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Lovera 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. Lovera has been shown to significantly improve the ability of obtaining a hard erect penis suitable for sexual activity.
Lovera contains the active substance tadalafil which belongs to a group of medicines called phosphodiesterase type 5 inhibitors. Following sexual stimulation Lovera 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. Lovera will not help you if you do not have erectile dysfunction.
It is important to note that Lovera 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.
Lovera 5 mg is used to treat adult men with urinary symptoms associated with a common condition called benign prostatic hyperplasia. This is when the prostate gland gets bigger with age. Symptoms include difficulty in starting to pass water, a feeling of not completely emptying the bladder and a more frequent need to pass water even at night. Lovera improves blood flow to, and relaxes the muscles of, the prostate and bladder which may reduce symptoms of benign prostatic hyperplasia. Lovera has been shown to improve these urinary symptoms as early as 1-2 weeks after starting treatment.
Do not take Lovera
- If you are allergic (hypersensitive) to tadalafil or any of the other ingredients of Lovera (listed in section 6).
- 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”). Lovera 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 have had a recent heart attack within the last 90 days.
- If you have had a recent stroke within the last 6 months.
- If you have low blood pressure or uncontrolled high blood pressure.
- If you have 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 Lovera, have been shown to increase the hypotensive effects of this medicine. If you are taking riociguat or are unsure tell your doctor.
Take special care with Lovera
Talk to your doctor before taking Lovera.
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.
The following are reasons why Lovera may also not be suitable for you. If any of them apply to you, talk to your doctor before you take the medicine:
- You have sickle cell anaemia (an abnormality of red blood cells).
- You have multiple myeloma (cancer of the bone marrow).
- You have leukaemia (cancer of the blood cells).
- You have any deformation of your penis.
- You have a serious liver problem.
- You have a severe kidney problem
It is not known if Lovera 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 nonnerve-sparing prostatectomy).
If you experience sudden decrease or loss of vision, stop taking Lovera and contact your doctor immediately.
Lovera is not intended for use by women.
Children and adolescents
Lovera is not intended for use by children and adolescents under the age of 18.
Using other medicines
Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without prescription, because they might interact. Do not take Lovera if you are already taking nitrates.
Some medicines may be affected by Lovera or they may affect how well Lovera 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.
Taking Lovera with food and drink
Information on the effect of alcohol is in section 3. Grapefruit juice may affect how well Lovera 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 Lovera in clinical studies have reported dizziness. Check carefully how you react to the medicines before driving or using any machines.
Important information about some of the ingredients of Lovera
Lovera 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 Lovera exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.
Lovera tablets are for oral use in men only. Swallow the tablet whole with some water. The tablets can be taken with or without food.
For Lovera 5 mg film-coated tablets:
For the treatment of erectile dysfunction
The recommended dose is one 5 mg tablet taken once a day at approximately the same time of the day.
Do not take Lovera more than once a day.
When taken once a day Lovera 5 mg allows you to obtain an erection, when sexually stimulated, at any time point during the 24 hours of the day. Once a day dosing of Lovera 5 mg may be useful to men who anticipate having sexual activity two or more times per week.
It is important to note that Lovera 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.
For the treatment benign prostatic hyperplasia
The dose is one 5 mg tablet taken once a day at approximately the same time of the day.
If you have benign prostatic hyperplasia and erectile dysfunction, the dose remains one 5 mg tablet taken once a day.
Do not take Lovera more than once a day.
For Lovera 10 and 20 mg film-coated tablets:
The recommended starting dose is one 10 mg tablet before sexual activity. If the effect of this dose is too weak your doctor may increase the dose to 20 mg.
You may take a Lovera tablet at least 30 minutes before sexual activity. Lovera may still be effective up to 36 hours after taking the tablet.
Do not take Lovera more than once a day. Lovera 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 Lovera 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. Drinking alcohol may temporarily lower your blood pressure. If you have taken or are planning to take Lovera, 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 Lovera than you should
Contact your doctor. You may experience side effects described in section 4.
