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Urologia 2017; 84 (Suppl 2): S1-S10
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REVIEW
most include the three main accepted dimensions of this
condion: short IELT, inability to control ejaculaon, and both
personal and interpersonal distress.
In 2014, the Internaonal Society for Sexual Medicine
(ISSM) introduced a new denion of lifelong and acquired
PE, represenng the rst evidence-based, in contrast to pure-
ly expert-based, denion (4). According to this denion, PE
(lifelong or acquired) is a male sexual dysfuncon character-
ized by: (1) ejaculaon that always or nearly always occurs
prior to or within about 1 minute of vaginal penetraon start-
ing at me of the rst sexual experience (lifelong PE) or a clin-
ically signicant and bothersome reducon in IELT, oen to
about 3 minutes or less (acquired PE); (2) the inability to delay
ejaculaon during all or nearly all vaginal penetraons; and,
(3) negave personal consequences, such as distress, bother,
frustraon, and/or the avoidance of sexual inmacy (4, 5).
Epidemiology of PE and quality of life
PE is more than just a short me to ejaculaon and the
determinants of PE are complex and mulfactorial (6). IELT,
control over ejaculaon, and the sexual sasfacon of the
man and his partner have been idened as important inter-
related determinants of PE (7). By causing signicant personal
and interpersonal distress for both the paent and partner, a
vicious cycle can develop where the emoonal reacons to
DOI: 10.5301/uj.5000275
Fortacin™ spray for the treatment of premature
ejaculaon
Hartmut Porst, Andrea Burri
Private Instute for Urology, Andrology and Sexual Medicine, Hamburg - Germany
Introducon
Premature ejaculaon (PE) is a frequent complaint of
male sexual dysfuncon and a major source of sexual distress
(1). Increased sensivity of the glans penis and abnormali-
es of the aerent-eerent reex pathway within the ejacula-
tory process are implicated in the occurrence of PE and may
contribute to penile hypersensivity and PE (2). Therefore, a
reducon in penile sensivity is ancipated to prolong intra-
vaginal ejaculaon latency me (IELT) without aecng the
sensaon of ejaculaon and orgasmic feelings (3).
There are several denions of PE and how to accurately
capture the phenomenon remains a major debate. Although
there is lile consensus amongst dierent organizaons and
sociees regarding the denion and classicaon of PE,
ABSTRACT
Premature ejaculaon (PE) is a common complaint of male sexual dysfuncon aecng men and their partners
and consequently causing signicant personal and interpersonal distress. Increased sensivity of the glans penis
and abnormalies of the aerent-eerent reex pathway within the ejaculatory process are involved in the oc-
currence of PE. Drugs that either selecvely reduce penile sensizaon or modify the aerent-eerent reex are
well established therapeuc opons for PE. Fortacin™ is the rst topical treatment to be ocially approved for
the treatment of primary PE in adult men, and is menoned as an experimental aerosol (as TEMPE) in the current
European Associaon of Urology guidelines. It was approved for use in the European Union and launched in the
United Kingdom in November 2016. Fortacin™ is a eutecc-like mixture of lidocaine 150 mg/mL and prilocaine
50 mg/mL that meets the requirements of an ideal treatment for PE because it is fast acng (within 5 minutes),
has durable eects, can be easily used “on-demand”, and shows minimal side-eects. The metered-dose spray
delivery system allows the desensizing agents to be deposited in a dose-controlled, concentrated lm onto the
glans penis consequently reducing its sensivity. This is translated into a delaying of the ejaculatory latency me
without adversely aecng the sensaon of ejaculaon and orgasmic pleasure. The ecacy and safety of Forta-
cin™ have been proven by means of increased ejaculatory latency, control, and sexual sasfacon in large scale
studies demonstrang the signicant benets for both paents and their partners.
Keywords: Fortacin™, Intravaginal ejaculatory latency me, Lidocaine/Prilocaine, Premature ejaculaon, Topical
anesthesia
Accepted: November 24, 2017
Published online: December 18, 2017
Corresponding author:
Hartmut Porst
Private Instute for Urology
Andrology and Sexual Medicine
Neuer Jungfernseg 6a
20354 Hamburg, Germany
Porst20354@aol.com
Fortacin™ for premature ejaculaon
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PE by both pares can exacerbate or perpetuate the problem
(6). Indeed, men with PE report having more interpersonal
dicules and higher levels of personal distress than men
without PE, and partners of men with PE report having higher
levels of relaonship problems compared with partners of
men without PE (5). Importantly, men with PE feel they are
“leng their partner down” and that the quality of their rela-
onship would improve without PE (8).
