Fluoksetin-Kanon

General characteristics. Structure:

Active agents – fluoxetine of a hydrochloride of 22,36 mg in terms of fluoxetine of 20,00 mg;
excipients – starch corn, lactoses monohydrate (sugar milk), magnesium stearate;
No. 3 gelatinous solid capsule, including: gelatin, titanium dioxide, индигокармин&.
Description: capsules No. 3 of blue color. Contents of capsules - mix of granules and powder of color, white or white with a yellowish shade. Existence of separate lumps is allowed.

Pharmacological properties:

Antidepressive means. Selectively inhibits the return serotonin reuptake that leads to increase in its concentration in a synaptic gap, to strengthening and prolongation of action on postsynaptic receptors. Increasing serotonergic transfer, on a negative feedback mechanism fluoxetine inhibits exchange of a neurotransmitter. At prolonged use fluoxetine oppresses activity of 5-HT1-retseptorov. Poorly influences the return capture of noradrenaline and dopamine. Has no direct effect on serotoninovy, m - cholinergic, H1-histamine and alpha adrenoceptors. Unlike the majority of antidepressants, does not cause decrease of the activity of postsynaptic beta adrenoceptors.
It is effective at endogenous depressions and obsessivno-compulsive frustration. Improves mood, reduces tension, uneasiness and sensation of fear, eliminates a dysphoria. Has anorexigenic effect, can cause loss of body weight. Does not cause orthostatic hypotension, sedation, некардиотоксичен. The lasting clinical effect occurs in 1-2 weeks of treatment.

Pharmacokinetics. Absorption is high. Time of achievement of the maximum concentration (15-55 ng/ml) in a blood plasma after administration of drug inside in a dose of 40 mg makes 6-8 h. Bioavailability at intake - more than 60%. Meal does not influence bioavailability.
Linkng with proteins of a blood plasma makes 94,5% (including albumine and an alfa1-acid glycoprotein). It is distributed on all organism. Easily gets through a blood-brain barrier. Equilibrium concentration in a blood plasma is reached after administration of drug within several weeks.
Is exposed to intensive biotransformation in a liver to an active metabolite of a norfluoksetin and some other not identified metabolites. Is inhibitor of isoenzymes CYP2C19, CYP3A2, CYP3A3, CYP3A5 and CYP3A7.
It is removed by kidneys in the form of metabolites (80%) and intestines (15%), it is preferential in the form of glucuronides. The fluoxetine elimination half-life after achievement of equilibrium concentration in a blood plasma makes 4-6 days. The elimination half-life of an active metabolite of a norfluoksetin at a single dose and after achievement of equilibrium concentration in a blood plasma makes 4-16 days. At patients with cirrhosis the elimination half-life is extended by 3-4 times.

Indications to use:

- depression of various etiology;
- nervous bulimia;
- obsessivno-compulsive frustration.

Route of administration and doses:

Depression. The initial recommended dose makes 20 mg/days of 1 times. If necessary the dose is increased by 20 mg/days weekly. The maximum daily dose makes 80 mg in 2-3 receptions.
Bulimia. The recommended dose makes 60 mg/days in 3 receptions.
Obsessivno-kompulsivnye frustration. The recommended dose makes 20-60 mg/days.
All indications. The recommended dose can be reduced or increased. Doses more than 80 mg/days systematically were not studied.
Age. There are no data on need of change of doses depending on age.
Meal. Fluoxetine can be accepted irrespective of meal at any time.
Associated diseases and/or accompanying treatment. At patients with abnormal liver functions, associated diseases or accepting other drugs, it is necessary to reduce doses and to reduce reception frequency.

Features of use:

