Treatment of men ≥ 18 years of age with erectile dysfunction, which is the inability to
achieve or maintain a penile erection sufficient for satisfactory sexual performance

Vitaros is applied to the tip of the penis.
Vitaros is available in two dosage strengths of 200 and 300 mcg alprostadil in 100 mg of
cream. Vitaros should be used as needed to achieve an erection. Each Vitaros AccuDose
container is for single use only and should be properly discarded after use. The onset of
effect is within 5 to 30 minutes after administration. The duration of effect is
approximately 1 to 2 hours. However, the actual duration will vary from patient to
patient. Each patient should be instructed by a medical professional on proper technique
for administration of Vitaros prior to self-administration. The maximum frequency of use
no more than 2-3 times per week and only once per 24-hour period.
The initial dose should be recommended by a physician. A starting dose with the 300 mcg
dose can be considered especially in patients with serious ED, co-morbidity or failure to
PDE-5 inhibitors. Those patients that do not tolerate the 300 mcg dose due to local side
effects can be titrated to the lower 200 mcg dose.
Patients should be given instruction on proper administration technique, information on
possible side effects (e.g., dizziness, fainting) and the need to avoid operating machinery
until one is aware of their tolerance to the drug. In the clinical trial there was a higher
withdrawal rate in the 300 mcg treated group compared to the 200 mcg group, 30%
compared to 20% respectively.
Method of administration:
Apply Vitaros to the tip of the penis (meatus) within 5 to 30 minutes prior to attempting
intercourse by following the instructions below:
1) Wash your hands before applying Vitaros. Remove the AccuDose container from the
sachet by tearing fully down the seal from the middle of the top edge. Remove the
AccuDose container from the sachet. Save the sachet for discarding the used AccuDose
container later. Remove the cap from the tip of the AccuDose container. See Fig. 1.
2) Grasp the tip of the penis with one hand and gently manipulate to widen the opening of
the penis. See Fig. 2 (Note, if you are not circumcised, first retract and hold the foreskin
back prior to widening the opening of the penis).
3) Hold the barrel of the AccuDose container between your fingers and place the tip of
the container over the opening of the penis and carefully push down the plunger with your
thumb or finger until all the cream is expelled from the AccuDose container barrel into
the opening and surrounding skin. (Figure 3). Note: Do not insert the tip of the
AccuDose container into the opening of the penis.
4) Hold the penis in an upright position for approximately 30 seconds in order to allow
the cream to penetrate. There will likely be some cream that does not fit into the opening
of the penis. The amount of extra cream will vary depending on the patient and it is not
unusual that half of the dose will remain at the edge of the opening. Do not use a second
AccuDose to compensate for cream not expelled into the opening of the penis. Any
excess cream covering the opening may be rubbed gently into the opening and skin
surrounding the application site with the tip of a finger.
5) Remember, each Vitaros dose is good for a single administration only. Replace the cap
on the AccuDose container and place in the opened sachet, fold and discard in
accordance with local requirements.
6) Vitaros may be irritating to the eyes. W ash your hands after applying Vitaros.

