BIOZAC 20 mg. 30 capsules
• Obsessive - compulsive disorders .
BIOZAC 20 mg. 30 capsules
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains a solid medicament hydrochloride - 22.36 mg, equivalent to 20 mg of Fluoxetine
3 PHARMACEUTICAL FORM
4 CLINICAL DATA
• Depression. It is indicated for the treatment of depressive symptoms with or without the presence of anxiety and in the case where no sedative effect;
• Obsessive - compulsive disorders;
• Bulimia nervosa. Biozac is indicated for reducing attacks of bulimia and suppression samopredizvikanoto vomiting.
4.2. Dosage and method of administration
Biozac capsules are taken orally before or after meals. Depression. In adults and elderly patients the recommended dose is 20 mg daily. As a rule, this dose is sufficient to obtain a therapeutic effect. Onset of antidepressant effect can be expected after a two-week latency period. In the absence of a satisfactory therapeutic effect, the daily dose may be increased to 40-60 mg, being administered in 2 - in the morning and evening. Dose increases should be gradual. Because extending the half-life in elderly patients with liver and kidney disease, the dose should be lower and the intervals are taking extensio. Obsessive - compulsive disorders recommended that 20 to 60 mg
daily adult patients, the starting dose should be 20 mg. Dose escalation should be done gradually over several weeks.
4.5. Medicaments and other forms of interaction
Fluoxetine is metabolised by cytochrome P450 isoenzyme P4502 D6 and in this regard may interact with other drugs at the level of drug metabolism.
Plasma concentrations of anticonvulsants - phenytoin (Difenin), carbamazepine (Tagretol) may be increased when co-administered with fluoxetine.
Plasma concentrations of antipsychotics - haloperidol and clozapine may be increased when co-administered with fluoxetine, which could pose a risk for serious side effects.
The half-life of diazepam and alprazolam extended by concomitant use of fluoxetine. This creates the prerequisite for induction of adverse reactions and toxic effects. Upon treatment with lithium salts of patients receiving fluoxetine is observed if both increase and decrease the levels of lithium in plazmata.Osven this literature reports of tosichnost with lithium during concomitant use of medicinal products with serotonergic activity. This requires the application of lithium to be monitored,.
Patients treated with fluoxetine and tryptophan showed side effects such as agitation, restlessness and gastrointestinal discomfort.
In the application of tricyclic antidepressants (desipramine, imipramine), their dose should be reduced and their plasma levels should be monitored, if you start treatment with fluoxetine or its treatment is interrupted.
In applying the MAOIs and fluoxetine, the interval between them should not be less than 14 days, as can be observed serious side effects.
Fluoxetine binds to 95% bound to plasma proteins. This creates the possibility of interaction of fluoxetine with other drug substances having a high affinity to plasma proteins. Anticoagulation coumarin group compete with fluoxetine for plasma proteins and, in some cases, displaced from the relationship of plasma proteins may result in undesirable effects, such as e. bleeding.
Digitalis glycosides (eg. Digitoxin, digoxin) may also be displaced from their relationship to plasma proteins and fluoxetine as they act in very small doses can lead to bradycardia, violation of antrioventrikularnoto conduct, disturbances in heart
Adults and elderly patients the recommended dose is 60 mg daily. When multiple doses must be considered that, due to the prolonged half-life of fluoxetine after stopping treatment, plasma concentrations can be maintained for several weeks.
Children - safety Biozac not been studied in this patient category. Not recommended for use in children.
Duration of treatment - for the treatment of acute episodes appropriate administration of the preparation for 4-8 weeks.
- Hypersensitivity to fluoxetine;
- Severe renal failure (renal clearance <10 ml / min);
- During lactation;
- Co-administration of a MAOI (target range of not less than 14 days).
4.4. Special warnings and precautions
At the beginning of treatment with fluoxetine is possible intensification of certain symptoms, such as insomnia, anxiety, requiring adjustment of their preparation.
In consideration of fluoxetine must be given to patients with bulimia nervosa with significant changes in body weight.
Because of the danger of reinforcing the manic or hipomaniynite conditions, administration of fluoxetine in patients with these events requires due attention.
Careful and continuous monitoring fluoxetine may be administered to patients with a history of seizures. In patients with epilepsy drug can be applied only in cases of successful seizure control.
Fluoxetine has an extended half-life. This requires careful specification of dosage in patients with concomitant diseases - liver, kidney.
In patients with diabetes may require adjustment of the dose of the antidiabetic agents, owing to disturbances in glucose control in the administration of fluoxetine.
In case of skin rash or any other sign of hypersensitivity to fluoxetine treatment should be discontinued.
Careful application is required in patients with heart disease as there is no adequate experience in this regard.
