Paroxetine, 20 mg 30 pcs

Indications

Depression

Depression of all types, including reactive and severe depression as well as depression accompanied by anxiety.

In the treatment of depressive disorders, paroxetine is about as effective as tricyclic antidepressants. There is evidence that paroxetine may give good results in patients where standard antidepressant therapy has been ineffective.

Paroxetine administration in the morning has no adverse effect on the quality and duration of sleep. In addition, sleep may improve as the effects of paroxetine treatment manifest themselves.

When using short-acting sleeping pills in combination with antidepressants, no additional side effects occurred. In the first few weeks of therapy, paroxetine is effective in reducing symptoms of depression and suicidal ideation.

The results of studies in which patients took paroxetine for up to 1 year showed that the drug effectively prevents relapses of depression.

Paroxetine is effective in the treatment of obsessive-compulsive disorder (OCD), including as maintenance and prophylactic therapy. In addition, paroxetine was effective in preventing relapses of OCD.

Panic disorder

Paroxetine is effective in treating panic disorder with and without agoraphobia, including as maintenance and preventive therapy.

The combination of paroxetine and cognitive-behavioral therapy has been found to be significantly more effective in treating panic disorder than cognitive-behavioral therapy alone.

In addition, paroxetine was effective in preventing recurrences of panic disorder.

Social phobia

Paroxetine is an effective treatment for social phobia, including as a long-term maintenance and preventive therapy.

Generalized anxiety disorder

Paroxetine is effective in generalized anxiety disorder, including as long-term maintenance and preventive therapy. Paroxetine is also effective in preventing relapses in this disorder.

Post-traumatic stress disorder.

Paroxetine is effective in treating post-traumatic stress disorder.

Active ingredient

Composition

Active ingredient:

Paroxetine hydrochloride hemihydrate – 22.77 mg, in terms of paroxetine – 20.00 mg.

Excipients: calcium hydrophosphate dihydrate – 209.73 mg; microcrystalline cellulose – 60.00 mg; sodium carboxymethyl starch – 3.00 mg; colloidal silicon dioxide – 1.50 mg; magnesium stearate – 3.00 mg.

Shell composition: hypromellose, 4.54 mg; macrogol-4000, 1.06 mg; titanium dioxide, 2.40 mg.

How to take, the dosage

Paroxetine is recommended to be taken once a day in the morning with a meal. The tablet should be swallowed whole without chewing. Depression The recommended dose in adults is 20 mg per day. If necessary, depending on the therapeutic effect, the daily dose may be increased weekly by 10 mg per day up to a maximum dose of 50 mg per day.

As with any antidepressant treatment, the effectiveness of therapy should be evaluated and, if necessary, the dose of paroxetine should be adjusted 2-3 weeks after the start of treatment and thereafter, depending on clinical indications. To relieve depressive symptoms and prevent relapses, an adequate duration of relieving and supporting therapy should be observed. This period may be several months.

Obsessive-compulsive disorder

The recommended dose is 40 mg per day. Treatment is started with a dose of 20 mg per day, which may be increased weekly by 10 mg per day. If necessary, the dose may be increased to 60 mg per day. Adequate duration of therapy (several months or longer) should be observed.

Panic disorder

The recommended dose is 40 mg per day. Patients should be started with a dose of 10 mg per day and the dose should be increased 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 duration of therapy (several months or longer) should be observed.

Social phobia

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

Post-traumatic stress disorder

The recommended dose is 20 mg daily. If necessary, the dose may be increased weekly by 10 mg per day, depending on 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 L-tryptophan, triptans, tramadol, SSRI drugs, fentanyl, lithium and herbal agents containing St. John’s wort) may cause effects associated with 5-NT (serotonin syndrome), caution and close clinical monitoring are required.

The concomitant use of paroxetine with MAO inhibitors (including linezolid, an antibiotic that converts to a non-selective MAO inhibitor, and methylthionine chloride (methylene blue)) is contraindicated.

Pimozide

In a study of the possibility of using paroxetine and pimozide together in a single low dose (2 mg), an increase in pimozide levels was reported. This fact is explained by the known property of paroxetine to inhibit the CYP2D6 system. Due to the narrow therapeutic index of pimozide and its known ability to prolong the QT interval, simultaneous use of pimozide and paroxetine is contraindicated.