Apart from interpersonal fricon and distress, PE is also
associated with signicant sexual and psychological comor-
bidies. The Premature Ejaculaon Prevalence and Atudes
(PEPA) survey (9), a comprehensive Internet-based survey
conducted on 12,133 men aged 18-70 years in the United
States, Germany, and Italy, for example, found that the per-
centage of men self-reporng comorbid condions including
sexual dysfuncons (e.g., anorgasmia, low libido, erecle dys-
funcon) and psychological disturbances (e.g., depression,
anxiety, excessive stress), was signicantly higher in men with
PE (22.7% of the total sample) than in men without PE (all
p<0.05) (9). In the survey, men were classied as having PE
based on self-reporng of low or absent control over ejacu-
laon, resulng in distress for them, their sexual partner, or
both, with similar prevalence rates among the parcipang
countries (United States 24%, Germany 20.3 %, Italy 20%).
Despite the fact that PE can have serious eects on the
psychological well-being and overall quality of life of the suf-
ferer and his partner, only a minority of men seek profes-
sional help. The PEPA survey, for example, showed that only
9% of men with self-reported PE had consulted a doctor (9).
Embarrassment and a belief that there is no eecve treat-
ment available are the main reasons for not discussing PE
with their physician (10).
Neurophysiology of ejaculaon
The male sexual-response cycle consists of four phases:
desire, arousal (erecon), orgasm (ejaculaon), and resoluon
(Fig. 1) (11). The process of ejaculaon is classied by two dis-
nct phases, “emission” and “expulsion”. Sympathec, para-
sympathec, and somac nervous systems are involved in the
Fig. 1 - Nor ma l male sexu al response
compared with premature ejacu-
laon. Figure adapted from Kirby
2014 (11).
ejaculatory response and are coordinated by the spinal ejacula-
tory generator (SEG) (12, 13). Sensory aerents received by the
SEG are coordinated with inhibitory and excitatory inuences
from supra-spinal sites, as well as biochemical or mechanical
informaon from the accessory sex organs (14). The ejaculato-
ry process starts with the emission of semen into the posterior
urethra, induced by increased acvity of the sympathec ef-
ferent bers causing sequenal contracons of the epididymis,
vas deferens, seminal vesicles, and prostate, alongside the clo-
sure of the bladder neck (15). Emission of the semen with dila-
on of the posterior urethra results in the forceful expulsion of
semen out of the urethral orice induced by acvaon of the
somac pudendal nerve with subsequent contracons of the
bulbospongiosus, bulbocavernosus, and perineal muscles (16).
The rhythmical expulsion is mainly inuenced by the somac
nervous system and represents an involuntary spinal cord re-
ex (13). Various neurotransmiers also play a major role in
the control of ejaculaon, such as the excitatory role of dopa-
mine and the inhibitory role of serotonin or nitric oxide (13).
Although numerous preclinical and clinical studies in re-
cent years have been able to provide a beer understand-
ing of the ejaculatory process, many details remain unknown
regarding the exact physiology of the ejaculatory process. At
present, it is commonly accepted that PE is the result of a
dysregulaon of the normal ejaculatory process with either
over-acvaon of ejaculaon smulatory or inhibion of
ejaculaon delaying 5-HT (serotonin) receptors, leading to
an involuntary lack of control over ejaculaon (17). Clearly,
a more in-depth understanding of the normal physiological
ejaculatory reex (Fig. 2) is essenal in order to determine
the exact underlying pathophysiology of PE.