Local effects: prolonged erections lasting > 4 hours (priapism), although rare, were
observed with the use of Vitaros. Priapism was observed in the two 3-month studies in 1
patient (0.06%) and in the > 6-month study in 5 (0.4%) patients, including 4 (0.3%) in the
200 mcg and 1 (0.1%) in the 300 mcg groups. If priapism occurs, the patient should seek
immediate medical assistance. If priapism is not treated immediately, penile tissue
damage and permanent loss of potency may result.
Symptomatic hypotension (dizziness) and syncope occurred in a small percent of
patients (2/459 (0.4%), 6/1591 (0.4%), and 6/1280 (0.5%) at the 100, 200 and 300 mcg
alprostadil doses, respectively, during dosing in the Phase 3 studies. Patients should be
cautioned to avoid activities, such as driving or hazardous tasks, where injury could result
if hypotension or syncope occurs after Vitaros administration.
Before initiation of treatment with Vitaros, causes of erectile dysfunction, that are
treatable, should be excluded by appropriate diagnostic methods.
In addition, patients with underlying disorders, such as orthostatic hypotension, myocardial
infarction and syncope, should not use Vitaros (see CONTRAINDICATIONS, section 4.3).
Clinical studies have not been conducted in patients with a history of neurological disease
or spinal injury.
The pharmacokinetics of Vitaros have not been formally studied in patients with hepatic
and /or renal insufficiency. The dose may need to be lowered in these populations due to
impaired metabolism.
General Precautions:
Vitaros should be applied according to the instructions above. Inadvertent intraurethral
exposure may result in penile burning or tingling sensation and pain. Repeated longer
term intraurethral exposure of Vitaros is unknown.
Patients should be informed that Vitaros offers no protection from the transmission of
sexually transmitted diseases. Patients and partners who use Vitaros need to be counselled
about the protective measures that are necessary to guard against the spread of sexually
transmitted agents, including the human immunodeficiency virus (HIV).
Health care professionals should encourage their patients to inform their sexual partners
that they are using Vitaros. Partners of Vitaros users can experience adverse events, most
commonly vaginal irritation. A condom barrier is therefore recommended.
The effects of Vitaros on the oral or anal mucosa has not been studied. A condom barrier
should be used for oral sex (fellatio) or anal sex.
Vitaros has no contraceptive properties. It is recommended that couples using Vitaros use
adequate contraception if the female partner is of childbearing potential
There is no information on the effects on early pregnancy of alprostadil at the levels
received by the female partners. A condom barrier should be used for sexual intercourse
with women of childbearing age, pregnant or lactating women.
Only latex material based condoms have been investigated together with its use and other
materials may not exclude possible risk for occurrence of damage to the condom.

Pharmacokinetic or pharmacodynamic interaction studies with Vitaros were not done.
Based on the nature of metabolism (see “Pharmacokinetics”) drug-drug interactions are
considered unlikely.
Effect of Interaction
The safety and efficacy for Vitaros in combination with other treatments for erectile
dysfunction, especially for the treatment with Phosphodiesterase-5 inhibitors (PDE-5) or
sildenafil, tadalafil and vardenafil, has not been studied. Therefore, Vitaros should not be
used in combination with PDE5 inhibitors. As both Vitaros and PDE5 inhibitors have
cardiovascular effects, an additive increased cardiovascular risk cannot be excluded.
No interaction studies have been performed for Vitaros in combination with penile
implants or smooth muscle relaxants such as papaverine; drugs used to induce erections
such as alpha blocking drugs (e.g. intracavernosal phentolamine, thymoxamine). There is
a risk of priapism (painful prolonged abnormal erection) when used in combination.
No interaction studies have been performed for Vitaros in combination with
sympathomimetics, decongestants and appetite suppressants. When used in combination
there may be a reduced effect of alprostadil (drug interaction inhibition).
No interaction studies have been performed for Vitaros in combination with
anticoagulants and platelet aggregation inhibitors. When used in combination there may
be an increased risk of urethral bleeding, haematuria.
Patients concomitantly treated with antihypertensive drugs and vasoactive medications
may show an increased risk for hypotension, especially in elderly patients.

Pregnancy
There are no data on the use of Vitaros in pregnant women. The indirect exposure to
alprostadil in women is likely to be low.
Animal data on higher doses of alprostadil show reproductive toxicity (see section 5.3).
Pregnant women should not be exposed to Vitaros.
Breast-feeding
It is not known if indirect exposure to alprostadil via Vitaros will lead to significant
excretion in breast milk. It is not recommended to use Vitaros while breastfeeding.
Fertility
In male rabbits, atrophy of the seminiferous tubules of the testes was observed after
repeated dosing. It is not known whether Vitaros has an effect on human male fertility.

No studies on the effects of the ability to drive and use machines have been performed.
As dizziness and syncope (fainting) have been reported rarely in clinical trials with
Vitaros, patients should avoid activities, such as driving or hazardous tasks, where injury
could result if syncope occurs within 1 to 2 hours after administration of Vitaros.

