Paxil pills 20mg №100

Composition

Active ingredient: paroxetine hydrochloride hemihydrate 22.8 mg (equivalent to 20.0 mg paroxetine);

Excipients: Calcium dihydrophosphate dihydrate; sodium carboxymethyl starch type A; Magnesium stearate;

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

Mechanism of action

Paxil - antidepressant activity due to the specific inhibition of serotonin reuptake in brain neurons.

Pharmacodynamics

It has a low affinity for muscarinic cholinergic receptors, and animal studies have shown that anticholinergic properties are poorly expressed. In vitro studies have shown that paroxetine has a weak affinity for alpha₁ -, alpha₂ - and beta-adrenoreceptors, as well as dopamine (D₂ ), serotonin 5-HT₁ - and 5-HT₂ - and histamine (H₁ ) receptors. The lack of interaction with postsynaptic receptors in vitro is confirmed by the results of in vivo studies, which demonstrated the lack of ability of paroxetine to inhibit the central nervous system and cause arterial hypotension. It does not violate psychomotor functions and does not enhance the inhibitory effect of ethanol on the central nervous system.

Like other selective serotonin reuptake inhibitors (SSRIs), paroxetine causes symptoms of over-stimulation of 5-HT receptors when administered to animals that have previously received MAO inhibitors or tryptophan.

Studies on behavior and EEG changes have demonstrated that paroxetine causes weak activating effects at doses higher than those required to inhibit serotonin reuptake. By nature, its activating properties are not amphetamine-like.

Animal studies have shown that paroxetine does not affect the cardiovascular system.

In healthy individuals, paroxetine does not cause clinically significant changes in blood pressure, heart rate and ECG.

When ingested, it is well absorbed and metabolized during the "first pass" through the liver. Due to the “first pass” metabolism, less paroxetine is released into the systemic circulation than is absorbed from the gastrointestinal tract. As the amount of paroxetine in the body increases with a single dose of large doses or with multiple doses of usual doses, the first-pass metabolic pathway becomes partially saturated and the clearance of paroxetine from plasma decreases. This leads to a disproportionate increase in plasma concentrations of paroxetine. Therefore, its pharmacokinetic parameters are unstable, resulting in non-linear kinetics. It should be noted, however, that non-linearity is usually mild and is observed only in those patients who, while receiving low doses of the drug in plasma, achieve low levels of paroxetine. Equilibrium concentration in plasma is reached in 7-14 days.Paroxetine is widely distributed in tissues, and pharmacokinetic calculations show that only 1% of the total amount of paroxetine in the body remains in plasma. At therapeutic concentrations, approximately 95% of paroxetine in plasma is associated with proteins. No correlation was found between plasma concentrations of paroxetine and its clinical effect (adverse reactions and efficacy). It is established that paroxetine in small quantities penetrates into the breast milk of women, as well as into the embryos and fruits of laboratory animals.

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

Indications

• Depression of all types in adults, including reactive and severe depression, as well as depression, accompanied by anxiety;
• OCD in adults (including as a means of supportive and prophylactic therapy), as well as in children and adolescents from 7 to 17 years old;
• panic disorder in adults, with agoraphobia and without it (including as a means of supportive and prophylactic therapy;
• social phobia in adults (including as a means of supportive and preventive therapy), as well as in children and adolescents aged 8-17 years;
• generalized anxiety disorder in adults (including as a means of supportive and prophylactic therapy);
• post-traumatic stress disorder in adults.

Use during pregnancy and lactation

Pregnancy

Animal studies have not revealed teratogenic or selective embryotoxic activity in paroxetine, and data on a small number of women who took paroxetine during pregnancy indicate the absence of an increased risk of congenital abnormalities in the newborn. There are reports of preterm labor in women who received paroxetine or other drugs of the SSRI group during pregnancy, but the causal relationship between these drugs and preterm labor has not been established. Paroxetine should not be used during pregnancy, if its potential benefit does not exceed the possible risk.