If you forget to take Lovera
Take your dose as soon as you remember but do not take a double dose to make up for a forgotten tablet. You should not take Lovera more than once a day.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
Like all medicines, Lovera 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).
- Prolonged and possibly painful erection after taking Lovera (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, indigestion and reflux.
Uncommon (seen in 1 to 10 in every 1,000 patients)
- Dizziness, stomach ache, blurred vision, eye pain, increased sweating, difficulty in breathing, penile bleeding, presence of blood in semen and/or urine, pounding heartbeat sensation, a fast heart rate, high blood pressure, low blood pressure, nose bleeds and ringing in the ears.
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).
Heart attack and stroke have also been reported rarely in men taking Lovera. 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 Lovera 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 effects dizziness and diarrhoea have been reported more frequently in men over 75 years of age taking Lovera.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Keep out of the reach and sight of children.
Do not use Lovera after the expiry date stated on the carton and blister after ‘EXP’.
The expiry date refers to the last day of that month.
Store in the original package in order to protect from moisture. 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.
Each film-coated tablet of Lovera 5 mg contains 5 mg of tadalafil.
Each film-coated tablet of Lovera 10 mg contains 10 mg of tadalafil.
Each film-coated tablet of Lovera 20 mg contains 20 mg of tadalafil.
The other ingredients are:
Lactose NF Fast Flow-BMS 35957, Avicel PH 10, Crospovidone NF, Hydroxypropyl Methylcellulose, Sodium Lauryl Sulphate, Purified Water BP, Avicel PH 102, Colloidal Silicon Dioxide, Magnesium Stearate (Mallinkrodt), and Opadry II 31F82689 Yellow.
Dammam Pharma
Saudi Arabia
Address: 1st industrial city, unit No.1, PO.BOX: 7137, Dammam 32234-4384
Phone: +966138216444
Fax: +966138216422
Email: regulatory-affairs@dammampharma.sa
لوفيرا هو علاج للرجال البالغين الذين يعانون من ضعف الإنتصاب. ويحدث ذلك عندما يعجز الرجل عن جعل – أو الإبقاء على – القضيب صلباً ومنتصباً بما يلائم النشاط الجنسي. يؤدي لوفيرا إلى تحسن كبير في القدرة علي الحصول علي قضيب منتصب صلب مناسب للنشاط الجنسي.
يحتوي لوفيرا علي المادة الفعالة (تادالافيل) و التي تنتمي لمجموعة من الأدوية تسمى مثبطات إنزيم فوسفو داي إستريز نوع 5. ويعمل لوفيرا - عقب الإثارة الجنسية - علي المساعدة علي ارتخاء الأوعية الدموية الموجودة في القضيب، بما يسمح بتدفق الدم إلي القضيب. وينتج عن ذلك تحسن وظيفة الإنتصاب. لن يساعدك لوفيرا إن لم تكن مصاباً بضعف الإنتصاب.
من المهم أن تعلم أن لوفيرا لا يعمل إن لم تكن هناك إثارة جنسية. لذا ستكون أنت وشريكتك بحاجة إلى مداعبة ما قبل الجماع، تماماً كما تفعل إن لم تكن تتناول دواءً لعلاج ضعف الإنتصاب.
يستخدم لوفيرا 5 ملجم لعلاج الرجال البالغين المصابين بالأعراض البولية المصاحبة للحالة الشائعة التي تسمى تضخم البروستاتا الحميد. و التي تحدث عندما تكبرغدة البروستاتا مع تقدم العمر. وتتضمن الأعراض صعوبة في البدء في التبول، وشعور بعدم تفريغ المثانة تماما والحاجة أكثر تكرارا للتبول حتى في الليل. يحسن لوفيرا من تدفق الدم إلي ويريح عضلات البروستاتا والمثانة مما قد يقلل من أعراض تضخم البروستاتا الحميد. وقد تبين أن لوفيرا يحسن هذه الأعراض البولية في أقرب وقت بعد 1-2 أسابيع بعد بدء العلاج.
