Chemical formula: C₁₉H₂₀FNO₃ Molecular mass: 329.365 g/mol PubChem compound: 43815
Paroxetine interacts in the following cases:
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), 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.
Increased plasma concentrations of paroxetine occur in patients with hepatic impairment. Therefore, dosage should be restricted to the lower end of the dosage range.
As with other psychotropic drugs patients should be advised to avoid alcohol use while taking paroxetine.
Increased plasma concentrations of paroxetine occur in patients with severe renal impairment (creatinine clearance less than 30 ml/min). Therefore, dosage should be restricted to the lower end of the dosage range.
In vitro data have shown that dissociation of paroxetine from the oral suspension is pH-dependant. Therefore, 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.
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.
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.
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.
Animal data have shown that paroxetine may affect sperm quality. In vitro data with human material may suggest some effect on sperm quality; however, 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.
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.
SSRIs may reduce plasma cholinesterase activity resulting in a prolongation of the neuromuscular blocking action of mivacurium and suxamethonium.
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.
Daily administration of paroxetine increases significantly the plasma levels of procyclidine. If anticholinergic effects are seen, the dose of procyclidine should be reduced.
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs.
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.
As with all antidepressants, paroxetine should be used with caution in patients with a history of mania.
As with other SSRIs, paroxetine can cause mydriasis and should be used with caution in patients with narrow angle glaucoma or history of glaucoma.
In patients with diabetes, treatment with an SSRI may alter glycaemic control. Insulin and/or oral hypoglycaemic dosage may need to be adjusted. Additionally, there have been studies suggesting that an increase in blood glucose levels may occur when paroxetine and pravastatin are co-administered.
As with other antidepressants, paroxetine should be used with caution in patients with epilepsy.
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.
Animal studies showed reproductive toxicity, but did not indicate direct harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.
Small amounts of paroxetine are excreted into breast milk. In published studies, 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.
Animal data have shown that paroxetine may affect sperm quality. In vitro data with human material may suggest some effect on sperm quality; however, 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.
Uncommon: abnormal bleeding, predominantly of the skin and mucous membranes (including ecchymosis and gynaecological bleeding).
Very rare: thrombocytopenia.
Very rare: severe and potentially fatal allergic reactions (including anaphylactoid reactions and angioedema).
Very rare: syndrome of inappropriate anti-diuretic hormone secretion (SIADH).
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).
Common: somnolence, insomnia, agitation, abnormal dreams (including nightmares).
Uncommon: confusion, hallucinations.
Rare: manic reactions, anxiety, depersonalisation, panic attacks, akathisia.
Frequency not known: suicidal ideation, suicidal behaviour, aggression, bruxism.
Cases of suicidal ideation and suicidal behaviour have been reported during paroxetine therapy or early after treatment discontinuation.
Cases of aggression were observed in post marketing experience.
These symptoms may also be due to the underlying disease
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.
Common: blurred vision.
Uncommon: mydriasis.
Very rare: acute glaucoma.
Frequency not known: tinnitus.
Uncommon: sinus tachycardia.
Rare: bradycardia.
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.
Common: yawning.
Very common: nausea.
Common: constipation, diarrhoea, vomiting, dry mouth.
Very rare: gastrointestinal bleeding.
Rare: elevation of hepatic enzymes.
Very rare: hepatic events (such as hepatitis, sometimes associated with jaundice and/or liver failure).
Elevation of hepatic enzymes have 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.
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.
Uncommon: urinary retention, urinary incontinence.
Very common: sexual dysfunction.
Rare: hyperprolactinaemia/galactorrhoea, menstrual disorders (including menorrhagia, metrorrhagia, amenorrhoea, menstruation delayed and menstruation irregular).
Very rare: priapism.
Rare: arthralgia, myalgia
Epidemiological studies, mainly conducted 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.
Common: asthenia, body weight gain
Very rare: peripheral oedema.
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.
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 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 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.
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