The enzymes involved in drug metabolism

The metabolism and pharmacokinetics of paroxetine may be altered by the induction or inhibition of enzymes that are involved in drug metabolism.

When using paroxetine concomitantly with enzyme inhibitors 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).

Fosamprenavir/ritonavir

Concomitant use of fosamprenavir/ritonavir with paroxetine resulted in a significant decrease in plasma paroxetine concentrations. Plasma concentrations of fosamprenavir/ritonavir when concomitantly used with paroxetine were similar to control values from other studies, indicating no significant effect of paroxetine on fosamprenavir/ritonavir metabolism. There are no data on the effects of long-term co-administration of paroxetine with fosamprenavir/ritonavir. Any subsequent dose adjustment of paroxetine should be determined by its clinical effect (tolerability and efficacy).

Procyclidine

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

Anticonvulsants

The concomitant use of paroxetine and anticonvulsants (carbamazepine, phenytoin, sodium valproate) does not affect their pharmacokinetic and pharmacodynamic profiles in patients with epilepsy.

Nerve and muscle blockers

The drugs of the SSRI group may decrease plasma cholinesterase activity, resulting in increased duration of neuromuscular blocking action of mivacurium and suxamethonium.

Paroxetine’s ability to inhibit the CYP2D6 isoenzyme

Like other antidepressants, including other drugs in the SSRI group, paroxetine inhibits the hepatic CYP2D6 enzyme belonging 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. Such drugs include some tricyclic antidepressants (e.g., amitriptyline, nortriptyline, imipramine and desipramine), phenothiazine neuroleptics (perphenazine and thioridazine), risperidone, atomoxetine, some class 1 C antiarrhythmic agents (such as propafenone and flecainide) and metoprolol. Paroxetine in combination with metoprolol is not recommended for heart failure due to the narrow therapeutic index of metoprolol in this indication.

The irreversible inhibition of the CYP2D6 system by paroxetine may lead to decreased plasma concentrations of its active metabolite, endoxifene, and as a consequence, decrease the effectiveness of tamoxifen.

The ability of paroxetine to inhibit the CYP3A4 isoenzyme.

The in vivo interaction study of concomitant use, under equilibrium conditions, of paroxetine and terfenadine, which is a substrate of the CYP3A4 isoenzyme, showed that paroxetine has no effect on the pharmacokinetics of terfenadine. A similar in vivo interaction study found no effect of paroxetine on the pharmacokinetics of alprazolam, and vice versa. Simultaneous use of paroxetine with terfenadine, alprazolam and other drugs that are substrates of CYP3A4 isoenzyme is unlikely to cause harm to the patient.

The clinical studies have shown that the absorption and pharmacokinetics of paroxetine are independent or almost independent (i.e., existing dependence does not require dose changes) of food, antacids, digoxin, propranololol, and alcohol (paroxetine does not increase the negative effects of ethanol on psychomotor functions; however, it is not recommended that paroxetine and alcohol be taken simultaneously).

Peroral anticoagulants

Perhaps a pharmacodynamic interaction between paroxetine and oral anticoagulants may occur. Concomitant use of paroxetine and oral anticoagulants may increase anticoagulant activity and risk of bleeding. Therefore, paroxetine should be used with caution in patients receiving oral anticoagulants.

NSAIDs, acetylsalicylic acid and other antiplatelet agents

Possible pharmacodynamic interaction between paroxetine and NSAIDs/acetylsalicylic acid. Concomitant use of paroxetine and NSAIDs/acetylsalicylic acid may increase the risk of bleeding.

. Caution should be exercised when treating patients receiving SSRIs concomitantly with oral anticoagulants, with drugs that affect platelet function or increase the risk of bleeding (e.g., atypical neuroleptics such as clozapine, phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, NSAIDs, COX-2 inhibitors), and when treating patients with a history of clotting disorders or conditions that may cause a predisposition to bleeding.

Contraindications

equipment for close monitoring of serotonin syndrome symptoms and blood pressure monitoring should be available. Treatment with paroxetine is acceptable:

– 2 weeks after stopping treatment with irreversible IMAOs or

– at least 24 hours after stopping treatment with reversible IMAOs (e.g.,

moclobemide, linezolid, methylthionine chloride (methylene blue)),

– at least 1 week must pass between discontinuing paroxetine and starting therapy with any IMAO;

combined use with thioridazine. Paroxetine should not be used in combination with thioridazine because, like other drugs that inhibit hepatic CYP2D6 isoenzyme activity, paroxetine may increase plasma thioridazine concentrations, which may lead to prolonged QTc interval and associated potentially life-threatening ventricular pirouette arrhythmia and sudden death;

combined use with pimozide;

use in children and adolescents less than 18 years of age. Controlled clinical trials of paroxetine in the treatment of depression in children and adolescents have not proven its effectiveness, so the drug is not indicated for the treatment of this age group. Safety and efficacy of paroxetine have not been studied when used in younger patients (under 7 years of age).