All drugs that are metabolized by P4502D6 system and that have a narrow therapeutic index should be used in small doses in the initial period of patients treated with fluoxetine or who were treated with fluoxetine during the last five weeks. Such substances are the medicines fleksamid, vinblatin, tricyclic antidepressants. Fluoxetine, although less may be metabolised by P4503A4. Thus for example. in vitro studies showed that ketoconazole (a potent inhibitor of P4503A4) is about one hundred times more potent enzyme substrate as compared with fluokseti and norfluoxetine.
Concomitant administration of single doses of fluoxetine in conjunction with terfenadine (specific substrate of cytochrome P4503A4) does not increase the plasma level Terfenadine.
4.6. Pregnancy and lactation
Although no evidence of embryotoxic and teratogenic effects of fluoxetine, its use in pregnant women may be done only for serious medical reasons for this. Fluoxetine is excreted in significant concentrations in breast milk. Because of the risk of harm to the infant is not recommended intake of the preparation during lactation.
4.7. Effects on ability to drive and use machines.
Fluoxetine and other antidepersivni agents may impair the ability of concentration, reflexes and alertness. It is recommended that extreme caution be used in patients -guide of motor vehicles and working machines.
4.8. Undesirable effects
Fluoxetine is different from tricyclic antidepressants with better tolerability and lower incidence of adverse actions.
Manifested early in therapy with drug side effects usually diminish in the course of treatment.
General reactions - Common: asthenia; Rare: fever, sweating, vasodilation, chills. Hypersensitivity reactions may occur as itching, skin rashes, urticaria, vasculitis, photosensitivity anaphylactoid reactions; Extremely rare neuroleptic malignant
Cardiovascular system -
Common: hemorrhage, hypertension;
Rare: angina pectoris, angina attacks, tachycardia, migraine, syncope, Artim.
Extremely rare: AV - block I degree., Bradycardia, vascular headache, thrombophlebitis, ventricular arrhythmia, ventricular ekstrasistuli, thrombophlebitis, ventricular arrhythmia.
Digestive system -
Common: increased appetite, nausea, vomiting;
Rare: aphthous stomatitis, cholelithiasis, colitis, diarrhea, hiccups, gastritis, gastroenteritis, glossitis, gum bleeding, hyperchlorhydria, increased salivation, melena, ulceration in the mouth;
Extremely rare: pain in the liver, duodenal ulcer, fatty degeneration of the liver, heparin.
Central nervous system -
Common: agitation, amnesia, embarrassing situations, emotional lability;
Rare disorder of brain activity, akathisia, apathy, ataxia, speech disorder, depression, depersonalization, paranoid reactions, manic reaction, vertigo, hyperkinesia, increased muscle tone, myoclonus.
Extremely rare: abnormal electroencephalogram, extrapyramidal disorder, stupor, myoclonus, torticollis, coma.
Skin and appendages -
Rarely: alopecia, acne, contact dermatitis, dry skin, herpes simplex, maculopapular rash, and urticaria, eczema.
Extremely rare: erythema multiforme, fungal dermatitis, pustular rash, seborrhea, vesicular rash.
Respiratory system -
Rare: asthma, epistaxis, hiccups
Extremely rare apnea, suppression of cough, hypoxia, edema of the larynx
Rare hypothyroidism, diabetic ketoacidosis, diabetes
Metabolic disorders -
Common: nama.yavane weight;
Rarely: dehydration, generalized edema, hypercholesterolemia, hypokalemia.
Extremely rare: increased alkaline phosphatase and kreatifosfokinazata.
Rare: anemia, ecchymosis;
Extremely rare hipohromna anemia, leukopenia, lymphocytosis, lymphoedema.
Urogenital System -
Common: frequent urination;
Rare: abortion, albuminuria, cystitis, urethritis, changes in libido, impotence, breast pain, lactation amenorrhea;
Extremely rare: oliguria, hematuria, vaginitis, epididymitis, metrorrhagia, kidney pain, priapism.
Rare spinal pain, arthralgia, myalgia, arthritis, bone pain, bursitis, tenosynovitis.
Izklyuchtelno rare arthrosis, hondrodistrofiya, myasthenia, myopathy, myositis, osteporoza.
Sensory organs -
Common: ear pain, change in sense of taste, tinnitus;
Rare: conjunctivitis, dry eye, mydriasis, photophobia;
Extremely rare: blepharitis, diploliya, exophthalmos, bleeding in the eye, glaucoma, iritis, scleritis, strabismus
Physical and psychological addiction to fluoxetine
Not carried out systematic studies of response to fluoxetine in mental and physical focus. Preliminary clinical observations when taking fluoxetine no evidence of a trend of occurrence of withdrawal symptoms have stopped. Also there is no evidence for directed search of fluoxetine in patients who were treated with it or have taken on another occasion. However, physicians should carefully monitor patients being treated with fluoxetine and who have a addiction.
Cases of overdose, especially fatal are very rare. As a rule, they are mild with full recovery. Reported observed patient received 3000 mg fluoxetine and received two grand mal seizure type, which resolved spontanno.Simptomite of overdose are: nausea, vomiting, psychomotor hyperactivity, agitation, hypomania, and other signs of CNS excitation.
