Instructions for Rexetin film-coated tablets 20 mg No. 30
Composition
active ingredient: paroxetine;
1 tablet contains 20 mg of paroxetine (as 22.76 mg of paroxetine hydrochloride hemihydrate);
excipients:
composition of the tablet core: magnesium stearate, sodium starch glycolate (type A), hypromellose, calcium hydrogen phosphate dihydrate;
shell composition: polysorbate 80, macrogol 400, macrogol 6000, titanium dioxide (E 171), hypromellose.
Dosage form
Film-coated tablets.
Main physicochemical properties: white or almost white, round, biconvex, film-coated tablets, scored on one side and engraved on the other. The tablet can be divided into equal doses.
Pharmacotherapeutic group
Antidepressants. Selective serotonin reuptake inhibitors. ATX code N06A B05.
Pharmacological properties
Pharmacodynamics.
Paroxetine is a potent selective 5-hydroxytryptamine (5-HT, serotonin) reuptake inhibitor. Its antidepressant action and efficacy in the treatment of obsessive-compulsive and panic disorders are due to the specific inhibition of 5-HT uptake by brain neurons. Paroxetine differs in its chemical structure from tricyclic, tetracyclic and other known antidepressants.
The drug has low affinity for muscarinic cholinergic receptors. Unlike tricyclic antidepressants, it has low affinity for alpha1-, alpha2- and beta-adrenergic receptors, dopamine (D2), 5-HT1-like, 5-HT2- and histamine (H1-) receptors; it does not affect psychomotor function and does not enhance the depressive effect of ethanol.
Rexetin® does not affect the activity of the cardiovascular system, does not cause clinically significant changes in blood pressure, heart rate and ECG parameters.
Rexetin®, unlike antidepressants that inhibit norepinephrine uptake, has a significantly smaller effect on the hypotensive effect of guanethidine.
Pharmacokinetics.
After oral administration, it is rapidly absorbed and undergoes transformation in the liver.
The main metabolites of the active substance Rexetin (paroxetine) are polar and conjugated oxidation and methylation products, which are rapidly excreted from the body.
Approximately 64% of an administered dose of paroxetine is excreted in the urine, with less than 2% excreted unchanged paroxetine. Approximately 36% of an administered dose of paroxetine is excreted in the feces as metabolites.
Paroxetine metabolites are eliminated in two stages - first by first-pass metabolism through the liver, and then by systemic elimination of paroxetine.
The half-life is on average approximately 1 day.
A constant concentration in the blood is achieved 7-14 days after the start of treatment, and during further long-term treatment, the pharmacokinetics of the drug almost does not change.
No correlation was found between paroxetine plasma concentrations and clinical effect (efficacy and adverse reactions).
Due to the breakdown of the drug in the liver, the amount of paroxetine circulating in the blood is less than the amount absorbed from the gastrointestinal tract. With an increase in a single dose or with repeated dosing, the effect of partial saturation of the metabolic pathway of the first pass through the liver occurs and a decrease in plasma clearance is observed. This leads to a disproportionate increase in the concentration of paroxetine in the blood plasma and changes in pharmacokinetic parameters with the appearance of a nonlinear relationship. However, such nonlinearity is mostly insignificant and is observed only in patients in whom low doses achieve a low concentration of the drug in the blood plasma.
Paroxetine is widely distributed in body tissues. Calculated pharmacokinetic parameters indicate that only 1% of the administered dose remains in the blood plasma.
When used in therapeutic concentrations, approximately 95% of paroxetine binds to plasma proteins.
In elderly patients and patients with renal or hepatic insufficiency, an increase in the concentration of paroxetine in the blood plasma is observed, but it does not exceed the concentration fluctuations in healthy adult volunteers.
Indication
Adults
Major depressive disorder. Treatment of major depressive disorder.
Obsessive-compulsive disorder. Treatment of symptoms and prevention of relapses of obsessive-compulsive disorder.
Panic disorder. Treatment of symptoms and prevention of relapse of panic disorder with or without concomitant agoraphobia.
Social phobias/social anxiety disorders. Treatment of social phobias/social anxiety disorders.
Generalized anxiety disorder. Treatment of symptoms and prevention of relapse of generalized anxiety disorder.
Post-traumatic stress disorder. Treatment of post-traumatic stress disorder.
Contraindication
Hypersensitivity to the active substance or to any of the excipients of the drug.
