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

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.

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 tadalafil is not recommended in patients with severe renal impairment.
Men with Hepatic Impairment
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 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
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
Tadalafil 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. 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 preexisting 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 nonarteritic anterior ischaemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure. 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

Before treatment 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. Tadalafil has vasodilator properties, resulting in mild and transient decreases
in blood pressure, and as such potentiates the hypotensive effect of nitrates.
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 may occur in most of the patients who had preexisting
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. The combination of tadalafil and doxazosin is
not recommended.
Vision
Visual defects and cases of NAION may occur 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.
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.
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.

Excipients
Lactose
Tadalafil tablets contain lactose. Patients with rare hereditary problems of galactose
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take
this medicinal product.
Sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially
'sodium-free'.

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 (20mg) exposure (AUC) 4-foId 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-fo1d with no change in Cmax. 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. Consequently, the
incidence of the adverse reactions 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
Tadalafil (5 mg, 10 mg and 20 mg) may augment the hypotensive effects of nitrates.
Therefore, administration of tadalafil to patients who are using any form of organic nitrate is
contraindicated. In a patient prescribed any dose of tadalafil (2.5 mg – 20 mg), where nitrate
administration is deemed medically necessary in a life-threatening situation, at least 48 hours
should have elapsed after the last dose of 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.

In interaction studies performed in a limited number of healthy volunteers, these effects were
not reported with alfuzosinor 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-bloodpressure
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. 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

5- alpha reductase inhibitors
When 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 coadministered
with 5-ARIs.
CYP1A2 substrates (e.g. theophylline)
When tadalafil 10 mg was administered with theophylline (a non-selective phosphodiesterase
inhibitor), there will be 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, 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 (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 alter alcohol). Tadalafil (20mg) did not augment the mean blood pressure
decrease produced by alcohol (0.7g/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 (0.6g/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 Swarfarin
or R-warfarin (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. 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

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 or benign prostatic hyperplasia were headache, dyspepsia, back pain
and myalgia, in which the incidences increase with increasing dose of Tadalafil. The adverse
reactions reported were transient, and generally mild or moderate. The majority of headaches
reported with Tadalafil once-a-day dosing are experienced within the first 10 to 30 days of
starting treatment.
Tabulated summary of adverse reactions
The table below lists the adverse reactions observed from spontaneous reporting and in
placebo controlled clinical trials(comprising a total of 7116 patients on tadalafil and 3718
patients on placebo) for on-demand and once-a-day treatmentof 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
(≥1/1000 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).

Common (may affect up to 1 in 10 people)
- headache, back pain, muscle aches, pain in arms and legs, facial
flushing, nasal congestion, and indigestion.
Uncommon (may affect up to 1 in 100 people)
- dizziness, stomach ache, feeling sick, being sick (vomiting), reflux,
blurred vision, eye pain, difficulty in breathing, presence of blood in
urine, prolonged erection, pounding heartbeat sensation, a fast heart
rate, high blood pressure, low blood pressure, nose bleeds, ringing in
the ears, swelling of the hands, feet or ankles and feeling tired.
Rare (may affect up to 1 in 1,000 people)
- fainting, seizures and passing memory loss, swelling of the eyelids, red
eyes, sudden decrease or loss of hearing, hives (itchy red welts on the
surface of the skin), penile bleeding, presence of blood in semen and
increased sweating.
Heart attack and stroke have also been reported rarely in men taking
Tadafect. 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
Tadafect that were not seen in clinical trials. These include:
- migraine, swelling of the face, serious allergic reaction which causes
swelling of the face or throat, serious skin rashes, some disorders
affecting blood flow to the eyes, irregular heartbeats, angina and
sudden cardiac death.
The side effect dizziness has been reported more frequently in men over
75 years of age taking Tadafect. Diarrhoea has been reported more
frequently in men over 65 years of age taking Tadafect.

 

Single doses of up to 500 mg have been given to healthy subjects and multiple daily doses up
to 100 mg have been given to patients. Adverse events were similar to those seen at lower
doses. In cases of overdose, standard supportive measures should be adopted, as required.
Haemodialysis contributes negligibly to tadalafil elimination.

