسیت کبد شوند ،اجتناب کنید. از تزریق والپروات به بیمار دچار ترومای حاد سرو به منظور پیشگیری از تشنج بعد از تروما استفاده نکنید ( این کار با میزان مرگ بیشتری همراه بوده است ) سودمندی واثر بخشی دی والپروئکس برای درمان مانیا در افراد کمتر از 18 سال و برای درمان میگرن در افراد کمتر از 16 سال ثابت نشده است . در تجویز والپروات با سایر داروهایی که با انعقاد خون در ارتباط هستند ( مثل آسپیرین و وارفارین ) احتیاط کنید . در بیماران مبتلا به لوپوس اریتماتوز با احتیاط تجویز کنید

در دمای 30-15 درجه سانتی گراد و در ظروف مقاوم به هوا نگهداری کنید

برای استفاده از خدمات مشاوره و نوبت دهی آنلاین با عضویت در دکتر ساینا به خانواده ی بزرگ سلامت الکترونیک ایران بپیوندید.

تمامی حقوق مادی و معنوی متعلق به شرکت دانش بنیان نوین فناوران همراه ساینا میباشد.

1Sandoz Development Center Holzkirchen, Holzkirchen, Germany

2inVentiv Health Clinical, Montréal, Quebec, Canada

1Sandoz Development Center Holzkirchen, Holzkirchen, Germany

2inVentiv Health Clinical, Montréal, Quebec, Canada

قرص sandoz

3Center of Drug Absorption and Transport, Institute of Pharmacy, University of Greifswald, Greifswald, Germany

The aim was to assess the bioequivalence of Sandoz methylphenidate osmotic-controlled release (OCR) tablets (Sandoz [Methylphenidate[ MPH OCR) with Concerta®, a methylphenidate formulation indicated for the treatment of attention deficit/hyperactivity disorder (ADHD). Four open-label, randomized, single-dose, two-way crossover bioequivalence studies were conducted in healthy subjects: three fasting studies with 54-, 36- and 18-mg doses of methylphenidate, and one fed study with the 54-mg dose. The d- and l-threo-methylphenidate plasma levels were quantified using liquid chromatographic methods with tandem mass spectrometry (LC MS/MS). Bioequivalence of the formulations was accepted if the 90% geometric confidence intervals of the ratio of least-squares means of Sandoz MPH OCR to Concerta® of ln-transformed area under the curve (AUC0–t) and Cmax were within the acceptance range of 80–125%. All studies met the bioequivalence criteria, and 90% geometric confidence intervals for AUC0–t and Cmax were within the predefined range. All plasma concentration time curves for Sandoz MPH OCR under fasting conditions showed a biphasic profile comparable with Concerta®, confirmed by bioequivalence of the partial metrics AUC0–2h, AUC2-24 h, Cmax(0–2 h) and Cmax(2–24 h). Both products were well tolerated and no relevant differences in the safety profiles were observed. It was concluded that Sandoz MPH OCR is bioequivalent to Concerta® in terms of rate and extent of absorption when administered as a single dose of one extended-release tablet of 54, 36, or 18 mg under fasting conditions and at a dose of 54 mg under fed conditions.

Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioural disorder which causes impairment in multiple domains of everyday functioning (Weisler and Childress 2011). Estimates of prevalence range from 1.7 to 17.8% depending on the population assessed and the diagnostic criteria applied (Markowitz et al. 2003). ADHD first presents in childhood and for many it persists into adulthood (Markowitz et al. 2003). Methylphenidate (MPH), a psychostimulant affecting both the dopaminergic and the noradrenergic systems, has an established safety and efficacy profile and is one of the most frequently prescribed treatments for ADHD in children and adults (Markowitz et al. 2003; Engert and Pruessner 2008; Janssen-Cilag 2013). It is available in both immediate-release formulations, which release MPH quickly upon ingestion, and extended-release formulations, which release some or all of the active substance more slowly over several hours. (Markowitz et al. 2003).

