Multizine H

Uses

Thioridazine is used for the management of schizophrenic patients who fail to respond adequately to treatment with other antipsychotic drugs. Due to the risk of significant, potentially life-threatening, proarrhythmic effects with thioridazine treatment, thioridazine should be used only in patients who have failed to respond adequately to treatment with appropriate courses of other antipsychotic drugs, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs. Consequently, before initiating treatment with thioridazine, it is strongly recommended that a patient be given at least 2 trials, each with a different antipsychotic drug product, at an adequate dose, and for an adequate duration.

However, the prescriber should be aware that thioridazine has not been systematically evaluated in controlled trials in treatment refractory schizophrenic patients and its efficacy in such patients is unknown.

Anxiety states: It controls excessive anxiety, tension, and agitation seen in neuroses or associated with somatic conditions. The treatment or prevention of nausea and vomiting of various causes. The management of psychotic disorders, such as acute or chronic catatonic, hebephrenic and paranoid schizophrenia; psychosis due to organic brain damage, toxic psychosis, and the manic phase of manic-depressive illness.

Multizine H is also used to associated treatment for these conditions: Psychosis, SchizophreniaAgitation, Psychosis, Schizophrenia, Acute non-psychotic Anxiety

How Multizine H works

Thioridazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; blocks alpha-adrenergic effect, depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.

Trifluoperazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.

Dosage

Multizine H dosage

Since thioridazine is associated with a dose-related prolongation of the QTc interval, which is a potentially life-threatening event, its use should be reserved for schizophrenic patients who fail to respond adequately to treatment with other antipsychotic drugs. Dosage must be individualized and the smallest effective dosage should be determined for each patient

Adults: The usual starting dose for adult schizophrenic patients is 50 to 100 mg three times a day, with a gradual increment to a maximum of 800 mg daily if necessary. Once effective control of symptoms has been achieved, the dosage may be reduced gradually to determine the minimum maintenance dose. The total daily dosage ranges from 200 to 800 mg, divided into two to four doses.

Pediatric: For pediatric patients with schizophrenia who are unresponsive to other agents, the recommended initial dose is 0.5 mg/kg/day given in divided doses. Dosage may be increased gradually until optimumtherapeuticeffect is obtained or the maximum dose of 3 mg/kg/day has been reached.

Schizophrenia and other psychoses:

• Adults and child over 12 years: Recommended starting dose is 2-5 mg b.i.d, increased by 5 mg daily after 1 week then at interval of 3 days, according to response.
• Children (6-12 years): Dosage should be adjusted to the weight of the child and severity of the symptoms. The starting dosage is 1 mg b.i.d. Dosage may be increased gradually until symptoms are controlled or until side effects become troublesome. While it is usually not necessary to exceed dosages of 15 mg daily.
• Elderly: Reduce initial dose by at least half

Short-term management of severe anxiety:

• Adult and child over 12 years: 1-2 mg b.i.d, increased if necessary to 6 mg daily.
• Child (3-5 years): 1 mg daily
• Child (6-12 years): Up to 4 mg daily in divided dose.
• Elderly: Reduce initial dose by at least half

Antiemetic:

• Adult: 2-4 mg daily in divided doses; max. 6 mg daily;
• Child 3-5 years: up to 1 mg daily, 6-12 years up to 4 mg daily.

Side Effects

Tardive dyskinesia; leucopenia, neutropenia, agranulocytosis; drowsiness, pseudoparkinsonism and other extrapyramidal symptoms; dry mouth, blurred vision, constipation, nausea, vomiting, diarrhoea, nasal stuffiness, pallor; galactorrhoea, breast engorgement, amenorrhoea, inhibition of ejaculation, peripheral oedema; dermatitis, skin eruptions. Rarely, nocturnal confusion, hyperactivity, lethargy, psychotic reactions, restlessness, headache, photosensitivity, parotid swelling.

Common side effects are transient restlessness, dystonias or may resemble parkinsonism. Other CNS Reactions are drowsiness, dizziness, fatigue, blurred vision, seizures. Without these Peripheral oedema, blood dyscrasias, jaundice may occasionally occur. Tachycardia, constipation, urinary hesitancy and retention and hyperpyrexia have been reported very rarely.

