Treatment of
- Major Depressive Episode
- Obsessive Compulsive Disorder
- Panic Disorder with and without agoraphobia
- Social Anxiety Disorders/Social phobia
- Generalised Anxiety Disorder
- Post-Traumatic Stress Disorder

Route of administration: Oral.
Posology
- MAJOR DEPRESSIVE EPISODE

- The recommended dose is 20 mg daily. In general, improvement in patients starts after one
week but may only become evident from the second week of therapy.
- As with all antidepressant medicinal products, dosage should be reviewed and adjusted if
necessary within 3 to 4 weeks of initiation of therapy and thereafter as judged clinically
appropriate. In some patients, with insufficient response to 20 mg, the dose may be
increased gradually up to a maximum of 50 mg a day in 10 mg steps according to the
patient's response.
- Patients with depression should be treated for a sufficient period of at least 6 months to
ensure that they are free from symptoms.
- OBSESSIVE COMPULSIVE DISORDER
- The recommended dose is 40 mg daily. Patients should start on 20 mg/day and the dose
may be increased gradually in 10 mg increments to the recommended dose. If after some
weeks on the recommended dose insufficient response is seen some patients may benefit
from having their dose increased gradually up to a maximum of 60 mg/day.
- Patients with OCD should be treated for a sufficient period to ensure that they are free from
symptoms. This period may be several months or even longer .
- PANIC DISORDER
- The recommended dose is 40 mg daily. Patients should be started on 10 mg/day and the
dose gradually increased in 10 mg steps according to the patient's response up to the
recommended dose. A low initial starting dose is recommended to minimise the potential
worsening of panic symptomatology, which is generally recognised to occur early in the
treatment of this disorder. If after some weeks on the recommended dose insufficient
response is seen some patients may benefit from having their dose increased gradually up
to a maximum of 60 mg/day.
- Patients with panic disorder should be treated for a sufficient period to ensure that they are
free from symptoms. This period may be several months or even longer .
- SOCIAL ANXIETY DISORDER/SOCIAL PHOBIA
- The recommended dose is 20 mg daily. If after some weeks on the recommended dose
insufficient response is seen some patients may benefit from having their dose increased
gradually in 10 mg steps up to a maximum of 50 mg/day. Long-term use should be
regularly evaluated
- GENERALISED ANXIETY DISORDER
- The recommended dose is 20 mg daily. If after some weeks on the recommended dose
insufficient response is seen some patients may benefit from having their dose increased
gradually in 10 mg steps up to a maximum of 50 mg/day. Long-term use should be
regularly evaluated.
- POST-TRAUMATIC STRESS DISORDER
- The recommended dose is 20 mg daily. If after some weeks on the recommended dose
insufficient response is seen some patients may benefit from having their dose increased
gradually in 10 mg steps up to a maximum of 50 mg/day. Long-term use should be
regularly evaluated.
- GENERAL INFORMATION
- WITHDRAWAL SYMPTOMS SEEN ON DISCONTINUATION OF PAROXETINE
- Abrupt discontinuation should be avoided. The taper phase regimen used involved
decreasing the daily dose by 10 mg at weekly intervals. If intolerable symptoms occur
following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue
decreasing the dose, but at a more gradual rate.
- Special Populations:
- Older people
- Increased plasma concentrations of paroxetine occur in elderly subjects, but the range of
concentrations overlaps with that observed in younger subjects. Dosing should commence
at the adult starting dose. Increasing the dose might be useful in some patients, but the
maximum dose should not exceed 40 mg daily.
- Children and adolescents (7-17 years)
- Paroxetine should not be used for the treatment of children and adolescents, paroxetine to
be associated with increased risk for suicidal behaviour and hostility. In addition, efficacy
has not been adequately demonstrated.
- Children aged below 7 years
- Paroxetine should not be used, as long as safety and efficacy in this age group have not
been established.
- Renal/hepatic impairment
- Increased plasma concentrations of paroxetine occur in patients with severe renal
impairment (creatinine clearance less than 30 ml/min) or in those with hepatic impairment.
Therefore, dosage should be restricted to the lower end of the dosage range.
Method of administration
- It is recommended that paroxetine is administered once daily in the morning with food.
- The tablet should be swallowed rather than chewed.

