JAMP PAROXETINE TABLETS

Canada - English - Health Canada

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Active ingredient:
PAROXETINE (PAROXETINE HYDROCHLORIDE)
Available from:
JAMP PHARMA CORPORATION
ATC code:
N06AB05
INN (International Name):
PAROXETINE
Dosage:
30MG
Pharmaceutical form:
TABLET
Composition:
PAROXETINE (PAROXETINE HYDROCHLORIDE) 30MG
Administration route:
ORAL
Units in package:
100
Prescription type:
Prescription
Therapeutic area:
SELECTIVE-SEROTONIN REUPTAKE INHIBITORS
Product summary:
Active ingredient group (AIG) number: 0123131001; AHFS: 28:16.04.20
Authorization status:
APPROVED
Authorization number:
02507803
Authorization date:
2020-11-17

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Page 1 of 57

PRODUCT MONOGRAPH

Pr

JAMP Paroxetine Tablets

Paroxetine Tablets USP

10 mg, 20 mg, 30 mg paroxetine (as paroxetine hydrochloride)

Antidepressant – Antiobsessional – Antipanic – Anxiolytic Agent –

Social Phobia (Social Anxiety Disorder) - Posttraumatic Stress Disorder Therapy

JAMP Pharma Corporation

1310, rue Nobel

Boucherville, Québec

J4B 5H3

Date of Preparation:

November 12, 2020

Submission Control No.: 236302

.

Page 2 of 57

Table of Contents

PART I: HEALTH PROFESSIONAL INFORMATION .........................................................3

SUMMARY PRODUCT INFORMATION .........................................................................3

INDICATIONS AND CLINICAL USE ..............................................................................3

CONTRAINDICATIONS ....................................................................................................5

WARNINGS AND PRECAUTIONS ..................................................................................6

ADVERSE REACTIONS ..................................................................................................14

DRUG INTERACTIONS ..................................................................................................24

DOSAGE AND ADMINISTRATION ..............................................................................29

OVERDOSAGE .................................................................................................................33

ACTION AND CLINICAL PHARMACOLOGY .............................................................34

STORAGE AND STABILITY ..........................................................................................36

DOSAGE FORMS, COMPOSITION AND PACKAGING ..............................................37

PART II: SCIENTIFIC INFORMATION ................................................................................38

PHARMACEUTICAL INFORMATION ..........................................................................38

CLINICAL TRIALS ..........................................................................................................39

DETAILED PHARMACOLOGY .....................................................................................41

TOXICOLOGY .................................................................................................................43

REFERENCES ...................................................................................................................46

PART III: CONSUMER INFORMATION ..............................................................................52

Page 3 of 57

Pr

JAMP Paroxetine Tablets

Paroxetine Tablets USP

PART I: HEALTH PROFESSIONAL INFORMATION

SUMMARY PRODUCT INFORMATION

Route of

Administration

Dosage Form /

Strength

Nonmedicinal Ingredients

Oral

Tablet / 10 mg, 20 mg,

30 mg

Dicalcium phosphate dihydrate,

hydroxypropyl methylcellulose, magnesium

stearate, polyethylene glycol, polysorbate

sodium starch glycolate, titanium

dioxide,

and one or more of the following:

D&C Red

No. 30 aluminum lake, D&C

Yellow No. 10

aluminum lake, FD&C Blue

No. 2 aluminum

lake, FD&C Yellow No. 6 aluminum lake.

INDICATIONS AND CLINICAL USE

Adults

Depression

JAMP Paroxetine Tablets

(paroxetine tablets) is indicated for symptomatic relief of

Major Depressive Disorder (MDD).

Clinical trials have provided evidence that continuation treatment with paroxetine

tablets

patients with moderate to moderately severe depressive disorder is effective

for at least

6 months (see Clinical Trials, Depression).

Obsessive-Compulsive Disorder

JAMP Paroxetine Tablets

is indicated for the symptomatic treatment of obsessive-

compulsive disorder

(OCD). The obsessions or compulsions must be experienced as

intrusive, markedly

distressing, time-consuming, or interfering significantly with the

person’s social or

occupational functioning.

Page 4 of 57

Panic Disorder

JAMP Paroxetine Tablets

is indicated for the symptomatic treatment of panic disorder,

with or without

agoraphobia.

Panic disorder (DSM-IV) is characterized by recurrent unexpected panic attacks, i.e., a

discrete period of intense fear or discomfort in which four (or more) of the following

symptoms develop abruptly and reach a peak within 10 minutes: (1) palpitations,

pounding heart, or accelerated heart rate; (2) sweating; (3) trembling or shaking; (4)

sensations of shortness of breath or smothering; (5) feeling of choking; (6) chest pain or

discomfort; (7) nausea or abdominal distress; (8) feeling dizzy, unsteady, lightheaded, or

faint; (9) derealization (feelings of unreality) or depersonalization (being detached from

oneself); (10) fear of losing control; (11) fear of dying; (12) paresthesias (numbness or

tingling sensations); (13) chills or hot flushes.

Social Phobia (Social Anxiety Disorder)

JAMP Paroxetine Tablets

is indicated for the symptomatic relief of generalized social

phobia (social

anxiety disorder), a disorder characterized by marked and persistent fear,

anxious

anticipation, or avoidance of multiple social situations (e.g. interacting with

strangers,

attending social gatherings, dealing with authority figures) and/or performance

situations

(e.g. eating, writing, working while being observed, or public speaking). A

diagnosis of social phobia/social anxiety disorder should not be made unless the fear,

anxious

anticipation, or avoidance of social and/or performance situations interferes

significantly

with the person’s normal routine, occupational functioning, social life, or

causes marked

distress.

Generalized Anxiety Disorder

JAMP Paroxetine Tablets

is indicated for the symptomatic relief of anxiety causing

significant distress in

patients with Generalized Anxiety Disorder (GAD).

Posttraumatic Stress Disorder

JAMP Paroxetine Tablets

is indicated for the symptomatic treatment of posttraumatic

stress disorder

(PTSD).

PTSD as defined by DSM-IV requires exposure to a traumatic event that involved actual

or threatened death or serious injury, or threat to the physical integrity of self or others,

and a response which involves intense fear, helplessness, or horror. Symptoms that occur

as a result of exposure to the traumatic event include re-experiencing of the event in the

form of intrusive thoughts, flashbacks or dreams, and intense psychological distress and

physiological reactivity on exposure to clues to the event; avoidance of situations

reminiscent of the traumatic event, inability to recall details of the event, and/or numbing

of general responsiveness manifested as diminished interest in significant activities,

estrangement from others, restricted range of affect, or sense of foreshortened future; and

symptoms of autonomic arousal including hypervigilance, exaggerated startle response,

sleep disturbance, impaired concentration, and irritability or outbursts of anger.

Page 5 of 57

A diagnosis of PTSD requires that the symptoms are present for at least one month and

that they cause clinically significant distress or impairment in social, occupational, or

other important areas of functioning.

Long-Term Use Of JAMP Paroxetine Tablets

The effectiveness of paroxetine tablets

in long-term use (i.e. more than 8 weeks for GAD and

12 weeks for other indications) has not yet been established in controlled trials for OCD,

panic disorder, social phobia (social anxiety disorder), generalized anxiety disorder and

posttraumatic stress disorder. Therefore, the physician who elects to use JAMP

Paroxetine Tablets

extended periods in these indications should periodically re-

evaluate the long-term

usefulness of the drug for individual patients (see DOSAGE

AND ADMINISTRATION, Dosing Considerations).

Geriatrics (> 65 years of age)

Evidence from clinical studies indicates that there are differences in the pharmacokinetic

profile of paroxetine in the geriatric population relative to younger adults, which may be

associated with differences in safety or effectiveness. A brief discussion can be found in

the appropriate sections (see WARNINGS AND PRECAUTIONS, Special Populations-

Geriatrics; ACTIONS AND CLINICAL PHARMACOLOGY; DOSAGE AND

ADMINISTRATION).

Pediatrics (< 18 years of age)

JAMP Paroxetine Tablets

is not indicated for use in patients below the age of 18

years (see

WARNINGS AND PRECAUTIONS, General, Potential Association

With Behavioural and Emotional Changes, Including Self-Harm)

CONTRAINDICATIONS

Hypersensitivity: JAMP Paroxetine Tablets

is contraindicated in patients who are

known to be

hypersensitive to the drug or any of its components. For a complete

listing, see

DOSAGE FORMS, COMPOSITION AND PACKAGING.

Monoamine Oxidase Inhibitors: In patients receiving serotonin reuptake inhibitors

(SSRIs) in combination with a MAO inhibitor, there have been reports of serious,

sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic

instability with possible rapid fluctuations of vital signs, and mental status changes that

include extreme agitation progressing to delirium and coma. These reactions have also

been reported in patients who have recently discontinued SSRI treatment and have begun

treatment on a MAO inhibitor. Some cases presented with features resembling serotonin

syndrome or neuroleptic malignant syndrome (see WARNINGS AND PRECAUTIONS,

Serotonin Syndrome/Neuroleptic Malignant Syndrome). Therefore, JAMP Paroxetine

Tablets

should not

be used in combination with MAO inhibitors [including linezolid, an

antibiotic which is a

reversible non-selective MAO inhibitor and methylthioninium

chloride (methylene blue)]

or within a minimum of 2 weeks of terminating treatment

with MAO inhibitors.

Treatment with JAMP Paroxetine Tablets

should then be initiated cautiously and dosage

increased gradually until optimal response is reached. MAO inhibitors should not be

introduced

within 2 weeks of cessation of therapy with JAMP Paroxetine Tablets.

Page 6 of 57

Thioridazine: Thioridazine administration alone produces prolongation of the QTc

interval, which is associated with serious ventricular arrhythmias, such as torsade de

pointes-type arrhythmias, and sudden death. This effect appears to be dose-related.

An in vivo study suggests that drugs which inhibit P450 2D6, including certain SSRIs

such as paroxetine, fluoxetine and fluvoxamine, will elevate plasma levels of

thioridazine. Therefore, JAMP Paroxetine Tablets

should not be used in combination with

thioridazine or

within a minimum of 2 weeks of terminating treatment with thioridazine.

At least 2 weeks should be allowed after discontinuing JAMP Paroxetine Tablets

therapy

before initiating treatment with thioridazine.

Pimozide: The concomitant use of JAMP Paroxetine Tablets

and pimozide is

contraindicated as paroxetine tablets

has been shown to increase plasma pimozide levels.

Elevation of pimozide blood

concentration may result in QT interval prolongation and

severe arrhythmias including

torsade de pointes (see Drug Interactions).

WARNINGS AND PRECAUTIONS

General

POTENTIAL ASSOCIATION WITH BEHAVIOURAL AND EMOTIONAL

CHANGES, INCLUDING SELF-HARM.

Pediatrics: Placebo-Controlled Clinical Trial Data

Recent analyses of placebo-controlled clinical trial safety databases from

SSRIs and other newer antidepressants suggests that use of these drugs in

patients under the age of 18 may be associated with behavioural and

emotional changes, including an increased risk of suicidal ideation and

behaviour over that of placebo.

The small denominators in the clinical trial database, as well as the

variability in placebo rates, preclude reliable conclusions on the relative

safety profiles among these drugs.

Adult and Pediatrics: Additional data

There are clinical trial and post-marketing reports with SSRIs and other

newer antidepressants, in both pediatrics and adults, of severe agitation-type

adverse events coupled with self-harm or harm to others. The agitation-type

events include: akathisia, agitation, disinhibition, emotional lability, hostility,

aggression, and depersonalization. In some cases, the events occurred within

several weeks of starting treatment.

Page 7 of 57

Rigorous clinical monitoring for suicidal ideation or other indicators of potential for

suicidal behaviour is advised in patients of all ages. This includes monitoring for

agitation-type emotional and behavioural changes.

An FDA meta-analysis of placebo-controlled clinical trials of antidepressant drugs in

adult patients ages 18 to 24 years with psychiatric disorders showed an increased risk of

suicidal behaviour with antidepressant compared to placebo.

Discontinuation Symptoms: Patients currently taking JAMP Paroxetine Tablets

should NOT be discontinued abruptly, due to risk of discontinuation symptoms.

At the time that a medical decision is made to discontinue an SSRI or other newer

antidepressant drug, a gradual reduction in the dose rather than an abrupt

cessation is

recommended.

Discontinuation of Treatment with JAMP Paroxetine Tablets

When discontinuing treatment, regardless of the indication for which JAMP Paroxetine

Tablets

is being prescribed, patients should be monitored for symptoms which may be

associated with

discontinuation (e.g. dizziness, sleep disturbances including abnormal

dreams, sensory

disturbances (including paresthesias, electric shock sensations and

tinnitus), agitation,

anxiety, headache, tremor, confusion, diarrhea, nausea, vomiting and

sweating) or other

symptoms which may be of clinical significance [see ADVERSE

REACTIONS, Adverse Events following Discontinuation of Treatment (or Dose

Reduction)-Post-Marketing]. A

gradual reduction in the dose rather than abrupt cessation

is recommended whenever

possible. If intolerable symptoms occur following a decrease

in the dose or upon discontinuation of treatment, dose titration should be managed on the

basis of the patient’s clinical response (see ADVERSE REACTIONS and DOSAGE

AND ADMINISTRATION).

JAMP Paroxetine Tablets

Treatment During Pregnancy Effects on Newborns

Epidemiological studies of pregnancy outcomes following maternal exposure to

antidepressants in the first trimester have reported an increase in the risk of congenital

malformations, particularly cardiovascular (e.g. ventricular and atrial septal defects),

associated with the use of paroxetine. If a patient becomes pregnant while taking

JAMP

Paroxetine Tablets, consideration should be given to switching to other treatment options.

Treatment with JAMP Paroxetine Tablets

should only be continued for an individual

pregnant patient, if

the potential benefits outweigh the potential risks. Initiation of

paroxetine, for women

who intend to become pregnant, or are in their first trimester of

pregnancy, should be

considered only after other treatment options have been evaluated

(see WARNINGS AND PRECAUTIONS, Special Populations).

Post-marketing reports indicate that some neonates exposed to paroxetine tablets, SSRIs

(Selective

Serotonin Reuptake Inhibitors), or other newer antidepressants late in the

third trimester

have developed complications requiring prolonged hospitalization,

respiratory support,

and tube feeding. Such complications can arise immediately upon

delivery. When

treating a pregnant woman with JAMP Paroxetine Tablets

during the

third trimester, the physician should carefully consider the potential risks and benefits of

treatment (see WARNINGS AND PRECAUTIONS, Special Populations and DOSAGE

AND ADMINISTRATION, Special Patient Populations-Treatment of Pregnant Women

Page 8 of 57

During the Third Trimester).

Sexual Dysfunction

Selective serotonin reuptake inhibitors (SSRIs) may cause symptoms of sexual

dysfunction (see ADVERSE REACTIONS, Male and Female Sexual Dysfunction with

SSRIs). Patients should be informed that there have been reports of long-lasting sexual

dysfunction where the symptoms have continued despite discontinuation of SSRIs.

Potential for reduced efficacy of Tamoxifen with concomitant SSRI use, including

JAMP Paroxetine Tablets

The antitumor agent tamoxifen is a pro-drug requiring metabolic activation by CYP2D6.

Inhibition of CYP2D6 can lead to reduced plasma concentrations of a primary active

metabolite (endoxifen). Chronic use of CYP2D6 inhibitors, including certain SSRIs,

together with tamoxifen can lead to persistent reduction in levels of endoxifen (see also

DRUG INTERACTIONS, Tamoxifen). Some studies have shown that the efficacy of

tamoxifen, as measured by the risk of breast cancer relapse/mortality, may be reduced

when coprescribed with JAMP Paroxetine Tablets

as a result of paroxetine’s irreversible

inhibition of CYP2D6. This risk may increase with longer duration of coadministration.

When

tamoxifen is used for the treatment of breast cancer, prescribers should consider

using an

alternative antidepressant with little or no CYP2D6 inhibition.

Psychomotor Impairment

Although paroxetine did not cause sedation or interfere with psychomotor performance in

placebo-controlled studies in normal subjects, patients should be advised to avoid driving

a car or operating hazardous machinery until they are reasonably certain that JAMP

Paroxetine Tablets

does not affect them adversely.

Bone Fracture Risk

Epidemiological studies show an increased risk of bone fractures following exposure to

some antidepressants, including SSRIs. The risks appear to be greater at the initial stages

of treatment, but significant increased risks were also observed at later stages of

treatment. The possibility of fracture should be considered in the care of patients treated

with JAMP Paroxetine Tablets. Elderly patients and patients with important risk factors

for bone fractures should be advised of possible adverse events which increase the risk of

falls, such as dizziness and orthostatic hypotension, especially at the early stages of

treatment but also

soon after withdrawal. Preliminary data from observational studies

show association of SSRIs and low bone mineral density in older men and women. Until

further information

becomes available, a possible effect on bone mineral density with

long-term treatment

with SSRIs, including JAMP Paroxetine Tablets, cannot be

excluded, and may be a potential concern for patients with osteoporosis or major risk

factors for bone fractures.