امتنع عن تناول لوفيرا في الحالات الآتية:
• إذا كنت مصابًا بفرط الحساسية لمادة تادالافيل أو أي من المكونات الأخرى لـ لوفيرا (المذكورة فى فقرة 6).
• إذا كنت تتناول أياً من صيغ مُعطِيات النيترات العضوي أو أكسيد النيتريك مثل أميل نيتريت. وهي مجموعة من الأدوية تسمى "نيترات" وتستخدم في علاج الذبحة الصدرية ("ألم الصدر"). فقد تبين أن لوفيرا يزيد من تأثير تلك الأدوية. إن كنت تتناول أياً من أشكال النيترات أو كنت غير واثق، فبادر باستشارة طبيبك المعالج.
• إذا كنت مصاباً بمرض قلبي خطير أو أصابتك مؤخراً أزمة قلبية خلال الـ 90 يوم السابقين.
• إذا كنت قد أصبت مؤخراً بسكتة دماغية خلال الـ 6 أشهر السابقة.
• إذا كنت تعاني من انخفاض ضغط الدم أو ارتفاع ضغط الدم غير المنضبط.
• إذا سبقت لك الإصابة بفقد البصر بسبب اعتلال عصبي بصري إقفاري أمامي غير ناتج عن التهاب شرياني (NAION)، وهي حالة توصف بـ "سكتة العين".
• إذا كنت تتناول ريوسيجوات. يستخدم هذا الدواء لعلاج ارتفاع ضغط الدم الشرياني الرئوي (أي ارتفاع ضغط الدم في الرئتين) وارتفاع ضغط الدم الرئوي الانسدادي التجلطي المزمن (أي ارتفاع ضغط الدم في الرئتين الثانوي لتجلط الدم). وقد ثبت زيادة مثبطات إنزيم فوسفو داي إستريز نوع 5، مثل لوفيرا، آثار انخفاض ضغط الدم لهذا الدواء. إذا كنت تتناول ريوسيجوات أو غير متأكد أخبر طبيبك.
ينبغي توخي الحذر عند تناول لوفيرا
تحدث إلى طبيبك قبل تناول لوفيرا.
عليك أن تدرك أن النشاط الجنسي ينطوي على خطورة محتملة بالنسبة لمرضى القلب لأنه يضع جهداً إضافياً علي القلب. إذا كنت تعاني من مشكلة قلبية، فإنه ينبغي لك أن تخبر طبيبك المعالج.
فيما يلي الأسباب التي قد تجعل أقراص لوفيرا غير ملائمة لك. إذا كان أي منها ينطبق عليك، فعليك التواصل مع طبيبك المعالج قبل أن تبدأ في تناول الدواء:
• إذا كنت مصاباً بأنيميا الخلايا المنجلية (وهو مرض يصيب خلايا الدم الحمراء).
• إذا كنت مصاباً بالورم النخاعي المتعدد (وهو سرطان بنخاع العظام).
• إذا كنت مصاباً بلوكيميا (وهو سرطان بخلايا الدم).
• إذا كنت مصاباً بأية تشوهات في القضيب.
• إذا كنت تعاني من مشكلة خطيرة بالكبد.
• إذا كنت تعاني من مشكلة خطيرة بالكلي.
ليس من المعلوم ما إذا كان لوفيرا فعالاً بالنسبة للمرضى الذين سبق أن:
• خضعوا لعملية جراحية بمنطقة الحوض.
• خضعوا لعملية استئصال كلي أو جزئي للبروستاتا دون المحافظة على الأعصاب (استئصال البروستاتا الجذري بدون تجنيب الأعصاب).
إذا تعرضت لانخفاض مفاجئ في قوة الإبصار أو لفقد البصر، فعليك التوقف عن تناول أقراص لوفيرا والتواصل مباشرة مع طبيبك المعالج.
