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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)

Fortzaar is a combination of an angiotensin II receptor antagonist (losartan) and a diuretic (hydrochlorothiazide). Angiotensin II is a substance produced in the body which binds to receptors in blood vessels, causing them to tighten. This results in an increase in blood pressure.

Losartan prevents the binding of angiotensin II to these receptors, causing the blood vessels to relax which in turn lowers the blood pressure. Hydrochlorothiazide works by making the kidneys pass more water and salt. This also helps to reduce blood pressure.

 

Fortzaar is indicated for the treatment of essential hypertension (high blood pressure).


Do not take Fortzaar

·            if you are allergic to losartan, hydrochlorothiazide or to any of the other ingredients of this medicine (listed in section 6),

·            if you are allergic to other sulfonamide-derived substances (e.g. other thiazides, some antibacterial drugs such as co-trimoxazole, ask your doctor if you are not sure),

·            if you have severely impaired liver function,

·            if you have low potassium, low sodium or high calcium levels which cannot be corrected by treatment,

·            if you are suffering from gout,

·            if you are more than 3 months pregnant (It is also better to avoid Fortzaar in early pregnancy - see Pregnancy section),

·            if you have severely impaired kidney function or your kidneys are not producing any urine,

·            if you have diabetes or impaired kidney function and you are treated with a blood pressure lowering medicine containing aliskiren.

 

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before taking Fortzaar.

 

You must tell your doctor if you think you are (or might become) pregnant. Fortzaar is not recommended in early pregnancy, and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby if used at that stage (see pregnancy section).

 

It is important to tell your doctor before taking Fortzaar:

 

·            if you have previously suffered from swelling of the face, lips, throat or tongue

·            if you take diuretics (water pills)

·            if you are on a salt-restricted diet

·            if you have or have had severe vomiting and/or diarrhoea

·            if you have heart failure

·            if your liver function is impaired (see section 2 “Do not take Cozaar Comp”)

·            if you have narrow arteries to your kidneys (renal artery stenosis) or only have one functioning kidney, or you have recently had a kidney transplant

·            if you have narrowing of the arteries (atherosclerosis), angina pectoris (chest pain due to poor heart function)

·            if you have ‘aortic or mitral valve stenosis’ (narrowing of the valves of the heart) or ‘hypertrophic cardiomyopathy’ (a disease causing thickening of heart muscle)

·            if you are diabetic

·            if you have had gout

·            if you have or have had an allergic condition, asthma or a condition that causes joint pain, skin rashes and fever (systemic lupus erythematosus).

·            if you have high calcium or low potassium levels or you are on a low potassium diet

·            if you need to have an anaesthetic (even at the dentist) or before surgery, or if you are going to have tests to check your parathyroid function, you must tell the doctor or medical staff that you are taking losartan potassium and hydrochlorothiazide tablets.

·            if you suffer from primary hyperaldosteronism (a syndrome associated with increased secretion of the hormone aldosterone by the adrenal gland, caused by an abnormality within the gland),

·            if you are taking any of the following medicines used to treat high blood pressure:

o      an ACE-inhibitor (for example enalapril, lisinopril, ramipril), in particular if you have diabetes-related kidney problems.

o      aliskiren

Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g. potassium) in your blood at regular intervals.

See also information under the heading “Do not take Fortzaar”.

 

Children and adolescents

There is no experience with the use of Fortzaar in children. Therefore, Fortzaar should not be given to children.

 

Other medicines Fortzaar

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

 

Diuretic agents such as the hydrochlorothiazide contained in Fortzaar may interact with other medicines.

 

Preparations containing lithium should not be taken with Fortzaar without close supervision by your doctor.

 

Special precautionary measures (e.g. blood tests) may be appropriate if you take potassium supplements, potassium-containing salt substitutes or potassium-sparing medicines, other diuretics

 

(“water tablets”), some laxatives, medicines for the treatment of gout, medicines to control heart rhythm or for diabetes (oral agents or insulins).

 

It is also important for your doctor to know if you are taking:

·            other medicines to reduce your blood pressure

·            steroids

·            medicines to treat cancer

·            pain killers

·            drugs for treatment of fungal infections

·            arthritis medicines

·            resins used for high cholesterol, such as colestyramine

·            medicines which relax your muscles

·            sleeping tablets

·            opioid medicines such as morphine

·            ‘pressor amines’ such as adrenaline or other drugs from the same group

·            oral agents for diabetes or insulins

 

Your doctor may need to change your dose and/or to take other precautions:

If you are taking an ACE-inhibitor or aliskiren (see also information under the headings “Do not take Fortzaar” and “Warnings and precautions”)

 

Please also inform your doctor you are taking Fortzaar if you will be undergoing a radiographic procedure and will be given iodine contrast media.

 

Fortzaar with food and drink

You are advised not to drink alcohol whilst taking these tablets: alcohol and Fortzaar tablets may increase each other’s effects.

 

Dietary salt in excessive quantities may counteract the effect of Fortzaar  tablets. Fortzaar tablets may be taken with or without food.

Pregnancy and breast-feeding Pregnancy

You must tell your doctor if you think you are (or might become) pregnant. Your doctor will normally advise you to stop Fortzaar before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Fortzaar. Fortzaar is not recommended during pregnancy, and must not be taken when more than 3 months pregnant, as it may cause serious harm to your baby if used after the third month of pregnancy.

 

Breast-feeding

Tell your doctor if you are breast-feeding or about to start breast-feeding. Fortzaar is not recommended for mothers who are breast-feeding, and your doctor may choose another treatment for you if you wish to breast-feed.

 

Use in elderly patients

Fortzaar works equally well in and is equally well tolerated by most older and younger adult patients. Most older patients require the same dose as younger patients.

 

Driving and using machines

When you begin treatment with this medication, you should not perform tasks which may require special attention (for example, driving an automobile or operating dangerous machinery) until you know how you tolerate your medicine.

 

Fortzaar contains lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

 


Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. Your doctor will decide on the appropriate dose of Fortzaar depending on your condition and whether you are taking other medicines. It is important to continue taking Fortzaar for as long as your doctor prescribes it in order to maintain smooth control of your blood pressure.

 

High Blood Pressure

The usual dose of Fortzaar/Hyzaar for most patients with high blood pressure is 1 tablet of Hyzaar 50 mg/12.5 mg per day to control blood pressure over the 24-hour period. This can be increased to 2 tablets once daily of Losartan / Hydrochlorothiazide 50 mg/12.5 mg Film-Coated Tablets or changed to 1 tablet daily of Losartan / Hydrochlorothiazide 100 mg/25 mg Film-Coated Tablets (a stronger strength) per day. The maximum daily dose is 2 tablets per day of Losartan / Hydrochlorothiazide 50 mg/12.5 mg Film-Coated Tablets or 1 tablet daily of Losartan / Hydrochlorothiazide 100 mg/25 mg Film-Coated Tablets

 

Administration

The tablets should be swallowed whole with a glass of water.

 

If you take more Fortzaar than you should

In case of an overdose, contact your doctor immediately so that medical attention may be given promptly. Overdose can cause a drop in blood pressure, palpitations, slow pulse, changes in blood composition, and dehydration.

 

If you forget to take Fortzaa

Try to take Fortzaar daily as prescribed. However, if you miss a dose, do not take an extra dose. Just resume your usual schedule.

 


 

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

 

If you experience the following, stop taking Fortzaar tablets and tell your doctor immediately or go to the casualty department of your nearest hospital:

 

A severe allergic reaction (rash, itching, swelling of the face, lips, mouth or throat that may cause difficulty in swallowing or breathing).

 

This is a serious but rare side effect, which affects more than 1 out of 10,000 patients but fewer than 1 out of 1,000 patients. You may need urgent medical attention or hospitalisation.

