Paxil, 20 mg 30 pcs

Paxil – antidepressant activity is due to specific inhibition of serotonin reuptake in brain neurons.

Pharmacodynamics

Paxil has low affinity for muscarinic cholinergic receptors, and animal studies have shown that the anticholinergic properties are weakly expressed. In-vitro studies have shown that paroxetine has weak affinity for alpha₁-, alpha₂– and beta-adrenoceptors, as well as to dopamine (D₂), serotonin 5-NT₁– and 5-NT₂– and histamine (H₁) receptors.

The absence of interaction with postsynaptic receptors in vivo is confirmed by the results of in vivo studies, which demonstrated that paroxetine has no ability to depress the CNS and cause arterial hypotension. It does not impair psychomotor functions and does not increase the CNS depressant effect of ethanol.

Like other selective serotonin reuptake inhibitors (SSRIs), paroxetine causes symptoms of overstimulation of 5-NT receptors when administered to animals that previously received MAOIs or tryptophan inhibitors.

Studies of behavior and EEG changes have demonstrated that paroxetine causes weak activating effects at doses greater than those required to inhibit serotonin reuptake. Its activating properties are not amphetamine-like in nature.

Animal studies have shown that paroxetine has no effect on the cardiovascular system.

In healthy individuals, paroxetine does not cause clinically significant changes in BP, HR and ECG.

Pharmacokinetics

In oral administration, it is well absorbed and metabolized by “first pass” through the liver. Due to “first pass” metabolism, a smaller amount of paroxetine enters the systemic bloodstream than is absorbed from the gastrointestinal tract. As the amount of paroxetine in the body increases with a single high-dose administration or with multiple conventional doses, there is partial saturation of the “first-pass” metabolic pathway and the clearance of paroxetine from plasma decreases.

This results in a disproportionate increase in plasma concentrations of paroxetine. Therefore, its pharmacokinetic parameters are unstable, a consequence of which is nonlinear kinetics. It should be noted, however, that nonlinearity is usually weak and is observed only in those patients in whom low plasma levels of paroxetine are achieved at low doses of the drug. Equilibrium plasma concentrations are reached after 7-14 days.

Paroxetine is widely distributed in tissues, and pharmacokinetic calculations show that only 1% of all paroxetine present in the body remains in plasma. At therapeutic concentrations, approximately 95% of plasma paroxetine is bound to proteins. No correlation has been found between the plasma concentrations of paroxetine and its clinical effects (adverse reactions and efficacy). Paroxetine has been found to penetrate in small amounts into the breast milk of women, as well as into the embryos and fetuses of laboratory animals.

Biotransformed into inactive polar and conjugated products (oxidation and methylation processes). T_1/2 varies, but is usually about one day (16-24 h). About 64% is excreted in the urine as metabolites, less than 2% unchanged; the remainder is excreted in the feces (probably entering it with bile) as metabolites, less than 1% unchanged. Excretion of metabolites is biphasic, including primary metabolism (first phase) and systemic elimination.

Indications

Active ingredient

Composition

Active ingredient:

Paroxetine hydrochloride hemihydrate 22.8 mg (equivalent to 20.0 mg of paroxetine);

Auxiliary substances:

calcium dihydrophosphate dihydrate;

Sodium carboxymethyl starch type A;

Magnesium stearate;

Pill sheath:

Opadry white YS-1R-7003 (hypromellose, titanium dioxide, macrogol 400, polysorbate 80);

How to take, the dosage

Orally (tablet should be swallowed whole, without chewing), once a day (in the morning, with meals).

Depression. The recommended dose for adults is 20 mg per day; if necessary, depending on the therapeutic effect, the dose can be increased weekly by 10 mg per day up to a maximum daily dose of 50 mg. As with any antidepressant therapy, the therapy efficacy should be assessed and, if necessary, the dose of paroxetine should be adjusted after 2-3 weeks of treatment and further depending on clinical indications.

In order to relieve depressive symptoms and prevent relapses, an adequate duration of relieving and supporting therapy should be observed. The use of paroxetine in children and adolescents (7-17 years) for treatment of depression is not recommended due to the lack of data on the effectiveness of therapy.

