Trade Name
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CASBOL
SEROXAT
AROPAX
PAXIL
TAGONIS
FROSINOR
DEROXAT
SEREUPIN
MOTIVAN
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Generic Name
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paroxetine (INN)
paroxetine hydrochloride (INN)
paroxetine mesylate (USAN)
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Lab Code
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FR 7051
BRL 29060
BRL 29060A
SI 211103
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Latest News
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20 March 2006: On 23 January 2006 GlaxoSmithKline reported that paroxetine hydrochloride has been approved in Japan for the treatment of obsessive compulsive disorder. Filings seeking approval of the product in Japan for the treatment of social anxiety disorders, generalized anxiety disorders and post-traumatic stress disorders are planned. In addition, it was reported that the CDFS's Committee on Safety of Drugs has approved a change in the labeling of paroxetine in Japan, involving removing use of the drug in patients with major depressive disorder under the age of 18 as a contraindication, and including this information as a special precaution. ....Paroxetine hydrochloride, a 5HT reuptake inhibitor, is marketed in most countries worldwide for the treatment of depression, panic disorder and obsessive compulsive disorders, and has been approved in several countries for the treatment of social anxiety disorder and generalized anxiety disorder.
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Minor Update
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03 Aug 2009 Analyst prediction.
27 Jul 2009 Chemical data added.
27 Jul 2009 Synonyms added.
06 Jul 2009 Patent data added.
29 Jun 2009 Indexing modified.
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Licensor
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Novo Nordisk
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Licensee
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FAES
Han Dok Remedia
Janssen-Cilag
Novartis
Ravizza
Solvay
GlaxoSmithKline
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Latest Phase
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Marketed
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Active Program
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Yes
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Indication
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depression
obsessive compulsive disorder
anxiety
panic disorder
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Action
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5HT reuptake inhibitor
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Mode of Administration
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oral
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Class Description
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SSRI antidepressants (N6A4)
Tranquillisers (N5C)
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Company
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Novo Nordisk (Denmark)
FAES (Spain)
Han Dok Remedia (South Korea)
sanofi-aventis (France)
Janssen-Cilag (Belgium)
Johnson & Johnson (USA)
Novartis (Switzerland)
Ravizza (Italy)
BASF (Germany)
Solvay (Belgium)
GlaxoSmithKline (UK)
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Franchise
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Company
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Nationality
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Corporation
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Corp Nationality
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Relationship
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License Region
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Novo Nordisk
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Denmark
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Novo Nordisk
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Denmark
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licensor
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FAES
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Spain
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FAES
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Spain
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licensee
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Spain
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Han Dok Remedia
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South Korea
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sanofi-aventis
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France
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licensee
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South Korea
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Janssen-Cilag
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Belgium
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Johnson & Johnson
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USA
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licensee
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USA
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Novartis
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Switzerland
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Novartis
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Switzerland
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licensee
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Spain
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Ravizza
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Italy
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BASF
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Germany
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licensee
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Italy
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Solvay
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Belgium
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Solvay
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Belgium
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licensee
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Spain
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GlaxoSmithKline
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UK
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GlaxoSmithKline
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UK
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licensee : licensor
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Worldwide
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Country Status
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Phase
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Country
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Indication
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Marketed
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Worldwide
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depression
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Registered
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UK
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anxiety
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Registered
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USA
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anxiety
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Registered
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USA
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panic disorder
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Registered
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USA
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obsessive compulsive disorder
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Registered
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Canada
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anxiety
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Registered
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Japan
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obsessive compulsive disorder
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Chemical Name
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(3S,4R)-3-[(1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine
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CAS Number
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61869-08-7 paroxetine
110429-35-1 paroxetine
hydrochloride hemihydrate (1:1:0.5)
78246-49-8 paroxetine
hydrochloride (1:1)
121368-57-8 paroxetine
hydrobromide (1:1)
64006-44-6 paroxetine maleate
(1:1)
217797-14-3 paroxetine
mesylate (1:1)
63952-24-9 replaced by
61869-08-7
172501-13-2 replaced by
78246-49-8
217797-12-1 replaced by
64006-44-6
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Patentee
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Ferrosan
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Patent Data
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Product (Ferrosan;
paroxetine): GB 1422263 1976, priority GB 4496 1973. Equivalents
identified. Product (paroxetine HCl, crystalline): EP 223403 B
1993, priority GB 26407 1985. Equivalents identified.
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Dev. Summary
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Commercial overview
Paroxetine (SEROXAT;PAXIL), a
5HT reuptake inhibitor, was first launched in the UK in February
1991 for the treatment of depression, and has since been marketed
in more than 50 countries worldwide. Paroxetine is also approved
in several territories for the treatment of panic disorder,
obsessive compulsive disorder and social anxiety disorder.
Paroxetine hydrochloride is also approved in the USA and Canada
for the treatment of generalized anxiety disorder (GAD) and in the
USA and Europe for the treatment of post-traumatic stress disorder
(PTSD). In 1973, Ferrosan, a subsidiary of Novo Nordisk, filed a
priority product patent application for paroxetine in the UK.
