Treatment of
- Major depressive episode.
- Obsessive compulsive disorder (OCD).
- Panic disorder with or without agoraphobia.
- Social anxiety disorder/social phobia.
- Generalized anxiety disorder.
- Post-traumatic stress disorde

It is recommended that paroxetine is administered once daily in the morning with food.
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 of even longer (see section 5.1).
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 minimize 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 (see section 5.1).
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 (see section 5.1).
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 (see section 5.1).
Post-traumatic stress disorder
The recommended dose is 20mg daily. If after some weeks on the recommended dose 
insufficient response is seen some patients may benefit from having their dose increased 
gradually in 10mg steps up to a maximum of 50mg/day. Long-term use should be regularly 
evaluated (see section 5.1).
General information
Withdrawal symptoms seen on discontinuation of Paroxat.
Abrupt discontinuation should be avoided (see section 4.4 and section 4.8).
The taper phase regimen used in clinical trials 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
Elderly
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)
Paroxat should not be used for the treatment of children and adolescents as controlled clinical 
trials have found paroxetine to be associated with increased risk for suicidal behaviour and 
hostility. In addition, in these trials, efficacy has not been adequately demonstrated (see section 
4.4 and section 4.8).
Children aged below 7 years
The use of paroxetine has not been studied in children less than 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.

 

Known hypersensitivity to paroxetine or any of the excipients. Paroxat is contraindicated in combination with monoamine oxidase inhibitors (MAOIs). Treatment with Paroxat can be initiated: - Two weeks after discontinuation of an irreversible MAOI, or - At least 24 hours after discontinuation of a reversible MAOI (e.g. moclobemide). At least one week should elapse between discontinuation of Paroxat and initiation of therapy with any MAOI. Paroxat should not be used in combination with thioridazine, because, as with other drugs which inhibit the hepatic enzyme CYP450 2D6, Paroxat can elevate plasma levels of thioridazine (see section 4.5). 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 Paroxat 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 Paroxat should be increased gradually until an optimal response is reached (see 
section 4.3 and section 4.5).
Children and adolescents (7-17 years)
Paroxat should not be used in the treatment of children and adolescents under the age of 18 
years. In clinical trials, increased suicidal-related behaviours (suicide attempts and suicidal 
thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were more
frequently observed in children and adolescents treated with paroxetine compared to those 
treated with placebo. In addition, in these trials, efficacy has not been adequately demonstrated 
and long-term safety data in children and adolescents concerning growth, maturation and 
cognitive and behavioural development are lacking (see section 4.8).
Suicide/suicidal ideation
Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide. 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 with all antidepressant therapies that the risk of suicide 
may increase in the early stages of recovery.
Other psychiatric conditions for which Paroxat is prescribed can also be associated with an 
increased risk of suicidal behaviour. In addition, these conditions may be co-morbid 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 suicidal behaviour or thoughts, or those exhibiting a significant degree 
of suicidal ideation prior to commencement of treatment are at a greater risk of suicidal thoughts 
or suicide attempts, and should receive careful monitoring during treatment.
There is a possibility of an increased risk of suicide-related behaviour in young adults aged 18-
29. Young adults should therefore be monitored carefully throughout treatment.
There are insufficient data concerning the risk of suicide-related behaviour in treatment-naïve 
patients, but careful monitoring might be warranted.
Patients (and caregivers of patients) should be alerted about the need to monitor for the 
emergence of suicidal ideation/behaviour or thoughts of harming themselves and to seek medical 
advice immediately if these symptoms occur.
Akathisia
The use of Paroxat has been associated with the development of akathisia, which is characterised 
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 with Paroxat, particularly when given in 
combination with other serotonergic and/or neuroleptic drugs. As these syndromes may result in potentially lifethreatening conditions, treatment with Paroxat 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. Paroxat should not be used in combination
with serotonin precursors (such as L-tryptophan, oxitriptan) due to the risk of serotonergic 
syndrome (see section 4.3 and section 4.5).
Mania
As with all antidepressants, Paroxat should be used with caution in patients with a history of 
mania. Paroxat 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 (see section 4.2).
Diabetes
In patients with diabetes, treatment with an SSRI may alter glycaemia control.
Insulin and/or oral hypoglycaemic dosage may need to be adjusted.
Epilepsy
As with other antidepressants, Paroxat should be used with caution in patients with epilepsy.
Seizures
Overall, the incidence of seizures is less than 0.1% in patients treated with Paroxat. Paroxat 
should be discontinued in any patient who develops seizures.
Electroconvulsive therapy (ECT)
There is little clinical experience of concurrent administration of Paroxat with Electroconvulsive
therapy (ECT).
Glaucoma
As with other SSRIs, paroxetine infrequently causes 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 Paroxat.
Haemorrhage
There have been reports of cutaneous bleeding abnormalities such as ecchymoses and purpura 
with SSRIs. Other haemorrhagic manifestations e.g. gastrointestinal haemorrhage have been 
reported. Elderly patients may be at an increased risk.
Caution is advised in patients taking SSRIs concomitantly with oral anticoagulants, drugs known 
to affect platelet function or other drugs that may increase the 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.
SSRIs/SNRIs may increase the risk of postpartum hemorrhage.