In exceptional cases, linezolid (an antibiotic that is a reversible non-selective MAO inhibitor) may be used in combination with paroxetine if facilities are available for close observation of symptoms of serotonin syndrome and with blood pressure monitoring (see section “Interaction with other medicinal products and other types of interactions”).
Paroxetine can be used:
2 weeks after discontinuation of treatment with irreversible MAO inhibitors;
at least 24 hours after discontinuation of treatment with reversible MAO inhibitors [e.g. moclobemide, linezolid, methylthioninium chloride (methylene blue)].
Treatment with any MAO inhibitor should not be started earlier than 1 week after stopping treatment with paroxetine.
Rexetin® is contraindicated in combination with thioridazine or pimozide (see section “Interaction with other medicinal products and other types of interactions”).
Interaction with other medicinal products and other types of interactions
Serotonergic drugs
The use of paroxetine, as with other selective serotonin reuptake inhibitors (SSRIs), with serotonergic drugs may increase the frequency of 5-HT-related effects and may cause serotonin syndrome, a potentially life-threatening condition (see sections 4.4 and 4.8).
Paroxetine should be used with caution and with careful clinical monitoring of the patient's clinical condition when used with serotonergic drugs such as L-tryptophan, triptans, linezolid, methylthioninium chloride (methylene blue), other SSRIs, lithium, opioids (e.g. tramadol, fentanyl, pethidine, buprenorphine (or its combination with naloxone)) and St. John's wort Hypericum perforatum. Concomitant use of paroxetine and MAO inhibitors is contraindicated due to the risk of serotonin syndrome (see section 4.3).
It is recommended to use fentanyl with caution during general anesthesia or for the treatment of chronic pain.
Pimozide
A study of the co-administration of a single low dose of pimozide (2 mg) and 60 mg of paroxetine showed an increase in pimozide levels. This may be due to the known CYPD26 inhibitory properties of paroxetine; due to the narrow therapeutic index of pimozide and its potential to prolong the QT interval, the concomitant use of pimozide and paroxetine is contraindicated (see section 4.3).
QT-prolonging drugs
The risk of QTc prolongation and/or ventricular arrhythmias (e.g. torsades de pointes) is increased by concomitant use of other drugs that prolong the QTc interval (e.g. some antipsychotics) (see section 4.4). Concomitant use of thioridazine and paroxetine is contraindicated because, like other drugs that inhibit the hepatic enzyme CYP450 2D6, paroxetine may increase plasma levels of thioridazine, which may lead to QT prolongation (see section 4.4).
Enzymes involved in drug metabolism
The metabolism and pharmacokinetic parameters of paroxetine may be altered by induction or inhibition of enzymes involved in drug metabolism.
When paroxetine is used concomitantly with enzyme-inhibiting drugs, it is recommended to use the lowest effective dose.
There is no need to change the initial dose of paroxetine when co-administered with enzyme-inducing drugs (carbamazepine, rifampicin, phenobarbital, phenytoin) or with fosamprenavir/ritonavir. The dose of paroxetine (both after initiation and after discontinuation of enzyme inhibitor therapy) should be adjusted according to clinical response (tolerability and efficacy).
Muscle relaxants
SSRIs may reduce plasma cholinesterase activity, leading to a prolongation of the neuromuscular blocking effect of mivacurium and suxamethonium.
Fosamprenavir/ritonavir
Co-administration of fosamprenavir/ritonavir 700/100 mg twice daily with paroxetine 20 mg daily for 10 days significantly reduced plasma levels of paroxetine. Dose adjustments should be made based on clinical response by approximately 55%. Plasma fosamprenavir/ritonavir levels during co-administration with paroxetine were similar to control values, indicating that paroxetine had no significant effect on the metabolism of fosamprenavir/ritonavir. There are no data on the effects of long-term co-administration of paroxetine and fosamprenavir/ritonavir beyond 10 days.
Procyclidine
Daily administration of paroxetine significantly increases plasma concentrations of procyclidine. If anticholinergic effects occur, the dose of procyclidine should be reduced.
Anticonvulsants
Carbamazepine, phenytoin, sodium valproate: concomitant use does not affect the pharmacokinetic/pharmacodynamic profile of paroxetine in patients with epilepsy.