Raonale for the use of topical anesthecs
The use of drugs that selecvely reduce penile sensiza-
on or which modify the aerent-eerent reex could pro-
vide eecve therapy for PE, as has been shown with the
o-label use of topical desensizing creams (2). Due to the
variable nature of sexual intercourse, spontaneity is an im-
portant factor in the treatment of PE. The ideal treatment
Porst and Burri S3
© 2017 The Authors. Published by Wichg Publishing
for PE should therefore be characterized, among others, by a
rapid on-set of acon, which is eecve for “on-demand” use
from the rst dose, and which is reversible (18). An ideal PE
medicaon should also demonstrate high ecacy on IELT re-
ected in paent-reported outcomes and, in addion, should
show a good safety prole with minimal side-eects and no
undesirable eects on the sexual partner.
The use of topical anesthecs to reduce sensivity of the
glans penis has been shown to improve ejaculatory latency
without having any adverse eects on the sensaon of ejacu-
laon and impairment of orgasmic capacity (19, 20). Unlike the
majority of systemic treatments for PE, topical treatments can
be used “on-demand” and are unlikely to have systemic side-
eects (20). There are, however, a number of disadvantages to
some topical treatments including dicult dosing with the po-
tenal of either over- or under-dosing causing either erecle
dicules or lack of ecacy, which may interfere with sponta-
neity (20). Some topical treatments may also need to be used
with a condom or washed o prior to intercourse, and again
may potenally interfere with spontaneity and arousal.
The paucity of approved pharmacological treatments for
PE, has led to an increased “o-label” use of oral andepres-
sants and local anesthecs.
Clearly, an approved treatment that can be used “on-
demand” and which is eecve from rst use with minimal
systemic side-eects is essenal (2, 21).
Exisng treatments for PE
Of the oral and locally acng topical therapies currently
used to manage PE in Europe, only Fortacin™ and dapoxene
have been ocially approved for the treatment of PE.
Oral therapies
Dapoxene, a short-acng selecve serotonin reuptake
inhibitor (SSRI), was the rst oral pharmacological agent de-
veloped for the treatment of PE and ocially approved for
“on-demand” use in adult men aged 18 to 64 years (22). Its
mechanism of acon in the treatment of PE is presumed to
be linked to the inhibion of neuronal reuptake of serotonin
and the subsequent potenaon of the neurotransmier’s
acon at pre- and post-synapc receptors (23). The recom-
mended starng dose for all paents is 30 mg, taken approxi-
mately 1 to 3 hours prior to sexual acvity, with no more than
one dose taken every 24 hours (23).
Dapoxene was shown to signicantly improve all as-
pects of PE, including prolonging stopwatch-measured IELT
(as primary outcome) and increasing paent-reported out-
come measures (i.e. the Premature Ejaculaon Prole [PEP]
quesonnaire and the clinical global impression of change
[CGIC] as secondary outcomes), in four randomized, double-
blind, placebo-controlled, mulcenter, phase III studies of
12-24 weeks’ duraon in men with PE (n = 4,843) (24-26).
A pooled analysis of these studies showed that oral dapox-
ene 30 mg or 60 mg (taken as needed) induced signicantly
greater improvements from baseline in the geometric mean
IELT at all me points measured, compared with placebo (27).
At week 12, the geometric mean IELT increased from a base-
line of approximately 0.8 minutes to 2.0 and 2.3 minutes with
dapoxene 30 mg and 60 mg, respecvely, compared with
1.3 minutes for placebo (both p<0.001), corresponding to a
2.5-fold and 3.0-fold increase in the geometric mean IELT re-
specvely (vs. a 1.6-fold increase for placebo; p<0.0001 for
both) (27). Signicant improvements in PEP items and CGIC
Fig. 2 - The physiological ejacula-
tory reex. Ejaculaon results from
coordinated contracle acvity
organized by the spinal ejaculatory
generator (SEG). Sensory aerent
informaon is received by the SEG
which, alongside supra-spinal infor-
maon arising from specic brain
regions, triggers the ejaculatory
mechanism during sexual acvity.
Topical anesthecs applied to the
glans penis inhibit penile sensory re-
ceptors. Figure adapted from Saitz
and Serefoglu 2015 (12).
Fortacin™ for premature ejaculaon
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© 2017 The Authors. Published by Wichg Publishing
were also shown with both doses of dapoxene (all p<0.001
vs. placebo) (27).