Concerta® (Janssen-Cilag), indicated for the treatment of ADHD in children and adults aged 6–65 years, is an extended-release formulation that has an immediate-release portion of 22% of the total drug load in a water soluble outer coating and an extended-release core that delivers 78% of the MPH dose. The extended-release core is an osmotic controlled-release oral delivery system (OROS) which is surrounded by the IR overcoat (López and Leroux 2013). Sandoz has developed a generic osmotic-controlled release (OCR) methylphenidate formulation (Sandoz MPH OCR) to be bioequivalent to Concerta®.

The Concerta® formulation delivers a biphasic plasma concentration curve for MPH with two phases of drug release. The first phase is determined by the immediate-release dose fraction, which provides a therapeutic drug level shortly after administration and is thought to prevent the development of acute tolerance to MPH (Markowitz et al. 2003; Swanson et al. 2003). The second phase provides the dose of MPH required to maintain an effective therapeutic level for a prolonged period (Markowitz et al. 2003; Swanson et al. 2003). The European Medicines Agency (EMA) guidelines (The European Medicines Agency 1999) in general require bioequivalence studies under fasting, fed, and multiple doses for a generic modified-release product. In the case of Sandoz MPH OCR, a multiple-dose study was not required as no drug accumulation occurs (Sandoz 2011). Furthermore, for biphasic products, bioequivalence must be established in both the immediate- and extended-release phases (The European Medicines Agency 2013). In vivo bioequivalence is almost always established in healthy adult volunteers and this is regarded as adequate for extrapolation to all populations in which the drug is approved, including both adults and children (EMA CPMP/QWP/EWP/1401/98 Rev. 1, 2010).

It was the goal of the studies to assess bioequivalence, compare the rate and extent of absorption, and characterize the pharmacokinetic profile of Sandoz MPH OCR relative to Concerta® in healthy adult human male subjects at 54-, 36- and 18-mg doses under fasting conditions, and with a 54-mg dose under fed conditions. Furthermore, the safety of the formulations was also assessed during the study program on the basis of clinical and laboratory examinations and adverse events were documented.

Four open-label, randomized, single-dose, two-way crossover bioequivalence studies were conducted between November 2009 and April 2010 at a single centre in Québec, Canada. The duration of the clinical part of each trial was approximately 9 days (approximately 10 h prior to the dose administration in Period I until 24 h after the administration of the product in Period II). This included a washout period of 7 days (at least 10 times the mean half-life of methylphenidate hydrochloride [Janssen-Cilag 2013[), which was chosen to allow the complete elimination of the drug before subsequent dosing and to avoid carry-over effects (Fig.(Fig.1).1). A total of 22 blood samples were collected prior to drug administration and up to 24 h post-dose, in each period, in each study.

Design of the four bioequivalence studies.

Three studies were conducted under fasting conditions with MPH doses of 54, 36 and 18 mg, respectively; the fourth study was conducted under fed conditions with a dose of 54 mg. The pharmacokinetic profile of Sandoz MPH OCR was characterized relative to Concerta®, and bioequivalence was assessed. For the fasting studies, subjects were fasted for at least 10 h before dosing and were served a controlled meal not less than 4 h post-dose and at appropriate times thereafter, in each period. For the 54-mg dose fed study, after a supervised overnight fast of at least 10 h, and 30 min before drug administration, subjects were served a high-fat, high-caloric breakfast of ∼800–1000 calories, which was in line with EMA and FDA guidelines (The US Food and Drug Administration 2002). The breakfast consisted of two eggs fried in butter, two slices of toast with butter, two strips of bacon, approximately 128 g of hash brown potatoes, and 200 mL of whole milk (3.25% milk fat). Subsequent to dosing, subjects were served a controlled meal not less than 4 h post-dose, and at appropriate times thereafter, in each period.