Paroxetine, like other antidepressants, including other SSRIs, inhibits the cytochrome P450 enzyme CYP2D6. Inhibition of CYP2D6 may lead to increased plasma concentrations of concomitantly administered drugs that are metabolized by this enzyme. These drugs include some tricyclic antidepressants (e.g., clomipramine, amitriptyline, nortriptyline, imipramine, and desipramine), phenothiazine neuroleptics (e.g., perphenazine and thioridazine, see Contraindications and Drugs Prolonging the QT Interval above), risperidone, atomoxetine, some type 1c antiarrhythmics (e.g., propafenone and flecainide), and metoprolol. The combination of paroxetine with metoprolol in heart failure is not recommended due to the narrow therapeutic index of metoprolol in this indication.
Tamoxifen has an important active metabolite, endoxifen, which is produced by CYP2D6 and is an important component of tamoxifen efficacy. Irreversible inhibition of CYP2D6 by paroxetine results in a decrease in plasma endoxifen concentrations (see section 4.4). A pharmacokinetic interaction between inhibitors of the CYP2D6 enzyme and tamoxifen has been reported in the literature, resulting in a 65-75% decrease in plasma levels of one of the active metabolites of tamoxifen, endoxifen. Reduced efficacy of tamoxifen has been reported with concomitant use of some SSRI antidepressants. Since a reduction in the effect of tamoxifen cannot be excluded, concomitant use with potent CYP2D6 inhibitors (including paroxetine) should be avoided whenever possible (see section 4.4).
CYP3A4
In in vivo experiments, the combined use of Rexetin and terfenadine - a substrate for the CYP3A4 enzyme - when achieving a constant concentration in the blood was not accompanied by the effect of paroxetine on the pharmacokinetics of terfenadine. A similar in vivo interaction study did not reveal any effect of the drug on the pharmacokinetics of alprazolam and vice versa. The simultaneous administration of Rexetin and terfenadine, alprozalam and other drugs that are substrates for CYP3A4 cannot be dangerous.
In clinical studies, the absorption or pharmacokinetics of paroxetine were found to be unaffected or substantially unaffected (i.e., do not require dosage adjustment) by the following factors: food, antacids, digoxin, propranolol, alcohol.
Paroxetine does not increase the impairment of mental and motor reactions caused by alcohol, however, drinking alcoholic beverages during treatment with the drug is not recommended.
Alcohol
As with other psychotropic drugs, patients should be advised not to drink alcoholic beverages during treatment with paroxetine.
Oral anticoagulants
When oral anticoagulants are used together with paroxetine, a pharmacodynamic interaction may occur, which may lead to increased anticoagulant activity and the risk of bleeding, therefore paroxetine should be prescribed with caution to patients treated with oral anticoagulants (see section "Special warnings and precautions for use").
Nonsteroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, and other antiplatelet agents
When NSAIDs/acetylsalicylic acid are used concomitantly with paroxetine, a pharmacodynamic interaction may occur, which may lead to an increased risk of bleeding (see section 4.4). Therefore, paroxetine should be administered with caution to patients treated with drugs that affect platelet function or who are at increased risk of bleeding.
SSRIs should be prescribed with caution in combination with oral anticoagulants, drugs that affect platelet function or increase the risk of bleeding (e.g. atypical antipsychotics such as clozapine, phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, NSAIDs, COX-2 inhibitors), and in patients with a history of coagulopathy or diseases that may lead to bleeding.
Pravastatin
The interaction between paroxetine and pravastatin observed in studies suggests that concomitant use of paroxetine and pravastatin may lead to an increase in blood glucose levels. Diabetic patients receiving both paroxetine and pravastatin may require dosage adjustments of oral hypoglycemic agents and/or insulin (see section 4.4).
Application features
It is recommended that paroxetine treatment be initiated with caution two weeks after discontinuation of an irreversible MAOI or 24 hours after discontinuation of a reversible MAOI. The dosage of paroxetine should be increased gradually until the optimal response is achieved (see sections 4.3 and 4.5).
Children and adolescents
Antidepressant treatment is associated with an increased risk of suicidal behaviour and thoughts in children and adolescents with major depressive disorder and other psychiatric disorders. In clinical trials, suicidal behaviour (suicide attempt and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour, irritability and anger) were observed more frequently in children and adolescents treated with antidepressants than in the placebo group. If, based on clinical need, a decision to treat is nevertheless made, the patient should be closely monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents regarding growth, puberty, 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). The risk persists until significant remission occurs. As improvement may not occur within the first few weeks of treatment or even later, close monitoring is necessary until the patient's condition improves. Based on available clinical experience, the risk of suicide may be increased in the initial phase of recovery.
