Zepradon

Uses

Zepradon is used for the treatment of schizophrenia, as monotherapy for the acute treatment of bipolar manic or mixed episodes, and as an adjunct to lithium or valproate for the maintenance treatment of bipolar disorder. Zepradon intramuscular is used for acute agitation in schizophrenic patients. When deciding among the alternative treatments available for the condition needing treatment, the prescriber should consider the finding of ziprasidone's greater capacity to prolong the QT/QTc interval compared to several other antipsychotic drugs. Prolongation of the QTc interval is associated in some other drugs with the ability to cause torsade de pointes-type arrhythmia, a potentially fatal polymorphic ventricular tachycardia, and sudden death. In many cases this would lead to the conclusion that other drugs should be tried first. Whether ziprasidone will cause torsade de pointes or increase the rate of sudden death is not yet known

Zepradon is also used to associated treatment for these conditions: Acute Agitation, Agitation, Bipolar 1 Disorder, Psychosis, Schizophrenia, Treatment Resistant Major Depressive Disorder, Acute Manic episode, Acute Mixed manic depressive episode

How Zepradon works

The effects of ziprasidone are differentiated from other antispychotics based on its preference and affinity for certain receptors. Zepradon binds to serotonin-2A (5-HT2A) and dopamine D2 receptors in a similar fashion to other atypical antipsychotics; however, one key difference is that ziprasidone has a higher 5-HT2A/D2 receptor affinity ratio when compared to other antipsychotics such as olanzapine, quetiapine, risperidone, and aripiprazole. Zepradon offers enhanced modulation of mood, notable negative symptom relief, overall cognitive improvement and reduced motor dysfunction which is linked to it's potent interaction with 5-HT2C, 5-HT1D, and 5-HT1A receptors in brain tissue. Zepradon can bind moderately to norepinephrine and serotonin reuptake sites which may contribute to its antidepressant and anxiolytic activity. Patient's taking ziprasidone will likely experience a lower incidence of orthostatic hypotension, cognitive disturbance, sedation, weight gain, and disruption in prolactin levels since ziprasidone has a lower affinity for histamine H1, muscarinic M1, and alpha1-adrenoceptors.

Dosage

Zepradon dosage

Schizophrenia:

• Adult: Initially, 20 mg bid, increase if necessary at intervals of not
• Elderly: Lower initial dose and slower titration.

Acute mixed or manic episodes in bipolar disorder:

• Adult: Initially, 40 mg bid, increased to 60 mg or 80 mg bid on the 2nd day. Adjust subsequent doses according to patient's response and tolerance level. Maintenance treatment of bipolar I disorder (adjunctive therapy to either lithium or valproate): Continue at the same dosage on which the patient was initially stabilised within 40-80 mg bid.
• Elderly: Lower initial dose and slower titration.

Should be taken with food.

Side Effects

Somnolence, rash or urticaria, GI disturbances, dizziness, flu-like symptoms, HTN, headache, agitation, confusion, dyspnoea, orthostatic hypotension, increased prolactin levels, wt gain, sexual dysfunction, extrapyramidal symptoms, tardive dyskinesia, hyperglycaemia. Rarely, cholestatic jaundice, hepatitis, seizures, leucopenia, neutropenia, thrombocytopenia, hyperlipidaemia.

Toxicity

The most common adverse reactions reported with ziprasidone include somnolence, respiratory tract infections, extrapyramidal symptoms, dizziness, akathisia, abnormal vision, asthenia, vomiting, headache and nausea.

Precaution

Patient with history of seizures or conditions that lower the seizure threshold, CV or cerebrovascular disease, conditions which predispose to hypotension. Renal impairment. Elderly with dementia-related psychosis. Pregnancy and lactation.

Interaction

May antagonise effects of levodopa and dopaminergics. May enhance effects of other CNS depressants and certain antihypertensives. Altered metabolism with CYP3A4 inducers (e.g. carbamazepine), and inhibitors (e.g. ketoconazole).

Food Interaction

• Avoid alcohol.
• Take with food.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Zepradon Cholesterol interaction

[Moderate] Atypical antipsychotic drugs have been associated with undesirable alterations in lipid levels.

While all agents in the class have been shown to produce some changes, each drug has its own specific risk profile.

Before or soon after initiation of antipsychotic medication, obtain a fasting lipid profile at baseline and monitor periodically during treatment.

Zepradon Drug Interaction

Major: escitalopram, fluoxetine, quetiapine, topiramate, lisdexamfetamine, sertralineModerate: aripiprazole, duloxetine, clonazepam, lamotrigine, lurasidone, lithium, pregabalin, albuterol, cariprazine, alprazolamUnknown: amphetamine / dextroamphetamine, omega-3 polyunsaturated fatty acids, cyanocobalamin, cholecalciferol

Zepradon Disease Interaction

Major: dementia, acute alcohol intoxication, CNS depression, NMS, tardive dyskinesia, QT interval prolongationModerate: depression, aspiration, seizure, hematologic abnormalities, hyperglycemia/diabetes, hypotension, lipid alterations, priapism, weight gain, hyperprolactinemia, liver disease, parkinsonism

Volume of Distribution

The mean apparent volume of distribution of Zepradon is 1.5 L/kg.

Elimination Route

In the absence of food, ziprasidone's oral bioavailability is 60%, and absorption may reach 100% if ziprasidone is taken with a meal containing at least 500 kcal. The difference in bioavailability has little to do with the fat content of the food and appears to be related to the bulk of the meal since more absorption occurs the longer ziprasidone remains in the stomach.

Half Life

The half life of ziprasidone is 6-7 hours.

Clearance

The mean apparent systemic clearance is 7.5 mL/min/kg.

Elimination Route

Zepradon is extensively metabolized after oral administration with only a small amount excreted in the urine (<1%) or feces (<4%) as unchanged drug.

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.

Contraindication

Patient with history of QT prolongation or cardiac arrhythmias, recent acute MI or decompensated heart failure. Concurrent use with other drugs known to prolong the QT interval.

Acute Overdose

Symptoms: Minimal sedation, slurred speech, transitory HTN, extrapyramidal symptoms, somnolence, tremor, anxiety. Management: Establish and maintain an airway, ensure adequate oxygenation and ventilation. Consider admin of activated charcoal together with a laxative, gastric lavage (after intubation for unconscious patient); established IV access. Treat hypotension and circulatory collapse with IV fluids. In case of severe extrapyramidal symptoms, anticholinergic medication should be given.

Storage Condition

Store between 15-30° C.

Innovators Monograph

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