Healthy Caucasian male volunteers were enrolled; all were aged between 18 and 55 years, were non-smokers and had a Body Mass Index (BMI) of 19–27 kg/m2, with no significant illness or clinically significant abnormal findings during screening. Other exclusion criteria included known history of allergic reactions to MPH, and participation in another clinical trial within a period of 30 days prior to the first dose of study medication.

Eligible subjects were enrolled after signing informed consent documents. The clinical study protocol, informed consent documents and information forms were reviewed and approved by an Institutional Review Board (Institutional Review Board Services, Québec, Canada) and the Therapeutic Product Division (TPD) of Health Canada prior to beginning associated study procedures. The study was conducted in accordance with the Declaration of Helsinki and local regulatory requirements.

For each study, 24 subjects were randomized and dosed with Sandoz MPH OCR (Sandoz Development Center Holzkirchen, Holzkirchen, Germany), and with Concerta® (Janssen-Cilag, Neuss, Germany), according to the randomisation schedule. Whole blood samples were collected prior to dosing, and over a period of 24 h following each dose. All blood samples were drawn into pre-chilled (ice-water bath) blood collection tubes (1 × 3 mL) containing ethylenediaminetetraacetic acid (EDTA) K2. After collection, blood samples were cooled in an ice bath, prior to being centrifuged at 3000 rpm (corresponding to approximately 1900 g) for at least 10 min at approximately 4°C. Two aliquots of at least 0.5 mL (when possible) of plasma were dispensed into polypropylene tubes (as soon as possible), containing a stabilizing solution (EDTA Na2 10% w/v, citric acid 10% w/v in water), resulting in a buffer : plasma ratio of 5% v/v and were vortexed. The aliquots were subsequently transferred to a −80°C freezer, pending transfer to the bioanalytical facility.

d-threo-methylphenidate and l-threo-methylphenidate plasma levels were both quantified using fully validated liquid chromatographic methods with tandem mass spectrometry (LC MS/MS). The method was developed by inVentiv Health Clinical, Montréal, Canada. The validation of the bioanalytical method followed international guidelines (FDA, 2001).

The analytes d-threo-methylphenidate and l-threo-methylphenidate and their internal standard methylphenidate-d9 were extracted from a 0.200 mL aliquot of human EDTA K2 plasma using an automated liquid–liquid extraction. The extracted samples were injected into a liquid chromatograph equipped with a Chirobiotic (V), 150 × 4.6 mm, 5 μm column. The mobile phase was a mixture of methanol and acetic acid 0.15% (v/v) and ammonium hydroxide 0.05% (v/v). The isocratic chromatographic separation was performed at room temperature at a flow rate of 1.5 mL/min. The detection was made with a tandem mass spectrometry detector API 5000 (AB SCIEX, Concord, ON, Canada).

The lower limit of quantification of the analytical method for d-threo-methylphenidate was 0.15, 0.15, and 0.05 ng/mL for the 54, 36 and 18 mg doses, respectively. The lower limit of quantification of the analytical method for l-threo-methylphenidate was 6, 4, and 2 pg/mL for the 54, 36, and 18 mg doses, respectively. The upper limit of quantification of the analytical method for d-threo-methylphenidate was 30, 30, and 10 ng/mL for the 54, 36, and 18 mg doses, respectively. The upper limit of quantification of the analytical method for l-threo-methylphenidate was 600, 400, and 200 pg/mL for the 54, 36, and 18 mg doses, respectively. Plasma samples from subjects who did not complete the study were analysed and reported, but results were not used for statistical analysis. All bioanalytical work was conducted in compliance with Good Laboratory Practices.