Despite its ecacy in the treatment of PE, dapoxene
has also been associated with dose-related systemic adverse
eects (AEs), with nausea, dizziness, headache, diarrhea,
insomnia, and fague as the most frequently reported drug-
related adverse events in ve randomized, double-blind, pla-
cebo-controlled, mulcenter, phase III studies in men with PE
(n = 6,081) (24-26, 28). Indeed, an integrated analysis of these
studies showed that AEs were reported in 47.0% and 60.3% of
paents receiving 30 mg and 60 mg dapoxene, respecvely,
with AE-related disconnuaon occurring in 3.5% and 8.8%
of these paents (27). In addion, the Summary of Product
Characteriscs states that orthostac vital signs (blood pres-
sure and heart rate) must be measured prior to starng
dapoxene, which should not be used in paents using PDE5
inhibitors due to possible reduced orthostac tolerance (23).
High disconnuaon rates of this drug have also been
reported in the seng of real clinical pracce. In a study
by Mondaini et al. (n = 120), 20% of paents decided not
to start dapoxene with fear of using a “drug” being the
most frequently reported reason (29). Moreover, of the 80%
who started therapy, 26% stopped taking dapoxene aer
1 month due to side eects and lack of ecacy. Only 10.4% of
paents connued the treatment for over one year. The main
reasons for disconnuing the treatment were: eect below
expectaon, costs, side eects, loss of interest in sex, and lack
of ecacy.
The o-label use of other SSRIs (including paroxene, ser-
traline, and citalopram) in the treatment of PE is based on
the side-eect of delayed ejaculaon that was observed in
depressed paents with normal sexual funcon who were
treated with SSRIs for their depression. This increase in IELT
is most likely the consequence of increased concentraons
of serotonin in the synapc cle, causing an inhibion in the
ejaculatory reex and therefore a delay or even absence of
ejaculaon (2). Although doses of prescribed SSRIs tend to be
generally lower for PE than for depression, the AEs are simi-
lar and there is also the potenal for serious drug interacon
that may result in rare cases of the so-called serotonin syn-
drome and suicidal ideaon (30).
Locally acng topical therapies
Topical therapies that can be applied directly to the glans
penis in order to produce some degree of penile desensiza-
on are directed to the hypersensivity aspect of PE. These
topical treatments can be used “on-demand” with minimal
systemic eects but may interfere with sexual spontaneity
and have dosing dicules with the potenal of either over-
or under-dosing, which may either cause penile hypoesthe-
sia with subsequent erecle dysfuncon and/or transvaginal
transmission resulng in vaginal numbness and anorgasmia
or lack of ecacy, respecvely (20). Their ease of applicaon
and tolerability is further limited by the presence of a number
of excipients in the formulaon of the majority of creams and
topical products causing dicules in applying the correct
measured dose.
Creams/ointments that have been frequently used in
clinical pracce, but that have not been specically approved
for the management of PE, include a local anesthec cream
containing lidocaine and prilocaine (2.5% each) that was de-
veloped for the topical anesthesia of intact skin. Although
studies have shown some ecacy of lidocaine/prilocaine
cream 5% in prevenng PE (31, 32), it is slow-acng and cum-
bersome to use, with genital hypoesthesia reported in both
sexual partners (20). In addion, dicules in applying the
cream have been reported along with a decrease in penile
and vaginal sensivity, penile hypoesthesia and loss of erec-
on, and penile irritaon (31, 32). Local anesthec creams
may also contain a mixture of base and ionized forms of local
anesthecs where only the uncharged base forms are able to
penetrate skin or mucous membranes (33).
Fortacin™ (Lidocaine/Prilocaine, Recorda) is the rst of-
cially approved topical therapy for PE. It is indicated for the
treatment of primary PE in adult men and was approved for
use in the European Union in 2013 and launched in the United
Kingdom in November 2016 (34, 35). During its clinical devel-
opment, Fortacin™ was referred to by two separate names,
Topical Eutecc Mixture for Premature Ejaculaon (TEMPE)
and PSD502, with both names having been used in the pub-
lished literature. Notably, Fortacin™ (denoted as TEMPE) is
menoned as an experimental aerosol in current European
Associaon of Urology Guidelines (10).
