Therapeutic indications
Treatment of erectile dysfunction in adult males.
In order for tadalafil to be effective for the treatment of erectile dysfunction, sexual stimulation is
required.
5 mg only: Treatment of the signs and symptoms of benign prostatic hyperplasia in adult males.
REDEX 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 REDEX (i.e., at least twice weekly) a once daily
regimen with the lowest doses of REDEX 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 REDEX the recommended dose of
REDEX is 10 mg taken prior to anticipated sexual activity and with or without food. There is
limited clinical data on the safety of REDEX 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 REDEX in the paediatric population with regard to the treatment of
erectile dysfunction.
Method of administration
REDEX is available as 2.5, 5, 10, and 20 mg film-coated tablets for oral use.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. In clinical studies, tadalafil was shown to augment the hypotensive effects of nitrates. This is thought to result from the combined effects of nitrates and tadalafil on the nitric oxide/cGMP pathway. Therefore, administration of REDEX to patients who are using any form of organic nitrate is contraindicated (see section 4.5). REDEX must not be used in men with cardiac disease for whom sexual activity is inadvisable. Physicians should consider the potential cardiac risk of sexual activity in patients with pre-existing cardiovascular disease. The following groups of patients with cardiovascular disease were not included in clinical trials and the use of tadalafil is therefore contraindicated: - patients with myocardial infarction within the last 90 days, - patients with unstable angina or angina occurring during sexual intercourse, - patients with New York Heart Association Class 2 or greater heart failure in the last 6 months, - patients with uncontrolled arrhythmias, hypotension (<90/50 mm Hg), or uncontrolled hypertension, - patients with a stroke within the last 6 months. REDEX 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 REDEX
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 REDEX 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 REDEX, 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 REDEX 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 REDEX
and other PDE5 inhibitors. The patient should be advised that in case of sudden visual defect, he
should stop taking REDEX 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 REDEX is not recommended in patients
with severe renal impairment.
There is limited clinical data on the safety of single-dose administration of REDEX in patients with
severe hepatic insufficiency (Child-Pugh Class C). Once-a-day administration has not been
evaluated in patients with hepatic insufficiency. If REDEX 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 REDEX in patients with
severe hepatic insufficiency (Child-Pugh Class C). If REDEX 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.
REDEX, 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 REDEX 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).
REDEX and other treatments for erectile dysfunction
The safety and efficacy of combinations of REDEX and other PDE5 inhibitors or other treatments
for erectile dysfunction have not been studied. The patients should be informed not to take
REDEX in such combinations.

Lactose
REDEX 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 REDEX 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 REDEX (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 REDEX 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-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 alphablockers
- 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 coadministering
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 (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.

REDEX 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 REDEX 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. REDEX 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).
4.7 Effects on ability to drive and use machines
REDEX 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 REDEX before driving or using machines.

REDEX 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 REDEX before driving or using machines.

Summary of the safety profile
The most commonly reported adverse reactions in patients taking REDEX 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 REDEX. The adverse reactions
reported were transient, and generally mild or moderate. The majority of headaches reported with
REDEX 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 placebocontrolled
clinical trials (comprising a total of 8022 patients on REDEX and 4422 patients on
placebo) for on-demand and once-a-day treatment of erectile dysfunction and the once-a-day
treatment of benign prostatic hyperplasia.
Frequency convention: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000
to <1/100), Rare (≥1/10,000 to <1/1,000), Very Rare (<1/10,000) and Not known (cannot be
estimated from the available data).

                                   

Very common	Common	Uncommon	Rare
Immune system disorders
		Hypersensitivity reactions	Angioedema2
Nervous system disorders
	Headache	Dizziness	Stroke1 (including haemorrhagic events), Syncope, Transient ischaemic attacks1, Migraine2, Seizures2, Transient amnesia
Eye disorders
		Blurred vision, Sensations described as eye pain	Visual field defect, Swelling of eyelids, Conjunctival hyperaemia, Non-arteritic anterior ischaemic optic neuropathy (NAION)2, Retinal vascular occlusion2
Ear and labyrinth disorders
		Tinnitus	Sudden hearing loss
Cardiac disorders1
		Tachycardia, Palpitations	Myocardial infarction, Unstable angina pectoris2, Ventricular arrhythmia2
Vascular disorders
	Flushing	Hypotension3, Hypertension
Respiratory, thoracic and mediastinal disorders
	Nasal congestion	Dyspnoea, Epistaxis
Gastrointestinal disorders
	Dyspepsia	Abdominal pain, Vomiting, Nausea, Gastrooesophageal reflux
Skin and subcutaneous tissue disorders
		Rash	Urticaria, Stevens-Johnson syndrome2, Exfoliative dermatitis2, Hyperhydrosis (sweating)
Musculoskeletal, connective tissue and bone disorders
	Back pain, Myalgia, Pain in extremity
Renal and urinary disorders
		Haematuria
Reproductive system and breast disorders
		Prolonged erections	Priapism, Penile haemorrhage, Haematospermia
General disorders and administration site conditions
		Chest pain1, Peripheral oedema, Fatigue	Facial oedema2, Sudden cardiac death1,2

