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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)

Helt® is a treatment for adult men with erectile dysfunction. This is when a man cannot get, or keep a hard, erect penis suitable for sexual activity. Helt® has been shown to significantly improve the ability of obtaining a hard erect penis suitable for sexual activity.

Helt® contains the active substance tadalafil which belongs to a group of medicines called phosphodiesterase type 5 inhibitors. Following sexual stimulation Helt® works by helping the blood vessels in your penis to relax, allowing the flow of blood into your penis. The result of this is improved erectile function. Helt® will not help you if you do not have erectile dysfunction.  

It is important to note that Helt® does not work if there is no sexual stimulation. You and your partner will need to engage in foreplay, just as you would if you were not taking a medicine for erectile dysfunction.


Do not take Helt® tablets:

·       If you are allergic to tadalafil or any of the other ingredients of this medicine.

·       If you are taking any form of organic nitrate or nitric oxide donors such as amyl nitrite. This is a group of medicines (“nitrates”) used in the treatment of angina pectoris (“chest pain”). Helt® has been shown to increase the effects of these medicines. If you are taking any form of nitrate or are unsure tell your doctor.

·       If you have serious heart disease or recently had a heart attack within the last 90 days.

·       If you recently had a stroke within the last 6 months.

·       If you have low blood pressure or uncontrolled high blood pressure.

·       If you ever had loss of vision because of non-arteritic anterior ischemic optic neuropathy (NAION), a condition described as “stroke of the eye”.

·       If you are taking riociguat. This drug is used to treat pulmonary arterial hypertension (i.e., high blood pressure in the lungs) and chronic thromboembolic pulmonary hypertension (i.e., high blood pressure in the lungs secondary to blood clots). PDE5 inhibitors, such as Helt®, have been shown to increase the hypotensive effects of this medicine. If you are taking riociguat or are unsure tell your doctor.

Warnings and precautions

Talk to your doctor before taking Helt®.

Be aware that sexual activity carries a possible risk to patients with heart disease because it puts an extra strain on your heart. If you have a heart problem you should tell your doctor.

Before taking the tablets, tell your doctor if you have:

·     Sickle cell anaemia (an abnormality of red blood cells).

·     Multiple myeloma (cancer of the bone marrow).

·     Leukaemia (cancer of the blood cells).

·     Any deformation of your penis.

·     A serious liver problem.

·     A severe kidney problem.

It is not known if Helt® is effective in patients who have had:

·     Pelvic surgery.

·     Removal of all or part of the prostate gland in which nerves of the prostate are cut (radical non-nerve-sparing prostatectomy).

If you experience sudden decrease or loss of vision, stop taking Helt® and contact your doctor immediately.

Decreased or sudden hearing loss has been noted in some patients taking tadalafil. Although it is not known if the event is directly related to tadalafil, if you experience decreased or sudden hearing loss, stop taking Helt® and contact your doctor immediately.

Helt® is not intended for use by women.

Children and adolescents

Helt® is not intended for use by children and adolescents under the age of 18.

Other medicines and Helt®

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

Do not take Helt® if you are already taking nitrates.

Some medicines may be affected by Helt® or they may affect how well Helt® will work. Tell your doctor or pharmacist if you are already taking:

·     An alpha blocker (used to treat high blood pressure or urinary symptoms associated with benign prostatic hyperplasia).

·     Other medicines to treat high blood pressure.

·     Riociguat.

·     A 5- alpha reductase inhibitor (used to treat benign prostatic hyperplasia).

·     Medicines such as ketoconazole tablets (to treat fungal infections) and protease inhibitors for treatment of AIDS or HIV infection.

·     Phenobarbital, phenytoin and carbamazepine (anticonvulsant medicines).

·     Rifampicin, erythromycin, clarithromycin or itraconazole.

·     Other treatments for erectile dysfunction.

Helt® with drink and alcohol

Information on the effect of alcohol is in section 3. Grapefruit juice may affect how well Helt® will work and should be taken with caution. Talk to your doctor for further information.

Fertility

When dogs were treated there was reduced sperm development in the testes. A reduction in sperm was seen in some men. These effects are unlikely to lead to a lack of fertility.

Driving and using machines

Some men taking Helt® in clinical studies have reported dizziness. Check carefully how you react to the tablets before driving or using machines.

Helt® contains lactose

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


Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Helt® tablets are for oral use in men only. Swallow the tablet whole with some water. The tablets can be taken with or without food.

The recommended starting dose is 10 mg before sexual activity. However, you have been given the dose of one 20 mg tablet as your doctor has decided that the recommended dose of 10 mg is too weak.

You may take Helt® tablet at least 30 minutes before sexual activity. Helt® may still be effective up to 36 hours after taking the tablet.

Do not take Helt® more than once a day. Helt® 10 mg and 20 mg is intended for use prior to anticipated sexual activity and is not recommended for continuous daily use.

It is important to note that Helt® does not work if there is no sexual stimulation. You and your partner will need to engage in foreplay, just as you would if you were not taking a medicine for erectile dysfunction.

Drinking alcohol may affect your ability to get an erection and may temporarily lower your blood pressure. If you have taken or are planning to take Helt®, avoid excessive drinking (blood alcohol level of 0.08 % or greater), since this may increase the risk of dizziness when standing up.

If you take more Helt® than you should

Contact your doctor. You may experience side effects described in section 4.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.


Like all medicines, this medicine can cause side effects, although not everybody gets them. These effects are normally mild to moderate in nature.

If you experience any of the following side effects stop using the medicine and seek medical help immediately:

·     Allergic reactions including rashes (frequency uncommon).

·     Chest pain - do not use nitrates but seek immediate medical assistance (frequency uncommon).

·     Priapism, a prolonged and possibly painful erection after taking tadalafil (frequency rare). If you have such an erection, which lasts continuously for more than 4 hours you should contact a doctor immediately.

·     Sudden loss of vision (frequency rare).

Other side effects have been reported:

Common (seen in 1 to 10 in every 100 patients)

·     Headache, back pain, muscle aches, pain in arms and legs, facial flushing, nasal congestion and indigestion.

Uncommon (seen in 1 to 10 in every 1,000 patients)

·     Dizziness, stomach ache, feeling sick, being sick (vomiting), reflux, blurred vision, eye pain, difficulty in breathing, presence of blood in urine, prolonged erection, pounding heartbeat sensation, a fast heart rate, high blood pressure, low blood pressure, nose bleeds, ringing in the ears, swelling of the hands, feet or ankles and feeling tired.

Rare (seen in 1 to 10 in every 10,000 patients)

·       Fainting, seizures and passing memory loss, swelling of the eyelids, red eyes, sudden decrease or loss of hearing and hives (itchy red welts on the surface of the skin), penile bleeding, presence of blood in semen and increased sweating.

Heart attack and stroke have also been reported rarely in men taking tadalafil. Most of these men had known heart problems before taking this medicine.

Partial, temporary, or permanent decrease or loss of vision in one or both eyes has been rarely reported.

Some additional rare side effects have been reported in men taking tadalafil that were not seen in clinical trials. These include:

·     Migraine, swelling of the face, serious allergic reaction which causes swelling of the face or throat, serious skin rashes, some disorders affecting blood flow to the eyes, irregular heartbeats, angina and sudden cardiac death.

The side effect dizziness has been reported more frequently in men over 75 years of age taking tadalafil. Diarrhea has been reported more frequently in men over 65 years of age taking tadalafil.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.


Keep out of the reach and sight of children.

Do not use Helt® after the expiry date (EXP) which is stated on the blister and the carton.