Hypersensitivity to the active substance(s) or to any of the excipients Paroxetine is contraindicated in combination with monoamine oxidase inhibitors (MAOIs). In exceptional circumstances, linezolid (an antibiotic which is a reversible non-selective MAOI) can be given in combination with paroxetine provided that there are facilities for close observation of symptoms of serotonin syndrome and monitoring of blood pressure. Treatment with paroxetine can be initiated: - two weeks after discontinuation of an irreversible MAOI, or - at least 24hrs after discontinuation of a reversible MAOI (e.g. moclobemide, linezolid, methylthioninium chloride (methylene blue); a preoperative visualising agent which is a reversible non-selective MAOI)). At least one week should elapse between discontinuation of paroxetine and initiation of therapy with any MAOI. Paroxetine should not be used in combination with thioridazine, because, as with other drugs which inhibit the hepatic enzyme CYP450 2D6, paroxetine can elevate plasma levels of thioridazine. Administration of thioridazine alone can lead to QTc interval prolongation with associated serious ventricular arrhythmia such as torsades de pointes, and sudden death. Paroxetine should not be used in combination with pimozide.

Treatment with paroxetine should be initiated cautiously two weeks after terminating
treatment with an irreversible MAOI or 24 hours after terminating treatment with a reversible MAO inhibitor. Dosage of paroxetine should be increased gradually until an
optimal response is reached.
- Paediatric population
- Paroxetine should not be used in the treatment of children and adolescents under the age of
18 years. Suicide-related behaviours (suicide attempt and suicidal thoughts), and hostility
(predominantly aggression, oppositional behaviour and anger) were more frequently
observed among children and adolescents treated with antidepressants. If, based on clinical
need, a decision to treat is nevertheless taken, the patient should be carefully monitored for
the appearance of suicidal symptoms. In addition, long-term safety data in children and
adolescents concerning growth, maturation and cognitive and behavioural development are
lacking.
- Suicide/suicidal thoughts or clinical worsening
- Depression is associated with an increased risk of suicidal thoughts, self harm and suicide
(suicide-related events). This risk persists until significant remission occurs. As
improvement may not occur during the first few weeks or more of treatment, patients
should be closely monitored until such improvement occurs. It is general clinical
experience that the risk of suicide may increase in the early stages of recovery.
- Other psychiatric conditions for which paroxetine are prescribed can also be associated
with an increased risk of suicide-related events. In addition, these conditions may be comorbid
with major depressive disorder. The same precautions observed when treating
patients with major depressive disorder should therefore be observed when treating patients
with other psychiatric disorders.
- Patients with a history of suicide-related events, or those exhibiting a significant degree of
suicidal ideation prior to commencement of treatment are known to be at greater risk of
suicidal thoughts or suicide attempts, and should receive careful monitoring during
treatment.
- Close supervision of patients and in particular those at high risk should accompany drug
therapy especially in early treatment and following dose changes. Patients (and caregivers
of patients) should be alerted about the need to monitor for any clinical worsening, suicidal
behaviour or thoughts and unusual changes in behaviour and to seek medical advice
immediately if these symptoms present.
- Akathisia/psychomotor restlessness
- The use of paroxetine has been associated with the development of akathisia, which is
characterized by an inner sense of restlessness and psychomotor agitation such as an
inability to sit or stand still usually associated with subjective distress. This is most likely
to occur within the first few weeks of treatment. In patients who develop these symptoms,
increasing the dose may be detrimental.
- Serotonin Syndrome/Neuroleptic Malignant Syndrome
- On rare occasions development of a serotonin syndrome or neuroleptic malignant
syndrome-like events may occur in association with treatment of paroxetine, particularly
when given in combination with other serotonergic and/or neuroleptic drugs. As these
syndromes may result in potentially life-threatening conditions, treatment with paroxetine
should be discontinued if such events (characterised by clusters of symptoms such as
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) occur and supportive symptomatic treatment should be initiated. Paroxetine should not be used in combination with serotonin-precursors (such as
L-tryptophan, oxitriptan) due to the risk of serotonergic syndrome.
- Mania
- As with all antidepressants, paroxetine should be used with caution in patients with a
history of mania. Paroxetine should be discontinued in any patient entering a manic phase.
- Renal/hepatic impairment
- Caution is recommended in patients with severe renal impairment or in those with hepatic
impairment.
- Diabetes
- In patients with diabetes, treatment with an SSRI may alter glycaemic control. Insulin
and/or oral hypoglycaemic dosage may need to be adjusted. Additionally, an increase in
blood glucose levels may occur when paroxetine and pravastatin are co-administered.
- Epilepsy
- As with other antidepressants, paroxetine should be used with caution in patients with
epilepsy.
- Seizures
- Overall the incidence of seizures is less than 0.1% in patients treated with paroxetine. The
drug should be discontinued in any patient who develops seizures.
- Electroconvulsive therapy (ECT)
- There is little clinical experience of the concurrent administration of paroxetine with ECT.
- Glaucoma
- As with other SSRIs, paroxetine can cause mydriasis and should be used with caution in
patients with narrow angle glaucoma or history of glaucoma.
- Cardiac Conditions
- The usual precautions should be observed in patients with cardiac conditions.
- Hyponatraemia
- Hyponatraemia has been reported rarely, predominantly in the elderly. Caution should also
be exercised in those patients at risk of hyponatraemia e.g. from concomitant medications
and cirrhosis. The hyponatraemia generally reverses on discontinuation of paroxetine.
- Haemorrhage
- SSRIs/SNRIs may increase the risk of postpartum hemorrhage.
- There have been reports of cutaneous bleeding abnormalities such as ecchymoses and
purpura with SSRIs. Other haemorrhagic manifestations e.g. gastrointestinal and
gynaecological haemorrhage have been reported. Elderly patients may be at an increased
risk for non-menses related events of bleeding.
- Caution is advised in patients taking SSRIs concomitantly with oral anticoagulants, drugs
known to affect platelet function or other drugs that may increase risk of bleeding (e.g.
atypical antipsychotics such as clozapine, phenothiazines, most TCAs, acetylsalicylic acid,
NSAIDs, COX-2 inhibitors) as well as in patients with a history of bleeding disorders or
conditions which may predispose to bleeding.
- Interaction with tamoxifen
- Paroxetine, a potent inhibitor of CYP2D6, may lead to reduced concentrations of
endoxifen, one of the most important active metabolites of tamoxifen. Therefore,
paroxetine should whenever possible be avoided during tamoxifen treatment.

