Olanzapine Canon, 5 mg 28 pcs

Pharmacotherapeutic group:

antipsychotic (neuroleptic)

ATC code: N05AH03

Indications

Schizophrenia, Anxiety, Manic Depressive Psychosis

• Schizophrenia in adults. Olanzapine Canon is indicated for the treatment of exacerbations, maintenance and long-term antiretroviral therapy in patients with schizophrenia.
• Bipolar affective disorder in adults. Olanzapine Canon, as monotherapy or in combination with lithium or valproic acid, is indicated for the treatment of acute manic or mixed episodes of bipolar affective disorder with/without psychotic manifestations and with/without rapid phase change. Olanzapine Canon is indicated to prevent relapse in patients with bipolar disorder in whom olanzapine has been effective in treating the manic phase.
• In combination with fluoxetine, Olanzapine Canon is indicated for treatment of depression associated with bipolar disorder.
• Therapeutically resistant depression
• .In combination with fluoxetine, Olanzapine Canon is indicated for the treatment of treatment-resistant depression in adult patients (major depressive episodes with a history of ineffective use of two antidepressants at a dose and duration of therapy adequate for the episode).
  

Active ingredient

Olanzapine

Composition

1 film-coated tablet, 5 mg contains:

active substance:

olanzapine 5 mg;

auxiliary substances:

Hyprolose (hydroxypropylcellulose) low-substituted 2.5 mg,

Calcium hydrophosphate 40 mg,

croscarmellose sodium 1 mg,

Mannitol 50.5 mg,

Magnesium stearate 1 mg;

Composition of the film coating:

opadray II yellow 3 mg, including: polyvinyl alcohol 1.2 mg, macrogol (polyethylene glycol) 0.606 mg, talc 0.444 mg, titanium dioxide 0.705 mg, iron oxide yellow dye 0.045 mg

How to take, the dosage

The recommended therapeutic dose of Olanzapine Canon is 5 mg to 20 mg per day. Daily dose should be adjusted individually depending on the clinical condition of the patient.

Schizophrenia in adults. The recommended starting dose of Olanzapine Canon is 10 mg once daily.
Acute mania in bipolar disorder in adults. The recommended starting dose of Olanzapine Canon is 15 mg once daily as monotherapy or 10 mg once daily in combination with lithium or valproic acid.
Maintenance therapy in bipolar disorder in adults. The recommended starting dose of Olanzapine Canon is 10 mg once daily. Patients who have received Olanzapine Canon for the treatment of acute mania are recommended to continue maintenance therapy at the same dose.

Depression within bipolar disorder in adults. Olanzapine Canon in combination with fluoxetine should be administered once daily, in the evening. The starting dose is 5 mg of olanzapine and 20 mg of fluoxetine.

Antidepressant activity has been confirmed with olanzapine at a dose of 6-12 mg (average daily dose is 7.4 mg) and fluoxetine at a dose of 25-30 mg (average daily dose is 39.3 mg). If necessary, it is possible to change the doses of both olanzapine and fluoxetine.

Therapeutic resistant depression. Olanzapine Canon should be administered in combination with fluoxetine once daily, in the evening. The initial dose is 5 mg olanzapine and 20 mg fluoxetine. If necessary, it is possible to change the doses of both olanzapine and fluoxetine.

Particular patient groups

In elderly patients, reducing the starting dose (to 5 mg daily) is not usually recommended, but may be possible in patients over 65 years of age if there are risk factors (see section “Special Precautions”).

In patients with hepatic and/or renal disease, reduction of the initial dose to 5 mg/day is recommended. In patients with moderate hepatic impairment (liver cirrhosis, class A and B according to Child-Pugh classification) the initial dose is 5 mg/day, further dose increase is possible with caution.
Women do not require change of dosage in comparison with men.

In non-smoking patients, no dose adjustment is required compared to smokers. A reduction in the starting dose may be recommended for patients with a combination of factors (female sex, older age, nonsmoker) that may slow down olanzapine metabolism.

Interaction

Metabolism of olanzapine may be altered by cytochrome P450 isoenzyme inhibitors or inducers with specific activity against CYP1A2 isoenzyme. Clearance of olanzapine is increased in smoking patients and in patients taking carbamazepine (due to increased activity of CYP1A2 isoenzyme). Known potential inhibitors of CYP1A2 isoenzyme may decrease clearance of olanzapine. Olanzapine is not a potential inhibitor of CYP1A2 isoenzyme activity, therefore pharmacokinetics of drugs such as theophylline, which are mainly metabolized with participation of CYP1A2 isoenzyme, is not changed when taking olanzapine.