The expiry date refers to the last day of that month.

Helt® tablets: Store below 30°C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.


The active substance is tadalafil.

The other ingredients are lactose monohydrate, croscarmellose sodium, sodium lauryl sulfate, povidone K30, microcrystalline cellulose, magnesium stearate, Opadry II OY-L white 28900 powder, yellow iron oxide, FD & C yellow #6 lake, polyethylene glycol 6000, ethanol absolute.

 


Helt® 20 mg: Peach colored, almond shape film coated tablets engraved with H7 on one face, Packed in PVC/PVDC/Alu. blister, intended for oral use. Pack size: 1 tablet, (1 tablet in PVC/PVDC/Alu. blister, 1 blister/pack). 4 tablets, (1 tablet in PVC/PVDC/Alu. blister, 4 blisters/pack).

Med City Pharma-KSA

1st Industrial city, Phase 5, Jeddah –KSA.

Tel: 00966920003288

Mobile: 00966555786968

P.O .Box: 4072 - Jeddah 22429

E-mail: info@medcitypharma.com 


05/2023
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

يعد هيلت® علاجاً للرجال البالغين الذين يعانون من قصور في انتصاب القضيب. وهذا عندما لا يستطيع الرجل الحصول، أو المحافظة على انتصاب القضيب المناسب للنشاط الجنسي. أظهر هيلت® تحسين القدرة على الحصول على انتصاب القضيب المناسب للنشاط الجنسي بشكل واضح.

يحتوي هيلت® على المادة الفعالة تادالافيل والتي تنتمي إلى مجموعة من الأدوية تعرف بمثبطات فوسفودايإستيريز نوع 5. بعد التحفيز الجنسي يعمل هيلت® عن طريق المساعدة في إرخاء الأوعية الدموية في القضيب، مما يسمح بتدفق الدم داخل القضيب. و ينتج عن ذلك تحسين وظيفة الانتصاب. لن يساعدك هيلت® إن لم تكن تعاني من قصور في انتصاب القضيب.

من الضروري معرفة بأن هيلت® لا يعمل إذا لم يكن هنالك تحفيز جنسي. ستحتاج أنت و الشريك البدء بالمداعبة، كما هو الحال تماماً إذا لم تكن تتناول دواء لعلاج قصور انتصاب القضيب.

يجب عدم تناول أقراص هيلت® في الحالات التالية:

إذا كنت تعاني من تحسس لتادالافيل أو لأي مكونات أخرى في هذا الدواء.

إذا كنت تتناول أي شكل من النترات العضوية أو مانحات أكسيد النتريك مثل أميل نترات. هذه مجموعة من الأدوية («النترات») تستعمل في علاج الذبحة الصدرية («ألم الصدر»). أظهر هيلت® تأثيره في زيادة مفعول هذه الأدوية. إذا كنت تتناول أي شكل من النترات أو إذا لم تكن متأكداً أخبر طبيبك.

إذا كنت تعاني من مرض قلبي خطير أو عانيت مؤخراً من نوبة قلبية خلال فترة 90 يوم ماضية.

إذا عانيت مؤخراً من سكتة دماغية خلال الشهور الستة الماضية.

إذا كنت تعاني من انخفاض في ضغط الدم أو ارتفاع في ضغط الدم غير مسيطر عليه.

إذا عانيت في السابق من فقدان للبصر نتيجة لاعتلال عصبي بصري ناتج عن فقر دم موضعي احتباسي أمامي غير شرياني، و هي حالة مرضية توصف كأنها «سكتة للعين».

إذا كنت تتناول ريوكيجوت. وهو دواء يستعمل لعلاج ارتفاع ضغط الدم الشرياني الرئوي (مثل ارتفاع ضغط الدم في الرئتين) و ارتفاع ضغط الدم الرئوي المزمن الناتج عن الانسداد التجلطي (مثل ارتفاع ضغط الدم في الرئتين الناتج عن تجلط الدم). إن مثبطات فوسفودايإستيريز 5، مثل هيلت®، أظهرت زيادة التأثير الخافض لضغط الدم لهذا الدواء. إذا كنت تتناول ريوكيجوت أو إذا لم تكن متأكداً أخبر طبيبك.

الاحتياطات والمحاذير

تحدث مع الطبيب قبل تناول هيلت® .

كن على حذر حيث أن النشاط الجنسي يعرض المرضى الذي يعانون من مرض قلبي لخطر محتمل حيث يضع مجهود إضافي على القلب. إذا كنت تعاني من مشكلة قلبية يجب عليك إخبار الطبيب.

قبل البدء بتناول الأقراص، أخبر طبيبك إذا كنت تعاني من الحالات التالية:

فقر الدم المنجلي (اضطراب في خلايا الدم الحمراء).

ورم نخاعي متعدد (سرطان نخاع العظم).

لوكيميا (سرطان خلايا الدم).

أي تغير في شكل القضيب.

مشكلة خطيرة في الكبد.

مشكلة خطيرة في الكلى.

من غير المعروف إذا كان هيلت® فعالاً في علاج المرضى الذين خضعوا في السابق لأي مما يلي:

جراحة في منطقة الحوض.

إزالة لجميع أجزاء غدة البروستات أو لأي جزء منها حيث يتم قطع أعصاب غدة البروستات (استئصال جذري لمنطقة واسعة حول غدة البروستات بما في ذلك الأعصاب في الجزء المستأصل).

إذا حدث لديك نقصان أو فقدان مفاجىء للرؤية، توقف عن تناول هيلت® واتصل مع الطبيب فوراً.

لقد تم ملاحظة حدوث ضعف أو فقدان مفاجئ للسمع عند بعض المرضى الذين يتناولون تادالافيل، على الرغم من أنه من غير المعروف إذا كان هذا الحدث مرتبط بتناول تادالافيل بشكل مباشر، إذا عانيت من ضعف أو فقدان مفاجئ للسمع توقف عن تناول هيلت ®و اتصل مع الطبيب فورا.

 

لا يستعمل هيلت® للنساء.

الأطفال و المراهقون

لا يستعمل هيلت® للأطفال و المراهقين الأقل من 18 عاماً.

أدوية أخرى مع هيلت®

أخبر طبيبك إذا كنت تتناول، تناولت مؤخراً أو من الممكن أن تتناول أي أدوية أخرى.

لا تتناول هيلت® إذا كنت تتناول النترات.

قد تتأثر بعض الأدوية بتناول هيلت® أو قد تؤثر تلك الأدوية على  فاعليته. أخبر طبيبك أو الصيدلي إذا كنت تتناول:

أحد حاصرات ألفا (يستعمل لعلاج ارتفاع ضغط الدم أو الأعراض البولية المرتبطة بتضخم غدة البروستات الحميد).

أدوية أخرى لعلاج ارتفاع ضغط الدم.

ريوكيجوت.

مثبط الإنزيم المختزل 5-ألفا (يستعمل لعلاج تضخم غدة البروستات الحميد).

أدوية مثل أقراص كيتوكونازول (لعلاج الالتهابات الفطرية) و مثبطات البروتياز لعلاج الإيدز أو التهاب ڤيروس نقص المناعة المكتسبة.

فينوباربيتال، فينيتوين و كاربامازيباين (أدوية مضادة للتشنجات).

ريفامبيسين، إريثرومايسين، كلاريثرومايسين أو إتراكونازول.

علاجات أخرى لقصور انتصاب القضيب.