 

The following side effects have been reported:

 

Common (may affect up to 1 in 10 people):

·            Cough, upper airway infection, congestion in the nose, sinusitis, sinus disorder

·            Diarrhoea, abdominal pain, nausea, indigestion

·            Muscle pain or cramps, leg pain, back pain

·            Insomnia, headache, dizziness

·            Weakness, tiredness, chest pain

·            Increased potassium levels (which can cause an abnormal heart rhythm), decreased haemoglobin levels

·            Changes in kidney function including kidney failure

·            Too low sugar in the blood (hypoglycaemia)

 

Uncommon (may affect up to 1 in 100 people):

·            Anaemia, red or brownish spots on the skin (sometimes especially on the feet, legs, arms and buttocks, with joint pain, swelling of the hands and feet and stomach pain), bruising, reduction in white blood cells, clotting problems, reduced number of platelets

·            Loss of appetite, increased uric acid levels or frank gout, increased blood sugar levels, abnormal blood electrolyte levels

·            Anxiety, nervousness, panic disorder (recurring panic attacks), confusion, depression, abnormal dreams, sleep disorders, sleepiness, memory impairment

·            Pins and needles or similar sensations, pain in the extremities, trembling, migraine, fainting

·            Blurred vision, burning or stinging in the eyes, conjunctivitis, worsening eyesight, seeing things in yellow

·            Ringing, buzzing, roaring or clicking in the ears, vertigo

·            Low blood pressure, which may be associated with changes in posture (feeling light-headed or weak when you stand up, angina (chest pain), abnormal heartbeat, cerebrovascular accident (TIA, “mini-stroke”), heart attack, palpitations

·            Inflammation of blood vessels, which is often associated with a skin rash or bruising

·            Sore throat, breathlessness, bronchitis, pneumonia, water on the lungs (which causes difficulty breathing), nosebleed, runny nose, congestion

·            Constipation, obstipation, wind, stomach upsets, stomach spasms, vomiting, dry mouth, inflammation of a salivary gland, toothache

·            Jaundice (yellowing of the eyes and skin), inflammation of the pancreas

·            Hives, itching, inflammation of the skin, rash, redness of the skin, sensitivity to light, dry skin, flushing, sweating, hair loss

·            Pain in the arms, shoulders, hips, knees or other joints, joint swelling, stiffness, muscle weakness

·            Frequent urination including at night, abnormal kidney function including inflammation of the kidneys, urinary tract infection, sugar in the urine

·            Decreased sexual appetite, impotence

·            Swelling of the face, localised swelling (oedema), fever

 

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

·            Hepatitis (inflammation of the liver), abnormal liver function tests

 

Not known (frequency cannot be estimated from the available data):

·            Flu-like symptoms

·            Unexplained muscle pain with dark (tea-colored) urine (rhabdomyolysis)

·            Low levels of sodium in the blood (hyponatraemia)

·            Generally feeling unwell (malaise)

·            Disturbed taste (dysgeusia)

 

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), SFDA”. By reporting side effects, you can help provide more information on the safety of this medicine.


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

 

Do not use this medicine after the expiry date which is stated on the container. The expiry date is written on both carton & inner label.

 

Store below 30°C

 

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.

 


1.          What Fortzaar contains

The active substances are losartan potassium and hydrochlorothiazide.

 

 

Fortzaar 100 mg/25 mg contains 100 mg of losartan potassium and 25 mg of hydrochlorothiazide as the active ingredients.

 

Fortzaar 100 mg/25 mg contain the following inactive ingredients:

microcrystalline cellulose (E460), lactose monohydrate, pregelatinized maize starch, magnesium stearate (E572), hydroxypropyl cellulose (E463), hypromellose (E464).

 

Fortzaar 100 mg/25 mg contain 8.48 mg (0.216 mEq) of potassium.

 

Fortzaar 100 mg/25 mg also contain titanium dioxide (E171), quinoline yellow aluminum lake (E104) and carnauba wax (E903).

 

 


Fortzaar 100 mg/25 mg is supplied as light yellow, oval film-coated tablets marked 747 on one side and plain on the other. Fortzaar 100 mg/25 mg - PVC/PE/PVDC blister packages with aluminum foil lidding in cartons containing 7, 14, 28, 30, 50, 56, 84, 90, 98, or 280 tablets and unit-dose packages of 28, 56 and 98 tablets for hospital use. HDPE bottles of 100 tablets. Not all pack sizes may be marketed.

Marketing Authorization Holder:
 Merck Sharp & Dohme B.V., Waarderweg 39,
2031 BN Haarlem, P.O. Box 581, 2003 PC Haarlem, 
The Netherlands

Manufacturer:                                 
Merck Sharp & Dohme Ltd. Shotton Lane, 
Cramlington, Northumberland NE23 3JU
UK.

Packed by:
Pharma Pharmaceutical Industries,
Second Industrial Area,
P.O. Box 11351 Riyadh, Saudi Arabia


 


This leaflet was last revised in Oct 2017.Version No. (03)
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

فورتزار توليفة من دواء يُعرَف بمثبط مستقبلات الأنجيوتنسين الثاني (لوسارتان) ودواء مُدرّ للبول (هيدروكلوروثيازيد). الأنجيوتنسين الثاني مادة يتمّ إنتاجها في الجسم، تلتصق بالمستقبلات في الأوعية الدمويّة، ما يسبّب تضييقها ويؤدّي إلى ارتفاع في ضغط الدم. يمنع لوسارتان التصاق مادة الأنجيوتنسين الثاني بالمستقبلات، ممّا يؤدّي إلى استرخاء الأوعية الدمويّة التي، بدورها، تُخفّض ضغط الدم.

أمّا الهيدروكلوروثيازيد، فيُساعد الكلى على تمرير كميّة أكبر من المياه والملح، ممّا يُساهم في تخفيض ضغط الدم.

يتم استخدام فورتزار لمعالجة إرتفاع ضغط الدم.

 

لا تتناول فورتزار

في الحالات التالية:

-لديك حساسيّة تجاه مادة لوسارتان أو هيدروكلوروثيازيد أو أي مكوّنات أخرى من أقراص فورتزار (المدرجة في القسم ٦)

- إذا كان لديك حساسيّة على المواد الأخرى الناشئة عن السولفوناميد (مثلاً، مواد الثيازيد الأخرى، وبعض الأدوية المُضادة للبكتيريا، مثل كو-تريموكسازول، إسأل الطبيب في حال لم تكن متأكّدًا).

- إذا كنت تُعاني قصورًا حادًا في وظيفة الكبد.

- إذا كان مستوى البوتاسيوم أو الصوديوم منخفضًا جدًّا وإذا كان مستوى الكلسيوم مرتفعًا جدًّا، لا يُمكن تصحيحه بواسطة العلاج.

- إذا كنت تُعاني من مرض النقرس (داء المفاصل).

-إذا كنت حاملاً لأكثر من ثلاثة أشهر (كما من الأفضل تفادي تناول فورتزار في بداية الحمل - راجعي قسم الحمل)

-في حال وجود قصور حاد في وظيفة الكلى أو إذا كانت الكلى لا تُنتج البول.

-إذا كنت مصابًا بداء السكري أو تُعاني قصورًا في وظيفة الكلى وإذا كنت تخضغ لعلاج بواسطة دواء يُخفّض ضغط الدم يحتوي على الإليسكيرين.

التحذير والوقاية

إسأل الطبيب أو الصيدلي أو الممرضة قبل تناول فورتزار.

عليك إطلاع طبيبك إذا كنت تظنّين أنّك حامل (أو قد تصبحين حاملاً). لا يوصى بتناول فورتزار في بداية الحمل ويجب عدم تناوله إذا كنت حاملاً لأكثر من ٣ أشهر، لأنّه قد يُسبّب أذىً خطيرًا لجنينك في حال تناوله في هذه المرحلة (راجع قسم الحمل).

من المهمّ إبلاغ طبيبك قبل تناول فورتزار في الحالات التالية:

-      تعرّضت في الماضي لانتفاخ الوجه، أو الشفتَيْن، أو الحنجرة، أو اللسان

-      تتناول مدرّات للبول (أقراص ماء)

-       تتّبع حميّة غذائيّة بلا الملح

-      إنّك مصاب بالتقيّؤ أو الإسهال الحاد

-      تُعاني قصورًا في القلب

-      تُعاني قصورًا في وظيفة الكبد (راجع القسم 2 "لا تتناول فورتزار")

-      إذا كانت أوعيتك الدمويّة المؤدّية إلى الكلى ضيّقة أو إذا كانت لديك كلية واحدة تعمل أو إذا حصلت مؤخّرًا على زرع كلى

-      إذا كانت شراينيك الدمويّة ضيّقة (التصلّب الشرياني) أو تعرّضت لذبحة صدريّة (ألم في الصدر بسبب قصور في وظيفة القلب)

-      كنت مُصابًا بتضييق الصمّام الإكليلي أو تضييق الأبهر أو باعتلال قلبي تضخّمي (مرض يُسبّب تسميك عضلة القلب)

-      كنت مُصابًا بداء السكري

-      كنت مُصابًا بمرض النقرس (داء التهاب المفاصل)

-      كنت مُصابًا في الماضي أو في الحاضر بحساسيّة، أو الربو، أو حالة تُسبّب ألمًا في المفاصل، وطفح جلدي، وحمى (ذِئْبَة حُمَامِيَّة مَجْموعِيَّة).

-      إذا كان مستوى الكالسيوم لديك مرتفعًا أو مستوى البوتاسيوم منخفضًا أو إذا كنت تتّبع حمية غذائيّة خفيفة البوتاسيوم.

-      إذا كنت بحاجة إلى مُخدّر (حتى عند طبيب الأسنان) أو قبل الجراحة أو إذا كنت ستخضع لفحوصات للتأكّد من وظيفة الغدة  الجار درقية، عليك إطلاع الطبيب أو الموظّفين الطبيّين أنّك تتناول أقراص بوتاسيوم لوسارتان وهيدروكلوروثيازيد.