In clinical studies it has been shown that a single dose of olanzapine against the background of therapy with the following drugs is not accompanied by inhibition of metabolism of the following drugs: imipramine or its metabolite desipramine (CYP2D6, CYP3A, CYP1A2), warfarin (CYP2C19), theophylline (CYP1A2) or diazepam (CYP3A4, CYP2C19). No evidence of drug interaction was found when using olanzapine in combination with lithium or biperiden. No changes in the pharmacokinetics of ethanol have been observed against the background of stable concentrations of olanzapine. However, taking ethanol together with olanzapine. may be accompanied by an increase in the pharmacological effects of olanzapine, such as sedation. A single dose of aluminum- or magnesium-containing antacid or cimetidine does not impair bioavailability of olanzapine when taken orally. Concomitant use of activated charcoal reduces oral bioavailability of olanzapine by up to 50-60%. Fluoxetine (60 mg once or 60 mg daily for 8 days) increases maximal concentration of olanzapine by an average of 16% and decreases clearance of olanzapine by an average of 16%. The magnitude of this effect is significantly less than the severity of individual differences in these indices, so it is generally not recommended to change the dose of olanzapine when it is prescribed in combination with fluoxetine.

Fluvoxamine, a CYP1A2 isoenzyme inhibitor, reduces the clearance of olanzapine. This results in a mean increase in olanzapine Stache with fluvoxamine administration of 54% in non-smoking women and 77% in smoking men, a mean increase in the area under the pharmacokinetic curve (AUC) of olanzapine of 52% and 108%, respectively. Low-dose olanzapine should be administered to patients who are co-treated with fluvoxamine.

In in vitro studies using human liver microsomes, olanzapine has been shown to slightly inhibit the formation of valproate glucuronide (the main metabolic pathway of valproic acid). Valproic acid also has little effect on in vitro metabolism of olanzapine, so a clinically significant pharmacokinetic interaction between olanzapine and valproic acid is unlikely.

According to in vitro studies using human liver microsomes, olanzapine has also demonstrated very little potential to inhibit the activity of the following cytochrome P450 isoenzymes: CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A. As with other antipsychotics, caution should be exercised when using olanzapine concomitantly with medications that prolong the QTc interval and also affect the Central Nervous System.

Special Instructions

Clinical improvement may take several days and requires patient monitoring.
Malignant neuroleptic syndrome

Malignant neuroleptic syndrome (MNS) (a potentially fatal symptom complex) can develop with treatment with any neuroleptic drug, including olanzapine Canon, but to date there is no evidence to confirm a reliable link between olanzapine administration and the development of this condition. Clinical manifestations of malignant neuroleptic syndrome include significant increases in body temperature, muscle rigidity, altered mental status, and autonomic disturbances (unstable pulse or blood pressure, tachycardia, cardiac arrhythmias, increased sweating). Additional signs may include increased creatinine phosphokinase levels, myoglobinuria (rhabdomyolysis), and acute renal failure. Clinical manifestations of malignant neuroleptic syndrome or significant increase in body temperature without other symptoms of malignant neuroleptic syndrome require withdrawal of all neuroleptics, including Olanzapine Canon.

Late dyskinesia
Treatment with olanzapine is less likely to result in dyskinesia requiring medication correction than with haloperidol. However, the risk of tardive dyskinesia with prolonged therapy with neuroleptics should be considered. If signs of tardive dyskinesia develop, dose reduction or withdrawal of Olanzapine Canon is recommended. It should be considered that when transferring to Olanzapine Canon, symptoms of tardive dyskinesia may develop due to a one-step withdrawal of previous therapy. Symptoms of tardive dyskinesia may increase or manifest after drug withdrawal.

Parkinson’s disease

Efficacy when used in Parkinson’s disease does not exceed placebo (for the purpose of controlling iatrogenic psychosis). Olanzapine Canon is not recommended for treatment of psychosis induced by dopamine receptor agonists in Parkinson’s disease; these patients have increased symptoms of Parkinsonism and hallucinations.

Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including deaths, have been reported in elderly patients with psychosis with dementia. In placebo-controlled studies, a higher incidence of cerebrovascular adverse events was noted in patients in the olanzapine group compared to the placebo group. These patients had prior risk factors (cerebrovascular disorders (history), transient ischemic attack, arterial hypertension, smoking) as well as comorbidities and/or medication use that were temporally associated with cerebrovascular disorders.

The efficacy of olanzapine in elderly patients with psychosis with dementia has not been established. The main risk factors for increased mortality in this group of patients when treated with olanzapine are age > 80 years, sedation, concomitant use with benzodiazepines, or the presence of pulmonary pathology (e.g., pneumonia with or without aspiration). There are insufficient data to establish differences in the incidence of cerebrovascular events and/or mortality (compared to placebo), and in risk factors in this patient group when olanzapine is taken orally and when it is injected intramuscularly. Olanzapine Canon is not recommended for therapy of patients with psychosis in dementia.

The development of the risk of sudden death

Periodic experience with any neuroleptic, including olanzapine, has shown a similar, dose-dependent, two-fold increase in the risk of death due to acute heart failure compared to death due to acute heart failure in patients not taking neuroleptics.

QT interval duration
Infrequent clinically significant QT interval prolongation has been observed in patients receiving olanzapine, with no significant difference from placebo in the incidence of cardiac adverse events. However, as with other antipsychotics, caution is recommended when prescribing Olanzapine Canon in combination with drugs that may prolong the QT interval, especially in elderly patients with congenital prolongation of the QT interval, with congestive heart failure, myocardial hypertrophy, hypokalemia and hypomagnesemia.

Postural hypotension
Postural hypotension is uncommon in elderly patients. As with other neuroleptics, it is recommended that blood pressure be controlled in patients over 65 years of age if Olanzapine Canon is prescribed.

Thromboembolism
The development of venous thromboembolism during therapy with olanzapine is extremely rare. A causal relationship between olanzapine administration and venous thromboembolism has not been established. However, considering that patients with schizophrenia often have acquired risk factors for venous thromboembolism, a combined assessment of all possible risk factors for this complication, including immobilization of patients, is required, and necessary preventive measures should be taken.

Liver function abnormalities
In isolated cases, administration of olanzapine is usually accompanied by transient, asymptomatic increases in serum hepatic “transaminases” (ACT and ALT) in the early stages of therapy. Rare cases of hepatitis were noted. In very rare cases, hepatic cholestasis and other mixed liver damage have been noted. Special caution is necessary in case of increase of serum ACT and/or ALT in patients with liver function insufficiency, with limited liver functional reserve or in patients treated with potentially hepatotoxic drugs. If ACT and/or ALT values increase during treatment with olanzapine, close monitoring of the patient and, if necessary, reduction of the dose of olanzapine Canon is required. If hepatitis, including hepatocellular, cholestatic or mixed hepatitis, Olanzapine Canon should be discontinued.

Hyperglycemia and diabetes
A higher prevalence of diabetes mellitus has been noted in patients with schizophrenia. As with some other antipsychotics, very rare cases of hyperglycemia, diabetes mellitus, exacerbation of pre-existing diabetes mellitus, ketoacidosis, and diabetic coma have been reported. A causal relationship between antipsychotic medications and these conditions has not been established. Close clinical monitoring of patients with diabetes mellitus and patients with risk factors for diabetes mellitus is recommended. For all groups of patients, regardless of BMI, a clinically significant increase in body weight was observed. An increase of 7% or more of the mean value after a short course of treatment (mean duration of 47 days) was observed very frequently (22.2%), an increase of 15% or more was frequent (4.2%), and an increase of 25% or more was infrequent (0.8%). In patients receiving longer treatment (at least 48 weeks), increases of > 7% > 15% and > 25% were very frequent (64.4%, 31.7%, 12.3%, respectively).

Changes in lipid profile
Undesirable changes in the lipid spectrum have been observed in patients receiving olanzapine. Monitoring of lipid profile and clinical monitoring is recommended.

Epileptic seizures
Olanzapine Canon should be used with caution in patients with a history of epileptic seizures or who are exposed to factors that lower the seizure threshold. Seizures are rarely seen in such patients when treated with olanzapine.

