Mesoridazine , dosing

Mesoridazine (Serentil). This antipsychotic has effects similar to its other low potency counterparts. It should also be started at a low dose and gradually increased. 

Ziprasidone, pimozide, mesoridazine, and thioridazine have been shown to prolong the QT interval, and drugs with this potential have been associated with torsade de pointes-type arrhythmias and sudden death. Perform a baseline ECG and measure serum potassium and magnesium before initiation of treatment and periodically during treatment, especially during a period of dose adjustment. Patients with QT interval over 450 msec should not receive mesoridazine or thioridazine. Avoid ziprasidone in patients with histories of significant cardiovascular illness (eg. 

Initiate therapy of these drugs, particularly those with a narrow therapeutic index, at the lowest effective dose. Interaction is likely to be important with substrates for which CYP2D6 is considered the only metabolic pathway (e.g. hydrocodone, oxycodone, desipramine, paroxetine, chlorpheniramine, mesoridazine, alprenolol, amphetamines, atomoxetine)... 

Dose. The equivalent of 150 mg of mesoridazine daily up to 400 mg daily has been given. 

Disposition in the Body. Readily absorbed after oral administration. It is metabolised mainly by sulphoxidation to give the side-chain sulphoxide (mesoridazine), the side-chain sulphone (sulforidazine), both of which are active, and the ring sulphoxide and sulphone A-demethylation also occurs. Other metabolites are produced by combinations of these metabolic reactions. It is metabolised in the liver, secreted in the bile, and excreted mainly in the faeces. Less than about 10% of a dose is excreted in the... 

The effects of mesoridazine on the QTc interval are dose-dependent, so start low and go slow while carefully monitoring QTc interval... 

Because mesoridazine may dose-dependenfly prolong QTc interval, use wifh caufion in pafienfs who have bradycardia or who are faking drugs fhaf can induce bradycardia (e.g., befa blockers, calcium channel blockers, clonidine, digifalis)... 

Mesoridazine produces a dose-dependent prolongation of QTc Interval, which may be enhanced by the existence of bradycardia, hypokalemia, congenital or acquired long QTc Interval, which should be evaluated prior to administering mesoridazine... 

Phenothiazine derivatives cause postural or orthostatic hypotension. This may be more pronounced in patients with reduced vascular volume resulting from acute hemorrhage or dehydration, and when used with diuretic agents. Hypotension is more frequent with phenothiazine derivatives having either an aliphatic substitution on NIO (e.g., chlorpromazine) or a piperidine substitution on NIO (e.g., mesoridazine or thioridazine). It occurs less frequently with compounds containing a piperazine substitution (e.g., trifluoperazine). The hypotension is due to direct vasodilation and an alpha-adrenergic-receptor-blocking effect. The pressor effects of epinephrine can be reduced, blocked, or reversed by appropriate doses of chlorpromazine. 

In a large study in patients taking phenytoin with various phenothiazines (chlorpromazine, tMoridazine or mesoridazine), phenytoin levels were decreased by 44% when the phenothiazines were started, and by 33% when the phenothiazine dose was increased. A number of patients experienced an increased frequency of seizures. In patients who had these phenothiazines discontinued or the dosage decreased, the phenytoin levels increased by 55% and 71%, respectively, and toxic levels occurred in some patients. ... 

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