Tabulated list of adverse reactions
The most frequently reported adverse events in treatment with Vitaros are presented in
the table below. (Very common ≥ 1/10; Common ≥ 1/100, <1/10; Uncommon ≥1/1000,
<1/100; Rare ≥1/10000, <1/1000; Very rare <1/10000)
Priapism (an erection lasting longer than 4 hours) is a serious condition that requires
prompt treatment by a physician.
Table 1 Adverse Reactions
System Organ Class Frequency Adverse Reaction
(MedDRA)
Nervous System Uncommon Hyperesthesia
Disorders
Vascular Systems Uncommon Dizziness Syncope Hypotension
Disorders*
Skin and subcutaneous Common Rash
tissue disorders
Musculoskeletal and Uncommon Pain in Extremity
Connective tissue
Disorders
Renal Disorder Common Urethral pain
Urinary disorder Uncommon Urethral stenosis
Urinary Tract Inflammation
Reproductive system Common Penile Burning
and breast disorders Penile Pain
Penile Erythema
Genital Pain
Penile Erythema
Genital Discomfort
Genital Erythema
Erection Increased
Pruritis Genital
Penile Oedema
Balantitis
Penile Tingling
Penile throbbing
Penile numbness
In women partners:
Vulvovaginal Burning Sensation
Vaginitis
Uncommon Penile Itching
Genital Rash
Scrotal Pain
Fullness genital
Excessive rigidity
Lack of sensation to Penis
Prolonged erection/priapism
In women partners:
Vulvovaginal Pruritis
General Disorders and Uncommon Application Site Pain
Administration
Site Conditions
Special populations
*There is no clear indication that alprostadil increases the risk of cardiovascular events,
other than the vasodilative effects, but it cannot be excluded that patients with underlying
disease/risk factors are at increased risk in combination with increased sexual/physical
activity that is associated with alprostadil use (see 4.3 and 4.4)
To report any side effects: Saudi Arabia
National Pharmacovigilance and Drug Safety Center (NPC)
Fax: +966-11-205-7662
To call the executive management of vigilance and crisis management:
+966-11-2038222 ext.: 2353 – 2356 – 2317 – 2354 – 2334 – 2340
Toll-free: 8002490000
E-mail: npc.drug@sfda.gov.sa
Website: www.sfda.gov.sa/npc.

Over dosage requiring treatment has not been reported with Vitaros. Over dosage with
Vitaros may result in hypotension, syncope, dizziness, penile pain and possible priapism
(rigid erection lasting > 4 hours). Priapism can result in permanent worsening of erectile
function. Patients suspected of overdose who develop these symptoms should be under
medical supervision until systemic or local symptoms have been resolved.
Should a prolonged erection lasting 4 or more hours occur, the patient should be advised
to seek medical help. The following actions can be taken:
• The patient should be supine or lying on his side. Apply an ice pack alternately
for two minutes to each upper inner thigh (this may cause a reflex opening of the
 venous valves). If there is no response after 10 minutes, discontinue treatment.
If this treatment is ineffective and a rigid erection has lasted for more than 6 hours,
penile aspiration should be performed. Using aseptic technique, insert a 19-21 gauge
butterfly needle into the corpus cavernosum and aspirate 20-50 ml of blood.
This may detumesce the penis. If necessary, the procedure may be repeated on
the opposite side of the penis.
• If still unsuccessful, intracavernous injection of α-adrenergic medication is
recommended. Although the usual contraindication to intrapenile administration
of a vasoconstrictor does not apply in the treatment of priapism, caution is
advised when this option is exercised. Blood pressure and pulse should be
continuously monitored during the procedure. Extreme caution is required in
patients with coronary heart disease, uncontrolled hypertension, cerebral
ischaemia, and in subjects taking monoamine oxidase inhibitors. In the latter
 case, facilities should be available to manage a hypertensive crisis.
• A 200 microgram/ml solution of phenylephrine should be prepared, and 0.5 to 1.0 ml
of the solution injected every 5-10 minutes. Alternatively, a 20 microgram/ml
solution of adrenaline should be used. If necessary, this may be followed by further
aspiration of blood through the same butterfly needle. The maximum dose of
 phenylephrine should be 1 mg, or adrenaline 100 micrograms (5ml of the solution).
• As an alternative metaraminol may be used, but it should be noted that fatal
hypertensive crises have been reported. If this still fails to resolve the priapism,
the patient should immediately be referred for surgical management.