The following additional precautions are listed alphabetically.

Carcinogenesis and Mutagenesis

See TOXICOLOGY for animal data.

Page 9 of 57

Cardiovascular

Paroxetine tablets

has not been evaluated or used to any appreciable extent in patients

with a

recent history of myocardial infarction or unstable heart disease. The usual

precautions

should be observed in patients with cardiac conditions.

Concomitant Illnesses

Clinical experience with paroxetine tablets

in patients with certain concomitant systemic

illnesses

is limited.

Caution is advisable in using JAMP Paroxetine Tablets

in patients with

diseases or conditions

that could affect metabolism or hemodynamic responses.

Dependence Liability

Paroxetine tablets

has not been systematically studied, in animals or humans, for its potential

for abuse, tolerance, or physical dependence. Physicians should carefully evaluate patients

history of drug abuse and follow such patients closely, observing them for signs of misuse or

abuse of JAMP Paroxetine Tablets.

Endocrine and Metabolism

Serum Cholesterol Elevation: Several public domain studies have shown increased

LDL-

cholesterol levels of ~10% in volunteers and patients taking paroxetine for 8 to 12

weeks,

which generally normalized after paroxetine discontinuation. In addition, of the

patients in

placebo-controlled clinical trials for whom baseline and on-treatment

measurements were

taken, total serum levels of cholesterol showed a mean increase of ~ 1.5 mg/dL in paroxetine-

treated patients (n = 653), compared to a mean decrease of ~ 5.0 mg/dL in placebo-treated

patients (n = 379). Increases from baseline of 45 mg/dL

or greater were recorded in 6.6% of

paroxetine-treated patients compared to 2.6% of placebo-treated patients (see Monitoring and

Laboratory Tests, Serum Cholesterol

Elevation).

These data should be taken into consideration when treating patients with underlying

cardiac

risk factors.

Hematologic

Abnormal Bleeding: SSRIs including JAMP Paroxetine

Tablets

may increase the risk of

bleeding events by causing abnormal platelet aggregation. Concomitant use of acetylsalicylic

acid

(ASA), nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin and other

anticoagulants may add to the risk. Case reports and epidemiological studies (case- control

and cohort design) have demonstrated an association between use of drugs that

interfere with

serotonin reuptake and the occurrence of gastrointestinal bleeding.

Bleeding events related to SSRIs use have ranged from ecchymoses, hematomas, epistaxis,

and petechiae to life-threatening haemorrhages. Gastrointestinal and

gynaecological bleeding

have also been reported following treatment with paroxetine tablets.

Patients should be cautioned about the risk of bleeding associated with the concomitant

use of

JAMP Paroxetine

Tablets

and NSAIDs, ASA, or other drugs that affect coagulation (see

DRUG INTERACTIONS, Drugs Affecting Platelet Function). Caution is advised in patients

with a history of bleeding disorder or predisposing conditions (e.g. thrombocytopenia) (see

ADVERSE REACTIONS).

Page 10 of 57

Hepatic/Biliary/Pancreatic

Hepatic Impairment: Pharmacokinetic studies of paroxetine tablets

in subjects with clinically

significant hepatic impairment suggest that prolongation of the elimination half-life and

increased

plasma levels can be expected in this patient group. JAMP Paroxetine

Tablets

should be used

with

caution and dosages restricted to the lower end of the range in patients with

clinically significant

hepatic impairment (see DOSAGE AND ADMINISTRATION, Special Patient Populations and

ACTIONS AND CLINICAL PHARMACOLOGY, Hepatic Insufficiency).

Immune

Hypersensitivity: The 10 mg tablet coating contains an azo dye (FD&C Yellow No. 6 aluminium

lake) which may cause allergic reactions.

Neurologic

Epilepsy: As with other antidepressants, JAMP Paroxetine

Tablets

should be used with caution in

patients with epilepsy.

Seizures: During clinical trials, the overall incidence of seizures was 0.15% in patients

treated with

paroxetine tablets. However, patients with a history of convulsive disorders were

excluded from

these studies. Caution is recommended when the drug is administered to

patients with a history of

seizures. The drug should be discontinued in any patient who develops seizures.

Serotonin Syndrome/Neuroleptic Malignant Syndrome: On rare occasions serotonin

syndrome

or neuroleptic malignant syndrome-like events have occurred in association with treatment of

paroxetine tablets, particularly when given in combination with other

serotonergic and/or

neuroleptic/antipsychotic drugs. As these syndromes may result in

potentially life-threatening

conditions, treatment with JAMP Paroxetine Tablets

should be discontinued if

patients develop a

combination of symptoms possibly including hyperthermia, rigidity,

myoclonus, autonomic

instability with possible rapid fluctuations of vital signs, mental

status changes including confusion,

irritability, extreme agitation progressing to delirium

and coma, and supportive symptomatic

treatment should be initiated. Due to the risk of serotonergic syndrome or neuroleptic malignant

syndrome JAMP Paroxetine Tablets

should not be used in

combination with MAO inhibitors

[including linezolid, an antibiotic which is a reversible

non-selective MAO inhibitor and

methylthioninium chloride (methylene blue)] or serotonin precursors (such as L-tryptophan,

oxitriptan) and should be used with caution in patients receiving other serotonergic drugs (e.g.,

triptans, lithium, tramadol, St. John’s Wort, most tricyclic antidepressants) or

neuroleptics/antipsychotics (see

CONTRAINDICATIONS and DRUG INTERACTIONS).

Ophthalmologic

Angle-Closure Glaucoma: As with other antidepressants, JAMP Paroxetine Tablets

can cause

mydriasis which may trigger an angle-closure attack in a patient with anatomically narrow ocular

angles. Caution should be used when JAMP Paroxetine Tablets

is prescribed for patients with

untreated

narrow angles. Open-angle glaucoma is not a risk factor for angle-closure glaucoma.

Patients should be informed to seek immediate medical assistance if they experience eye

pain,

changes in vision or swelling or redness in or around the eye.

Page 11 of 57

Psychiatric

Suicide: The possibility of a suicide attempt is inherent in depression and may persist

until

remission occurs. Patients with depression may experience worsening of their depressive

symptoms and/or the emergence of suicidal ideation and behaviours

(suicidality) whether or not

they are taking antidepressant medications. Notwithstanding,

high risk patients should be closely

supervised throughout therapy with appropriate

consideration to the possible need for

hospitalization. In order to minimize the opportunity for overdosage, prescriptions for JAMP

Paroxetine Tablets

should be written for the smallest

quantity of drug consistent with good patient

management.

Because of the well established comorbidity between depression and other psychiatric

disorders, the

same precautions observed when treating patients with depression should

be observed when

treating patients with other psychiatric disorders (see WARNINGS AND PRECAUTIONS,

Potential Association with Behavioural and Emotional Changes, Including Self-Harm).

Activation of Mania/Hypomania: During clinical testing in a patient population

comprised

primarily of unipolar depressed patients, approximately 1% of paroxetine tablets-

treated patients

experienced manic reactions. When bipolar patients were considered as a

sub-group the incidence

of mania was 2%. As with all drugs effective in the treatment of depression, JAMP Paroxetine

Tablets

should be used with caution in patients with a history of mania.

A major depressive episode may be the initial presentation of bipolar disorder. Patients

with bipolar

disorder may be at an increased risk of experiencing manic episodes when

treated with

antidepressants alone. Therefore, the decision to initiate symptomatic

treatment of depression

should only be made after patients have been adequately assessed to determine if they are at risk for

bipolar disorder.

Electroconvulsive Therapy (ECT): The efficacy and safety of the concurrent use of paroxetine

tablets

and ECT have not been studied.

Renal

Hyponatremia: Several cases of hyponatremia have been reported. The hyponatremia

appeared to

be reversible when paroxetine tablets

were discontinued. The majority of these occurrences have

been in elderly individuals, some in patients taking diuretics or who were otherwise volume

depleted.

Renal Impairment: Since JAMP Paroxetine Tablets

is extensively metabolized by the liver

excretion of

unchanged drug in urine is a minor route of elimination. However, single dose

pharmacokinetic studies in subjects with clinically significant renal impairment suggest

that plasma

levels of paroxetine are elevated in such subjects. Paroxetine should therefore be used with caution

and the dosage restricted to the lower end of the range in

patients with clinically significant renal

impairment (see DOSAGE AND

ADMINISTRATION, Special Patient Populations; ACTIONS

AND CLINICAL

PHARMACOLOGY, Renal Insufficiency).

Sexual Function/Reproduction

Sexual Dysfunction: See WARNING AND PRECAUTIONS, Sexual Dysfunction

Page 12 of 57

Sperm Quality: Some clinical studies have shown that SSRIs (including paroxetine tablets) may

affect sperm

quality.

This effect appears to be reversible following discontinuation of treatment.

Changes in sperm quality may affect fertility in some men (see also Part II: TOXICOLOGY,

Reproduction and Impairment of Fertility Studies).

Special Populations

Pregnant Women and Newborns:

Risk of Cardiovascular Malformations following first trimester exposure to SSRIs:

Epidemiological studies of pregnancy outcomes following maternal exposure to antidepressants in

the first trimester have reported an increase in the risk of congenital

malformations, particularly

cardiovascular (e.g. ventricular and atrial septal defects), associated with the use of paroxetine. The

data suggest that the risk of having an infant

with a cardiovascular defect following maternal

paroxetine exposure is approximately 1/50 (2%), compared with an expected rate for such defects of

approximately 1/100 (1%) infants in the general population. In general, septal defects range from

those that are symptomatic and may require surgery, to those that are

asymptomatic and may

resolve spontaneously. Information about the severity of the

septal defects reported in the studies is

not available.

While on JAMP Paroxetine Tablets: Pregnancy, or intent to become pregnant:

If a patient becomes pregnant while taking JAMP Paroxetine Tablets, or intends to become

pregnant, she

should be informed of the current estimate of increased risk to the fetus with JAMP

Paroxetine Tablets

over other antidepressants. Examinations of additional databases, as well as

updated analyses, may result in changes to the current risk estimates. Consideration should be

given to switching to other treatment options, including another antidepressant or non-

pharmaceutical treatment such as cognitive behavioural therapy. Treatment with

JAMP Paroxetine

Tablets

should only be continued for an individual patient, if the potential benefits outweigh the

potential risks.

Due to the potential for discontinuation symptoms, if a decision is taken to discontinue

JAMP

Paroxetine Tablets

treatment, a gradual reduction in the dose rather than an abrupt cessation is

recommended (see WARNINGS AND PRECAUTIONS, Discontinuation of Treatment

With JAMP

Paroxetine Tablets; ADVERSE REACTIONS, Adverse Reactions Following Discontinuation

Treatment and DOSAGE AND ADMINISTRATION, Discontinuation of Treatment).

Initiation of paroxetine: For women who intend to become pregnant, or are in their first

trimester

of pregnancy, initiation of paroxetine should be considered only after other

treatment options have

been evaluated.

Complications following late third trimester exposure to SSRIs:

Post-marketing reports indicate that some neonates exposed to paroxetine tablets, SSRIs (Selective

Serotonin Reuptake Inhibitors), or other newer antidepressants late in the third trimester

have

developed complications requiring prolonged hospitalization, respiratory support, and tube feeding.

Such complications can arise immediately upon delivery. Reported clinical findings have included

respiratory distress, cyanosis, apnea, seizures, temperature

instability, feeding difficulty, vomiting,

hypoglycemia, hypotonia, hypertonia,

hyperreflexia, tremor, jitteriness, irritability, and constant

crying. These features are

consistent with either a direct toxic effect of SSRIs and other newer

antidepressants, or,

possibly, a drug discontinuation syndrome. It should be noted that, in some

Page 13 of 57

cases, the

clinical picture is consistent with serotonin syndrome (see WARNINGS AND

PRECAUTIONS, Neurologic-Serotonin Syndrome/Neuroleptic Malignant Syndrome).

When treating a pregnant woman with JAMP Paroxetine Tablets

during the third trimester, the

physician

should carefully consider the potential risks and benefits of treatment (see DOSAGE

AND ADMINISTRATION, Special Patient Populations-Treatment of Pregnant Women

During the

Third Trimester).

Risk of PPHN and exposure to SSRIs (including paroxetine):

Epidemiological studies on persistent pulmonary hypertension of the newborn (PPHN)

have shown

that the use of SSRIs (including paroxetine tablets) in pregnancy, particularly use in

late pregnancy,

was associated with an increased risk of PPHN. PPHN occurs in 1 to 2 per 1000 live births in the

general population and is associated with substantial neonatal

morbidity and mortality. In a

retrospective case-control study of 377 women whose infants were born with PPHN and 836

women whose infants were born healthy, the risk

for developing PPHN was approximately six-fold

higher for infants exposed to SSRIs after the 20th week of gestation compared to infants who had

not been exposed to antidepressants during pregnancy (Odds Ratio 6.1, 95% CI 2.2-16.8). A study

using data

from the Swedish Medical Birth Register for 831,324 infants born in 1997 to 2005 found

an increased risk of PPHN of approximately 2-fold associated with patient-reported maternal use of

SSRIs in the first trimester of pregnancy (Risk Ratio 2.4, 95% CI 1.2- 4.3), and an increased risk of

PPHN of approximately 4-fold associated with a

combination of patient-reported maternal use of

SSRIs in the first trimester and an

antenatal SSRI prescription in later pregnancy (Risk Ratio 3.6,

95% CI 1.2-8.3).

Nursing Women: The concentrations of paroxetine detected in the breast milk of lactating women

are similar to those in the mother’s plasma. Lactating women should not nurse their infants while

receiving paroxetine unless in the opinion of the treating

physician, breast feeding is necessary, in

which case the infant should be closely

monitored.

Pediatrics (< 18 years of age): JAMP Paroxetine Tablets

is not indicated for use in patients

below the age of 18 years (see WARNINGS AND PRECAUTIONS, Potential Association with

Behavioural and Emotional Changes, Including Self Harm). (See also INDICATIONS,

Pediatrics and DOSAGE AND ADMINISTRATION, Special Patient

Populations-Children).

Controlled clinical studies in depression failed to demonstrate efficacy and do not support the use

of paroxetine in the treatment of children under the age of 18 years with

depression. Moreover, a

higher incidence of adverse events related to behavioural and

emotional changes, including self

harm, was reported with paroxetine treatment compared to placebo during controlled clinical trials

in depression, OCD and social

anxiety disorder (see ADVERSE DRUG REACTIONS, Clinical

Trial Adverse Drug Reactions-Pediatrics).

Geriatrics (≥ 65 years of age): Administration of paroxetine tablets

to the elderly is associated

with increased plasma levels and prolongation of the elimination half life relative to

younger adults

(see ACTION AND CLINICAL PHARMACOLOGY). Elderly patients

should be initiated and

maintained at the lowest daily dose of paroxetine which is associated with clinical efficacy (see

DOSAGE AND ADMINISTRATION).

Evaluation of approximately 800 elderly patients (≥ 65 years) treated with paroxetine tablets

(10 to

40 mg daily) in worldwide premarketing clinical trials revealed no unusual pattern of adverse

events relative to the clinical experience in younger patients. However, it is not

possible to rule out

potential age-related differences in safety and effectiveness during

chronic use, particularly in

Page 14 of 57

elderly patients who have concomitant systemic illnesses or who are receiving concomitant drugs.

Monitoring and Laboratory Tests

Serum Cholesterol Elevation: Of the patients in placebo-controlled clinical trials for whom

baseline and on-treatment measurements were taken, increases from baseline of 45 mg/dL or

greater were recorded in 6.6% of paroxetine-treated patients compared to 2.6% of placebo-

treated patients (see ADVERSE REACTIONS, Laboratory Changes-

Cholesterol and

WARNINGS AND PRECAUTIONS, Endocrine and Metabolism).

These data should be taken into consideration when treating patients with underlying

cardiac

risk factors.

ADVERSE REACTIONS

Adverse Drug Reaction Overview

Commonly Observed Adverse Events:

The most commonly observed adverse experiences associated with the use of paroxetine

tablets

clinical trials and not seen at an equivalent incidence among placebo-treated

patients were: nausea, somnolence, sweating, tremor, asthenia, dizziness, dry mouth,

insomnia,

constipation, diarrhea, decreased appetite and male sexual dysfunction (see Tables

1 and 2).

Adverse Events Leading to Discontinuation of Treatment:

Twenty-one percent of over 4000 patients who received paroxetine tablets

in worldwide

clinical

trials in depression discontinued treatment due to an adverse experience. In

obsessive- compulsive disorder, panic disorder, social phobia (social anxiety disorder),

generalized

anxiety disorder and posttraumatic stress disorder studies, 11.8% (64/542), 9.4%

(44/469), 16.1% (84/522), 10.7% (79/735) and 11.7% (79/676), respectively, of patients

treated with paroxetine tablets

discontinued treatment because of adverse events. The most

common events leading to discontinuation (reported by 1% or more of subjects) included:

asthenia, headache, nausea, somnolence, insomnia, agitation, tremor, dizziness,

constipation,

impotence, abnormal ejaculation, sweating and diarrhea.