Other psychiatric conditions for which paroxetine is prescribed may also be associated with an increased risk of suicide-related events. In addition, these conditions may coexist with major depressive disorder. Therefore, the same precautions should be observed in the treatment of major depressive disorder as in the treatment of other psychiatric disorders.
The risk of suicidal thoughts or suicide attempts is known to be increased in patients with a history of suicide-related events or a significant degree of suicidal ideation prior to initiation of treatment, and patients should be monitored closely during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders showed an increased risk of suicidal behavior with antidepressants compared with placebo in patients under 25 years of age.
Close monitoring of patients is necessary, especially at the beginning of treatment and when changing the dose of the drug, this is especially important for patients at increased risk. Patients (and their caregivers) should be warned about the need to monitor for any signs of clinical worsening, suicidal behavior or suicidal thoughts and unusual changes in behavior and to seek medical advice immediately if such symptoms present.
Young adults, especially those with major depressive disorder, may be at increased risk of suicidal behavior while taking paroxetine. In a meta-analysis of placebo-controlled clinical trials in adult patients with psychiatric disorders, young adults (approximately 18-24 years of age) were at increased risk of suicidal behavior compared with placebo, although this difference was not statistically significant. This increased risk was not observed in older patients (25-64 years of age and 65 years of age and older). In patients with major depressive disorder (of any age) taking paroxetine, there was a statistically significant increase in the incidence of suicidal behavior compared with placebo. However, the majority of suicide attempts during treatment with paroxetine occurred in young adults aged 18-30 years. These data on the treatment of major depressive disorders suggest that the higher risk of these complications observed in a group of young patients with psychiatric disorders may extend to patients aged 24 years and older.
Patients with depressive disorders may experience worsening of depressive symptoms and/or suicidal ideation and behavior (suicidality) whether or not they are taking antidepressants. This risk persists until significant remission occurs. It is a general clinical experience with all courses of antidepressants that the risk of suicide may be increased in the early stages of recovery.
Other psychiatric disorders for which Rexetin® is prescribed may be associated with an increased risk of suicidal behavior, and such disorders may also be combined with major depressive disorders. In addition, patients with a history of suicidal behavior and intentions, young patients, and patients with persistent suicidal thoughts before the start of treatment are at increased risk for suicide attempts and suicidal thoughts. All patients should be closely monitored for clinical worsening (including the development of new symptoms) and suicidality during treatment, particularly at the beginning of treatment or during changes in dosage (both increases and decreases).
A change in therapeutic regimen, including discontinuation of the drug, should be considered in patients with clinical worsening (including development of new symptoms) and/or emergence of suicidal ideation/behavior, especially if these symptoms are severe, sudden in onset, or not part of the patient's previous symptom complex.
Akathisia/psychomotor restlessness
The use of paroxetine has been associated with the development of akathisia, a condition characterised by a feeling of inner restlessness and psychomotor agitation, such as an inability to sit or stand still, combined with a subjective feeling of discomfort. This is most likely to occur during the first weeks of treatment. In patients who experience these symptoms, increasing the dose may be harmful.
Serotonin syndrome/neuroleptic malignant syndrome
In rare cases, when taking paroxetine, especially in combination with other serotonergic drugs and/or neuroleptics or opioids (e.g. buprenorphine (as monotherapy or in combination with naloxone), peptidine, tramadol), serotonin syndrome or symptoms resembling neuroleptic malignant syndrome may develop (see sections "Interaction with other drugs and other types of interactions", "Overdose" and "Adverse reactions"). Since these syndromes can lead to a potentially life-threatening condition, treatment with paroxetine should be discontinued if the following groups of symptoms occur: hyperthermia, gastrointestinal symptoms, neuromuscular disorders, muscle rigidity, myoclonus, autonomic instability with possible rapid changes in vital signs, changes in mental status, including confusion, irritability, extreme agitation progressing to delirium and coma, and initiate supportive symptomatic therapy.
Paroxetine should not be used in combination with serotonin precursors (e.g. L-tryptophan, oxitriptan) due to the risk of serotonin syndrome (see sections "Contraindications" and "Interaction with other medicinal products and other types of interactions").
If concomitant treatment with other serotonergic drugs is clinically warranted, the patient should be closely monitored, especially at the start of treatment and when the dose is increased. Withdrawal of the serotonergic drugs usually results in rapid improvement.