GlaxoSmithKline and Janssen have signed an agreement to co-promote
paroxetine in the USA. Ravizza has rights to co-promote paroxetine
in Italy with GlaxoSmithKline and in Spain with Novartis, Fournier
(now known as Solvay) and Faes.
Launches
Paroxetine was launched for
depression in the UK, its first market, in February 1991. It has
since been marketed in over 50 countries, including the USA,
Canada, Europe, Latin America, South Africa, New Zealand and
Japan. A controlled-release formulation of paroxetine (PAXIL CR)
has been approved in the USA for the treatment of panic disorder,
premenstrual dysphoric disorder and social anxiety disorder.
Regulatory progress
GlaxoSmithKline has received
follow up approval in many markets for paroxetine as a treatment
for panic disorder and for obsessive compulsive disorders.
Approval has also been obtained in some markets including the UK
(SmithKline Beecham, OCT 1998) and USA (SmithKline Beecham, MAY
1999) for social anxiety disorder. GlaxoSmithKline has
additionally received US approval for the use of paroxetine in
generalized anxiety disorder (GAD) (GlaxoSmithKline, APR 2001).
The product has also been approved for this indication in Canada
(GlaxoSmithKline, OCT 2001). Paroxetine was approved for the
treatment of post-traumatic stress disorder (PTSD) in Europe in
September 2000 and in the USA in December 2001. Paroxetine has
been approved in Japan for the treatment of obsessive compulsive
disorder. Filings seeking approval of the product in Japan for the
treatment of social anxiety disorders, generalized anxiety
disorders and post-traumatic stress disorders are planned (Pharma
Japan, FEB 2006). The European Medicines Evaluation Agency has
begun a safety review of paroxetine because of concern that the
drug causes suicidal tendencies (EMEA, JUN 2003). The US FDA and
the UK MCA ruled in June 2003 that the drug should not be given to
children. The CDFS's Committee on Safety of Drugs has approved a
change in the labeling of paroxetine in Japan, to remove use of
the drug in patients with major depressive disorder under the age
of 18 as a contraindication, and to include this information as a
special precaution (Pharma Japan, FEB 2006).
Controlled-release
formulation
Approval was obtained in the
USA in February 2002 for a controlled release formulation of
paroxetine for panic disorder (GlaxoSmithKline, APR 2002). The
controlled release formulation, PAXIL CR, was approved for
continuous treatment of premenstrual dysphoric disorder (PMDD) in
August 2003. In October 2003 PAXIL CR was approved for social
anxiety disorder.
R&D progress
A trial of paroxetine
involving over 1200 patients with generalized anxiety disorder
(GAD) in the USA, Europe and Canada has been conducted to
determine therapeutic efficacy and safety of the compound for this
indication (SmithKline Beecham, MAY 2000).
SmithKline Beecham reviewed,
OCT 1997. GlaxoSmithKline, confirmed status, FEB 2003.
GlaxoSmithKline confirmed status, DEC 2003.
Licensing/Partnering
Paroxetine was originally
developed by Ferrosan, a subsidiary of Novo Nordisk, which retains
rights to it in Scandinavia. Novo Nordisk markets the product in
Scandinavia.
In the USA, GlaxoSmithKline
and Janssen have signed an agreement to co-promote paroxetine with
Janssen's risperidone.
Ravizza will co-promote
paroxetine with GlaxoSmithKline in Italy, and with Novartis,
Fournier (now known as Solvay) and Faes in Spain.
Analyst predictions
Latest prediction
Analyst, Morgan Stanley,
reporting on GlaxoSmithKline, estimates sales for SEROXAT/PAXIL
(paroxetine hydrochloride) of STG534 million in 2009, STG480
million in 2010, STG432 million in 2011 and STG389 million in 2012
(Morgan Stanley, JUL 2009).
Morgan Stanley
Analyst, Morgan Stanley,
reporting on GlaxoSmithKline, estimates sales for SEROXAT/PAXIL
(paroxetine hydrochloride) of STG551 million in 2007, STG480
million in 2008, STG436 million in 2009, STG396 million in 2010,
STG361 million in 2011, STG330 million in 2012 and STG302 million
in 2013 (Morgan Stanley, JUL 2007).
Merrill Lynch
Analyst, Merrill Lynch,
reporting on GlaxoSmithKline, estimates sales for PAXIL
(paroxetine hydrochloride) of STG590 million in 2007, 2008, STG433
million in 2009, STG365 million in 2010, STG332 million in 2011
and STG304 million in 2012 (Merrill Lynch, JUN 2007).
Morgan Stanley
Analyst, Morgan Stanley,
reporting on GlaxoSmithKline, estimates sales for SEROXAT/PAXIL
(paroxetine hydrochloride) of STG567 million in FY2007, STG492
million in FY2008, STG447 million in FY2009, STG407 million in
FY2010, STG371 million in FY2011, STG339 million in FY2012 and
STG311 million in FY2013 (Morgan Stanley, MAR 2007).