Adverse Events following Discontinuation of Treatment (or Dose Reduction)

Clinical Trials

The following adverse events have been reported at an incidence of 2% or greater for

paroxetine tablets

and were at least twice that reported for placebo: abnormal dreams (2.3

vs 0.5%), paresthesias (2.0 vs 0.4%), and dizziness (7.1 vs 1.5%).

The majority of these events were mild to moderate, self-limiting and did not require

medical

intervention. These adverse events were noted in GAD and PTSD clinical trials

employing a

taper phase regimen for discontinuation of treatment. This regimen involved an incremental

decrease in the daily dose by 10 mg/day at weekly intervals. When a daily dose of 20 mg/day

was reached, patients were continued on this dose for 1 week

before treatment was stopped.

Post-Marketing

There have been spontaneous reports of adverse events upon the discontinuation of paroxetine

Page 15 of 57

tablets

(particularly when abrupt), including but not limited to the following: dizziness,

sensory disturbances (including paresthesias, electric shock sensations and tinnitus),

agitation/restlessness, anxiety, nausea, tremor, confusion, diarrhea, vomiting, sweating,

headache, and sleep disturbances (abnormal dreams). Generally these symptoms are mild

moderate, however, in some patients they may be severe in intensity. They usually

occur

within the first few days of discontinuing treatment, but there have been very rare

reports of

such symptoms in patients who have inadvertently missed a dose. Generally these symptoms

are self-limiting and usually resolve within 2 weeks, though in some

individuals they may be

prolonged (2 to 3 months or more). Symptoms associated with

discontinuation have been

reported for other selective serotonin reuptake inhibitors.

Patients should be monitored for these or any other symptoms when discontinuing

treatment,

regardless of the indication for which JAMP Paroxetine Tablets

is being prescribed. If

intolerable symptoms occur following a decrease in the dose or upon discontinuation of

treatment, dose titration should be managed on the basis of the patient’s clinical response (see

WARNINGS AND PRECAUTIONS and DOSAGE AND ADMINISTRATION).

Clinical Trial Adverse Drug Reactions

Because clinical trials are conducted under very specific conditions the adverse

reaction rates observed in the clinical trials may not reflect the rates observed in

practice and should not be compared to the rates in the clinical trials of another drug.

Adverse drug reaction information from clinical trials is useful for

identifying drug-

related adverse events and for approximating rates.

Incidence in Controlled Clinical Trials

Adults

Multiple doses of paroxetine tablets

were administered to 4126 subjects in clinical trials for

depression, 542 subjects in clinical trials for OCD, 469 subjects in clinical trials for panic

disorder, 522 subjects in clinical trials for social phobia (social anxiety disorder),

735 subjects in clinical trials for generalized anxiety disorder and 676 subjects in clinical

trials

for posttraumatic stress disorder. Untoward experiences associated with this

exposure were

recorded by clinical investigators using descriptive terminology of their

own choosing.

Consequently, it is not possible to provide a meaningful estimate of the proportion of

individuals experiencing adverse experiences without first grouping similar types of

untoward

experiences into a limited (i.e. reduced) number of standardized experience

categories.

Table 1 lists adverse experiences that occurred at an incidence of 1% or higher in short

term

(6-week) flexible dose (20 to 50 mg/day) placebo-controlled trials in depression. (An

additional 460 patients participated in a fixed-dose, placebo-controlled study).

Table 2 enumerates adverse events that occurred at a frequency of 2% or more among

patients on paroxetine tablets

who participated in placebo-controlled OCD trials of 12-weeks

duration in which patients were dosed in the range of 20 to 60 mg/day, in placebo- controlled

panic disorder trials of 10 to 12 weeks duration in which patients were dosed

in the range of

10 to 60 mg/day, in placebo-controlled social phobia (social anxiety

disorder) trials of 12

weeks duration in which patients were dosed in a range of 20 to 50 mg/day, in placebo-

Page 16 of 57

controlled generalized anxiety disorder trials of 8 weeks in which

patients were dosed in a

range from 10 to 50 mg/day and in placebo-controlled

posttraumatic stress disorder trials of

12 weeks in which patients were dosed in a range

from 20 to 50 mg/day.

The prescriber should be aware that these figures cannot be used to predict the incidence

side effects in the course of usual medical practice where patient characteristics and other

factors differ from those which prevailed in the clinical trials. Similarly the cited

incidences

cannot be compared with figures obtained from other clinical investigations

involving

different treatments, uses and investigators. The cited frequencies do however

provide the

prescribing physician with some basis for estimating the relative contribution of drug and

non-drug factors to the side effect incidence rate in the population studied.

Reported adverse experiences were classified using a COSTART-based dictionary

terminology for the depression trials and an ADECS (a modified COSTART dictionary)

for OCD and panic disorder trials.

Page 17 of 57

Table 1

Treatment-Emergent Adverse Events in Short Term Flexible Dose Placebo-

Controlled Clinical Trials in Depression

1

Body System

Preferred Term

Paroxetine

(n=421)

Placebo

(n=421)

Body as a Whole

Headache

17.6%

17.3%

Asthenia

15.0%

5.9%

Abdominal Pain

3.1%

4.0%

Fever

1.7%

1.7%

Chest Pain

1.4%

2.1%

Trauma

1.4%

0.5%

Back Pain

1.2%

2.4%

Cardiovascular

Palpitation

2.9%

1.4%

Vasodilation

2.6%

0.7%

Postural Hypotension

1.2%

0.5%

Dermatological

Sweating

11.2%

2.4%

Rash

1.7%

0.7%

Gastrointestinal

Nausea

25.7%

9.3%

Dry Mouth

18.1%

12.1%

Constipation

13.8%

8.6%

Diarrhea

11.6%

7.6%

Decreased Appetite

6.4%

1.9%

Flatulence

4.0%

1.7%

Vomiting

2.4%

1.7%

Oropharynx Disorder

2.1%

0.0%

Dyspepsia

1.9%

1.0%

Increased Appetite

1.4%

0.5%

Musculoskeletal

Myopathy

2.4%

1.4%

Myalgia

1.7%

0.7%

Myasthenia

1.4%

0.2%

Nervous System

Somnolence

23.3%

9.0%

Dizziness

13.3%

5.5%

Insomnia

13.3%

6.2%

Tremor

8.3%

1.9%

Nervousness

5.2%

2.6%

Anxiety

5.0%

2.9%

Paraesthesia

3.8%

1.7%

Libido Decreased

3.3%

0.0%

Agitation

2.1%

1.9%

Drugged Feeling

1.7%

0.7%

Myoclonus

1.4%

0.7%

CNS Stimulation

1.2%

3.6%

Confusion

1.2%

0.2%

Respiration

Respiratory Disorder

5.9%

6.4%

Yawn

3.8%

0.0%

Pharyngitis

2.1%

2.9%

Special Senses

Blurred Vision

3.6%

1.4%

Taste Perversion

2.4%

0.2%

Urogenital System

*Abnormal Ejaculation

12.9%

0.0%

*Male Genital Disorders

8.0%

0.0%

Urinary Frequency

3.1%

0.7%

Urination Impaired

2.9%

0.2%

*Impotence

2.5%

0.5%

*Female Genital Disorders

1.8%

0.0%

Events reported by at least 1% of patients treated with paroxetine tablets

are included.

* Percentage corrected for gender

Placebo: male, n=206 female, n=215

Paroxetine: male, n=201 female, n=220

+ Primarily ejaculatory delay. In a trial of fixed doses of paroxetine, the incidence of ejaculatory disturbance in males with 20 mg per day of paroxetine.

was 6.5% (3/46) versus 0% (0/23) in the placebo group.

Includes mostly lump in throat and tightness in throat

Includes mostly cold symptoms or URI

Includes anorgasmia, erectile difficulties, delayed ejaculation/orgasm, sexual dysfunction and impotence

Includes difficulty with micturition and urinary hesitancy

Includes anorgasmia and difficulty reaching climax/orgasm

Page 18 of 57

Table 2

Treatment-Emergent Adverse Experience Incidence in Placebo-Controlled Clinical

Trials for Obsessive-Compulsive Disorder, Panic Disorder, Social Phobia (Social

Anxiety Disorder), Generalized Anxiety Disorder and Posttraumatic Stress

Disorder .

1

Obsessive-Compulsive

Disorder

Panic Disorder

Social Phobia (Social

Anxiety Disorder)

Generalized Anxiety

Disorder

Posttraumatic Stress

Disorder

Body System

Preferred Term

Paroxet-

Tablets

(n=542)

Placebo

(n=265)

Paroxet-

Tablets

(n=469)

Placebo

(n=324)

Paroxet-

Tablets

(n=425)

Placebo

(n=339)

Paroxet-

Tablets

(n=735)

Placebo

(n=529)

Paroxet-

Tablets

(n=676)

Placebo

(n=504)

Body as a Whole

Headache

25.3%

29.1%

25.4%

25.3%

22.4%

21.8%

16.9%

14.0%

18.9%

19.2%

Asthenia

21.8%

13.6%

13.6%

4.6%

22.4%

13.6%

14.3%

6.4%

11.8%

4.2%

Infection

5.4%

4.9%

5.3%

6.8%

3.8%

5.9%

5.6%

3.4%

4.9%

3.8%

Abdominal Pain

4.8%

4.9%

4.3%

3.1%

2.1%

4.7%

4.5%

3.6%

4.3%

3.2%

Chest Pain

2.8%

1.9%

2.3%

3.1%

0.7%

0.3%

1.0%

0.6%

1.2%

0.8%

Back Pain

2.4%

4.9%

3.2%

2.2%

1.6%

4.1%

2.3%

3.6%

3.4%

3.4%

Chills

2.0%

0.8%

2.3%

0.6%

0.2%

0.3%

1.0%

0.0%

0.1%

0.4%

Trauma

3.1%

3.8%

3.6%

3.7%

2.6%

0.9%

2.6%

3.4%

5.8%

5.2%

Cardiovascular

Vasodilation

3.9%

1.1%

2.1%

2.8%

1.4%

0.6%

2.7%

0.8%

2.2%

1.2%

Palpitation

2.0%

0.4%

2.3%

2.5%

1.2%

1.8%

1.1%

1.1%

1.0%

0.8%

Dermatologic

Sweating

8.9%

3.0%

14.3%

5.9%

9.2%

2.1%

6.3%

1.5%

4.6%

1.4%

Rash

3.1%

1.9%

2.3%

1.5%

0.7%

0.3%

1.5%

0.9%

1.5%

2.0%

Gastrointestinal

Nausea

23.2%

9.8%

22.8%

17.3%

24.7%

6.5%

20.1%

5.3%

19.2%

8.3%

Dry Mouth

18.1%

8.7%

18.1%

10.8%

8.9%

2.9%

10.9%

4.7%

10.1%

4.8%

Constipation

15.7%

6.4%

7.9%

5.2%

5.4%

1.8%

10.5%

1.7%

5.5%

3.4%

Diarrhea

10.3%

9.8%

11.7%

6.5%

8.5%

5.9%

9.1%

6.6%

10.5%

5.4%

Decreased

Appetite

9.0%

3.4%

7.0%

2.8%

7.8%

1.5%

5.2%

1.1%

5.9%

2.6%

Dyspepsia

3.9%

6.8%

3.8%

6.8%

4.0%

2.4%

4.5%

4.9%

4.6%

3.4%

Flatulence

3.0%

4.2%

1.7%

2.8%

4.0%

2.4%

1.4%

2.1%

1.0%

1.0%

Increased Appetite

4.2%

3.0%

2.1%

0.6%

1.2%

1.8%

0.4%

1.1%

1.5%

1.0%

Vomiting

2.2%

3.4%

1.9%

1.5%

2.4%

0.6%

2.7%

2.5%

3.0%

2.0%

Musculoskeletal

Myalgia

3.1%

3.8%

2.3%

3.4%

4.0%

2.7%

2.9%

2.6%

1.8%

1.8%

Nervous System

Somnolence

24.4%

7.2%

18.8%

10.8%

21.6%

5.3%

15.4%

4.5%

16.0%

4.6%

Insomnia

23.8%

13.2%

17.9%

10.2%

20.9%

15.9%

10.7%

7.9%

11.8%

11.3%

Dizziness

12.4%

6.0%

14.1%

9.9%

11.3%

7.1%

6.1%

4.5%

6.1%

4.6%

Tremor

10.5%

1.1%

8.5%

1.2%

8.7%

1.2%

4.6%

0.8%

4.3%

1.4%

Nervousness

8.5%

8.3%

7.9%

8.3%

7.5%

6.5%

3.9%

2.8%

3.0%

4.4%

Libido Decreased

7.2%

3.8%

8.5%

1.2%

11.5%

0.9%

9.4%

1.5%

5.2%

1.8%

Anxiety

4.1%

6.8%

4.5%

4.0%

4.7%

4.1%

1.6%

0.9%

3.8%

4.0%

Abnormal

Dreams

3.9%

1.1%

2.8%

3.4%

1.9%

1.5%

0.5%

1.1%

2.5%

1.6%

Myoclonus

3.3%

0.4%

3.2%

1.5%

2.1%

0.9%

1.6%

0.6%

1.0%

0.6%

Concentration

Impaired

2.8%

1.5%

1.1%

0.9%

3.5%

0.6%

1.1%

0.6%

1.5%

1.0%

Depersonalization

2.6%

0.4%

1.7%

2.2%

0.7%

0.9%

0.7%

0.0%

0.9%

0.2%

Amnesia

2.2%

1.1%

0.6%

0.0%

0.5%

0.3%

0.4%

0.6%

1.3%

1.0%

Hyperkinesia

2.2%

1.5%

0.9%

0.9%

1.2%

0.0%

0.8%

0.0%

1.3%

0.2%

Agitation

1.7%

2.3%

4.7%

3.7%

2.6%

0.9%

1.8%

1.1%

1.9%

3.2%

Respiratory

Pharyngitis

3.7%

4.9%

3.2%

3.1%

3.8%

2.1%

2.3%

2.1%

2.4%

2.2%

System

Rhinitis

1.5%

3.4%

2.6%

0.3%

1.2%

3.2%

1.5%

1.1%

1.0%

2.0%

Sinusitis

1.5%

4.9%

5.8%

4.6%

2.1%

2.4%

3.5%

3.4%

3.8%

4.4%

Yawn

1.7%

0.4%

1.9%

0.0%

4.9%

0.3%

4.2%

0.2%

2.1%

0.2%

Cough Increased

1.1%

1.9%

2.3%

1.5%

0.7%

0.9%

0.8%

0.8%

1.2%

0.6%

Respiratory

Disorder

1

6.8%

5.1%

3.3%

1.0%

Special Senses

Abnormal Vision

3.7%

2.3%

3.0%

2.8%

4.0%

0.3%

2.2%

0.6%

0.3%

0.0%

Taste Perversion

2.0%

0.0%

1.1%

0.6%

0.7%

0.6%

0.7%

0.8%

0.7%

0.8%

Page 19 of 57

Table 2 (cont’d)

Treatment-Emergent Adverse Experience Incidence in Placebo-

Controlled Clinical Trials for Obsessive-Compulsive Disorder, Panic

Disorder, Social Phobia (Social Anxiety Disorder), Generalized

Anxiety Disorder and Posttraumatic Stress Disorder .

1

Obsessive-

Compulsive

Disorder

Panic Disorder

Social Phobia

(Social Anxiety

Disorder)

Generalized Anxiety

Disorder

Posttraumatic Stress

Disorder

Body System

Preferred Term

Paroxet-

Tablets

(n=542)

Placebo

(n=265)

Paroxet-

Tablets

(n=469)

Placebo

(n=324)

Paroxet-

Tablets

(n=425)

Placebo

(n=339)

Paroxet-

Tablets

(n=735)

Placebo

(n=529)

Paroxet-

Tablets

(n=676)

Placebo

(n=504)

Urogenital

Abnormal

23.3%

1.3%

20.5%

0.9%

27.6%

1.1%

24.7%

2.0%

12.6%

1.6%

System

Ejaculation

Dysmenorrhea

1.4%

1.9%

2.0%

2.3%

4.6%

4.4%

1.3%

1.2%

1.6%

1.3%

Impotence

8.2%

1.3%

5.4%

0.0%

5.3%

1.1%

4.2%

3.0%

9.2%

0.5%

Female Genital

Disorder

3.3%

0.0%

8.9%

0.5%

8.6%

0.6%

4.4%

0.6%

4.8%

0.6%

Urinary

Frequency

3.3%

1.1%

2.1%

0.3%

1.6%

1.8%

1.0%

0.6%

1.0%

0.2%

Urination

Impaired

3.3%

0.4%

0.4%

0.3%

1.9%

0.0%

1.0%

0.0%

0.6%

0.0%

Urinary Tract

Infection

1.5%

1.1%

2.1%

1.2%

0.2%

1.2%

1.2%

1.1%

0.6%

0.8%

Events reported by at least 2% of either OCD, Panic Disorder, Social Phobia (Social Anxiety Disorder), Generalized Anxiety

Disorder or Posttraumatic Stress Disorder paroxetine tablet-treated patients are included, except the following events which had an

incidence

on placebo ≥ paroxetine tablets: [OCD]: depression, paraesthesia, and respiratory disorder. [Panic Disorder]: flu syndrome,

depression,

paraesthesia, respiratory disorder. [Social Phobia (Social Anxiety Disorder)]: depression, respiratory disorder.