It is necessary to carefully monitor the health of those newborns whose mothers took paroxetine in late pregnancy, since there are reports of complications in newborns exposed to paroxetine or other products of the SSRI group in the third trimester of pregnancy. It should be noted, however, that in this case the causal link between the mentioned complications and this drug therapy has not been established.The described clinical complications included: respiratory distress, cyanosis, apnea, convulsive seizures, instability of body temperature, difficulties with feeding, vomiting, hypoglycemia, arterial hypertension, hypotension, hyperreflexia, tremor, tremors, irritability, lethargy, constant 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 birth or shortly after them (

Lactation

A small amount of paroxetine penetrates into breast milk. However, paroxetine should not be taken during breastfeeding, except in cases where its benefits to the mother outweigh the potential risk to the baby.

Contraindications

Hypersensitivity to paroxetine and drug components.

The combined use of paroxetine with MAO inhibitors (paroxetine should not be used simultaneously with MAO inhibitors or for 2 weeks after their withdrawal; MAO inhibitors should not be prescribed for 2 weeks after stopping treatment with paroxetine).

Combined use with thioridazine (paroxetine should not be prescribed in combination with thioridazine, because, like other drugs that inhibit the activity of the CYP2D6 enzyme, cytochrome P450, paroxetine may increase plasma thiordidine concentrations).

Side effects

Disorders of the blood and lymphatic system: sometimes - abnormal bleeding, mainly hemorrhage into the skin and mucous membranes (most often bruises); very rarely - thrombocytopenia.

Immune system disorders: very rarely, allergic reactions (including urticaria and angioedema).

Endocrine disorders: very rarely - syndrome of violation of secretion of ADH.

Metabolic disorders: often - loss of appetite; rarely - hyponatremia (occurs predominantly in elderly patients and may be due to the syndrome of impaired secretion of ADH).

Mental disorders: often - drowsiness, insomnia; sometimes - confusion, hallucinations; rarely manic reactions. These symptoms may also be due to the disease itself.

Violations by the organs of vision: often - blurred vision; very rarely - exacerbation of glaucoma.

Heart disorders: sometimes - sinus tachycardia.

Vascular disorders: sometimes - transient increase or decrease in blood pressure, incl. in patients with preexisting arterial hypertension or anxiety.

Disorders of the respiratory system, chest and mediastinum: often - yawning.

Violations of the nervous system: often - convulsive seizures.

Gastrointestinal disorders: very often - nausea; often - constipation, diarrhea, dry mouth; very rarely - Gastrointestinal bleeding .

Hepatobiliary disorders: rarely - increased levels of liver enzymes; very rarely, hepatitis, sometimes accompanied by jaundice and / or liver failure.
Sometimes there is an increase in liver enzyme levels.Post-marketing reports of liver damage such as hepatitis, sometimes with jaundice, and / or liver failure are very rare. The question of whether to discontinue treatment with paroxetine should be addressed in cases where there is a long-term increase in functional liver function tests.

Violations of the skin and subcutaneous tissues: often - sweating; rarely, skin rashes; very rarely - photosensitivity reactions.

Disturbances from the kidneys and urinary tract: rarely - urinary retention.

Disorders of the reproductive system and mammary glands: very often - sexual dysfunction; rarely, hyperprolactinemia / galactorrhea.

General disorders: often - asthenia; very rarely - peripheral edema.

Symptoms that occur when stopping treatment with paroxetine: often - dizziness, sensory disturbances, sleep disturbances, anxiety, headache; sometimes - agitation, nausea, tremor, confusion, sweating, diarrhea.

Interaction

Serotonergic drugs. The use of paroxetine, as well as other drugs of the group of SSRIs, simultaneously with serotonergic drugs (including inhibitors of MAO, L-tryptophan, triptans, tramadol, linezolid, other drugs of the SSRI group, lithium and herbal remedies containing St. John's wort), can be accompanied by the development of effects caused by serotonin. When using these drugs in combination with paroxetine, care must be taken to conduct careful clinical monitoring.

