Treatment of erectile dysfunction in adult males.
In order for Tadalafil to be effective, sexual stimulation is required.
Tadalafil is not indicated for use by women.
 

Posology
Adult men
In general, the recommended dose is 10mg taken prior to anticipated sexual activity and with or without
food. In those patients in whom Tadalafil 10mg does not produce an adequate effect, 20mg might be
tried. It may be taken at least 30 minutes prior to sexual activity.
The maximum dose frequency is once per day.
Tadalafil 10mg and 20mg 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 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.
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, 10mg is the maximum recommended dose. Once-a-day dosing of tadalafil is
not recommended in patients with severe renal impairment. (See sections 4.4 and 5.2.)
Men with Hepatic Impairment
The recommended dose of Tadalafil is 10mg 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 10mg of tadalafil to patients with hepatic impairment.
Once-a-day dosing 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 Tadalafil in the paediatric population with regard to the treatment of erectile
dysfunction.
Method of administration
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 Tadalafil to patients who are using any form of organic nitrate is contraindicated. (See section 4.5.) 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 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 (<90/50mmHg), or uncontrolled hypertension. • Patients with a stroke within the last 6 months. Tadalafil 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 Tadalafil
A medical history and physical examination should be undertaken to diagnose erectile dysfunction 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 Tadalafil is effective in patients who have undergone pelvic surgery or radical non-nerve-sparing
prostatectomy.
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.
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 Tadalafil 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.
Hepatic 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, 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.
Tadalafil, 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 Tadalafil 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).
Tadalafil and other treatments for erectile dysfunction
The safety and efficacy of combinations of Tadalafil and other PDE5 inhibitors or other treatments for
erectile dysfunction have not been studied. The patients should be informed not to take Tadalafil in such
combinations.
Lactose
Tadalafil 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 10mg and/or 20mg tadalafil, as indicated below. With regard to
those interaction studies where only the 10mg 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
(200mg daily), increased tadalafil (10mg) exposure (AUC) 2-fold and Cmax by 15%, relative to the
AUC and Cmax values for tadalafil alone. Ketoconazole (400mg daily) increased tadalafil (20mg)
exposure (AUC) 4-fold and Cmax by 22%. Ritonavir, a protease inhibitor (200mg twice daily), which is
an inhibitor of CYP3A4, CYP2C9, CYP2C19, and CYP2D6, increased tadalafil (20mg) 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 (10mg). 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 (5mg, 10mg and 20mg) was shown to augment the hypotensive effects of
nitrates. Therefore, administration of Tadalafil 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 received
daily doses of tadalafil 20mg for 7 days and 0.4mg 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 (2.5mg - 20mg), where nitrate
administration is deemed medically necessary in a life-threatening situation, at least 48 hours should
have elapsed after the last dose of Tadalafil 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 8mg daily) and tadalafil (5mg daily dose and 20mg 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 (10mg, except
for studies with angiotensin II receptor blockers and amlodipine in which a 20mg dose was applied) had
no clinically significant interaction with any of these classes. In another clinical pharmacology study,
tadalafil (20mg) 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 20mg 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 10mg 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 coadministration
with tadalafil (10mg or 20mg). 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 (20mg)
did not augment the mean blood pressure decrease produced by alcohol (0.7g/kg or approximately
180ml 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 (0.6g/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 (10mg).
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 (10mg and 20mg) had no clinically significant effect on exposure (AUC) to S-warfarin or Rwarfarin
(CYP2C9 substrate), nor did tadalafil affect changes in prothrombin time induced by warfarin.
Aspirin
Tadalafil (10mg and 20mg) 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.

Tadalafil 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 pregnancy, embryonal/foetal development, parturition or
postnatal development (see section 5.3). As a precautionary measure, it is preferable to avoid the use of
Tadalafil 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. Tadalafil 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).

Tadalafil 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 Tadalafil 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 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 placebocontrolled
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.
Frequency convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to
<1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000) and not known (cannot be estimated from
the available data).

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

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 absence of sexual stimulation.

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
Three clinical studies were conducted in 1054 patients in an at-home setting to define the period of
responsiveness to Tadalafil. 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.
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.
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.
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 (flexibledose,
on demand) of 48% as compared to 17% with placebo.

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, this tadalafil 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 63l, indicating that Tadalafil is distributed into
tissues. At therapeutic concentrations, 94% of tadalafil in plasma is bound in 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 2.5l/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 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.
Other 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 impairment
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 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 doses higher than
10mg 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 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.

Lactose Monohydrate
Hydroxypropyl Cellulose
Croscarmellose Sodium
Sodium Lauryl Sulphate
Microcrystalline cellulose
Magnesium Stearate
Hypromellose
Titanium dioxide
Triacetin
Yellow iron oxide-non irradiated
Talc.

Not applicable.

2 years

Do not store above 30° C.

Primary Packaging: Alu-PVC/Aclar blister.
Secondary Packaging: Carton and PIL

Any unused medicinal product or waste material should be disposed of in accordance with local
requirements.