[Generalized Anxiety

Disorder]: not applicable, [Posttraumatic Stress Disorder]: depression, respiratory disorder

Incidence is gender-corrected. OCD:

Placebo: male, n=158; female, n=107

Paroxetine: male, n=330; female, n=212

PANIC:

Placebo: male, n=111; female, n=213

Paroxetine: male, n=166; female, n=303

SOCIAL PHOBIA:

Placebo: male, n=180; female, n=159

(SOCIAL ANXIETY DISORDER)

Paroxetine: male, n=228; female, n=197

GENERALIZED ANXIETY DISORDER: Placebo: male, n=197; female, n=332

Paroxetine: male, n=283; female, n=452

POSTTRAUMATIC STRESS DISORDER Placebo: male, n=190; female, n=314

Paroxetine: male, n=238; female, n=438

Includes anorgasmia and difficulty reaching climax/orgasm

Male and Female Sexual Dysfunction With SSRIs

Although changes in sexual desire, sexual performance and sexual satisfaction often

occur as manifestations of a psychiatric disorder, they may also be a consequence of

pharmacologic treatment. In particular, some evidence suggests that selective serotonin

reuptake inhibitors (SSRIs) can cause such untoward sexual experiences. Furthermore,

there have been reports of long-lasting sexual dysfunction where these symptoms have

continued despite discontinuation of SSRIs.

Reliable estimates of the incidence and severity of untoward experiences involving

sexual desire, performance and satisfaction are difficult to obtain, however, in part

because patients and physicians may be reluctant to discuss them. Accordingly, estimates

of the incidence of untoward sexual experience and performance cited in product labeling

are likely to underestimate their actual incidence.

Page 20 of 57

Incidence of Sexual Adverse Events in Pooled Data

In placebo-controlled clinical trials involving more than 3,200 patients, the ranges for the

reported incidence of sexual side effects in males and females with major depressive

disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD are displayed in

Table 3 below.

Table 3

Incidence of Sexual Adverse Events in Controlled Clinical Trials

Paroxetine Tablets

Placebo

n (males)

1446

1042

Decreased Libido

6-15%

0-5%

Ejaculatory Disturbance

13-28%

0-2%

Impotence

2-9%

0-3 %

n (females)

1822

1340

Decreased Libido

0-9%

0-2%

Orgasmic Disturbance

2-9%

0-1%

There are no adequate and well-controlled studies examining sexual dysfunction with

paroxetine treatment.

Paroxetine treatment has been associated with several cases of priapism. In those cases

with a known outcome, patients recovered without sequelae.

While it is difficult to know the precise risk of sexual dysfunction associated with the use

of SSRIs, physicians should routinely inquire about such possible side effects.

Laboratory Changes - Cholesterol

Clinically and statistically relevant increases in cholesterol levels have been noted in

studies using paroxetine (see WARNINGS AND PRECAUTIONS, Endocrine and

Metabolism).

Of the patients in placebo-controlled clinical trials for whom baseline and on-treatment

measurements were taken, total serum levels of cholesterol showed a mean increase of

~ 1.5 mg/dL in paroxetine-treated patients (n = 653), compared to a mean decrease of ~

5.0 mg/dL in placebo-treated patients (n = 379). Increases from baseline of 45 mg/dL or

greater were recorded in 6.6% of paroxetine-treated patients compared to 2.6% of

placebo-treated patients.

Pediatrics

In placebo-controlled clinical trials conducted with pediatric patients aged 7 to 18 years

with depression, OCD and Social Anxiety Disorder (involving 633 patients treated with

paroxetine and 542 patients treated with placebo), the following adverse events were

reported in at least 2% of pediatric patients treated with paroxetine tablets

and occurred at

a rate at

least twice that for pediatric patients receiving placebo: emotional lability

(including self-harm, suicidal thoughts, attempted suicide, crying, and mood fluctuations),

hostility,

(predominantly aggression, oppositional behaviour and anger) decreased

appetite, tremor,

sweating, hyperkinesia, and agitation.

Page 21 of 57

In the pediatric clinical trials in depression, OCD and Social Anxiety Disorder that

included a taper phase regimen (307 patients aged 7 to 18 years treated with paroxetine

and 291 patients treated with placebo), events reported upon discontinuation of treatment,

which occurred in at least 2% of patients who received paroxetine tablets

and which

occurred at a

rate at least twice that of placebo, were: emotional lability (including

suicidal ideation, suicide attempt, mood changes, and tearfulness), nervousness,

dizziness, nausea, and

abdominal pain (see WARNINGS AND PRECAUTIONS,

Discontinuation of Treatment

With paroxetine tablets).

Other Events Observed During the Clinical Development of Paroxetine

In the tabulations which follow, a COSTART or modified COSTART-based dictionary

terminology has been used to classify reported adverse experiences. The frequencies

presented therefore represent the portion of the 4126, 542, 469, 522, 735 and 676

paroxetine tablet-exposed individuals in depression, OCD, panic, social phobia (social

anxiety

disorder), generalized anxiety disorder and posttraumatic stress disorder trials,

respectively, who experienced an event of the type cited on at least one occasion while

receiving paroxetine tablets. Experiences are further classified within body system

categories and

enumerated in order of decreasing frequency using the following

definitions: frequent

experiences are defined as those occurring on one or more occasion

in at least 1/100

patients; infrequent adverse experiences are those occurring in less than

1/100 but at least

1/1000 patients; rare experiences are those occurring in less than 1/1000

patients.

All adverse experiences are included except those already listed in Table 1 and Table 2,

those reported in terms so general as to be uninformative and those experiences for which

the drug cause was remote. It is important to emphasize that although the experiences

reported did occur during treatment with paroxetine tablets, they were not necessarily

caused by it.

Body as a Whole

Frequent: Malaise, pain. Infrequent: Allergic reaction, chills, face edema, infection,

moniliasis, neck pain, overdose. Rare: Abnormal laboratory value, abscess, adrenergic

syndrome, cellulitis, chills and fever, cyst, hernia, intentional overdose, neck rigidity,

pelvic pain, peritonitis, substernal chest pain, sepsis, ulcer.

Immune System Disorders: Very rare were severe allergic reactions (including

anaphylactoid reactions and angioedema).

Cardiovascular System

Frequent: Hypertension, syncope, tachycardia. Infrequent: Bradycardia, conduction

abnormalities, electrocardiogram abnormal, hypotension, migraine, ventricular

extrasystoles. Rare: Angina pectoris, arrhythmia, atrial arrhythmia, atrial fibrillation,

bundle branch block, cardiac disorder, cerebral ischemia, cerebrovascular accident,

cerebrovascular disorder, congestive heart failure, extrasystoles, low cardiac output,

myocardial infarct, myocardial ischemia, pallor, phlebitis, pulmonary embolus,

supraventricular extrasystoles, thrombosis, varicose vein, vascular disorder, vascular

Page 22 of 57

headache.

Dermatological

Frequent: Pruritus. Infrequent: Acne, alopecia, dry skin, ecchymosis, eczema,

furunculosis, herpes simplex, urticaria. Rare: Angioedema, contact dermatitis, erythema

nodosum, exfoliative dermatitis, herpes zoster, maculopapular rash, photosensitivity, skin

discolouration, skin ulcer, skin hypertrophy, sweating decreased. Very rare: severe

cutaneous adverse reactions (including erythema multiforme, Stevens-Johnson syndrome

and toxic epidermal necrolysis).

Endocrine

Rare: Diabetes mellitus, fertility decreased female, goiter, hyperthyroidism,

hypothyroidism, thyroiditis.

Gastrointestinal

Frequent: Nausea and vomiting. Infrequent: Bruxism, buccal cavity disorders,

dysphagia, eructation, gastroenteritis, gastrointestinal flu, glossitis, increased salivation,

liver function tests abnormal, mouth ulceration, vomiting and diarrhea, rectal

hemorrhage. Rare: Aphthous stomatitis, bloody diarrhea, bulimia, cardiospasm, colitis,

duodenitis, esophagitis, fecal impaction, fecal incontinence, gastritis, gingivitis,

hematemesis, hepatitis, ileitis, ileus, jaundice, melena, peptic ulcer, salivary gland

enlargement, sialadenitis, stomach ulcer, stomatitis, tongue edema, tooth caries.

Hematologic and Lymphatic

Infrequent: Anemia, leukopenia, lymphadenopathy, purpura, WBC abnormality.

Rare: Abnormal bleeding, predominately of the skin and mucous membranes, bleeding

time increased, eosinophilia, iron deficiency anemia, leukocytosis, lymphedema,

lymphocytosis, microcytic anemia, monocytosis, normocytic anemia, thrombocytopenia.

Metabolic and Nutritional

Frequent: Weight gain, weight loss, increases in cholesterol levels. Infrequent: Edema,

hyperglycemia, peripheral edema, thirst. Rare: Alkaline phosphatase increased,

bilirubinemia, cachexia, dehydration, gout, hypocalcemia, hypoglycemia, hypokalemia,

hyponatremia (predominantly in the elderly) which is sometimes due to syndrome of

inappropriate anti-diuretic hormone secretion (SIADH), non-protein nitrogen (NPN)

increased, obesity, SGOT increased, SGPT increased.

Page 23 of 57

Musculoskeletal

Infrequent: Arthralgia, arthritis, traumatic fracture. Rare: Arthrosis, bone disorder,

bursitis, cartilage disorder, myositis, osteoporosis, tetany.

Nervous System

Frequent: CNS stimulation, concentration impaired, depression, emotional lability,

vertigo. Infrequent: Akinesia, alcohol abuse, amnesia, ataxia, convulsion,

depersonalization, hallucinations, hyperkinesia, hypertonia, incoordination, lack of

emotion, manic reaction, paranoid reaction, thinking abnormal, hypesthesia.

Rare: Abnormal electroencephalogram, abnormal gait, antisocial reaction, brain edema,

choreoathetosis, circumoral paraesthesia, confusion, delirium, delusions, diplopia, drug

dependence, dysarthria, dyskinesia, dystonia, euphoria, fasciculations, grand mal

convulsion, hostility, hyperalgesia, hypokinesia, hysteria, libido increased, manic

depressive reaction, meningitis, myelitis, neuralgia, neuropathy, nystagmus, psychosis,

psychotic depression, reflexes increased, stupor, torticollis, withdrawal syndrome.

Respiratory System

Frequent: Cough increased, rhinitis. Infrequent: Asthma, bronchitis, dyspnea, epistaxis,

hyperventilation, pneumonia, respiratory flu, sinusitis. Rare: Hiccup, lung fibrosis,

sputum increased, stridor, trachea disorder, voice alteration.

Special Senses

Infrequent: Abnormality of accommodation, conjunctivitis, ear pain, eye pain, mydriasis,

otitis media, tinnitus. Rare: Amblyopia, cataract specified, conjunctival edema, corneal

lesion, corneal ulcer, exophthalmos, eye hemorrhage, acute glaucoma, hyperacusis, otitis

externa, photophobia, retinal hemorrhage, taste loss, anisocoria, deafness,

keratoconjunctivitis.

Urogenital system

Infrequent: Abortion*, amenorrhea*, breast pain*, cystitis, dysmenorrhea*, dysuria,

menorrhagia*, nocturia, polyuria, urinary incontinence, urinary retention, urinary tract

infection, urinary urgency, vaginitis*. Rare: Breast atrophy*, cervix disorder*,

endometrial disorder*, female lactation*, hematuria, kidney calculus, kidney function

abnormal, kidney pain, mastitis*, nephritis, oliguria, salpingitis*, spermatogenesis arrest*

urethritis, urinary casts, urine abnormality, uterine neoplasm*, vaginal moniliasis*.

* Incidence corrected for gender.

Post-Marketing Adverse Drug Reactions

Adverse events not listed above which have been reported since market introduction in

patients taking paroxetine tablets

include acute pancreatitis, hepatic events such as

elevation of hepatic enzymes, and hepatitis, sometimes associated with jaundice, and/or

liver failure (in very rare circumstances, with fatal outcomes), Guillain-Barré syndrome,

Page 24 of 57

priapism,

thrombocytopenia, aggravated hypertension, syndrome of inappropriate ADH

secretion,

symptoms suggestive of hyperprolactinemia and galactorrhea, menstrual

disorders

(including menorrhagia, metrorrhagia and amenorrhea), blurred vision;

extrapyramidal

symptoms which have included akathisia, (characterized by an inner

sense of restlessness

and psychomotor agitation such as an inability to sit or stand still

usually associated with

subjective distress), bradykinesia, cogwheel rigidity, dystonia,

hypertonia, oculogyric

crisis which has been associated with concomitant use of

pimozide, tremor and trismus, abnormal dreams (including nightmares), restless legs

syndrome (RLS), neuroleptic

malignant syndrome-like events and serotonin syndrome

(see WARNINGS AND PRECAUTIONS, Neurologic-Serotonin Syndrome/Neuroleptic

Malignant Syndrome), persistent pulmonary hypertension (PPHN; see also

WARNINGS AND PRECAUTIONS, Pregnant Women and Newborns, Risk of PPHN

and exposure to SSRIs). There has been a case report of an elevated phenytoin level

after 4 weeks of paroxetine tablets

and phenytoin co-administration.

There has been a case report of severe hypotension when paroxetine tablets

was added to

chronic

metoprolol treatment. The causal relationship between paroxetine tablets

and the

emergence of these events has not been established.

There have been spontaneous reports of adverse events upon the discontinuation of

paroxetine tablets

and other selective serotonin reuptake inhibitors (particularly when

abrupt) (see

WARNINGS AND PRECAUTIONS, General-Discontinuation of

Treatment with

JAMP Paroxetine Tablets

and ADVERSE REACTIONS, Adverse

Events Following Discontinuation of treatment).

DRUG INTERACTIONS

Overview

Like some other selective serotonin re-uptake inhibitors, paroxetine inhibits the specific

hepatic cytochrome P450 isozyme CYP2D6 which is responsible for the metabolism of

debrisoquine and sparteine. Poor metabolizers of debrisoquine/sparteine represent

approximately 5 to 10% of Caucasians. The median C

(ss) for paroxetine tablets

(20 mg

daily)

at steady state in poor metabolizers (n=8) was almost triple that reported for extensive

metabolizers (n=9). Although the full clinical significance of this effect has not been

established, inhibition of CYP2D6 can lead to elevated plasma levels of co-administered

drugs

which are metabolized by this isozyme. Consideration should be given to decreasing the dose

of the CYP2D6 metabolized drug or paroxetine and/or monitoring of drug plasma levels,

especially when JAMP Paroxetine Tablets

is co-administered with drugs with a

narrow

therapeutic index.

Serious Drug Interactions

Monoamine Oxidase Inhibitors: See CONTRAINDICATIONS

Thioridazine: See CONTRAINDICATIONS

Pimozide: See CONTRAINDICATIONS

Page 25 of 57

Paroxetine tablets

co-administration has been associated with elevated levels of the anti-

cholinergic procyclidine, certain neuroleptics/antipsychotics (e.g. perphenazine,

risperidone), tricyclic antidepressants (e.g. desipramine), atomoxetine, type 1C

antiarrhythmics (e.g. propafenone), and theophylline.

Co-administration of phenobarbitol or phenytoin with paroxetine tablets

has been

associated with

decreased levels of paroxetine tablets. When co-administered with

cimetidine, paroxetine tablets

levels were elevated.

The concomitant use of paroxetine tablets

and alcohol has not been studied.

Drug-Drug Interactions

Monoamine Oxidase Inhibitors: Combined use of JAMP Paroxetine Tablets

monoamine oxidase inhibitors [including linezolid, an antibiotic which is a reversible

non-selective MAO

inhibitor and methylthioninium chloride (methylene blue)] is

contraindicated due to the

potential for serious reactions with features resembling

serotonin syndrome or neuroleptic

malignant syndrome (see CONTRAINDICATIONS

and WARNINGS AND PRECAUTIONS, Serotonin Syndrome/Neuroleptic Malignant

Syndrome).

Thioridazine: Combined use of JAMP Paroxetine Tablets

and thioridazine is

contraindicated due to a

potential for elevated thioridazine plasma levels. Thioridazine

treatment alone produces

prolongation of the QTc interval, which is associated with

serious ventricular arrhythmias, such as torsade de pointes-type arrhythmias, and

sudden death (see CONTRAINDICATIONS).

