Class

• Neuroscience-based Nomenclature: dopamine receptor antagonist (D-RAn)
• Conventional antipsychotic (neuroleptic, phenothiazine, dopamine 2 antagonist, antiemetic)

PERPHENAZINE commonly prescribed for

(Bold for FDA approved)

How PERPHENAZINE works

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis

• Combination of dopamine D2, histamine H1, and cholinergic M1 blockade in the vomiting center may reduce nausea and vomiting

How long until PERPHENAZINE works

• Psychotic symptoms can improve within 1 week, but may take several weeks for full effect on behavior

• Injection: initial effect after 10 minutes, peak after 1–2 hours

• Actions on nausea and vomiting are immediate

Notable Side Effects

• Neuroleptic-induced deficit syndrome

• Akathisia

• Drug-induced parkinsonism

• Tardive dyskinesia

• Risk of potentially irreversible involuntary dyskinetic movements may increase with cumulative dose and treatment duration

• Galactorrhea, amenorrhea

• Dizziness, sedation

• Dry mouth, constipation, urinary retention, blurred vision

• Decreased sweating

• Sexual dysfunction

• Hypotension, tachycardia, syncope

• Weight gain

Life Threatening Side Effects

• Rare neuroleptic malignant syndrome may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability with elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure

• Rare jaundice, agranulocytosis

• Rare seizures

• As a class, antipsychotics are associated with an increased risk of death and cerebrovascular events in elderly patients with dementia; not approved for treatment of dementia-related psychosis

weight gain

common

sedation

common

What to do about PERPHENAZINE side effects

• Wait

• Wait

• Wait

• For drug-induced parkinsonism, add an anticholinergic agent

• Beta blockers, benzodiazepines, or serotonin 2A antagonists may reduce akathisia

• Reduce the dose

• For sedation, give at night

• Switch to an atypical antipsychotic

• Weight loss, exercise programs, and medical management for high BMIs, diabetes, dyslipidemia

• Metformin may help prevent or reverse antipsychotic-induced weight gain

usual dosage range

• Psychosis: oral: 12–24 mg/day; 16–64 mg/ day in hospitalized patients

• Nausea/vomiting: 8–16 mg/day oral, 5 mg intramuscularly

Dosage Forms

• Tablet 2 mg, 4 mg, 8 mg, 16 mg

• Injection 5 mg/mL (discontinued in USA)

long term use

• Should periodically reevaluate long-term usefulness in individual patients, but treatment may need to continue for many years

habit forming

• No

Renal Impairment

• Use with caution

Hepatic Impairment

• Use with caution; may not be recommended as long-term treatment because perphenazine may increase risk of further liver damage

Cardiac Impairment

• Cardiovascular toxicity can occur, especially orthostatic hypotension

Elderly

• Lower doses should be used and patient should be monitored closely

• Although conventional antipsychotics are commonly used for behavioral disturbances in dementia, no agent has been approved for treatment of elderly patients with behavioral symptoms of dementia such as agitation

• Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo, and also have an increased risk of cerebrovascular events

Children and Adolescents

• Not recommended for use in children under age 12

• Over age 12: if given intramuscularly, should receive lowest adult dose

• Generally consider second-line after atypical antipsychotics

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Controlled studies have not been conducted in pregnant women

• There is a risk of abnormal muscle movements and withdrawal symptoms in newborns whose mothers took an antipsychotic during the third trimester; symptoms may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty feeding

• Reports of drug-induced parkinsonism, jaundice, hyperreflexia, hyporeflexia in infants whose mothers took a phenothiazine during pregnancy

• Perphenazine should only be used during pregnancy if clearly needed

• Psychotic symptoms may worsen during pregnancy and some form of treatment may be necessary

• Atypical antipsychotics may be preferable to conventional antipsychotics or anticonvulsant mood stabilizers if treatment is required during pregnancy

Breast Feeding

• Unknown if perphenazine is secreted in human breast milk, but all psychotropics are assumed to be secreted in breast milk

• Recommended either to discontinue drug or bottle feed