Side effects

The frequency and intensity of some of the paroxetine adverse reactions listed below may decrease as treatment continues, and such reactions do not usually require withdrawal of the drug. The adverse reactions presented below are listed according to organ and organ system involvement and frequency of occurrence.

The incidence is defined as follows: very common (≥1/10), frequent (≥1/100, ≥1/10), infrequent (≥1/1000, ≥1/100), rare (≥1/10000, ≥1/1000), very rare (≥1/10000), including individual cases, and frequency unknown. The incidence of frequent and infrequent adverse reactions was determined based on summarized safety data from more than 8000 patients participating in clinical trials, calculated from the difference between the incidence of adverse reactions in the paroxetine group and in the placebo group. The incidence of rare and very rare adverse reactions was determined based on post-marketing data, and it refers to the frequency of reported reactions rather than the true incidence of the reactions themselves.

Hematopoietic system disorders: infrequent – abnormal bleeding, mainly bleeding in the skin and mucous membranes (most often – bruising); very rare – thrombocytopenia.

The immune system: very rare – allergic reactions (including anaphylactoid reactions and angioedema).

Endocrine system disorders: very rare – syndrome of impaired secretion of antidiuretic hormone. Metabolic and nutrition disorders: often – decreased appetite, increased cholesterol concentration; rarely – hyponatremia. Hyponatremia occurs mainly in elderly patients and may be caused by antidiuretic hormone secretion disorders.

Mental disorders: frequently – somnolence, insomnia, agitation, unusual dreams (including nightmares); infrequently – confusion, hallucinations; rarely – manic reactions, anxiety, depersonalization, panic attacks, akathisia; frequency is unknown – suicidal thoughts, suicidal behavior.

Cases of suicidal ideation and suicidal behavior have been reported during treatment with paroxetine or early after discontinuation of treatment. These symptoms may also be due to the disease itself.

Nervous system disorders: frequently – dizziness, tremor, headache, concentration disorders; infrequently – extrapyramidal disorders; rarely – seizures, restless legs syndrome; very rarely – serotonin syndrome (symptoms may include agitation, confusion, increased sweating, hallucinations, hyperreflexia, myoclonus, tachycardia with shaking, and tremor). The development of extrapyramidal symptoms, including orofacial dystonia, has been reported infrequently in patients with impaired motor function or who have received neuroleptics.

Overlooking organ: often – blurred vision; infrequently – mydriasis; very rarely – acute glaucoma.

Hearing organ and balance: frequency unknown – tinnitus.

Cardiovascular system: infrequent – sinus tachycardia, postural hypotension, transient increase and decrease of blood pressure. Short-term increase and decrease of blood pressure have been reported after treatment with paroxetine, usually in patients with previous hypertension or anxiety; rarely – bradycardia.

Respiratory system disorders: often – yawning.

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

Hepatic and biliary tract: rarely – increased liver enzymes activity; very rare – hepatitis, sometimes accompanied by jaundice and/or liver failure.

Postmarketing reports of adverse reactions from the liver (such as hepatitis, sometimes accompanied by 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 – increased sweating; infrequently – skin rash, itching; very rarely – photosensitivity reactions, severe skin reactions (including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis), urticaria.

Urinary system disorders: infrequent – urinary retention, urinary incontinence.

As to the reproductive system and mammary glands: very often – sexual dysfunction; rarely – hyperprolactinemia, galactorrhea, menstrual cycle disorders (including menorrhagia, metrorrhagia and amenorrhea); very rarely – priapism.

Musculoskeletal system disorders: rarely – arthalgia, myalgia. Epidemiological studies, mainly conducted in patients aged 50 years and older, have shown an increased risk of bone fractures in patients receiving SSRIs and tricyclic antidepressants. The mechanism leading to this risk is unknown.

Others: frequently, asthenia, weight gain; very rarely, peripheral edema.