تناول هيلت® مع المشروبات والكحول

المعلومات عن تأثير الكحول مذكورة في قسم 3. قد يؤثر عصير الجريب فروت على فاعلية عمل هيلت® و يجب تناوله بحذر. للمزيد من المعلومات تحدث مع طبيبك.

الخصوبة

عند علاج الكلاب لوحظ انخفاض في نمو الحيوانات المنوية في الخصيتين. لوحظ هذا الانخفاض عند بعض الرجال. ومن غير المتوقع أن تؤدي هذه التأثيرات إلى انخفاض الخصوبة.

القيادة و استخدام الآلات

تم تسجيل حدوث الشعور بالدوار لدى بعض الرجال الذين تناولوا هيلت® في الدراسات السريرية. تأكد بحذر من كيفية تفاعلك مع الأقراص قبل القيادة أو استخدام الآلات.

يحتوي هيلت® على اللاكتوز

يحتوي هذا الدواء على لاكتوز مونوهيدرات. إذا أخبرت من قبل الطبيب أنك تعاني من عدم القدرة على تحمل بعض أنواع السكريات، اتصل مع طبيبك قبل تناول هذا الدواء.

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دائما تناول هذا الدواء تماما كما أخبرك طبيبك. تأكد من طبيبك أو الصيدلي إذا لم تكن متأكدا.

إن أقراص هيلت® للاستعمال عن طريق الفم للرجال فقط. قم بتناول القرص كاملاً مع بعض الماء. من الممكن تناول الأقراص مع أو بدون تناول الطعام.

الجرعة الابتدائية الموصى بها هي 10 ملغم قبل النشاط الجنسي. لكن، يجب إعطاؤك جرعة 20 ملغم مرة واحدة عندما يقرر طبيبك أن جرعة 10 ملغم الموصى بها غير كافية.

قد تحتاج لتناول قرص هيلت® قبل 30 دقيقة على الأقل من النشاط الجنسي. وقد يستمر مفعول هيلت® لغاية 36 ساعة من تناول القرص.

لا تتناول هيلت® أكثرمن مرة واحدة يومياً. يستعمل هيلت® 10 ملغم و 20 ملغم قبل النشاط الجنسي المتوقع حدوثه ولا يوصى باستعماله يومياً بشكل مستمر.

من الضروري معرفة بأن هيلت® لا يعمل إذا لم يكن هنالك تحفيز جنسي. ستحتاج أنت و الشريك للبدء بالمداعبة، كما هو الحال إذا لم تكن تتناول دواء لعلاج قصور انتصاب القضيب.

قد يؤثر شرب الكحول على قدرتك في حصول انتصاب القضيب وقد يؤدي إلى انخفاض ضغط الدم بشكل مؤقت. إذا تناولت هيلت® سابقاً أو كنت تخطط لتناوله، تجنب الإفراط في شرب الكحول (مستوى الكحول في الدم 0.08% أو أعلى)، حيث قد يزيد ذلك من خطر التعرض للشعور بالدوار عند الوقوف.

إذا قمت بتناول هيلت® أكثر مما يجب

قم بالاتصال مع الطبيب. قد تتعرض لآثار جانبية مذكورة في قسم 4.

إذا كان لديك أية أسئلة إضافية عن استعمال هذا الدواء، اسأل طبيبك أو الصيدلي.

مثل جميع الأدوية، قد يسبب هذا الدواء آثار جانبية، على الرغم من عدم حصولها لدى الجميع. وتكون هذه الآثار عادةً معتدلة إلى متوسطة في طبيعتها.

إذا حصل لديك أي من الآثار الجانبية التالية توقف عن استعمال الدواء واطلب المساعدة الطبية فوراً:

تفاعلات تحسسية بما في ذلك الطفح (التكرار غير شائع).

ألم في الصدر- لا تستعمل النترات لكن اطلب المساعدة الطبية الفورية (التكرار غير شائع).

القساح، هو انتصاب مطوّل و من الممكن أن يكون مؤلماً بعد تناول تادالافيل (التكرار نادر).
إذا حصل لديك مثل هذا الانتصاب، الذي يستمر لفترة أطول من 4 ساعات يجب عليك الاتصال مع الطبيب فوراً.

فقدان مفاجىء للرؤية (التكرار نادر).

آثار جانبية أخرى تم تسجيلها:

شائعة (لوحظت عند 1 إلى 10 من كل 100 مريض)

صداع، ألم الظهر، ألم مستمر في العضلات، ألم في الذراعين و الساقين، احمرار الوجه، احتقان الأنف و عسر الهضم.

غير شائعة (لوحظت عند 1 إلى 10 من كل 1000 مريض)

الشعور بالدوار، ألم المعدة، الشعور بالغثيان، قيء، الارتداد المعدي المريئي، ضبابية الرؤية، ألم العين، صعوبة في التنفس، ظهور الدم في البول، انتصاب مطول، شعور بخفقان القلب بشدة، تسارع معدل نبضات القلب، ارتفاع ضغط الدم، انخفاض ضغط الدم، نزيف الأنف، رنين في الأذنين، تورم اليدين، القدمين أو الكاحلين والشعور بالتعب.

 

نادرة (لوحظت عند 1 إلى 10 من كل 10000 مريض)

إغماء، نوبات صرع و فقدان الذاكرة، تورم الجفون، احمرار العيون، نقصان أو فقدان مفاجىء للسمع و شرى (بقع حمراء على سطح الجلد تسبب الحكة)، نزيف في القضيب، ظهور الدم في المني و زيادة التعرق.

تم تسجيل أيضاً حدوث نوبة قلبية و سكتة دماغية بشكل نادر عند الرجال الذين يتناولون تادالافيل. معظم هؤلاء الرجال كان لديهم مشاكل قلبية معروفة قبل البدء بتناول هذا الدواء.

تم تسجيل بشكل نادر حدوث نقصان أو فقدان جزئي، مؤقت أو دائم للرؤية في إحدى العينين أو كلاهما.

تم تسجيل بعض الآثار الجانبية النادرة الإضافية عند الرجال الذين يتناولون تادالافيل والتي لم يتم ملاحظتها في التجارب السريرية. و تتضمن:

الشقيقة، تورم الوجه، تفاعل تحسسي خطير الذي يسبب تورم الوجه أو الحلق، طفح جلدي خطير، بعض الاضطرابات التي تؤثر على تدفق الدم إلى العيون، عدم انتظام نبضات القلب، ذبحة صدرية و موت مفاجىء للقلب.

تم تسجيل الأثر الجانبي الشعور بالدوار بتكرار أكبر عند الرجال الذين تزيد أعمارهم عن 75 عاماً و يتناولون تادالافيل. تم تسجيل الأثر الجانبي الإسهال بتكرار أكبر عند الرجال الذين تزيد أعمارهم عن 65 عاماً و يتناولون تادالافيل.

إذا حصل لديك أي من الآثار الجانبية، تحدث مع طبيبك أو الصيدلي. وهذا يتضمن أي آثار جانبية غير مذكورة في هذه النشرة.

يحفظ بعيدا عن متناول الأطفال و نظرهم.

لا تستخدم أقراص هيلت® بعد تاريخ انتهاء الصلاحية المذكورعلى الشريط و العلبة الخارجية.

تاريخ الانتهاء يشير إلى اليوم الأخير من ذلك الشهر.

هيلت® أقراص: يحفظ  بدرجة حرارة دون 30 °م.

يحفظ في العبوة الأصلية بعيداً عن الرطوبة.

يجب أن لا يتم التخلص من الأدوية عن طريق مياه الصرف الصحي أو النفايات المنزلية. اسأل الصيدلي عن كيفية التخلص من الأدوية التي لم تعد مطلوبة. وسوف تساعد هذه التدابير في حماية البيئة.