Hematologic changes
As with other neuroleptics, caution should be exercised in therapy with olanzapine in patients with decreased peripheral blood leukocyte and/or neutrophil counts due to various causes; with signs of bone marrow suppression or toxic bone marrow dysfunction caused by drugs in the history; with suppression of bone marrow function due to concomitant disease, radiotherapy or chemotherapy in the history; with hypereosinophilia or myeloproliferative disease. In clinical trials, use of olanzapine in patients with a history of clozapine-dependent neutropenia or agranulocytosis has not been associated with recurrence of these disorders. Neutropenia has mainly been reported with combined therapy with olanzapine and valproic acid.

Anticholinergic activity
Therapy with olanzapine is rarely accompanied by anticholinergic side effects. However, clinical experience with olanzapine in patients with comorbidities is limited, so caution is advised when prescribing olanzapine Canon in patients with clinically significant prostatic hypertrophy, paralytic bowel obstruction and similar conditions.

Dopaminergic antagonism
Under in vitro conditions, olanzapine exhibits antagonism to dopamine receptors and, like other neuroleptics, can theoretically inhibit the effects of levodopa and dopamine agonists. General activity with respect to the CNS. Given olanzapine’s main effect on the CNS, caution should be exercised when using olanzapine in combination with other centrally acting medications and alcohol.

Suicide
The risk of suicide attempt in patients with schizophrenia and type 1 bipolar disorder is due to the diseases themselves. In connection with this, during pharmacotherapy, close monitoring of those patients in whom the risk of suicide is particularly high is required. When prescribing Olanzapine Canon, care should be taken to minimize the number of pills the patient takes in order to reduce the risk of overdose.

Cancellation of therapy
If olanzapine is abruptly withdrawn, sweating, insomnia, tremors, nausea and vomiting rarely (0.01 to 0.1%) develop. A gradual reduction in the dose is recommended when the drug is withdrawn.

Children and adolescents under 18 years
Olanzapine is not recommended for use in children and adolescents under 18 years, due to a lack of sufficient efficacy and safety data. In short-term studies conducted in adolescents 13-17 years old, there was a greater increase in body weight and changes in lipid and prolactin concentrations than in similar studies in adults.

Influence on driving ability
Patients taking olanzapine Canon should exercise caution when driving motor vehicles and working requiring rapid psychomotor reactions, as olanzapine may cause drowsiness and dizziness.

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Contraindications

• High sensitivity to any of the ingredients of the drug
• Risk of glaucoma
• .Closed-angle glaucoma
• Age under 18 years of age (efficacy and safety not proven)
• Breastfeeding

Side effects

Prevalence of side effects (WHO):
very common > 10%
common< 10%> 1%
infrequent< 1%>0.1%
rare< 0.1%>0.01%
very rare<0.01% including isolated reports

Disorders of the blood and lymphatic system
often: eosinophilia;
infrequent: leukopenia, neutropenia;
rare: thrombocytopenia;

Immune system disorders
very rare: allergic reactions (anaphylactic shock, angioedema, skin itching, urticaria);

Metabolic disorders
very rare: development or decompensation of diabetes mellitus, in some cases accompanied by ketoacidosis and diabetic coma, including fatal; after withdrawal of therapy, after 9-12 months of treatment, a decrease in blood glucose concentration is possible;

Metabolic and nutrition disorders
very often: increased body weight;
often: increased cholesterol concentration, triglycerides, glucosuria, increased appetite;

Changes in glucose concentration from normal fasting (<5.5b mmol/l) to elevated (>7 mmol/l) are common. Changes in glucose concentration from borderline values (>5.5b mmol/l – <7 mmol/l) to elevated (>7 mmol/l) are observed very frequently;
very rare: hypertriglyceridemia, hypercholesterolemia; frequency is not known: Abdominal bloating;

Nervous system disorders very common: somnolence;
frequent: dizziness, akathisia, parkinsonism, dyskinesia;
infrequent: Seizures (more often against a background of seizure syndrome in the anamnesis);
very rarely: Malignant neuroleptic syndrome, dystonia (including oculogyric crisis), tardive dyskinesia, “withdrawal” syndrome (sweating, insomnia, tremor, anxiety, nausea or vomiting);

Cardiac disorders
infrequent: bradycardia, QT interval prolongation;
very rarely: Ventricular tachycardia/ventricular fibrillation, sudden death;

vascular disorders frequently: orthostatic hypotension;
very rarely: pulmonary embolism, deep vein thrombosis;

Gastrointestinal disorders
frequent: transient anticholinergic effects, including dry mouth, constipation; rare: pancreatitis;

Liver and biliary tract disorders
often: Transient increase in the activity of “hepatic” transferases (alanine aminotransferase (ALT), aspartate aminotransferase (ACT)), especially in the early period of the study;
rare: hepatitis (including hepatic-cellular, hepatocellular or mixed).