Pimozide: In an open label study of healthy volunteers, co-administration of a single

dose

of 2 mg pimozide, under steady state conditions of paroxetine tablets

(titrated to 60 mg

daily) was associated with mean increases in pimozide AUC of 151% and C

of 62%,

compared to pimozide administered alone. This is likely explained by the known

CYP2D6 inhibitory properties of paroxetine. Due to the narrow therapeutic index of

pimozide, and its known ability to prolong the QT interval, and produce severe cardiac

arrhythmias including torsade de pointes, concomitant use of pimozide and JAMP

Paroxetine Tablets

contraindicated (see CONTRAINDICATIONS).

Neuromuscular Blockers: In vitro studies, as well as a small number of clinical reports

suggest that some antidepressants including paroxetine may reduce plasma cholinesterase

activity resulting in a prolongation of the neuromuscular blocking action of

succinylcholine.

Drugs Metabolized by Cytochrome P450 (CYP2D6): In two studies, daily dosing of

paroxetine tablets

(20 mg qd) under steady state conditions increased the following mean

pharmacokinetic parameters for a single (100 mg) dose of desipramine in extensive

metabolizers: C

2 fold), AUC (6 fold), and T½ (3-5 fold). Concomitant steady-state

paroxetine tablets treatment did not result in any further impairment of desipramine elimination

in poor metabolizers. Insufficient information is available to provide recommendations on the

necessary dosage adjustments for tricyclic antidepressants or paroxetine tablets, if these drugs

are to be used in combination. Plasma tricyclic antidepressant concentrations may need to be

Page 26 of 57

monitored in such instances.

Concomitant use of paroxetine tablets

with other drugs metabolized by CYP2D6 has not

been

formally studied but may require lower doses than usually prescribed for either

paroxetine tablets

or the other drug. Drugs metabolized by CYP2D6 include certain

tricyclic

antidepressants (e.g. nortriptyline, amitriptyline, imipramine and desipramine),

selective

serotonin reuptake inhibitors (e.g. fluoxetine), phenothiazine neuroleptics (e.g.

perphenazine), risperidone, atomoxetine, Type IC antiarrhythmics (e.g. propafenone and

flecainide), and metoprolol. Due to the risk of serious ventricular arrhythmias and sudden

death potentially associated with elevated plasma levels of thioridazine, JAMP

Paroxetine Tablets

thioridazine should not be co-administered (see

CONTRAINDICATIONS).

Fosamprenavir/ritonavir: Co-administration of fosamprenavir/ritonavir with paroxetine

significantly decreased plasma levels of paroxetine (by ~ 60% in one study). Any dose

adjustment should be guided by clinical effect (tolerability and efficacy).

Tamoxifen: Tamoxifen has an important active metabolite, endoxifen, which is produced

by CYP2D6 and contributes significantly to the efficacy of tamoxifen. Irreversible

inhibition of CYP2D6 by paroxetine leads to reduced plasma concentrations of endoxifen

(see WARNINGS AND PRECAUTIONS, Potential for reduced efficacy of Tamoxifen

with concomitant SSRI use, including JAMP Paroxetine Tablets).

Drugs Metabolized by Cytochrome P450 (CYP3A4): An in vivo interaction study

involving the co-administration under steady state conditions of paroxetine tablets

terfenadine,

a substrate for CYP3A4, revealed no effect of paroxetine tablets

terfenadine pharmacokinetics.

In addition, in vitro studies have shown ketoconazole, a

potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than paroxetine

as an inhibitor of the

metabolism of several substrates for this enzyme, including

terfenadine, astemizole,

cisapride, triazolam and cyclosporin. Based on the assumption

that the relationship between paroxetine’s in vitro Ki and its lack of effect on

terfenadine’s in vivo clearance

predicts its effect on other CYP3A4 substrates,

paroxetine’s extent of inhibition of CYP3A4 activity would not be expected to be of

clinical significance.

Microsomal Enzyme Inhibition/Induction: The metabolism and pharmacokinetics of

JAMP Paroxetine Tablets

may be affected by the induction or inhibition of drug

metabolizing enzymes.

Drugs Highly Bound to Plasma Protein: Paroxetine is highly bound to plasma protein,

therefore administration of JAMP Paroxetine Tablets

to a patient taking another drug that

is highly protein

bound may cause increased free concentrations of the other drug,

potentially resulting in

adverse events. Conversely, adverse effects could result from

displacement of paroxetine

by other highly bound drugs.

Page 27 of 57

Alcohol: The concomitant use of paroxetine tablets

and alcohol has not been studied and is

recommended. Patients should be advised to avoid alcohol while taking JAMP

Paroxetine Tablets.

Anti-cholinergic Drugs: Paroxetine tablets

has been reported to increase significantly the

systemic bioavailability of procyclidine. Steady state plasma levels of procyclidine (5 mg

daily) were elevated by about 40% when 30 mg paroxetine was co-administered to

steady-

state. If anti-cholinergic effects are seen, the dose of procyclidine should be

reduced.

Antiretroviral: Co-administration of fosamprenavir/ritonavir with paroxetine

significantly

decreased plasma levels of paroxetine (by ~ 60% in one study). Any dose adjustment should

be guided by clinical effect (tolerability and efficacy).

Phenobarbital: Chronic daily dosing with phenobarbital (100 mg qid for 14 days) decreased

the systemic availability of a single 30 mg dose of paroxetine in some subjects. The AUC

and T

of paroxetine tablets

were reduced by an average of 25 and 38% respectively

compared to paroxetine tablets

administered alone. The effect of paroxetine tablets

phenobarbital

pharmacokinetics was not studied. No initial JAMP Paroxetine Tablets

dosage adjustment is considered necessary when co-administered with phenobarbital; any

subsequent adjustment should be guided by clinical effect.

Anticonvulsants: In a limited number of patients with epilepsy on long-term treatment

with

anticonvulsants (carbamazepine 600 to 900 mg/day, n=6; phenytoin 250 to 400 mg/day, n=6;

sodium valproate 300 to 2500 mg/day, n=8) the co-administration of paroxetine tablets

mg/day for 10 days) had no significant effect on the plasma concentrations of these

anticonvulsants. In healthy volunteers, co-administration of paroxetine with

phenytoin has

been associated with decreased plasma levels of paroxetine and an increased incidence of

adverse experiences. However, no initial dosage adjustment of JAMP Paroxetine Tablets

considered necessary when the drug is to be co-administered with known drug metabolizing

enzyme inducers (e.g. carbamazepine, phenytoin, sodium valproate) and any subsequent

dosage adjustment should be guided by clinical effect. Co-administration

of JAMP

Paroxetine Tablets

with anticonvulsants may be associated with an increased incidence of

adverse experiences.

Antipsychotic Drugs/Neuroleptic Malignant Syndrome: As with other SSRIs, JAMP

Paroxetine

Tablets

should be used with caution in patients already receiving

antipsychotics/neuroleptics, since symptoms suggestive of Neuroleptic Malignant Syndrome

cases have

been reported with this combination (see WARNINGS AND PRECAUTIONS,

Serotonin

Syndrome/Neuroleptic Malignant Syndrome).

Serotonergic Drugs: Based on the mechanism of action of paroxetine and the potential

serotonin syndrome, caution is advised when JAMP Paroxetine Tablets

is coadministered

with other

drugs or agents that may affect the serotonergic neurotransmitter systems, such as

tryptophan, triptans, serotonin reuptake inhibitors, lithium, fentanyl and its anologues,

dextromethorphan, tramadol, tapentadol, meperidine, methadone and pentazocine or St.

John's Wort (see WARNINGS AND PRECAUTIONS, Serotonin Syndrome/Neuroleptic

Malignant Syndrome). Concomitant use of JAMP Paroxetine Tablets

and MAO inhibitors

(including linezolid, an antibiotic which is a reversible non-selective MAO inhibitor) is

Page 28 of 57

contraindicated (see CONTRAINDICATIONS).

Drugs Affecting Platelet Function (e.g. NSAIDs, ASA and other anticoagulants):

Serotonin release by platelets plays an important role in hemostasis. Epidemiological

studies

of the case-control and cohort design that have demonstrated an association between use of

psychotropic drugs that interfere with serotonin reuptake and the

occurrence of upper

gastrointestinal bleeding have also shown that concurrent use of an

NSAID, ASA or other

anticoagulants may potentiate the risk of bleeding .

Altered anticoagulant effects, including increased bleeding, have been reported when

SSRIs

are co-administered with warfarin. Patients receiving warfarin therapy should be

carefully

monitored when JAMP Paroxetine Tablets

is initiated or discontinued (see WARNINGS

AND PRECAUTIONS, Hematologic, Abnormal Bleeding).

Lithium: In a study of depressed patients stabilized on lithium, no pharmacokinetic

interaction between paroxetine and lithium was observed. However, due to the potential

serotonin syndrome, caution is advised when JAMP Paroxetine Tablets

is coadministered

with lithium.

Triptans: There have been rare postmarketing reports describing patients with weakness,

hyperreflexia, and incoordination following the use of a selective serotonin reuptake

inhibitor

(SSRI) and the 5HT

agonist, sumatriptan. If concomitant treatment with triptan

and an

SSRI (e.g. fluoxetine, fluvoxamine, paroxetine, sertraline) is clinically warranted,

appropriate observation of the patient is advised. The possibility of such interactions should

also be considered if other 5HT

agonists are to be used in combination with

SSRIs (see

WARNINGS AND PRECAUTIONS, Serotonin Syndrome/Neuroleptic

Malignant

Syndrome).

Tryptophan: Tryptophan can be metabolized to serotonin. As with other serotonin reuptake

inhibitors, the use of JAMP Paroxetine Tablets

together with tryptophan may result in

adverse

reactions consisting primarily of headache, nausea, sweating and dizziness as well as

serotonin syndrome. Consequently, concomitant use of JAMP Paroxetine Tablets

with

tryptophan is not

recommended (see WARNINGS AND PRECAUTIONS, Serotonin

Syndrome/Neuroleptic Malignant Syndrome).

CNS Drugs: Experience in a limited number of healthy subjects has shown that paroxetine

tablets

does not increase the sedation and drowsiness associated with haloperidol,

amylbarbitone

or oxazepam, when given in combination. Since the effects of concomitant

administration of paroxetine tablets

with neuroleptics have not been studied, the use of JAMP

Paroxetine Tablets

with these drugs should be approached with caution.

Diazepam: A multiple dose study of the interaction between paroxetine tablets

and diazepam

showed no alteration in the pharmacokinetics of paroxetine tablets

that would warrant

changes in

the dose of JAMP Paroxetine

Tablets

for patients receiving both drugs. The

effects of paroxetine tablets

on the

pharmacokinetics of diazepam were not evaluated.

Page 29 of 57

Cardiovascular Drugs: Multiple dose treatment with paroxetine tablets

30 mg/day has

little or no

effect on the steady-state pharmacokinetics of digoxin (0.25 mg qd) or

propanolol (80 mg bid).

Theophylline: Reports of elevated theophylline levels associated with paroxetine tablets

treatment

have been reported. While this interaction has not been formally studied, it is

recommended that theophylline levels be monitored when these drugs are concurrently

administered.

Cimetidine: Steady state levels of paroxetine tablets

(30 mg daily) were elevated by

about 50% when cimetidine (300 mg tid), a known drug metabolizing enzyme inhibitor,

was co- administered to steady-state. Consideration should be given to using doses of

JAMP Paroxetine Tablets

towards the lower end of the range when co-administered with

known drug metabolizing enzyme inhibitors.

Drug-Food Interactions

The absorption and pharmacokinetics of paroxetine tablets

are not affected by food or antacids.

Drug-Herb Interactions

St. John’s Wort: In common with other SSRI’s, pharmakodynamic interactions

between paroxetine and the herbal remedy St. John’s Wort may occur and may result in

an increase in undesirable effects.

Drug-Laboratory Interactions

Interactions with laboratory tests have not been established.

DOSAGE AND ADMINISTRATION

Dosing Considerations

General

JAMP Paroxetine Tablets

is not indicated for use in children under 18 years of age

(see WARNINGS AND PRECAUTIONS, Potential Association with Behavioural

and Emotional

Changes, Including Self-Harm).

Lower initial doses of JAMP Paroxetine Tablets

are recommended for elderly and

debilitated patients, and

patients with renal or hepatic impairment (see DOSAGE AND

ADMINISTRATION, Special Patient Populations).

JAMP Paroxetine Tablets

should be administered once daily in the morning and may be

taken with or without food. The tablet should be swallowed rather than chewed.

Dose Adjustments: Based on pharmacokinetic parameters, steady-state paroxetine

plasma levels are achieved over a 7 to 14 day interval. Hence, dosage adjustments in

10 mg increments should be made at 1 to 2 week intervals or according to clinician

judgment.

Page 30 of 57

Maintenance: During long-term therapy for any indication, the dosage should be

maintained at the lowest effective level.

There is no body of evidence available to answer the question of how long a patient

should continue to be treated with JAMP Paroxetine Tablets. It is generally agreed that

acute episodes of depression require several months or longer of sustained

pharmacologic therapy.

Whether the dose of an antidepressant needed to induce remission is identical to the dose

needed to maintain and/or sustain euthymia is unknown.

Systematic evaluation of the efficacy of paroxetine hydrochloride has shown that efficacy

is maintained for at least 6 months with doses that averaged about 30 mg (see CLINICAL

TRIALS, Depression).

Discontinuation of Treatment: Symptoms associated with the discontinuation of

paroxetine tablets

have been reported in clinical trials and post marketing. Patients

should be

monitored for these and other symptoms when discontinuing treatment,

regardless of the

indication for which JAMP Paroxetine Tablets

is being prescribed.

(see WARNINGS AND PRECAUTIONS, Discontinuation of Treatment With JAMP

Paroxetine Tablets

and ADVERSE

REACTIONS, Adverse Reactions Following

Discontinuation of Treatment).

A gradual reduction in the dose rather than abrupt cessation is recommended whenever

possible. If intolerable symptoms occur following a decrease in the dose or upon

discontinuation of treatment, dose titration should be managed on the basis of the

patient’s clinical response (see ADVERSE REACTIONS).

Adults

Depression

Usual Adult Dose: The administration of JAMP Paroxetine Tablets

should be initiated at

20 mg daily. For most patients, 20 mg daily will also be the optimum dose. The therapeutic

response may

be delayed until the third or fourth week of treatment.

Dose Range: For those patients who do not respond adequately to the 20 mg daily dose, a

gradual increase in dosage up to 40 mg daily may be considered. The maximum

recommended daily dose is 50 mg.

Obsessive-Compulsive Disorder

Usual Adult Dose: The administration of JAMP Paroxetine Tablets

should be initiated at

20 mg/day. The

recommended dose of JAMP Paroxetine Tablets

in the treatment of

OCD is 40 mg daily.

Page 31 of 57

Dose Range: For those patients who do not respond adequately to the 40 mg daily dose, a

gradual increase in dosage may be considered. The maximum recommended daily dose is

60 mg.

Panic Disorder

Usual Adult Dose: The recommended starting dose of JAMP Paroxetine Tablets

in the

treatment of panic

disorder is 10 mg/day. The recommended dose of JAMP Paroxetine

Tablets

in the treatment of panic

disorder is 40 mg daily.

Dose Range: For those patients who do not respond adequately to the 40 mg daily dose, a

gradual increase in dosage may be considered. The maximum recommended daily dose is

60 mg.

Social Phobia (Social Anxiety Disorder)

Usual Adult Dose: The recommended initial dosage is 20 mg/day. No clear dose-

relationship has been demonstrated over a 20 to 60 mg/day dose range.

Dose Range: Some patients not responding adequately to a 20 mg dosage may benefit

from gradual dosage increases, in 10 mg/day increments, up to a maximum of 50 mg/day.

Generalized Anxiety Disorder

Usual Adult Dose: The recommended initial dosage is 20 mg/day.

Dose Range: Some patients not responding adequately to a 20 mg dosage may benefit

from gradual dosage increases, in 10 mg/day increments, up to a maximum of 50 mg/day.

Posttraumatic Stress Disorder

Usual Adult Dose: The recommended starting dosage is 20 mg/day.

Dose Range: Some patients not responding adequately to a 20 mg/day dosage may

benefit from gradual dosage increases, in 10 mg/day increments, up to a maximum of

50 mg/day.

Page 32 of 57

Special Patient Populations

Treatment of Pregnant Women: Epidemiological studies of pregnancy outcomes

following maternal exposure to antidepressants in the first trimester have reported an

increase in the risk of congenital malformations, particularly cardiovascular (e.g.

ventricular and atrial septal defects), associated with the use of paroxetine. If a patient

becomes pregnant while taking JAMP Paroxetine Tablets, she should be informed of the

current estimate of risk to the fetus (see WARNINGS AND PRECAUTIONS, Special

Populations) and

consideration should be given to switching to other treatment options.

