Plisil N, pills 20mg 30pcs

Composition

Active ingredient:

paroxetine mesylate 25.83 mg (equivalent to 20 mg of paroxetine);

Auxiliary substances:

calcium hydrophosphate anhydrous-317.75 mg;

sodium carboxymethyl starch-5.95 mg;

magnesium stearate-7 mg;

Film shell:

lactose monohydrate-3.81 mg; hypromellose-2.97 mg; titanium dioxide (E 171) – 2.6 mg; macrogol 4000-1.06 mg; iron oxide yellow (E 172) – 0.16 mg; iron oxide red (E 172) – 0.002 mg

Pharmacological action

Plizil is an antidepressant.

Pharmacodynamics

Paroxetine is a selective inhibitor of 5-hydroxytryptamine (5-HT, serotonin) reuptake by brain neurons, which determines its antidepressant effect and effectiveness in the treatment of obsessive-compulsive and panic disorders.

The main metabolites of paroxetine are polar and conjugated products of oxidation and methylation, which are rapidly eliminated from the body, have weak pharmacological activity and do not affect its therapeutic effect. During the metabolism of paroxetine, the selective uptake of 5-HT by neurons due to its action is not disturbed.

Paroxetine has a low affinity for muscarinic cholinergic receptors.

Having a selective effect, in contrast to tricyclic antidepressants, paroxetine showed low affinity for_α1-, _α2-, β-adrenergic receptors, as well as for dopamine,5 –HT1-and 5-HT2_{-serotonin and H1}–histamine receptors.

Paroxetine does not interfere with psychomotor functions and does not potentiate the depressing effect of ethanol on them.

According to a behavioral and EEG study, paroxetine has weak activating properties when given at doses higher than those required to inhibit 5-HT uptake. In healthy volunteers, it does not cause significant changes in blood pressure, heart rate, and EEG.

Unlike antidepressants, which inhibit norepinephrine reuptake, paroxetine is much less likely to inhibit the antihypertensive effects of guanethidine.

Pharmacokinetics

Paroxetine is well absorbed after oral use and undergoes first-pass metabolism through the liver. Urinary excretion of unchanged paroxetine is usually less than 2% of the dose, with metabolites accounting for about 64% of the dose. The intestine excretes about 36% of the dose, probably through bile, in which unchanged paroxetine is less than 1% of the dose. Thus, paroxetine is mainly excreted in the form of metabolites.

The elimination of paroxetine metabolites from the body is biphasic, first as a result of the metabolism of the first passage through the liver, and then it is controlled by systemic elimination. T_1/2varies, but is usually about 16-21 hours. C_ss is reached by 7-14 days after the start of treatment, and the pharmacokinetics do not change during long-term treatment. The clinical effects of paroxetine (side effects and efficacy) do not correlate with its plasma concentration.

Since the metabolism of paroxetine involves the first stage of passage through the liver, its amount determined in the systemic circulation is less than that absorbed from the gastrointestinal tract. With an increase in the dose of paroxetine or with repeated dosing, when the load on the body increases, the first-pass effect through the liver is partially absorbed and the plasma clearance of paroxetine decreases. As a result, it is possible to increase the concentration of paroxetine in plasma and fluctuate pharmacokinetic parameters, which can be observed only in those patients who, when taking low doses, reach low levels of the drug in plasma.

Paroxetine is extensively distributed in tissues, and pharmacokinetic calculations show that only 1% of it is present in plasma, and at therapeutic concentrations 95% is bound to plasma proteins.

Indications

• depression of all types, including reactive, severe endogenous depression and depression accompanied by anxiety;
• obsessive-compulsive disorder (OCD);
• panic disorder, including those with agoraphobia;
• social anxiety disorder/social phobia;
• generalized anxiety disorder;
• post-traumatic stress disorder.

Use during pregnancy and lactation

The drug is contraindicated during pregnancy and lactation (breastfeeding).

Contraindications

• hypersensitivity to the components of the drug;
• concomitant use with MAO inhibitors and for 14 days after their withdrawal;
• pregnancy;
• lactation;
• children and adolescents under 18 years of age (efficacy and safety have not been established).

With caution:  hepatic insufficiency, renal insufficiency, angle-closure glaucoma, prostatic hyperplasia, mania, heart pathology, epilepsy (with unstable epilepsy, avoid taking the drug), convulsive states, the appointment of electric pulse therapy, taking drugs that increase the risk of bleeding, the presence of risk factors for increased bleeding, diseases that increase the risk of bleeding, the elderly.

Side effects

Nervous system disorders:  sleepiness, tremor, asthenia, insomnia, dizziness, fatigue, convulsions, extrapyramidal disorders, hallucinations, mania, confusion, agitation, anxiety, depersonalization, panic attacks, nervousness, paresthesia, decreased ability to concentrate, serotonin syndrome.

From the musculoskeletal system:  arthralgia, myalgia, myopathy, myasthenia gravis.

From the side of the senses:  visual impairment, change in taste.

From the genitourinary system:  sexual dysfunction, including impotence and ejaculation disorders, decreased libido, anorgasmia, urinary retention, and increased urination.

From the digestive system:  decreased appetite, nausea, vomiting, dry mouth, constipation, or diarrhea, and in very rare cases, hepatitis.

From the CCC side:  orthostatic hypotension.

Other services:  increased sweating, allergic reactions (rash, urticaria, ecchymosis, pruritus, angioedema), hyponatremia, impaired ADH secretion, hyperprolactinemia/galactorrhea, withdrawal syndrome with abrupt withdrawal of the drug.