Drugs affecting gastric pH
- In patients receiving oral suspension, the paroxetine plasma concentration may be
influenced by gastric pH. In vitro data have shown that an acidic environment is required
for release of the active drug from the suspension, hence absorption may be reduced in
patients with a high gastric pH or achlorhydria, such as after the use of certain drugs
(antacid drugs, histamine H2-receptor antagonists, proton pump inhibitors), in certain
disease states (e.g. atrophic gastritis, pernicious anemia, chronic Helicobacter
pylori infection), and after surgery (vagotomy, gastrectomy). The pH dependency should
be taken into account when changing paroxetine formulation (e.g. the plasma paroxetine
concentration may decrease after changing from tablet to oral suspension in patients with a
high gastric pH). Caution is therefore recommended in patients when initiating or ending
treatment with drugs increasing gastric pH. Dose adjustments may be necessary in such
situations.
- Withdrawal symptoms seen on discontinuation of paroxetine treatment
- Withdrawal symptoms when treatment is discontinued are common, particularly if
discontinuation is abrupt. adverse events seen on treatment discontinuation occurred in
30% of patients treated with paroxetine. The occurrence of withdrawal symptoms is not the
same as the drug being addictive or dependence producing.
- The risk of withdrawal symptoms may be dependent on several factors including the
duration and dose of therapy and the rate of dose reduction.
- Dizziness, sensory disturbances (including paraesthesia, electric shock sensations and
tinnitus), sleep disturbances (including intense dreams), agitation or anxiety, nausea,
tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability,
irritability, and visual disturbances have been reported. Generally these symptoms are mild
to 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 two weeks, though in some
individuals they may be prolonged (two-three months or more). It is therefore advised that
paroxetine should be gradually tapered when discontinuing treatment over a period of
several weeks or months, according to the patient's needs