Treatment with

JAMP Paroxetine Tablets

should only be continued for an individual

patient, if the potential benefits outweigh the potential risks. For women who intend to

become pregnant, or are in their first trimester of pregnancy, initiation of paroxetine

should be considered only after other

treatment options have been evaluated (see

WARNINGS AND PRECAUTIONS, Special

Populations for more details).

Post-marketing reports indicate that some neonates exposed to paroxetine tablets, SSRIs,

or other

newer antidepressants late in the third trimester have developed complications

requiring

prolonged hospitalization, respiratory support, and tube feeding (see

WARNINGS AND PRECAUTIONS, Special Populations). When treating pregnant

women with JAMP Paroxetine Tablets

during the third trimester, the physician should

carefully consider the potential risks and benefits of treatment. The physician may

consider tapering JAMP Paroxetine Tablets

in the third trimester.

Geriatrics: (> 65 years): Administration of paroxetine tablets

to the elderly is associated

with

increased plasma levels and prolongation of the elimination half life relative to

younger

adults (see ACTION AND CLINICAL PHARMACOLOGY). The

recommended initial

dose is 10 mg/day for elderly and/or debilitated patients. The dose

may be increased, if

indicated, up to a maximum of 40 mg daily.

Pediatrics: JAMP Paroxetine Tablets

is not indicated for use in children under 18

years of age (see

INDICATION and WARNINGS AND PRECAUTIONS, Potential

Association with Behavioural and Emotional Changes, Including Self-Harm).

Renal/Hepatic Impairment: JAMP Paroxetine Tablets

should be used with caution in

patients with renal

or hepatic impairment. The recommended initial dose is 10 mg/day

in patients with

clinically significant renal or hepatic impairment. A maximum dose of

40 mg should not

be exceeded (See WARNINGS and PRECAUTIONS and ACTION

AND CLINICAL PHARMACOLOGY).

Page 33 of 57

OVERDOSAGE

The largest known ingestion from which a patient has recovered is 2000 mg. The

smallest known dose of paroxetine alone associated with a fatal outcome is

approximately 400 mg.

Symptoms of Overdosage

The most commonly reported adverse events subsequent to paroxetine-only

overdose include: somnolence, nausea, tremor, dizziness, vomiting, diarrhea, agitation,

aggression, anxiety, confused state, headache, fatigue, insomnia, tachychardia,

hyperhydrosis, mydriasis, convulsion, paraethesia, serotonin syndrome, fever, blood

pressure changes, involuntary muscle contraction and loss of consciousness. It should be

noted that in some cases, patients may have consumed alcohol in addition to taking an

overdose of paroxetine. Some of these symptoms may also be seen with clinical use.

Events such as coma and ECG changes have also been reported.

Treatment of Overdosage

The physician should consider contacting a poison control centre for additional

information on the treatment of any overdose.

No specific antidote is known. Treatment should consist of those general measures

employed in the management of overdose with any antidepressant. Establish and

maintain an airway; ensure adequate oxygenation and ventilation.

Induction of emesis is not recommended. Due to the large volume of distribution of

JAMP Paroxetine Tablets, forced diuresis, dialysis, hemoperfusion and exchange

transfusion are unlikely to be of benefit.

Supportive care with frequent monitoring of vital signs and careful observation is

indicated. An ECG should be taken and monitoring of cardiac function instituted if there

is any evidence of abnormality. Patient management should be as clinically indicated, or

as recommended by the national poisons centre, where available.

In managing overdosage, consider the possibility of multiple drug involvement.

A specific caution involves patients taking or recently having taken JAMP Paroxetine

Tablets

who might

ingest, by accident or intent, excessive quantities of a tricyclic

antidepressant. In such a

case, accumulation of the parent tricyclic and its active

metabolite may increase the

possibility of clinically significant sequelae and extend the

time needed for close medical

observation.

For management of a suspected drug overdose, contact your regional Poison Control

Centre.

Page 34 of 57

ACTION AND CLINICAL PHARMACOLOGY

Mechanism of Action

Paroxetine is a potent and selective serotonin (5-hydroxytryptamine, 5-HT) reuptake

inhibitor (SSRI). This activity of the drug on brain neurons is thought to be responsible

for its antidepressant and anxiolytic action in the treatment of depression, obsessive-

compulsive disorder (OCD), panic disorder, social phobia (social anxiety disorder),

generalized anxiety disorder (GAD) and posttraumatic stress disorder (PTSD).

Paroxetine is a phenylpiperidine derivative which is chemically unrelated to the tricyclic

or tetracyclic antidepressants. In receptor binding studies, paroxetine did not exhibit

significant affinity for the adrenergic (α

, α

, β), dopaminergic, serotonergic (5HT

), or histaminergic receptors of rat brain membrane. A weak affinity for the

muscarinic acetylcholine receptor was evident. The predominant metabolites of

paroxetine are essentially inactive as 5-HT reuptake inhibitors.

Pharmacokinetics

No clear dose relationship has been demonstrated for the antidepressant effects of

paroxetine at doses above 20 mg/day. The results of fixed-dose studies comparing

paroxetine and placebo in the treatment of depression, panic disorder, generalized anxiety

disorder and posttraumatic stress disorder revealed a dose dependency for some adverse

events.

Absorption: Paroxetine is well absorbed after oral administration. In healthy

volunteers, the absorption of a single 30 mg oral dose of paroxetine was not appreciably

affected by the presence or absence of food.

Both the rate of absorption and the terminal elimination half-life appear to be independent

of dose. Steady-state plasma concentrations of paroxetine are generally achieved in 7 to

14 days. No correlation has been established between paroxetine plasma

concentrations

and therapeutic efficacy or the incidence of adverse reactions.

In healthy young volunteers receiving a 20 mg daily dose of paroxetine for 15 days, the

mean maximal plasma concentration was 41 ng/mL at steady state (see Table 4). Peak

plasma levels generally occurred within 3 to 7 hours.

Distribution: Owing to the extensive distribution of paroxetine into the tissues, less than

1% of the total drug in the body is believed to reside in the systemic circulation.

At therapeutic concentrations, the plasma protein binding of paroxetine is approximately

95%.

Metabolism: Paroxetine is subject to a biphasic process of metabolic elimination which

involves presystemic (first-pass) and systemic pathways. First-pass metabolism is

extensive, but may be partially saturable, accounting for the increased bioavailability

observed with multiple dosing. The metabolism of paroxetine is accomplished in part by

cytochrome P450 (2D

). Saturation of this enzyme at clinical doses appears to account

for the nonlinearity of paroxetine kinetics with increasing dose and increasing duration of

Page 35 of 57

treatment. The role of this enzyme in paroxetine metabolism also suggests potential

drug-drug interactions (see DRUG INTERACTIONS). The majority of the dose appears

to be oxidized to a catechol intermediate which is converted to highly polar glucuronide

and sulphate metabolites through methylation and conjugation reactions. The

glucuronide and sulphate conjugates of paroxetine are about > 10,000 and 3,000 times

less potent, respectively, than the parent compound as inhibitors of 5-HT reuptake in rat

brain synaptosomes.

Elimination: Following the single or multiple dose administration of paroxetine at doses

of 20 to 50 mg, the mean elimination half-life value for healthy subjects appears to be

about 24 hours, although a range of 3 to 65 hours has been reported.

Approximately 64% of an administered dose of paroxetine is eliminated by the kidneys

and 36% in the feces. Less than 2% of the dose is recovered in the form of the parent

compound.

Special Populations and Conditions

Geriatrics: In elderly subjects, increased steady-state plasma concentrations and

prolongation of the elimination half life were observed relative to younger adult controls

(Table 4). Elderly patients should, therefore, be initiated and maintained at the lowest

daily dosage of paroxetine which is associated with clinical efficacy (see DOSAGE AND

ADMINISTRATION).

Hepatic Insufficiency: The results from a multiple dose pharmacokinetic study in

subjects with severe hepatic dysfunction suggest that the clearance of paroxetine is

markedly reduced in this patient group (see Table 4). As the elimination of paroxetine is

dependent upon extensive hepatic metabolism, its use in patients with hepatic impairment

should be undertaken with caution (see DOSAGE AND ADMINISTRATION, Special

Patient Populations).

Renal Insufficiency: In a single dose pharmacokinetic study in patients with mild to

severe renal impairment, plasma levels of paroxetine tended to increase with deteriorating

renal function (see Table 5). As multiple-dose pharmacokinetic studies have not been

performed in patients with renal disease, paroxetine should be used with caution in such

patients (see DOSAGE AND ADMINISTRATION, Special Patient Populations).

Page 36 of 57

Table 4

Steady state pharmacokinetics of paroxetine after doses of 20 mg daily

(mean and range)

Young Healthy

Subjects

[n=22]

Elderly Healthy

Subjects

[n=22]

Hepatically*

Impaired Subjects

[n=10]

(ss)

(ng/mL)

(12-90)

(18-154)

(11-147)

(ss)

(hours)

(3-7)

(1-10)

(2-11)

(ss)

(ng/mL)

(4-51)

(9-127)

(7-128)

AUC (ss) (ng

h/mL)

(179-1436)

1580

(221-3286)

1720

(194-3283)

(hour)

(8-43)

(13-92)

(17-152)

*Galactose elimination capacity 30-70% of normal.

A wide range of interindividual variation is observed for the pharmacokinetic parameters.

Table 5

Pharmacokinetics of paroxetine after a single 30 mg dose in normal subjects and

those with renal impairment

Renally Impaired

Severe

[n=6]

Renally Impaired

Moderate

[n=6]

Healthy young

subjects

[n=6]

(ng/mL)

46.2

(35.9-56.7)

(3.6-59.4)

19.8

(1.4-54.8)

(hour)

(4.0-11.0)

(1.5-9.0)

(1-7)

h/mL)

2046

(605-3695)

1053

(48-2087)

(21-2196)

(hour)

29.7

(10.9-54.8)

18.3

(11.2-32.0)

17.3

(9.6-25.1)

Creatinine clearance = 13-27 mL/min

Creatinine clearance = 32-46 mL/min

Creatinine clearance > 100 mL/min

Abbreviations:

= maximum plasma concentration; T

= time to reach C

= Area under the plasma concentration time curve at infinity

= terminal elimination half-life

STORAGE AND STABILITY

Store at 15 to 30°C

Page 37 of 57

DOSAGE FORMS, COMPOSITION AND PACKAGING

Description of the tablets:

JAMP Paroxetine Tablets 10 mg

Paroxetine Tablets USP 10 mg are immediate release, yellow colored, oval shaped, biconvex,

film-coated tablets with 'PA' debossed on one side and ‘1’ and ‘0’ on either of score line on

other side of tablet.

JAMP Paroxetine Tablets 20 mg

Paroxetine Tablets USP 20 mg are immediate release, pink colored, oval shaped, biconvex,

film-coated tablets with 'PA' debossed on one side and ‘2’ and ‘0’ on either of score line on

other side of tablet.

JAMP Paroxetine Tablets 30 mg

Paroxetine Tablets USP 20 mg are immediate release, blue colored, oval shaped, biconvex,

film-coated tablets with 'PA' debossed on one side and '30' on the other side.

Available

in package sizes of:

10 mg -

Bottles of 30’s and 100’s

20 mg -

Bottles of 30’s,100's and 500's

30 mg -

Bottles of 30's and 100’s

Composition

JAMP Paroxetine Tablets

tablets contain either 10 mg, 20 mg or 30 mg of paroxetine

(as paroxetine

hydrochloride). The tablets also contain the following non-medicinal

ingredients:

Dicalcium phosphate dihydrate, hydroxypropyl methylcellulose,

magnesium

stearate, polyethylene glycol, polysorbate 80, sodium starch glycolate,

titanium

dioxide, and one or more of the following: D&C Red No. 30 aluminum lake,

D&C

Yellow No. 10 aluminum lake, FD&C Blue No. 2 aluminum lake, FD&C Yellow

No. 6 aluminum lake.

Page 38 of 57

(-)-trans-4R-(4'-fluorophenyl)-3S-(3',4'-methylene-

dioxyphenoxymethyl)-piperidine hydrochloride hemihydrate.

PART II: SCIENTIFIC INFORMATION

PHARMACEUTICAL INFORMATION

Drug Substance

Proper Name:

Paroxetine hydrochloride

Chemical Name:

Molecular Formula:

FHCl

Molecular Weight:

374.8 g/mol (as hemihydrate salt)

329.4 g/mol (as free base)

Structural Formula:

paroxetine hydrochloride

Physicochemical properties:

Description:

a white to off-white solid

Melting point:

120-138°C

Page 39 of 57

pKa and pH Values:

It is not possible to measure directly the pKa of paroxetine in water owing to the aliphatic

nature of the piperidine ring system and the low solubility of paroxetine base.

Measurements in 50% aqueous dimethyl sulphoxide indicate an aqueous pKa of 9.90

compared to a calculated value of 9.84.

The pH of a saturated solution of paroxetine hydrochloride is 5.7 and a solution

containing 2 mg/mL of paroxetine hydrochloride is 6.3.

Oil-Water Coefficient of Partition:

The apparent partition coefficient of paroxetine hydrochloride in the octanol-water

system (Poct/water) is 3.38 (log P=0.53).

The partition coefficient of paroxetine base between octanol-water determined using a

solution of paroxetine hydrochloride in octanol and an aqueous phase of sodium

hydroxide solution (1M) is 222 (log P=2.35).

Paroxetine hydrochloride is slightly soluble in water (4.9 mg pure free base/mL).

CLINICAL TRIALS

Comparative Bioavailability Study

randomized,

double

blinded,

two-treatment,

two-period,

two-sequence,

single-dose,

crossover, comparative bioavailability study of

JAMP Paroxetine Tablets 30 mg tablets

(JAMP Pharma Corporation) and

PAXIL

30 mg tablets (GlaxoSmithKline Inc.), was

conducted in healthy, adult subjects under fasting conditions. A summary of the bioavailability

data from the 45 subjects completing the study is presented in the following table:

SUMMARY TABLE OF THE COMPARATIVE BIOAVAILABILITY DATA

Paroxetine

(1 x 30 mg)

Geometric Mean**

Arithmetic Mean (CV %)

Parameter

Test

Reference

% Ratio of

Geometric

Means

90% Confidence

Interval

(ng.h/mL)

465.73

600.60 (79.18)

421.61

543.83 (81.38)

110.5

105.2 - 116.0

(ng.h/mL)

503.50

715.29 (108.57)

453.84

649.25 (112.52)

110.9

105.6 - 116.6

(ng/mL)

22.26

24.79 (47.48)

21.28

23.60 (46.08)

104.6

99.5 - 110.0

5.33

(3.00-8.00)

5.00

(3.00-10.00)

17.40

(58.12)

17.00

(58.88)

Page 40 of 57

** Expressed as Geometric least square mean

JAMP Paroxetine Tablets (paroxetine as paroxetine hydrochloride) tablets, 30 mg (JAMP Pharma Corporation,

Canada)

† Pr

PAXIL

(paroxetine as paroxetine hydrochloride) tablets, 30 mg (GlaxoSmithKline Inc., Canada)

Expressed as the median (range) only

Expressed as the arithmetic mean (CV%) only

Depression

The efficacy of paroxetine tablets

(paroxetine hydrochloride) as a treatment for

depression has been established in six placebo-controlled clinical trials of 6 weeks in

duration performed

in patients with depression (ages 18 to 73). In these studies,

paroxetine tablets

was shown to be

significantly more effective than placebo in treating

depression according to the following measures: Hamilton Depression Rating Scale

(HDRS), the Hamilton depressed mood item, and the Clinical Global Impression (CGI)

– Severity of Illness.

A study of outpatients with recurrent major depressive disorder who had responded to

paroxetine tablets

(HDRS total score < 8) during an initial 8-week open-treatment phase

and were

then randomized to continuation on paroxetine tablets

or placebo for 1 year

demonstrated that a

significantly lower proportion of patients treated with paroxetine

tablets

(15%) compared to

placebo (39%) met criteria for partial relapse

. Criteria for

full relapse

were met by a

significantly lower percentage of paroxetine tablets

treated

patients (12%) compared to placebo

treated patients (28%). Effectiveness was similar for

male and female patients.

Partial relapse was characterized by requirement for additional antidepressant medication and fulfillment

of DSM IIIR criteria for major depressive episode

Full relapse was characterized by requirement for additional antidepressant treatment, fulfillment of DSM

IIIR criteria for major depressive episode, deterioration in depressive symptoms for at least 1 week,

increase in CGI-Severity of Illness score by ≥ 2 points and CGI-Severity of Illness score of ≥4 (least

moderately ill).