أقراص لوفيرا ليست معدة للإستعمال من قبل النساء.
الأطفال والمراهقين
أقراص لوفيرا ليست معدة للإستعمال من قبل الأطفال والمراهقين الذين تقل أعمارهم عن 18 عاما.
استعمال أدوية أخرى
يرجى أن تخبر طبيبك المعالج إن كنت تتناول حالياً أو تناولت مؤخراً أية أدوية أخرى، بما في ذلك الأدوية التي تصرف دون وصفة طبية، لأن تلك الأدوية قد تتداخل مع لوفيرا . ويتسم هذا الأمر بأهمية خاصة إذا كنت تتناول أحد أدوية النيترات. لا تتناول لوفيرا إذا كنت تتناول أدوية النيترات.
قد تتأثر بعض الأدوية بـ لوفيرا أو أنها قد تؤثر على طريقة عمل لوفيرا. أخبر طبيبك أو الصيدلي إذا كنت تتناول بالفعل:
- مانع ألفا (التي تستخدم لعلاج ارتفاع ضغط الدم أو الأعراض البولية المرتبطة بتضخم البروستاتا الحميد).
- ادوية أخرى لعلاج ارتفاع ضغط الدم.
- ريوسيجوات.
- مانع مختزل 5- ألفا (الذي يستخدم لعلاج تضخم البروستاتا).
- أدوية مثل أقراص كيتوكونازول (لعلاج العدوي الفطرية) ومثبطات الأنزيم البروتيني لعلاج عدوي الإيدز أو فيروس نقص المناعة البشرية.
- فينوباربيتال، فينيتوين وكاربامازيبين (أدوية مضادة للتشنجات).
- ريفامبيسين، إريثروميسين، كلاريثروميسين أو إيتراكونازول.
- العلاجات الأخرى لضعف الإنتصاب.
تناول لوفيرا مع الطعام والشراب
المعلومات حول تأثير الكحول في القسم 3. قد يؤثر عصير الجريب فروت على طريقة عمل لوفيرا وينبغي أن يؤخذ بحذر. تحدث إلى طبيبك للحصول على مزيد من المعلومات.
الخصوبة
عندما عولجت الكلاب كان هناك انخفاض في تطوير الحيوانات المنوية في الخصيتين. شوهد انخفاض في الحيوانات المنوية عند بعض الرجال. من غير المرجح أن تؤدي هذه التأثيرات إلى نقص الخصوبة.
قيادة المركبات وتشغيل الآلات
سجل بعض الرجال الذين تناولوا لوفيرا من خلال دراسات إكلينيكية، حدوث دوار. ينبغي أن تتحقق وبحرص من كيفية تفاعلك مع الأدوية قبل أن تقدم على القيادة أو تشغيل أية ماكينات.
معلومات مهمة عن بعض مكونات أقراص لوفيرا
يحتوي لوفيرا على لاكتوز. فإذا كان طبيبك قد أخبرك من قبل أنك لا تستطيع تحمل بعض السكريات، فعليك التواصل مع طبيبك قبل أن تبدأ في تناول هذا المنتج الدوائي.
احرص دائما على تناول لوفيرا كما ينصحك طبيبك. وينبغي عليك أن تراجع طبيبك أو الصيدلي الذي تتعامل معه إذا كنت غير واثق من طريقة تناول هذا الدواء.
أقراص لوفيرا معدة للتناول عن طريق الفم. قم بإبتلاع القرص كاملاً مع الماء. يمكنك تناول أقراص لوفيرا مع الطعام أو بدونه.
أقراص لوفيرا 5 ملجم المغلفة بطبقة رقيقة:
لعلاج ضعف الإنتصاب
الجرعة الموصى بها هي قرص واحد من 5 ملجم يؤخذ مرة واحدة يوميا في نفس الوقت تقريبا من اليوم.