Overview of Fortacin™
Fortacin™ is a metered-dose aerosol spray that delivers
topical anesthesia to the glans penis. It contains purely base
(uncharged) forms of the local anesthecs lidocaine 150 mg/
mL and prilocaine 50 mg/mL, with no excipients except the
spray propellant (norurane) (34). This oers a potenal ad-
vantage over other exisng topical anesthecs in terms of a
reduced risk of allergic reacon due to excipients. Although
lidocaine and prilocaine are crystalline solids at room tem-
perature, they form a eutecc mixture when mixed together,
resulng in an oily liquid that remains in liquid form at tem-
peratures that are lower than their individual melng points
(33). Deployment of the metered-dose chamber causes the
instant vaporizaon of the propellant forcing the lidocaine
and prilocaine out of the soluon and into a eutecc-like mix-
ture. This forms a slightly oily substance that enhances ad-
herence to the penile surface by creang a thin layer of local
anesthec molecules on the glans mucosa. Consequently, the
absorpon of the acve components in their free-base form
through the non- or poorly-keranized ssue of the glans pe-
nis can be opmized (33, 36), the extent of neural blockage
maximized, and the onset of numbness minimized.
Furthermore, in contrast to the applicaon of creams, the
metered-dose spray delivery system allows the desensizing
agents to be deposited in a dose-controlled, concentrated
lm onto the glans penis (33). Due to its formulaon, the
uncharged base forms of lidocaine and prilocaine are read-
ily absorbed through the glans penis mucous membrane, but
not through normal keranized skin (i.e. the sha of the pe-
nis); this minimizes absorpon through normal skin so that
a full sensaon can be maintained in the sha of the penis
(33, 36). Furthermore, by reducing the permeability of the
neuronal membranes to sodium ions, Fortacin™ produces
localized reversible inhibion of nerve conducon (33). The
Porst and Burri S5
© 2017 The Authors. Published by Wichg Publishing
acve substances, lidocaine and prilocaine, block transmis-
sion of nerve impulses in the glans penis, reducing its sensi-
vity, which is then translated into a delaying of the ejacula-
tory latency me without adversely aecng the sensaon
of ejaculaon and orgasm (34).
Ecacy of Fortacin™
The clinical ecacy of Fortacin™ in the treatment of pri-
mary PE in adult men has been evaluated in ve studies: one
proof-of-concept phase II study (3); one supporve phase II
study (37); two pivotal phase III studies (38, 39); and, com-
bined data from the two pivotal phase III studies, including
the open-label extension of 5 and 9 months (2, 40).
Posive outcomes in terms of increased IELT, sexual sat-
isfacon, and minimal local AEs were inially shown from
the proof-of-concept and supporve phase II studies. In the
prospecve, open-label, proof-of-concept study, a signicant
increase in IELT (p = 0.008 versus baseline), improved sexual
sasfacon, and minimal local AEs were demonstrated in
11 men with self-reported PE who applied Fortacin™ to the
glans penis 15 minutes prior to intercourse (3). Similarly, the
supporve phase II study (37) conducted on 54 men with
PE (according to DSM-IV criteria) also showed posive out-
comes with an increased IELT, beer ejaculatory control, and
improved sexual quality of life compared with the placebo
group (41).
Primary evidence for the ecacy of Fortacin™ in the treat-
ment of paents with PE was derived from two pivotal phase
III, mulcenter, randomized, double-blind, placebo-controlled
studies, with open-label follow-up in paents with lifelong
PE and their sexual partners (38, 39). In both studies, the
3-month treatment phase with 30 mg Fortacin™ was followed
by a 9-month open-label treatment phase in the rst study
(39) and a 5-month open-label treatment phase in the second
study (38). Inclusion criteria for both studies were heterosex-
ual men aged ≥18 years in stable, monogamous relaonships
with lifelong PE diagnosed according to both the DSM-IV cri-
teria (41) and the ISSM denion (42), and a baseline IELT of
≤1 minute for at least two of the rst three sexual encounters
during the 4-week screening period. Men taking tricyclic an-
depressants, monoamine oxidase inhibitors or short- acng
SSRIs, in which the dose had changed within the 4-week
screening period or was expected to change, were excluded
from the trials, as were those with erecle dysfuncon.
