Rexep 5mg 28 tablets

Form

tableti saghech i

Dosage mg

5

Pack

28

Rexepin 10 mg film-coated tablets: Each tablet contains 5mg of olanzapine as the active substance and titanium dioxide as a colorant. Pharmacological properties Olanzapine is an atypical antipsychotic agent with affinity for 5HT2A/2C, 5HT3, 5HT6, dopamine D4, D3, D1, D2, muscarinic cholinergic (m1-m5), α-1 adrenergic, and H1 histamine receptors. Studies on olanzapine have shown that olanzapine selectively interacts with the mesolimbic system without significant interaction with the extrapyramidal system. Olanzapine binds more to 5HT2A receptors than to D2 receptors. Olanzapine has less interaction with D2 receptors than other traditional neuroleptic agents. This action leads to a relatively low incidence of acute extrapyramidal side effects and tardive dyskinesia. Rexepin acts on both negative and positive symptoms of the disease. Pharmacokinetic properties Rexepin is well absorbed after oral administration and reaches maximum plasma concentration within 5-8 hours. Food intake does not affect the absorption of Rexepin. Olanzapine is metabolized in the liver by conjugation and oxidation. Its main circulating metabolite is 10-N-glucuronide, a substance that does not cross the blood-brain barrier. Other metabolites include N-desmethyl and 2-hydroxymethyl, which do not exhibit in vivo activity. Olanzapine is responsible for the main pharmacological effects of the preparation. The half-life of olanzapine after oral administration varies with age and sex. Men under 65 years: 29 hours. Men 65 years and older: 49 hours. Women under 65 years: 39 hours. Women 65 years and older: 55 hours. The half-life of olanzapine is relatively longer in the elderly than in younger individuals. Renal insufficiency or mild, moderate, and severe hepatic impairment do not cause significant pharmacokinetic changes in olanzapine. The plasma clearance of olanzapine is lower in young individuals, women, and non-smokers than in older individuals, men, and smokers. Nevertheless, the effect of age, sex, and tobacco consumption on olanzapine clearance and half-life is relatively less than the variation between individual subjects. Olanzapine is 93% bound to plasma proteins at concentrations of 7-1000 ng/mL. Olanzapine primarily binds to albumin and α1-acid glycoprotein. 50% of the administered dose of olanzapine is excreted in urine, and 30% in feces. The half-life of the preparation is approximately 30 hours. Indications Olanzapine is used for the treatment of schizophrenia and also for short-term treatment of acute manic episodes associated with bipolar disorder. Contraindications Hypersensitivity to any ingredient of Rexepin and angle-closure glaucoma. Warnings Rarely, worsening of existing diabetes mellitus, hyperglycemia with ketoacidosis, and diabetic coma have been reported. In some cases, weight gain indicated an increased risk of developing similar conditions. Regular clinical monitoring is recommended for patients with diabetes and those at risk of developing diabetes mellitus. Orthostatic hypotension: Olanzapine, likely due to its alpha1-adrenergic antagonist properties, may cause orthostatic hypotension, especially during the initial dose titration period, with associated dizziness, tachycardia, and in some patients, syncope. If hypotension develops, it is preferable to gradually increase the dose of the preparation to the target dose. Olanzapine should be used with particular caution in patients with established cardiovascular (history of myocardial infarction or ischemia, heart failure, or conduction disorders) and cerebrovascular diseases, and conditions predisposing to hypotension (dehydration, hypovolemia, and treatment with antihypertensive drugs). Comorbidities: The preparation should be administered with caution to patients with prostatic hypertrophy, paralytic ileus, or similar conditions (due to the possible anticholinergic activity of olanzapine). Improvement in the clinical status of patients may take several days or weeks. During this period, patients should be under strict monitoring. Especially at the beginning of treatment, asymptomatic, transient increases in liver transaminases, ALT, AST, were frequently observed. Caution is required in patients with elevated ALT and AST, signs of liver damage, and pre-existing conditions associated with impaired liver function. If ALT and AST levels increase during treatment, the dose must be reduced. If hepatitis is diagnosed, treatment with olanzapine should be discontinued. As with all neuroleptic agents, caution is advised when using olanzapine in patients with leukopenia and/or neutropenia of any etiology, history of drug-induced bone marrow depression or toxicity, comorbid conditions, bone marrow depression due to radio- and chemotherapy, and finally, hypereosinophilic conditions or myeloproliferative disorders. Neuroleptic Malignant Syndrome (NMS): NMS was not observed in any patient during clinical trials with Rexepin. Neuroleptic Malignant Syndrome, as a potentially fatal symptom complex, is characterized by the use of other antipsychotic medications. Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and autonomic nervous system instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additionally, elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure may occur. If such symptoms appear, the use of all antipsychotic drugs, including Rexepin, should be immediately discontinued. Rexepin is used with caution in patients with a history of seizures or conditions that involve seizures. Tardive Dyskinesia: In comparative studies, the incidence of tardive dyskinesia induced by Rexepin was significantly lower than with other medications. If signs and symptoms of dyskinesia appear during treatment with Rexepin, the use of the preparation should be discontinued. Nevertheless, some patients with this syndrome may still require treatment with olanzapine. Postural hypotension was rarely observed during clinical trials with Rexepin. As with other antipsychotic drugs, blood pressure control is recommended in patients over 65 years of age. In clinical trials, Rexepin did not cause permanent prolongation of the QT interval. Out of 1685 patients, only eight patients showed prolongation of the QTc interval. Body Temperature Regulation: Antipsychotic drugs have the ability to impair the body's ability to reduce temperature. Appropriate attention should be paid when prescribing olanzapine to patients who will subsequently engage in physical exertion, be in hot environments, take other medications with anticholinergic activity concurrently, or be dehydrated. Interaction with Cognitive and Motor Spheres: Somnolence is a side effect associated with olanzapine administration, observed in 26% of patients in clinical trials, compared to 15% of patients receiving placebo. This side effect is also dose-dependent. Hyperprolactinemia: Olanzapine, like other dopamine D2 receptor antagonists, causes an increase in prolactin concentration, which remains elevated on average throughout long-term treatment. Suicide: Suicidal attempts are characteristic of patients with schizophrenia and bipolar disorder. The use of the preparation in these high-risk groups requires strict monitoring. Dysphagia: Impaired esophageal peristalsis and aspiration are associated with the use of antipsychotic drugs. Aspiration pneumonia is a major cause of morbidity and mortality in Alzheimer's disease. Olanzapine and other antipsychotic drugs are used with great caution in patients at high risk of developing this type of pneumonia. Like other drugs affecting the central nervous system, olanzapine is used with caution in dementia and/or Parkinson's disease. Smoking and Sex: Their effect on Rexepin metabolism is already known. The half-life of the preparation is longer in non-smokers and women than in smokers and men. If there are at least 2 factors that slow down olanzapine metabolism, a relatively low starting dose of Rexepin is required. In such patients, dose escalation should be conservative. Driving and Operating Machinery: Since olanzapine causes somnolence, patients should exercise caution when operating machinery, including automobiles. Children: The use of Rexepin in patients under 18 years of age has not been studied. Elderly: In healthy individuals over 65 years of age, the mean half-life of olanzapine was prolonged, but pharmacokinetic changes remained within the normal range (as in younger individuals). Rexepin has been shown to be equally safe at doses of 5-20 mg/day in elderly and young patients. Therefore, there is no special dosing regimen for patients in this group. Patients with Impaired Liver and/or Kidney Function: The pharmacokinetics of olanzapine do not change significantly with impaired renal function. However, impaired liver function may cause a slight prolongation of the preparation's half-life. Dose reduction is not recommended for patients in this group. Pregnancy and Lactation: No clinical studies have been conducted on the use of olanzapine during pregnancy. Patients must