لا تتناول لوفيرا أكثر من مرة واحدة في اليوم.
عندما يؤخذ لوفيرا 5 ملجم مرة واحدة يوميا فإنه يسمح لك بالحصول على الإنتصاب عند الإثارة الجنسية، في أي وقت خلال الـ 24 ساعة في اليوم. الجرعة مرة واحدة يوميا من لوفيرا 5 ملجم قد يكون من مفيد للرجال الذين يتوقعون نشاط جنسي مرتين أو أكثر في الأسبوع.
من المهم أن نبين أن لوفيرا لا يعمل ما لم تحدث إثارة جنسية. لذا ستكون أنت وشريكتك بحاجة إلى الإنشغال بمداعبة ما قبل الجماع، تماماً كما تفعل إن لم تكن تتناول دواءً لعلاج ضعف الإنتصاب.
قد يؤثر شرب الكحول قدرتك على الحصول على الإنتصاب.
لعلاج تضخم البروستاتا الحميد
الجرعة هي قرص واحد 5 ملجم يؤخذ مرة واحدة يوميا في نفس الوقت تقريبا من اليوم.
إذا كان لديك تضخم البروستاتا الحميد وضعف الإنتصاب، تبقى الجرعة قرص واحد 5 ملجم يؤخذ مرة واحدة في اليوم.
لا تتناول لوفيرا أكثر من مرة واحدة يوميا.
أقراص لوفيرا 10 و 20 ملجم المغلفة بطبقة رقيقة:
الجرعة التي ينصح بتناولها في بداية العلاج هي قرص واحد 10 ملجم يتم تناوله قبل الممارسة الجنسية. في حالة ما إذا كان تأثير هذه الجرعة ضعيفاً جداً بالنسبة لك، فقد يزيد طبيبك المعالج الجرعة إلى 20 ملجم.
يمكنك تناول قرص لوفيرا قبل الممارسة الجنسية بثلاثين دقيقة على الأقل. قد تمتد فعالية لوفيرا لمدة تصل إلى 36 ساعة بعد تناول القرص.
لا تتناول لوفيرا أكثر من مرة واحدة يوميا. يستخدم لوفيرا 10 و 20 ملجم قبل النشاط الجنسي المتوقع ولا يوصى الإستخدام اليومي المستمر.
من المهم أن نبين أن لوفيرا لا يعمل ما لم تحدث إثارة جنسية. لذا ستكون أنت وشريكتك بحاجة إلى الإنشغال بمداعبة ما قبل الجماع، تماماً كما تفعل إن لم تكن تتناول دواءً لعلاج ضعف الإنتصاب.
قد يؤثر تناول المشروبات الكحولية على قدرتك على الإنتصاب. وقد يسبب تناول المشروبات الكحولية انخفاض ضغط الدم لديك على نحو مؤقت. إذا تناولت أقراص لوفيرا أو عزمت على تناولها، فعليك أن تتجنب الإفراط في الشراب (بمعنى أن يصل مستوى الكحول في الدم إلى 0.08 % أو أعلى)، فإن ذلك قد يزيد من احتمالية الشعور بالدوار عند الوقوف.
إذا تناولت جرعة زائدة من لوفيرا
اتصل بطبيبك. قد تواجه الأعراض الجانبية الموضحة في فقرة 4.
إذا كنت قد نسيت أن تتناول لوفيرا
تناول الجرعة في أقرب وقت عندما تتذكر ولكن لا تتناول جرعة مضاعفة لتعويض القرص المنسي. يجب أن لا تتناول لوفيرا أكثر من مرة في اليوم.
إذا كانت لديك أي أسئلة أخرى بشأن استعمال هذا الدواء، يمكنك سؤال طبيبك أو الصيدلي الذي تتعامل معه.
