Perphenazine Disease Interactions

Antipsychotic drugs are not approved for the treatment of patients with dementia-related psychosis. Older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death; although the causes were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. A causal relationship with antipsychotic use has not been established. In controlled trials in older patients with dementia-related psychosis, patients randomized to risperidone, aripiprazole, and olanzapine had higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, compared to patients treated with placebo.

Perphenazine is contraindicated in patients with suspected or established subcortical brain damage, with or without hypothalamic involvement. Perphenazine can interfere with thermoregulatory mechanisms, and a hyperthermic reaction with temperatures in excess of 40C (104F) may occur in such patients, sometimes not until 14 to 16 hours after drug administration.

The manufacturer considers the use of perphenazine to be contraindicated in patients with preexisting liver damage. Phenothiazines are extensively metabolized by the liver and may accumulate in patients with hepatic impairment.

Phenothiazines are contraindicated in the presence of large amounts of central nervous system depressants such as alcohol. The risk of suicide and the danger of overdose may be increased in patients who use alcohol excessively. Phenothiazines should be used with caution in patients experiencing alcohol withdrawal.

The use of phenothiazines is contraindicated in comatose patients and patients with severe central nervous system depression. Phenothiazines may potentiate the CNS and respiratory depression in these patients.

Phenothiazines may cause hematologic toxicity. In patients with preexisting blood dyscrasias, bone marrow suppression, or a history of drug-induced leukopenia or neutropenia, phenothiazines should not be used or are contraindicated. Complete blood counts should be regularly monitored in patients with risk factors for blood dyscrasias. If white blood cell counts indicate cellular depression, discontinue treatment and institute appropriate therapy.

Phenothiazines may cause hypotension. Patients with pheochromocytoma, cerebral vascular or renal insufficiency, cardiovascular disease, or a severe cardiac reserve deficiency (e.g., mitral insufficiency) may be more prone to hypotensive reactions. Close monitoring is recommended during treatment if used in at-risk patients; some products may be contraindicated (e.g., thioridazine). Large doses and parenteral administration should be used cautiously, or avoided, in patients with impaired cardiovascular systems.

Therapy with phenothiazines should be administered cautiously or are contraindicated in patients with preexisting liver disease or with a history of jaundice due to phenothiazine hypersensitivity. Patients with a history of hepatic encephalopathy due to cirrhosis may have increased sensitivity to the central nervous system effects of some phenothiazines (e.g., chlorpromazine). Treatment should be discontinued if jaundice occurs.

The chronic use of phenothiazines is associated with persistent elevations in prolactin levels. The clinical significance in patients with a history of breast cancer is unknown and should be considered prior to therapy; approximately one-third of human breast cancers are thought to be prolactin-dependent. Chronic administration of neuroleptic drugs has been associated with mammary tumorigenesis in animal studies; however, evidence is inconclusive in humans.

Therapy with phenothiazines may precipitate or aggravate a potentially fatal symptom complex known as neuroleptic malignant syndrome (NMS). Treatment should not be initiated in patients with active NMS, and should be immediately discontinued if currently administered in such patients. In patients with a history of NMS, introduction or reintroduction of phenothiazines should be carefully considered, since NMS may recur.

Phenothiazines should be used with caution in patients with renal dysfunction. Patients with renal insufficiency may be more prone to hypotension. Periodic renal function tests are recommended for all patients during prolonged therapy.

Phenothiazines can lower the seizure threshold. Caution is recommended during administration in patients with a history of convulsive disorders or EEG abnormalities. Anticonvulsant therapy should be maintained or adequately adjusted during phenothiazine treatment.