Remital

Remital Uses, Dosage, Side Effects, Food Interaction and all others data.

Olanzapine is an antipsychotic agent and has affinities for serotonin 5HT2A/2C, 5HT3, 5HT6; dopamine D1, D2, D3, D4, D5; cholinergic muscarinic receptors M1-M5; α1 adrenergic; and histamine H1 receptors. The mechanism of action of Olanzapine, as with other drugs having efficacy in schizophrenia, is unknown. However, it has been proposed that this drug’s efficacy in schizophrenia is mediated through a combination of dopamine and serotonin type 2 (5HT2) antagonism.

Olanzapine is well absorbed after oral administration, reaching peak plasma concentrations within 5 to 8 hours. The absorption is not affected by food. Olanzapine is not mutagenic or clastogenic as well as not carcinogenic.

The effect of olanzapine in the D2 receptor is reported to produce the positive effects of this drug such as a decrease in hallucinations, delusions, disorganized speech, disorganized thought, and disorganized behavior. On the other hand, its effect on the serotonin 5HT2A receptor prevents the onset of anhedonia, flat affect, alogia, avolition and poor attention. Based on the specific mechanism of action, olanzapine presents a higher affinity for the dopamine D2 receptor when compared to the rest of the dopamine receptor isotypes. This characteristic significantly reduces the presence of side effects.

Clinical trials for the original use of olanzapine demonstrated significant effectiveness in the treatment of schizophrenia and bipolar disorder in adults and acute manic or mixed episodes associated with bipolar disorder in adolescents.

The effect of olanzapine on dopamine and serotonin receptors has been suggested to reduce chemotherapy-induced nausea and vomiting as those receptors are suggested to be involved in this process. For this effect, several clinical trials have been conducted and it has been shown that olanzapine can produce a significant increase in total control of nausea and vomiting. In a high-level study of the effect of olanzapine for this condition, a complete response on the delay phase was observed in 84% of the individual and control of emesis of over 80% despite the phase.

Trade Name Remital
Generic Olanzapine + Olanzapine
Weight 5mg, 10mg
Type Tablet
Therapeutic Class
Manufacturer
Available Country Indonesia
Last Updated: September 19, 2023 at 7:00 am
Remital
Remital

Uses

Olanzapine is used for the acute and maintenance treatment of schizophrenia and related psychoses where positive symptoms (e.g. delusions, hallucinations, disordered thinking, hostility and suspiciousness) and/or negative symptoms (e.g. flattened affect, emotional and social withdrawal, poverty of speech) are prominent.

Olanzapine is used for the treatment of acute manic or mixed episodes in bipolar disorder, with or without psychotic features and with or without a rapid cycling course

Remital is also used to associated treatment for these conditions: Acute Agitation, Acute Depressive Episode, Bipolar 1 Disorder, Bipolar Disorder With Manic or Mixed Episodes, Delirium, Delusional Parasitosis, Gilles de la Tourette's Syndrome, Major depressive disorder, recurrent episode, Mixed manic depressive episode, Post Traumatic Stress Disorder (PTSD), Psychosis, Schizophrenia, Acute Manic episode

How Remital works

The activity of olanzapine is achieved by the antagonism of multiple neuronal receptors including the dopamine receptor D1, D2, D3 and D4 in the brain, the serotonin receptors 5HT2A, 5HT2C, 5HT3 and 5HT6, the alpha-1 adrenergic receptor, the histamine receptor H1 and multiple muscarinic receptors.

As abovementioned, olanzapine presents a wide profile of targets, however, its antagonistic effect towards the dopamine D2 receptor in the mesolimbic pathway is key as it blocks dopamine from having a potential action at the post-synaptic receptor. The binding of olanzapine to the dopamine D2 receptors is easily dissociable and hence, it allows for a certain degree of dopamine neurotransmission.

On the other hand, olanzapine acts in the serotonin 5HT2A receptors in the frontal cortex in a similar manner than the reported on dopamine D2 receptors. This determined effect allows for a decrease in adverse effects.

Dosage

Remital dosage

The recommended starting dose for Olanzapineis 10 mg/day, administered as a single daily dose without regard to meals. Daily dosage may subsequently be adjusted on the basis of individual clinical status within the range of 5-20 mg daily. An increase to a dose greater than the routine therapeutic dose of 10 mg/day i.e. to a dose of 15 mg/day or greater, is recommended only after appropriate clinical reassessment.

Children: Olanzapine has not been studied in subjects under 18 years of age.

Elderly patients (age 65 and over): starting dose 5 mg/day

Patients with hepatic and/or renal impairment: starting dose 5 mg/day

When more than one factor is present which might result in slowermetabolism (female gender, geriatric age, non-smoking status), consideration should be given to decreasing the starting dose. Dose escalation, when indicated, should be conservative in such patients.