Interaction with tamoxifen
Some studies have shown that the efficacy of tamoxifen, as measured by the risk of breast cancer 
relapse/mortality, may be reduced when co-prescribed with paroxetine as a result of paroxetine's 
irreversible inhibition of CYP2D6 (see section 4.5). Paroxetine should whenever possible be 
avoided during tamoxifen use for treatment or prevention of breast cancer.
Withdrawal symptoms seen on discontinuation of Paroxat treatment
Withdrawal symptoms when treatment is discontinued are common, particularly if 
discontinuation is abrupt (see section 4.8). In clinical trials, adverse events seen on treatment 
discontinuation occurred in 30% of patients treated with paroxetine compared to 20% of patients 
treated with placebo. 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 and electric shock sensations), sleep 
disturbances (including intense dreams), agitation of 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 2 weeks, though in some 
individuals they may be prolonged (2-3 months or more). It is therefore advised that Paroxat 
should be gradually tapered when discontinuing treatment, over a period of several weeks or 
months, according to the patient's needs (see "Withdrawal symptoms seen on discontinuation of
Paroxat “section 4.2).

Serotonergic drugs
As with other SSRIs, co-administration with serotonergic drugs (including MAOIs, Ltryptophan, triptans, tramadol, linezolid, SSRIs, lithium and St John's Wort – Hypericum 
perforatum - preparations) may lead to an incidence of 5-HT associated effects (serotonin 
syndrome: see section 4.3 and section 4.4).
Caution should be advised and a closer clinical monitoring is required when these drugs are 
combined with Paroxat.
Drug-metabolising enzymes
The metabolism and pharmacokinetics of Paroxat may be affected by the induction or inhibition 
of drug-metabolising enzymes. When Paroxat is to be co-administered with a known drugmetabolising enzyme inhibitor, consideration should be given to using doses at the lower end of 
the range. No initial dosage adjustment is considered necessary when the drug is to be 
coadministered with known drug-metabolising enzyme inducers (e.g. carbamazepine, rifampicin, 
phenobarbital, phenytoin). Any subsequent dosage adjustment should be guided by clinical effect
(tolerability and efficacy).
Procyclidine
Daily administration of Paroxat significantly increases the plasma levels of procyclidine. If anticholinergic effects are seen, the dose of procyclidine should be reduced.
Anticonvulsants: carbamazepine, phenytoin, sodium valproat

Concomitant administration does not seem to show any effect on the 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 
co-administered 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), risperidone, certain Type Ic 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.
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 section 4.4).
Alcohol
As with other psychotropic drugs, patients should be advised to avoid alcohol 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 increased anticoagulant 
activity and haemorrhagic risk. Therefore, paroxetine should be used with caution in patients 
who are treated with oral anticoagulants (see section 4.4).
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 (see section 4.4).
Caution is advised in patients taking SSRIs concomitantly with oral anticoagulants, drugs known 
to affect platelet function or increase the 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.
Pravastatin
An interaction between paroxetine and pravastatin has been observed in studies suggesting that 
co-administration 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 (see section 4.4).
Pimozide
Increased pimozide levels of on average 2.5 times have been demonstrated in a study of a single 
low dose pimozide (2 mg) when co-administered with 60 mg paroxetine. 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 (see section 4.3).

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%. The plasma levels of fosamprenavir/ritonavir during co-administration of 
paroxetine were similar to reference values of other studies, indicating that paroxetine had no 
significant effect on metabolism of fosamprenavir/ritonavir. There are no data available about 
the effects of long-term co-administration of paroxetine and fosamprenavir/ritonavir exceeding 
10 days.