Fortacin™ (or matched placebo) was applied to the glans
penis (aer retracng any foreskin) approximately 5 minutes
before intercourse with excess spray wiped o prior to pen-
etraon. Paents recorded stop-watch measured IELT during
each sexual encounter and completed the Index of Prema-
ture Ejaculaon (IPE) and PEP quesonnaires at study entry
and monthly visits.
The 10-item IPE quesonnaire assesses subjecve as-
pects of PE, covering three domains: ejaculatory control (four
quesons), sexual sasfacon (four quesons), and distress
(two quesons) (43). Each queson is answered on a 6-point
Likert-type scale with nal scores for control/sasfacon
and distress ranging from 4-20 points and 2-10 points, re-
specvely (38). The PEP quesonnaire consists of four ques-
ons relang to perceived control over ejaculaon, personal
distress related to ejaculaon, sasfacon with sexual inter-
course, and interpersonal diculty related to ejaculaon.
Each queson is answered on a 5-point Likert-type scale (44).
Primary ecacy outcome variables for the pivotal studies
included the change from baseline to study end in mean IELT
and in the IPE quesonnaire domains of ejaculatory control,
sexual sasfacon, and distress (distress was a primary e-
cacy variable for the second study only). Secondary ecacy
outcome variables included the proporon of paents with a
mean IELT of >1 minute and >2 minutes during the 3-month
double-blind treatment period, the change in the IPE domain
of distress from baseline to month 3 (rst study only), and
the PEP quesonnaire at months 1, 2, and 3. As drug-induced
ejaculatory performance has been shown to disclose a posi-
vely skewed IELT distribuon, the geometric mean IELT and
the fold increase of the geometric mean IELT were used in
order to avoid overesmaon of treatment ecacy (45).
The rst pivotal phase III study (n = 290; 191 paents
treated with Fortacin™ and 99 with placebo) produced sig-
nicant, clinically meaningful improvements in ejaculatory
latency, control, and sexual sasfacon with acve treatment
(39). The geometric mean IELT increased from a baseline
of 0.6 minutes in both treatment groups to 3.8 minutes in
the Fortacin™ group vs. 1.1 minutes in the placebo group at
study end aer 3 months (Fig. 3). Aer adjusng for treat-
ment-group imbalances, these numbers eecvely represent
a 6.3-fold and 1.7-fold increase in adjusted geometric mean
IELT, demonstrang a signicant between-treatment dier-
ence in favor of the acve treatment (p<0.001), which was
also ecacious in restoring control with signicantly greater
increases from baseline to month 3 for the IPE domain scores
of ejaculatory control, sexual sasfacon, and distress (7.0,
5.9, and 2.8 point dierence between acve treatment and
placebo, respecvely; all p<0.001) (Fig. 4).
Fortacin™ was well received with 65.9% (of 182) paents
rang the medicaon as “good” or “excellent”, as opposed to
14.6% (of 96) paents in the placebo group. In addion, the
topical spray improved sexual sasfacon for both paents
and their partners at the end of the 3-month double-blind
phase, with signicantly more paents and partners report-
ing improvements of at least one point in each of the PEP
domains compared with those using placebo (p<0.001 for all
between-treatment comparisons) (Fig. 5).
The advantageous eects of Fortacin™ were replicated
and reinforced by the ndings from the second pivotal phase
III study (n = 249; 167 paents with acve treatment and 82
with placebo) (38). In this study, greater improvements in the
geometric mean IELT from baseline to month 3 were observed
for the acve treatment group compared with placebo (0.56
to 2.6 minutes vs. 0.53 to 0.8 minutes, respecvely), with a
signicant between-treatment dierence in the adjusted
geometric mean IELT in favor of the acve treatment (4.7 vs.
1.5 for placebo; p<0.0001) (Fig. 3). Scores for the IPE domains
of ejaculatory control, sexual sasfacon, and distress in the
acve treatment group were also signicantly higher than in
the placebo group (all p<0.001) (Fig. 4) (38). Similarly, signi-
cantly more paents and partners reported improvements of
at least one point for all four domains of the PEP queson-
naire at 3 months with use of the topical spray (all p<0.0001
vs. the placebo group) (Fig. 5).