Serotonergic drugs
As with other SSRIs, co-administration with serotonergic drugs may lead to an incidence of 5-HT
associated effects. Caution should be advised and a closer clinical monitoring is required when
serotonergic drugs (such as L-tryptophan, triptans, tramadol, linezolid, methylthioninium chloride
(methylene blue)), SSRIs, lithium, pethidine and St. John's Wort – Hypericum perforatum –
preparations) are combined with paroxetine. Caution is also advised with fentanyl used in general
anaesthesia or in the treatment of chronic pain. Concomitant use of paroxetine and MAOIs is
contraindicated because of the risk of serotonin.
Pimozide
Increased pimozide levels of on average 2.5. This may be explained by the known CYP2D6
inhibitory properties of paroxetine. Due to the narrow therapeutic index of pimozide and its known
ability to prolong QT interval, concomitant use of pimozide and paroxetine is contraindicated.

Drug metabolising enzymes
The metabolism and pharmacokinetics of paroxetine may be affected by the induction or inhibition
of drug metabolising enzymes.
When paroxetine is to be co-administered with a known drug metabolising enzyme inhibitor,
consideration should be given to using paroxetine doses at the lower end of the range.
No initial dosage adjustment is considered necessary when the drug is to be co-administered with
known drug metabolising enzyme inducers (e.g. carbamazepine, rifampicin, phenobarbital,
phenytoin) or with fosamprenavir/ritonavir. Any paroxetine dosage adjustment (either after
initiation or following discontinuation of an enzyme inducer) should be guided by clinical effect
(tolerability and efficacy).
Neuromuscular Blockers
SSRIs may reduce plasma cholinesterase activity resulting in a prolongation of the neuromuscular
blocking action of mivacurium and suxamethonium.
Fosamprenavir/ritonavir: Co-administration of fosamprenavir/ritonavir 700/100 mg twice daily
with paroxetine 20 mg daily in healthy volunteers for 10 days significantly decreased plasma
levels of paroxetine by approximately 55%. Paroxetine had no significant effect on metabolism of
fosamprenavir/ritonavir. There are no data available about the effects of long-term coadministration
of paroxetine and fosamprenavir/ritonavir exceeding 10 days.
Procyclidine: Daily administration of paroxetine increases significantly the plasma levels of
procyclidine. If anti-cholinergic effects are seen, the dose of procyclidine should be reduced.
Anticonvulsants: carbamazepine, phenytoin, sodium valproate. Concomitant administration does
not seem to show any effect on pharmacokinetic/dynamic profile in epileptic patients.
CYP2D6 inhibitory potency of paroxetine
As with other antidepressants, including other SSRIs, paroxetine inhibits the hepatic cytochrome
P450 enzyme CYP2D6. Inhibition of CYP2D6 may lead to increased plasma concentrations of coadministered
drugs metabolised by this enzyme. These include certain tricyclic antidepressants
(e.g. clomipramine, nortriptyline, and desipramine), phenothiazine neuroleptics (e.g. perphenazine
and thioridazine, see section 4.3 Contraindications), risperidone, atomoxetine, certain Type 1c
antiarrhythmics (e.g. propafenone and flecainide) and metoprolol. It is not recommended to use
paroxetine in combination with metoprolol when given in cardiac insufficiency, because of the
narrow therapeutic index of metoprolol in this indication.
Pharmacokinetic interaction between CYP2D6 inhibitors and tamoxifen, showing a 65-75%
reduction in plasma levels of one of the more active forms of tamoxifen, i.e. endoxifen, has been
reported in the literature. Reduced efficacy of tamoxifen has been reported with concomitant usage
of some SSRI antidepressants. As a reduced effect of tamoxifen cannot be excluded, coadministration
with potent CYP2D6 inhibitors (including paroxetine) should whenever possible be avoided.
Alcohol
As with other psychotropic drugs patients should be advised to avoid alcohol use while taking paroxetine.
Oral anticoagulants
A pharmacodynamic interaction between paroxetine and oral anticoagulants may occur.
Concomitant use of paroxetine and oral anticoagulants can lead to an increased anticoagulant
activity and haemorrhagic risk. Therefore, paroxetine should be used with caution in patients who
are treated with oral anticoagulants.