كما هو شأن كافة الأدوية، يمكن أن تسبب أقراص لوفيرا أعراض جانبية، ولو أن تلك الأعراض لا تحدث لكل من يتناول الدواء. وعادة ما تكون تلك التأثيرات بسيطة إلى متوسطة الشدة.
إذا كنت تواجه أي من الأعراض الجانبية التالية. توقف عن استخدام الدواء واطلب المساعدة الطبية على الفور:
- ردود الفعل التحسسية بما في ذلك الطفح الجلدي (التردد: غير شائع).
- ألم في الصدر - لا تستخدم النيترات ولكن اطلب مساعدة طبية فورية (التردد: غير شائع).
- الإنتصاب لفترات طويلة، وربما المؤلم بعد تناول لوفيرا (التردد: نادر). إذا كان لديك مثل هذا الإنتصاب، والذي يستمر لأكثر من 4 ساعات بشكل مستمر. يجب عليك الاتصال بالطبيب فورا.
- عدم الرؤية الفجائي (نادر الحصول).
تم الإبلاغ عن أعراض جانبية أخرى:
شائعة (تحدث في 1 - 10 في كل 100 مريض):
- الصداع، ألم الظهر، ألم في العضلات، وألم في الذراعين والساقين، واحمرار الوجه، واحتقان الانف، وعسر الهضم و الإرتجاع.
غير شائعة (تحدث في 1 - 10 في كل 1000 مريض):
- الدوخة، وألم في المعدة، عدم وضوح الرؤية، وألم في العين، وزيادة التعرق، وصعوبة في التنفس، نزيف في القضيب ، وجود دم في السائل المنوي و / أو البول، الإحساس بزيادة في ضربات القلب، وسرعة دقات القلب، وارتفاع ضغط الدم، وانخفاض ضغط الدم، و نزيف في الأنف وطنين في الأذنين.
نادرة (تحدث في 1 - 10 في كل 10000مريض):
- الإغماء، و التشنجات، و فقدان الذاكرة، وتورم في الجفون واحمرار في العينين، وانخفاض مفاجئ أو فقدان السمع وخلايا النحل (بقع حمراء وحكة على سطح الجلد).
كما تم الإبلاغ عن النوبات القلبية والسكتة الدماغية بشكل نادر في الرجال الذين يتناولون لوفيرا. وكان معظم هؤلاء الرجال لديهم مشاكل معروفة في القلب قبل تناول هذا الدواء.
تم الإبلاغ عن نقصان أو فقدان البصر الجزئي المؤقت أو الدائم في إحدى أو كلتا العينين بشكل نادر.
وقد تم الإبلاغ عن بعض الأعراض الجانبية الإضافية النادرة في الرجال الذين يتناولون لوفيرا التي لم تحدث في التجارب السريرية. وتشمل هذه:
- الصداع النصفي، وتورم في الوجه، تفاعلات الحساسية الخطيرة التي تؤدي إلي تورم في الوجه أو الحلق، طفح جلدي خطير، بعض الإضطرابات التي تؤثر على تدفق الدم إلي العينين، وعدم انتظام ضربات القلب، والذبحة الصدرية، والموت القلبي المفاجئ.
تم الإبلاغ عن أعراض جانبية مثل الدوخة والإسهال بشكل متكرر أكثر في الرجال فوق 75 سنة من العمر مع تناول لوفيرا.
إذا لاحظت أن أياً من الأعراض الجانبية قد أصبح جسيماً، أو إذا لاحظت ظهور أي أعراض جانبية لم ترد في هذه النشرة، فإنه يرجى أن تخبر طبيبك أو الصيدلي.
يحفظ الدواء بعيداً عن متناول ونظر الأطفال.
لا تستعمل لوفيرا بعد تاريخ انتهاء الصلاحية المدون على العبوة والشريط. بعد "EXP" و تاريخ الإنتهاء يشير إلي آخر يوم في هذا الشهر.
يحفظ الدواء في العبوة الأصلية لحمايته من الرطوبة. و يحفظ في درجة حرارة تقل عن 30 درجة مئوية.