(1) Most of the patients had pre-existing cardiovascular risk factors (see section 4.4).
(2) Postmarketing surveillance reported adverse reactions not observed in placebo-controlled
clinical trials.
(3) More commonly reported when tadalafil is given to patients who are already taking
antihypertensive medicinal products.
Description of selected adverse reactions
A slightly higher incidence of ECG abnormalities, primarily sinus bradycardia, has been reported
in patients treated with tadalafil once a day as compared with placebo. Most of these ECG
abnormalities were not associated with adverse reactions.
Other special populations
Data in patients over 65 years of age receiving tadalafil in clinical trials, either for the treatment of
erectile dysfunction or the treatment of benign prostatic hyperplasia, are limited. In clinical trials
with tadalafil taken on demand for the treatment of erectile dysfunction, diarrhoea was reported
more frequently in patients over 65 years of age. In clinical trials with tadalafil 5 mg taken once a
day for the treatment of benign prostatic hyperplasia, dizziness and diarrhoea were reported more
frequently in patients over 75 years of age.
Reporting of suspected adverse reactions
To report any side effects(s):
Saudi Arabia:
National Pharmacovigilance and Drug Safety Center (NPC)
Fax: +966-11-205-7662
Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.
Toll free phone: 8002490000
Email: npc.drug@sfda.gov.sa
Website: www.sfda.gov.sa/npc
Other GCC States: Please contact the relevant competent authority.

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

Pharmacotherapeutic group: Urologicals, Drugs used in erectile dysfunction. ATC code:
G04BE08.
Mechanism of action
Tadalafil is a selective, reversible inhibitor of cyclic guanosine monophosphate (cGMP)-specific
phosphodiesterase type 5 (PDE5). When sexual stimulation causes the local release of nitric
oxide, inhibition of PDE5 by tadalafil produces increased levels of cGMP in the corpus
cavernosum. This results in smooth muscle relaxation and inflow of blood into the penile tissues,
thereby producing an erection. Tadalafil has no effect in the treatment of erectile dysfunction in
the absence of sexual stimulation.
Tadalafil 5 mg - The effect of PDE5 inhibition on cGMP concentration in the corpus cavernosum
is also observed in the smooth muscle of the prostate, the bladder and their vascular supply. The
resulting vascular relaxation increases blood perfusion which may be the mechanism by which
symptoms of benign prostatic hyperplasia are reduced. These vascular effects may be
complemented by inhibition of bladder afferent nerve activity and smooth muscle relaxation of the
prostate and bladder.

Pharmacodynamic effects
Studies in vitro have shown that tadalafil is a selective inhibitor of PDE5. PDE5 is an enzyme
found in corpus cavernosum smooth muscle, vascular and visceral smooth muscle, skeletal
muscle, platelets, kidney, lung, and cerebellum. The effect of tadalafil is more potent on PDE5
than on other phosphodiesterases. Tadalafil is >10,000-fold more potent for PDE5 than for PDE1,
PDE2, and PDE4 enzymes which are found in the heart, brain, blood vessels, liver, and other
organs. Tadalafil is >10,000-fold more potent for PDE5 than for PDE3, an enzyme found in the
heart and blood vessels. This selectivity for PDE5 over PDE3 is important because PDE3 is an
enzyme involved in cardiac contractility. Additionally, tadalafil is approximately 700-fold more
potent for PDE5 than for PDE6, an enzyme which is found in the retina and is responsible for
phototransduction. Tadalafil is also >10,000-fold more potent for PDE5 than for PDE7 through
PDE10.
Clinical efficacy and safety
Tadalafil administered to healthy subjects produced no significant difference compared to placebo
in supine systolic and diastolic blood pressure (mean maximal decrease of 1.6/0.8mmHg,
respectively), in standing systolic and diastolic blood pressure (mean maximal decrease of
0.2/4.6mmHg, respectively), and no significant change in heart rate.
In a study to assess the effects of tadalafil on vision, no impairment of colour discrimination
(blue/green) was detected using the Farnsworth-Munsell 100-hue test. This finding is consistent
with the low affinity of tadalafil for PDE6 compared to PDE5. Across all clinical studies, reports of
changes in colour vision were rare (<0.1%).
Three studies were conducted in men to assess the potential effect on spermatogenesis of
REDEX 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 REDEX 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 REDEX improved their erections as compared to 35% with placebo. Also,
patients with erectile dysfunction in all severity categories reported improved erections whilst
taking REDEX (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 REDEX-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 REDEX 5mg, 50% on REDEX 2.5mg as compared to 31 and 37%
with placebo. In the study in patients with erectile dysfunction secondary to diabetes, the mean
per-subject proportion of successful attempts were 41 and 46% on REDEX 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 REDEX 5mg once a
day vs. placebo. The mean per-subject proportion of successful sexual intercourse attempts was
68% for REDEX patients compared to 52% for patients on placebo.
Benign prostatic hyperplasia
REDEX 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 REDEX 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 REDEX 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 REDEX 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 REDEX 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 REDEX 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 REDEX may be
taken with or without food. The time of dosing (morning versus evening) had no clinically relevant
effects on the rate and extent of absorption.
Distribution
The mean volume of distribution is approximately 63 l, indicating that tadalafil is distributed into
tissues. At therapeutic concentrations, 94% of tadalafil in plasma is bound to proteins. Protein
binding is not affected by impaired renal function.
Less than 0.0005% of the administered dose appeared in the semen of healthy subjects.
Biotransformation
Tadalafil is predominantly metabolised by the cytochrome P450 (CYP) 3A4 isoform. The major
circulating metabolite is the methylcatechol glucuronide. This metabolite is at least 13,000-fold
less potent than tadalafil for PDE5. Consequently, it is not expected to be clinically active at
observed metabolite concentrations.
Elimination
The mean oral clearance for tadalafil is 2.5 l/h and the mean half-life is 17.5 hours in healthy
subjects.
Tadalafil is excreted predominantly as inactive metabolites, mainly in the faeces (approximately
61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).
Linearity/Non-Linearity