inform their treating physician about any planned or actual pregnancy while taking olanzapine. The preparation should be prescribed during pregnancy only when the potential benefit justifies the potential risk to the fetus. Lactation: It is recommended that mothers do not use the preparation during lactation. Labor: The effect of olanzapine on labor is unknown. Side Effects General Events: Frequent (at least 1%): Toothache. Flu-like syndrome, intentional self-harm, and attempted suicide. Infrequent (0.1%-1.0%): Chills, asthenia, facial edema, candidiasis, occipital pain and rigidity, pelvic pain, and photosensitization. Rare (<0.1%): Sudden death. Cardiovascular System: Frequent (at least 1%): Hypotension. Infrequent (0.1%-1.0%): Bradycardia, cerebrovascular accident, congestive heart failure, asystole, hemorrhage, migraine, pallor, vasodilation, tachycardia, and ventricular extrasystole. Rare (<0.1%): Arteritis, atrial fibrillation, heart failure, and pulmonary embolism. Digestive System: Frequent (at least 1%): Increased salivation and thirst. Infrequent (0.1%-1.0%): Dysphagia, heartburn, obstruction, flatulence, gastritis, gastroenteritis, gingivitis, hepatitis, melena, mouth ulceration, nausea and vomiting, oral candidiasis, periodontal abscess, rectal hemorrhage, stomatitis, tongue swelling, and dental caries. Rare (<0.1%): Aphthous stomatitis, enteritis, esophageal ulcers, glossitis, ileus, intestinal obstruction, fatty liver degeneration, and tongue discoloration. Endocrine System: Infrequent (0.1%-1.0%): Diabetes mellitus. Rare (<0.1%): Diabetic acidosis and goiter. Blood and Lymphatic System: Frequent (at least 1%): Leukopenia. Infrequent (0.1%-1.0%): Anemia, cyanosis, leukocytosis, lymphadenopathy, thrombocytopenia, and thrombocythemia. Rare (<0.1%): Normocytic anemia. Metabolic and Nutritional Disorders: Infrequent (0.1%-1.0%): Acidosis, elevated alkaline phosphatase, bilirubinemia, dehydration, hypercholesterolemia, hyperglycemia, hyperlipidemia, hyperuricemia, hypoglycemia, hypokalemia, hyponatremia, lower and upper extremity edema, water intoxication. Rare (<0.1%): Gout, hyperkalemia, hypernatremia, hypoproteinemia, and ketosis. Musculoskeletal System: Frequent (at least 1%): Limited joint movement. Infrequent (0.1%-1.0%): Arthritis, arthrosis, bursitis, lower extremity muscle cramps, and myasthenia. Rare (<0.1%): Bone pain, myopathy, osteoporosis, and rheumatoid arthritis. Nervous System: Frequent (at least 1%): Abnormal dreams, emotional lability, euphoria, decreased libido, paresthesia. Infrequent (0.1%-1.0%): Alcoholism, amnesia, antisocial behavior, ataxia, CNS stimulation, coma, delirium, depersonalization, dysarthria, facial paresis, hyperesthesia, hypokinesia, hypotonia, incoordination, obsessive-compulsive symptoms, phobias, somatization, stimulant abuse, stupor, stammering, tardive dyskinesia, tobacco abuse, vertigo, and withdrawal syndrome. Rare (<0.1%): Akinesia, circumoral paresthesia, encephalopathy, neuralgia, neuropathy, nystagmus, paralysis, subarachnoid hemorrhage. Respiratory System: Frequent (at least 1%): Dyspnea. Infrequent (0.1%-1.0%): Apnea, aspiration pneumonia, bronchial asthma, atelectasis, epistaxis, hemoptysis, hyperventilation, laryngitis, pneumonia, and voice change. Rare (<0.1%): Hiccups, hypoventilation, hypoxia, pulmonary edema, and stridor. Skin and Appendages: Frequent (at least 1%): Sweating. Infrequent (0.1%-1.0%): Alopecia, contact dermatitis, dry skin, eczema, maculopapular rash, pruritus, seborrhea, skin ulceration, and vesicular bullous rash. Rare (<0.1%): Hirsutism, pustular rash, skin discoloration, and urticaria. Sensory Organs: Frequent (at least 1%): Conjunctivitis. Infrequent (0.1%-1.0%): Accommodation disorder, blepharitis, cataract, corneal injury, deafness, diplopia, dry eyes, ear pain, ecchymosis, eye inflammation, eye pain, extraocular muscle damage, taste perversion, and tinnitus. Rare (<0.1%): Glaucoma, keratoconjunctivitis, macular hypopigmentation, miosis, mydriasis, and pigment deposits in the iris. Urogenital System: Frequent (at least 1%): Amenorrhea*, hematuria, metrorrhagia*, and vaginitis. Infrequent (0.1%-1.0%): Abnormal ejaculation*, breast pain, cystitis, decreased menstruation*, dysuria, lactation* in women, glycosuria, impotence*, increased menstruation, menorrhagia, polyuria, premenstrual syndrome*, pyuria, urinary frequency, urinary retention, worsening of urination, increased uterine fibroid* size, and vaginal hemorrhage*. Rare (<0.1%): Albuminuria, gynecomastia, mastitis, oliguria. *Sex-dependent. Other