Composition, structure and packing Paroxetine Hydrochloride
Paroxetine Hydrochloride Tablets, film-coated white, round, biconvex, coated with risk, with a rough surface. 1 tab. paroxetine hydrochloride hemihydrate 22.76 mg, equivalent to paroxetine 20 mg. Excipients: calcium phosphate, microcrystalline cellulose, crospovidone, kopovidon, colloidal silicon dioxide, magnesium stearate, talc. The composition of the shell: hypromellose, macrogol 6000, talc, titanium dioxide.
Tablets, film-coated white, round, biconvex, with risk, with a rough surface. 1 tab. paroxetine hydrochloride hemihydrate 34.14 mg, equivalent to paroxetine 30 mg. Excipients: calcium phosphate, microcrystalline cellulose, crospovidone, kopovidon, colloidal silicon dioxide, magnesium stearate, talc. The composition of the shell: hypromellose, macrogol 6000, talc, titanium dioxide.
Clinico-pharmacological group: Antidepressant.
Pharmacological action Paroxetine Hydrochloride
Antidepressant. Is a selective serotonin reuptake inhibitor (5-hydroxytryptamine, 5-HT) neurons in the brain that determines its antidepressant action and efficacy in the treatment of obsessive-compulsive (OCD) and panic disorder. Paroxetine has low affinity for the m-cholinergic receptors (anticholinergic action has the weak), α1-, α2-and β-adrenoceptors, as well as dopamine (D2), 5HT1-like, 5HT2-like and histamine H1-receptors. Paroxetine does not affect psychomotor function and does not potentiate the inhibitory effect of ethanol on them. According to the study of behavior and EEG of paroxetine revealed weak activating properties when it is administered in doses higher than those needed to inhibit serotonin reuptake. There is no significant change in blood pressure, heart rate and EEG.
Pharmacokinetics Paroxetine Hydrochloride
Absorption
After oral administration, paroxetine is well absorbed from the gastrointestinal tract and is metabolized through the liver first pass.
Distribution
Css achieved within 7-14 days after initiation of therapy. With increasing doses and / or duration of treatment is observed nonlinear dependence of the pharmacokinetic parameters of the dose. Paroxetine is extensively distributed in tissues, only 1% of its present in plasma. Protein binding by 95%.
Metabolism
Metabolized in the liver to form inactive metabolites. Is an inhibitor of isoenzyme CYP2D6. The main metabolites of paroxetine are polar and conjugated products of oxidation and methylation, which are rapidly cleared from the body, have weak pharmacological activity and do not affect its therapeutic effect. In the metabolism of paroxetine is not disturbed due to its selective action of uptake of serotonin neurons.
Breeding
About 64% of paroxetine is excreted in urine (2% – unchanged, 64% – in the form of metabolites), approximately 36% excreted in the bile through the intestines, primarily in the form of metabolites, less than 1% – unchanged.
Excretion of metabolites of paroxetine biphasic, first in the metabolism of the first passage through the liver, then it is controlled by systemic elimination. T1 / 2 of paroxetine varies, but averages 24 hours
Pharmacokinetics in special clinical situations
The concentration of paroxetine in plasma increases with abnormal liver function and kidney, as well as in the elderly.
Statement Paroxetine Hydrochloride
depression of all types, including reactive, severe endogenous depression and depression accompanied by anxiety;
obsessive-compulsive disorder (OCD);
panic disorder, including with agoraphobia;
Social anxiety disorder / social phobia;
generalized anxiety disorder.
Dosage regimen Paroxetine Hydrochloride
Tablets, taken orally, 1 time / day in the morning, while eating, swallowing whole with water. The dose is adjusted individually for the first 2-3 weeks after initiation of therapy and subsequently adjusted if necessary. In depression the recommended dose is 20 mg 1 time / day.
If necessary, gradually increase the dose of 10 mg / day, maximum daily dose should not exceed 50 mg. Priobsessivno-compulsive disorders initial therapeutic dose is 20 mg / day, followed by a weekly increase of 10 mg. Recommended average therapeutic dose – 40 mg / day, if necessary, the dose may be increased to 60 mg / day.
With panic disorder starting dose – 10 mg / day (to reduce the possible risk of acute panic symptoms), followed by a weekly increase of 10 mg. The average therapeutic dose – 40 mg / day. The maximum dose – 50 mg / day.
When social anxiety disorder / social phobia starting dose is 20 mg / day, with no effect for at least 2 weeks may increase the dose to a maximum of 50 mg / day. Dose should be increased to 10 mg at intervals of not less than a week in accordance with the clinical effect.
In generalized anxiety disorders, and initial therapeutic dose is 20 mg / day. In renal and / or hepatic impairment the recommended dose is 20 mg / day. For elderly patients the daily dose should not exceed 40 mg. In order to prevent the development of withdrawal symptoms stop taking the drug should be gradual.