Toxicity

LD₅₀=956-1034 mg/kg (Orally in rats); Agitation, blurred vision, coma, confusion, constipation, difficulty breathing, dilated or constricted pupils, diminished flow of urine, dry mouth, dry skin, excessively high or low body temperature, extremely low blood pressure, fluid in the lungs, heart abnormalities, inability to urinate, intestinal blockage, nasal congestion, restlessness, sedation, seizures, shock

Symptoms of overdose include agitation, coma, convulsions, difficulty breathing, difficulty swallowing, dry mouth, extreme sleepiness, fever, intestinal blockage, irregular heart rate, low blood pressure, and restlessness.

Precaution

Patient with severe CV disease, narrow-angle glaucoma, Parkinson's disease, seizure disorder. Avoid abrupt withdrawal. Hepatic and renal impairment. Elderly with dementia-related psychosis. Pregnancy and lactation.

Care should be taken when treating elderly patients, and initial dosage should be reduced. Such patients can be specially sensitive, particularly to extra pyramidal and hypotensive effects. Patients with cardiovascular disease including arrhythmias should also be treated with caution. Care should be taken in patients with angina pectoris.

Interaction

May potentiate the effects of CNS depressants (e.g. anaesth, barbiturates, narcotics, opiates, other psychoactive drugs).

Trifluoperazine may diminish the effect of oral anticoagulants. Concomitant administration of propranolol with trifluoperazine results in increased plasma levels of both drugs. Antihypertensive effects of guanethidine and related compounds may be counteracted when phenothiazines are used concurrently. Potentiation may occur if antipsychotic drugs are combined with CNS depressants such as alcohol. hypnotics and anticonvulsant.

Elimination Route

60%

Half Life

21-25 hours

10-20 hours

Pregnancy & Breastfeeding use

Pregnancy Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Pregnancy: Safety for the use of trifluoperazine during pregnancy has not been established. Therefore, it is not recommended that the drug be given to pregnant patients except when, in the judgement of the physician, it is essential. The potential benefits should clearly outweigh possible hazards. There are reported instances of prolonged jaundices, extrapyramidal signs, hyperreflexia or hypoflexia in newborn infants whose mother received phenothiazines.

Lactation: Adequate human data are not available in case of lactation.

Contraindication

Patients with reduced levels of CYP2D6 isoenzyme, congenital long QT syndrome or history of cardiac arrhythmias; severe CNS depression or comatose states of any cause; hypertensive or hypotensive heart disease of extreme degree. Concomitant use with drugs that prolong QTc interval, CYP2D6 isoenzyme inhibitors and drugs which reduce thioridazine clearance by other mechanisms.

Do not use Trifluoperazine in comatose patients, or in those with existing blood dyscrasias or known liver damage, or in those hypersensitive to the active ingredient or related compounds.

Special Warning

Renal Impairment: Lower initial doses and more gradual dosage increase.

Hepatic Impairment: Lower initial doses and more gradual dosage increase.

Acute Overdose

Symptoms: Cardiotoxicity (e.g. prolongation of QT interval and QRS complex).

Management: Symptomatic and supportive treatment with CV (e.g. ECG) monitoring. Establish a patent airway and ensure adequate oxygenation and ventilation. Employ gastric lavage and administer repeated doses of activated charcoal. May include ventricular pacing, defibrillation, admin of IV Mg sulfate, lidocaine, phenytoin or isoproterenol, correction of electrolyte abnormalities and/or acid-base balance to manage arrhythmias. Administer lidocaine with caution as it may increase the risk of developing seizures.

Signs and symptoms will be predominantly extrapyramidal; hypotension may occur. Treatment consists of gastric lavage together with supportive and symptomatic measures. Do not induce vomiting. Extra pyramidal symptoms may be treated with an anticholinergic, antiparkinsonism drug. Treat hypotension with fluid replacement; if severe or persistent. nor adrenaline may be considered. Adrenaline is contraindicated.

Storage Condition

Store between 15-30° C. Protect from light.

It should be store at room temperature between 15-30° C away from light and moisture.

Innovators Monograph

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