NSAIDs and acetylsalicylic acid, and other antiplatelet agents
A pharmacodynamic interaction between paroxetine and NSAIDs/acetylsalicylic acid may occur.
Concomitant use of paroxetine and NSAIDs/acetylsalicylic acid can lead to an increased
haemorrhagic risk.
Caution is advised in patients taking SSRIs, concomitantly with oral anticoagulants, drugs known
to affect platelet function or increase risk of bleeding (e.g. atypical antipsychotics such as
clozapine, phenothiazines, most TCAs, acetylsalicylic acid, NSAIDs, COX-2 inhibitors) as well as
in patients with a history of bleeding disorders or conditions that may predispose to bleeding.
Pravastatin
An interaction between paroxetine and pravastatin has been observed suggesting that coadministration
of paroxetine and pravastatin may lead to an increase in blood glucose levels.
Patients with diabetes mellitus receiving both paroxetine and pravastatin may require dosage
adjustment of oral hypoglycaemic agents and/or insulin.
Drugs affecting gastric pH
Drugs that alter gastric pH (such as antacid drugs, proton pump inhibitors or histamine H2-receptor
antagonists) may affect plasma paroxetine concentrations in patients taking the oral suspension

Pregnancy:
Some epidemiological studies suggest an increased risk of congenital malformations, particularly
cardiovascular (e.g. ventricular and atrial septum defects), associated with the use of paroxetine
during the first trimester. The mechanism is unknown. The data suggest that the risk of having an
infant with a cardiovascular defect following maternal paroxetine exposure is less than 2/100
compared with an expected rate for such defects of approximately 1/100 in the general population.
Paroxetine should only be used during pregnancy when strictly indicated. The prescribing
physician will need to weigh the option of alternative treatments in women who are pregnant or are
planning to become pregnant. Abrupt discontinuation should be avoided during pregnancy.
Neonates should be observed if maternal use of paroxetine continues into the later stages of
pregnancy, particularly the third trimester.
The following symptoms may occur in the neonate after maternal paroxetine use in later stages of
pregnancy: respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding
difficulty, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremor, jitteriness,
irritability, lethargy, constant crying, somnolence and difficulty in sleeping. These symptoms could
be due to either serotonergic effects or withdrawal symptoms. In a majority of instances the
complications begin immediately or soon (<24 hours) after delivery.
Epidemiological data have suggested that the use of SSRIs in pregnancy, particularly in late
pregnancy, may have an increased risk of persistent pulmonary hypertension of the newborn
(PPHN). The observed risk was approximately five cases per 1000 pregnancies. In the general
population one to two cases of PPHN per 1000 pregnancies occur.
Observational data indicate an increased risk (less than 2-fold) of postpartum hemorrhage
following SSRI/SNRI exposure within the month prior to birth.
Breast-feeding
Small amounts of paroxetine are excreted into breast milk. Serum concentrations in breast-fed
infants were undetectable (<2 nanograms/ml) or very low (<4 nanograms/ml), and no signs of drug
effects were observed in these infants. Since no effects are anticipated, breast-feeding can be
considered.

Fertility
Human case reports with some SSRIs (including paroxetine) have shown that an effect on sperm
quality appears to be reversible.
Impact on human fertility has not been observed so far.