-      تعاني فرط الألدوستيرونيّة الأولي (أحد اضطرابات الغدة الكظريّة حيث تقوم الغدة بإنتاج كميّة كبيرة جدًا من هرمون الألدوستيرون، سببه خلل في الغدّة)

-      إذا كنت تتناول أحد الأدوية التالية المستخدمة لمعالجة ارتفاع ضغط الدم:

- مثبط إنزيم محوّل للأنجيوتنسين (مثلاً، إينالابريل، ليزينوبريل، راميبريل)، لا سيّما إذا كنت تُعاني مشاكل كلى سببها السكرّي

- دواءً إسمه اليسكيرين لتخفيض ضغط الدم

قد يتأكّد الطبيب من وظيفة الكلى، وضغط الدم، وكميّة الالكتروليت (مثلاً البوتاسيوم) في دمك ضمن فترات منتظمة.

راجع أيضًا المعلومات الواردة تحت عنوان "لا تتناول فورتزار ".

الأطفال والمراهقون

لا تجربة سابقة لاستخدام فورتزار لدى الأطفال. وبالتالي، يجب عدم إعطاء فورتزار إلى الأطفال.

تناول فورتزار مع أدوية أخرى

أطلع الطبيب أو الصيدلي في حال كنت تتناول دواءً آخر، أو قد تناولت دواءً مؤخّرًا، أو قد تتناول أي دواء آخر.

قد تتفاعل الأدوية المدرّة للبول مثل الهيدروكلوروثيازيد في فورتزار مع أدوية أخرى.

يجب عدم تناول مواد تحتوي على الليثيوم مع فورتزار من دون إشراف طبيبك.

وقد يكون من الملائم اتّخاذ إجراءات وقائيّة (مثلاً فحوصات دم) في حال تناولت مكمّلات بوتاسيوم، أو بدائل ملح تحتوي على البوتاسيوم، أو الأدوية الموفّرة للبوتاسيوم، أو مدرّات بول أخرى (أقراص مياه)، أو بعض المليّنات، أو الأدوية لمعالجة النقرس، أو أدوية لضبط دقّات القلب أو السكري (إنسولين أو أدوية فمويّة).

من المهمّ أيضًا أن يعرف طبيبك إذا كنت تتناول ما يلي:

-      أدوية أخرى لتخفيض ضغط الدم

-      ستيرويدات

-      أدوية لمعالجة السرطان

-      مسكّنات الألم

-      أدوية لمعالجة إلتهابات فطريّة

-      أدوية لمعالجة التهاب المفاصل

-      الراتين المُستخدَم لمعالجة مستوى الكولسترول المرتفع، مثل الكوليستيرامين

-      الأدوية لإرخاء العضلات

-      أقراص النوم

-      أدوية أفيونيّة، مثل المورفين

-      "أمينات  الضغط"، مثل الأدرينالين أو أدوية أخرى من المجموعة نفسها

-      الادوية الفمويّة لداء السكري أو الإنسولين

قد يحتاج الطبيب إلى تبديل جرعتك و/أو يطلب منك اتخاذ إجراءات وقائيّة أخرى:

إذا كنت تتناول مثبط الإنزيم المحوّل للأنجيوتنسين أو الأليسكيرين (راجع أيضًا المعلومات في القسم "لا تتناول فورتزار " و"التحذير والوقاية").

يُرجى إطلاع الطبيب في حال كنت تتناول فورتزار إذا كنت ستخضع لتصوير إشعاعي وستُعطى مادة اليود المُباينة.

تناول فورتزار مع المأكولات والمشروبات

يُنصح بعدم شرب الكحول عند تناول هذه الأقراص: فالكحول وأقراص فورتزار قد تزيد من آثار بعضها البعض.

كما قد يُبطل تناول الملح بكميّات كبيرة مفعول أقراص فورتزار.

يُمكن تناول فورتزار مع الأكل أو من دونه.

الحمل والرضاعة

الحمل

عليك إطلاع الطبيب في حال كنت تظنّين أنك حامل أو قد تصبحين حاملاً. ينصحك الطبيب عادةً بالتوقّف عن تناول فورتزار قبل أن تصبحي حاملاً أو ما أن تعرفي أنّك حامل وينصحك باستبداله بدواء آخر. لا يوصى بتناول فورتزار في بداية الحمل ويجب عدم تناوله بعد مرور ٣ أشهر على الحمل، بما أنّه قد يُلحق ضررًا خطيرًا بالجنين في هذه الحالة.

 

 

الرضاعة

أطلعي الطبيب في حال كنت ترضعين أو على وشك البدء بالرضاعة. لا يوصى فورتزار للأم المرضعة وقد يستبدل الطبيب فورتزار بدواء آخر في حال كنت ترغبين بالرضاعة.

الاستخدام لدى المرضى البالغين

يعمل فورتزار بشكل متساوٍ وتتقبّله غالبية المرضى البالغين الأكبر سنًا والأصغر. ويحتاج المرضى الأكبر سنًا في غالبيّتهم إلى الجرعة نفسها مقارنةً مع المرضى الأصغر سنًّا.

القيادة واستعمال الآليّات

عند البدء بالعلاج بواسطة هذا الدواء، عليك الامتناع عن القيام بأعمال تحتاج إلى انتباه خاص (مثلاً قيادة سيّارة أو تشغيل آليّات خطرة) حتى معرفة إذا كنت تتقبّل الدواء.

يحتوي فورتزار على اللاكتوز

إذا قال لك طبيبك إنّك لا تتقبَّل بعض السكريّات، اتصّل بطبيبك قبل تناول هذا الدواء.

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تناول فورتزار  دائمًا بحسب وصفة الطبيب أو الصيدلي. يجب مراجعة الطبيب أو الصيدلي في حال لم تكن متأكّدًا من ذلك. يقرّر الطبيب الجرعة الملائمة من فورتزار، حسب وضعك وإذا ما كنت تتناول أدوية أخرى. من المهمّ الاستمرار في تناول فورتزار  بناءً على وصفة الطبيب من أجل المحافظة على مُراقبة سهلة لضغط الدم.

ارتفاع ضغط الدم:

جرعة فورتزار و هيزار الاعتياديّة لغالبيّة المرضى المصابين بارتفاع ضغط الدم هي قرص واحد من  هيزار 50 ملغ/١٢.5 ملغ يوميًّا للسيطرة على مستوى ضغط الدم على فترة ٢٤ ساعة. يُمكن زيادة هذه الجرعة إلى قرصَيْن مرّةً واحدةً يوميًّا من الأقراص المغلّفة لوسارتان/هيدروكلوروثيازيد ٥۰ ملغ/١٢.5 ملغ أو تبديلها إلى قرص واحد يوميًّا من الأقراص المغلّفة لوسارتان/هيدروكلوروثيازيد ١۰۰ ملغ/٢٥ ملغ (قوّة أعلى يوميًّا). الجرعة اليوميّة القصوى هي قرصان يوميًّا للوسارتان/هيدروكلوروثيازيد ٥۰ ملغ/١٢.5 ملغ أو قرص واحد يوميًّا لوسارتان/هيدروكلوروثيازيد 100 ملغ/25 ملغ.

 

طريقة إعطاء الدواء:

ينبغي ابتلاع الأقراص كاملة مع كوب الماء.

 

 

 

اذا تناولت جرعات فورتزار أكثر من التي عليك تناولها

في حال تناولت جرعةً زائدةً، اتّصل بالطبيب على الفور للحصول على الرعاية الطبيّة بشكل سريع. من بين أعراض الجرعة الزائدة، انخفاض ضغط الدم، ودقّات القلب المتسارعة، وانخفاض محتمل لدقّات القلب، والجفاف، والتبدّلات في تركيبة الدم

 

إذا نسيت تناول فورتزار

حاول تناول فورتزار يوميًّا بحسب الوصفة. لكن، في حال فوّت جرعةً، لا تتناول جرعةً إضافيّة، بل استنأنف الجدول الزمني المُعتاد .

على غرار الأدوية كافةً، يُمكن أن يُسبّب فورتزار أعراض جانبيّة لبعض الأشخاص، وإن كانت لا تُصيب الجميع.

في حال اختبارك الأعراض الجانبيّة التالية، توقّف عن تناول أقراص فورتزار  وأخبر طبيبك فورًا أو توجَّه إلى قسم الطوارئ في أقرب مستشفى لك:

ردّة فعل حساسيّة حادة (طفح جلدي، حكاك، تورّم الوجه، أو الشفتَيْن، أو الفم، أو الحنجرة، ما قد يُسبّب صعوبةً في البلع أو التنفّس).

إنّه أثر خطير، إنّما نادر، يُصيب أكثر من مريض من أصل ١٠٠٠٠، إنّما أقلّ من مريض من أصل ١٠٠٠. قد تحتاج إلى دخول المستشفى أو إلى رعاية طبيّة طارئة.