Mania
A major depressive episode may be the initial manifestation of bipolar disorder. It has been suggested (although not confirmed by controlled clinical trials) that treatment of such episodes with an antidepressant alone may increase the likelihood of accelerated onset of mixed/manic episodes in patients at increased risk of developing bipolar disorder. Before initiating treatment with antidepressants, patients should be carefully evaluated to identify any risk factors for bipolar disorder. Such evaluation should include a detailed history of the patient, including history of suicide attempts, bipolar disorder, and family history of depression. It should be noted that Rexetin® is not approved for the treatment of depression in bipolar disorder. As with other antidepressants, Rexetin® should be used with caution in patients with a history of mania. Paroxetine should be discontinued if a patient develops a manic episode.
Bone fractures
Epidemiological studies investigating the risk of bone fractures have reported an association with fractures with some antidepressants, including SSRIs. The risk appears to be present during treatment and is greatest in the early stages of therapy. The possibility of bone fractures should be considered when treating patients with Rexetin.
Renal/hepatic impairment
Caution is recommended when using the drug in patients with severe renal or hepatic impairment (see section "Method of administration and dosage").
Diabetes mellitus
In patients with diabetes mellitus, glycemic control may be altered during treatment with SSRIs. Dosage adjustments of insulin and/or oral hypoglycemic agents may be necessary. In addition, there is evidence that concomitant use of paroxetine and pravastatin may increase glucose levels.
Epilepsy
As with other antidepressants, paroxetine should be used with caution in patients with epilepsy.
Convulsive seizures
Among patients taking paroxetine, seizures occur with a frequency of less than 0.1%. If seizures occur, paroxetine treatment should be discontinued.
Electroconvulsive therapy (ECT)
Experience with the concomitant use of paroxetine and ECT is limited.
Glaucoma
Paroxetine, like other SSRIs, can cause mydriasis, so the drug should be used with caution in patients with current or history of narrow-angle glaucoma.
Cardiological diseases
When treating patients with cardiac disease, usual precautions are required.
QT prolongation
Paroxetine should be used with caution in patients with a family history of QT prolongation, in patients taking concomitant antiarrhythmics or other medicinal products that may prolong the QT interval, in the presence of conditions such as heart failure, coronary artery disease, heart block, ventricular arrhythmias, bradycardia, hypokalaemia or hypomagnesaemia (see sections 4.3 and 4.5).
Hyponatremia
Hyponatremia has been reported rarely during treatment with paroxetine, mainly in elderly patients. Caution should be exercised in patients at risk of hyponatremia, for example due to concomitant medication or cirrhosis. Hyponatremia usually resolves after discontinuation of paroxetine.
Bleeding
Bleeding into the skin (ecchymoses and purpura) and mucous membranes (including gastrointestinal and gynaecological bleeding) has been reported following treatment with paroxetine. SSRIs/SNRIs may increase the risk of postpartum haemorrhage (see sections 4.8 and 4.8). SSRIs should be used with caution in patients taking oral anticoagulants, medicinal products that affect platelet function, or other medicinal products that may increase the risk of bleeding (e.g. atypical antipsychotics such as clozapine, phenothiazines, most tricyclic antidepressants [TCAs], acetylsalicylic acid, NSAIDs, COX-2 inhibitors), and in patients with a history of frequent coagulopathies or conditions that may predispose to bleeding (see section 4.8). Elderly patients may be at increased risk of non-menstrual bleeding.
Interaction with tamoxifen
Paroxetine, a potent CYP2D6 inhibitor, may lead to decreased concentrations of endoxifen, one of the major active metabolites of tamoxifen. Therefore, paroxetine should be avoided during tamoxifen treatment (see section 4.5). Some studies have shown that the efficacy of tamoxifen, as measured by the risk of breast cancer recurrence/fatality, may be reduced when co-administered with Rexetin, as paroxetine is an irreversible CYP2D6 inhibitor (see section 4.5). This risk increases with increasing duration of co-administration. When treating breast cancer with tamoxifen, the patient should be given an alternative antidepressant with little or no CYP2D6 inhibition.
Withdrawal symptoms observed when stopping paroxetine
Withdrawal symptoms are common when treatment is discontinued, particularly if the drug is discontinued abruptly (see section 4.8). In clinical trials in adults, adverse reactions to paroxetine treatment were reported in 30% of patients compared with 20% of patients on placebo. The occurrence of withdrawal symptoms is not the same as that which occurs with drug abuse or dependence.
The risk of developing withdrawal symptoms may depend on several factors, including the duration of therapy, dose, and rate of tapering.
