TADALAFIL SANDOZ

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

, 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 judgement. In these patients the recommended dose is 5 mg taken once a day at approximately the same time of day.

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 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. 5 mg for the treatment of benign prostatic hyperplasia has not been demonstrated.

Pulmonary arterial hypertension Treatment should only be initiated and monitored by a physician experienced in the treatment of PAH. Adults The recommended dose is 40 mg (2 x 20 mg) taken once daily with or without food. Paediatric population (age 2 years to 17 years) The recommended once daily doses based on age and weight categories in paediatric patients are shown below.

Paediatric patient’s age and/or weight Recommended daily dose and dosing regimen Age ≥ 2 years old Body weight ≥ 40 kg Body weight < 40 kg 40 mg (two 20 mg tablets) once daily 20 mg (one 20 mg tablet or 10 mL of oral suspension (OS), 2 mg/mL tadalafil*) once daily *Other suitable formulations, such as an oral suspension, should be checked for their availability for administration to paediatric patients who require 20 mg and are not able to swallow tablets.

For patients < 2 years old no PK or efficacy data are available from clinical trials. The most appropriate dose of tadalafil in children aged between 6 months to < 2 years has not been established. Therefore, tadalafil is not recommended in this age subset.

Delayed dose, missed dose, or vomiting If there is a delay in the administration of tadalafil, but yet within the same day, the dose should be taken with no changes to the subsequent dose schedules. Patients should not take an extra dose if a dose is missed.

Patients should not take an extra dose if vomiting occurs. Special populations Elderly Dose adjustments are not required in elderly patients. • Renal impairmentAdult men with erectile dysfunction or benign prostatic hyperplasia: 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 for on-demand treatment. 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.

2). • Pulmonary arterial hypertension: Adults and paediatric population (2 to 17 years, weighing at least 40 kg) In patients with mild to moderate renal impairment a starting dose of 20 mg once per day is recommended. The dose may be increased to 40 mg once per day, based on individual efficacy and tolerability.

In patients with severe renal impairment the use of tadalafil is not recommended. 2). Paediatric population (2 to 17 years, weighing less than 40 kg) In patients < 40 kg and with mild to moderate renal impairment a starting dose of 10 mg once per day is recommended.

The dose may be increased to 20 mg once per day, based on individual efficacy and tolerability. 2). Hepatic impairment • Adult men with erectile dysfunction or benign prostatic hyperplasia: 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 of tadalafil 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.

2). • Pulmonary arterial hypertension: - Adults and paediatric population (2 to 17 years, weighing at least 40 kg) Due to limited clinical experience in patients with mild to moderate hepatic cirrhosis (Child-Pugh Class A and B), a starting dose of 20 mg once per day may be considered.

Paediatric population (2 to 17 years, weighing less than 40 kg) In patients < 40 kg and with mild to moderate hepatic impairment, a starting dose of 10 mg once per day may be considered. For patients of all ages, if tadalafil is prescribed, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician.

Patients with severe hepatic cirrhosis (Child-Pugh Class C) have […]

Tadalafil for erectile dysfunction or benign prostatic hyperplasia 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 list of adverse reactions The table below lists the adverse reactions observed from spontaneous reporting and in placebo- controlled clinical studies (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). 4). (2) Postmarketing surveillance reported adverse reactions not observed in placebo- controlled clinical studies.

(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 studies, either for the treatment of erectile dysfunction or the treatment of benign prostatic hyperplasia, are limited.

In clinical studies with tadalafil taken on demand for the treatment of erectile dysfunction, diarrhoea was reported more frequently in patients over 65 years of age. In clinical studies with tadalafil 5 mg 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.

Tadalafil for pulmonary arterial hypertension Summary of the safety profile The most commonly reported adverse reactions, occurring in ≥ 10 % of patients in the tadalafil 40 mg treatment arm, were headache, nausea, back pain, dyspepsia, flushing, myalgia, nasopharingitis and pain in extremity.

The adverse reactions reported were transient, and generally mild or moderate. Adverse reaction data are limited in patients over 75 years of age. 5 mg to 40 mg once daily and 82 patients were treated with placebo. The duration of treatment was 16 weeks.