Enzymes involved in the metabolism of drugs.The metabolism and pharmacokinetics of paroxetine may be altered by the induction or inhibition of enzymes that are involved in the metabolism of drugs. When using paroxetine simultaneously with inhibitors of enzymes involved in the metabolism of drugs, it is necessary to assess the feasibility of using a dose of paroxetine, which is in the lower part of the range of therapeutic doses. The initial dose of paroxetine does not need to be adjusted if it is used simultaneously with the drug, which is a known inducer of enzymes involved in the metabolism of drugs (for example, Carbamazepine , rifampicin, phenobarbital, phenytoin). Any subsequent adjustment of the dose of paroxetine should be determined by its clinical effects (tolerability and effectiveness).

CYP3A4. The study of the interaction in vivo with simultaneous use of paroxetine and terfenadine in an equilibrium state, which is a substrate of the enzyme CYP3A4 , showed that paroxetine does not affect the pharmacokinetics of terfenadine. In a similar in vivo interaction study, no effect of paroxetine on the pharmacokinetics of alprozalam and vice versa was found. The simultaneous use of paroxetine with terfenadine, alprozalam and other drugs that serve as a substrate for the enzyme CYP3A4, is unlikely to cause harm to the patient.

The ability of paroxetine 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 the CYP2D6 enzyme can lead to an increase in plasma concentrations of simultaneously used drugs that are metabolized by this enzyme. Such drugs include tricyclic antidepressants (for example, Amitriptyline , nortriptyline, imipramine, and desipramine), the neuroleptics of the phenothiazine series, Risperidone , and some antiarrhythmic drugs of type 1C (for example, propafenone and flecainide) and Metoprolol .

Procyclidine. Daily paroxetine significantly increases plasma concentrations of procyclidine. If anticholinergic effects occur, the dose of procyclidine should be reduced.

Anticonvulsant drugs: carbamazepine, phenytoin, sodium valproate. The simultaneous use of paroxetine and these drugs does not affect their pharmacokinetics and pharmacodynamics in patients with epilepsy.

Clinical studies have shown that the absorption and pharmacokinetics of paroxetine are independent or practically independent (that is, the existing dependence does not require a dose change) on food intake, antacids, Digoxin , propranolol, alcohol.

How to take, the course of administration and dosage

Inside (the pill should be swallowed whole, without chewing), 1 time per day (in the morning, during 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 medication,efficacy of therapy should be evaluated and, if necessary, the dose of paroxetine should be adjusted 2-3 weeks after the start of treatment and further depending on the clinical indications. To relieve depressive symptoms and prevent recurrence, it is necessary to observe adequate duration of stopping and supporting therapy. The use of paroxetine in children and adolescents (7-17 years) for the 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 begins with a dose of 20 mg per day, which can be increased weekly by 10 mg per day. If necessary, the dose can be increased to 60 mg per day. Adequate duration of therapy should be observed. For children and adolescents (7–17 years old), the initial dose is 10 mg per day; it can be increased by 10 mg per day per week. If necessary, the dose can be increased to 50 mg per day.

Panic disorder. The recommended dose for adults is 40 mg per day. Treatment of patients should begin with a dose of 10 mg per day and weekly increase the dose of 10 mg per day, focusing on the clinical effect. If necessary, the dose can be increased to 60 mg per day. A low initial dose is recommended to minimize the possible increase in the symptoms of panic disorder, which may occur at the beginning of treatment with any antidepressants. It is necessary to observe adequate terms of therapy.

Social phobia.The recommended dose for adults is 20 mg per day. If necessary, the dose can 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 old) should be started 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 can be increased to 50 mg per day.

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

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

Overdose

Symptoms: In addition to the symptoms described in the “Side Effects” section, vomiting, dilated pupils, fever, changes in blood pressure, involuntary muscle contractions, agitation, anxiety, tachycardia are observed.

The condition of patients usually returned to normal without serious consequences even with a single dose of up to 2000 mg. A number of reports describe symptoms such as coma and ECG changes; deaths were very rare, usually in situations where patients took paroxetine with other psychotropic drugs or with alcohol.

Treatment: general measures used in the overdose of any antidepressants; if necessary, gastric lavage, the appointment of Activated carbon (20-30 mg every 4-6 hours during the first days after overdose),maintenance therapy and frequent monitoring of basic physiological parameters.

The specific antidote paroxetine does not exist.

Special instructions

style="font-size>