NONDEP

International nonproprietary name: Fluoxetin

Dosage band: capsules

Formula:

1 capsule contains:

Active substance: Fluoxetin 20mg;

Additives: gelatinous corn starch, dimeticone;

Pharmacotheraputical group: Antidepressant

Pharmacodynamics

Nondep- the antidepressant, selective inhibitor of serotonin reuptake.

The mechanism is connected with the selective block of neuronal reuptake of serotonin (5HT- receptors) in synapsis of central nervous system neurons, slightly affects noradrenaline and dopamine reuptake. Nondep is the weak antagonist of cholinergic and adrenergic alpha 1- and alpha 2- receptors, H1- histamine receptors. In continuous intake Nondep causes decrease of sensitivity and functional activity of C1- receptors. Unlike most antidepressants, Nondep does not down-regulate postsynaptic beta-adrenergic receptors.

In therapeutic doses the preparation blocks thrombocyte reuptake of serotonin.

According to action spectrum Nondep belongs to antidepressants combining thymoanaleptic and stimulating effects. Moreover, it causes reduction of obsessive-compulsive disorders.

The preparation favors lifting the mood, reduces sensation за fear and tension, removes dysphoria. It causes reduction of appetite and may lead to reduction of body weight.

Does not cause sedation.

In average therapeutical doses intake it does not affect cardio-vascular and other systems.

Stable clinical performance is developed in 2 weeks after regular intake of the preparation and lasts during several weeks after its cancellation.

Pharmacokinetics:

Nondep is well absorbed (up to 95%) from gastrointestinal tract. Food intake does not influence the degree of absorption, but slightly lowers its rate.

Maximal concentration of the preparation in plasma is determined after 6–8 hours after the intake. Plasma protein — binding — 65–90%. Bioavailability — more than 60%. Maximal effect is observed in 8–10 hours after the intake. It penetrates into the tissues well, including hematoencephalic barrier.

It is extensively metabolized in the liver by the means of dimethylation to active metabolite of norfluoxetine, and other, unidentified metabolites. It is eliminated mainly through kidneys (the amount of fluoxetin clearance is 94-704ml/min), 12% through the intestinal tract. Fluoxetin half-life comprises 3–6 days, norfluoxetine- 4–16 days. Kidney insufficiency does not significantly affect elimination rate. In patients with liver insufficiency half-life is prolonged (in deficiency of Р45011D6). It penetrates into breast milk (25% of concentration in plasma).

Indications:

The preparation should be applied according to doctor’s prescription for the avoidance of complications!

• Depressions of different genesis;
• Obsessive-compulsive conditions;
• Bulimia Nervosa;
• In complex treatment of alcohol abuse;

Method of application and dosage:

The preparation is taken orally, starting with 20mg once daily regardless food intake. If required, dosage can be gradually increased up to 40-60mg daily, divided in two (morning and midday) or three administrations during a day.

Maximal daily dose is 80 mg/day. In depressions of different genesis, obsessive-compulsive conditions initial doe of the preparation is 20mg once daily in the first part of the day (in the morning) regardless food intake. Therapeutical effect of the preparation appears in 2–4 weeks after the beginning of treatment, in some patients it can be reached later.

In absence or insufficiency o the required effect, in some weeks the dose can be increased, but not more than 80mg in 2–3 administrations.

In bulimia nervosa fluoxetin is applied in the daily dose of 60mg, divided in 2–3 administrations.

In patients with liver and kidney disfunction the dose should be gradually decreased, or the interval between the administrations should be prolonged.

Overdosage:

Symptoms: hypomania, agitation and motor anxiety, sickness and vomiting, seizures, arrhythmia, tachycardia.

Treatment: gastric lavage, administration of activated carbon, maintenance of heart activity. There are no specific antidotes for fluoxetin.

Contraindications:

• hypersensitivity to the preparation;
• atony of bladder;
• intense kidney malfunction;
• closed-angle glaucoma;
• prostate gland adenoma;
• convulsive disorder of different genesis;
• epilepsy;
• simultaneous prescription of monoamine oxidase inhibitors;
• pregnancy;
• lactation (breast-feeding);
• infancy;

Side effects:

Nondep is usually tolerated well.

In the beginning of therapy in the increase of dose following reactions can be observed:

• Central nervous system and peripheral nervous system: psychic tension, irritation, intensification of tension, increased fatigability, sleep disturbance or drowsiness, nightmares, headache, failure of vision sharpness, mydriasis, gustatory sensation disorder, paralogia, tremor, akathisia, ataxy, depersonalization, muscular twitching, buccoglossal syndrome, myoclonia.
  If during Nondep administration expanded seizure occurs, the preparation should be cancelled;
• Gastrointestinal tract: dry mouth, dyspepsia- sickness, vomiting (rare), diarrhea, constipation, dysphagia. Development of anorexia and decrease of body weight are possible.
• Excretory tract: dysuria, urinary urgency, urinary incontinence.
• Reproductive system: decrease of libido, ejaculation disorder, anorgasmy, impotence, dysmenorrhea;
• Cardio-vascular system: heart beating, orthostatic hypotension;
• Coagulative blood system: skin hemorrhage;
• Allergic reactions: in Nondep administration allergic reactions are possible: skin rash, itching, angioneurotic edema, hives or disorders similar to serum disease, shiver, temperature increase, pain in muscles and joints. In skin rash and arthropathy fluoxetin administration should be cancelled. The intake of antihistaminic and steroid preparations is acceptable.
• Other: in patients with diabetes progression of hypoglycemia is possible during Nondep therapy; and progression of hyperglycemia after the cancellation of the preparation. Hyponatremia is possible in patients of old age.

Drug interaction:

Nondep is incompatible with monoamine oxidase inhibitors, furasolidone, procarbazine, selegeline, tryptophane- the emergence of «serotonin syndrome» is possible (hyperthermia, muscle rigidity, myoclonia, agitation, cramps, dysarthria, hypertensic crisis, shiver, tremor, sickness, vomiting, diarrhea). In simultaneous intake of preparations causing suppressive effect on central nervous system (including ethanolom), intensifies their action. It intensifies the effect of tricyclic and tetracyclic antidepressants, trazodon, carbamazepine, diazepam, metoprolol, terfenadine, phenytoin, diphenylhydantoin, anticoagulants and hypoglycemic agents. Simultaneous intake of lithium preparations leads to the increase of concentrations of lithium in plasma.

Precaution measures and special remarks:

Long elimination half-lives of fluoxetin and its metabolites can be the reason of retention of therapeutical drug concentration in plasma for several weeks after its cancellation.

With care, under the strict control, Nondep is prescribed to patients with vascular heart diseases, liver and kidney disfunction. The treatment should be started with half doses.

In patients with diabetes during Nondep therapy the development of hypoglycemia is possible, after its cancellation- the development of hyperglycemia, which requires the correction of dosage regimen of hypoglycemic agents. In patients with epilepsy (including epilepsy in history) after the administration of Nondep there is a possibility of epileptic seizures.

The period between the cancellation of monoamine oxidase inhibitors and the beginning of Nondep administration should be not less than 2 weeks; and the period between the cancellation of Nondep and the beginning of monoamine oxidase inhibitors administration- not less than 5 weeks.

During the administration of the preparation alcohol should be excluded; it is recommended to abstain from potentially dangerous activities, which require high attention and quick psychomotor reactions.

Form of issue: capsules 20mg

Conditions of delivery at chemistry stores:

Delivered according to prescription.

Expiry period:

Do not take the preparation after the expiry date printed on the package.

Terms of storage:

Should be stored under temperature -not above 25˚ С, in the dark place.

Keep out of reach of children.