Side Effects

Very common undesirable effects are somnolence and weight gain. Besides increased appetite, elevated glucose levels, elevated triglyceride levels, dizziness, akathisia, Parkinson's disease, dyskinesia, orthostatic hypotension, mild and transient anticholinergic effects including constipation and dry mouth, asthenia, edema and photosensitivity reaction etc. may be observed.

Toxicity

The toxicity symptoms of olanzapine are known to include somnolence, mydriasis, blurred vision, respiratory depression, hypotension, extrapyramidal symptoms and anticholinergic effects. The overdosage effects in children are generally associated with more significant side effects.

The maximum registered dosage of olanzapine in clinical trials was of 300 mg and it was reported to present drowsiness and slurred speech. However, on post-marketing surveillance, a wide range of symptoms have been presented including agitation, dysarthria, tachycardia, extrapyramidal symptoms, and reduced consciousness. One case of overdosage-driven death was reported after ingestion of 450 mg of olanzapine. In the cases of acute overdosage, the establishment of adequate oxygenation and ventilation, gastric lavage and administration of activated charcoal with a laxative is recommended.

In carcinogenesis studies, olanzapine was showed to present an increase in the incidence of liver hemangiomas and hemangiosarcomas as well as mammary gland adenomas, and adenocarcinomas. On fertility studies, there was solely found impairment in male mating performance and delays in ovulation. There is no evidence of mutagenic, genotoxic potential not adverse events on fertility.

Precaution

Olanzapine should be used cautiously in patients who have a history of seizures or have conditions associated with seizures. Olanzapine should be used cautiously in patients with low leukocyte and/or neutrophil counts for any reason, drug induced bone marrow depression/toxicity caused by radiation therapy or chemotherapy, hypereosinophilic conditions, impaired hepatic function, and patients using hepatotoxic medicines, centrally acting drug and medicines know to increase QT interval, especially in the elderly. Patients should be cautioned about operating hazardous machinery, including motor vehicles.

Interaction

Drugs that induce CYP1A2 or glucoronyl transferase enzymes (omeprazole, rifampicin), inhibitor of CYP1A2 (fluvoxamine), centrally acting drugs, antihypertensive agents.

Volume of Distribution

The volume of distribution of olanzapine is reported to be of 1000 liters which indicate a large distribution throughout the body.

Elimination Route

Olanzapine presents a linear pharmacokinetic profile and, after daily administration, it reaches steady-state in about a week. Under the administration of a normal dosage of olanzapine, the steady-state plasma concentration does not seem to exceed 150 ng/ml with an AUC of 333 ng/h/ml.

The absorption of olanzapine is not affected by the concomitant administration of food. The pharmacokinetic profile of olanzapine is characterized by reaching peak plasma concentration of 156.9 ng/ml approximately 6 hours after oral administration.

Half Life

Olanzapine presents a half-life ranging between 21 to 54 hours with an average half-life of 30 hours.

Clearance

The mean clearance rate of olanzapine is of 29.4 L/hour however, some studies have reported an apparent clearance of 25 L/h.

Elimination Route

Olanzapine is mainly eliminated through metabolism and hence, only 7% of the eliminated drug can be found as the unchanged form. It is mainly excreted in the urine which represents around 53% of the excreted dose followed by the feces that represent about 30%.

Pregnancy & Breastfeeding use

Olanzapine should be used in pregnancy only if the potential benefits justify the potential risk to the foetus. So, patients should be advised to notify their physician if they become pregnant or intend to become pregnant during treatment with Olanzapine. There is no report to show teratogenecity. Patients should not breast feed if they are taking Olanzapine.

Contraindication

This is contraindicated in those patients with a known hypersensitivity to Olanzapine as well as in patients with known risk for narrow-angle glaucoma.

Concomitant illness: Olanzapine in patients with concomitant illness is limited, caution is advised when prescribing for patients with prostatic hypertrophy, or paralytic ileus and related conditions.

Neuroleptic Malignant Syndrome (NMS): If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all antipsychotic medicines, including olanzapine must be discontinued.

Acute Overdose

Symptoms: Tachycardia, agitation/aggressiveness, dysarthria, extrapyramidal symptoms, reduced level of consciousness ranging from sedation to coma.

Management: Symptomatic and supportive treatment. Gastric lavage and admin of activated charcoal may be effective.

Storage Condition

Store below 30˚ C. Protect from light and moisture. Keep out of the reach of children.

Innovators Monograph

You find simplified version here Remital


*** Taking medicines without doctor's advice can cause long-term problems.
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