Analyst, Morgan Stanley,
reporting on GlaxoSmithKline, estimates sales for SEROXAT
(paroxetine hydrochloride) of STG632 million in FY2006, STG509
million in FY2007, STG452 million in FY2008, STG411 million in
FY2009, STG374 million in FY2010, STG342 million in FY2011 and
STG313 million in FY2012 (Morgan Stanley, SEP 2006).
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Scientific Summary
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Preclinical data
Paroxetine is a
phenylpiperidine which acts by specifically inhibiting the
reuptake of 5HT into brain neurons.
Clinical data
Paroxetine had comparable
efficacy to amitriptyline but a better side effect profile. Trial
results showed an elevation of mood in patients usually within 14
days from start of treatment as well as an improvement on the
Hamilton depression rating scale and the clinical global
impression scale.
Results from a study of
paroxetine on seizure length during electroconvulsive therapy
showed the mean length of seizures of the paroxetine group to be
about twice that of the control group (who were taking tricyclic
antidepressants) (Curran, S., EMBASE: 95248259).
In panic disorder, paroxetine
was as active as clomipramine, may have been faster acting and
better tolerated, and was effective for at least one year. In a
ten-week study, paroxetine was significantly better than placebo
at reducing the number of panic attacks, and in patients switched
to placebo after paroxetine treatment, relapse risk was
significantly greater than those patients maintained on
paroxetine. Side effects in clinical trials for panic disorder and
obsessive compulsive disorder with an incidence of 10% or greater
were sleepiness, nausea, dry mouth, constipation, dizziness,
tremor, abnormal ejaculation, sweating, and weakness.
Results from a comparative
meta-analysis study indicated that paroxetine is an effective
alternative first-line therapy for treatment of depression in the
elderly (Dunbar, G.C., EMBASE: 95262866).
In patients with social
phobia, treatment with paroxetine resulted in greater reductions
in the Liebowitz Social Anxiety Scale from baseline than for
placebo (SmithKline Beecham, APR 1998; 11th World Congress of
Psychiatry, AUG 1999).
Results of two double-blind,
placebo-controlled, multicenter trials involving 897 patients with
generalized anxiety disorder (GAD) showed that administration of
the drug resulted in a 60% reduction of anxiety symptoms as
measured by the Hamilton Anxiety Scale (GlaxoSmithKline, APR
2001).
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History
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JAN 2006 Registered, Japan
(obsessive compulsive disorder).
JUL 2005 Fournier acquired by
Solvay.
MAR 2002 Phase III, USA,
Europe, (PMDD - controlled release formulation).
FEB 2002 Registered, USA
(panic disorder - controlled release formulation).
DEC 2001 Registered, USA
(PTSD).
APR 2001 Registered, USA
(GAD).
SEP 2000 Registered, Europe
(PTSD).
2000 Pre-registration, USA,
Canada (GAD). Marketed, Japan.
MAY 1999 Registered, USA
(social anxiety).
OCT 1998 Registered, UK
(social anxiety).
MAR 1997 Registered,
Australia (panic, OCD).
1996 Marketed, Norway.
MAY 1996 Registered, USA
(panic disorder, OCD). Phase III, Japan.
SEP 1995 Registered, Austria
(panic disorder, OCD). Phase III, South Korea.
MAR 1995 Marketed, France.
MAY 1994 Marketed, Peru.
1993 Marketed, Canada,
Switzerland, Brazil, Belgium, Hong Kong, Austria, Greece, Mexico,
Chile, Venezuela, Denmark.
SEP 1993 Copromotion
agreement with Ravizza, Italy.
APR 1993 Care program
established, USA.
JAN 1993 Marketed, USA.
DEC 1992 Marketed, Finland,
Spain. Registered, USA.
OCT 1992 Recommended for
approval, USA. Marketed, Germany. Registered, Spain, Greece,
France, New Zealand.
JUL 1992 Marketed, South
Africa. Phase II, Japan.
MAR 1992 Marketed,
Netherlands. Registered, Italy, South Africa.
SEP 1991 Marketed, Sweden.
JUN 1991 Marketed, Ireland.
MAR 1991 Marketed, UK.
DEC 1990 Registered, UK.
JAN 1990 Pre-registration,
Scandinavia, USA.
SEP 1989 Pre-registration,
UK.
MAY 1988 Pre-registration,
Denmark.
FEB 1988 Phase III, USA.
NOV 1986 Phase III, France,
West Germany.
JUL 1986 Phase III, Denmark.
MAR 1986 Phase III, UK.
NOV 1985 Phase III, Europe.
OCT 1985 Priority product
(paroxetine HCl, crystalline) patent application filed in the UK,
by Ferrosan.
MAY 1984 Phase II, Denmark.
FEB 1983 Phase I, Denmark.
OCT 1980 License agreement
with SmithKline Beecham.
JAN 1973 Priority product
(paroxetine) patent application filed in the UK, by Ferrosan.
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