المادة الفعالة هي تادالافيل.

المكونات الأخرى هي لاكتوز مونوهيدرات، كروسكارميللوز صوديوم، صوديوم لوريل سلفات، بوفيدون K30، ميكروكريستالين سيليلوز، ستيرات المغنيسيوم، مسحوق أوبادري أبيض 28900، أكسيد الحديد الأصفر، لون أصفر FD & C # 6، بولي ايثيلين جلايكول 6000، إيثانول نقي.

هيلت® 20 ملغم هي أقراص مغلفة لوزية الشكل، ذات لون مشمشي، محفور على أحد الأوجه H7 معبأة في أشرطة بي ڤي سي/بي ڤي دي سي/ألومنيوم، معدة للاستخدام عن طريق الفم.

حجم العبوة:

قرص واحد، (قرص داخل شريط بي ڤي سي/بي ڤي دي سي/ألومنيوم، شريط/علبة).

4 أقراص، (قرص واحد داخل شريط بي ڤي سي/بي ڤي دي سي/ألومنيوم، 4 أشرطة/علبة).

 

مدينة الدواء للصناعات الدوائية - المملكة العربية السعودية  

المدينة الصناعية الأولى، المرحلة الخامسة، جدة - المملكة العربية السعودية.

هاتف: 00966920003288

جوال: 00966555786968

ص.ب: 4072 - جدة 22429

بريد الكتروني: info@medcitypharma.com

05/2023
 Read this leaflet carefully before you start using this product as it contains important information for you

Helt® 5 mg film-coated tablets. Helt® 10 mg film-coated tablets. Helt® 20 mg film-coated tablets.

Helt® 5 mg Tablets: Each tablet contains 5 mg tadalafil. Helt® 10 mg Tablets: Each tablet contains 10 mg tadalafil. Helt® 20 mg Tablets: Each tablet contains 20 mg tadalafil. For a full list of excipients, see section 6.1.

Helt® tablets are film coated tablets. Helt® 5 mg tablets are peach normal round biconvex film coated tablets engraved with H3 on one face and scored on the other face, packed in PVC/PVDC/Alu. blisters, intended for oral use. Helt® 10 mg tablets are peach normal round, biconvex film coated tablets engraved with H5 on one face and scored on the other face, packed in PVC/PVDC/Alu. blisters, intended for oral use. Helt® 20 mg: Peach colored, almond shape film coated tablets engraved with H7 on one face, packed in PVC/PVDC/Alu. blister, intended for oral use.

Treatment of erectile dysfunction in adult males.

In order for tadalafil to be effective for the treatment of erectile dysfunction, sexual stimulation is required.

5 mg only: Treatment of the signs and symptoms of benign prostatic hyperplasia in adult males.

Helt® is not indicated for use by women.


Posology

Erectile dysfunction in adult Men

In general, the recommended dose is 10 mg taken prior to anticipated sexual activity and with or without food.

In those patients in whom tadalafil 10 mg does not produce an adequate effect, 20 mg might be tried. It may be taken at least 30 minutes prior to sexual activity.

The maximum dose frequency is once per day.

Tadalafil 10 and 20 mg is intended for use prior to anticipated sexual activity and it is not recommended for continuous daily use.

In patients who anticipate a frequent use of tadalafil (i.e., at least twice weekly) a once daily regimen with the lowest doses of tadalafil might be considered suitable, based on patient choice and the physician's judgment.

In these patients, the recommended dose is 5mg taken once a day at approximately the same time of day. The dose may be decreased to 2.5 mg once a day based on individual tolerability.

The appropriateness of continued use of the daily regimen should be reassessed periodically.

 

Benign prostatic hyperplasia in adult men (tadalafil 5 mg only)

The recommended dose is 5 mg, taken at approximately the same time every day with or without food. For adult men being treated for both benign prostatic hyperplasia and erectile dysfunction the recommended dose is also 5 mg taken at approximately the same time every day. Patients who are unable to tolerate tadalafil 5 mg for the treatment of benign prostatic hyperplasia should consider an alternative therapy as the efficacy of tadalafil 2.5 mg for the treatment of benign prostatic hyperplasia has not been demonstrated.

 

Special Populations

Elderly Men

Dose adjustments are not required in elderly patients.

 

Men with Renal Impairment

Dose adjustments are not required in patients with mild to moderate renal impairment. For patients with severe renal impairment, 10 mg is the maximum recommended dose.

Once-a-day dosing of 2.5 or 5 mg tadalafil both for the treatment of erectile dysfunction or benign prostatic hyperplasia is not recommended in patients with severe renal impairment (see sections 4.4 and 5.2).

 

Men with Hepatic Impairment

For the treatment of erectile dysfunction using on-demand tadalafil the recommended dose of tadalafil is 10 mg taken prior to anticipated sexual activity and with or without food. There is limited clinical data on the safety of tadalafil in patients with severe hepatic impairment (Child-Pugh class C); if prescribed, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician. There are no available data about the administration of doses higher than 10 mg of tadalafil to patients with hepatic impairment.

Once-a-day dosing both for the treatment of erectile dysfunction and benign prostatic hyperplasia has not been evaluated in patients with hepatic impairment; therefore, if prescribed, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician (see sections 4.4 and 5.2).

 

Men with Diabetes

Dose adjustments are not required in diabetic patients.

 

Paediatric population

There is no relevant use of Helt® in the paediatric population with regard to the treatment of erectile dysfunction.

 

Method of administration

Helt® is available as 5 mg, 10 mg and 20 mg film-coated tablets for oral use.


-Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. In clinical studies, tadalafil was shown to augment the hypotensive effects of nitrates. This is thought to result from the combined effects of nitrates and tadalafil on the nitric oxide/cGMP pathway. Therefore, administration of Helt® to patients who are using any form of organic nitrate is contraindicated (see section 4.5). Helt® must not be used in men with cardiac disease for whom sexual activity is inadvisable. Physicians should consider the potential cardiac risk of sexual activity in patients with pre-existing cardiovascular disease. The following groups of patients with cardiovascular disease were not included in clinical trials and the use of tadalafil is therefore contraindicated: - Patients with myocardial infarction within the last 90 days, - Patients with unstable angina or angina occurring during sexual intercourse, - Patients with New York Heart Association Class 2 or greater heart failure in the last 6 months, - Patients with uncontrolled arrhythmias, hypotension (<90/50 mm Hg), or uncontrolled hypertension, - Patients with a stroke within the last 6 months. Helt® is contraindicated in patients who have loss of vision in one eye because of non-arteritic anterior ischaemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure (see section 4.4). The co-administration of PDE5 inhibitors, including tadalafil, with guanylate cyclase stimulators, such as riociguat, is contraindicated as it may potentially lead to symptomatic hypotension (see section 4.5).

Before treatment with Helt®

A medical history and physical examination should be undertaken to diagnose erectile dysfunction or benign prostatic hyperplasia and determine potential underlying causes, before pharmacological treatment is considered.

Prior to initiating any treatment for erectile dysfunction, physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. Tadalafil has vasodilator properties, resulting in mild and transient decreases in blood pressure (see section 5.1) and as such potentiates the hypotensive effect of nitrates (see section 4.3).

The evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following an appropriate medical assessment. It is not known if Helt® is effective in patients who have undergone pelvic surgery or radical non-nerve-sparing prostatectomy.

Tadalafil 5 mg - Prior to initiating treatment with tadalafil for benign prostatic hyperplasia patients should be examined to rule out the presence of carcinoma of the prostate and carefully assessed for cardiovascular conditions (see section 4.3).

