Parotin

/ CTS

Depressive disorder
Adults: The recommended dose is 20 mg daily. Some patients not responding to a 20 mg dose may benefit from dose increases in 10mg/day increments, up to a maximum dosage of 50mg/day according to the patient’s response. As with all antidepressant drugs, dosage should be reviewed and adjusted if necessary within 2 to 3 weeks of initiation of therapy and thereafter as judged clinically appropriate. Patients with depression should be treated for a sufficient period to ensure that they are free from symptoms.This period may be several months.
Obsessive compulsive disorder
Adults: The recommended dose is 40 mg daily. Patients should start on 20 mg and can be increased weekly in 10 mg increments. Some patients will benefit from having their dose increased 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
Adults: The recommended dose is 40 mg daily. Patients should be started on 10mg/day and the dose increased weekly in 10mg increments according to patient’s response. Some patients may benefit from having their dose increased up to a maximum of 60mg/day. A low initial starting dose is recommended to minimize the risk of a potential worsening of panic symptomatology, which is generally recognized to occur early in the treatment of this disorder. 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 Phobia
Adults: The recommended dose is 20 mg daily. Some patients not responding to a 20 mg dose may benefit from having dose increases in 10 mg increments as required, up to a maximum of 50 mg/day according to the patient’s response.
Generalised Anxiety Disorder
Adults: The recommended dose is 20 mg daily. Some patients not responding to a 20 mg dose may benefit from having dose increases in 10 mg increments as required, up to a maximum of 50 mg/day to the patient’s response. 
Post-traumatic stress disorder
Adults: The recommended dose is 20mg daily. Some patients not responding to a 20mg dose may benefit from having dose increases in 10mg increments as required, up to a maximum of 50 mg/day according to the patient’s response.
For full information see prescribing information.

Treatment of symptoms of depression of all types, including depression accompanied by anxiety, and prevention of relapse. Treatment of symptoms and prevention of relapse of obsessive compulsive disorder (OCD) and of panic disorders with or without agoraphobia. Treatment of symptoms of social phobia, post traumatic stress disorder, generalized anxiety disorders.

Known hypersensitivity to paroxetine and excipients. Paroxetine should not be used in combination with monoamine oxidase (MAO) inhibitors (including linezolid, an antibiotic which is a reversible non-selective MAO inhibitor) or within 2 weeks of terminating treatment with MAO inhibitors. Likewise, MAO inhibitors should not be introduced within 2 weeks of cessation of therapy with paroxetine.
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.