إلى ذلك، تم التبليغ عن الأعراض الجانبيّة التالية لدى الأشخاص الذين يتناولون فورتزار:

 

الأعراض الشائعة (قد تؤثّر على شخص من أصل ١٠)

-السعال، إلتهاب المجاري الهوائيّة العُليا، إحتقان الأنف، إلتهاب الجيوب الأنفيّة، اضطرابات في الجيوب الأنفيّة

- الاسهال، الألم البطني، الغثيان،  عسر في الهضم

- الم في العضلات، تشنجات، الم في الساق، الم في الظهر

- الأرق، الصداع، الدوار

- الوهن، التعب، الألم في الصدر

- ارتفاع مستوى البوتاسيوم (ممّا قد يُسبّب دقّات قلب غير منتظمة) وانخفاض مستوى الهيموغلوبين

- خلل في وظيفة الكلى، بما في ذلك الفشل الكلوي

-انخفاض حاد لمستوى السكر في الدم

 

الأعراض غير الشائعة (قد تؤثّر على شخص من أصل ١٠٠):

-      فقر الدم أو بقع حمراء أو مائلة إلى اللون البني على الجلد (أحيانًا، بشكل خاص، على القدمَيْن، والساقَيْن، والذراعَيْن، والردفَيْن، مع ألم في المفاصل، وانتفاخ اليدَيْن والقدمَيْن وألم في المعدة)، والتكّدم، وانخفاض عدد خلايا الدم البيضاء، ومشاكل تخثّر، وانخفاض عدد الصفيحات الدموية.

-      فقدان الشهيّة، وزيادة مستويات الحمض البولي أو  مرض النقرس، وزيادة مستوى السكر في الدم، مستوى غير طبيعي للالكتروليت في الدم.

-      الأرق، والتوتّر، واضطرابات الهلع (نوبات هلع متكرّرة)، والارتباك، والاكتئاب، والأحلام غير الطبيعيّة، واضطرابات النوم، والشعور بالنعاس، وعجز الذاكرة.

-      الإبر والوخز أو أحاسيس مُشابهة، وألم في الأطراف، ورجفان، وصداع نصفي، وفقدان الوعي

-      تغيّم الرؤية، و حرقة أو وخز في العينَيْن، والتهاب الملتحمة، وتدهور النظر، ورؤية الأشياء باللون الأصفر

-      الرنين، أو الأزيز أو الطنين أو القلقلة في الأذنَيْن، الشعور بالدوار

-      إنخفاض ضغط الدم، الذي  يصاحب تغيير الوضعيّة (الشعور بالدوخة أو بالوهن عند الوقوف)، الذبحة (ضيق النفس)، دقّات قلب غير طبيعيّة، وحادثة وعائيّة دماغيّة (سكتة مُصغّرة)، ونوبة قلبيّة،  وخفقان

-      إلتهاب الأوعية الدمويّة، الذي غالبًا ما يكون مربوطًا بالتكدّم أو الطفح الجلدي

-      ألم في الحنجرة، وانقطاع النفس، والتهاب الشعب الهوائيّة، والالتهاب الرئوي، ومياه في الرئتَيْن (ممّا يُسبّب صعوبة في التنفّس)، ونزيف الأنف، ورشح، واحتقان الأنف

-      امساك، وإمساك عنيد، وريح، وتقلّبات المعدة، وتقلصات في المعدة، وتقيّؤ، وجفاف في الفم، والتهاب الغدة اللعابيّة، وألم في الأسنان

-      اليرقان (إصفرار العينَيْن والبشرة) وإلتهاب البنكرياس

-      الشرى، والحكة، والتهاب  الجلد، والطفح الجلدي، واحمرار البشرة، والحساسيّة  من الضوء، وجفاف البشرة، والهبّات الساخنة، والتعرّق، وفقدان الشعر

-      ألم في الذراعَيْن، أو الكتفَيْن، أو الوركَيْن، أو الركبة، أو المفاصل الأخرى، وانتفاخ المفاصل، والتصلّب، والوهن في العضلات

-      التبوّل  المتكرر، بما في ذلك التبوّل ليلًا،  خلل في وظيفة الكلى، بما في ذلك التهاب الكلى، والتهاب المجاري البوليّة، ووجود سكر في  البول

-      انخفاض الرغبة الجنسيّة، والعجز الجنسي

-      انتفاخ الوجه، وانتفاخ مُحدَّد الموقع (وذمة)، والحمى

 

أعراض جانبيّة نادرة (قد تؤثّر على شخص من أصل ١٠٠٠):

-التهاب الكبد ونتائج غير طبيعيّة لاختبارات وظيفة الكبد

 

أعراض جانبيّة غير معروفة الوتيرة (لا يُمكن تقدير الوتيرة بناءً على البيانات المتوفّرة):

- الأعراض الشبيهة بأعراض الرشح

- الألم غير  مبرر في العضل مع بول داكن (بلون الشاي) (انحلال الربيدات)

- مستوى الصوديوم المنخفض في الدم

- الشعور العام بالانزعاج

- تبدّل حاسة الذوق (خلل الذوق)

الابلاغ عن الأعراض الجانبيّة

في حال لاحظت أعراض جانبيّةً، حتى تلك غير واردة في هذا الكتيّب، يُرجى إطلاع الطبيب أو الصيدلي أو الممرّضة. يمكنك أيضا الابلاغ عن الأعراض الجانبيّة عن طريق الاتصال ب " المركز الوطني للتيقظ والسلامة الدوائية، التابع لهيئة العامة للغذاء والدواء السعودية ".من خلال الإبلاغ عن الأعراض الجانبيّة، يُمكنك المساهمة في تأمين معلومات إضافيّة حول سلامة هذا الدواء.

 

يُحفظ بعيدًا عن متناول أيدي ومرأى الأطفال

لا تستعمل الدواء إذا انتهت مدّة صلاحيته الواردة على العبوة. يُشير تاريخ إنتهاء الصلاحيّة إلى آخر يوم من الشهر.

يُحفظ في درجة حرارة أقل من 30 درجة مئوية.

لا تتخلّص من الأدوية عبر مياه الصرف الصحي أو النفايات المنزليّة. إسأل الصيدلي عن كيفيّة التخلّص من الأدوية التي لم تعد تستعملها. قد تُساعدك هذه الإجراءات على حماية البيئة.

تركيبة فورتزار

المادتان  الفعالتان هما لوسارتان البوتاسيوم وهيدروكلوروثيازيد.

يحتوي كل قرص فورتزار ١۰۰ ملغم /٢٥ ملغم على ١۰۰ ملغم من لوسارتان البوتاسيوم وعلى ٢٥ ملغم من هيدروكلوروثيازيد كمادتَيْن  فعالتين.

يحتوي كل قرص فورتزار ١۰۰ ملغم /٢٥ ملغم على على المواد الغير الفعالة التالية هي: سيليلوز ميكروكريستالين (E460)، واللاكتوز أحادي هيدرات، ونشا الذرة المطلي مُسبقًا بالجلاتين، وستيرات الماغنيسيوم (E572)،  هيدروكسي بروبايل سيليلوز (E463)، وهيبروميلوز (E464).

يحتوي كل قرص فورتزار ١۰۰ ملغم /٢٥ ملغم على 8.48 ملغم (0.216 ميلّي مكافئ) من البوتاسيوم.

يحتوي كل قرص و فورتزار ١۰۰ ملغم /٢٥ ملغم على ثاني أكسيد التيتانيوم (E171)، وألومينيوم أصفر الكيلونين (E104)، وشمع كرنوبا (E903).

 

 

الشكل الصيدلاني ومحتوى العبوة أقراص فورتزار ١۰۰ ملغم /٢٥ ملغم أقراص مغلّفة بويضيّة الشكل ولونها أصفر فاتح، مطبوع 747)) على جهة منها ولا شيء مطبوع على الجهة الثانية منها. يتمّ تسويق فورتزار في الأحجام التالية: فورتزار ١۰۰ ملغم /٢٥ ملغم - عبوات PVC/PE/PVDC على شكل شريط مغلف بواجهة بلاستيكية شفافة مع فتحة مصنوعة من ورق الألومينيوم في رزم ٧، و١٤، و٢٨، و۳۰، و ٥۰، و٥٦، و٨٤، و٩٠، و٩٨، و٢٨۰ قرصًا أو رزمة بجرعة واحدة من ٢٨، و٥٦، و٩٨ قرصًا للاستعمال في المستشفى. قد لا يتمّ تسويق أحجام الدواء كلّها.

الشركة المالكة لحقوق التسويق:
ميرك شارب ودوم، بي. في.، 
واردرويج ٣٩، بوستبوس ٥٨١، ٢۰۰۳ بي سي
 بي ان هارلم، ٢٠٣١
هولندا

الشركة الصانعة:
ميرك شارب ودوم المحدودة، شوتون لين، 
كراملينجتون، نورثمبرلاند، إن إي ٣٣٢جي يو، 
المملكة المتحدة 

التغليف بواسطة:
فارما للصناعات الدوائية
المنطقة الصناعية الثانية،
ص ب: 11351 الرياض، المملكة العربية السعودية

 

تمّت آخر مراجعة لهذه النشرة في أكنوبر 2017الاصدار رقم (3)
 Read this leaflet carefully before you start using this product as it contains important information for you

Fortzaar® 100 mg/25 mg film-coated tablets

Fortzaar 100 mg/25 mg Each tablet contains 100 mg of losartan potassium and 25 mg of hydrochlorothiazide (HCTZ). Fortzaar 100 mg/25 mg: each tablet contains 126.26 mg lactose monohydrate. For the full list of excipients, see section 6.1.