 

Cardiovascular

Serious cardiovascular events, including myocardial infarction, sudden cardiac death, unstable angina pectoris, ventricular arrhythmia, stroke, transient ischaemic attacks, chest pain, palpitations and tachycardia, have been reported either post marketing and/or in clinical trials. Most of the patients in whom these events have been reported had pre-existing cardiovascular risk factors. However, it is not possible to definitively determine whether these events are related directly to these risk factors, to tadalafil, to sexual activity, or to a combination of these or other factors.

Tadalafil 2.5 mg and 5 mg - In patients receiving concomitant antihypertensive medicinal products, tadalafil may induce a blood pressure decrease. When initiating daily treatment with tadalafil, appropriate clinical considerations should be given to a possible dose adjustment of the antihypertensive therapy.

In patients who are taking alpha1 blockers, concomitant administration of tadalafil may lead to symptomatic hypotension in some patients (see section 4.5). The combination of tadalafil and doxazosin is not recommended.

 

Vision

Visual defects and cases of NAION have been reported in connection with the intake of tadalafil and other PDE5 inhibitors. Analyses of observational data suggest an increased risk of acute NAION in men with erectile dysfunction following exposure to tadalafil or other PDE5 inhibitors. As this may be relevant for all patients exposed to tadalafil, the patient should be advised that in case of sudden visual defect, he should stop taking Helt® and consult a physician immediately (see section 4.3).

 

Decreased or sudden hearing loss

Cases of sudden hearing loss have been reported after the use of tadalafil. Although other risk factors were present in some cases (such as age, diabetes, hypertension and previous hearing loss history) patients should be advised to stop taking tadalafil and seek prompt medical attention in the event of sudden decrease or loss of hearing.

 

Renal and hepatic impairment (tadalafil 2.5 mg and 5 mg)

Due to increased tadalafil exposure (AUC), limited clinical experience and the lack of ability to influence clearance by dialysis, once-a-day dosing of Helt® is not recommended in patients with severe renal impairment.

There is limited clinical data on the safety of single-dose administration of tadalafil in patients with severe hepatic insufficiency (Child-Pugh Class C). Once-a-day administration has not been evaluated in patients with hepatic insufficiency. If tadalafil is prescribed, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician.

 

Hepatic impairment (tadalafil 10 mg and 20 mg)

There is limited clinical data on the safety of single-dose administration of tadalafil in patients with severe hepatic insufficiency (Child-Pugh Class C). If tadalafil is prescribed, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician.

 

Priapism and anatomical deformation of the penis

Patients who experience erections lasting 4 hours or more should be instructed to seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result.

 

Helt®, should be used with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease) or in patients who have conditions which may predispose them to priapism (such as sickle cell anaemia, multiple myeloma or leukaemia).

 

Use with CYP3A4 inhibitors

Caution should be exercised when prescribing Helt® to patients using potent CYP3A4 inhibitors (ritonavir, saquinavir, ketoconazole, itraconazole, and erythromycin), as increased tadalafil exposure (AUC) has been observed if the medicinal products are combined (see section 4.5).

 

Helt® and other treatments for erectile dysfunction

The safety and efficacy of combinations of Helt® and other PDE5 inhibitors or other treatments for erectile dysfunction have not been studied. The patients should be informed not to take Helt® in such combinations.

 

Lactose

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


Interaction studies were conducted with 10 mg and/or 20 mg tadalafil, as indicated below. With regard to those interaction studies where only the 10 mg tadalafil dose was used, clinically relevant interactions at higher doses cannot be completely ruled out.

Effects of Other Substances on Tadalafil

Cytochrome P450 inhibitors

Tadalafil is principally metabolised by CYP3A4. A selective inhibitor of CYP3A4, ketoconazole (200 mg daily), increased tadalafil (10 mg) exposure (AUC) 2-fold and Cmax by 15%, relative to the AUC and Cmax values for tadalafil alone. Ketoconazole (400 mg daily) increased tadalafil (20 mg) exposure (AUC) 4-fold and Cmax by 22%. Ritonavir, a protease inhibitor (200 mg twice daily), which is an inhibitor of CYP3A4, CYP2C9, CYP2C19, and CYP2D6, increased tadalafil (20 mg) exposure (AUC) 2-fold with no change in Cmax. Although specific interactions have not been studied, other protease inhibitors, such as saquinavir, and other CYP3A4 inhibitors, such as erythromycin, clarithromycin, itraconazole, and grapefruit juice, should be co-administered with caution, as they would be expected to increase plasma concentrations of tadalafil (see section 4.4). Consequently, the incidence of the adverse reactions listed in section 4.8 might be increased.

 

Transporters

The role of transporters (for example, p-glycoprotein) in the disposition of tadalafil is not known. Therefore, there is the potential of drug interactions mediated by inhibition of transporters.

 

Cytochrome P450 inducers

A CYP3A4 inducer, rifampicin, reduced tadalafil AUC by 88%, relative to the AUC values for tadalafil alone (10 mg). This reduced exposure can be anticipated to decrease the efficacy of tadalafil; the magnitude of decreased efficacy is unknown. Other inducers of CYP3A4, such as phenobarbital, phenytoin, and carbamazepine, may also decrease plasma concentrations of tadalafil.

 

Effects of Tadalafil on Other Medicinal Products

Nitrates

In clinical studies, tadalafil (5, 10 and 20 mg) was shown to augment the hypotensive effects of nitrates. Therefore, administration of Helt® to patients who are using any form of organic nitrate is contraindicated (see section 4.3). Based on the results of a clinical study in which 150 subjects receiving daily doses of tadalafil 20 mg for 7 days and 0.4 mg sublingual nitroglycerin at various times, this interaction lasted for more than 24 hours and was no longer detectable when 48 hours had elapsed after the last tadalafil dose. Thus, in a patient prescribed any dose of tadalafil (2.5 mg- 20 mg), where nitrate administration is deemed medically necessary in a life-threatening situation, at least 48 hours should have elapsed after the last dose of Helt® before nitrate administration is considered. In such circumstances, nitrates should only be administered under close medical supervision with appropriate haemodynamic monitoring.

 

Anti-hypertensives (including calcium channel blockers)

The co-administration of doxazosin (4 and 8 mg daily) and tadalafil (5 mg daily dose and 20 mg as a single dose) increases the blood pressure-lowering effect of this alpha-blocker in a significant manner. This effect lasts at least twelve hours and may be symptomatic, including syncope. Therefore, this combination is not recommended (see section 4.4).

In interaction studies performed in a limited number of healthy volunteers, these effects were not reported with alfuzosin or tamsulosin. However, caution should be exercised when using tadalafil in patients treated with any alpha-blockers, and notably in the elderly. Treatments should be initiated at minimal dosage and progressively adjusted.