Pharmacotherapeutic Group: Drugs used in erectile dysfunction
ATC Code: G04BE01
Mechanism of Action:
Alprostadil is chemically identical to prostaglandin E1, the actions of which include
vasodilatation of blood vessels in the erectile tissues of the corpora cavernosa and
increase in cavernosal artery blood flow, causing penile rigidity.
After application of Vitaros the onset of erection is within 5 to 30 minutes. Alprostadil
has a short half-life in man and improvement of erections may last from 1 to 2 hours after
dosing.
Efficacy: Two Pivotal Phase 3 studies evaluated the efficacy of Vitaros in patients with
Erectile Dysfunction. Relative to placebo, a statistically significant overall improvement
was observed in the 100, 200 and 300 mcg alprostadil treatment groups in each of the
primary efficacy endpoints; i.e., the erectile function (EF) domain of the IIEF
(International Index of Erectile Function) score and increased success in vaginal
penetration and ejaculation. Additionally, there were also overall improvements and
statistical significance of the treatment groups compared to placebo in several of the
secondary efficacy variables, including the other IIEF domain scores (orgasmic function,
intercourse satisfaction, and overall satisfaction), Patient Self-Assessment of Erection
(PSAE), and Global Assessment Questionnaire (GAQ).
Subpopulation Efficacy: Similar improvements to those of all patients were generally
observed within the subpopulations (diabetic, cardiac, prostatectomy, hypertensive
patients, and patients who failed previous therapy with Viagra) and two age groups (< 65
and > 65 years) in the IIEF EF domain scores.

Absorption: Absolute bioavailability by the topical route was not determined. In a
pharmacokinetic study, patients with erectile dysfunction were treated with 100 mg of
Vitaros Cream at doses of 100, 200 and 300 mcg of alprostadil. Plasma levels of PGE1,
and its metabolite, PGE0 were low or undetectable in most subjects at most of the postdose
blood sampling times and pharmacokinetic parameters could not be estimated.
Cmax values and AUC values of 15-keto-PGE0 were low and showed a less than dose
proportional increase over the 100 – 300 mcg dose range. The maximum plasma
concentrations of 15-keto-PGE0 were achieved within one hour after administration.
Table 2: Mean (SD) Pharmacokinetic Parameters f or 15-keto-PGE0
Placebo Vitaros 100 Vitaros 200 mcg Vitaros 300
Parameter (N=5) mcg (N=5) (N=5) mcg (N=5)
AUC
a
388 (256) 439 (107) 504 (247) 960 (544)
(pg*hr/mL)
Cmax (pg/mL) 23 (19) 202 (229) 120 (103) 332 (224)
Tmax (hr) 6 (8) 0.6 (0.4) 1 (0.7) 0.7 (0.3)
T1/2 (hr) 4 (--)
b
5 (3) 3 (1)
c
6 (6)
a
AUC is the area under the plasma concentration curve from time zero to hour
24
b
Only 1 subject had sufficient data for estimation of half-life.
c
Only 3
subjects had sufficient data for estimation of half-life.
SD = standard deviation
Distribution: After alprostadil administration to the meatus and glans of the penis,
alprostadil is rapidly absorbed into the corpus spongiosum and corpora cavernosa through
collateral vessels. The remainder passes into the pelvic venous circulation through veins
draining the corpus spongiosum.
Metabolism: Following topical administration, PGE1 is rapidly metabolized locally by
enzymatic oxidation of the 15-hydroxyl group to 15-keto-PGE1. 15keto-PGE1 retains
only 1-2% of the biological activity of PGE1 and is rapidly reduced to form the most
abundant inactive metabolite, 13, 14-dihydro, 15keto-PGE which is cleared primarily by
the kidney and liver.
Excretion: After intravenous administration of tritium-labelled alprostadil in man,
labelled drug disappears rapidly from the blood in the first 10 minutes and only low-level
radioactivity remains in the blood after 1 hour. The metabolites of alprostadil are excreted
primarily by the kidney with approximately 90% of the administered intravenous dose
excreted in the urine within 24 hours after administration. The remainder is excreted in
the faeces. There is no evidence of tissue retention of alprostadil or its metabolites
following intravenous administration.
Pharmacokinetics in Special Populations:
Pulmonary Disease: Patients with pulmonary disease may have a reduced capacity to
clear the drug. In patients with adult respiratory distress syndrome, pulmonary extraction
of intravenously administered PGE1 was reduced by approximately 15% compared to a
control group of patients with normal respiratory function.
Gender: The effects of gender on the pharmacokinetics of the Vitaros have not been
studied and pharmacokinetic studies have not been conducted in female partners.
Geriatric, Pediatric: The effects of age on the pharmacokinetics of topical alprostadil
have not been studied. The Vitaros is not indicated for use in children or in individuals
below 18 years of age.