Film coated tablet Fortzaar 100 mg/25 mg Light yellow, oval film-coated tablets marked 747 on one side and plain on the other.

 

Fortzaar is indicated for the treatment of essential hypertension in patients whose blood pressure is not adequately controlled on losartan or hydrochlorothiazide alone.

 


Posology

 

Hypertension

Losartan and hydrochlorothiazide is not for use as initial therapy, but in patients whose blood pressure is not adequately controlled by losartan potassium or hydrochlorothiazide alone.

 

Dose titration with the individual components (losartan and hydrochlorothiazide) is recommended.

 

When clinically appropriate direct change from monotherapy to the fixed combination may be considered in patients whose blood pressure is not adequately controlled.

 

The usual maintenance dose of Hyzaar and Fortzaar is one tablet of

Hyzaar 50 mg/12.5 mg (losartan 50 mg/HCTZ 12.5 mg) once daily. For patients who do not respond adequately to Hyzaar 50 mg/12.5 mg, the dosage may be increased to one tablet of

Fortzaar 100 mg/25 mg (losartan 100 mg/ HCTZ 25 mg) once daily. The maximum dose is one tablet of Fortzaar 100 mg/25 mg once daily. In general, the antihypertensive effect is attained within three to four weeks after initiation of therapy.

 

Use in patients with renal impairment and haemodialysis patients

No initial dosage adjustment is necessary in patients with moderate renal impairment (i.e. creatinine clearance 30-50 ml/min). Losartan and hydrochlorothiazide tablets are not recommended for haemodialysis patients. Losartan/HCTZ tablets must not be used in patients with severe renal impairment (i.e. creatinine clearance <30 ml/min) (see section 4.3).

 

Use in patients with intravascular volume depletion

Volume and /or sodium depletion should be corrected prior to administration of losartan/HCTZ tablets.

 

Use in patients with hepatic impairment

Losartan/HCTZ is contraindicated in patients with severe hepatic impairment (see section 4.3.).

 

 

Use in the elderly

Dosage adjustment is not usually necessary for the elderly.

 

Paediatric population

 

Use in children and adolescents (< 18 years)

There is no experience in children and adolescents. Therefore, losartan/hydrochlorothiazide should not be administered to children and adolescents.

 

Method of administration

Fortzaar may be administered with other antihypertensive agents (see sections 4.3, 4.4, 4.5 and 5.1).

Fortzaar tablets should be swallowed whole with a glass of water. Fortzaar may be administered with or without food.


• Hypersensitivity to losartan, sulphonamide-derived substances (as hydrochlorothiazide) or to any of the excipients listed in section 6.1. • Therapy resistant hypokalaemia or hypercalcaemia • Severe hepatic impairment; cholestasis and biliary obstructive disorders • Refractory hyponatraemia • Symtomatic hyperuricaemia/gout • 2nd and 3rd trimesters of pregnancy (see sections 4.4 and 4.6) • Severe renal impairment (i.e. creatinine clearance <30 ml/min) • Anuria • The concomitant use of Fortzaar with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m2) (see sections 4.5 and 5.1).

Losartan

 

Angiooedema

Patients with a history of angiooedema (swelling of the face, lips, throat, and/or tongue) should be closely monitored (see section 4.8).

 

Hypotension and Intravascular volume depletion

Symptomatic hypotension, especially after the first dose, may occur in patients who are volume- and/or sodium-depleted by vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such conditions should be corrected before the administration of Fortzaar tablets (see sections 4.2. and 4.3).

 

Electrolyte  imbalances

Electrolyte imbalances are common in patients with renal impairment, with or without diabetes, and should be addressed. Therefore, the plasma concentrations of potassium and creatinine clearance values should be closely monitored; especially patients with heart failure and a creatinine clearance between 30-50 ml/min should be closely monitored.

 

The concomitant use of potassium-sparing diuretics, potassium supplements and potassium containing salt substitutes with losartan/ hydrochlorothiazide is not recommended (see section 4.5).

 

Liver function impairment

Based on pharmacokinetic data which demonstrate significantly increased plasma concentrations of losartan in cirrhotic patients, Fortzaar should be used with caution in patients with a history of mild to moderate hepatic impairment. There is no therapeutic experience with losartan in patients with severe hepatic impairment. Therefore Fortzaar is contraindicated in patients with severe hepatic impairment (see sections 4.2, 4.3 and 5.2).

 

Renal function impairment

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function, including renal failure, have been reported (in particular, in patients whose renal function is dependent on the renin-angiotensin-aldosterone system, such as those with severe cardiac insufficiency or pre- existing renal dysfunction).

 

As with other drugs that affect the renin-angiotensin-aldosterone system, increases in blood urea and serum creatinine have also been reported in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney; these changes in renal function may be reversible upon discontinuation of therapy. Losartan should be used with caution in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney.

 

Renal  transplantation

There is no experience in patients with recent kidney transplantation.

 

Primary  hyperaldosteronism

Patients with primary aldosteronism generally will not respond to antihypertensive drugs acting through inhibition of the renin-angiotensin system. Therefore, the use of Fortzaar tablets is not recommended.

 

Coronary heart disease and cerebrovascular disease

As with any antihypertensive agents, excessive blood pressure decrease in patients with ischaemic cardiovascular and cerebrovascular disease could result in a myocardial infarction or stroke.

 

Heart failure

In patients with heart failure, with or without renal impairment, there is - as with other drugs acting on the renin-angiotensin system - a risk of severe arterial hypotension, and (often acute) renal  impairment.

 

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyophathy

As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.

 

Ethnic differences

As observed for angiotensin converting enzyme inhibitors, losartan and the other angiotensin antagonists are apparently less effective in lowering blood pressure in black people than in non-blacks, possibly because of higher prevalence of low-renin states in the black hypertensive population.

 

Pregnancy

AIIRAs should not be initiated during pregnancy. Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).

 

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia, and decreased renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended (see sections 4.5 and 5.1).

 

If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure. ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

 

Hydrochlorothiazide

 

Hypotension and electrolyte/fluid imbalance

As with all antihypertensive therapy, symptomatic hypotension may occur in some patients. Patients should be observed for clinical signs of fluid or electrolyte imbalance, e.g. volume depletion, hyponatremia, hypochloremic alkalosis, hypomagnesemia or hypokalemia which may occur during intercurrent diarrhea or vomiting. Periodic determination of serum electrolytes should be performed at appropriate intervals in such patients. Dilutional hyponatraemia may occur in oedematous patients in hot weather.

 

Metabolic and endocrine effects

Thiazide therapy may impair glucose tolerance. Dosage adjustment of antidiabetic agents, including insulin, may be required (see section 4.5). Latent diabetes mellitus may become manifest during thiazide therapy.

 

Thiazides may decrease urinary calcium excretion and may cause intermittent and slight elevation of serum calcium. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.

 

Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.

 

Thiazide therapy may precipitate hyperuricemia and/or gout in certain patients. Because losartan decreases uric acid, losartan in combination with hydrochlorothiazide attenuates the diuretic-induced hyperuricemia.

 

Hepatic impairment

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, as it may cause intrahepatic cholestasis, and since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

 

Fortzaar is contraindicated for patients with severe hepatic impairment (see section 4.3 and 5.2).

 

Other

In patients receiving thiazides, hypersensitivity reactions may occur with or without a history of allergy or bronchial asthma. Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazides.

 

Excipient

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

 


Losartan

 

Rifampicin and fluconazole have been reported to reduce levels of active metabolite. The clinical consequences of these interactions have not been evaluated.

 

As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g. spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium. Co-medication is not advisable.

 

As with other medicines which affect the excretion of sodium, lithium excretion may be reduced. Therefore, serum lithium levels should be monitored carefully if lithium salts are to be co- administered with angiotensin II receptor antagonists.

 

When angiotensin II antagonists are administered simultaneously with NSAIDs (i.e. selective COX-2 inhibitors, acetylsalicylic acid at anti-inflammatory doses and non-selective NSAIDs), attenuation of the antihypertensive effect may occur. Concomitant use of angiotensin II antagonists or diuretics and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor pre-existing renal function. The combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.

 

In some patients with compromised renal function who are being treated with non-steroidal anti- inflammatory drugs, including selective cyclooxygenase-2 inhibitors, the co-administration of angiotensin II receptor antagonists may result in a further deterioration of renal function. These effects are usually reversible.

 

Clinical trial data have shown that dual blockade of the renin-angiotensin-aldosterone system (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia, and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent (see sections 4.3, 4.4, and 5.1).

 

Other substances inducing hypotension like tricyclic antidepressants, antipsychotics, baclofene, amifostine: Concomitant use with these drugs that lower blood pressure, as main or side-effect, may increase the risk of hypotension.

