Dosing and uses of Thorazine (chlorpromazine)
Adult dosage forms and strengths
tablet
- 10mg
- 25mg
- 50mg
- 100mg
- 200mg
injectable solution
- 25mg/mL
Schizophrenia, Psychotic Disorders
PO: 30-75 mg/day divided q6-12hr initially; maintenance: usually 200 mg/day (up to 800 mg/day in some patients; some patients may require 1-2 g/day)
IV/IM: 25 mg initially, followed PRN with 25-50 mg after 1-4 hours, then increased to maximum of 400 mg q4-6hr until patient is controlled; usual dosage 300-800 mg/day
Nausea & Vomiting
PO: 10-25 mg q4-6hr PRn
IV/IM: 25-50 mg q4-6hr PRn
Preoperative Apprehension
25-50 mg PO 2-3 hours before surgery
12.5-25 mg IM 1-2 hours before surgery
Intraoperative Sedation
12.5 IM q30min or 2 mg IV q2min; total dose not to exceed 25 mg
Intractable Hiccups
25-50 mg PO q6-8hr; if hiccups persist after 2-3 days of oral therapy, administer 25-50 mg IM q3-4hr; if symptoms persist, administer 25-50 mg by slow IV infusion with patient lying flat in bed; monitor Bp
Acute Intermittent Porphyria
25-50 mg PO q6-8hr
Migraine Headache (Off-label)
5-50 mg IV as single dose
Pediatric dosage forms and strengths
tablet
- 10mg
- 25mg
- 50mg
- 100mg
- 200mg
injectable solution
- 25mg/mL
Behavioral Disorders, Hyperactivity
<6 months: Safety and efficacy not established
>6 months: 50-100 mg/day PO/IM; 200 mg/day or more may be necessary for older hospitalized patients; for outpatients, may administer 0.55 mg/kg q4-6hr PRn
Nausea & Vomiting
<6 months: Safety and efficacy not established
>6 months: 0.5-1 mg/kg PO/IM q6-8hr PRn
Preoperative Apprehension
<6 months: Safety and efficacy not established
>6 months: 0.55 mg/kg PO/IM 1-2 hours before surgery
Thorazine (chlorpromazine) adverse (side) effects
Frequency not defined
Extrapyramidal symptoms
- Akathisia
- Dystonia
- Muscle stiffness
- Neuroleptic malignant syndrome (NMS; infrequent but serious)
- Parkinsonism
- Tardive dyskinesia
Common
- Anticholinergic effects
- Sedation
- Weight gain
- Erectile dysfunction
- Oligomenorrhea or amenorrhea
Less common
- Cerebral edema, orthostatic hypotension (after IM injection), tachycardia
- Agitation, anxiety, depression, dizziness, euphoria, headache, insomnia, poikilothermia, restlessness, weakness
- Anorexia, constipation, dyspepsia, ileus
- Lens opacities (prolonged use)
Uncommon
- ECG changes
- Photosensitivity
- Pruritus
- Galactorrhea
- Ejaculatory disorder
- Diarrhea
- Blood dyscrasia
Rare
- Seizure
- Priapism
- Cholestatic jaundice
Warnings
Black box warnings
Patients with dementia-related psychosis who are treated with antipsychotic drugs are at increased risk for death, as shown in short-term controlled trials; deaths in these trials appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature
This drug is not approved for treatment of patients with dementia-related psychosis
Contraindications
Hypersensitivity to phenothiazines
Coma, severe hypotension, severe central nervous system (CNS) depression, concurrent administration of large amounts of CNS depressants, subcortical brain damage, poorly controlled seizure disorder
Severe cardiovascular disease
Lactation
Cautions
Avoid using in children with suspected Reye syndrome
Use caution in glaucoma, prostatic hypertrophy, stenosing peptic ulcer disease (PUD), history of NMS, Parkinson disease, hypocalcemia, renal or hepatic impairment, history of severe reaction to insulin or electroconvulsive therapy (ECT), history of seizures, asthma, respiratory tract infection, cardiovascular disease, myelosuppression
Risk of extrapyramidal symptoms (EPS), NMS, hypotension
Significant hypotension may occur, especially with parenteral administraiton; hypotension may be particularly severe in patients with pheochromocytoma or mitral insufficiency; in case of severe hypotension, use norepinephrine or phenylepinephrine, and do not use epinephrine or dopamine
May alter cardiac conduction; life threatening arrhythmias reported with therapeutic doses of phenothiazines; may cause QT prolongation and subsequent torsade de pointes; avoid use in patients diagnosed or suspected congenital long QT syndrome
May cause anticholinergic effects; use caution in patients with paralytic ileus, gastrointestinal motility, urinary retention, xerostomia, or visual problems
Agranulocytosis, leukopenia, and neutropenia reported with antipsychotic use; periodic blood count assessment recommended in patients with history of risk factors, including history of drug-induced leuko/neutropenia or preexisting low WBC
Esophageal dysmotility and aspiration reported with antipsychotic use; use caution in patients at risk of pneumonia
May cause extrapyramidal symptoms, including akathisia, acute dystonic reactions, and pseudoparkinsonism, and tardive dyskinesia; risk of dystonia greater with increased doses
Therapy is associated with increased prolactin levels; significance unknown
May cause pigmentary retinopathy, and lenticular and corneal deposits with prolonged therapy
May cause orthostatic hypotension; use caution in patients with risk factors, including patients who do not tolerate transient hypotensive episodes such as hypovolemia, cerebrovascular disease, cardiovascular disease, or medicatioin predisposing to hypotension/bradycardia
May impair physical or mental abilities due to sedating properties; use caution when operating heavy machinery
Depresses hypothalamic thermoregulatory mechanism; exposure to extreme temperatures may cause hypo- or hyperthermia
Antiemetic effect may obscure toxicity of chemotherapeutic drugs
Anticholinergic antiparkinsonian agent may be needed to counter EPs
Strong anticholinergic agent and alpha blocker
Potential for priapism
US Food and Drug Administration (FDA) warning regarding off-label use for dementia in elderly
Pregnancy and lactation
Pregnancy category: C; neonates exposed to antipsychotic drugs during 3rd trimester of pregnancy are at risk for EPS or withdrawal symptoms after delivery; these complications vary in severity, with some being self-limited and others necessitating ICU support and prolonged hospitalization
Lactation: Drug enters breast milk; not recommended (American Academy of Pediatrics [AAP] states that this is "of concern")
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Thorazine (chlorpromazine)
Mechanism of action
Phenothiazine; antagonizes dopamine D2 receptors in brain; depresses release of hypothalamic and hypophyseal hormones; may also depress reticular activating system
Absorption
Bioavailability: 20%; extensive 1st-pass metabolism
Onset: 30-60 min
Duration: 4-6 hr; extended release, 10-12 hr
Distribution
Protein bound: 92-97%
Vd: 20 L/kg
Metabolism
Metabolized by hepatic P450 enzyme CYP2D6
Metabolites: 10-12 different compounds
Elimination
Half-life: 30 hr
Excretion: Urine
Administration
Direct IV injection is only for control of nausea and vomiting during surgery and for adjunctive treatment of tetanus
IV infusion is only for adjunctive treatment of intractable hiccups in adults
IV Administration
Direct IV injection: Dilute with NS to concentration no higher than 1 mg/mL, and administer at rate of 1 mg/min in adults and 0.5 mg/min in children; avoid administering undiluted drug
IV infusion: Add appropriate dose to 500-1000 mL of NS, and administer slowly