Data: Plasma prolactin levels are often elevated, but associated symptoms such as gynecomastia, galactorrhea, and breast enlargement are very rare. In almost all patients, prolactin levels returned to normal despite continued treatment. Over-prolongation of the corrected QT interval (QTc) occurred with olanzapine treatment compared to the placebo group. In some cases, asymptomatic increases in eosinophil count were observed. Increased creatine phosphokinase levels were rarely reported. In some cases, transient and asymptomatic increases in liver transaminases (ALT, AST) occurred. In patients at risk of developing acute liver pathology, transaminase levels should be determined before starting Rexepin treatment and during treatment according to clinical data. In case of adverse effects, consult a doctor. Drug Interactions Due to the CNS effects of olanzapine, caution is advised when combining it with other centrally acting drugs and alcohol. Since Rexepin exhibits dopamine antagonism in vivo, it may interfere with the action of levodopa and dopamine agonists. Potential effects of other drugs on Rexepin: Single doses of antacids (aluminum, magnesium) or cimetidine do not affect the oral bioavailability of Rexepin, but activated charcoal reduces it by 50-60%. Smoking or the use of carbamazepine group drugs may increase the metabolism of olanzapine. Potential effects of Rexepin on other drugs: Clinical studies with single doses of Rexepin did not show inhibition of the metabolism of imipramine/desipramine (P450-CYP2D6), warfarin (P450-CYP2C9), or diazepam (P450-CYP3A4). No interaction occurred between Rexepin and lithium or biperiden when used concurrently. Dosage Regimen Schizophrenia The initial recommended dose of Rexepin is 5-10 mg, taken on an empty stomach or after meals. Depending on the patient's clinical status, subsequent dosing should range from 5-20 mg. Doses of 15 mg and higher per day are recommended only after at least 4 days from the start of treatment. For maintenance therapy in schizophrenia, the need for a particular maintenance dose should be periodically re-evaluated. Bipolar Mania Oral olanzapine is generally administered at 10 or 15 mg once daily, regardless of food intake. If necessary, dose adjustments should be made at intervals of at least 24 hours, and daily dose increases/decreases are recommended by 5 mg. Maintenance Therapy In bipolar mania, after the acute episode subsides, treatment should be continued to consolidate the achieved results and prevent relapse. In Children: The effect of olanzapine in patients under 18 years of age has not been studied. In Elderly Patients: A low starting dose (5 mg/day) is not routinely recommended, but it should be considered in patients over 65 years of age based on clinical factors. Overdose Data on Rexepin overdose are very limited. In clinical studies, accidental or intentional overdose was observed in 67 patients. In the patient who received the highest dose (300 mg), only somnolence and slurred speech were observed. Patients examined in the clinic, including the one who received 300 mg, had no side effects according to laboratory analyses or ECG. Vital signs were generally within normal limits. Overdose may result in potentiation of the known pharmacological effects of the preparation. This may manifest as somnolence, mydriasis, blurred vision, respiratory depression, hypotension, and possible extrapyramidal disorders. Rexepin has no specific antidote, so appropriate symptomatic treatment is required. In case of acute overdose, airway patency should be assessed to ensure adequate oxygenation and ventilation. Administration of activated charcoal is recommended, as it reduces the bioavailability of oral Rexepin by 50-60%. Gastric lavage may also be performed (if the patient is unconscious, after intubation). In case of hypotension and circulatory collapse, IV fluid infusion and/or use of sympathomimetic agents are necessary. (Sympathomimetic agents with beta-agonist activity, such as epinephrine, dopamine, cannot be used, as beta-stimulation may worsen olanzapine-induced hypotension due to alpha-blockade). Cardiovascular monitoring, including electrocardiographic monitoring, should be performed immediately to detect possible arrhythmias. Medical supervision and monitoring should continue until the patient recovers. Storage Conditions The preparation should be stored at room temperature, below 25ºC, in a dark and dry place. Expiration Date 2 years Dispensing Rule The preparation is dispensed by prescription.