Treatment of overdose: no specific antidote. Treatment is symptomatic. Patients received a higher dose of fluoxetine should be monitored for a longer period. Carry out measures to maintain the vital centers and the use of medications for treatment of symptoms. If patients tricyclic antidepressants may occur toxic symptoms. Furthermore activated carbon or sorbitol may also be effective in treating non-specific.
Due to the large volume of distribution of fluoxetine in body enhanced diuresis, dialysis, hemoperfusion and not essential in the treatment of overdosage.
5.1. Pharmacodynamic properties
ATC code. Antidepressants - specific inhibitors of reuptake of serotonin.
Fluoxetine is a racemic mixture of R and S isomers in the ratio of 50-50. Both isomers have a specific effect on the reuptake of serotonin. S isomer is eliminated more slowly and is present for a longer time in the plasma. Antidepressant fluoxetine has expressed antikompulsivni and antibulimichni properties. The main mechanism of its action is associated with the ability to inhibit the reuptake of serotonin in the presynaptic side of the serotonergic nerve terminals in the CNS.
Serotonergic receptors are expressed primarily in limbic sisitema and certain subcortical structures. Studies in recent years show that the underlying endogenous serotonin or serotonin drugs with the same similar structures play an important role in the flow of emotional mental processes.
It differs from tricyclic antidepressants with low affinity for muscarinic, histamine and af-adrenergic receptors. This explains and better tolerability and lack of cardiotoxic effects. The main metabolite of fluoxetine - S norfluoxetine holds significantly pronounced activity at inhibiting reuptake of serotonin, which makes the major pharmacological properties of fluoxetine.
5.2. Pharmacokinetics -
absorption, distribution, metabolism and excretion
Fluoxetine has rapid and complete absorption after oral administration. Peak plasma concentrations are observed 6-8 hours after administration of a single dose of 40 mg, the values ranging from 15 to 55 rjg / ml. Food had no significant effect on the absorption and time-to-peak. At concentrations of fluoxetine of 200-1000 r | g / ml, approximately 95% bound to plasma (albumin and agglikoprotein). This fact suggests the possibility of significant interactions fluoxetine with other drugs having a high affinity for proteins.
Fluoxetine intensively metabolized in the liver by demethylation by forming its main metabolite norfluoxetine and a number of other inactive metabolites. Norfluoxetine S-isomer is 14 times more pharmacologically active than the other isomer R norfluoxetine. The metabolism of fluoxetine significantly depends on cytochrome P4502D6 isoenzyme. Approximately 7% of the individual activity of this system can be significantly reduced.
These facts give reason to explain the observed clinic large individual variations in the metabolism of the drug. On the other hand, the ability of inhibiting the isozyme fluoxetine P4502D6, determines the possible interactions with a large number of drugs. Fluoxetine is characterized by a slow elimination.
After a single dose elimination half-life is approximately 1-3 days and 4-6 days after repeated administration. This creates the potential for accumulation of the drug. The half-life of the main metabolite -norfluoksetin varies between 4-16 days after single and repeated administration of the drug. The half-life is significantly prolonged in patients with liver and kidney diseases, as well as in elderly patients. Due to the prolonged half-life of fluoxetine and norfluoxetine, they can persist in the body weeks after cessation of treatment, which may have important clinical significance, both in terms of therapeutic effect and the occurrence of side effects. The main part of the preparation (80%) was eliminated in urine and 15% in faeces.
5.3. Preclinical safety data
- Toxicity. Fluoxetine relates to pharmacologically active substances of low toxicity. Prolonged treatment of experimental animals at doses many times the therapeutic dose does not cause behavioral, clinical, haematological, biochemical, macroscopic and histological changes.
- Carcinogenicity. The introduction of fluoxetine for 2 years in doses of 10-20 mg / kg weight of the mice and rats showed no difference in the development of tumors in control and experimental groups.
- Mutagenicity. No evidence of genotoxicity of fluoxetine and its metabolite norfluoxetine when tested in vitro and in vivo models.
- Teratogenicity, Embryotoxicity and impact on fertility. There were no embryotoxic and teratogenic effects of fluoxetine when tested on rats and rabbits at doses of 12.5 to 15 mg / kg weight. Fluoxetine does not affect fertility study in rats at doses of 7.5 to 12,5 mg / kg weight:
6 PHARMACEUTICAL PARTICULARS
Cellulose microcrystalline -17.50 mg Magnesium stearate - 1.00 mg
Lactose monohydrate - 40.32 mg
6.2. Physico - chemical incompatibilities
No evidence of physical - chemical incompatibilities.
6.3. Shelf life
Three (3) years.
Dry and protected from light, at temperatures below 25 ° C.
Blisters of PVC aluminum foil 7 in the number of hard gelatin capsules.
Two and four blisters in a pack.
20 pcs. hard gelatin capsules in dark glass jars.