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Pronunciation |
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(klor
PROE ma
zeen) |

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U.S. Brand
Names |
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Ormazine; Thorazine® |

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Generic
Available |
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Yes |

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Canadian Brand
Names |
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Apo®-Chlorpromazine; Chlorprom®;
Chlorpromanyl®; Largactil®;
Novo-Chlorpromazine |

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Synonyms |
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Chlorpromazine Hydrochloride |

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Pharmacological Index |
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Antipsychotic Agent, Phenothiazine, Aliphatic |

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Use |
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Psychoses and mania; to control nausea and vomiting; relief of restlessness
and apprehension before surgery; acute intermittent porphyria; adjunct in the
treatment of tetanus; intractable hiccups; combativeness and/or explosive
hyperexcitable behavior in children 1-12 years of age and in short-term
treatment of hyperactive children |

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Pregnancy Risk
Factor |
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C |

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Contraindications |
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Hypersensitivity to chlorpromazine or any component (cross reactivity between
phenothiazines may occur); severe CNS depression, coma |

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Warnings/Precautions |
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Highly sedating, use with caution in disorders where CNS depression is a
feature. Use with caution in Parkinson's disease. Caution in patients with
hemodynamic instability; bone marrow suppression; predisposition to seizures,
subcortical brain damage, severe cardiac, hepatic, renal, or respiratory
disease. Esophageal dysmotility and aspiration have been associated with
antipsychotic use - use with caution in patients at risk of pneumonia (ie,
Alzheimer's disease). Caution in breast cancer or other prolactin-dependent
tumors (may elevate prolactin levels). May alter temperature regulation or mask
toxicity of other drugs due to antiemetic effects. May alter cardiac conduction
- life-threatening arrhythmias have occurred with therapeutic doses of
neuroleptics. May cause orthostatic hypotension - use with caution in patients
at risk of this effect or those who would tolerate transient hypotensive
episodes (cerebrovascular disease, cardiovascular disease, or other medications
which may predispose). Significant hypotension may occur, particularly with
parenteral administration. Injection contains sulfites and benzyl alcohol.
May cause extrapyramidal reactions, including pseudoparkinsonism, acute
dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions
is low-moderate relative to other neuroleptics). May be associated with
neuroleptic malignant syndrome (NMS) or pigmentary retinopathy.
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Adverse
Reactions |
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Cardiovascular: Postural hypotension, tachycardia, dizziness, nonspecific QT
changes
Central nervous system: Drowsiness, dystonias, akathisia, pseudoparkinsonism,
tardive dyskinesia, neuroleptic malignant syndrome, seizures
Dermatologic: Photosensitivity, dermatitis, skin pigmentation (slate gray)
Endocrine & metabolic: Lactation, breast engorgement, false-positive
pregnancy test, amenorrhea, gynecomastia, hyper- or hypoglycemia
Gastrointestinal: Xerostomia, constipation, nausea
Genitourinary: Urinary retention, ejaculatory disorder, impotence
Hematologic: Agranulocytosis, eosinophilia, leukopenia, hemolytic anemia,
aplastic anemia, thrombocytopenic purpura
Hepatic: Jaundice
Ocular: Blurred vision, corneal and lenticular changes, epithelial
keratopathy, pigmentary retinopathy |

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Overdosage/Toxicology |
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Symptoms of overdose include deep sleep, coma, extrapyramidal symptoms,
abnormal involuntary muscle movements, hypotension
Following initiation of essential overdose management, toxic symptom
treatment and supportive treatment should be initiated. Hypotension usually
responds to I.V. fluids or Trendelenburg positioning. If unresponsive to these
measures, the use of a parenteral inotrope may be required. Seizures commonly
respond to diazepam (I.V. 5-10 mg bolus in adults every 15 minutes if needed up
to a total of 30 mg; I.V. 0.25-0.4 mg/kg/dose up to a total of 10 mg in
children) or to phenytoin or phenobarbital; critical cardiac arrhythmias often
respond to I.V. phenytoin (15 mg/kg up to 1 g), while other antiarrhythmics can
be used. Neuroleptics often cause extrapyramidal symptoms (eg, dystonic
reactions) requiring management with benztropine mesylate I.V. 1-2 mg (adults)
may be effective. These agents are generally effective within 2-5 minutes.
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Drug
Interactions |
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CYP1A2, 2D6, and 3A3/4 enzyme substrate; CYP2D6 enzyme inhibitor
Benztropine (and other anticholinergics) may inhibit the therapeutic response
to CPZ and excess anticholinergic effects may occur
Chloroquine may increase CPZ concentrations
Cigarette smoking may enhance the hepatic metabolism of CPZ. Larger doses may
be required compared to a nonsmoker.
Concurrent use of CPZ with an antihypertensive may produce additive
hypotensive effects
Antihypertensive effects of guanethidine and guanadrel may be inhibited by
CPZ
Concurrent use with TCA may produce increased toxicity or altered therapeutic
response
CPZ may inhibit the antiparkinsonian effect of levodopa; avoid this
combination
CPZ plus lithium may rarely produce neurotoxicity
Barbiturates may reduce CPZ concentrations
Propranolol may increase CPZ concentrations
Sulfadoxine-pyrimethamine may increase CPZ concentrations
CPZ and possibly other low potency antipsychotics may reverse the pressor
effects of epinephrine
CPZ and CNS depressants (ethanol, narcotics) may produce additive CNS
depressant effects
CPZ and trazodone may produce additive hypotensive effects
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Stability |
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Protect from light; a slightly yellowed solution does not indicate potency
loss, but a markedly discolored solution should be discarded; diluted injection
(1 mg/mL) with NS and stored in 5 mL vials remains stable for 30
days |