The overall frequency of discontinuation due to adverse events was low (tadalafil 11 %, placebo 16 %). Three hundred and fifty seven (357) patients who completed the pivotal study entered a long-term extension study. Doses studied were 20 mg and 40 mg once daily.

Tabulated summary of adverse reactions The table below lists the adverse reactions reported during the placebo-controlled clinical trial in patients with PAH treated with tadalafil. Also included in the table are some adverse reactions which have been reported in clinical trials and/or post- marketing with tadalafil in the treatment of male erectile dysfunction.

These events have either been assigned a frequency of “Not known,” as the frequency in PAH patients cannot be estimated from the available data or assigned a frequency based on the clinical trial data from the pivotal placebo-controlled study of tadalafil.

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 Not known1 Immune system disorders Hypersensitivity reactions5 Angioedema Nervous system disorders Headache6 Syncope, Migraine5 Seizures5, Transient amnesia5 Stroke2 (including haemorrhagic events) Eye disorders Blurred vision Non-arteritic anterior ischemic optic neuropathy (NAION), Retinal vascular occlusion, Visual field defect Ear and labyrinth disorders Tinnitus Sudden hearing loss Cardiac disorders Palpitations2, 5 […]

Before treatment of adult men with erectile dysfunction or benign prostatic hyperplasia with tadalafil 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. 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 tadalafil is effective in patients who have undergone pelvic surgery or radical non-nerve- sparing prostatectomy. 3). Cardiovascular diseases Serious cardiovascular events, including myocardial infarction, sudden cardiac death, unstable angina pectoris, ventricular arrhythmia, stroke, transient ischemic attacks, chest pain, palpitations and tachycardia, have been reported either post marketing and/or in clinical studies using tadalafil for the treatment of erectile dysfunction or benign prostatic hyperplasia.

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.

The following groups of patients with cardiovascular disease were not included in PAH clinical trials: • Patients with clinically significant aortic and mitral valve disease • Patients with pericardial constriction • Patients with restrictive or congestive cardiomyopathy • Patients with significant left ventricular dysfunction • Patients with life-threatening arrhythmias • Patients with symptomatic coronary artery disease • Patients with uncontrolled hypertension.

Since there are no clinical data on the safety of tadalafil in these patients, the use of tadalafil is not recommended. Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD).

Since there are no clinical data on administration of tadalafil to patients with veno-occlusive disease, administration of tadalafil to such patients is not recommended. Should signs of pulmonary oedema occur when tadalafil is administered, the possibility of associated PVOD should be considered.

Tadalafil has systemic vasodilatory properties that may result in transient decreases in blood pressure. Physicians should carefully consider whether their patients with certain underlying conditions, such as severe left ventricular outflow obstruction, fluid depletion, autonomic hypotension or patients with resting hypotension, could be adversely affected by such vasodilatory effects.

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.

5). Therefore, 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.

3). Patients with known hereditary degenerative retinal disorders, including retinitis pigmentosa, were not included in the clinical trials for pulmonary arterial hypertension, and use in these patients is not recommended. Decreased or sudden hearing loss Cases of sudden hearing loss have been reported after use of tadalafil.

Although other risk factors were present in some cases (such as age, diabetes, hypertension, previous hearing loss history and associated connective tissue diseases), patients should be advised to seek prompt medical attention in the event of sudden decrease or loss of hearing.

Renal and hepatic impairment Due to increased tadalafil exposure (AUC), limited clinical experience and the lack of ability to influence clearance by dialysis, once-a-day dosing of tadalafil 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). If tadalafil is prescribed for on demand use, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician.

Once-a-day administration has not been studied in patients with severe hepatic cirrhosis (Child-Pugh Class C) and, therefore, daily dosing of tadalafil is not recommended. Priapism and anatomical deformation of the penis Priapism has been reported in men treated with PDE5 inhibitors.

Patients who experience erections lasting 4 hours or more should be instructed to seek immediate medical assistance. If priapism is not treated […]

1. In clinical trials, 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. 5). Tadalafil, 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 studies 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.

4). 5).