Obsessive-compulsive disorder. The recommended dose for adults is 40 mg per day. Treatment is started with a dose of 20 mg per day, which can be increased weekly by 10 mg per day. If necessary, the dose may be increased to 60 mg per day. Adequate duration of therapy should be observed. For children and adolescents (7-17 years) the initial dose is 10 mg per day, which can be increased weekly by 10 mg per day. If necessary, the dose can be increased to 50 mg per day.

Panic disorder. The recommended dose for adults is 40 mg per day. Patients should begin treatment with a dose of 10 mg per day and increase the dose weekly by 10 mg per day, guided by clinical effect. If necessary, the dose may be increased to 60 mg daily. A low initial dose is recommended to minimize the possible exacerbation of panic disorder symptoms that may occur at the beginning of treatment with any antidepressant. Adequate timing of therapy should be observed.

Social phobia. The recommended dose for adults is 20 mg per day. If necessary, the dose may be increased weekly by 10 mg per day, depending on the clinical effect, up to 50 mg per day. Treatment of children and adolescents (8-17 years) should begin with a dose of 10 mg per day and weekly increase the dose by 10 mg per day, focusing on the clinical effect. If necessary, the dose may be increased to 50 mg daily.

Generalized anxiety disorder. The recommended dose for adults is 20 mg per day. If necessary, the dose may be increased weekly by 10 mg per day depending on the clinical effect, up to 50 mg per day.

Post-traumatic stress disorder. The recommended dose for adults is 20 mg per day. If necessary, the dose can be increased weekly by 10 mg/day depending on the clinical effect – up to 50 mg per day.

Interaction

Serotonergic drugs. The use of paroxetine, as well as other drugs of the SSRI group, simultaneously with serotonergic drugs (including MAO inhibitors, L-tryptophan, triptans, tramadol, linezolid, other drugs of the SSRI group, lithium and herbal agents containing St. John’s wort) may be accompanied by the development of serotonin-related effects. Caution and close clinical monitoring are required when using these drugs in combination with paroxetine.

The enzymes involved in drug metabolism. Metabolism and pharmacokinetics of paroxetine may be altered by the induction or inhibition of enzymes involved in drug metabolism. When using paroxetine concomitantly with inhibitors of enzymes involved in drug metabolism, the appropriateness of using a paroxetine dose that is at the lower end of the therapeutic dose range should be assessed.

The initial dose of paroxetine does not need to be adjusted if it is used simultaneously with a drug that is a known inducer of enzymes involved in drug metabolism (e.g. carbamazepine, rifampicin, phenobarbital, phenytoin). Any subsequent dose adjustment of paroxetine should be determined by its clinical effects (tolerability and efficacy).

CYP3A4. An in vivo interaction study of concomitant equilibrium use of paroxetine and terfenadine, which is a substrate of the CYP3A4 enzyme, showed that paroxetine does not affect the pharmacokinetics of terfenadine. In a similar in vivo interaction study, there was no effect of paroxetine on the pharmacokinetics of alprosalam and vice versa. Simultaneous use of paroxetine with terfenadine, alprosalam and other drugs that are substrates of CYP3A4 enzyme is unlikely to cause harm in patients.

Paroxetine’s ability to inhibit the CYP2D6 enzyme (see also Contraindications). Like other antidepressants, including other drugs of the SSRI group, paroxetine inhibits the hepatic enzyme CYP2D6, which belongs to the cytochrome P450 system. Inhibition of CYP2D6 enzyme may lead to increased plasma concentrations of simultaneously used drugs that are metabolized by this enzyme. These drugs include tricyclic antidepressants (e.g. amitriptyline, nortriptyline, imipramine and desipramine), phenothiazine-type neuroleptics, risperidone, some type 1C antiarrhythmic agents (such as propafenone and flecainide) and metoprolol.

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. Simultaneous use of paroxetine and the above mentioned drugs does not affect their pharmacokinetics and pharmacodynamics in patients with epilepsy.