Children and Adolescents (<18 years): Treatment with antidepressants is associated with an increased risk of suicidal thinking and behaviour in children and adolescents with major depressive disorder and other psychiatric disorders. In clinical trials of paroxetine in children and adolescents, adverse events related to suicidality (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in patients treated with paroxetine compared to those treated with placebo. Long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.
Clinical worsening and suicide risk in adults: Young adults, especially those with Major Depressive Disorder (MDD), may be at increased risk for suicidal behaviour during treatment with paroxetine. An analysis of placebo controlled trials of adults with psychiatric disorders showed a higher frequency of suicidal behaviour in young adults (prospectively defined as aged 18-24 years) treated with paroxetine compared with placebo (17/776 [2.19%] versus 5/542 [0.92%]), although this difference was not statistically significant. In the older age groups (aged 25-64 years and ≥65 years), no such increase was observed. In adults with MDD (all ages), there was a statistically significant increase in the frequency of suicidal behaviour in patients treated with paroxetine compared with placebo (11/3455 [0.32%] versus 1/1978 [0.05%]; all of the events were suicide attempts). However, the majority of these attempts for paroxetine (8 of 11) were in younger adults aged 18-30 years. These MDD data suggest that the higher frequency observed in the younger adult population across psychiatric
disorders may extend beyond the age of 24. 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. This risk persists until significant remission 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 paroxetine is prescribed can also be associated with an increased risk of suicidal behaviour and these conditions may be co-morbid with MDD. Additionally, patients with a history of suicidal behaviour or thoughts, young adults, and those patients exhibiting a significant degree of suicidal ideation prior to commencement of treatment, are at a greater risk of suicidal thoughts or suicide attempts. All patients should be monitored for clinical worsening (including development of new symptoms) and suicidality throughout treatment, and especially at the beginning of a course of treatment, or at the time of dose changes, either increases or decreases. Patients, ( families and caregivers of patients) should be alerted about the need to monitor for any worsening of their condition (including development of new symptoms) and/or the emergence of suicidal ideation/behaviour or thoughts of harming themselves and to seek medical advice immediately if these symptoms present. It should be recognised that the onset of some symptoms, such as agitation, akathisia or mania, could be related either to the underlying disease state or the drug therapy. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients who experience clinical worsening (including development of new symptoms) and/or the emergence of suicidal ideation/behaviour, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.
Akathisia: Rarely, the use of paroxetine or other SSRIs 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.
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 drugs (including triptans) , with drugs that impair metabolism of serotonin (including MAOIs), or with antipsychotic or other dopamine antagonists. Symptoms of serotonin syndrome may include mental status changes (eg, agitation, hallucinations, and coma), autonomic instability (eg, tachycardia, labile blood pressure, and hyperthermia), neuromuscular aberrations (eg, hyperreflexia and incoordination), and/or gastrointestinal tract symptoms (eg, nausea, vomiting, and diarrhea). Severe cases can resemble NMS, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS-like signs and symptoms.
A concomitant treatment of depression with MAOIs and Paroxetine is contraindicated. Parotin-treated patients receiving triptans should be observed closely, particularly during initiation of therapy, dose increases, or the addition of another serotonergic drug. Concomitant use of Parotin with serotonin precursors (eg, tryptophan) is not recommended. Treatment with Parotin and any concomitant serotonergic or antidopaminergic agents, including antipsychotics, should be discontinued immediately in patients in whom symptoms of serotonin syndrome develop.
Mania and Bipolar disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone can increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that paroxetine is not approved for use in treating bipolar depression. As with all antidepressants, paroxetine should be used with caution in patients with a history of mania.
Monoamine Oxidase Inhibitors: Treatment with paroxetine should be initiated cautiously at least 2 weeks after terminating treatment with MAO inhibitors and dosage of paroxetine should be increased gradually until optimal response is reached.
Renal/hepatic impairment: Caution is recommended in patients with severe renal impairment or in those with hepatic impairment.
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.
ECT: There is little clinical experience of the concurrent administration of paroxetine with ECT.
Glaucoma: As with other SSRI’s, paroxetine can cause mydriasis and should be used with caution in patients with narrow angle glaucoma.
Hyponatremia: Hyponatraemia has been reported rarely, predominantly in the elderly. The hyponatraemia generally reverses on discontinuation of paroxetine.
Hemorrhage: Skin and mucous membrane bleedings (including gastrointestinal bleeding) have been reported following treatment with paroxetine. Paroxetine should therefore be used with caution in patients concomitantly treated with drugs that give an increased risk for bleeding, and in patients with a known tendency for bleeding or those with predisposing conditions.
Cardiac conditions: The usual precautions should be observed in patients with cardiac conditions.
Symptoms seen on discontinuation of paroxetine treatment in adults: In clinicals trials in adults, 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 discontinuation symptoms is not the same as the drug being addictive or dependence producing as with a substance of abuse. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including intense dreams), agitation or anxiety, nausea, tremor, confusion, sweating, headache, diarrhoea 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 selflimiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 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.
Symptoms seen on discontinuation of paroxetine treatment in children and adolescents: In clinical trials in children and adolescents, adverse events seen on treatment discontinuation occurred in 32% of patients treated with paroxetine compared to 24% of patients treated with placebo. Events reported upon discontinuation of paroxetine at a frequency of at least 2% of patients and which occured 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.
For full details see prescribing information.

Some of the adverse experiences 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. The frequencies of the common and uncommon events were generally determined from pooled safety data from a clinical trial population of >8000 paroxetine-treated patients and are quoted as excess incidence over placebo. Rare and very rare events were generally determined from postmarketing data and refer to reporting rate rather than true frequency.
Blood & lymphatic system disorders: Uncommon: abnormal bleeding, predominantly of the skin and mucous membranes (mostly ecchymosis).
Metabolism & nutrition disorders: Common: increases in cholesterol levels, decreased appetite.
Psychiatric disorders: Common: somnolence, insomnia, agitation. 
Nervous system disorders: Common: dizziness, tremor, headache .
Eye disorders: Common: blurred vision. Uncommon: mydriasis.
Cardiac disorders: Uncommon: sinus tachycardia
Vascular disorders: Common: yawning.
Gastrointestinal disorders: Very common: nausea. Common: constipation, diarrhoea, dry mouth.
Skin & subcutaneous tissue disorders: Common: sweating. Uncommon: skin rashes.
Renal & urinary disorders: Uncommon: urinary retention.
Reproductive system & breast disorders: Very common: sexual dysfunction.
General disorders & administration site conditions: Common: asthenia, body weight gain.
For full details see prescribing information.