Symptoms such as dizziness, sensory disturbances (including paraesthesia, electric shock sensations and tinnitus), sleep disturbances (including intense dreams), agitation or anxiety, nausea, tremor, confusion, increased sweating, headache, diarrhoea, palpitations, emotional lability, irritability and visual disturbances have been reported. These symptoms are generally mild to moderate in nature, although in some patients they may be very intense. They usually occur within the first few days after discontinuation of the drug, but there have been isolated cases of these symptoms in patients who have accidentally missed a dose. These symptoms usually resolve spontaneously within 2 weeks, although in some patients this process may be longer (2-3 months or longer). Therefore, it is recommended that when discontinuing paroxetine, the dose be reduced gradually over a period of several weeks or months, depending on the individual characteristics of the patient (see “Discontinuation of paroxetine” in the “Dosage and administration” section).
In children and adolescents, adverse reactions on discontinuation of paroxetine occurred in 32% of patients compared with 24% of patients on placebo. The following adverse reactions occurred after discontinuation of the drug (with an incidence of at least 2% of patients and with an incidence twice that of placebo): emotional lability (including suicidal ideation, suicide attempts, mood swings and tearfulness), nervousness, dizziness, nausea and abdominal pain (see section "Adverse reactions").
Sexual dysfunction
SSRIs/serotonin norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section 4.8). Long-term sexual dysfunction has been reported where symptoms persist despite discontinuation of SSRIs/SNRIs.
Excipients
This medicine contains less than 1 mmol (23 mg) sodium per tablet, i.e. essentially 'sodium-free'.
Fertility
Some clinical studies have shown that SSRIs, including paroxetine, may affect sperm quality. These effects are thought to reverse after treatment is discontinued. Altered sperm quality may affect the fertility of some men.
Pregnancy
According to animal studies, no teratogenic or embryotoxic effects were detected.
Epidemiological studies of pregnancy outcomes in women treated with antidepressants during the first trimester of pregnancy have reported an increased risk of congenital malformations, mainly cardiovascular (e.g. atrial or ventricular septal defect), associated with paroxetine. Based on these data, it can be assumed that the risk of having an infant with a cardiovascular defect in a woman treated with paroxetine during pregnancy is approximately 1 in 50 compared with the expected risk of such a defect in the general population, which is approximately 1 in 100.
The physician should consider alternative treatment options for pregnant women or women planning to become pregnant and should only prescribe paroxetine if the expected benefit to the mother outweighs the potential risk to the fetus. If a decision is made to discontinue treatment during pregnancy, the appropriate sections of the Summary of Product Characteristics should be consulted for further information on the dosage and symptoms of discontinuation of paroxetine (see sections 4.4 and 4.8).
There have been reports of premature birth in women treated with paroxetine or other SSRIs, although a causal relationship to the drug has not been established.
Newborns should be monitored if paroxetine is continued in the third trimester of pregnancy, as there have been reports of neonatal complications following maternal treatment with paroxetine or other SSRIs during this period, although a causal relationship to the drug has not been established. The following effects have been reported: respiratory distress, cyanosis, apnea, convulsions, temperature fluctuations, feeding difficulties, vomiting, hypoglycemia, hypertension, hypotension, hyperreflexia, tremor, shaking, irritability, lethargy, constant crying and drowsiness. In some reports, symptoms have been described as neonatal withdrawal symptoms. In most cases, they occurred immediately or shortly (< 24 hours) after delivery.
Epidemiological studies have shown that the use of SSRIs (including paroxetine) during pregnancy, particularly in late pregnancy, has been associated with an increased risk of persistent pulmonary hypertension of the newborn. In women who used SSRIs in late pregnancy, the risk was 4- to 5-fold higher than in the general population (1-2 cases per 1000 pregnancies in the general population).
Observational data indicate an increased risk (less than 2-fold) of postpartum hemorrhage after use of SSRIs/NSAIDs during the month before delivery (see sections “Special Uses”, “Adverse Reactions”).
Breastfeeding period
Small amounts of paroxetine are excreted in breast milk. No evidence of effects on the newborn has been found, however, paroxetine should not be used during breastfeeding unless the expected benefit to the mother outweighs the potential risk to the infant.
Ability to influence reaction speed when driving vehicles or other mechanisms
Clinical experience with paroxetine suggests that it does not affect cognitive or psychomotor function. However, as with other psychoactive drugs, patients should be cautioned about the effects on their ability to drive or operate machinery.
The simultaneous use of paroxetine and alcohol is not recommended, although paroxetine does not enhance the negative effects of alcohol on psychomotor functions.
Method of application