Pregnancy
Pregnancy category: D
Data on a limited number of exposed pregnancies provide no indication of an increased risk of 
congenital malformations in the newborn.
Paroxat should only be used during pregnancy when strictly indicated.
Women planning a pregnancy and those becoming pregnant during therapy should be asked to 
consult their physician. Abrupt discontinuation should be avoided during pregnancy (see 
"Withdrawal symptoms seen on discontinuation of Paroxat ", section 4.2).
Neonates should be observed if maternal use of Paroxat continues into the later stages of 
pregnancy, particularly the third trimester.
The following symptoms may occur in the neonate after maternal Paroxat use in the 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.
Animal studies showed reproductive toxicity, but did not indicate direct harmful effects with 
respect to pregnancy, embryonal/fetal development, parturition or post-natal development (see 
section 5.3).
Observational data indicate an increased risk (less than 2-fold) of postpartum hemorrhage following SSRI/SNRI exposure within the month prior to birth.
Lactation
Small amounts of Paroxat are excreted into breast milk. In published studies, serum 
concentrations in breast-fed infants were undetectable (< 2 ng/ml) or very low (< 4 ng/ml). No 
signs of drug effects were observed in these infants. Nevertheless, Paroxat should not be used 
during lactation unless the expected benefits to the mother justify the risks for the infant

Clinical experience has shown that therapy with Paroxat 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 Paroxat does not increase the mental and motor skill impairments caused by alcohol, 
the concomitant use of Paroxat 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 (mostly 
ecchymosis).
Very rare: thrombocytopenia.
Immune system disorders
Very rare: allergic reaction (including urticaria 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 (see section 4.4).
Rare: hyponatraemia.
Hyponatraemia has been reported predominantly in elderly patients and is sometimes due to SIADH.
Psychiatric disorders
Common: somnolence, insomnia, agitation, abnormal dreams (including nightmares).
Uncommon: confusion, hallucinations.
Rare: manic reactions, agitation, anxiety, depersonalisation, panic attacks, akathisia (see section 4.4)
Frequency not known: suicidal ideation and suicidal behaviour. aggression*.
Cases of suicidal ideation and suicidal behaviours have been reported during paroxetine therapy or early after treatment discontinuation (see section 4.4).
These symptoms may also be due to the underlying disease.
*cases of aggression were observed in post marketing experience
Nervous system disorders
Very common: concentration impaired.
Common: dizziness, tremor, headache.
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 (see section 4.4).
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 of decreases in 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 Paroxat 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, photosensitivity reactions.
Renal and urinary disorders
Uncommon: urinary retention, urinary incontinence.
Reproductive system and breast disorders
Very common: sexual dysfunction.
Rare: hyperprolactinaemia/galactorrhoea.
Very rare: priapism.
Unknown: postpartum haemorrhage (* This event has been reported for the therapeutic class of SSRIs/SNRIs).
Musculoskeletal disorders
Rare: arthralgia, myalgia.
General disorders 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 Paroxat (particularly when abrupt) commonly leads to withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), 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 self-limiting, however, in some patients they 
may be severe and/or prolonged. It is therefore advised that when Paroxat treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see section 4.2 and section 4.4).

Adverse events from paediatric clinical trials
In short-term (up to 10-12 weeks) clinical trials in children and adolescents, the following adverse events were observed in paroxetine-treated patients at a frequency of at least 2% of patients and occurred at a rate at least twice that of placebo: increased suicidal-related behaviors(including suicide attempts and suicidal thoughts), self-harm behaviors and increased hostility. Suicidal thoughts and suicide attempts were mainly observed in clinical trials of 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 more often seen in the paroxetine compared to placebo group were decreasedappetite, tremor, sweating, hyperkinesia, agitation, emotional lability (including crying and mood fluctuations).
In studies that used a tapering regimen, symptoms reported during the taper phase or upon discontinuation of paroxetine at a frequency of at least 2% of patients and occurred at a rate of at least twice that of placebo were emotional lability (including crying, mood fluctuations, selfharm, suicidal thoughts and attempted suicide), nervousness, dizziness, nausea and abdominalpain (see section 4.4)

 

To report any side effect(s): For Saudi Arabia: The National Pharmacovigilance and Drug Safety Centre (NPC) Fax: +966-11-205-7662  SFDA Call Center: 19999  E-mail: npc.drug@sfda.gov.sa Website: https://ade.sfda.gov.sa For UAE: Pharmacovigilance & Medical Device section P.O.Box: 1853 Tel: 80011111 Email: pv@moh.gov.ae Drug Department Ministry of Health & Prevention Dubai For OMAN: Department of Pharmacovigilance & Drug Information Directorate General of Pharmaceutical Affairs & Drug Control Ministry of Health, Sultanate of Oman Phone Nos. 22357687 / 22357686 Fax: 22358489 Email: dg-padc@moh.gov.om Website: www.moh.gov.om