Side effect Paroxetine Hydrochloride
From the central and peripheral nervous system: drowsiness, tremor, fatigue, insomnia, dizziness, fatigue, convulsions, extrapyramidal disorder, serotonin syndrome, hallucinations, delusions, confusion, agitation, anxiety, depersonalization, panic attacks, anxiety, amnesia, myoclonia.
From the senses: visual disturbances.
With the Musculoskeletal System: arthralgia, myalgia, muscle weakness, myopathy.
The urinary system: urinary retention, urinary frequency.
With the reproductive system: sexual dysfunction, including impotence and ejaculation disorders, hyperprolactinaemia / galactorrhoea, anorgasmia.
From the digestive system: the reduction or increase in appetite, change in taste, nausea, vomiting, dry mouth, constipation or diarrhea and in some cases – Hepatitis.
Cardio-vascular system: orthostatic hypotension. Allergic reactions: rash, urticaria, ecchymosis, pruritus, angioedema. Other: increased sweating, rhinitis, hyponatremia, impaired secretion of antidiuretic hormone.
Contraindications Paroxetine Hydrochloride
concomitant use of MAO inhibitors and the period of 14 days after their withdrawal;
unstable epilepsy;
pregnancy;
Lactation (breastfeeding);
Infancy;
hypersensitivity to the drug.
Precautions should be prescribed the drug for hepatic failure, renal failure, angle-closure glaucoma, prostatic hyperplasia, mania, heart disease, epilepsy, convulsive states, concomitant administration of electro-therapy, simultaneous administration of drugs that increase the risk of bleeding, risk factors for bleeding disorders and diseases, increase the risk of bleeding.
Pregnancy and lactation Paroxetine Hydrochloride
The drug is contraindicated during pregnancy and lactation.
Use in hepatic dysfunction
Precautions should be prescribed the drug for hepatic failure. In hepatic insufficiency the recommended dose is 20 mg / day.
Use in renal impairment
Precautions should be prescribed the drug for renal failure. In renal insufficiency, the recommended dose is 20 mg / day.
Cautions Paroxetine Hydrochloride
In order to avoid the development of neuroleptic malignant syndrome with caution should be used paroxetine for patients taking neuroleptics. Treatment with paroxetine administered 2 weeks after discontinuation of MAO inhibitors. Elderly patients in patients receiving paroxetine possible hyponatremia. In some cases, a dose adjustment while using insulin and / or oral hypoglycemic agents.
With the development of seizures paroxetine treatment is discontinued. At the first sign of mania should be discontinued therapy with paroxetine. During the first few weeks of treatment with paroxetine should carefully monitor the patient in connection with possible suicide attempts. During treatment with paroxetine should abstain from alcohol due to the enhancement of its toxicity.
Use in Pediatrics
The use of paroxetine in children is not recommended because of its safety and efficacy in this patient group have not been established.
Effects on ability to drive and control mechanisms
Despite the fact that paroxetine does not impair cognitive and psychomotor function, patients should avoid or exercise extreme caution while driving lessons and other potentially hazardous activities that require your full attention and psychomotor speed of reaction.
Overdose Paroxetine Hydrochloride
Symptoms include nausea, vomiting, tremor, mydriasis, dry mouth, irritability, nystagmus, agitation, sweating, drowsiness, sinus tachycardia, seizures, bradycardia, increased blood pressure, a nodal rhythm. In very rare cases, when taken with other psychotropic drugs and / or alcohol may be ECG changes, coma. In severe overdose – serotonin syndrome, is rare – rhabdomyolysis. Treatment: gastric lavage, activated charcoal. If necessary, symptomatic therapy. No specific antidote.
Drug Interactions Paroxetine Hydrochloride
Simultaneous administration of antacids does not affect the absorption and pharmacokinetic parameters of paroxetine. Concurrent use of paroxetine is contraindicated with MAO inhibitors.
When concomitant administration of paroxetine increases the concentration of protsiklidina. Because inhibition of cytochrome P450 with paroxetine may increase the effect of barbiturates, phenytoin, indirect anticoagulants, tricyclic antidepressants, antipsychotics and antiarrhythmics fenotiazinovyh class 1C, metoprolol, and increased risk of side effects, while the appointment of these medicines.
When concomitant administration with drugs that inhibit liver enzymes may require dose reduction of paroxetine. Paroxetine increases the bleeding during warfarin odnovoremennogo (with unchanged prothrombin time).
When concomitant administration of paroxetine with atypical antipsychotics, tricyclic antidepressants, drugs of the phenothiazine series, NSAIDs (including aspirin) may prevent blood clotting prootsessa. Simultaneous with the appointment of paroxetine with serotonergic drugs (tramadol, sumatriptan) may lead to increased serotonergic effect. Noted synergism of tryptophan, lithium, and paroxetine.
When concomitant administration of paroxetine with phenytoin and other anticonvulsant drugs may increase the frequency of side effects. Paroxetine inhibits the much weaker antihypertensive effects guanetidina compared with antidepressants that inhibit norepinephrine capture.