 

Hydrochlorothiazide

 

When given concurrently, the following drugs may interact with thiazide diuretics:

 

Alcohol, barbiturates, narcotics or antidepressants

Potentiation of orthostatic hypotension may occur.

 

Antidiabetic drugs (oral agents and insulin)

The treatment with a thiazide may influence the glucose tolerance. Dosage adjustment of the antidiabetic drug may be required. Metformin should be used with caution because of the risk of lactic acidosis induced by possible functional renal failure linked to hydrochlorothiazide.

 

Other antihypertensive drugs

Additive effect.

 

Cholestyramine and colestipol resins

Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85 and 43 percent, respectively.

 

Corticosteroids,  ACTH

Intensified electrolyte depletion, particularly hypokalemia.

 

Pressor amines (e.g. adrenaline)

Possible decreased response to pressor amines but not sufficient to preclude their use.

 

Skeletal muscle relaxants, nondepolarizing (e.g. tubocurarine)

Possible increased responsiveness to the muscle relaxant.

 

Lithium

Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity; concomitant use is not recommended.

 

Medicinal products used in the treatment of gout (probenecid, sulfinpyrazone and allopurinol) Dosage adjustment of uricosuric medicinal products may be necessary since hydrochlorothiazide may raise the level of serum uric acid. Increase in dosage of probenecid or sulfinpyrazone may be necessary. Coadministration of a thiazide may increase the incidence of hypersensitivity reactions to allopurinol.

 

Anticholinergic agents (e.g. atropine, biperiden)

Increase of the bioavailability to thiazide-type diuretics by decreasing gastrointestinal motility and stomach emptying rate.

 

Cytotoxic agents (e.g. cyclophosphamide, methotrexate)

Thiazides may reduce the renal excretion of cytotoxic medicinal products and potentiate their myelosuppressive  effects.

 

Salicylates

In case of high dosages of salicylates hydrochlorothiazide may enhance the toxic effect of the salicylates on the central nervous system.

 

Methyldopa

There have been isolated reports of haemolytic anaemia occurring with concomitant use of hydrochlorothiazide and methyldopa.

 

Cyclosporine

Concomitant treatment with cyclosporine may increase the risk of hyperuricaemia and gout-type complications.

 

Digitalis glycosides

Thiazide-induced hypokalaemia or hypomagnesaemia may favour the onset of digitalis-induced cardiac arrhythmias.

 

Medicinal products affected by serum potassium disturbances

Periodic monitoring of serum potassium and ECG is recommended when losartan/hydrochlorothiazide is administered with medicinal products affected by serum potassium disturbances (e.g. digitalis glycosides and antiarrhythmics) and with the following torsades de pointes (ventricular tachycardia)- inducing medicinal products (including some antiarrhythmics), hypokalaemia being a predisposing factor to torsades de pointes (ventricular tachycardia):

 

·            Class Ia antiarrythmics (e.g. quinidine, hydroquinidine, disopyramide).

·            Class III antiarrythmics (e.g. amiodarone, sotalol, dofetilide, ibutilide).

·            Some antipsychotics (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol).

·            Others (e.g. bepridil, cisapride, diphemanil, erythromycin IV, halofantrin, mizolastin, pentamidine, terfenadine, vincamine IV).

 

Calcium salts

Thiazide diuretics may increase serum calcium levels due to decreased excretion. If calcium supplements must be prescribed, serum calcium levels should be monitored and calcium dosage should be adjusted accordingly.

 

Laboratory Test Interactions

Because of their effects on calcium metabolism, thiazides may interfere with tests for parathyroid function (see section 4.4).

 

Carbamazepine

Risk of symptomatic hyponatremia. Clinical and biological monitoring is required.

 

Iodine Contrast Media

In case of diuretic-induced dehydration, there is an increased risk of acute renal failure, especially with high doses of the iodine product. Patients should be rehydrated before the administration.

 

Amphotericin B (parenteral), corticosteroids, ACTH, stimulant laxatives, or glycyrrhizin (found in liquorice)

Hydrochlorothiazide may intensify electrolyte imbalance, particularly hypokalaemia.


Pregnancy

Angiotensin II Receptor Antagonists (AIIRAs):

The use of AIIRAs is not recommended during the first trimester of pregnancy (see section 4.4). The use of AIIRAs is contraindicated during the 2nd and 3rd trimesters of pregnancy (see sections 4.3 and 4.4).

 

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II Receptor Inhibitors (AIIRAs), similar risks may exist for this class of drugs. Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative anti- hypertensive treatments which have an established safety profile for use in pregnancy. When

pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately and, if appropriate, alternative therapy should be started.

 

Exposure to AIIRA therapy during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3).

 

Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.

 

Infants whose mothers have taken AIIRAs should be closely observed for hypotension (see sections 4.3 and 4.4).

 

Hydrochlorothiazide:

There is limited experience with hydrochlorothiazide during pregnancy, especially during the first trimester. Animal studies are insufficient.

 

Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of hydrochlorothiazide, its use during second and third trimesters may compromise foeto-placental perfusion and may cause foetal and neonatal effects like icterus, disturbance of electrolyte balance and thrombocytopenia.

 

Hydrochlorothiazide should not be used for gestational oedema, gestational hypertension or preeclampsia due to the risk of decreased plasma volume and placental hypoperfusion, without a beneficial effect on the course of the disease.

 

Hydrochlorothiazide should not be used for essential hypertension in pregnant women except in rare situations where no other treatment could be used.

 

Breastfeeding

Angiotensin II Receptor Antagonists (AIIRAs):

Because no information is available regarding the use of Fortzaar during breastfeeding, Fortzaar is not recommended and alternative treatments with better established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm infant.

 

Hydrochlorothiazide:

Hydrochlorothiazide is excreted in human milk in small amounts. Thiazides in high doses causing intense diuresis can inhibit the milk production. The use of Fortzaar during breast feeding is not recommended. If Fortzaar is used during breast feeding, doses should be kept as low as possible.

 


 

No studies on the reactions on the ability to drive and use machines have been performed. However, when driving vehicles or operating machinery it must be borne in mind that dizziness or drowsiness may occasionally occur when taking antihypertensive therapy, in particular during initiation of treatment or when the dose is increased.


The adverse reactions below are classified where appropriate by system organ class and frequency according to the following convention:

 

very common:         ≥ 1/10

common:                  ≥ 1/100, < 1/10

uncommon:             ≥ 1/1,000, < 1/100

rare:                     ≥ 1/10,000, < 1/1,000

very rare:            < 1/10,000

not known:          cannot be estimated from the available data

 

In clinical trials with losartan potassium salt and hydrochlorothiazide, no adverse reactions peculiar to this combination of substances were observed. The adverse reactions were restricted to those which were formerly observed with losartan potassium salt and/or hydrochlorothiazide.

 

In controlled clinical trials for essential hypertension, dizziness was the only adverse reaction reported as substance-related that occurred with an incidence greater than placebo in 1% or more of patients treated with losartan and hydrochlorothiazide.

 

Next to these effects, there are further adverse reactions reported after the introduction of the product to the market as follows:

 

System organ class

Adverse reaction

Frequency

Hepato-biliary  disorders

Hepatitis

rare

Investigations

Hyperkalaemia, elevation of ALT

rare

 

The adverse reactions that have been seen with one of the individual components and may be potential adverse reactions with losartan potassium/ hydrochlorothiazide are the following:

 

Losartan:

 

The following adverse reactions have been reported for losartan in clinical studies and in post- marketing  experience:

 

System organ class

Adverse reaction

Frequency

Blood and lymphatic system disorders

anaemia, Henoch-Schönlein purpura, ecchymosis,  haemolysis

uncommon

thrombocytopenia

not known

Cardiac disorders

hypotension, orthostatic hypotension, sternalgia, angina pectoris, grade II-AV block, cerebrovascular event, myocardial infarction, palpitation, arrhythmias (atrial fibrillations, sinus bradycardia, tachycardia, ventricular tachycardia, ventricular fibrillation)

uncommon

Ear and labyrinth disorders

vertigo, tinnitus

uncommon

Eye disorders

blurred vision, burning/stinging in the eye, conjunctivitis, decrease in visual acuity

uncommon

Gastrointestinal  disorders

abdominal pain, nausea, diarrhea, dyspepsia

common

constipation, dental pain, dry mouth, flatulence, gastritis, vomiting, obstipation

uncommon

pancreatitis

not known

General disorders and administration site conditions

asthenia, fatigue, chest pain

common

facial oedema, oedema, fever

uncommon

flu-like symptoms, malaise

not known

Hepatobiliary  disorders

liver function abnormalities

not known

 