Tadalafil pharmacokinetics in healthy subjects are linear with respect to time and dose. Over a
dose range of 2.5 to 20 mg, exposure (AUC) increases proportionally with dose. Steady-state
plasma concentrations are attained within 5 days of once daily dosing.
Pharmacokinetics determined with a population approach in patients with erectile dysfunction are
similar to pharmacokinetics in subjects without erectile dysfunction.
Special Populations
Elderly
Healthy elderly subjects (65 years or over) had a lower oral clearance of tadalafil, resulting in
25% higher exposure (AUC) relative to healthy subjects aged 19 to 45 years. This effect of age is
not clinically significant and does not warrant a dose adjustment.
Renal Insufficiency
In clinical pharmacology studies using single dose tadalafil (5 to 20mg), tadalafil exposure (AUC)
approximately doubled in subjects with mild (creatinine clearance 51 to 80 ml/min) or moderate
(creatinine clearance 31 to 50 ml/min) renal impairment and in subjects with end-stage renal
disease on dialysis. In haemodialysis patients, Cmax was 41% higher than that observed in healthy
subjects. Haemodialysis contributes negligibly to tadalafil elimination.
Hepatic Insufficiency
Tadalafil exposure (AUC) in subjects with mild and moderate hepatic impairment (Child-Pugh
class A and B) is comparable to exposure in healthy subjects when a dose of 10 mg is
administered. There is limited clinical data on the safety of REDEX in patients with severe hepatic
insufficiency (Child-Pugh class C). If REDEX is prescribed, a careful individual benefit/risk
evaluation should be undertaken by the prescribing physician. There are no available data about
the administration of once-a-day dosing of tadalafil to patients with hepatic impairment. If REDEX
is prescribed once-a-day, a careful individual benefit/risk evaluation should be undertaken by the
prescribing physician. There are no available data about the administration of doses higher than
10 mg of tadalafil to patients with hepatic impairment.
Patients with Diabetes
Tadalafil exposure (AUC) in patients with diabetes was approximately 19% lower than the AUC
value for healthy subjects. This difference in exposure does not warrant a dose adjustment.

Non-clinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to
reproduction.
There was no evidence of teratogenicity, embryotoxicity, or foetotoxicity in rats or mice that
received up to 1000 mg/kg/day tadalafil. In a rat prenatal and postnatal development study, the
no observed effect dose was 30 mg/kg/day. In the pregnant rat the AUC for calculated free drug
at this dose was approximately 18-times the human AUC at a 20 mg dose.
There was no impairment of fertility in male and female rats. In dogs given tadalafil daily for 6 to
12 months at doses of 25 mg/kg/day (resulting in at least a 3-fold greater exposure [range 3.7-
18.6] than seen in humans given a single 20 mg dose) and above, there was regression of the
seminiferous tubular epithelium that resulted in a decrease in spermatogenesis in some dogs.
See also section 5.1.

Lactose Monohydrate
Croscarmellose Sodium
Microcrystalline Cellulose
Sodium Lauryl sulfate
Povidone K30
Magnesium Stearate
Yellow Iron Oxide
Opadry II white.

Not applicable.

3 years

Do not store above 30°C.

Redex 5 is supplied in 3 blisters packs of 30 film coated tablets.
Redex 10, 20 is supplied in blister packs of 2 or 5 film coated tablets.
Not all pack sizes may be marketed.

No special requirements.