The clinical studies have shown that the absorption and pharmacokinetics of paroxetine are independent or almost independent (i.e., the existing dependence does not require dose changes) of food, antacids, digoxin, propranololol, and alcohol.

Special Instructions

Paroxetine withdrawal. Withdrawal symptoms such as dizziness, sensory disturbances (including paresthesias and electric shocks), sleep disturbances (including vivid dreams), agitation and anxiety, nausea, tremors, confusion, sweating, headaches, and diarrhea have been described. These symptoms are usually mild to moderate, but may be severe in some patients. They usually occur in the first few days after withdrawal, but they rarely occur in patients who have accidentally missed just one dose. These symptoms usually go away spontaneously and disappear within 2 weeks, but in some patients they may last much longer (2-3 months or more).

As with other psychotropic medications, abrupt withdrawal of paroxetine should be avoided. The following withdrawal regimen may be recommended: decrease the daily dose by 10 mg at weekly intervals; after reaching a dose of 20 mg/day (or 10 mg/day in children and adolescents), patients continue taking this dose for 1 week and only then withdraw the drug completely.

If withdrawal symptoms develop during dose reduction or after withdrawal of the drug, it is advisable to resume the previously prescribed dose. The doctor may then continue reducing the dose, but at a slower rate.

The occurrence of withdrawal symptoms does not mean the medication is abused or addictive, as with drugs and psychotropics.

Symptoms that may occur when discontinuing paroxetine treatment in children and adolescents. Paroxetine withdrawal symptoms (emotional lability, including suicidal ideation, suicide attempts, mood changes and tearfulness, as well as nervousness, dizziness, nausea and abdominal pain) were reported in 2% of patients when the paroxetine dose was reduced or after complete withdrawal and were 2 times more common than in the placebo group.

Separate patient groups.

Elderly patients. Plasma concentrations of paroxetine may be elevated in elderly patients, but the range of concentrations is the same as in younger patients. In this category of patients, therapy should be started at the dose recommended for adults, which may be increased to 40 mg/day.

Patients with impaired renal or hepatic function. Plasma concentrations of paroxetine are elevated in patients with severe renal dysfunction (creatinine Cl less than 30 mL/min) and in patients with impaired liver function. Such patients should be prescribed doses of the drug that are in the lower part of the therapeutic dose range.

Children under 7 years of age. The use of paroxetine is not recommended due to the lack of studies of safety and effectiveness of the drug in this group of patients.

Children and adolescents 7-17 years old. In clinical trials, adverse events associated with suicidality (suicide attempts and suicidal ideation) and hostility (mainly aggression, deviant behavior and anger) were more frequently observed in children and adolescents who received paroxetine than in those patients in this age group who received placebo. There are currently no data on the long-term safety of paroxetine in children and adolescents that address the drug’s effects on growth, maturation, cognitive and behavioral development.

The clinical deterioration and suicidal risk associated with psychiatric disorders. In patients with depression, exacerbation of symptoms of the disorder and/or the occurrence of suicidal thoughts and suicidal behavior (suicidality) can be observed regardless of whether they receive antidepressants. This risk persists until significant remission is achieved. The patient may not improve in the first weeks of treatment or more, so the patient should be closely monitored for timely detection of clinical exacerbation and suicidality, especially at the beginning of treatment, and during periods of dose changes, whether they are increased or decreased. Clinical experience with all antidepressants shows that the risk of suicide may increase in the early stages of recovery.

Other psychiatric disorders treated with paroxetine may also be associated with an increased risk of suicidal behavior. In addition, these disorders may represent comorbid conditions accompanying major depressive disorder. Therefore, the same precautions should be taken when treating patients with other psychiatric disorders as when treating major depressive disorder.

Patients with a history of suicidal behavior or suicidal ideation, younger patients, and patients with significant suicidal ideation before treatment are at greatest risk for suicidal thoughts or suicide attempts, so all should be given special attention during treatment.

Patients (and their caregivers) should be warned to watch for deterioration and/or suicidal thoughts/suicidal behavior or thoughts of self-harm and to seek medical attention immediately if these symptoms occur.