Interaction

Food intake and antacids do not affect the absorption and pharmacokinetic parameters of the drug.

Paroxetine is incompatible with MAO inhibitors, thioridazine.

Concomitant use with paroxetine increases the concentration of procyclidine.

During therapy with paroxetine, you should refrain from taking alcohol due to the possible increase in the toxic effect of alcohol.

The metabolism and pharmacokinetics of paroxetine may change when co-administered with inducers/inhibitors of liver enzymes.

In connection with the inhibition by paroxetine of cytochrome P-450 may increase the effects of barbiturates, phenytoin, anticoagulants, tricyclic antidepressants (nortriptyline, amitriptyline, imipramine, and fluoxetine desipramine), phenothiazine neuroleptics (thioridazine) and antiarrhythmic drugs of class 1 ( including propafenone), metoprolol and increase the risk of side effects during concurrent use of these drugs.

When administered concomitantly with drugs that inhibit liver enzymes, it may be necessary to reduce the dose of paroxetine.

Paroxetine increases the bleeding time when taking warfarin, with constant PV.

When paroxetine is co-administered with atypical antipsychotics, phenothiazines, tricyclic antidepressants, aspirin, NSAIDs, caution is recommended due to possible blood clotting disorders.

Concomitant use with serotonergic drugs (tramadol, sumatriptan) may increase the serotonergic effect.

As with other SSRIs, there was a mutual increase in the effect of tryptophan, lithium and paroxetine. Co-use with lithium preparations is carried out under the control of their concentration in the blood.

Co-use with tryptophan-containing drugs is not recommended. When using paroxetine, as well as other SSRIs, with neuroleptics, neuroleptic malignant syndrome may develop.

Concomitant use of paroxetine with phenytoin and other anticonvulsants may reduce the concentration of paroxetine in plasma and increase the frequency of side effects.

How to take it, course of use and dosage

Inside,1 time a day, in the morning, with meals. The tablet is swallowed whole, washed down with water. The dose is selected individually during the first 2-3 weeks after the start of therapy and subsequently adjusted if necessary.

For depression:  20 mg once a day. If necessary, the dose is gradually increased by 10 mg / day, up to a maximum of 50 mg / day (depending on the patient’s reaction).

For OCD:  the initial therapeutic dose is 20 mg / day, followed by a weekly increase of 10 mg. The recommended average therapeutic dose is 40 mg / day, if necessary, the dose can be increased to 60 mg / day.

For panic disorders:  the initial dose is 10 mg / day (to reduce the possible risk of developing an exacerbation of panic symptoms), followed by a weekly increase of 10 mg. The average therapeutic dose is 40 mg / day. The maximum dose is 50 mg / day.

Social anxiety disorders/Social phobia: the initial dose is 20 mg / day, if there is no effect for at least 2 weeks, it is possible to increase the dose to a maximum of 50 mg / day. The dose should be increased by 10 mg at intervals of at least a week in accordance with the clinical effect.

Post-traumatic mental disorders: for most patients, the initial and therapeutic doses are 20 mg / day. In some cases, it is recommended to increase the dose of paroxetine to a maximum of 50 mg / day. The dose should be increased by 10 mg each week in accordance with the clinical effect.

Generalized anxiety disorders: the initial and recommended doses are 20 mg / day.

In case of renal and / or hepatic insufficiency: the recommended dose is 20 mg/day.

As with all other antidepressant medications, the dose of the drug should be evaluated and adjusted, if necessary, within 2-3 weeks at the beginning of therapy, and then-as necessary. Patients should continue treatment for a period sufficient for symptoms to disappear: at least 4-6 months after recovery for depression and more for OCD and panic disorder. As with many other psychotropic medications, abrupt discontinuation of the drug is not recommended.

For elderly patients: the daily dose should not exceed 40 mg.

In order to prevent the development of withdrawal syndrome, discontinuation of the drug is carried out gradually.

The use of paroxetine in children is not recommended, as its safety and efficacy in this population have not been established.

Overdose

Symptoms: nausea, vomiting, tremor, dry mouth, dilated pupils, fever, changes in blood pressure, headache, involuntary muscle contractions, restlessness, anxiety, sinus tachycardia, sweating, drowsiness, nystagmus, bradycardia, nodular rhythm.

In very rare cases, when taken simultaneously with other psychotropic drugs and/or alcohol, ECG changes and coma may occur.

Treatment: gastric lavage, use of activated charcoal. If necessary — symptomatic therapy. There is no specific antidote.

Special instructions

In order to avoid the development of neuroleptic malignant syndrome, patients taking neuroleptics should be prescribed with caution.

Paroxetine does not impair cognitive and psychomotor functions, however, as with treatment with other psychotropic drugs, patients should be careful when driving a car and moving mechanisms.

During the treatment period, you should refrain from drinking alcohol and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Treatment with paroxetine is prescribed 2 weeks after the withdrawal of MAO inhibitors.

Hyponatremia is possible in elderly patients.

In some cases, adjustment of the dose of insulin and/or oral hypoglycemic drugs is required.

If seizures develop, treatment with paroxetine is discontinued.

At the first sign of mania, paroxetine therapy should be discontinued.

During the entire treatment period, the patient’s condition should be carefully monitored for possible suicide attempts. The high-risk group, especially in the first weeks of treatment, as well as in the first weeks after discontinuation of the drug, consists of patients under the age of 25 years.

Form of production

Pills.

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

3 years

Active ingredient

Paroxetine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Mental disorders, Phobias and Panic attacks, Obsessive-Compulsive Disorder, Stress, Depression