Psychotropic Medication Audit Criteria and Guidelines

Chlorpromazine (Thorazine ®) Fluphenazine (Prolixin ®) Haloperidol (Haldol ®) Loxapine (Loxitane ®) Perphenazine (Trilafon ®) Thiothixene (Navane ®) Trifluoperazine (Stelazine ®) PEFC Approved: July 2021

Indications Label: ● Chlorpromazine: agitation/aggression (severe, acute) associated with psychiatric disorders; behavioral problems; hyperactivity; schizophrenia ● Fluphenazine: psychotic disorders ● Haloperidol: behavioral disorders, nonpsychotic; hyperactivity; schizophrenia; Tourette syndrome, management of tics ● Loxapine: schizophrenia ● Perphenazine: schizophrenia ● Thiothixene: schizophrenia ● Trifluoperazine: schizophrenia

Off label: • Chlorpromazine: bipolar disorder

Black Box Warning Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration, 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5% compared with a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational

1 Texas Health and Human Services ● hhs.texas.gov Antipsychotics, Typical studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Antipsychotics are not approved for the treatment of patients with dementia-related psychosis.

Contraindications ● Chlorpromazine: comatose states; concomitant use with large amounts of CNS depressants (e.g., alcohol, barbiturates, opioids); hypersensitivity to chlorpromazine, or any component of the formulation (cross-sensitivity between phenothiazines may occur) ● Fluphenazine: severe CNS depression; coma; patients receiving large doses of hypnotics; suspected or established subcortical brain damage; blood dyscrasias; hepatic disease; hypersensitivity to fluphenazine, or any component of the formulation (cross-sensitivity between phenothiazines may occur) ● Haloperidol: coma; severe CNS depression; Parkinson disease; dementia with Lewy bodies; hypersensitivity to haloperidol, or any component of the formulation ● Loxapine: comatose or severe drug-induced states (e.g., alcohol, barbiturates, opioids); known hypersensitivity to dibenzoxazepines, or any component of the formulation ● Perphenazine: severe CNS depression, coma, patients receiving large doses of CNS depressants (e.g., barbiturates, alcohol, opioids, analgesics, antihistamines); blood dyscrasias; bone marrow depression; hepatic disease; patients with suspected or established subcortical brain damage, with or without hypothalamic damage; hypersensitivity to perphenazine, or any component of the formulation ● Thiothixene: comatose states; CNS depression from any cause; circulatory collapse, blood dyscrasias; hypersensitivity to thiothixene, or any component of the formulation ● Trifluoperazine: comatose or generally depressed states because of CNS depressants; bone marrow depression, blood dyscrasias; hepatic disease; hypersensitivity to trifluoperazine, phenothiazines, or any component of the formulation

Warnings and Precautions ● Esophageal dysmotility/aspiration ● Extrapyramidal symptoms ● Neuroleptic malignant syndrome

2 Texas Health and Human Services ● hhs.texas.gov Antipsychotics, Typical

● Falls ● Discontinuation of therapy ● Hyperprolactemia ● Anticholinergic effects ● Seizure disorder ● Blood dyscrasias, hematologic effects ● Ophthalmic effects (except haloperidol)

● Chlorpromazine: dementia, cardiovascular disease, respiratory disease, Reye syndrome, aspiration of vomit, temperature regulation, myasthenia gravis, hypotension, altered cardiac conduction, benzyl alcohol and derivatives ● Fluphenazine: dementia, hepatic events, altered cardiac conduction, orthostatic hypotension, temperature regulation, cardiovascular disease, CNS depression, benzyl alcohol and derivatives ● Haloperidol: dementia, altered cardiac conduction, Parkinson disease, cardiovascular disease, bipolar disorder, thyroid dysfunction, myasthenia gravis, orthostatic hypotension, temperature regulation ● Loxapine: increased mortality in elderly patients with dementia-related psychosis, behavioral complications, seizures, antiemetic effect ● Perphenazine: depression, orthostatic hypotension, antiemetic effects, temperature regulation, respiratory disease, altered cardiac conduction, cardiovascular disease, poor metabolizers ● Thiothixene: increased mortality in elderly patients with dementia-related psychosis, sudden death, antiemetic effect, body temperature regulation, hepatic effects ● Trifluoperazine: hepatic effects, cardiovascular disease, orthostatic hypotension, temperature regulation, altered cardiac conduction, antiemetic effects

