Loxapine , dosing

L The answer is a. (Hardman, p 922) Lactulose is a synthetic disaccharide (galactose-fructose) that is not absorbed. In moderate doses, it acts as a laxative. In higher doses, it is capable of binding ammonia and other toxins that form in the intestine in severe liver deficiency and that are believed to cause the encephalopathy. Loperamide is an antidiarrheal opioid lorazepam is a CNS depressant loxapine is a heterocyclic antipsychotic. 

Loxapine (Loxitane). Loxapine is a medium potency antipsychotic, and it has several interesting features. First, it is chemically very similar to clozapine, the first of the atypical antipsychotics. In the test tube, loxapine actually behaves more like an atypical antipsychotic (more on that later), but when patients are treated with it, loxapine acts more like a traditional typical antipsychotic. A second point of interest is that loxapine is actually the major active metabolite of the antidepressant amoxa-pine (Ascendin). As a result, one can use a single medication (amoxapine) to treat both depression and psychosis. In practice, however, the use of what is essentially a fixed dose combination medication should be avoided. Using amoxapine does not allow separate adjustment of the antipsychotic and antidepressant, and most importantly, amoxapine is the only antidepressant associated with the risk of TD. 

As a medium potency antipsychotic, its dose and side effects are intermediate. Sometimes, it may be better to use a medium potency antipsychotic for patients who are especially sensitive to the EPS of high potency antipsychotics. Young, wellmuscled males are particularly prone to EPS and so loxapine may be a good choice for those individuals. 

Several studies have evaluated the use of low doses of the typical antipsychotics. These include studies of high potency antipsychotics such as haloperidol, medium potency antipsychotics such as loxapine, and low potency antipsychotics such as chlorpromazine and thioridazine. In general, the studies have shown that antipsychotics reduce impulsivity and protect from psychotic decompensation. 

LOXAPINE Individualize dosage. Administer 2 to 4 times/day in divided doses. 

Haloperidol is the best-studied antipsychotic medication in children and adolescents with schizophrenia. In a double-blind, placebo- and active-controlled study, haloperidol (2 to 16 mg per day) and loxapine (10 to 200 mg per day) were equally effective and superior to placebo ( 168). This finding was replicated in a placebo-controlled, crossover study of haloperidol (doses of 0.5 to 3.5 mg per day or 0.02 to 0.12 mg/kg per day) in children 5.5 to 12 years of age ( 169). In this study, haloperidol was more effective than placebo in reducing ideas of reference, persecutory ideas, hallucinations, and thought disorder. 

Dose. Usually the equivalent of 20 to 100 mg of loxapine daily maximum of 250 mg daily. 

Sedation is usually dose-dependent and may not be experienced at low doses where loxapine may function as an atypical antipsychotic (e.g., <50 mg/day especially 5-25 mg/day)... 

Binding studies, PET studies, and anecdotal clinical observations suggest that loxapine may be atypical at lower doses (perhaps 5-30 mg/day) but further studies needed... 

To augment partial responders to an atypical antipsychotic, consider doses of loxapine as low as 5-60 mg/day, but use full doses if necessary... 

When initiating therapy with an atypical antipsychotic in an acute situation, consider short-term intramuscular loxapine to lead in to orally administered atypical e.g., initiate oral dosing of an atypical... 

When using loxapine to top-up previously stabilized patients now decompensating, may use loxapine as single 25-50 mg doses as needed intramuscularly or as oral liquid or tablets... 

Theoretically, loxapine should have antidepressant actions, especially at high doses, but no controlled studies... 

For previously stabilized patients with breakthrough agitation or incipient decompensation, top-up the atypical antipsychotic with as-needed intramuscular or oral single doses of loxapine... 

The selected sample of 204 patients receiving typical neuroleptics included 58 Caucasian, 135 African American, and 11 Hispanic patients. Eight neuroleptics were taken by these patients chlor-promazine, thioridazine, thiothixine, loxapine, haloperidol, flu-phenazine, perphenazine, and trifluoperazine. A haloperidol-equivalent dose was chosen as the basis of comparison for all eight typical neuroleptics included in this study. All 11 Hispanics received haloperidol. The results of this study are shown in Table 5-3. 

Carbamazepinewasfound to decrease the plasma levels of phenothiazines by as much as 50% (described with chlorpromazine, perphenazine, and fluphenazine). It has been reported to decrease the serum levels of clozapine by about60-85% due to its hepatic cytochrome P450 (CYP) enzyme-inducing properties. Loxapine may induce carbamazepine metabolism. Carbamazepine has been shown to reduce the plasma levels of risperidone by as much as 50%, while it increases olanzapine clearance by 44% and reduces its half-life by 20%. Carbamazepine increases aripiprazole metabolism through CYP3A4 induction. Thus, the aripiprazoie dose should be doubled. 

Systematic Reviews Anew formulation of inhaled loxapine developed for agitation may only be used in hospitals where patients are monitored for bronchospasm for 1 h post dose (FDA-mandated REMS) [161 The risk of pulmonary... 

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