In clinical pharmacology studies, the potential for tadalafil to augment the hypotensive effects of antihypertensive medicinal products was examined. Major classes of antihypertensive medicinal products were studied, including calcium-channel blockers (amlodipine), angiotensin converting enzyme (ACE) inhibitors (enalapril), beta-adrenergic receptor blockers (metoprolol), thiazide diuretics (bendrofluazide), and angiotensin II receptor blockers (various types and doses, alone or in combination with thiazides, calcium-channel blockers, beta-blockers, and/or alpha-blockers). Tadalafil (10 mg, except for studies with angiotensin II receptor blockers and amlodipine in which a 20 mg dose was applied) had no clinically significant interaction with any of these classes. In another clinical pharmacology study, tadalafil (20 mg) was studied in combination with up to 4 classes of antihypertensives. In subjects taking multiple antihypertensives, the ambulatory-blood-pressure changes appeared to relate to the degree of blood pressure control. In this regard, study subjects whose blood pressure was well controlled, the reduction was minimal and similar to that seen in healthy subjects. In study subjects whose blood pressure was not controlled, the reduction was greater, although this reduction was not associated with hypotensive symptoms in the majority of subjects. In patients receiving concomitant antihypertensive medicinal products, tadalafil 20 mg may induce a blood pressure decrease, which (with the exception of alpha-blockers - see above) is, in general, minor and not likely to be clinically relevant. Analysis of Phase 3 clinical trial data showed no difference in adverse events in patients taking tadalafil with or without antihypertensive medicinal products. However, appropriate clinical advice should be given to patients regarding a possible decrease in blood pressure when they are treated with antihypertensive medicinal products.

 

Riociguat

Preclinical studies showed an additive systemic blood pressure lowering effect when PDE5 inhibitors were combined with riociguat. In clinical studies, riociguat has been shown to augment the hypotensive effects of PDE5 inhibitors. There was no evidence of favourable clinical effect of the combination in the population studied. Concomitant use of riociguat with PDE5 inhibitors, including tadalafil, is contraindicated (see section 4.3).

 

5- alpha reductase inhibitors

In a clinical trial that compared tadalafil 5 mg coadministered with finasteride 5 mg to placebo plus finasteride 5 mg in the relief of BPH symptoms, no new adverse reactions were identified. However, as a formal drug-drug interaction study evaluating the effects of tadalafil and 5-alpha reductase inhibitors (5-ARIs) has not been performed, caution should be exercised when tadalafil is co-administered with 5-ARIs.

CYP1A2 substrates (e.g. theophylline)

When tadalafil 10 mg was administered with theophylline (a non-selective phosphodiesterase inhibitor) in a clinical pharmacology study, there was no pharmacokinetic interaction. The only pharmacodynamic effect was a small (3.5 bpm) increase in heart rate. Although this effect is minor and was of no clinical significance in this study, it should be considered when co-administering these medicinal products.

 

Ethinylestradiol and terbutaline

Tadalafil has been demonstrated to produce an increase in the oral bioavailability of ethinylestradiol; a similar increase may be expected with oral administration of terbutaline, although the clinical consequence of this is uncertain.

 

Alcohol

Alcohol concentrations (mean maximum blood concentration 0.08%) were not affected by co-administration with tadalafil (10 mg or 20 mg). In addition, no changes in tadalafil concentrations were seen 3 hours after co-administration with alcohol. Alcohol was administered in a manner to maximise the rate of alcohol absorption (overnight fast with no food until 2 hours after alcohol). Tadalafil (20 mg) did not augment the mean blood pressure decrease produced by alcohol (0.7 g/kg or approximately 180 ml of 40% alcohol [vodka] in an 80 kg male) but, in some subjects, postural dizziness and orthostatic hypotension were observed. When tadalafil was administered with lower doses of alcohol (0.6 g/kg), hypotension was not observed and dizziness occurred with similar frequency to alcohol alone. The effect of alcohol on cognitive function was not augmented by tadalafil (10 mg).

 

Cytochrome P450 metabolised medicinal products

Tadalafil is not expected to cause clinically significant inhibition or induction of the clearance of medicinal products metabolised by CYP450 isoforms. Studies have confirmed that tadalafil does not inhibit or induce CYP450 isoforms, including CYP3A4, CYP1A2, CYP2D6, CYP2E1, CYP2C9 and CYP2C19.

 

CYP2C9 substrates (e.g. R-warfarin)

Tadalafil (10 mg and 20 mg) had no clinically significant effect on exposure (AUC) to S-warfarin or R-warfarin (CYP2C9 substrate), nor did tadalafil affect changes in prothrombin time induced by warfarin.

 

Aspirin

Tadalafil (10 mg and 20 mg) did not potentiate the increase in bleeding time caused by acetylsalicylic acid.

 

Antidiabetic medicinal products

Specific interaction studies with antidiabetic medicinal products were not conducted.


Helt® is not indicated for use by women.

Pregnancy

There are limited data from the use of tadalafil in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancyembryonal/foetal development, parturition or postnatal development (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Helt® during pregnancy.

 

Breast-feeding

Available pharmacodynamic/toxicological data in animals have shown excretion of tadalafil in milk. A risk to the suckling child cannot be excluded. Helt® should not be used during breast feeding.

 

Fertility

Effects were seen in dogs that might indicate impairment of fertility. Two subsequent clinical studies suggest that this effect is unlikely in humans, although a decrease in sperm concentration was seen in some men (see sections 5.1 and 5.3).


Helt® has negligible influence on the ability to drive or use machines. Although the frequency of reports of dizziness in placebo and tadalafil arms in clinical trials was similar, patients should be aware of how they react to Helt® before driving or using machines.


Summary of the safety profile

The most commonly reported adverse reactions in patients taking tadalafil for the treatment of erectile dysfunction or benign prostatic hyperplasia were headache, dyspepsia, back pain and myalgia, in which the incidences increase with increasing dose of tadalafil. The adverse reactions reported were transient, and generally mild or moderate. The majority of headaches reported with tadalafil once-a-day dosing are experienced within the first 10 to 30 days of starting treatment.

Tabulated summary of adverse reactions

The table below lists the adverse reactions observed from spontaneous reporting and in placebo-controlled clinical trials (comprising a total of 8022 patients on tadalafil and 4422 patients on placebo) for on-demand and once-a-day treatment of erectile dysfunction and the once-a-day treatment of benign prostatic hyperplasia.

Frequency convention: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very Rare (<1/10,000) and Not known (cannot be estimated from the available data).

Very common

Common

Uncommon

Rare

Immune system disorders

 

 

Hypersensitivity reactions

Angioedema2

Nervous system disorders

 

Headache

Dizziness

Stroke(including haemorrhagic events), Syncope, Transient ischaemic attacks1, Migraine2, Seizures2, Transient amnesia

Eye disorders

 

 

Blurred vision, Sensations described as eye pain

Visual field defect, Swelling of eyelids, Conjunctival hyperaemia, Non-arteritic anterior ischaemic optic neuropathy (NAION)2, Retinal vascular occlusion2

Ear and labyrinth disorders

 

 

Tinnitus

Sudden hearing loss

Cardiac disorders1

 

 

Tachycardia, Palpitations

Myocardial infarction, Unstable angina pectoris2, Ventricular arrhythmia2

Vascular disorders

 

Flushing

Hypotension3, Hypertension

 

Respiratory, thoracic and mediastinal disorders

 

Nasal congestion

Dyspnoea, Epistaxis

 

Gastrointestinal disorders

 

Dyspepsia,

 

Abdominal pain,

Vomiting, Nausea,

Gastro-oesophageal reflux

 

Skin and subcutaneous tissue disorders

 

 

Rash

Urticaria, Stevens-Johnson syndrome2, Exfoliative dermatitis2, Hyperhydrosis (sweating)

Musculoskeletal, connective tissue and bone disorders

                   

Back pain, Myalgia, Pain in extremity

 

 

Renal and urinary disorders

 

 

Haematuria

 

Reproductive system and breast disorders

 

 

Prolonged erections

Priapism, Penile haemorrhage, Haematospermia

General disorders and administration site conditions

 

 

Chest pain1, Peripheral oedema, Fatigue

Facial oedema2, Sudden cardiac death1,2

     

(1) Most of the patients had pre-existing cardiovascular risk factors (see section 4.4).

