Aktaparoksetin

General characteristics. Structure:

Active agent - a paroksetina the hydrochloride of 22,22 mg or 33,33 mg corresponding to a paroksetin of 20,00 mg or 30,00 mg.
excipients: magnesium stearate 2255, sodium carboxymethylstarch, Mannitolum of DC, cellulose microcrystallic; methylmethacrylate, dimethylaminoethylmethacrylate and butylmethacrylate copolymer (Eudragit E 100); Опадрай AMV white (aqueous solution): the polyvinyl alcohol which is partially hydrolyzed titanium dioxide (Е 171), talc, lecithin soy (Е 322), xanthane gum (Е 415) - for tablets of 20 mg; Опадрай AMV blue (aqueous solution): the polyvinyl alcohol which is partially hydrolyzed titanium dioxide (Е 171), talc, indigo carmine (Е 132), lecithin soy (Е 322), xanthane gum (Е 415); dye a sunset yellow (Е ON), dye quinolinic yellow (Е 104) - for tablets of 30 mg).

Description:

Tablets of 20 mg: round biconvex tablets, film coated white or almost white color with risky on both sides and side risks, the text "Р" on the one hand and a text "20" on the other hand.

Tablets of 30 mg: round biconvex tablets, film coated blue color with risky on the one hand and a text of "P30" on the other hand.

Pharmacological properties:

Paroksetin is powerful and selection inhibitor of capture of a 5-gidroksitriptamin (5-HT, serotonin) brain neurons that defines its antidepressive action and efficiency at treatment of obsessivno-compulsive (ROC) and panic frustration.

The main metabolites of a paroksetin represent the polar and conjugated products of oxidation and methylation which are quickly brought out of an organism, have weak pharmacological activity and do not influence its therapeutic action. At metabolism of a paroksetin the selection capture caused by its action is not broken by 5-HT neurons.

Paroksetin has low affinity to muskarinovy cholinergic receptors. Possessing the selection action, in difference from tricyclic antidepressants, пароксетин showed low affinity to and-1, and-2, to V-adrenoceptors, and also to dopamine, 5-HT1 similar, 5-HT2 similar and histamine (H1) receptors. Paroksetin does not break psychomotor functions and does not potentiate oppressing effect of ethanol on them.

According to a research of behavior and EEG, at a paroksetin the weak activating properties when it is appointed in doses come to light is higher than those which are necessary for inhibition of capture 5-HT. It does not cause considerable change of level of arterial pressure, heart rate and EEG in healthy volunteers. Unlike antidepressants which inhibit capture of noradrenaline пароксетин suppresses anti-hypertensive effects of a guanitidin much more weakly.

Pharmacokinetics. Paroksetin is well soaked up after intake and is exposed to metabolism of the first passing through a liver. Allocation of not changed paroksetin with urine usually makes less than 2% of a dose, and metabolites make about 64% of a dose. Intestines excrete about 36% through bile in which not changed пароксетин makes less than 1% of a dose. Thus, пароксетин it is removed preferential as a result of metabolism.

Removal from an organism of metabolites of a paroksetin bi-phase, at first as a result of metabolism of the first passing through a liver, and then it is controlled by system elimination. The elimination half-life varies, but usually makes about one day. Steady system levels are reached by 7-14 day after an initiation of treatment, and the pharmacokinetics during prolonged treatment does not change. Clinical effects of a paroksetin (side effect and efficiency) do not correlate with its concentration in plasma.

As metabolism of a paroksetin includes a stage of the first passing through a liver, its quantity defined in system circulation is less than that which is absorbed from zheludochno - an intestinal path. At increase in a dose of a paroksetin or at repeated dosing when load of an organism increases, there is a partial absorption of effect of the first passing through a liver and decrease in plasma clearance of a paroksetin. As a result of it increase in concentration of a paroksetin in plasma and fluctuations of pharmacokinetic parameters is possible that can be observed only at those patients who at reception of low doses reach low levels of drug in plasma.

Paroksetin is extensively distributed in fabrics, and pharmacokinetic calculations show that only 1 his % is present at plasma, and in therapeutic concentration of 95% is connected with proteins of plasma.

At elderly patients, and also at those who have a heavy renal and liver failure concentration of a paroksetin in plasma is increased, and the range of plasma concentration at them almost matches the range of healthy adult volunteers.

Indications to use:

- a depression of all types, including the situational, heavy endogenous depression and a depression which is followed by alarm;
- obsessivno-compulsive frustration (OCF);
- panic frustration, including with an agoraphobia;
- social alarming frustration / social phobia;
- generalized alarming frustration;
- treatment of posttraumatic stressful frustration.

Route of administration and doses:

Inside, 1 time a day, in the morning, during food. The tablet is swallowed entirely, washing down with water. The dose is selected individually within the first two-three weeks after the beginning of therapy and afterwards if necessary is adjusted.

At depressions - 20 mg of 1 times a day. In case of need the dose is gradually increased by 10 mg/days, the maximum daily dose should not exceed 50 mg.

At obsessivno-compulsive frustration an initial therapeutic dose - 20 mg/days with the subsequent weekly increase by 10 mg. The recommended average therapeutic dose - 40 mg/days, if necessary a dose can be increased to 60 mg/days.

At panic frustration an initial dose - 10 mg/days (for decrease in possible risk of development of an aggravation of panic symptomatology), with the subsequent weekly increase by 10 mg. An average therapeutic dose - 40 mg/days. The maximum dose - 50 mg/days.

Social and alarming frustration / sociophobia: the initial dose makes 20 mg a day, in the absence of effect within at least two weeks increase in a dose as much as possible to 50 mg a day is possible. It is necessary to increase a dose by 10 bucketed mg not less than a week according to clinical effect.