Alprostadil, DDAIP and Vitaros (including DDAIP) have not shown genotoxic potential.
Carcinogenicity studies with alprostadil or Vitaros have not been conducted.
Carcinogenicity assessments of the excipient, DDAIP, found no tumor formation with
topical administration to mice and subcutaneously in rats. In the Tg.AC transgenic mouse
model administration of DDAIP at a concentration of 1.0% and 2.5% induced papillomas
in females and males respectively. This effect is not likely to be relevant for humans, as it
likely caused by irritation.
Alprostadil has no effect on sperm count or morphology. However, the excipient DDAIP
caused atrophy of the seminiferous tubules of the testes in rabbits when administered
locally at a concentration of 5%. A direct spermatotoxic effect of DDAIP could not be
tested, and the relevance for a possible reduced male fertility in humans is therefore
unknown. DDAIP administered subcutaneously to rats had no effect on fertility.
Alprostadil has been shown to be embryotoxic (decreased foetal weight) when
administered as a subcutaneous bolus to pregnant rats at low doses Higher doses resulted
in increased resorptions, reduced numbers of live foetuses, increased incidences of
visceral and skeletal variation and malformations, and maternal toxicity. Intravaginal
administration of PGE1 to pregnant rabbits resulted in no harm to the foetus.
Reproductive toxicity studies for DDAIP were performed after subcutaneous
administration to rats and rabbits. No effects were seen in rats, but in rabbits foetotoxicity
including increased malformations were seen at high doses, which was probably due to
maternal toxicity. No effects on post-natal; development were evident in rats.

Purified water
Ethanol, anhydrous
Ethyl laurate
Hydroxypropyl guar gum
Dodecyl-2-N, N-dimethylaminopropionate hydrochloride
Potassium dihydrogen phosphate
Sodium hydroxide, for pH adjustment
Phosphoric acid, for pH adjustment

Not applicable.

Store in a refrigerator (2°C - 8°C).
Do not freeze.
Unopened sachets may be kept out of the refrigerator by the patient, at a temperature
below 30 °C for up to 3 days prior to use.
At the end of this period, the product should be discarded if not used.
Store in the original sachet in order to protect from light.

Vitaros is supplied in individual sachets containing one (1) AccuDose container. Each single
container contains 100 mg cream. Vitaros is available in unit cartons containing four
(4) containers and one (1) container. The sachets are composed of aluminium foil/laminate.
The container components are composed of polypropylene and polyethylene.

Each container is for single use only.
Any unused medicinal product or waste material should be disposed of in accordance
with local requirements.