Pharmacokinetic assessment of bioequivalence was considered a suitable surrogate for efficacy evaluation. Evaluations were based on pharmacokinetic parameters (AUC0–t, AUC0-inf, Cmax, residual area: calculated as 100*(1 − AUC0–t/AUC0–inf), Tmax, Cmax, T½el, and Kel) of d-threo-methylphenidate, which were calculated using Bioequiv (version 3.50, Anapharm, Montreal, QC, Canada) software, developed and tested for bioequivalence studies. The partial metrics AUC0–2h, AUC2–24h, Cmax(0–2h), and Cmax(2–24h) were also calculated for the fasting studies to evaluate the biphasic pharmacokinetic profiles of the two products.

All subjects who received a treatment dose were considered for the safety evaluation. Safety and tolerability evaluations were based on adverse event monitoring, physical examination, vital sign measurements (including oral temperature), and standard laboratory evaluation (haematology, biochemistry, endocrinology, and urinalysis).

According to Hauschke et al. (1992), a sample size of 20 subjects was estimated to be sufficient to show bioequivalence (intra-subject coefficients of variation for AUC and Cmax for d-methylphenidate: 21% or smaller; significance level: 5%; expected deviation from the reference: 5% (point-estimate); power: 80%) with an acceptance range for the 90% confidence interval of AUC0-t and Cmax within 0.80 and 1.25 for d-threo-methylphenidate. To account for possible dropouts, 24 subjects were enrolled in each study in order to complete with a minimum of 20.

For statistical analysis, only subjects completing both treatment periods were considered for pharmacokinetic evaluation. Administration of MPH extended-release tablets has been shown to result in plasma concentrations of the l-isomer of MPH of approximately 1/40th the plasma concentrations of the d-isomer (Janssen-Cilag 2013). Due to the low concentration and the resulting minor contribution of the l-isomer to the pharmacological activity, only the active d-isomer was evaluated for bioequivalence determination, in line with EMA guidelines on the investigation of bioequivalence (The European Medicines Agency 2010). All analyses of variance (ANOVAs) were performed with the SAS (release 8.2 for Windows) general linear models procedure (GLM). The ratio of means (Sandoz MPH OCR/Concerta®) and 90% geometric confidence interval for the ratio of means, based on least-squares means from the ANOVA of the ln-transformed data, were calculated for AUC0–t, AUC0–inf, and Cmax. Tmax was reported descriptively. In accordance with the protocol, bioequivalence was based on the 90% geometric confidence interval of the ratio (Sandoz MPH OCR/Concerta®) of least-squares means from the ANOVA of the ln-transformed AUC0–t and Cmax falling within the range of 80% to 125% for d-threo-methylphenidate. In addition, ratio of means and 90% geometric confidence intervals were also calculated for the partial metrics AUC0–2h, AUC2–24h, Cmax(0–2h), and Cmax(2–24h) for the fasting studies, in order to also confirm bioequivalence for both the immediate- and extended-release phases.

As per the protocol, in all four studies, 24 normal healthy volunteers were enrolled and randomized and were all eligible for the safety analysis. For the 36-mg dose fasting study, two subjects withdrew (one for personal reasons and one for failure to attend Period II) and were not eligible for pharmacokinetic analysis. In the 54-mg fed study, three subjects were withdrawn after Period I (one due to positive urine cotinine test at check-in for Period II, one was unable to attend Period II and one was withdrawn due to positive alcohol breath test at check-in for Period II); the remaining 21 subjects completed the study and were eligible for pharmacokinetic analysis. For the 54, 36, and 18 mg fasting and 54 mg fed studies, enrolled subjects had a mean age of 37, 33, 33, and 37 years and mean BMI of 24.2, 24.2, 24.0, and 23.8, respectively (Table(Table11).

Baseline demographics by study.

Plasma samples from subjects who received any study medication were analysed and results reported. Samples from all subjects completing the study were included in the statistical analyses for d-threo-methylphenidate.