ينبغي عدم التخلص من الأدوية عن طريق مياه الصرف أو قمامة المنزل. اسأل الصيدلي الذي تتعامل معه عن كيفية التخلص من الأدوية التي لم تعد بحاجة إليها. فهذه الإجراءات ستساعد في حماية البيئة.
المادة الفعالة هي: تادالافيل.
يحتوي كل قرص مغلفة بطبقة رقيقة من لوفيرا 5 ملجم على 5 ملجم من تادالافيل.
يحتوي كل قرص مغلفة بطبقة رقيقة من لوفيرا 10 ملجم على 10 ملجم من تادالافيل.
يحتوي كل قرص مغلفة بطبقة رقيقة من لوفيرا 20 ملجم على 20 ملجم من تادالافيل.
المكونات الأخرى هي:
لاكتوز إن إف سريع التدفق بي إم إس 35957 و أفيسيل بي إتش 10 و كروسبوفيدون إن إف و هيدروكسيبروبايل ميثيلسيليلوز و صوديوم لورايل فوسفات و ماء منقي بى بى و أفسيل بى إتش 102 و ثنائي أوكسيد السيليكون الغروي و ستياريت الماغنسيوم و أوبادري II 31F82689 أصفر.
قرص لوفيرا 5 ملجم المغلف بطبقة رقيقة هو أصفر، مستدير، محدب الوجهين، مغلف بطبقة رقيقة، محفور على جانب "T63" و عادي على الجانب الآخر.
قرص لوفيرا 10 ملجم المغلف بطبقة رقيقة هو أصفر، لوزي الشكل، مغلف بطبقة رقيقة، محفور على جانب "T64" و عادي على الجانب الآخر.
قرص لوفيرا 20 ملجم المغلف بطبقة رقيقة هو أصفر، لوزي الشكل، محدب الوجهين، مغلف بطبقة رقيقة، محفور على جانب "T65" و عادي على الجانب الآخر.
تحتوي كل عبوة من لوفيرا 5 ملجم علي 30 قرص مغلف بطبقة رقيقة.
تحتوي كل عبوة من لوفيرا 10 ملجم علي 4 أو 6 أو 10 أو 12 قرص مغلف بطبقة رقيقة.
تحتوي كل عبوة من لوفيرا 20 ملجم علي 4 أو 6 أو 12 قرص مغلف بطبقة رقيقة.
قد لا يتم تسويق كل أحجام العبوات.
العنوان: المدينة الصناعية الأولى , وحدة رقم 1 , صندوق بريد: 7137 , الدمام 32234 – 4384
تليفون: 966138216444+
فاكس: 966138216422+
regulatory-affairs@dammampharma.saالبريد الإلكتروني:
Treatment of erectile dysfunction in adult males. In order for tadalafil to be effective for the treatment of erectile dysfunction, sexual stimulation is required. 5mg only: Treatment of the signs and symptoms of benign prostatic hyperplasia in adult males. LOVERA 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 LOVERA (i.e., at least twice weekly) a once daily regimen with the lowest doses of LOVERA might be considered suitable, based on patient choice and the physician's judgement. 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 2.5mg 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 LOVERA the recommended dose of LOVERA is 10 mg taken prior to anticipated sexual activity and with or without food. There is limited clinical data on the safety of LOVERA 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 10mg 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 LOVERA in the paediatric population with regard to the treatment of erectile dysfunction. Method of administration LOVERA is available as 5, 10, and 20 mg film-coated tablets for oral use. |
Before treatment with LOVERA
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 LOVERA 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 LOVERA, 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 LOVERA 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 LOVERA and other PDE5 inhibitors. The patient should be advised that in case of sudden visual defect, he should stop taking LOVERA and consult a physician immediately (see section 4.3).
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 LOVERA is not recommended in patients with severe renal impairment.