 

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 in section 4.8, vomiting, dilated pupils, fever, blood pressure changes, headache, 
involuntary muscle contractions, agitation, anxiety and tachycardia 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. Where appropriate, the stomach should be emptied, either by 
the induction of emesis, lavage or both.
Following evacuation, 20 to 30 g of activated charcoal may be administered every 4 to 6 h during 
the first 24 h after ingestion. Supportive care with frequent monitoring of vital signs and careful 
observation is 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, generalised anxiety 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 a low affinity for muscarinic cholinergic receptors and animal studies have indicated only weak anticholinergic properties. In accordance with this selective action, in vitro studies have indicated that, in contrast to tricyclic antidepressants, paroxetine has little affinity for alpha1, alpha2 or beta-adrenoceptors, dopamine (D2), 5-HT1-like, 5-HT2 and histamine (H1) receptors. This lack of interaction with post-synaptic receptors in vitro is substantiated by in vivo studies which demonstrate lack of CNS-depressant and hypotensive properties.
Pharmacodynamic effects
Paroxetine does not impair psychomotor function and does not potentiate the depressants 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.Behavioural and EEG studies indicate that paroxetine is weakly activating at doses generally above those required to inhibit 5-HT uptake. The activating properties are not "amphetaminelike" in nature. Animal studies indicate that paroxetine is well tolerated by the cardiovascular 
system. Paroxetine produces no clinically significant changes in blood pressure, heart rate and ECG after administration to healthy subjects.Studies indicate that, 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.
Dose-response
In the fixed dose studies there is a flat dose-response curve, providing no suggestion of advantage in terms of efficacy for using higher-than recommended doses. However, there are some clinical data suggesting that uptitrating the dose might be beneficial for some patients.
Long-term efficacy
The long-term efficacy of paroxetine in depression has been demonstrated in a 52-week maintenance study with relapse prevention design: 12% of patients receiving paroxetine (20-40 
mg daily) relapsed, versus 28% of patients on placebo.The long-term efficacy of paroxetine in treating obsessive compulsive disorder has been examined in three 24-week maintenance studies with relapse prevention design. One of the three 
studies achieved a significant difference in the proportion of relapsers between paroxetine (38%) compared to placebo (59%).The long-term efficacy of paroxetine in treating panic disorder has been demonstrated in a 24 week maintenance study with relapse prevention design: 5% of patients receiving paroxetine (10-40 mg daily) relapsed, versus 30% of patients on placebo. This was supported by a 36-week maintenance study.The long-term efficacy of paroxetine in treating social anxiety disorder and generalised anxiety 
disorder has not been sufficiently demonstrated.

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 pharmacokinetics. However, the non-linearity 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 the 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).Transfer to human breast milk, and to the fetuses of laboratory animals, occurs in small amounts.
Metabolism
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 the therapeutic effects of paroxetine.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 the 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 1 day.
Special patient populations
Elderly 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 imppairment, but the range of plasma 
concentrations overlaps with that of healthy adult subjects.

Toxicology studies have been conducted in rhesus monkeys and albino rats; in both, the metabolic pathway is similar to that described in humans. As expected with lipophilic amines, including tricyclic antidepressants, phospholipidosis was detected in rats. Phospholipidosis was not observed in primate studies of up to one-year's duration at doses that were 6 times higherthan the recommended range of clinical doses.
Carcinogesesis
In two-year studies conducted in mice and rats, paroxetine had no tumorigenic effect.
Genotoxicity
Genotoxicity was not observed in a battery of in vitro and in vivo tests.Reproduction toxicity studies in rats have shown that paroxetine affects male and female fertility. In rats, increased pup mortality and delayed ossification were observed. The latter effects were likely related to maternal toxicity and are not considered a direct effect on the fetus/neonate.

Dibasic Calcium Phosphate Dihydrate

Sodium Starch Glycolate

Polysorbate 80

Hydroxypropyl Cellulose (Klucel EF)

Magnesium Stearate

Titanium Dioxide

Purified Talc

Polyethylene Glycol MW 6000

Hydroxypropyl Methylcellulose

Purified Water

Not applicable.

48Months/4Years.

Store below 30°C.

Transparent PVC/PVDC blister strips with aluminum foil lid 30 film-coated tablets/pack

No Special Disposal