At treatment of patients with deficit of body weight it is necessary to consider anorexigenic effects of fluoxetine (the progressing loss of body weight is possible).
At patients with a diabetes mellitus purpose of fluoxetine increases risk of development of a hypoglycemia; at its cancellation - a hyperglycemia. In this regard the dose of insulin and/or any other hypoglycemic medicines applied inside has to be corrected. Patients have to be under observation of the doctor.
The interval between the end of therapy by MAO monoamine oxidase inhibitors and an initiation of treatment fluoxetine has to make at least 14 days; between the end of treatment by fluoxetine and the beginning of therapy by MAO inhibitors - not less than 5 weeks.
Careful observation of patients with suicide bents, especially in an initiation of treatment is required. The risk of a suicide at the patients who were earlier accepting other antidepressants, and patients at whom against the background of treatment fluoxetine notes excessive exhaustion, a hypersomnia or motive concern is highest.
When performing electroconvulsive therapy against the background of reception of fluoxetine long epileptic seizures are possible.
During treatment it is necessary to abstain from alcohol intake and occupations potentially dangerous types of activity requiring special attention and speed of mental and motor reactions.
At children, teenagers and young people (24 years are younger) with a depression, other mental disturbances antidepressants in comparison with placebo increase risk of emergence of suicide thoughts and suicidal behavior. Therefore at Fluoksitin's appointment or any other antidepressants at children, teenagers and young people (24 years are younger) it is necessary to correlate risk of a suicide and advantage of their use. In short-term researches at people 24 years are more senior the risk of a suicide did not increase, and 65 years are more senior than people decreased a little. Any depressive frustration in itself increases risk of a suicide. Therefore during treatment by antidepressants for all patients observation for the purpose of early identification of disturbances or changes of behavior, and also suicide bents has to be established.
It is reported about developing of skin rash, anaphylactic reactions and the progressing system disturbances, sometimes serious with involvement in pathological process of skin, kidneys, a liver and lungs at the patients accepting fluoxetine. At emergence of skin rash or other possible allergic reactions which etiology cannot be defined reception of fluoxetine should be cancelled.

Side effects:

Organism in general: autonomous symptoms (dryness in a mouth, perspiration, vasodilation, a fever), hypersensitivity (an itch, skin rashes, urticaria, anaphylactic reaction, a vasculitis, reaction like serumal, an angioedema), a serotoninovy syndrome (it is characterized by a complex of clinical manifestations of change of a mental state and neuromuscular activity in combination with disturbances of an autonomous nervous system), a photosensitivity, an erythema mnogoformny exudative).
Cardiovascular system: heartbeat, arrhythmias.
Alimentary system: gastrointestinal disturbances (diarrhea, nausea, vomiting, dysphagy, dyspepsia, food faddism), very seldom idiosyncratic hepatitis.
Endocrine system: abnormal secretion of antidiuretic hormone.
Hemopoietic and lymphatic system: ecchymoma.
Disturbances of metabolism and food: loss of body weight.

Skeletal and muscular system: arthritises, ostealgia, bursitis, spasms of legs, arthrosis, myasthenia, myopathy, osteomyelitis, osteoporosis, pseudorheumatism.
Nervous system: the abnormal movements / a tremor (twitchings, an ataxy, a bukko-glosalny syndrome, a myoclonus, a tremor), anorexia, alarm and its manifestations (heartbeat, concern, nervousness, agitation), dizziness, fatigue (drowsiness, an adynamy), disturbance of process of concentration and thinking (including depersonalization), maniacal frustration, sleep disorders (unusual dreams, sleeplessness), spasms.
Respiratory system: yawning.
Skin: alopecia.
Sense bodys: vision disorders (sight illegibility, mydriasis).
Urinogenital system: disturbances of an urination (including change of frequency of an urination), a priapism / a long erection, sexual dysfunction (decrease a libido, a delay or lack of an ejaculation, an anorgazmiya, impotence).

Interaction with other medicines:

Fluoxetine and its main metabolite норфлуоксетин have long elimination half-lives that needs to be considered at a fluoxetine combination to other drugs, and also at its replacement by other antidepressant.
Phenytoinum. Changes of concentration of Phenytoinum in blood at its combination to fluoxetine were revealed. Displays of intoxication were in some cases noted. Increase in a dose of Phenytoinum or fluoxetine at their co-administration should be carried out with care and under control of clinical dynamics of a state.
Serotonergic drugs. The concomitant use of serotonergic drugs (for example, a tramadol and triptanes) promotes increase in probability of development of a serotoninovy syndrome. The concomitant use of triptanes promotes also increase in probability of development of narrowing of coronary vessels and arterial hypertension.
Benzodiazepines. At simultaneous use of fluoxetine and benzodiazepines increase in an elimination half-life of the last is possible. At joint reception of an alprazolam and fluoxetine increase in concentration of an alprazolam in blood and strengthening of its sedative action was observed.
Lithium and tryptophane. It is known of cases of development of a serotoninovy syndrome at a concomitant use of the selective serotonin reuptake inhibitors (SSRI) and lithium, or tryptophane in this connection co-administration of fluoxetine with these drugs should be carried out with care. At a concomitant use of fluoxetine and lithium more frequent and careful control of a clinical state is necessary.
Medicines, metaboliziruyemy with participation of an isoenzyme of CYP2D6 (пропафенон, carbamazepine, tricyclic antidepressants). It is necessary to consider that fluoxetine metabolism (as well as tricyclic antidepressants, and also the selection serotonergic antidepressants) is carried out with the participation of an isoenzyme of CYP2D6 of system of tsitokhrom of a liver. The concomitant use of drugs which main way of biotransformation is metabolism with the participation of CYP2D6 isoenzyme, and therapeutic doses having a small interval (such, as пропафенон, carbamazepine, tricyclic antidepressants) should be carried out with use of the minimum therapeutic doses. The above, is applicable also if there passed less than 5 weeks after fluoxetine cancellation.
The indirect anticoagulants and other drugs influencing coagulant system of blood (Nonsteroid antiinflammatory means, acetylsalicylic acid). It is known of change of anticoagulating action (on laboratory indicators and/or clinical manifestations) without any general characteristic tendency, but with probability of strengthening of bleedings at a concomitant use of fluoxetine and oral anticoagulants. The functional condition of coagulant system of blood at the patients receiving warfarin has to be controlled carefully at appointment and cancellation of fluoxetine.
Electroconvulsive therapy (EST). The patients accepting fluoxetine and receiving EST have rare messages on increase in duration of spasms, in this regard it is recommended to be careful.
Alcohol. In pilot studies fluoxetine did not promote increase in concentration of alcohol in blood, and also to strengthening of effects of alcohol. However the concomitant use of SIOZS and alcohol is not recommended.
Means on the basis of Hypericum perforatum plant. As applicable and to others SIOZS, development of pharmakodinamichesky interaction between fluoxetine and means on the basis of Hypericum perforatum plant is possible that can lead to strengthening of undesirable action.