Page 41 of 57

Obsessive-Compulsive Disorder

Three double-blind, placebo-controlled clinical trials of 12 weeks in duration have been

performed to investigate the efficacy of paroxetine tablets

in obsessive-compulsive

disorder: two

flexible dose studies (20 to 60 mg/day) and one fixed dose study (20, 40,

& 60 mg/day). Results for the fixed dose study and one of the flexible dose studies

showed statistically significant differences from placebo in favour of paroxetine tablets

terms of mean change from

baseline to endpoint on the Yale-Brown Obsessive-

Compulsive Scale and/or the National

Institute of Mental Health Obsessive-Compulsive

Scale. In the fixed dose study, the

proportion of patients who were considered to be much

or very much improved at

endpoint according to a Clinical Global Impression of

Improvement was 15% (13/88) in

the placebo group, 20% (17/85) in the 20 mg/day

group, 36% (30/83) in the 40 mg/day group, and 37% (31/83) in the 60 mg/day group. In

the two flexible dose studies, placebo

response rates according to this criterion were 28%

(28/99) and 25% (19/75), while

paroxetine tablet

response rates were 45% (89/198) and

35% (28/79), respectively.

Panic Disorder

One fixed dose and three flexible dose placebo-controlled clinical trials of 10 to 12 weeks

in duration have been performed to investigate the efficacy of paroxetine tablets

in panic

disorder. The fixed dose study and two of the three flexible dose studies were supportive

of differences from placebo in favour of paroxetine tablets

for measures of panic attack

frequency. At

endpoint, in the fixed dose study, the proportion of patients who were free

of panic attacks was 44% (29/66) for the placebo group, 56% (33/59) for the 10 mg/day

paroxetine tablet

group, 57% (35/61) for the 20 mg/day paroxetine tablet

group, and 76%

(47/62) for the 40 mg/day paroxetine tablet

group.

Social Phobia (Social Anxiety Disorder)

One fixed dose and two flexible dose placebo-controlled clinical trials of 12 weeks in

duration have been performed to investigate the efficacy of paroxetine tablets

in social

phobia

(social anxiety disorder). These studies showed statistically significant

differences from

placebo in favour of paroxetine tablets

in terms of mean change from

baseline to endpoint on the

Liebowitz Social Anxiety Scale and the percentage of

therapeutic responders according

to the Clinical Global Impression of Improvement. In

the fixed dose study, the

proportion of patients who were considered to be much or very

much improved at week 12 of treatment according to the Clinical Global Impression of

Improvement was 28.3% (26/92) in the placebo group, 44.9% (40/89) in the 20 mg/day

group, 46.6% (41/88) in the 40 mg/day group, and 42.9% (39/91) in the 60 mg/day

group. In the two flexible

dose (20-50 mg/day) studies, placebo response rates

according to this criterion were

23.9% (22/92) and 32.4% (47/145), while paroxetine

tablet

response rates were 54.9% (50/91)

and 65.7% (90/137), respectively.

Generalized Anxiety Disorder

The effectiveness of paroxetine tablets

in the treatment of Generalized Anxiety

Disorder (GAD) (DSM IV) was demonstrated in two 8-week, multicentre, placebo-

controlled studies. One

trial was a flexible dose (20 to 50 mg/day) study while the

other was a multiple fixed dose (20 or 40 mg/day) study. In both studies paroxetine

tablets

demonstrated statistically

significant superiority over placebo on the primary

outcome measure - the Hamilton Rating Scale for Anxiety (HAM-A) total score, and on

a number of secondary outcomes including the HAM-A anxiety and tension items, the

Page 42 of 57

Clinical Global Impression (CGI) responder criterion and the Sheehan Disability Scale

(SDS). An additional 8-week

flexible dose study did not demonstrate a significant

difference between paroxetine tablets

(20 to

50 mg/day), and placebo on the primary

outcome measure. However, paroxetine tablets

(20 to

50 mg/day) was more effective

than placebo on many secondary study outcomes.

Posttraumatic Stress Disorder

The efficacy of paroxetine tablets

in the treatment of Posttraumatic Stress Disorder

(PTSD) was demonstrated in two 12 week, multicentre placebo controlled studies (Study

1 and Study 2) in adult patients who met the DSM-IV criteria for PTSD. Study outcome

was assessed by (i) the Clinician Administered PTSD Scale Part (CAPS-2) score and (ii)

the Clinical

Global Impression Global Improvement Item (CGI-I). The CAPS-2 is a

multi-item

instrument that measures the three PTSD diagnostic symptom clusters of:

reexperiencing/intrusion, avoidance/numbing and hyperarousal. The two primary

outcomes for each trial were (i) change from baseline to endpoint on the CAPS-2 total

score (17 items), and (ii) proportion of responders on the CGI-I, where responders were

defined as patients having a score of 1 (very much improved) or 2 (much improved).

Study 1 was a 12 week study comparing fixed paroxetine doses of 20 or 40 mg/day to

placebo. Paroxetine tablets

20 mg and 40 mg were demonstrated to be significantly

superior to placebo for the CAPS-2 total score, and on proportion of responders on the

CGI-I.

Study 2 was a 12-week flexible-dose study comparing paroxetine (20 to 50 mg daily) to

placebo. Paroxetine tablets

were demonstrated to be significantly superior to placebo for

the CAPS- 2 total scorer, and on proportion of responders on the CGI-I.

The majority (66-68%) of patients in these trials were women. Subgroup analyses did

not indicate differences in treatment outcomes as a function of gender. There were an

insufficient number of patients who were 65 years or older or were non-Caucasian to

conduct subgroup analyses on the basis of age or race, respectively.

DETAILED PHARMACOLOGY

Animal Pharmacology

In vitro: Paroxetine showed a high potency for the inhibition of 5-HT reuptake in rat

hypothalamic synaptosomes (K

=1.1nM), but exerted relatively weak effects upon

noradrenaline reuptake (K

=350nM). The predominant metabolites of paroxetine, a

sulphate and a glucuronide conjugate, were essentially inactive as 5-HT reuptake

inhibitors. Paroxetine has a low affinity for muscarinic cholinergic receptors

of 89 nM for displacement of [

H]quinuclidinyl benzilate). Animal studies have

indicated only weak anticholinergic properties.

Page 43 of 57

Radioligand binding techniques in rat brain, in vitro, have indicated that paroxetine has

little affinity for α

, α

and β-adrenoceptors, dopamine (D

), 5-HT

-like, 5-HT

histamine (H

) receptors at concentrations below 1 mcM. This lack of interaction with

post-synaptic receptors in vitro is substantiated by in vivo studies which demonstrate a

lack of CNS depressant and hypotensive properties.

In vivo: In mice, paroxetine (ED

=0.4 mg/kg p.o.) was associated with potent and

prolonged potentiation of the hypermotility induced by the 5-HT precursor,

5-hydroxytryptophan. Similarly, the anticonvulsant effects of 5-hydroxytryptophan in a

mouse electroshock model were potentiated by paroxetine (ED

=0.4 mg/kg p.o.). In rats,

paroxetine (ED

=0.8 mg/kg p.o.) inhibited the hypermotility induced by

p-chloroamphetamine, an agent which depletes neuronal 5-HT stores. Paroxetine,

1 mg/kg i.p., in conscious rats with chronically implanted cortical electrodes, produced

essentially no changes in the power spectrum and frequency analysis of the EEG.

Electrophysiological measures have demonstrated that paroxetine has a vigilance-

increasing activity in animals. Oral doses of paroxetine 0.32 to 18 mg/kg to rats

lengthened the waking period and shortened the slow-wave and paradoxical sleep periods

in a dose-dependent fashion. As with other selective 5-HT uptake inhibitors, paroxetine,

at a dose of 5 mg/kg i.p., causes symptoms of excessive 5-HT receptor stimulation when

administered to rats previously given monoamine oxidase (MAO) inhibitors such as

tranylcypromine or phenelzine, or the 5-HT precursor L-tryptophan.

Behavioural and EEG studies indicate that paroxetine is weakly activating at doses above

those generally required to inhibit 5-HT reuptake. The activating properties are not

"amphetamine-like" in nature. In rats trained to discriminate d-amphetamine, 1 mg/kg

i.p., from saline, no generalization to amphetamine was observed after administration of

paroxetine (0.3, 1, 3 or 10 mg/kg i.p.). Paroxetine caused seizures in mice at a lethal dose

of 300 mg/kg p.o. At a dose of 50 mg/kg p.o., paroxetine lowered the threshold for

electroshock-induced seizures in mice.

Animal studies indicate that paroxetine is well tolerated by the cardiovascular system.

When the cardiovascular effects of paroxetine and amitriptyline were compared in the

conscious rabbit and anaesthetized cat, intravenous doses of paroxetine approximately

2 to 4 times higher (on a mg/kg basis) than those of amitriptyline were required to

produce significant changes in blood pressure, heart rate and electrocardiographic

parameters. Similarly, in the pentobarbital anaesthetized dog, i.v. imipramine,

amitriptyline and clomipramine (in doses of 10 mg/kg) caused severe atrioventricular

block and ventricular arrhythmia’s, while equivalent doses of paroxetine resulted in only

slight prolongation of the PQ interval. In addition, low doses (0.3 to 1 mg/kg) of the

tricyclic antidepressants caused marked tachycardia, whereas paroxetine in doses up to

10 mg/kg had no effect on heart rate.

Studies in the spontaneous hypertensive rat indicate that, in contrast to antidepressants

which inhibit the uptake of noradrenaline, paroxetine at 5 mg/kg i.v. has a much reduced

propensity to inhibit the antihypertensive effects of guanethidine.

Page 44 of 57

5-HT is transported into blood platelets and central neurons by a similar active uptake

transporter mechanism in the cell membrane. Thus, in common with other selective

5-HT reuptake inhibitors, administration of paroxetine results in depletion of 5-HT from

platelets. This has been reported after repeated daily administration of paroxetine at

doses of 0.1, 1 and 10 mg/kg i.p. in mice and rats, 1 to 7.5 mg/kg p.o. in monkeys and

10-50 mg orally to healthy human volunteers. Similarly, whole blood 5-HT levels were

shown to be depleted in depressed patients after paroxetine administration.

Human Pharmacology

Paroxetine 30 mg administered in single doses to healthy non-depressed volunteers did

not impair psychomotor function which was measured by psychomotor tasks such as

Morse tapping and motor manipulation, assessment of subjective perception and general

assessment of arousal.

Paroxetine at doses of up to 40 mg daily produces no clinically significant changes in

blood pressure, heart rate or ECG after administration to healthy subjects.

TOXICOLOGY

General toxicity studies have been conducted in rhesus monkeys and rats, in both of

which the metabolic pathway for paroxetine is the same as in man.

Acute Toxicity

In relation to the clinical dose, the acute LD50 of paroxetine is very high in both mice

and rats (approximately 350 mg/kg).

Long-Term Toxicity

The no-toxic effect levels in the rhesus monkeys and rats were 4 to 10 times and 6 to 15

times the recommended range of clinical doses respectively. At higher doses (40 mg/kg

for 3 months and 25 mg/kg for 12 months), lipidosis was observed in several tissues of

rats (lungs, mesenteric lymph nodes, epididymides, retinal tissues - the latter by electron

microscopy only). As paroxetine is a lipophilic amine with both hydrophobic and

hydrophilic moieties, it may accumulate in lysosomes leading to an impairment of lipid

catabolism and, hence, the accumulation of lipids within the lysosomes. It should be

noted that the slight degree of lipidosis seen in the rat was restricted to doses and plasma

levels much higher than those observed in man. In a clinical study investigating

lamellated inclusion bodies in peripheral white blood cells during long-term therapy, no

difference between placebo and paroxetine could be detected.

Page 45 of 57

Carcinogenicity

No carcinogenic potential was detected in rat (dose levels of 1, 5 and 20 mg/kg/day) and

mouse (dose levels of 1, 5 and 25 mg/kg/day) life-span studies. A non dose-related

increase in malignant liver cell tumours occurred in male mice at 1 and 5 mg/kg/day

which was statistically significant at 5 mg/kg/day. There was no increase at

25 mg/kg/day or in female mice and the incidence was within the historical control range.

Reproduction and Impairment of Fertility Studies

5-Hydroxytryptamine and compounds modulating this amine are known to affect

reproductive function in animals and at high dose levels cause marked overt toxicity.

Paroxetine at 15 and 50 mg/kg (hydrochloride salt) has been shown to impair

reproductive function in rats.

In male rats, chronic administration of a 50 mg/kg dose has been associated with

granulomatous reactions in the epididymides accompanied by atrophy and degeneration

of the seminiferous tubules. There were no biologically significant effects on fertility of

female rats but corpora lutea count was slightly reduced and preimplantation loss slightly

increased at 50 mg/kg in association with marked maternal toxicity.

Teratology Studies

Reproduction studies were performed in rats and rabbits at doses up to 42 and 5 times the

maximum recommended daily human dose (60 mg) on a mg/kg basis. These are 8.3 (rat)

and 1.7 (rabbit) times the maximum recommended human dose on a mg/m

basis. These

studies have revealed no evidence of teratogenic effects or of selective toxicity to the

embryo.

Immunotoxicity Studies

Specific studies have demonstrated that paroxetine is unlikely to possess the potential for

immunotoxicity.

Serum samples were obtained from depressed patients who had received 30 mg of

paroxetine daily for between six and twelve months, from groups of rats on a repeat dose

toxicity study in which daily doses of 1, 5 and 25 mg/kg of paroxetine were administered

for 52 weeks, from guinea pigs epicutaneously exposed (topically under an occlusive

patch) to paroxetine and from New Zealand White (NZW) rabbits parenterally (i.m. and

s.c.) injected with paroxetine in Freund's adjuvant. In addition, as a positive control, sera

were obtained from NZW rabbits which had been immunized by i.m. and s.c. injections

of Freund's adjuvant emulsions containing paroxetine chemically conjugated to bovine

gamma globulin (BGG).

Page 46 of 57

Serum antibody levels were assessed by enzyme- or radio-immunoassays (ELISA or

RIA). No anti-paroxetine antibody activity was detected in serum samples from patients,

from rats in the toxicity study, from guinea pigs epicutaneously exposed to paroxetine, or

from rabbits parenterally injected with paroxetine. Serum anti-paroxetine antibody was

detected in rabbits immunized with Freund's adjuvant emulsions containing paroxetine

coupled with BGG, verifying that the RIA system employed was capable of detecting

antibodies directed against paroxetine.

Paroxetine also did not induce contact sensitivity reactions in guinea pigs following

epicutaneous exposure.

Page 47 of 57

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Paxil

(Paroxetine Tablets; 10 mg, 20 mg and 30 mg), Control No.: 237146,

Product Monograph, GlaxoSmithKline Inc., Date of revision: June 18, 2020.

IMPORTANT: PLEASE READ

Page 52 of 57

PART III: CONSUMER INFORMATION

Pr

JAMP Paroxetine Tablets

Paroxetine Tablets USP

This leaflet is part III of a three-part "Product Monograph"

published when JAMP Paroxetine Tablets

was approved

for sale in Canada and is designed specifically for

Consumers. This leaflet is a summary and will not tell you

everything about JAMP Paroxetine Tablets. Contact your

doctor or pharmacist if you have any questions about the

drug.

Please read this information before you start to take your

medication, even if you have taken this drug before. Keep

this information with your medicine in case you need to

read it again.

What the medication is used for:

JAMP Paroxetine Tablets

has been prescribed to you by

your doctor to relieve your symptoms of:

depression (feeling sad, a change in appetite or weight,

difficulty concentrating or sleeping, feeling tired,

headaches, unexplained aches and pain)

panic attacks

social phobia (social anxiety disorder) - avoidance and/or

fear of social situations

generalized anxiety or nervousness

obsessive

compulsive

disorder

(recurrent

intrusive

thought, feeling,

idea

sensation; recurrent pattern

behaviour, or unwanted thoughts or actions), or

posttraumatic stress disorder (anxiety following a traumatic

event, for example a car crash, physical

assault, natural

disaster such as an earthquake)

What it does:

JAMP Paroxetine Tablets

belongs to the family of medicines

called selective serotonin reuptake inhibitors. JAMP

Paroxetine Tablets

is thought to work by increasing the levels

of a chemical in the brain called serotonin

(5-hydroxytryptamine).

When it should not be used:

Do not use JAMP Paroxetine Tablets

if you are:

allergic to it or any of the components of its formulation

(see list of components at the end of this section)

currently taking or have recently taken monoamine

oxidase (MAO) inhibitor antidepressants (e.g.

phenelzine sulphate, moclobemide) or linezolid, a MAO

inhibitor antibiotic

currently taking or have recently taken thioridazine or

pimozide

What the medicinal ingredient is:

Paroxetine hydrochloride.

What the important nonmedicinal ingredients are:

FD&C yellow No. 6 Aluminium Lake (in JAMP

Paroxetine Tablets 10 mg only).

Other non-medicinal ingredients include: dicalcium phosphate

dihydrate, hydroxypropyl methylcellulose, magnesium stearate,

polyethylene glycol, polysorbate 80, sodium starch

glycolate,

titanium dioxide, and one or more of the following: D&C Red No.

30 aluminum lake, D&C Yellow No. 10 aluminum lake, FD&C

Blue No. 2 aluminum lake, FD&C Yellow No. 6 aluminum lake.

There is no ethanol, gluten, lactose, sulfite, or tartrazine in

JAMP Paroxetine Tablets.