The pharmacokinetic parameters for Sandoz MPH OCR and Concerta® for each of the four studies are summarised in TablesTables22 and and3.3. The ratio of means (Sandoz MPH OCR/Concerta®) and 90% geometric confidence interval for the ratio of means, based on least-squares means from the ANOVA of the ln-transformed data are summarized in TablesTables44 and and5.5. Bioequivalence between the two formulations being compared was concluded if the 90% geometric confidence intervals of the ratio of least-squares means of Sandoz MPH OCR/Concerta® of ln-transformed AUC0–t and Cmax were within the acceptance range of 80% to 125%. As an example, the ratio for key pharmacokinetic parameters for the 18-mg fasting study were: 95.83% (90% CI: 92.99–98.76%) for AUC0–t, 96.35% (90% CI: 93.64–99.13%) for AUC0–inf, and 96.08 (90% CI: 89.24–103.44%) for Cmax. All other studies also met the bioequivalence criteria as 90% geometric confidence intervals for both AUC0–t and Cmax were within the predefined range.

Descriptive statistics of pharmacokinetic parameters for Sandoz MPH OCR and Concerta® in the fasting studies.

Descriptive statistics of pharmacokinetic parameters for Sandoz MPH OCR and Concerta® in the fed study.

Ratio of means (Sandoz MPH OCR/Concerta®) and 90% confidence intervals based on least-squares means from the ANOVA of the ln-transformed data from the fasting studies.

Ratios calculated using least-squares means according to the formula: e(treatment A (test) − treatment B (reference)) × 100. 90% geometric confidence interval uses ln-transformed data.

Ratio of means (Sandoz MPH OCR/Concerta®) and 90% confidence intervals based on least-squares means from the ANOVA of the ln-transformed data from the fed study.

Ratios calculated using least-squares means according to the formula: e(treatment A (test) − treatment B (reference)) × 100. 90% geometric confidence interval uses ln-transformed data.

FigureFigure22 shows the mean plasma concentration of d-threo-methylphenidate over time, after administration of Sandoz MPH OCR and Concerta® for the 18-mg fasting study. The plasma concentration time curves under fasting conditions showed a biphasic profile, and were comparable with Concerta®. This was confirmed by bioequivalence of the partial metrics AUC0-2 h, AUC2-24 h, Cmax(0-2h), and Cmax(2–24h). The ratio for the partial pharmacokinetic parameters for the 18-mg fasting study were as follows: 100.30% (90% CI: 91.15–110.36%) for AUC0–2h, 95.58% (90% CI: 92.81–98.44%) for AUC2–24h, 101.99% (90% CI: 94.28–110.33%) for Cmax(0-2h), and 96.08% (90% CI: 89.04–103.44%) for Cmax(2-24h).

Mean plasma concentration of d-threo-methylphenidate over time, after administration of an 18-mg dose of Sandoz MPH OCR or Concerta® to healthy adult male subjects under fasting conditions.

Under fed conditions, only approximately 50% of the profiles under both Concerta® and the Sandoz product were biphasic, whereas the other 50% of profiles showed a continuous increase. Therefore, separation of the immediate-release and extended-release phases was not possible.

In all studies both formulations were well tolerated, with no major side effects and no relevant differences in safety profiles with respect to the number and pattern of adverse events. A summary of the numbers of treatment-emergent adverse events (TEAEs) for each product is given in TableTable6.6. The most commonly reported TEAEs were “headache,” “palpitations” and “procedural site reaction.” Of the 74 TEAEs reported from the four studies, 47 were suspected to be related to the study medication. In the 54-mg fed study and the 36-mg fasting study, the number of subjects who experienced TEAEs following the administration of Concerta® was greater than the number experienced after administration of Sandoz MPH OCR, but this was not considered significant. The majority of TEAEs were mild; there were no serious adverse events or deaths in any of the studies.

Summary of the number of common (≥2) treatment-emergent adverse events by product and study.