Fortacin™ for premature ejaculaon
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A higher proporon of paents treated with Fortacin™ had
a mean IELT of >1 minute, >2 minutes, >3 minutes or >4 min-
utes compared with placebo based on combined data of the
intent-to-treat populaon during the 3-month double-blind
treatment period from both pivotal studies (Fig. 6) (40). Most
paents (85.2%) in the acve treatment group achieved a mean
IELT of >1 minute versus only 46.4% in the placebo group.
Parcipants in both pivotal studies had the opon to enter
the open-label treatment phase in which all paents received
Fortacin™. In total, 497 paents (98.4% of those compleng
the double-blind phase) entered the open-label extension; of
these, 326 subjects had received acve treatment and 171
had received placebo in the double-blind phase (40).
Fortacin™ was shown to be as eecve for the treatment
of PE at the end of the open-label phase as it was at the end of
the double-blind treatment phase, with no evidence of tachy-
phylaxis despite repeated use. The posive changes in the geo-
metric mean IELT observed during the double-blind phase were
maintained and augmented during the open-label phase, with
a marked improvement in geometric mean IELT in paents who
converted from placebo to acve treatment (Fig. 7) (2). The ef-
fecveness of the topical spray increased with repeated use over
me (Fig. 8), and improvements could be observed for all IPE
domain scores (mean change from baseline for ejaculatory con-
trol, sexual sasfacon, and distress scores were 12.3, 10.9, and
5.3 points, respecvely, at the end of the open-label phase) (40).
Fig. 3 - Geometric mean intravagi-
nal ejaculaon latency me (IELT)
at baseline and at the end of the
3-month treatment period in pa-
ents treated with For tacin™ or
placebo. *p<0.001 versus baseline.
Figure adapted from Dinsmore and
Wyllie 2009 (39) and Carson and
Wyllie 2010 (38).
Fig. 4 - Change from baseline to
month 3 in the adjusted mean Index
of Premature Ejaculaon (IPE) do-
main scores for ejaculatory control,
sexual sasfac on, and distress in
paents treated with Fortacin™ or
placebo. *p<0.001 versus placebo.
Figure adapted from Dinsmore and
Wyllie 2009 (39) and Carson and
Wyllie 2010 (38).
Porst and Burri S7
© 2017 The Authors. Published by Wichg Publishing
Tolerability of Fortacin™
In all studies, Fortacin™ has shown a good safety prole
with only a low incidence of mild-to-moderate local AEs ac-
cording to a combined evaluaon of 596 male paents and
584 female partners who parcipated in the clinical trials
(40). In general, most treatment-related AEs occurred imme-
diately or within 24 hours and most were mild or moderate
in intensity (40). The incidence of treatment-related AEs was
low in both paents (9.6%) and their female partners (6.0%)
(40). The most frequent adverse reacons reported in male
paents were local eects of genital hypoesthesia (4.5%) and
erecle dysfuncon (4.4%), with disconnuaon of treatment
in 0.2% and 0.5% of paents, respecvely. The most frequent
adverse reacons reported in female partners were vulvo-
vaginal burning sensaon (3.9%), and genital hypoesthesia
Fig. 5 - Percentage of paents (A)
and female sexual partners (B) re-
porng an improvement of at least
one point in Premature Ejacula-
on Prole (PEP) domains aer
3 months’ treatment with Forta-
cin™ or placebo. *p<0.001 for all
between-treatment comparisons.
**p<0.0001 for all between-treat-
ment comparisons. Figure adapted
from Dinsmore and Wyllie 2009 (39)
and Carson and Wyllie 2010 (38).
Fortacin™ for premature ejaculaon
S8
© 2017 The Authors. Published by Wichg Publishing
(1.0%). Vulvovaginal discomfort or burning sensaon caused
disconnuaon of treatment in 0.3% of subjects. In addion
to moderate-to-low AEs, there was lile or no desensizaon
of the genitalia neither in the paent nor in their partner with
the topical spray, which did not detract from sexual sasfac-
on as evidenced by the increase in IPE and PEP scores aer
3-months’ treatment compared with baseline. It is also note-
worthy that the topical spray was unlikely to be associated
with systemic AEs (46).