Clinical experience has shown that therapy with paroxetine is not associated with impairment of
cognitive or psychomotor function. However, as with all psychoactive drugs, patients should be
cautioned about their ability to drive a car and operate machinery.
Although paroxetine does not increase the mental and motor skill impairments caused by alcohol,
the concomitant use of paroxetine and alcohol is not advised

Some of the adverse drug reactions listed below may decrease in intensity and frequency with
continued treatment and do not generally lead to cessation of therapy. Adverse drug reactions are
listed below by system organ class and frequency. Frequencies are defined as: very common (≥
1/10), common (≥ 1/100, <1/10), uncommon (≥ 1/1,000, <1/100), rare (≥ 1/10,000, <1/1,000), very
rare (<1/10,000), including isolated reports.
Blood and lymphatic system disorders
Uncommon: abnormal bleeding, predominantly of the skin and mucous membranes (including
ecchymosis and gynaecological bleeding).
Very rare: thrombocytopenia.
Immune system disorders
Very rare: severe and potentially fatal allergic reactions (including anaphylactoid reactions and
angioedema).
Endocrine disorders
Very rare: syndrome of inappropriate anti-diuretic hormone secretion (SIADH).
Metabolism and nutrition disorders
Common: increases in cholesterol levels, decreased appetite.
Uncommon: altered glycaemic control has been reported in diabetic patients.
Rare: hyponatraemia.
Hyponatraemia has been reported predominantly in elderly patients and is sometimes due to
syndrome of inappropriate anti-diuretic hormone secretion (SIADH).
Psychiatric disorders
Common: somnolence, insomnia, agitation, abnormal dreams (including nightmares).
Uncommon: confusion, hallucinations.
Rare: manic reactions, anxiety, depersonalisation, panic attacks, akathisia.
Frequency not known: suicidal ideation and suicidal behaviour.
Cases of suicidal ideation and suicidal behaviour have been reported during paroxetine therapy or
early after treatment discontinuation.
These symptoms may also be due to the underlying disease
Nervous system disorders
Common: dizziness, tremor, headache, concentration impaired.
Uncommon: extrapyramidal disorders.
Rare: convulsions, restless legs syndrome (RLS).

Very rare: serotonin syndrome (symptoms may include agitation, confusion, diaphoresis,
hallucinations, hyperreflexia, myoclonus, shivering, tachycardia and tremor).
Reports of extrapyramidal disorder including oro-facial dystonia have been received in patients
sometimes with underlying movement disorders or who were using neuroleptic medication.
Eye disorders
Common: blurred vision.
Uncommon: mydriasis.
Very rare: acute glaucoma.
Ear and labyrinth disorders
Frequency not known: tinnitus.
Cardiac disorders
Uncommon: sinus tachycardia.
Rare: bradycardia.
Vascular disorders
Uncommon: transient increases or decreases in blood pressure, postural hypotension.
Transient increases or decreases of blood pressure have been reported following treatment with
paroxetine, usually in patients with pre-existing hypertension or anxiety.
Respiratory, thoracic and mediastinal disorders
Common: yawning.
Gastrointestinal disorders
Very common: nausea.
Common: constipation, diarrhoea, vomiting, dry mouth.
Very rare: gastrointestinal bleeding.
Unknown : Colitis microscopic
Hepato-biliary disorders
Rare: elevation of hepatic enzymes.
Very rare: hepatic events (such as hepatitis, sometimes associated with jaundice and/or liver failure).
Elevation of hepatic enzymes has been reported. Post-marketing reports of hepatic events (such as
hepatitis, sometimes associated with jaundice and/or liver failure) have also been received very
rarely. Discontinuation of paroxetine should be considered if there is prolonged elevation of liver
function test results.
Skin and subcutaneous tissue disorders
Common: sweating.
Uncommon: skin rashes, pruritus
Very rare: severe cutaneous adverse reactions (including erythema multiforme, Stevens-Johnson
syndrome and toxic epidermal necrolysis), urticaria, and photosensitivity reactions.
Renal and urinary disorders
Uncommon: urinary retention, urinary incontinence.
Reproductive system and breast disorders
Very common: sexual dysfunction.
Rare: hyperprolactinaemia/galactorrhoea, menstrual disorders (including menorrhagia,
metrorrhagia, amenorrhoea, menstruation delayed and menstruation irregular).
Very rare: priapism
Postpartum haemorrhage*; frequency not known.
* This event has been reported for the therapeutic class of SSRIs/SNRIs