(2) Postmarketing surveillance reported adverse reactions not observed in placebo-controlled clinical trials.

(3) More commonly reported when tadalafil is given to patients who are already taking antihypertensive medicinal products.

Description of selected adverse reactions

A slightly higher incidence of ECG abnormalities, primarily sinus bradycardia, has been reported in patients treated with tadalafil once a day as compared with placebo. Most of these ECG abnormalities were not associated with adverse reactions.

 

Other special populations

Data in patients over 65 years of age receiving tadalafil in clinical trials, either for the treatment of erectile dysfunction or the treatment of benign prostatic hyperplasia, are limited. In clinical trials with tadalafil taken on demand for the treatment of erectile dysfunction, diarrhea was reported more frequently in patients over 65 years of age. In clinical trials with tadalafil 5 mg taken once a day for the treatment of benign prostatic hyperplasia, dizziness and diarrhea were reported more frequently in patients over 75 years of age. 


Single doses of up to 500 mg have been given to healthy subjects, and multiple daily doses up to 100 mg have been given to patients. Adverse events were similar to those seen at lower doses.

In cases of overdose, standard supportive measures should be adopted, as required. Haemodialysis contributes negligibly to tadalafil elimination.

 


Pharmacotherapeutic group: Urologicals, Drugs used in erectile dysfunction. ATC code: G04BE08.

 

Mechanism of action

Tadalafil is a selective, reversible inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). When sexual stimulation causes the local release of nitric oxide, inhibition of PDE5 by tadalafil produces increased levels of cGMP in the corpus cavernosum. This results in smooth muscle relaxation and inflow of blood into the penile tissues, thereby producing an erection. Tadalafil has no effect in the treatment of erectile dysfunction in the absence of sexual stimulation.

Tadalafil 5 mg - The effect of PDE5 inhibition on cGMP concentration in the corpus cavernosum is also observed in the smooth muscle of the prostate, the bladder and their vascular supply. The resulting vascular relaxation increases blood perfusion which may be the mechanism by which symptoms of benign prostatic hyperplasia are reduced. These vascular effects may be complemented by inhibition of bladder afferent nerve activity and smooth muscle relaxation of the prostate and bladder.

 

Pharmacodynamic effects

Studies in vitro have shown that tadalafil is a selective inhibitor of PDE5. PDE5 is an enzyme found in corpus cavernosum smooth muscle, vascular and visceral smooth muscle, skeletal muscle, platelets, kidney, lung, and cerebellum. The effect of tadalafil is more potent on PDE5 than on other phosphodiesterases. Tadalafil is >10,000-fold more potent for PDE5 than for PDE1, PDE2, and PDE4 enzymes which are found in the heart, brain, blood vessels, liver, and other organs. Tadalafil is >10,000-fold more potent for PDE5 than for PDE3, an enzyme found in the heart and blood vessels. This selectivity for PDE5 over PDE3 is important because PDE3 is an enzyme involved in cardiac contractility. Additionally, tadalafil is approximately 700-fold more potent for PDE5 than for PDE6, an enzyme which is found in the retina and is responsible for phototransduction. Tadalafil is also >10,000-fold more potent for PDE5 than for PDE7 through PDE10.

 

Clinical efficacy and safety

Tadalafil administered to healthy subjects produced no significant difference compared to placebo in supine systolic and diastolic blood pressure (mean maximal decrease of 1.6/0.8mmHg, respectively), in standing systolic and diastolic blood pressure (mean maximal decrease of 0.2/4.6mmHg, respectively), and no significant change in heart rate.

In a study to assess the effects of tadalafil on vision, no impairment of colour discrimination (blue/green) was detected using the Farnsworth-Munsell 100-hue test. This finding is consistent with the low affinity of tadalafil for PDE6 compared to PDE5. Across all clinical studies, reports of changes in colour vision were rare (<0.1%).

Three studies were conducted in men to assess the potential effect on spermatogenesis of tadalafil 10mg (one 6-month study) and 20mg (one 6-month and one 9-month study) administered daily. In two of these studies decreases were observed in sperm count and concentration related to tadalafil treatment of unlikely clinical relevance. These effects were not associated with changes in other parameters, such as motility, morphology, and FSH.

 

Erectile dysfunction

For tadalafil on demand, three clinical studies were conducted in 1054 patients in an at-home setting to define the period of responsiveness. Tadalafil demonstrated statistically significant improvement in erectile function and the ability to have successful sexual intercourse up to 36 hours following dosing, as well as patients' ability to attain and maintain erections for successful intercourse compared to placebo as early as 16 minutes following dosing. 

In a 12-week study performed in 186 patients (142 tadalafil, 44 placebo) with erectile dysfunction secondary to spinal cord injury, tadalafil significantly improved the erectile function leading to a mean per-subject proportion of successful attempts in patients treated with tadalafil 10 or 20 mg (flexible-dose, on demand) of 48% as compared to 17% with placebo.

Tadalafil at doses of 2 to 100mg has been evaluated in 16 clinical studies involving 3250 patients, including patients with erectile dysfunction of various severities (mild, moderate, severe), etiologies, ages (range 21-86 years), and ethnicities. Most patients reported erectile dysfunction of at least 1 year in duration. In the primary efficacy studies of general populations, 81% of patients reported that tadalafil improved their erections as compared to 35% with placebo. Also, patients with erectile dysfunction in all severity categories reported improved erections whilst taking tadalafil (86%, 83%, and 72% for mild, moderate, and severe, respectively, as compared to 45%, 42%, and 19% with placebo). In the primary efficacy studies, 75% of intercourse attempts were successful in tadalafil -treated patients as compared to 32% with placebo.

For once-a-day evaluation of tadalafil at doses of 2.5, 5, and 10 mg 3 clinical studies were initially conducted involving 853 patients of various ages (range 21-82 years) and ethnicities, with erectile dysfunction of various severities (mild, moderate, severe) and etiologies. In the two primary efficacy studies of general populations, the mean per-subject proportion of successful intercourse attempts were 57 and 67% on tadalafil 5mg, 50% on tadalafil 2.5mg as compared to 31 and 37% with placebo. In the study in patients with erectile dysfunction secondary to diabetes, the mean per-subject proportion of successful attempts were 41 and 46% on tadalafil 5mg and 2.5mg, respectively, as compared to 28% with placebo. Most patients in these three studies were responders to previous on-demand treatment with PDE5 inhibitors. In a subsequent study, 217 patients who were treatment-naive to PDE5 inhibitors were randomised to tadalafil 5mg once a day vs. placebo. The mean per-subject proportion of successful sexual intercourse attempts was 68% for tadalafil patients compared to 52% for patients on placebo.

 

Benign prostatic hyperplasia

Tadalafil was studied in 4 clinical studies of 12 weeks duration enrolling over 1500 patients with signs and symptoms of benign prostatic hyperplasia. The improvement in the total international prostate symptom score with tadalafil 5mg in the four studies were -4.8, -5.6, -6.1 and -6.3 compared to -2.2, -3.6, -3.8 and -4.2 with placebo. The improvements in total international prostate symptom score occurred as early as 1 week. In one of the studies, which also included tamsulosin 0.4 mg as an active comparator, the improvement in total international prostate symptom score with C tadalafil 5mg, tamsulosin and placebo were -6.3, -5.7 and -4.2 respectively.