What dosage forms it comes in:

JAMP Paroxetine Tablets

is available as tablets containing 10

mg (yellow), 20 mg (pink), or 30 mg (blue) paroxetine (as

paroxetine hydrochloride).

During treatment with these types of medications it is

important that you and your doctor have good ongoing

communication about how you are feeling.

JAMP Paroxetine Tablets

is not for use in children under 18 years of

age.

Changes in Feelings and Behaviour:

It is important that you have good communication with your

doctor about how you feel. Discussing your feelings and

treatment with a friend or relative who can tell you if they think

you are getting worse is also useful.

Some patients may feel worse when first starting or changing

the dose of drugs such as JAMP Paroxetine Tablets. You may

feel more anxious or may have thoughts of hurting yourself or

others, especially if you have had thoughts of hurting yourself

before. These changes in feelings can happen in patients treated

with drugs like JAMP Paroxetine Tablets

for any condition,

and at any age, although it may be more likely if you are aged

18 to 24 years old. If this happens, see your doctor

immediately. Do not stop taking JAMP Paroxetine Tablets

your own.

Taking medicines like JAMP Paroxetine Tablets may increase

your risk of experiencing sexual problems, which may continue

after JAMP Paroxetine Tablets has been discontinued,

including for months or years afterwards in some cases. Tell

your doctor if you experience symptoms such as a decrease in

sexual desire, performance or satisfaction.

Taking JAMP Paroxetine Tablets may increase your risk of breaking

a bone if you are elderly or have osteoporosis or have other major

risk factors for breaking a bone. You should take extra care to avoid

falls especially if you get dizzy or have low blood pressure.

Medicines like JAMP Paroxetine Tablets

may affect your sperm.

Fertility in some men may be reduced while taking JAMP

Paroxetine Tablets.

BEFORE you use JAMP Paroxetine Tablets

tell your doctor or

pharmacist:

WARNINGS AND PRECAUTIONS

ABOUT THIS MEDICATION

IMPORTANT: PLEASE READ

Page 53 of 57

all your medical conditions, including a history of

seizures, liver or kidney disease, heart problems

any medications (prescription or non prescription) which

you are taking or have recently taken, especially

monoamine oxidase inhibitor antidepressants (e.g.

phenelzine sulphate, moclobemide) or any other

antidepressants, thioridazine, pimozide, drugs used to

prevent fits (anticonvulsants), drugs for Parkinson’s

disease, or drugs containing tryptophan

if you are taking tamoxifen (used to treat breast cancer)

if you have ever had any allergic reaction to

medications, food, etc.

any natural or herbal products you are taking (e.g. St.

John’s Wort)

if you are pregnant or thinking about becoming

pregnant, or if you are breast feeding

your habits of alcohol and /or street drug consumption

if you drive a vehicle or perform hazardous tasks during

your work

if you had a recent bone fracture or were told you have

osteoporosis or risk factors for osteoporosis

if you have a bleeding disorder or have been told that

you have low platelets

if you are allergic to a particular yellow dye known as

FD&C Yellow No. 6 aluminium lake

Effects on Pregnancy and Newborns:

As stated above, ask your doctor or pharmacist for advice

before taking any medicine including JAMP Paroxetine

Tablets. If you are already taking/using JAMP

Paroxetine Tablets and have just found out that you are

pregnant, you should talk to your doctor immediately.

You should also talk to your doctor if you are planning

to become pregnant.

Taking JAMP Paroxetine Tablets

in early stages of

pregnancy:

Some studies have suggested an increased risk of birth

defects particularly heart defects, in babies whose mothers

received paroxetine tablets in the first few months of

pregnancy.

These studies found that about 2 in 100 babies (2%)

whose mothers received paroxetine in early pregnancy

had a heart defect, compared with the normal rate of 1 in

100 babies (1%) seen in the general population. Also, in

cases where paroxetine tablets has been used, there have

been reports of premature births although it is not known

if these premature births are due to the use of paroxetine

tablets.

Taking JAMP Paroxetine Tablets

in later stages of

pregnancy:

Possible complications at birth (from taking any newer

antidepressant, including JAMP Paroxetine Tablets):

Post-marketing reports indicate that some newborns whose

mothers took an SSRI (selective serotonin reuptake

inhibitor) or other newer antidepressant, during pregnancy

have developed complications at birth requiring prolonged

hospitalization, breathing support and tube feeding.

Reported symptoms included feeding and/or breathing difficulties,

seizures, tense or overly relaxed muscles, jitteriness and constant

crying.

In most cases, the newer antidepressant was taken during the

third trimester of pregnancy. These symptoms are consistent

with either a direct adverse effect of the antidepressant on the

baby, or possibly a discontinuation syndrome caused by sudden

withdrawal from the drug. These symptoms normally resolve

over time. However, if your baby experiences any of these

symptoms, contact your doctor as soon as you can.

Persistent Pulmonary Hypertension (PPHN) and newer

antidepressants, including JAMP Paroxetine Tablets:

The use of JAMP Paroxetine Tablets

during pregnancy, particularly

during late pregnancy, may increase the risk of a serious lung

condition called persistent pulmonary hypertension of the newborn

(PPHN) that causes breathing difficulties in newborns soon after

birth. In the general population, PPHN is known to occur in about 1

or 2 per 1000 newborns but this may be increased 4 to 6 times in

babies whose mothers used JAMP Paroxetine Tablets during late

pregnancy.

If you are pregnant and taking an SSRI, or other newer

antidepressants, you should discuss the risks and benefits of the

various treatment options with your doctor. It is very important

that you do NOT stop taking these medications without first

consulting your doctor. See SIDE EFFECTS AND WHAT TO

DO ABOUT THEM section for more information.

Angle-closure Glaucoma:

JAMP Paroxetine Tablets can cause an acute attack of glaucoma.

Having your eyes examined before you take JAMP Paroxetine

Tablets could help identify if you are at risk of having angle-closure

glaucoma. Seek immediate medical attention if you experience:

eye pain

changes in vision

swelling or redness in or around the eye

Do not use JAMP Paroxetine Tablets if you are taking or have

recently taken (within the last 2 weeks) monoamine oxidase

inhibitors, methylthioninium chloride (methylene blue),

thioridazine,

or pimozide.

You should tell your doctor if you are taking or have

recently taken any medications (prescription, non-

prescription or natural/herbal), especially:

other antidepressants, such as SSRIs and certain tricyclics

other drugs that affect serotonin such as, lithium, linezolid,

tramadol, tryptophan, St. John’s Wort, triptans used to treat

migraines

certain medicines used to treat pain, such as fentanyl (used

in anaesthesia or to treat chronic pain), tramadol,

tapentadol, meperidine, methadone, pentazocine

tamoxifen, which is used to treat breast cancer or fertility

problems

INTERACTIONS WITH THIS MEDICATION

IMPORTANT: PLEASE READ

Page 54 of 57

certain medicines used to treat patients with irregular

heart beats (arrhythmias)

certain medicines used to treat schizophrenia

certain medicines used to treat bipolar depression,

such as lithium

a combination of fosamprenavir and ritonavir, used to

treat Human Immunodeficiency Virus (HIV) infection

procyclidine, which is used to treat Parkinson’s

Disease or other movement disorders

metoprolol, which is used to treat high blood pressure

and angina

certain medicines which may affect blood clotting and

increase bleeding, such as oral anti-coagulants (e.g.

warfarin, dabigatran), acetylsalicylic acid (e.g. aspirin)

and other non-steroidal anti-inflammatory drugs (e.g.

ibuprofen)

certain medicines used to treat epilepsy

in general, drinking alcoholic beverages should be

kept to a minimum or avoided completely while

taking JAMP Paroxetine Tablets

certain medicines used to treat cough, such as

dextromethorphan

Usual dose:

It is very important that you take JAMP Paroxetine

Tablets

exactly as your doctor has instructed. Generally

most people take between 20 mg to 40 mg of JAMP

Paroxetine Tablets

per day for depression, obsessive-

compulsive disorder, panic disorder, social phobia

(social anxiety disorder), generalized anxiety disorder

and posttraumatic stress disorder; although your doctor

may start you at 10 mg per day for panic disorder.

Take your tablets in the morning, preferably with

food. You should swallow the tablets whole with

water. Do not chew them.

You should continue to take your medicine even if

you do not feel better, as it may take a number of

weeks for your medicine to work.

Keep taking your tablets, as instructed, until the doctor

tells you to stop.

Talk to your doctor before you stop taking your

medication on your own.

Remember: This medicine has been prescribed only for

you. Do not give it to anybody else, as they may

experience undesirable effects, which may be serious.

Missed Dose:

If you forget to take your tablet in the morning, take it as soon

as you remember. Take your next dose at the normal time the

next morning, then carry on as before. Do not try to make up

for a missed dose by taking a double dose the next time.

Overdose:

If you have taken a large number of tablets all at once,

contact your doctor or the nearest hospital emergency

department immediately, even though you may not feel

sick. Show the doctor your pack of tablets.

If you think you have taken too much JAMP Paroxetine

Tablets, contact your healthcare professional, hospital

emergency department or regional poison control centre

immediately, even if there are no symptoms.

Like all medications, JAMP Paroxetine Tablets

cause some side effects. You may not experience any of

them. For most patients these side effects are likely to

be minor and temporary. However, some may be

serious. Some of these side effects may be dose related.

Consult your doctor if you experience these or other

side effects, as the dose may have to be adjusted.

If you experience an allergic reaction (including skin rash,

hives, swelling, trouble breathing) or any severe or

unusual side

effects, stop taking the drug and contact

your doctor immediately.

The most common side effects of JAMP Paroxetine Tablets

are:

nausea/vomiting

dry mouth

drowsiness

weakness

dizziness

sweating

tremor

nervousness

feeling agitated

blurred vision

sleep disturbances

weight gain

sexual problems. Although psychiatric disorders are often

associated with decreases in sexual desire, performance and

satisfaction,

treatment with this class of medication may lead

to further decreases, which may continue after the drug is

stopped.

Other effects may include loss of appetite, constipation,

diarrhea, abnormal dreams (including nightmares), headache

and menstrual period disorders (including heavy periods,

bleeding between periods and absence of periods).

JAMP Paroxetine Tablets

does not usually affect people’s

normal activities. However, some people feel sleepy while

taking it, in which case they should not drive or operate

machinery.

JAMP Paroxetine Tablets

may raise cholesterol levels in some

patients.

Discontinuation Symptoms

Contact your doctor before stopping or reducing your dosage

of JAMP Paroxetine Tablets. Symptoms such as dizziness,

lightheadedness, nausea, vomiting, agitation/restlessness,

anxiety, sweating, headache, sleep disturbance, electric shock

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

PROPER USE OF THIS MEDICATION

IMPORTANT: PLEASE READ

Page 55 of 57

sensations, tinnitus (buzzing, hissing, whistling, ringing or

other persistent noise in the ears) and other symptoms have

been reported after stopping treatment, reducing the dosage of

paroxetine tablets, or when a dose is missed. These symptoms

usually disappear without needing treatment. Tell your doctor

immediately if you have these or any other symptoms. Your

doctor may adjust the dosage of JAMP Paroxetine Tablets to

alleviate the symptoms. See WARNINGS AND

PRECAUTIONS section for more information.

Effects on Newborns

Some newborns whose mothers took an SSRI (Selective

Serotonin Reuptake Inhibitor) or other newer antidepressant,

such as paroxetine tablets, during pregnancy have shown such

symptoms as breathing and feeding difficulties, jitteriness and

constant crying. If your baby experiences any of these

symptoms, contact your doctor as soon as you can. See

WARNINGS AND PRECAUTIONS section for more

information.

SERIOUS SIDE EFFECTS, HOW OFTEN THEY

HAPPEN AND WHAT TO DO ABOUT THEM

Symptom / effect

Talk with your

doctor or

pharmacist

right away

Seek

immediate

emergency

medical

assistance

Only

if

severe

In all

cases

Uncommon

Hallucinations

[strange visions

or sounds]

Uncommon

Uncontrollable

movements of

the body or

face

Uncommon

Inability to

urinate or loss

of control of

the bladder

(urinary

incontinence).

Uncommon

Dilated pupils

Uncommon

Low blood

pressure (may

cause dizziness,

lightheadedness

or fainting when

standing up from

a sitting down or

lying position)

Uncommon

Low Platelets

[bruising or

unusual

bleeding from

the skin or

other areas]

Rare

Severe allergic

reactions [red

and lumpy skin

rash, hives,

itching.

swelling of the

lips, face,

tongue, throat,

SERIOUS SIDE EFFECTS, HOW OFTEN THEY

HAPPEN AND WHAT TO DO ABOUT THEM

Symptom / effect

Talk with your

doctor or

pharmacist

right away

Seek

immediate

emergency

medical

assistance

Only

if

severe

In all

cases

trouble

breathing,

wheezing,

shortness of

breath, skin

rashes, collapse

or loss of

consciousness]

Rare

Allergic

reactions (skin

rash alone)

Rare

Low sodium

level in

blood

[symptoms of

tiredness,

weakness,

confusion

combined

with

achy, stiff or

uncoordinated

muscles]

Rare

Akathisia

[feeling restless

and unable to

sit or stand

still]

Rare

Mania

[overactive

behaviour and

thoughts]

Rare

Seizures [loss

consciousness

with

uncontrollable

shaking (“fit”)]

Rare

Restless Legs

Syndrome

(irresistible

urge to

move

the legs)

Rare

Angle-closure

Glaucoma [eye

pain, changes

in vision and

swelling or

redness in or

around the eye]

Rare

Abnormal

secretion

breast milk in

women

Rare

Increased

sensitivity

the skin to

sunlight

IMPORTANT: PLEASE READ

Page 56 of 57

SERIOUS SIDE EFFECTS, HOW OFTEN THEY

HAPPEN AND WHAT TO DO ABOUT THEM

Symptom / effect

Talk with your

doctor or

pharmacist

right away

Seek

immediate

emergency

medical

assistance

Only

if

severe

In all

cases

Rare

Swelling of

hands, ankles

or feet

Rare

Menstrual

period

disorders

(including

heavy periods,

bleeding

between

periods and

absence

periods).

Very Rare

Serotonin

syndrome

Neuroleptic

Malignant

Syndrome

combination of

most or all of

following:

confusion,

restlessness,

sweating,

shaking,

shivering, high

fever,

hallucinations,

sudden jerking

of the

muscles,

muscle

stiffness,

feeling very

agitated or

irritable, fast

heartbeat]. The

severity can

increase,

leading to loss

consciousness.

Very Rare

Gastrointestinal

bleeding

[vomiting

blood or

passing blood

in stools]

Very Rare

Liver disorder

[symptoms

include

nausea,

vomiting, loss

of appetite

combined with

itching,

yellowing of

the skin or

eyes, dark

urine]

SERIOUS SIDE EFFECTS, HOW OFTEN THEY

HAPPEN AND WHAT TO DO ABOUT THEM

Symptom / effect

Talk with your

doctor or

pharmacist

right away

Seek

immediate

emergency

medical

assistance

Only

if

severe

In all

cases

Very Rare

A severe

widespread

rash with

blisters and

peeling skin,

often

with

sores or pain in

the mouth or

eyes

Very Rare

Skin rash,

which

blister, and

looks like

small

targets

(central dark

spots

surrounded by

a paler area,

with a

dark

ring around the

edge) called

erythema

multiforme

Warnings

&

Precautions

- Changes in

feelings or

behaviour

(anger,

anxiety,

suicidal

violent

thoughts)

- Thoughts of

death or

suicide

This is not a complete list of side effects. For any unexpected

effects while taking JAMP Paroxetine Tablets

,

contact your

doctor or pharmacist.

Keep all medicines out of sight and reach of children

Store at room temperature (15-30°C) in a dry place

Keep container tightly closed

If your doctor tells you to stop taking

JAMP Paroxetine Tablets

please return any

leftover medicine to your pharmacist.

HOW TO STORE IT

IMPORTANT: PLEASE READ

Page 57 of 57

If you want more information about JAMP Paroxetine

Tablets:

Talk to your healthcare professional

Find the full Product Monograph that is prepared for

healthcare professionals and includes this Consumer

Information by visiting the Health Canada website

(https://health-products.canada.ca/dpd-bdpp/index-

eng.jsp); or by contacting the sponsor, JAMP Pharma

Corporation, at 1-866-399-9091.

This leaflet was prepared by JAMP Pharma Corporation:

1310 rue Nobel,

Boucherville, Quebec, J4B 5H3

Date Prepared: November 12, 2020.

REPORTING SIDE EFFECTS

You can report any suspected side effects associated with

use of health products to Health Canada by:

Visiting the Web page on Adverse Reaction

Reporting

https://www.canada.ca/en/health-

canada/services/drugs-health-products/medeffect-

canada/adverse-reaction-reporting.html) for

information on how to

report online, by mail or by

fax; or

Calling toll-free at 1-866-234-2345.

NOTE: Contact your health professional if you need

information about how to manage your side effects. The

Canada Vigilance Program does not provide medical advice.

MORE INFORMATION

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