Musculoskeletal and connective tissue disorders
Rare: arthralgia, myalgia
In patients 50 years of age and older, show an increased risk of bone fractures in patients receiving
SSRIs and TCAs. The mechanism leading to this risk is unknown.
General disorder and administration site conditions
Common: asthenia, body weight gain
Very rare: peripheral oedema.
WITHDRAWAL SYMPTOMS SEEN ON DISCONTINUATION OF PAROXETINE
TREATMENT
Common: dizziness, sensory disturbances, sleep disturbances, anxiety, headache.
Uncommon: agitation, nausea, tremor, confusion, sweating, emotional instability, visual
disturbances, palpitations, diarrhoea, irritability.
Discontinuation of paroxetine (particularly when abrupt) commonly leads to withdrawal
symptoms. Dizziness, sensory disturbances (including paraesthesia, electric shock sensations and
tinnitus), sleep disturbances (including intense dreams), agitation or anxiety, nausea, tremor,
confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual
disturbances have been reported.
Generally these events are mild to moderate and are self-limiting; however, in some patients they
may be severe and/or prolonged. It is therefore advised that when paroxetine treatment is no longer
required, gradual discontinuation by dose tapering should be carried out
ADVERSE EVENTS in PAEDIATRIC
The following adverse events were observed:
Increased suicidal related behaviours (including suicide attempts and suicidal thoughts), self-harm
behaviours and increased hostility. Suicidal thoughts and suicide attempts were mainly observed in
adolescents with Major Depressive Disorder. Increased hostility occurred particularly in children
with obsessive compulsive disorder and especially in younger children less than 12 years of age.
Additional events that were seen are: decreased appetite, tremor, sweating, hyperkinesia, agitation,
emotional lability (including crying and mood fluctuations), bleeding related adverse events,
predominantly of the skin and mucous membranes.
Events seen after discontinuation/tapering of paroxetine are: emotional lability (including crying,
mood fluctuations, self-harm, suicidal thoughts and attempted suicide), nervousness, dizziness,
nausea and abdominal pain.
To report any side effect(s):
• Saudi Arabia:
The National Pharmacovigilance Centre (NPC):
• Fax: +966-11-205-7662
• SFDA Call Center: 19999
• E-mail: npc.drug@sfda.gov.sa
• Website: https://ade.sfda.gov.sa
- Other GCC States:
Please contact the relevant competent authority.

Symptoms and Signs
A wide margin of safety is evident from available overdose information on paroxetine.
Experience of paroxetine in overdose has indicated that, in addition to those symptoms mentioned
under "Undesirable effects", fever and involuntary muscle contractions have been reported.
Patients have generally recovered without serious sequelae even when doses of up to 2000 mg
have been taken alone. Events such as coma or ECG changes have occasionally been reported and,
very rarely with a fatal outcome, but generally when paroxetine was taken in conjunction with
other psychotropic drugs, with or without alcohol.
Treatment
No specific antidote is known.
The treatment should consist of those general measures employed in the management of overdose
with any antidepressant. Administration of 20-30 g activated charcoal may be considered if
possible within a few hours after overdose intake to decrease absorption of paroxetine. Supportive
care with frequent monitoring of vital signs and careful observation is indicated. Patient
management should be as clinically indicated.

Pharmacotherapeutic group: Antidepressants – selective serotonin reuptake inhibitors, ATC code:
N06A B05
Mechanism of Action
Paroxetine is a potent and selective inhibitor of 5-hydroxytryptamine (5-HT, serotonin) uptake and
its antidepressant action and effectiveness in the treatment of OCD, Social Anxiety disorder/Social
Phobia, General Anxiety Disorder, Post-Traumatic Stress Disorder and Panic Disorder is thought
to be related to its specific inhibition of 5-HT uptake in brain neurones.
Paroxetine is chemically unrelated to the tricyclic, tetracyclic and other available antidepressants.
Paroxetine has low affinity for muscarinic cholinergic receptors.
In accordance with this selective action, in contrast to tricyclic antidepressants, paroxetine has
little affinity for alpha1, alpha2 and beta-adrenoceptors, dopamine (D2), 5-HT1 like, 5-HT2 and
histamine (H1) receptors. This lack of interaction with post-synaptic receptors lack of CNS
depressant and hypotensive properties.
Pharmacodynamic Effects
Paroxetine does not impair psychomotor function and does not potentiate the depressant effects of
ethanol.
As with other selective 5-HT uptake inhibitors, paroxetine causes symptoms of excessive 5-HT
receptor stimulation when administered to animals previously given monoamine oxidase (MAO)
inhibitors or tryptophan.
Paroxetine is weakly activating at doses generally above those required to inhibit 5-HT uptake.
The activating properties are not "amphetamine-like" in nature.
Paroxetine produces no clinically significant changes in blood pressure, heart rate and ECG after
administration to healthy subjects.