Symptoms occurring upon discontinuation of paroxetine treatment: frequently – dizziness, sensory disturbances, sleep disturbances, anxiety, headache; infrequently – agitation, nausea, tremor, confusion, increased sweating, diarrhea, irritability.

The abrupt discontinuation of the drug causes withdrawal syndrome. As with many psychotropic medications, discontinuing paroxetine treatment (especially abruptly) may cause symptoms such as dizziness, sensory disturbances (including paresthesias, electrical shocks and tinnitus), sleep disturbances (including vivid dreams), agitation or anxiety, nausea, headache, tremors, confusion, diarrhea, increased sweating, palpitations, emotional lability, irritability, visual disturbances. In most patients, these symptoms are mild to moderate and resolve spontaneously. No patient group is known to be at increased risk for these symptoms; therefore, if paroxetine treatment is no longer necessary, its dose should be reduced slowly until the drug is completely discontinued.

Overdose

Objective and Subjective Symptoms

The available information on paroxetine overdose indicates a wide range of safety. When paroxetine overdose, fever, BP changes, involuntary muscle contractions, anxiety, and tachycardia have been observed in addition to the symptoms described in the side effect section.

Patients generally normalized without serious consequences, even with single doses up to 2000 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
There is no specific antidote to paroxetine. Treatment should consist of general measures used in case of overdose of any antidepressants. Supportive therapy and frequent monitoring of basic physiological parameters are indicated. The patient should be treated according to the clinical picture or in accordance with the recommendations of the national poison center.

Pregnancy use

Fertility
According to animal studies, paroxetine may affect semen quality characteristics.
Data from in vitro human studies may indicate some effect on semen quality characteristics, but case reports of human use of some SSRI inhibitor drugs (including paroxetine) have shown that the effects on semen quality characteristics were reversible.
To date, no effects on human fertility have been observed.

Pregnancy
Animal studies have shown no teratogenic or selective embryotoxic activity with paroxetine.
Epidemiological studies of pregnancy outcomes while taking antidepressants in the first trimester have found an increased risk of congenital abnormalities, particularly cardiovascular (e.g., interventricular and interatrial septal defects), associated with paroxetine administration. The reported incidence of cardiovascular defects with paroxetine use during pregnancy is approximately 1/50, while the expected incidence of such defects in the general population is approximately 1/100 of newborns. When prescribing paroxetine, alternative treatments should be considered for pregnant women and women planning to become pregnant.

Paroxetine should be prescribed only if its potential benefit exceeds the possible risk. If the decision is made to discontinue paroxetine treatment during pregnancy, the physician should follow the recommendations in the Dosage and Administration – Discontinuation of Paroxetine and the Warnings – Symptoms that may occur when discontinuing paroxetine treatment in adults.
There are reports of premature births in women who received paroxetine or other SSRI drugs during pregnancy, but a causal relationship between taking these drugs and premature births has not been established. The health of newborns whose mothers were exposed to paroxetine during late pregnancy should be monitored, as complications have been reported in newborns exposed to paroxetine or other SSRIs in the third trimester of pregnancy. However, a causal relationship between these complications and these drug therapies has not been confirmed. Described clinical complications included: respiratory distress syndrome, cyanosis, apnea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, arterial hypertension, arterial hypotension, hyperreflexia, tremor, increased neuroreflexivity syndrome, irritability, lethargy, persistent crying, and sleepiness. Some reports have described the symptoms as neonatal manifestations of withdrawal syndrome. In most cases, the described complications occurred immediately after delivery or shortly thereafter (< 24 h). According to epidemiological studies, taking SSRIs (including paroxetine) during pregnancy, especially in the late term, is associated with an increased risk of neonatal persistent pulmonary hypertension.

The increased risk is observed in children born to mothers who took SSRIs in late pregnancy and is 4-5 times greater than that observed in the general population (1-2 per 1000 pregnancies).
Results of animal studies have shown reproductive toxicity of the drug, but no direct adverse effects on pregnancy, embryonic and fetal development, labor, or postnatal development were shown.

Breastfeeding
Minor amounts of paroxetine penetrate into breast milk. In published studies in breastfed infants, paroxetine concentrations were undetectable (<2 ng/mL) or very low (<4 ng/mL).
No evidence of drug exposure has been shown in children. However, paroxetine should not be taken during breastfeeding unless its benefit to the mother exceeds the potential risks to the baby.

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