System organ class

Adverse reaction

Frequency

Immune system disorders

hypersensitivity: anaphylactic reactions, angiooedema including swelling of the larynx and glottis causing airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue; in some of these patients angiooedema had been reported in the past in connection with the administration of other medicines, including ACE inhibitors;

rare

Metabolism and nutrition disorders

anorexia, gout

uncommon

Musculoskeletal and connective tissue disorders

muscle cramp, back pain, leg pain, myalgia

common

arm pain, joint swelling, knee pain, musculoskeletal pain, shoulder pain, stiffness, arthralgia, arthritis, coxalgia, fibromyalgia, muscle weakness

uncommon

rhabdomyolysis

not known

Nervous system disorders

headache, dizziness

common

nervousness, paraesthesia, peripheral neuropathy, tremor, migraine, syncope

uncommon

dysgeusia

not known

Psychiatric disorders

insomnia

common

anxiety, anxiety disorder, panic disorder, confusion, depression, abnormal dreams, sleep disorder, somnolence, memory impairment

uncommon

Renal and urinary disorders

renal impairment, renal failure

common

nocturia, urinary frequency, urinary tract infection

uncommon

Reproductive system and breast disorders

decreased libido, erectile dysfunction/impotence

uncommon

Respiratory, thoracic and mediastinal disorders

cough, upper respiratory infection, nasal congestion, sinusitis, sinus disorder

common

pharyngeal discomfort, pharyngitis, laryngitis, dyspnoea, bronchitis, epistaxis, rhinitis, respiratory congestion

uncommon

Skin and subcutaneous tissue disorders

alopecia, dermatitis, dry skin, erythema, flushing, photosensitivity, pruritus, rash, urticaria, sweating

uncommon

Vascular disorders

vasculitis

uncommon

dose-related orthostatic effects

not known

Investigations

hyperkalaemia, mild reduction of haematocrit and haemoglobin, hypoglycaemia

common

mild increase in urea and creatinine serum levels

uncommon

increase in hepatic enzymes and bilirubin

very rare

hyponatraemia

non known

Hydrochlorothiazide

 

System organ class

Adverse reaction

Frequency

Blood and lymphatic system disorders

Agranulocytosis, aplastic anaemia, haemolytic anaemia, leukopenia, purpura, thrombocytopenia

uncommon

Immune system disorders

Anaphylactic  reaction

rare

Metabolism and nutrition disorders

Anorexia,  hyperglycaemia,  hyperuricaemia, hypokalaemia,  hyponatraemia

uncommon

Psychiatric disorders

Insomnia

uncommon

Nervous system disorders

Cephalalgia

common

Eye disorders

Transient blurred vision, xanthopsia

uncommon

Vascular disorders

Necrotizing angiitis (vasculitis, cutaneous vasculitis)

uncommon

Respiratory, thoracic and mediastinal disorders

Respiratory distress including pneumonitis and pulmonary oedema

uncommon

Gastrointestinal  disorders

Sialoadenitis, spasms, stomach irritation, nausea, vomiting, diarrhoea, constipation

uncommon

Hepato-biliary  disorders

Icterus (intrahepatic cholestatis), pancreatitis

uncommon

Skin and subcutaneous tissue disorders

Photosensitivity, urticaria, toxic epidermal necrolysis

uncommon

cutaneous lupus erythematosus

not known

Musculoskeletal and connective tissue disorders

Muscle cramps

uncommon

Renal and urinary disorders

Glycosuria, interstitial nephritis, renal dysfunction, renal failure

uncommon

General disorders and administration site conditions

Fever, dizziness

uncommon

 

 

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:

·              Saudi Arabia:

The National Pharmacovigilance and Drug Safety Centre (NPC)

o Fax: +966-11-205-7662

o Call NPC at +966-11-20382222, Exts: 2317-2356-2353-2354-2334-2340.

o Toll free phone: 8002490000

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

o Website: www.sfda.gov.sa/npc

·              Other GCC States:

Please contact the relevant competent authority.

 

 


No specific information is available on the treatment of overdose with Fortzaar. Treatment is symptomatic and supportive. Therapy with Fortzaar should be discontinued and the patient observed closely. Suggested measures include induction of emesis if ingestion is recent, and correction of dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures.

Losartan

Limited data are available in regard to overdose in humans. The most likely manifestation of overdose would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted.

Neither losartan nor the active metabolite can be removed by hemodialysis. Hydrochlorothiazide

The most common signs and symptoms observed are those caused by electrolyte depletion

(hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.

 

The degree to which hydrochlorothiazide is removed by hemodialysis has not been established.

 

 


Pharmacotherapeutic group: Angiotensin II antagonists and diuretics, ATC code: C09DA01 Losartan-Hydrochlorothiazide

The components of Fortzaar have been shown to have an additive effect on blood pressure reduction, reducing blood pressure to a greater degree than either component alone. This effect is thought to be a result of the complimentary actions of both components. Further, as a result of its diuretic effect, hydrochlorothiazide increases plasma renin activity, increases aldosterone secretion, decreases serum potassium, and increases the levels of angiotensin II. Administration of losartan blocks all the physiologically relevant actions of angiotensin II and through inhibition of aldosterone could tend to attenuate the potassium loss associated with the diuretic.

 

Losartan has been shown to have a mild and transient uricosuric effect. Hydrochlorothiazide has been shown to cause modest increases in uric acid; the combination of losartan and hydrochlorothiazide tends to attenuate the diuretic-induced hyperuricemia.

 

The antihypertensive effect of Fortzaar is sustained for a 24-hour period. In clinical studies of at least one year's duration, the antihypertensive effect was maintained with continued therapy. Despite the significant decrease in blood pressure, administration of   Fortzaar had no clinically significant effect on heart rate. In clinical trials, after 12 weeks of therapy with losartan 50 mg/hydrochlorothiazide 12.5 mg, trough sitting diastolic blood pressure was reduced by an average of up to 13.2 mmHg.

 

Fortzaar is effective in reducing blood pressure in males and females, blacks and non-blacks and in younger (<65 years) and older (³65 years) patients and is effective in all degrees of hypertension.

 

Losartan

 

Losartan is a synthetically produced oral angiotensin-II receptor (type AT1) antagonist. Angiotensin II, a potent vasoconstrictor, is the primary active hormone of the renin-angiotensin system and an important determinant of the pathophysiology of hypertension. Angiotensin II binds to the AT1 receptor found in many tissues (e.g. vascular smooth muscle, adrenal gland, kidneys and the heart) and elicits several important biological actions, including vasoconstriction and the release of aldosterone.Angiotensin II also stimulates smooth-muscle cell proliferation.

Losartan selectively blocks the AT1 receptor. In vitro and in vivo losartan and its pharmacologically active carboxylic acid metabolite E-3174 block all physiologically relevant actions of angiotensin II, regardless of the source or route of its synthesis.

 

Losartan does not have an agonist effect nor does it block other hormone receptors or ion channels important in cardiovascular regulation. Furthermore, losartan does not inhibit ACE (kininase II), the enzyme that degrades bradykinin. Consequently, there is thus no increase in bradykinin-mediated undesirable effects.

 

During the administration of losartan the removal of the angiotensin II negative feedback on renin secretion leads to increased plasma-renin activity (PRA). Increase in the PRA leads to an increase in angiotensin II in plasma. Despite these increases, antihypertensive activity and suppression of the plasma aldosterone concentration are maintained, indicating effective angiotensin II receptor blockade. After the discontinuation of losartan, PRA and angiotensin II values fell within 3 days to the baseline values.

 

Both losartan and its principal active metabolite have a far greater affinity for the AT1 receptor than  for the AT2 receptor. The active metabolite is 10- to 40-times more active than losartan on a weight for weight basis.

 

In a study specifically designed to assess the incidence of cough in patients treated with losartan as compared to patients treated with ACE inhibitors, the incidence of cough reported by patients  receiving losartan or hydrochlorothiazide was similar and was significantly less than in patients treated with an ACE inhibitor. In addition, in an overall analysis of 16 double-blind clinical trials in 4131 patients, the incidence of spontaneously reported cough in patients treated with losartan was similar (3.1%) to that of patients treated with placebo (2.6%) or hydrochlorothiazide (4.1%), whereas the incidence with ACE inhibitors was 8.8%.

 

In nondiabetic hypertensive patients with proteinuria, the administration of losartan potassium significantly reduces proteinuria, fractional excretion of albumin and IgG. Losartan maintains glomerular filtration rate and reduces filtration fraction. Generally losartan causes a decrease in serum uric acid (usually <0.4 mg/dL) which was persistent in chronic therapy.

 

Losartan has no effect on autonomic reflexes and no sustained effect on plasma norepinephrine.

 

In patients with left ventricular failure, 25 mg and 50 mg doses of losartan produced positive hemodynamic and neurohormonal effects characterized by an increase in cardiac index and decreases in pulmonary capillary wedge pressure, systemic vascular resistance, mean systemic arterial pressure and heart rate and a reduction in circulating levels of aldosterone and norepinephrine, respectively.