Sandoz MPH OCR was found to be bioequivalent to Concerta® in terms of rate and extent of absorption when administered as a single dose of one extended-release tablet of 54, 36 or 18 mg under fasting conditions and at 54 mg under fed conditions. According to the relevant EMA Committee for Medicinal Products for Human Use (CHMP) guideline, bioequivalence can be established if the 90% confidence interval for the ratio Test/Reference of geometric least squares means for Cmax and AUC0–t falls within the acceptance limits of 80–125% (The European Medicines Agency 2010). Results from the studies confirmed that all pharmacokinetic parameters were clearly within the predefined acceptance limits. It is therefore possible to conclude that Sandoz MPH OCR is bioequivalent to Concerta® at doses of 54, 36, and 18 mg under fasting conditions and at a dose of 54 mg under fed conditions.قرص sandoz

Concerta® exhibits a biphasic plasma concentration profile. This biphasic drug release is thought to prevent acute tolerance to MPH and to maintain efficacy throughout the day (Markowitz et al. 2003; Swanson et al. 2003). Sandoz MPH OCR was found to be equivalent to the OROS of Concerta®, as evidenced by the similar biphasic pharmacokinetic profile shown for the two products. The partial pharmacokinetic metrics for the fasting studies confirmed that Sandoz MPH OCR was bioequivalent to Concerta® in both the immediate- and extended-release phases. The cut-off of 2 h was chosen in line with EMA guidance (The European Medicines Agency 2013) according to the overall shape of the pharmacokinetic profile. Partial metrics using a cut-off of 3 h (AUC0–3h, AUC3–24h, Cmax(0–3h) and Cmax(3–24h)) also demonstrated bioequivalence (data not shown).

Under fed conditions, only approximately 50% of profiles are biphasic for both Sandoz MPH OCR and Concerta®. The remaining profiles show a continuous increase, which means that drug release from the immediate-release and extended-release phase overlap and cannot be separated by a cut-off; hence the immediate-release and the extended-release phase cannot be adequately characterized using partial pharmacokinetic parameters under fed conditions (Modi et al. 2000). The two different types of profiles (biphasic or continuous) under fed conditions are most likely caused by differences in the first site of deposition of the dosage form within the stomach directly after ingestion. If the tablet is deposited in the antrum of the stomach, the dissolved drug from the immediate-release phase can bypass the stomach contents and is quickly transported to the intestine where is can be absorbed. In this case, a biphasic profile can be observed. On the other hand, if the tablet is deposited in the fundus of the stomach, the dissolved drug from the immediate-release phase is trapped by the high-fat meal in the stomach and only reaches the intestine with delay. Absorption only takes place at a later time when drug is already released from the extended-release phase of the dosage form. Thus, absorption from the two phases overlaps, resulting in a continuous profile. Such behaviour has been demonstrated for a biphasic amoxicillin/clavanulate fixed-dose combination. (Weitschies et al. 2008) It should be noted that, despite the differences in the shape of the pharmacokinetic profiles, the products can be taken under both fasting and fed conditions. (Janssen-Cilag 2013; Sandoz 2011).

Both products were well tolerated and no relevant differences in the safety profiles were observed between Sandoz MPH OCR and Concerta®. There were no serious adverse events or deaths in any of the studies.

Sandoz MPH OCR was shown to be bioequivalent to Concerta® in terms of rate and extent of absorption when administered as a single dose of one extended-release tablet of 54, 36, or 18 mg under fasting conditions and at a dose of 54 mg under fed conditions.

The authors acknowledge Synergy, who provided medical writing and editorial assistance on behalf of Sandoz. The authors had the final responsibility for the decision to submit for publication. Funding for these studies was provided by Sandoz Development Center Holzkirchen, Holzkirchen, Germany. All Authors contributed equally to the development of this manuscript.

E. S., H. D, and U. T.-F. are employees of Sandoz Development Center Holzkirchen. W. W. has received consultancy fees from Sandoz Development Center Holzkirchen. S. L. and F. V. are employees of inVentiv Health Clinical, which conducted the studies.

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