CHLORPROMAZINE

brands

Class

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

CHLORPROMAZINE commonly prescribed for

(Bold for FDA approved)

How CHLORPROMAZINE works

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis and improving other behaviors

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

How long until CHLORPROMAZINE works

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

• Immediate and short-term (a few hours) relief of severe behavioral problems if given during an acute exacerbation on a prn (as needed) basis (most common use in children)

• Actions on nausea and vomiting are immediate

Notable Side Effects

• Neuroleptic-induced deficit syndrome

• Akathisia

• Priapism

• Drug-induced parkinsonism

• Galactorrhea, amenorrhea

• Dizziness, sedation, impaired memory

• Dry mouth, constipation, urinary retention, blurred vision

• Decreased sweating

• Sexual dysfunction

• Hypotension, tachycardia, syncope

• Weight gain

• Tardive dyskinesia

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

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

problematic

What to do about CHLORPROMAZINE side effects

• Wait

• Wait

• Wait

• For drug-induced parkinsonism, add an anticholinergic agent

• Beta blockers, benzodiazepines, or serotonin 2A antagonists (e.g., mirtazapine, cyproheptadine) 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

• 200–800 mg/day

Dosage Forms

• Tablet 10 mg, 25 mg, 50 mg, 100 mg, 200 mg

• Capsule 30 mg, 75 mg, 150 mg (not in USA)

• Ampoule 25 mg/mL; 1 mL, 2 mL

• Liquid 10 mg/5 mL (discontinued in USA)

• Suppository 25 mg, 100 mg (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

Cardiac Impairment

• Cardiovascular toxicity can occur, especially orthostatic hypotension

Elderly

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

• Often do not tolerate sedating actions of chlorpromazine

• 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

• Can be used cautiously in children or adolescents over age 1 with severe behavioral problems

• Oral – 0.25 mg/lb every 4–6 hours as needed; rectal – 0.5 mg/lb every 6–8 hours as needed; intramuscular – 0.25 mg/lb every 6–8 hours as needed; maximum 40 mg/day (under 5), 75 mg/day (5–12)

• Do not use if patient shows signs of Reye’s syndrome

• 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

• Chlorpromazine should generally not be used during the first trimester

• Chlorpromazine should be used during pregnancy only 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

• Some drug is found in mother’s breast milk

• Effects on infant have been observed (dystonia, tardive dyskinesia, sedation)

• Recommended either to discontinue drug or bottle feed