The occurrence of hypotension was dose related in these heart failure patients. Hypertension Studies

In controlled clinical studies, once-daily administration of losartan to patients with mild to moderate essential hypertension produced statistically significant reductions in systolic and diastolic blood pressure. Measurement of blood pressure 24 hours post-dose relative to 5-6 hours post-dose demonstrated blood pressure reduction over 24 hours; the natural diurnal rhythm was retained. Blood pressure reduction at the end of the dosing interval was 70 – 80% of the effect seen 5-6 hours post- dose.

 

Discontinuation of losartan in hypertensive patients did not result in an abrupt rise in blood pressure (rebound). Despite the marked decrease in blood pressure, losartan had no clinically significant effect on heart rate.

 

Losartan is equally effective in males and females, and in younger (below the age of 65 years) and older hypertensive patients.

LIFE Study

 

The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study was a randomised, triple-blind, active-controlled study in 9193 hypertensive patients aged 55 to 80 years with ECG- documented left ventricular hypertrophy. Patients were randomised to once daily losartan 50 mg or once daily atenolol 50 mg. If goal blood pressure (<140/90 mmHg) was not reached, hydrochlorothiazide (12.5 mg) was added first and, if needed, the dose of losartan or atenolol was then increased to 100 mg once daily. Other antihypertensives, with the exception of ACE inhibitors, angiotensin II antagonists or beta-blockers were added if necessary to reach the goal blood pressure.

 

The mean length of follow up was 4.8 years.

 

The primary endpoint was the composite of cardiovascular morbidity and mortality as measured by a reduction in the combined incidence of cardiovascular death, stroke and myocardial infarction. Blood pressure was significantly lowered to similar levels in the two groups. Treatment with losartan resulted in a 13.0% risk reduction (p=0.021, 95% confidence interval 0.77-0.98) compared with atenolol for patients reaching the primary composite endpoint. This was mainly attributable to a reduction of the incidence of stroke. Treatment with losartan reduced the risk of stroke by 25% relative to atenolol (p=0.001, 95% confidence interval 0.63-0.89). The rates of cardiovascular death and myocardial infarction were not significantly different between the treatment groups.

 

Dual Blockade of the renin-angiotensin-aldosterone system (RAAS)

Two large randomised, controlled trials (ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in Diabetes)) have examined the use of the combination of an ACE-inhibitor with an angiotensin II receptor blocker.

 

ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular disease, or type 2 diabetes mellitus accompanied by evidence of end-organ damage.

VA NEPHRON-D was a study in patients with type 2 diabetes mellitus and diabetic nephropathy.

 

These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as compared to monotherapy was observed. Given their similar pharmacodynamic properties, these results are also relevant for other ACE-inhibitors and angiotensin II receptor blockers.

ACE-inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in patients with diabetic nephropathy.

 

ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor or an angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney disease, cardiovascular disease, or both. The study was terminated early because of an increased risk of adverse outcomes. Cardiovascular death and stroke were both numerically more frequent in the aliskiren group than in the placebo group and adverse events and serious adverse events of interest (hyperkalaemia, hypotension and renal dysfunction) were more frequently reported in the aliskiren group than in the placebo group.

 

Hydrochlorothiazide

 

Hydrochlorothiazide is a thiazide diuretic. The mechanism of the antihypertensive effect of thiazide diuretics is not fully known. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. The diuretic action of hydrochlorothiazide reduces plasma volume, increases plasma renin activity and increases aldosterone secretion, with consequent increases in urinary potassium and bicarbonate loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II and therefore coadministration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with thiazide diuretics.

After oral use, diuresis begins within 2 hours, peaks in about 4 hours and lasts about 6 to 12 hours the antihypertensive effect persists for up to 24 hours.


Absorption

 

Losartan

Following oral administration, losartan is well absorbed and undergoes first-pass metabolism, forming an active carboxylic acid metabolite and other inactive metabolites. The systemic bioavailability of losartan tablets is approximately 33%. Mean peak concentrations of losartan and its active metabolite are reached in 1 hour and in 3-4 hours, respectively. There was no clinically significant effect on the plasma concentration profile of losartan when the drug was administered with a standardized meal.

 

Distribution

 

Losartan

Both losartan and its active metabolite are ³99% bound to plasma proteins, primarily albumin. The volume of distribution of losartan is 34 liters. Studies in rats indicate that losartan crosses the blood- brain barrier poorly, if at all.

 

Hydrochlorothiazide

Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.

 

Biotransformation

 

Losartan

About 14% of an intravenously- or orally-administered dose of losartan is converted to its active metabolite. Following oral and intravenous administration of 14C-labeled losartan potassium, circulating plasma radioactivity primarily is attributed to losartan and its active metabolite. Minimal conversion of losartan to its active metabolite was seen in about one percent of individuals studied.

 

In addition to the active metabolite, inactive metabolites are formed, including two major metabolites formed by hydroxylation of the butyl side chain and a minor metabolite, an N-2 tetrazole glucuronide.

 

Elimination

 

Losartan

Plasma clearance of losartan and its active metabolite is about 600 ml/min and 50 ml/min, respectively. Renal clearance of losartan and its active metabolite is about 74 ml/min and 26 ml/min, respectively. When losartan is administered orally, about 4% of the dose is excreted unchanged in the urine, and about 6% of the dose is excreted in the urine as active metabolite. The pharmacokinetics of losartan and its active metabolite are linear with oral losartan potassium doses up to 200 mg.

 

Following oral administration, plasma concentrations of losartan and its active metabolite decline polyexponentially with a terminal half-life of about 2 hours and 6-9 hours, respectively. During once- daily dosing with 100 mg, neither losartan nor its active metabolite accumulates significantly in plasma.

 

Both biliary and urinary excretion contribute to the elimination of losartan and its metabolites. Following an oral dose of 14C-labeled losartan in man, about 35% of radioactivity is recovered in the urine and 58% in the feces.

 

Hydrochlorothiazide

Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 5.6 and 14.8 hours. At least 61 percent of the oral dose is eliminated unchanged within 24 hours.

 

Characteristics in Patients

 

Losartan-Hydrochlorothiazide

The plasma concentrations of losartan and its active metabolite and the absorption of hydrochlorothiazide in elderly hypertensives are not significantly different from those in young hypertensives.

 

Losartan

Following oral administration in patients with mild to moderate alcoholic cirrhosis of the liver, plasma concentrations of losartan and its active metabolite were, respectively, 5-fold and 1.7-fold greater than those seen in young male volunteers.

 

Pharmacokinetic studies showed that the AUC of losartan in Japanese and non-Japanese healthy male subjects is not different. However, the AUC of the carboxylic acid metabolite (E-3174) appears to be different between the two groups, with an approximately 1.5 fold higher exposure in Japanese subjects than in non-Japanese subjects. The clinical significance of these results is not known.

 

Neither losartan nor the active metabolite can be removed by hemodialysis.


Preclinical data reveal no special hazard for humans based on conventional studies of general pharmacology, genotoxicity and carcinogenic potential. The toxic potential of the combination of losartan/hydrochlorothiazide was evaluated in chronic toxicity studies for up to six months duration in rats and dogs after oral administration, and the changes observed in these studies with the combination were mainly produced by the losartan component. The administration of the losartan/hydrochlorothiazide combination induced a decrease in the red blood cell parameters (erythrocytes, haemoglobin, haematocrit), a rise in urea-N in the serum, a decrease in heart weight (without a histological correlate) and gastrointestinal changes (mucous membrane lesions, ulcers, erosions,  haemorrhages).

 

There was no evidence of teratogenicity in rats or rabbits treated with the losartan/hydrochlorothiazide combination. Foetal toxicity in rats, as evidenced by a slight increase in supernumerary ribs in the F1 generation, was observed when females were treated prior to and throughout gestation. As observed in studies with losartan alone, adverse foetal and neonatal reactions, including renal toxicity and foetal death, occurred when pregnant rats were treated with the losartan/hydrochlorothiazide combination during late gestation and/or lactation.


Fortzaar 100 mg/25 mg:

microcrystalline cellulose (E460),

lactose monohydrate, pregelatinized maize starch, magnesium stearate (E572), hydroxypropyl cellulose (E463), hypromellose (E464).

 

 Fortzaar 100 mg/25 mg contains 8.48 mg (0.216 mEq) of potassium.

 

Fortzaar 100 mg/25 mg also contains, Titanium dioxide (E171), Quinoline yellow aluminum lake (E104), and Carnauba wax (E903)


Not applicable.

 


3 Years

Do not store above 30°C.


Fortzaar 100 mg/25 mg> - PVC/PE/PVDC blister packages with aluminum foil lidding in cartons containing 7, 14, 28, 30, 50, 56, 84, 90, 98, or 280 tablets and unit-dose packages of 28, 56 and 98 tablets for hospital use.

 

Not all pack sizes may be marketed


No special requirements.


Marketing Authorization Holder: Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, P.O. Box 581, 2003 PC Haarlem, The Netherlands Manufacturer: Merck Sharp & Dohme Ltd. Shotton Lane, Cramlington, Northumberland NE23 3JU UK. Packed by: Pharma Pharmaceutical Industries, Second Industrial Area, P.O. Box 11351 Riyadh, Saudi Arabia

October 2017
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