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 Ltryptophan, triptans, tramadol, SSRIs, lithium and St. John’s Wort – Hypericum perforatum – preparations) are combined with paroxetine. Concomitant use of paroxetine and MAO inhibitors (including linezolid, an antibiotic which is a reversible nonselective MAO inhibitor) is contraindicated.
Pimozide: Increased pimozide levels have been demonstrated in a study of a single low dose pimozide (2 mg) when coadministered with paroxetine. This is 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 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). Any subsequent dosage adjustment should be guided by clinical effect (tolerability and efficacy).
Procyclidine: Daily administration of paroxetine increases significantly the plasma levels of procyclidine. If anticholinergic 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 co-administered drugs metabolised by this enzyme. These include certain tricyclic antidepressants (e.g. amitriptyline, nortriptyline,imipramine and desipramine), phenothiazine neuroleptics, risperidone, atomoxetine, certain Type 1c antiarrhythmics (e.g. propafenone and flecainide) and metoprolol. Tamoxifen is a pro-drug requiring metabolic activation by CYP2D6. Inhibition of CYP2D6 by paroxetine may lead to reduced plasma concentrations of an active metabolite and hence reduced efficacy of tamoxifen.
CYP3A4: An in vivo interaction study involving the co-administration under steady state conditions of paroxetine and terfenadine, a substrate for cytochrome CYP3A4, revealed no effect of paroxetine on terfenadine
pharmacokinetics. A similar in vivo interaction study revealed no effect of paroxetine on alprazolam pharmacokinetics and viceversa. Concurrent administration of paroxetine with terfenadine, alprazolam and other drugs that are CYP3A4 substrates would not be expected to cause a hazard. Clinical studies have shown the absorption and pharmacokinetics of paroxetine to be unaffected or only marginally affected (i.e. at a level which warrants no change in dosing regimen) by: food, antacids, digoxin, propranolol
alcohol: paroxetine does not increase the impairment of mental and motor skills caused by alcohol, however, the concomitant use of paroxetine and alcohol is not advised.

Pregnancy: Animal studies have not shown any teratogenic or selective embryotoxic effects. Recent 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, compared with an expected rate for such defects of approximately 1/100 infants in the general population. The prescribing physician will need to weigh the option of alternative treatments in women who are pregnant or are planning to become pregnant, and should only prescribe paroxetine if the potential benefit outweighs the potential risk. If a decision is taken to discontinue paroxetine treatment in a pregnant woman, the prescriber
should consult – Posology and method of administration – Discontinuation of Paroxetine and Special Precautions for use  Symptoms seen on discontinuation of paroxetine treatment in adults. There have been reports of premature birth in pregnant women exposed to paroxetine or others SSRIs, although a causal relationship with drug therapy has not been established. Neonates should be observed if maternal use of paroxetine continues into the later stages of pregnancy, becausethere have been reports of complications in neonates exposed to paroxetine or other SSRIs late in the third trimesterof pregnancy. However, a causal association with drug therapy has not been confirmed. Reported clinical findings have included: respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypertonia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying and somnolence. In some instances the reported symptoms were described as neonatal withdrawal symptoms. In a majority of instances the complications were reported to have arisen eithe immediately or soon (<24 hours) after delivery. In one epidemiological study, the use of SSRIs (including paroxetine) after the first 20 weeks of pregnancy, wasassociated with an increased risk of persistent pulmonary hypertension of the newborn (PPHN). The absolute risk among those who used SSRIs late in pregnancy was reported to be about 6 to 12 per 1000 women, compared to 1 to 2 per 1000 women in the general population.
Lactation: Small amounts of paroxetine are excreted into breast milk. In published studies, serum concentrations in breastfed infants were undetectable (<2 ng/ml) or very low (<4 ng/ml). No signs of drug effects were observed in these infants. Nevertheless, paroxetine should not be used during lactation unless the expected benefits to the mother justify the potential risks for the infant.

Symptoms and Signs: A wide margin of safety is evident from available overdose information on paroxetine. Experience of paroxetine in overdose has indicated that, vomiting, fever, blood pressure changes, involuntary muscle contractions, anxiety and tachycardia have been reported. Patients have generally recovered without serious sequelae even when doses of up to 2000 mg of paroxetine have been taken alone. Events such as coma or ECG changes have occasionally been reported and, very rarely 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 by lavage. 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.