Pharmacotherapeutic group: Urologicals, Drugs used in erectile dysfunction, ATC Code:
G04BE08.
Mechanism of action
Tadalafil is a selective, reversible inhibitor of cyclic guanosine monophosphate (cGMP)-
specific phosphodiesterase type5 (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.
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 phosphor diesterases. Tadalafil is > 10,000-foldmore 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 photo transduction. Tadalafil is also > 10,000-fold
more potent for PDE5 than forPDE7 through PDE10.
Clinical efficacy and safety
Tadalafil administered to healthy subjects produced no significant difference compared to
placebo in supine systolic and diastolic blood pressure (mean maximal decrease of
1.6/0.8mmHg, respectively), in standing systolic and diastolic blood pressure (mean maximal
decrease of 0.2/4.6mmHg, respectively), and no significant change in heart rate.
In a study to assess the effects of tadalafil on vision, no impairment of colour discrimination
(blue/green) was detected using the Farnsworth-Munsell 100-hue test. This finding is
consistent with the low affinity of tadalafil for PDE6 compared to PDE5. Across all clinical
studies, reports of changes in colour vision were rare (<0.1%).
Three studies were conducted in men to assess the potential effect on spermatogenesis of
tadalafil 10mg (one 6-monthstudy) 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 tadalafil on demand. Tadalafil demonstrated statistically
significant improvement in erectile function and the ability to have successful sexual
intercourse up to 36 hours following dosing, as well as patients' ability to attain and maintain
erections for successful intercourse compared to placebo as early as 16 minutes following
dosing.

In a 12-week study performed in 186 patients (142 tadalafil, 44 placebo) with erectile
dysfunction secondary to spinal cord injury, tadalafil significantly improved the erectile
function leading to a mean per-subject proportion of successful attempts in patients treated
with tadalafil 10 or 20 mg (flexible-dose, on demand) of 48% as compared to 17% with
placebo.
Tadalafil at doses of 2 to 100mg has been evaluated in 16 clinical studies involving 3250
patients, including patients with erectile dysfunction of various severities (mild, moderate,
severe), etiologies, ages (range 21-86 years), and ethnicities. Most patients reported erectile
dysfunction of at least 1 year in duration. In the primary efficacy studies of general
populations, 81% of patients reported that tadalafil improved their erections as compared to
35% with placebo. Also, patients with erectile dysfunction in all severity categories reported
improved erections whilst taking tadalafil (86%, 83%, and 72% for mild, moderate, and
severe, respectively, as compared to 45%, 42%, and 19% with placebo). In the primary
efficacy studies, 75% of intercourse attempts were successful in tadalafil- reated patients as
compared to 32% with placebo.
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 or 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 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 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.

Elimination
The mean oral clearance for tadalafil is 2.5 l/h and the mean half-life is 17.5 hours in healthy
subjects.
Tadalafil is excreted predominantly as inactive metabolites, mainly in the faeces
(approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of
the dose).
Linearity/non-linearity
Tadalafil pharmacokinetics in healthy subjects are linear with respect to time and dose. Over
a dose range of 2.5 to 20mg, exposure (AUC) increases proportionally with dose. Steadystate
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 (up to 20 mg), tadalafil exposure
(AUC) approximately doubled in subjects with mild (creatinine clearance 51 to 80 ml/min)
or moderate (creatinine clearance 31 to 50 ml/min) renal impairment and in subjects with
end-stage renal disease on dialysis.In haemodialysis patients, Cmax was 41 %higher than that observed in healthy subjects.
Haemodialysis contributes negligibly to tadalafil elimination.
Hepatic insufficiency
Tadalafil exposure (AUC) in subjects with mild and moderate hepatic impairment (Child-
Pugh Class A and B) is comparable to exposure in healthy subjects when a dose of 10 mg is
administered. There is limited clinical data on the safety of tadalafil in patients with severe
hepatic insufficiency (Child- Pugh Class C). If tadalafil is prescribed, a careful individual
benefit/risk evaluation should be undertaken by the prescribing physician. There are no
available data about the administration of 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, embryo toxicity 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 30 mg/kg/day. In the pregnant rat the AUC for calculated
free drug at this dose was approximately 18 times the human AUC at a 20 mg dose.
There was no impairment of fertility in male and female rats. In dogs given tadalafil daily for
6 to 12 months at doses of25 mg/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.

Lactose monohydrate, Copovidone, Macrogol
glycerol Hydroxy Stearate, Silica colloidal anhydrous, Cellulose microcrystalline,
Croscarmellose sodium, Magnesium stearate and Purified water and Opadry yellow
03K82780.

Not Applicable

4 Years

Do not store above 30°C. Protect from moisture.

Blister pack:
Tadalafil Tablets 20 mg: Blister of 8’s (4’s blister x 2)

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