There is limited clinical data on the safety of single-dose administration of LOVERA in patients with severe hepatic insufficiency (Child-Pugh Class C). Once-a-day administration has not been evaluated in patients with hepatic insufficiency. If LOVERA 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 LOVERA in patients with severe hepatic insufficiency (Child-Pugh Class C). If LOVERA 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.
LOVERA, 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 LOVERA 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).
LOVERA and other treatments for erectile dysfunction
The safety and efficacy of combinations of LOVERA and other PDE5 inhibitors or other treatments for erectile dysfunction have not been studied. The patients should be informed not to take LOVERA in such combinations.
Lactose
LOVERA 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 LOVERA 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 LOVERA (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 LOVERA 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. |
LOVERA is not indicated for use by women. Pregnancy Pregnancy Category: B 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 pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). As a precautionary measure, it is preferable to avoid the use of LOVERA during pregnancy. Breastfeeding Available pharmacodynamic/toxicological data in animals have shown excretion of tadalafil in milk. A risk to the suckling child cannot be excluded. LOVERA 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). |
LOVERA 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 LOVERA before driving or using machines. |
Summary of the safety profile The most commonly reported adverse reactions in patients taking LOVERA 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 LOVERA. The adverse reactions reported were transient, and generally mild or moderate. The majority of headaches reported with LOVERA 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 7116 patients on LOVERA and 3718 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).
(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 5mg taken once a day for the treatment of benign prostatic hyperplasia, dizziness and diarrhoea were reported more frequently in patients over 75 years of age.
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Single doses of up to 500mg have been given to healthy subjects, and multiple daily doses up to 100mg 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.
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 LOVERA 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
Three clinical studies were conducted in 1054 patients in an at-home setting to define the period of responsiveness to LOVERA. 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 LOVERA improved their erections as compared to 35% with placebo. Also, patients with erectile dysfunction in all severity categories reported improved erections whilst taking LOVERA (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 LOVERA-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 LOVERA 5mg. In the study in patients with erectile dysfunction secondary to diabetes, the mean per-subject proportion of successful attempts were 41 and 46% on LOVERA 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 LOVERA 5mg once a day vs. placebo. The mean per-subject proportion of successful sexual intercourse attempts was 68% for LOVERA patients compared to 52% for patients on placebo.
Benign prostatic hyperplasia
LOVERA 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 LOVERA 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 LOVERA 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 LOVERA 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 LOVERA 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 LOVERA 5mg.
Paediatric population
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 LOVERA 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 litres, 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 2.5mg to 20mg, 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 (5mg-20mg), tadalafil exposure (AUC) approximately doubled in subjects with mild (creatinine clearance 51 to 80ml/min) or moderate (creatinine clearance 31 to 50ml/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 10mg is administered. There is limited clinical data on the safety of LOVERA in patients with severe hepatic insufficiency (Child-Pugh class C). If LOVERA is 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 10mg of tadalafil to patients with hepatic impairment. There are no available data about the administration of once-a-day dosing of tadalafil to patients with hepatic impairment. If LOVERA is prescribed once-a-day, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician.
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 1000mg/kg/day tadalafil. In a rat prenatal and postnatal development study, the no observed effect dose was 30mg/kg/day. In the pregnant rat the AUC for calculated free drug at this dose was approximately 18-times the human AUC at a 20mg 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 25mg/kg/day (resulting in at least a 3-fold greater exposure [range 3.7-18.6] than seen in humans given a single 20mg 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.
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Not applicable.
Store in the original package in order to protect from moisture.
Store below 30°C
Transparent Thermoformed PVC/PE/PVDC reel with hard tempered aluminum foil lid.
Each pack of LOVERA 5 mg contains 30 film-coated tablets.
Each pack of LOVERA 10 mg contains 4 or 6 or 10 or 12 film-coated tablets.
Each pack of LOVERA 20 mg contains 4 or 6 or 12 film-coated tablets.
Not all pack sizes may be marketed.
No special requirements.