Posioning Fortacin™ in the treatment of PE
Due to the easy applicaon of Fortacin™ and short me to
ecacy (i.e. within 5 minutes) this new treatment is unlikely to
interfere with spontaneity of sexual acvies. Aer retracon
of the foreskin, the topical spray is applied to the glans penis
5 minutes before intercourse using three successive actua-
ons of the aerosol to deliver the approved dose and ensure
complete coverage, with any excess spray easily removed pri-
or to sexual intercourse minimizing transmission to the sexual
partner (27, 28). A maximum of 3 doses can be used within
24 hours, with a minimum interval of 4 hours between doses.
Based on results from clinical trials, which have shown sig-
nicant benets for both paents and their female partners in
ejaculatory latency, control, and sexual sasfacon, Fortacin™
should be recommended as a rst-line topical treatment of PE.
It is also noteworthy that the pivotal phase III studies demon-
strated increased eecveness of the topical spray over me,
Fig. 6 - Proporon of paents with
mean intravaginal ejaculaon laten-
cy me (IELT) >1 minute, >2 minutes,
>3 minutes, or >4 minutes during
the 3 month double-blind treatment
with Fortacin™ or placebo [com-
bined data of the intent-to-treat
populaon from both pivotal phase
III studies (38, 39)]. Figure adapt-
ed from the 2013 Commiee for
Medicinal Products for Human Use
assessment report on Lidocaine/Pri-
locaine (40).
Fig. 7 - Change in the geometric
mean intravaginal ejaculaon la-
tency me (IELT) over 12 months in
paents treated with Fortacin™ or
placebo [combined data from the
double-blind and open-label phases
of both pivotal phase III studies (38,
39)]. Figure adapted from Wyllie and
Powell 2012 (2).
Porst and Burri S9
© 2017 The Authors. Published by Wichg Publishing
which was most likely due to improved sexual condence (2).
By prolonging IELT with repeated use of the topical spray, pre-
sumably via acvity on neuro-biogenic factors, a paent’s psy-
chological mindset may be posively inuenced, which may
improve his condence and ability to control ejaculaon with
further improvement in the signs and symptoms of PE (2).
PE involves a complex sensory pathway controlled by the
SEG, which can be targeted for the treatment of PE at two
main sites: in the CNS, where SSRIs increase serotonin levels,
leading to a delay in the transmission of ejaculaon process-
ing neural smuli, and at the level of penile sensory receptors,
where topical anesthecs can reduce penile sensivity and af-
ferent sensory neural smuli. Hence, Fortacin™ could be con-
sidered not only as an alternave therapy to SSRIs but also,
because of their dierent site of acon, as an adjuncve ther-
apy to oral SSRIs in severe PE paents. It is also apparent that
paents with PE are somemes not sased when treated
regularly with SSRIs and therefore the addion of Fortacin™
to a paents’ regular SSRI regimen may be advantageous.
Conclusions
PE can have detrimental eects on the quality of life of the
paent and his partner with a negave impact on emoons,
habits, and behavior, ulmately aecng the relaonship and
even leading to relaonship break-ups. It is obvious that ad-
equate and ecient medical help is needed to address this
debilitang condion. Fortacin™ is the rst ocially approved
topical prescripon therapy for the treatment of primary PE in
adult men. Its formulaon opmizes fast penetraon through
the glans surface while the metered-dose spray delivery sys-
tem allows the desensizing agents, lidocaine and prilocaine,
to be deposited in a dose-controlled, concentrated lm onto
the glans penis. This leads to a reducon in penile sensivity,
thus delaying the ejaculatory latency me without adversely
aecng the sensaon of ejaculaon. The ecacy and safety
of Fortacin™ have been proven in numerous large scale studies
with improvements demonstrated in ejaculatory latency, con-
trol, and sexual sasfacon. The topical spray has a good safety
prole with only a low incidence of mild-to-moderate local AEs
seen in paents and partners, and is unlikely to be associated
with systemic side eects. Overall, Fortacin™ signicantly im-
proves the quality of the sexual performance, has a durable
eect over me, and may help break the vicious cycle of PE.
Disclosures
Financial support: Medical wring assistance was provided by
Dr. Melanie Ga, PhD, on behalf of Health Publishing & Services Srl.
This was funded by Recorda.
Conict of interest: AB is an advisory board member and consultant
for A. Menarini Pharmaceucals. Hartmut Porst is a consultant and
speaker for Berlin Chemie/Menarini group and Recorda.
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