Akathisia. Occasionally, treatment with paroxetine or another SSRI medication is accompanied by akathisia, which is manifested by feelings of inner restlessness and psychomotor agitation when the patient cannot sit or stand quietly; with akathisia, the patient usually experiences subjective distress. The likelihood of akathisia is highest in the first few weeks of treatment.

Serotonin syndrome/malignant neuroleptic syndrome. In rare cases, serotonin syndrome or symptoms similar to malignant neuroleptic syndrome may occur during treatment with paroxetine, especially if paroxetine is used in combination with other serotoninergic drugs and/or neuroleptics.

. These syndromes are potentially life-threatening, therefore if they occur, treatment with paroxetine should be discontinued (they are characterized by a combination of symptoms such as hyperthermia, muscle rigidity, myoclonus, autonomic disturbances with possible rapid changes in vital signs, changes in mental status including confusion, irritability, extremely severe agitation progressing to delirium and coma) and initiate supportive symptomatic therapy. Paroxetine should not be prescribed in combination with serotonin precursors such as L-tryptophan and oxytriptan due to the risk of serotoninergic syndrome.

Mania and bipolar disorder. A major depressive episode may be the initial manifestation of bipolar disorder. It is generally accepted (although not proven by controlled clinical trials) that treatment of such an episode with an antidepressant alone may increase the likelihood of an accelerated mixed/manic episode in patients at risk for bipolar disorder.

Before starting antidepressant treatment, a thorough screening should be performed to assess the risk of bipolar disorder in that patient; such a screening should include a detailed psychiatric history, including family history of suicide, bipolar disorder, and depression. Like all antidepressants, paroxetine is not registered for the treatment of bipolar depression. Paroxetine should be used with caution in patients with a history of mania.

MAO inhibitors. Treatment with paroxetine should be initiated cautiously, not earlier than 2 weeks after stopping therapy with MAO inhibitors; the dose of paroxetine should be increased gradually until optimal therapeutic effect is achieved (see also “Contraindications”).

Renal or hepatic impairment. Caution is recommended when treating patients with severe renal impairment and patients with impaired liver function with paroxetine.

Epilepsy. As with other antidepressants, paroxetine should be used with caution in patients with epilepsy.

Convulsive seizures. The incidence of seizures in patients taking paroxetine is less than 0.1%. If a seizure occurs, treatment with paroxetine should be discontinued.

Electroconvulsive therapy. There is limited experience with concomitant use of paroxetine and electroconvulsive therapy.

Glaucoma. As other drugs of the SSRI group, paroxetine occasionally causes mydriasis, and it should be used with caution in patients with closed-angle glaucoma.

Hyponatremia. When treated with paroxetine, hyponatremia occurs rarely and mainly in elderly patients.

Bleeding. Bleeding of the skin and mucous membranes (including gastrointestinal bleeding) has been reported in patients treated with paroxetine. Therefore, paroxetine should be used with caution in patients who simultaneously receive medications that increase the risk of bleeding, in patients with a known propensity for bleeding, and in patients with conditions that predispose to bleeding.

Heart diseases. The usual precautions should be observed when treating patients with heart disease.

The clinical experience with paroxetine indicates that it does not impair cognitive or psychomotor function. However, as with any other psychotropic medication, patients should be especially careful when driving and operating machinery.

Although paroxetine does not increase the negative effects of alcohol on psychomotor functions, it is not recommended to use paroxetine and alcohol at the same time.

Contraindications

Hypersensitivity to paroxetine and the drug components.

Combined use of paroxetine with MAO inhibitors (paroxetine should not be used concomitantly with MAO inhibitors or within 2 weeks after their withdrawal; MAO inhibitors should not be prescribed within 2 weeks after stopping treatment with paroxetine).

Combination with thioridazine (paroxetine should not be used in combination with thioridazine because, like other drugs inhibiting CYP2D6-cytochrome P450 enzyme activity, paroxetine may increase plasma concentrations of thioridazine).

Side effects

Blood and lymphatic system disorders: sometimes – abnormal bleeding, mainly bleeding into the skin and mucous membranes (most often bruising); very rarely – thrombocytopenia.