Contraindications:

- hypersensitivity;
- a concomitant use of monoamine oxidase inhibitors (MAO) and within 14 days after their cancellation;
- a concomitant use of thioridazine (and within 5 weeks after fluoxetine cancellation), Pimozidum;
- liver failure;
- renal failure (clearance of creatinine less than 10 ml/min.);
- bladder atony;
- closed-angle glaucoma;
- prostate hyperplasia;
- pregnancy;
- lactation period;
- deficit of lactase, lactose intolerance, glyukozo-galaktozny malabsorption;
- age up to 18 years.

With care:
Suicide risk: at depressions there is a probability of suicide attempts which can remain before permanent remission. Separate cases of suicide thoughts and suicide behavior were described against the background of therapy by fluoxetine or soon after its termination, like effect of other drugs of close pharmacological action (antidepressants). Careful observation of the patients belonging to risk group is necessary. Doctors should convince patients immediately to report about any thoughts and feelings causing disturbance.
Epileptic seizures: as well as in case of other antidepressants, it is necessary to appoint fluoxetine with care the patient at whom epileptic seizures were noted earlier.
Hyponatremia: hyponatremia cases were noted (in some cases sodium level in blood serum was less ON mmol/l). Generally similar cases were noted at elderly patients and at the patients receiving diuretics owing to reduction of volume of the circulating blood.
Glycemic control: at patients with diabetes during treatment fluoxetine noted a hypoglycemia, and after drug withdrawal the hyperglycemia developed. At the beginning or after the end of treatment by fluoxetine correction of doses of insulin and/or hypoglycemic drugs for intake can be required.
Liver/renal failure: fluoxetine is exposed to intensive metabolism in a liver and is removed by kidneys. Patients with the expressed abnormal liver functions are recommended to appoint lower doses of fluoxetine, or to appoint drug every other day. At reception of fluoxetine in a dose of 20 mg/days for two months patients with the expressed renal failures (clearance of creatinine <10 ml/min.), needing a hemodialysis, differences of concentration of fluoxetine and a norfluoksetin in a blood plasma from the healthy faces having normal function of kidneys were not revealed.

Use during pregnancy and breastfeeding:
Fluoxetine can be accepted during pregnancy provided that the estimated advantage for mother exceeds possible risk for a fruit.
Breastfeeding: fluoxetine to be removed with breast milk, therefore, nursing mothers should show care at purpose of fluoxetine.
Childbirth: influence of fluoxetine on process of childbirth at the person is not known.

Overdose:

The main manifestations of overdose included strengthening of side effects, spasms, drowsiness, nausea, tachycardia and vomiting.
Other serious manifestations about which it was reported at the fluoxetine overdose (as isolated, and in combination with other drugs), included a coma, a delirium, lengthening of an interval of QT and a ventricular tachyarrhythmia, including blinking trembling of ventricles and a cardiac standstill, a lowering of arterial pressure, a faint, a mania, a pyrexia, a stupor and a state, similar to a malignant antipsychotic syndrome.

Storage conditions:

List B. In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 4 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Capsules of 20 mg.
On 10 or 15 capsules in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.
On 1, 2, 3, 5 blister strip packagings on 10 capsules or on 1, 2, 3 blister strip packagings po15 capsules together with the application instruction place in a pack from a cardboard.