Fraxidep

Uses

Different types of anxiety, depression & apathy. These include- psychogenic depression, depressive neuroses, masked depression, psychosomatic affections accompanied by anxiety and apathy, menopausal depressions, dysphoria and depression in alcoholics and drug-addicts.

Fraxidep is also used to associated treatment for these conditions: Chronic Schizophrenia, Depression, Dysphoria, NeurastheniaAnxiety, Depression, Schizophrenia and other psychotic disorders

How Fraxidep works

The mechanism of action of flupentixol is not completely understood. The antipsychotic actions are mainly thought to arise from cis(Z)-flupentixol, the active stereoisomer, acting as an antagonist at both dopamine D₁ and D₂ receptors with equal affinities. Schizophrenia is a mental illness characterized by positive (such as hallucinations and delusions) and negative (such as affect flattening and apathy) symptoms. While several neurotransmitter systems are implicated in the pathophysiologic processes leading to the development of symptoms, the dopamine and glutamate systems have been extensively studied. It is generally understood that positive symptoms of schizophrenia arise from a dysregulated striatal dopamine pathway, leading to hyperstimulation of D₂ receptors. Many antipsychotic agents work by blocking D₂ receptors as antagonists; similarly, cis(Z)-flupentixol, the active stereoisomer, is an antagonist at D₂ receptors. However, there is now evidence that antipsychotic agents can work by blocking other dopamine receptor subtypes, such as D₁, D₃, or D₄ receptors. One study showed that cis(Z)-flupentixol is an antagonist at both dopamine D₁ and D₂ receptors with equal affinities, and binds to D3 and D4 receptors with lower affinities. It also binds to alpha-1 adrenoceptors. Antidepressant effects of flupentixol are understood to be mediated by antagonism at 5-HT_2A receptors, which are commonly downregulated following repeated antidepressant treatment. Flupentixol also binds to 5-HT_2C receptors.

Dosage

Fraxidep dosage

Adults: In general 2 tablets per day, morning and at midday. For the severe cases, the amount of the morning dose can be increased to 2 tablets.

Elderly patients: One tablet in the morning.

Maintenance dose: 1 tablet in the morning. In cases of insomnia or severe restlessness additional treatment with a sedative in acute phase is recommended.

Side Effects

In the recommended doses side effects are rare. These could be transient restlessness and insomnia.

Toxicity

The oral LD₅₀ is 423 mg/kg in mice and 791 mg/kg in rats. The intravenous LD₅₀ is 37 mg/kg in rats.[L31873]

Flupentixol overdose is characterized by sedation, frequently preceded by extreme agitation, excitement, confusion, somnolence, coma, convulsions, and hyperthermia or hypothermia. Extrapyramidal symptoms or respiratory and circulatory collapse may be observed. ECG changes, QT prolongation, Torsades de Pointes, cardiac arrest and ventricular arrhythmias have been reported from the combined use of drugs known to affect the heart with large doses of flupentixol. In case of overdose, symptomatic treatment should be initiated with airway management. In case of severe hypotension, epinephrine should not be used: instead, intravenous vasopressor drugs, such as levarterenol, can be used. Antiparkinsonian medication should be administered only if extrapyramidal symptoms develop. Gastric lavage should be initiated in the case of flupentixol tablet overdose. Further injections of flupentixol should be discontinued in case of an intramuscularly-administered drug overdose until the patient shows signs of relapse, in which the dosage can subsequently be decreased.

Neuroleptic malignant syndrome is associated with neuroleptic drugs, which should be responded to with immediate discontinuation of the drug and initiation of symptomatic treatment and medical monitoring.

Precaution

If previously the patient has been treated with tranquilizers with sedative effect these should be withdrawn gradually.

Interaction

Flupentixol-melitracen may enhance the response to alcohol, barbiturates and other CNS depressants. Simultaneous administration of MAO-inhibitors may cause hypertensive crises. Neuroleptics and thymoleptics reduce the antihypertensive effect of guanethidine and similar acting compounds and thymoleptics enhance the effects of adrenaline and noradrenaline.

Volume of Distribution

The apparent volume of distribution is about 14.1 L/kg. Following administration, the highest levels of flupentixol are found in the lungs, liver, and spleen. Lower concentrations of the drug are found in the blood and brain.

Elimination Route

Following oral administration, flupentixol is readily absorbed from the gastrointestinal tract, with oral bioavailability of about 40%. T_max ranges from three to eight hours. Steady-state plasma levels are achieved in about seven days and following once-daily oral administration of 5 mg flupentixol, the mean minimum steady-state level was about 1.7 ng/mL (3.9 nmol/L).

From the site of intramuscular injection, esterified flupentixol diffuses slowly from the oil solution and is slowly released into the extracellular fluid and the circulation to be distributed to different tissues. Peak drug concentrations are reached between four and seven days following intramuscular injection. Intramuscularly administered flupentixol is detectable in the blood three weeks after injection and reaches steady-state concentrations after about three months of repeated administration.

Half Life

The elimination half-life is about 35 hours following oral administration and three weeks following intramuscular administration.

Clearance

Following oral administration, the mean systemic clearance is about 0.29 L/min.

Elimination Route

Fecal excretion is more predominant than renal excretion. In the feces, flupentixol is recovered in the feces mainly as the unchanged form, as well as its lipophilic metabolites, such as dealkyl-flupentixol. Flupentixol is recovered in the urine as the unchanged form as well as its hydrophilic sulfoxide and glucuronide metabolites.

Pregnancy & Breastfeeding use

Flupentixol and Melitracen should preferably not be given during pregnancy and lactation.

Contraindication

The immediate recovery phase after myocardial infarction. Defects in bundle-branch conduction. Untreated narrow angle glaucoma. Acute alcohol, barbiturate and opiate intoxication. Flupentixol and Melitracen should not be given to patients who have received a MAO inhibitor within two weeks. Not recommended for excitable patient since its activating effect may lead to exaggeration of these characteristics.

Special Warning

Children: This tablet is not for paediatric use.

Storage Condition

Should be stored at a cool and dry place, protect from light and moisture.

Innovators Monograph

You find simplified version here Fraxidep