In contrast to antidepressants which inhibit the uptake of noradrenaline, paroxetine has a much
reduced propensity to inhibit the antihypertensive effects of guanethidine.
In the treatment of depressive disorders, paroxetine exhibits comparable efficacy to standard
antidepressants.
There is also some evidence that paroxetine may be of therapeutic value in patients who have
failed to respond to standard therapy.
Morning dosing with paroxetine does not have any detrimental effect on either the quality or
duration of sleep. Moreover, patients are likely to experience improved sleep as they respond to
paroxetine therapy.

Absorption
Paroxetine is well absorbed after oral dosing and undergoes first-pass metabolism. Due to firstpass
metabolism, the amount of paroxetine available to the systemic circulation is less than that
absorbed from the gastrointestinal tract. Partial saturation of the first-pass effect and reduced
plasma clearance occur as the body burden increases with higher single doses or on multiple
dosing. This results in disproportionate increases in plasma concentrations of paroxetine and hence
pharmacokinetic parameters are not constant, resulting in non-linear kinetics. However, the nonlinearity
is generally small and is confined to those subjects who achieve low plasma levels at low
doses.
Steady state systemic levels are attained by 7 to 14 days after starting treatment with immediate or
controlled release formulations and pharmacokinetics do not appear to change during long-term
therapy.
Distribution
Paroxetine is extensively distributed into tissues and pharmacokinetic calculations indicate that
only 1% of the paroxetine in the body resides in the plasma.
Approximately 95% of the paroxetine present is protein bound at therapeutic concentrations.
No correlation has been found between paroxetine plasma concentrations and clinical effect
(adverse experiences and efficacy).
Biotransformation
The principal metabolites of paroxetine are polar and conjugated products of oxidation and
methylation which are readily cleared. In view of their relative lack of pharmacological activity, it
is most unlikely that they contribute to paroxetine's therapeutic effects.
Metabolism does not compromise paroxetine's selective action on neuronal 5-HT uptake.
Elimination
Urinary excretion of unchanged paroxetine is generally less than 2% of dose whilst that of
metabolites is about 64% of dose. About 36% of the dose is excreted in faeces, probably via the
bile, of which unchanged paroxetine represents less than 1% of the dose. Thus paroxetine is
eliminated almost entirely by metabolism.
Metabolite excretion is biphasic, being initially a result of first-pass metabolism and subsequently
controlled by systemic elimination of paroxetine.
The elimination half-life is variable but is generally about one day.
Special Patient Populations
Older people and Renal/Hepatic Impairment Increased plasma concentrations of paroxetine occur
in elderly subjects and in those subjects with severe renal impairment or in those with hepatic
impairment, but the range of plasma concentrations overlaps that of healthy adult subjects.

Not applicable

Calcium hydrogen phosphate,
Sodium Starch Glycolate,
Magnesium stearate &
Opadry White OY-L-28900.

Not applicable.

24 months.

Store below 30°C, in a dry place.

PADO® 20 is packed in white opaque PVC/ PVDC/ Aluminum foil blister, in carton box
with a multi folded leaflet.
− Pack size: PADO® 20 is available in the pack size of 30 F.C. tablets (10 tablets/blister, 3
blisters/ pack).
Hospital packs are also available.

Any unused product or waste should be disposed of in accordance with local requirements.