Immune system disorders: very rare – allergic reactions (including urticaria and angioedema).

Endocrine disorders: very rare – ADH secretion disorder syndrome.

Metabolic disorders: often – decreased appetite; rarely – hyponatremia (occurs mainly in elderly patients and may be caused by ADH secretion disorder syndrome).

Psychiatric disorders: often – somnolence, insomnia; sometimes – confusion, hallucinations; rarely – manic reactions. These symptoms may also be due to the disease itself.

Visual disorders: often – blurred vision; very rare – exacerbation of glaucoma.

Chronic disorders: sometimes – sinus tachycardia.

vascular disorders: sometimes – transient increase or decrease of BP, including in patients with pre-existing arterial hypertension or anxiety.

Respiratory, chest and mediastinal disorders: often – yawning.

Nervous system disorders: often – seizures.

Gastrointestinal disorders: very common – nausea; common – constipation, diarrhea, dry mouth; very rare – gastrointestinal bleeding.

Hepatobiliary disorders: rare – increase in liver enzymes; very rare – hepatitis, sometimes accompanied by jaundice and/or liver failure. Post-marketing reports of liver damage such as hepatitis, sometimes with jaundice, and/or liver failure are very rare. The appropriateness of discontinuing treatment with paroxetine should be considered in cases of prolonged elevation of liver function tests.

Skin and subcutaneous tissue disorders: frequently – sweating; rarely – skin rash; very rarely – photosensitivity reactions.

River and urinary tract disorders: rare – urinary retention.

Reproductive system and mammary glands disorders: very common – sexual dysfunction; rarely – hyperprolactinemia/galactorrhea.

General disorders: frequent – asthenia; very rare – peripheral edema.

Symptoms occurring on discontinuation of paroxetine treatment: often – dizziness, sensory disturbances, sleep disturbances, anxiety, headache; sometimes – agitation, nausea, tremor, confusion, sweating, diarrhea.

Overdose

Symptoms: in addition to the symptoms described in the side effects section, vomiting, dilated pupils, fever, BP changes, involuntary muscle contractions, agitation, anxiety, tachycardia have been observed.

Patients usually normalized without serious consequences, even with single doses of up to 2,000 mg. A number of reports described symptoms such as coma and ECG changes; deaths were very rare, usually in situations in which patients took paroxetine with other psychotropic drugs or with alcohol.

Treatment: general measures used in overdose of any antidepressant; if necessary – gastric lavage, administration of activated charcoal (20-30 mg every 4-6 hours during the first days after overdose), supportive therapy and frequent monitoring of basic physiological parameters.

There is no specific antidote for paroxetine.

Pregnancy use

Pregnancy

Animal studies have found no teratogenic or selective embryotoxic activity with paroxetine, and evidence from the small number of women who have taken paroxetine during pregnancy suggests no increased risk of congenital anomalies in newborns.

There have been reports of preterm births in women who received paroxetine or other SSRIs during pregnancy, but a causal relationship between these drugs and preterm births has not been established. Paroxetine should not be used during pregnancy unless its potential benefit exceeds the possible risk.

The health of newborns whose mothers took paroxetine in late pregnancy should be monitored particularly closely, because there have been reports of complications in newborns exposed to paroxetine or other SSRIs in the third trimester of pregnancy.

It should be noted, however, that even in this case a causal relationship between the mentioned complications and this drug therapy has not been established. The clinical complications described included: respiratory distress, cyanosis, apnea, seizures, body temperature instability, feeding difficulties, vomiting, hypoglycemia, arterial hypertension, hypotension, hyperreflexia, tremors, tremors, irritability, lethargy, persistent crying and sleepiness.

In some reports, symptoms have been described as neonatal manifestations of withdrawal syndrome. In most cases, the described complications occurred immediately after delivery or shortly thereafter (

Lactation

New amounts of paroxetine penetrate into breast milk. However, paroxetine should not be taken during breastfeeding unless its benefit to the mother exceeds the potential risk to the baby.

Similarities