Posttraumatic disturbances of mentality: for most of patients initial and therapeutic doses make 20 mg a day. Increase in a dose of a paroksetin as much as possible to 50 mg a day is in certain cases recommended. The dose should be increased by 10 mg every week according to clinical effect.

Generalized alarming frustration: the initial and recommended doses - 20 mg a day.

At a renal and/or liver failure the recommended dose makes 20 mg a day.

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

For the prevention of development of a withdrawal the termination of administration of drug is carried out gradually.

Features of use:

In order to avoid development of a malignant antipsychotic syndrome with care appoint to the patients accepting neuroleptics.
Paroksetin does not worsen cognitive and psychomotor functions, nevertheless, as well as at treatment by other psychotropic drugs, patients have to be careful when driving and moving mechanisms.
During treatment it is necessary to abstain from the use of ethanol and from occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.
Treatment paroksetiny is appointed 2 weeks later after cancellation of MAO inhibitors. At patients of advanced age the hyponatremia is possible.
In certain cases it is required to dose adjustment of insulin and/or oral hypoglycemic drugs.
At development of spasms treatment paroksetiny is stopped.
At the first symptoms of a mania it is necessary to cancel therapy paroksetiny.
Within the first several weeks it is necessary to watch carefully a condition of the patient in connection with possible suicide attempts.

Side effects:

From a nervous system: drowsiness, a tremor, an adynamy, sleeplessness, dizziness, fatigue, spasms, extrapyramidal frustration, a serotoninovy syndrome, hallucinations, a mania, confusion of consciousness, agitation, alarm, depersonalization, panic attacks, the increased nervous irritability, paresthesias, decline in the ability to concentration of attention.

From a musculoskeletal system: arthralgia, mialgiya, myasthenia, myoclonia, myopathic syndrome.
From sense bodys: vision disorders, taste change.
From urinogenital system: disturbances of sexual function, including impotence and frustration of an ejaculation, an ischuria, гиперпролактинемия / a galactorrhoea, an anorgazmiya, increase of an urination.
From the alimentary system: a loss of appetite, nausea, vomiting, dryness in a mouth, locks or diarrhea, seldom or never - hepatitis.
From cardiovascular system: orthostatic hypotension.
Others: the increased sweating, allergic reactions (rash, urticaria, ekhimatoza, an itch, a Quincke's disease), a hyponatremia, disturbance of secretion of antidiuretic hormone, a withdrawal at sharp drug withdrawal, rhinitis.

Interaction with other medicines:

Meal and antiacid means does not influence absorption and pharmacokinetic parameters of drug.

Paroksetin is incompatible with MAO inhibitors.

At co-administration with paroksetiny concentration of a protsiklidin increases.,

During therapy paroksetiny it is necessary to abstain from alcohol intake in connection with strengthening of toxic effect of alcohol.

In communication iigibirovaniy paroksetiny P450 cytochrome strengthening of effect of barbiturates, Phenytoinum, indirect anticoagulants, tricyclic antidepressants, fenotiazinovy neuroleptics and antiaritmik of a class 1C, metoprolol and increase in risk of development of side effects at co-administration of these medicines is possible.

At co-administration with the drugs inhibiting liver enzymes the dose decline of a paroksetin can be required.

Paroksetin increases a bleeding time against the background of warfarin reception, at an invariable prothrombin time.

At co-administration of a paroksetin it is recommended to be careful with atypical antipsychotic means, fenotiazina, tricyclic antidepressants, acetylsalicylic acid, non-steroidal anti-inflammatory drugs in connection with possible disturbances of coagulability of blood. Co-administration with serotonergic drugs (трамадол, суматриптан) can lead to strengthening of serotonergic effect.

Mutual strengthening of effect of tryptophane, drugs of lithium and paroksetin is noted.

At co-administration of a paroksetin with Phenytoinum and other antikonvulsant decrease in concentration of a paroksetin in plasma and increase in frequency of side effects is possible.

Contraindications:

- hypersensitivity to drug components;
- a concomitant use with MAO inhibitors and within 14 days after their cancellation; concomitant use of thioridazine;
unstable epilepsy; pregnancy and period of a lactation;
- children's age (up to 18 years);

With care: liver failure; renal failure; closed-angle glaucoma; prostate hyperplasia; mania; heart pathology; epilepsy; convulsive states; purpose of a countershock; administration of drugs, increasing risk of bleeding; existence of risk factors of the raised bleeding and the diseases increasing risk of bleeding, advanced age.

Overdose:

Symptoms: nausea, mydriatic pupils, fever, increase in arterial pressure, headache, involuntary muscular contractions, agitation, uneasiness, sinus tachycardia, bradycardia, nodal rhythm.
Seldom or never, at a concomitant use with other psychotropic drugs and/or alcohol oppression of consciousness up to a coma is possible.
Treatment: gastric lavage, absorbent carbon. If necessary symptomatic therapy. There is no specific antidote.

Storage conditions:

At a temperature not above 25 °C. To store in the place, unavailable to children! Period of validity 3 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated 20 mg and 30 mg.
Tablets of 20 mg: on 6, 7 or 10 tablets in blisters the Aluminium foil / PVC / Aluminum foil. 1 or 2 blisters but 6 tablets, 1, 2, 4, 8 or 14 blisters on 7 tablets or 1, 2, 3, 5, 6 or 10 blisters on 10 tablets together with the application instruction in a cardboard pack.
Tablets of 30 mg: on 6, 7 or 10 tablets in blisters the Aluminium foil / PVC / Aluminum foil. 1 blister on 6 tablets, 2 or 4 blisters on 7 tablets or 1, 3 or 10 blisters on 10 tablets together with the application instruction in a cardboard pack.
On 20, 40, 60, 100 blisters together with application instructions in a cardboard box (for hospitals).