Skin and subcutaneous tissue disorders
frequently: skin rash;
infrequently: photosensitization reactions;
very rarely: alopecia;

Muscular and connective tissue disorders
rare: rhabdomyolysis;
frequency not known: Arthralgia;

Renal and urinary tract disorders
infrequent: urinary incontinence;
rare: delayed urinary onset;
frequency unknown: uric acid elevation;

Genital and mammary disorders
infrequent: priapism.

General disorders and disorders at the site of administration
often: asthenia, fatigue, edema;
rarely: hypothermia;
frequency unknown: fever;

Laboratory and instrumental findings
very common: increased plasma prolactin concentrations, but clinical manifestations (e.g., gynecomastia, galactorrhea, and breast enlargement) are rare. Most patients’ prolactin levels spontaneously normalized without drug withdrawal;
often: increased creatine phosphokinase (CPK) activity, total bilirubin;
very rarely: increased alkaline phosphatase activity.

Indesirable effects in special therapeutic groups
A very frequent (> 10%) undesirable effect when using olanzapine in patients with psychosis with dementia is gait disturbance and falls. Urinary incontinence and pneumonia are frequent (< 10% and > 1%) adverse effects of olanzapine in elderly patients with psychosis with dementia.

In patients with psychosis induced by dopamine receptor agonist drug administration in Parkinson’s disease, an increase in Parkinsonian symptoms is very common. Hallucinations are also very often observed in this group of patients. In patients with bipolar mania receiving olanzapine in combination with lithium or valproic acid drugs, weight gain, dry mouth, increased appetite, tremor, and frequent speech disorders are very common unwanted effects.
Data on the side effects of the drug from clinical trials:

In clinical trials, cases of parkinsonism and dystonia were more frequent in patients taking olanzapine, but the difference with the placebo group was not statistically significant.

In patients taking olanzapine, cases of parkinsonism, akathisia, and dystonia were less frequent than in patients receiving titrated doses of haloperidol. Because of the lack of similar information about patients’ history of acute and tardive dyskinesias, it cannot be concluded at this time that olanzapine is less likely to cause the development of tardive dyskinesias or other tardive extrapyramidal syndromes.

In clinical trials lasting up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of normal in approximately 30% of patients with normal baseline prolactin levels. In most of these patients, the increase in prolactin concentration was moderate, and less than twice the upper limit of normal. In patients taking olanzapine, genital and mammary disorders possibly related to olanzapine administration (aminorrhea, breast enlargement, galactorrhea in women, gynecomastia, and breast enlargement in men) were infrequent. Sexual dysfunction possibly related to olanzapine administration (erectile dysfunction in men, decreased libido in men and women) were observed frequently.

.

Overdose

Frequent symptoms: tachycardia, agitation/aggressiveness, articulation disorders, various extrapyramidal disorders and impaired consciousness of varying severity (from sedation to coma).

Other clinically significant effects: delirium, seizures, malignant neuroleptic syndrome, respiratory depression, aspiration, arterial hypertension or hypotension, cardiac arrhythmias (< 2 % of overdoses), cardiac and respiratory arrest. The minimum dose in acute overdose with fatal outcome according to studies is 450 mg, the maximum dose in overdose with a favorable outcome (survival) is 2000 mg.

Treatment: There is no specific antidote for olanzapine. Inducing vomiting is not recommended. Standard procedures for overdose may be indicated (gastric lavage, administration of activated charcoal). Concomitant administration of activated charcoal leads to a decrease in bioavailability of olanzapine when taken orally of up to 50-60%.

Symptomatic treatment is indicated according to the clinical condition and control of vital organ functions, including treatment of arterial hypotension, circulatory disorders and maintenance of respiratory function. Epinephrine, dopamine, and other sympathomimetics that are beta-adrenoreceptor agonists should not be used because stimulation of these receptors may exacerbate arterial hypotension.

Similarities

Zyprexa, Zalasta, Zalasta Ku-tab, Olanzapine