Adverse Reactions Side Effects Which Require Medical Attention ● Anticholinergic effects ● Visual changes ● Extrapyramidal side effects (dystonia, pseudo-Parkinsonism) ● Akathisia ● Tardive dyskinesia ● Hypotension ● Rashes, photosensitivity, altered pigmentation ● Early signs of agranulocytosis effects (fever, sore throat, weakness) ● Galactorrhea ● Amenorrhea

3 Texas Health and Human Services ● hhs.texas.gov Antipsychotics, Typical

● Poikilothermia ● Fluctuation vital signs ● Altered consciousness ● Signs and symptoms of neuroleptic malignant syndrome

Drug Interactions of Major Significance

See: Indiana Univ Drug Interaction Table

See: Lexicomp, Micromedex for more information

Special Populations ● Pediatrics/Adolescents  Chlorpromazine, haloperidol and perphenazine: See “Psychotropic Medication Utilization Parameters for Children and Youth in Texas Public Behavioral Health (6th Version)” for specific details.  Fluphenazine, thiothixene, and trifluoperazine: Not considered in “Psychotropic Medication Utilization Parameters for Children and Youth in Texas Public Behavioral Health (6th Version)”  Loxapine: Safety and efficacy have not been established in pediatric patients. ● Geriatric  Titrate slowly and monitor carefully ● Renal  Use with caution, no dosage adjustment necessary ● Hepatic  Use with caution: chlorpromazine, haloperidol, loxapine, thiothixene  Contraindicated: fluphenazine, perphenazine, trifluoperazine ● Hemodialysis  Not dialyzable, no dosage adjustment necessary ● Pregnancy and Breastfeeding  Review product-specific labeling. Consider risks/benefits in reviewing medication-specific labeling

Patient Monitoring Parameters Baseline Tests: ● Pregnancy test (females) ● Waist circumference and BMI (weight in lbs x 703)/height2 in inches ● FPG or HbgA1c ● Fasting lipid profile within 30 days of initiation if not done within last year ● EPS evaluation (exam for rigidity, tremor, akathisia)

4 Texas Health and Human Services ● hhs.texas.gov Antipsychotics, Typical

● TD assessment ● CMP ● CBC

Ongoing Tests: ● Pregnancy test (females) as clinically indicated ● BMI and waist circumference monthly for 6 months then quarterly when dose is stable ● FPG or HbgA1c repeat 3-4 months after starting then at least annually ● Fasting lipid panel 3-4 months after initiating a new antipsychotic and at least annually if lipid levels are in normal range; repeat every 6 months if LDL is > 130 mg/dL ● EPS evaluation weekly after initiation & dose increases, continue 2 weeks after last increase ● TD assessment every 3 months and as clinically indicated ● CMP, CBC as clinically indicated ● Inquiry for symptomatic prolactin elevation yearly (quarterly during 1st year for antipsychotics associated with increased prolactin) ● Prolactin level yearly if symptoms of prolactin elevation (e.g. gynecomastia, amenorrhea) ● Vision questionnaire and ocular evaluation yearly, ocular eval. every 2 years if ≤ 40 years old ● Determine if metabolic syndrome criteria (3 of the 5 criteria) are met 3-4 months after initiating a new antipsychotic medication and at least annually thereafter

Dosing ● See HHSC Psychiatric Drug Formulary for dosage guidelines. ● Exceptions to maximum dosage must be justified as per medication rule.

5 Texas Health and Human Services ● hhs.texas.gov