Although loxapine differs chemically from the phenothiazines and all adverse reactions of the phenothiazines have not been reported with loxapine, the possibility that they may occur should be considered. Adverse effects of loxapine and the phenothiazines are numerous and may involve nearly all organ systems; however, they are usually reversible when dosage is reduced or the drug is discontinued. Some adverse effects may be attributed to the actions of the drug on the central and autonomic nervous systems or the cardiovascular system, whereas others are hypersensitivity reactions. Unexpected deaths have been reported during phenothiazine therapy. In some patients, cardiac arrest or asphyxia resulting from failure of the cough reflex appeared to be the cause of death. In other cases, the cause of death could not be determined nor definitely attributed to phenothiazine therapy.
The most frequent adverse effect of loxapine is transient initial drowsiness to which tolerance usually develops with continuing therapy. Drowsiness may also occur when the dosage of loxapine is increased. Extrapyramidal syndromes such as akathisia or a parkinsonism-like condition, manifested by rigidity, tremor, excessive salivation, and/or masked facies, occur frequently during loxapine therapy; the frequency of extrapyramidal effects may be greater with IM administration of the drug (IM dosage form of loxapine hydrochloride no longer commercially available in the US) than with oral administration. Other adverse neuromuscular effects include dystonias such as oculogyric crises, tongue protrusion, opisthotonos or spasms of the neck and facial muscles, or dyskinetic reactions such as choreoathetoid movements. Patients who have experienced extrapyramidal syndromes in association with other antipsychotic drugs will probably react similarly to loxapine. Neuromuscular symptoms including extrapyramidal syndromes can be controlled by administering an anticholinergic antiparkinsonian drug and/or reducing dosage or withdrawing loxapine.
Because use of antipsychotic agents, including loxapine, may be associated with tardive dyskinesia (a syndrome of potentially irreversible, involuntary, dyskinetic movements), loxapine should be prescribed in a manner that is most likely to minimize the occurrence of this syndrome. Chronic antipsychotic treatment generally should be reserved for patients who suffer from a chronic illness that is known to respond to antipsychotic agents, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the lowest dosage and the shortest duration of treatment producing a satisfactory clinical response should be sought, and the need for continued treatment should be reassessed periodically. For additional information on tardive dyskinesia,
Neuroleptic malignant syndrome (NMS) may occur in patients receiving loxapine or other antipsychotic therapy. NMS is potentially fatal and requires immediate discontinuance of the drug and intensive symptomatic and supportive care. For additional information on NMS, .
Adverse effects attributed to the action of loxapine on the autonomic nervous system include dryness of the mouth, constipation, blurred vision, and nasal congestion. Adverse cardiovascular effects may include tachycardia, hypotension which is usually mild and transient, or, rarely, hypertension. A few cases of minor ECG changes similar to those seen with phenothiazine administration have been observed in patients receiving loxapine; however, these ECG changes have not been definitely attributed to loxapine.
Insomnia, dizziness, lethargy, lightheadedness, syncope, headache, ataxia, weakness, confusion, nausea, and vomiting may also occur during loxapine therapy. Other adverse effects which have occurred in a few patients include tinnitus, paresthesia, polydipsia, ptosis, dyspnea, hyperpyrexia, flushed facies, and weight gain or weight loss.
Dermatitis, facial edema, pruritus, and seborrhea have been observed during loxapine therapy. Rashes have also occurred in a few patients during hot weather. The possibility that loxapine may cause phototoxicity and/or photosensitivity reactions should be considered. Skin pigmentation and ocular changes have occurred in some patients receiving long-term therapy with some phenothiazines. Although these adverse effects have not yet been reported in patients receiving loxapine, patients receiving the drug should be carefully observed for pigmentary changes, and periodic ophthalmologic examinations (including slit-lamp examinations) should be performed in patients on prolonged loxapine therapy.
In clinical trial and/or postmarketing experience, leukopenia, neutropenia, and agranulocytosis have been temporally related to antipsychotic agents. Possible risk factors for leukopenia and neutropenia include preexisting low leukocyte count and a history of drug-induced leukopenia and neutropenia.(See Cautions: Precautions and Contraindications.)
Galactorrhea occurred in one patient receiving loxapine, and the possibility of other endocrine abnormalities should be considered. Transitory fluctuations in leukocyte counts, eosinophilia, and mildly elevated serum alkaline phosphatase concentrations without clinical symptoms have occurred rarely. Cholestatic jaundice or adverse hematologic effects (including hemolytic anemia, thrombocytopenia, and pancytopenia) have been reported in patients receiving other antipsychotic agents, and these possibilities should be considered.