One of these studies assessed improvements in erectile dysfunction and signs and symptoms of benign prostatic hyperplasia in patients with both conditions. The improvements in the erectile function domain of the international index of erectile function and the total international prostate symptom score in this study were 6.5 and -6.1 with tadalafil 5 mg compared to 1.8 and -3.8 with placebo, respectively. The mean per-subject proportion of successful sexual intercourse attempts was 71.9% with tadalafil 5 mg compared to 48.3% with placebo.

The maintenance of the effect was evaluated in an open-label extension to one of the studies, which showed that the improvement in total international prostate symptom score seen at 12 weeks was maintained for up to 1 additional year of treatment with tadalafil 5mg.

 

Paediatric population

A single study has been performed in paediatric patients with Duchenne Muscular Dystrophy (DMD) in which no evidence of efficacy was seen. The randomised, double-blind, placebo-controlled, parallel, 3-arm study of tadalafil was conducted in 331 boys aged 7-14 years with DMD receiving concurrent corticosteroid therapy. The study included a 48-week double-blind period where patients were randomised to tadalafil 0.3 mg/kg, tadalafil 0.6 mg/kg, or placebo daily. Tadalafil did not show efficacy in slowing the decline in ambulation as measured by the primary 6 minute walk distance (6MWD) endpoint: least squares (LS) mean change in 6MWD at 48 weeks was -51.0 meters (m) in the placebo group, compared with -64.7 m in the tadalafil 0.3 mg/kg group (p = 0.307) and -59.1 m in the tadalafil 0.6 mg/kg group (p = 0.538). In addition, there was no evidence of efficacy from any of the secondary analyses performed in this study. The overall safety results from this study were generally consistent with the known safety profile of tadalafil and with adverse events (AEs) expected in a paediatric DMD population receiving corticosteroids.

 

The European Medicines Agency has waived the obligation to submit the results of studies in all subsets of the paediatric population in the treatment of the erectile dysfunction. See section 4.2 for information on paediatric use.


Absorption

Tadalafil is readily absorbed after oral administration and the mean maximum observed plasma concentration (Cmax) is achieved at a median time of 2 hours after dosing. Absolute bioavailability of tadalafil following oral dosing has not been determined.

The rate and extent of absorption of tadalafil are not influenced by food, thus Helt® may be taken with or without food. The time of dosing (morning versus evening) had no clinically relevant effects on the rate and extent of absorption.

 

Distribution

The mean volume of distribution is approximately 63 l, indicating that tadalafil is distributed into tissues. At therapeutic concentrations, 94% of tadalafil in plasma is bound to proteins. Protein binding is not affected by impaired renal function.

Less than 0.0005% of the administered dose appeared in the semen of healthy subjects.

 

Biotransformation

Tadalafil is predominantly metabolised by the cytochrome P450 (CYP) 3A4 isoform. The major circulating metabolite is the methylcatechol glucuronide. This metabolite is at least 13,000-fold less potent than tadalafil for PDE5. Consequently, it is not expected to be clinically active at observed metabolite concentrations.

 

Elimination

The mean oral clearance for tadalafil is 2.5 l/h and the mean half-life is 17.5 hours in healthy subjects.

Tadalafil is excreted predominantly as inactive metabolites, mainly in the faeces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).

 

Linearity/Non-Linearity

Tadalafil pharmacokinetics in healthy subjects are linear with respect to time and dose. Over a dose range of 2.5 to 20 mg, exposure (AUC) increases proportionally with dose. Steady-state plasma concentrations are attained within 5 days of once daily dosing.

Pharmacokinetics determined with a population approach in patients with erectile dysfunction are similar to pharmacokinetics in subjects without erectile dysfunction.

 

Special Populations

Elderly

Healthy elderly subjects (65 years or over) had a lower oral clearance of tadalafil, resulting in 25% higher exposure (AUC) relative to healthy subjects aged 19 to 45 years. This effect of age is not clinically significant and does not warrant a dose adjustment.

 

Renal Insufficiency

In clinical pharmacology studies using single dose tadalafil (5 to 20mg), tadalafil exposure (AUC) approximately doubled in subjects with mild (creatinine clearance 51 to 80 ml/min) or moderate (creatinine clearance 31 to 50 ml/min) renal impairment and in subjects with end-stage renal disease on dialysis. In haemodialysis patients, Cmax was 41% higher than that observed in healthy subjects. Haemodialysis contributes negligibly to tadalafil elimination.

 

Hepatic Insufficiency

Tadalafil exposure (AUC) in subjects with mild and moderate hepatic impairment (Child-Pugh class A and B) is comparable to exposure in healthy subjects when a dose of 10 mg is administered. There is limited clinical data on the safety of tadalafil in patients with severe hepatic insufficiency (Child-Pugh class C). If tadalafil is prescribed, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician. There are no available data about the administration of once-a-day dosing of tadalafil to patients with hepatic impairment. If tadalafil is prescribed once-a-day, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician. There are no available data about the administration of doses higher than 10 mg of tadalafil to patients with hepatic impairment.

 

Patients with Diabetes

Tadalafil exposure (AUC) in patients with diabetes was approximately 19% lower than the AUC value for healthy subjects. This difference in exposure does not warrant a dose adjustment.


Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to reproduction.

There was no evidence of teratogenicity, embryotoxicity, or foetotoxicity in rats or mice that received up to 1000 mg/kg/day tadalafil. In a rat prenatal and postnatal development study, the no observed effect dose was 30 mg/kg/day. In the pregnant rat the AUC for calculated free drug at this dose was approximately 18-times the human AUC at a 20 mg dose.

There was no impairment of fertility in male and female rats. In dogs given tadalafil daily for 6 to 12 months at doses of 25 mg/kg/day (resulting in at least a 3-fold greater exposure [range 3.7-18.6] than seen in humans given a single 20 mg dose) and above, there was regression of the seminiferous tubular epithelium that resulted in a decrease in spermatogenesis in some dogs. See also section 5.1.


Lactose monohydrate

Croscarmellose sodium

Sodium lauryl sulfate

Povidone K30

Microcrystalline cellulose

Magnesium stearate

Opadry II OY-L white 28900 powder

Yellow iron oxide

FD & C yellow #6 lake

Polyethylene glycol 6000

Ethanol absolute


Not applicable.

 

2 years.

Store below 30°C.

Store in the original package in order to protect from moisture


Helt® 5 mg tablets are peach normal round biconvex film coated tablets engraved with H3 on one face and scored on the other face, packed in PVC/PVDC/Alu. blisters, intended for oral use.

Pack size:

30 tablets, (10 tablets in PVC/PVDC/Alu. blister, 3 blisters/pack).

 

Helt® 10 mg tablets are peach normal round, biconvex film coated tablets engraved with H5 on one face and scored on the other face, packed in PVC/PVDC/Alu. blisters, intended for oral use.

Pack size:

1 tablet (1 tablet in PVC/PVDC/Alu. blister, 1 blister/pack).

4 tablets, (1 tablet in PVC/PVDC/Alu. blister, 4 blisters/pack).

 

Helt® 20 mg: Peach colored, almond shape film coated tablets engraved with H7 on one face, packed in PVC/PVDC/Alu. blister, intended for oral use.

Pack size:

1 tablet, (1 tablet in PVC/PVDC/Alu. blister, 1 blister/pack).

4 tablets, (1 tablet in PVC/PVDC/Alu. blister, 4 blisters/pack).


No special requirements.


Med City Pharma- KSA Tel: 00966920003288 Fax: 00966126358138 Mobile: 00966555786968 P.O .Box: 42512 - Jeddah 21551 E-mail: MD.admin@axantia.com

05/2023
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