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Mechanism of
Action |
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Blocks postsynaptic mesolimbic dopaminergic receptors in the brain; exhibits
a strong alpha-adrenergic blocking effect and depresses the release of
hypothalamic and hypophyseal hormones; believed to depress the reticular
activating system, thus affecting basal metabolism, body temperature,
wakefulness, vasomotor tone, and emesis |

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Pharmacodynamics/Kinetics |
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Peak concentration after oral dose: 1-2 hours
Distribution: Crosses the placenta; appears in breast milk
Metabolism: Extensively in the liver to active and inactive metabolites
Half-life, biphasic: Initial: 2 hours; Terminal: 30 hours
Elimination: <1% excreted in urine as unchanged drug within 24 hours
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Usual Dosage |
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Children >6 months:
Psychosis:
Oral: 0.5-1 mg/kg/dose every 4-6 hours; older children may require 200 mg/day
or higher
I.M., I.V.: 0.5-1 mg/kg/dose every 6-8 hours; maximum dose for <5 years
(22.7 kg): 40 mg/day; maximum for 5-12 years (22.7-45.5 kg): 75 mg/day
Nausea and vomiting:
Oral: 0.5-1 mg/kg/dose every 4-6 hours as needed
I.M., I.V.: 0.5-1 mg/kg/dose every 6-8 hours; maximum dose for <5 years
(22.7 kg): 40 mg/day; maximum for 5-12 years (22.7-45.5 kg): 75 mg/day
Rectal: 1 mg/kg/dose every 6-8 hours as needed
Adults:
Psychosis:
Oral: Range: 30-2000 mg/day in 1-4 divided doses, initiate at lower doses and
titrate as needed; usual dose: 400-600 mg/day; some patients may require 1-2
g/day
I.M., I.V.: Initial: 25 mg, may repeat (25-50 mg) in 1-4 hours, gradually
increase to a maximum of 400 mg/dose every 4-6 hours until patient is
controlled; usual dose: 300-800 mg/day
Intractable hiccups: Oral, I.M.: 25-50 mg 3-4 times/day
Nausea and vomiting:
Oral: 10-25 mg every 4-6 hours
I.M., I.V.: 25-50 mg every 4-6 hours
Rectal: 50-100 mg every 6-8 hours
Elderly (nonpsychotic patient; dementia behavior): Initial: 10-25 mg 1-2
times/day; increase at 4- to 7-day intervals by 10-25 mg/day. Increase dose
intervals (bid, tid, etc) as necessary to control behavior response or side
effects; maximum daily dose: 800 mg; gradual increases (titration) may prevent
some side effects or decrease their severity.
Dosing adjustment/comments in hepatic impairment: Avoid use in severe
hepatic dysfunction |

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Dietary
Considerations |
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Alcohol: Additive CNS effects, avoid use |

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Monitoring
Parameters |
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Orthostatic blood pressures; tremors, gait changes, abnormal movement in
trunk, neck, buccal area, or extremities; monitor target behaviors for which the
agent is given; watch for hypotension when administering I.M. or
I.V. |

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Reference Range |
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Therapeutic: 50-300 ng/mL (SI: 157-942 nmol/L)
Toxic: >750 ng/mL (SI: >2355 nmol/L); serum concentrations poorly
correlate with expected response |

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Test
Interactions |
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False-positives for phenylketonuria, amylase, uroporphyrins, urobilinogen;
may cause photosensitivity; avoid excessive sunlight; do not stop taking without
consulting physician |

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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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Most pharmacology textbooks state that in presence of phenothiazines,
systemic doses of epinephrine paradoxically decrease the blood pressure. This is
the so called "epinephrine reversal" phenomenon. This has never been observed
when epinephrine is given by infiltration as part of the anesthesia
procedure. |

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Dental Health:
Effects on Dental Treatment |
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Significant hypotension may occur, especially when the drug is administered
parenterally; orthostatic hypotension is due to alpha-receptor blockade, the
elderly are at greater risk for orthostatic hypotension
Extrapyramidal reactions are more common in elderly with up to 50% developing
these reactions after 60 years of age; drug-induced Parkinson's syndrome
occurs often; Akathisia is the most common extrapyramidal reaction in
elderly
Increased confusion, memory loss, psychotic behavior, and agitation
frequently occur as a consequence of anticholinergic effects
Antipsychotic associated sedation in nonpsychotic patients is extremely
unpleasant due to feelings of depersonalization, derealization, and dysphoria
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Patient
Information |
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Use exactly as directed (do not increase dose or frequency); may cause
physical and/or psychological dependence. Do not discontinue without consulting
prescriber. Tablets/capsules may be taken with food. Mix oral solution with 2-4
ounces of liquid (eg, juice, milk, water). Do not take within 2 hours of any
antacid. Store away from light. Avoid excess alcohol or caffeine and other
prescription or OTC medications not approved by prescriber. Maintain adequate
hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). May
turn urine red-brown (normal). You may experience excess drowsiness,
lightheadedness, dizziness, or blurred vision (use caution driving or when
engaging in tasks requiring alertness until response to drug is known); dry
mouth, upset stomach, nausea, vomiting, anorexia (small frequent meals, frequent
mouth care, sucking lozenges, or chewing gum may help); constipation (increased
exercise, fluids, or dietary fruit and fiber may help); postural hypotension
(use caution climbing stairs or when changing position from lying or sitting to
standing); urinary retention (void before taking medication); ejaculatory
dysfunction (reversible); decreased perspiration (avoid strenuous exercise in
hot environments); or photosensitivity (use sunscreen, wear protective clothing
and eyewear, and avoid direct sunlight). Report persistent CNS effects
(trembling fingers, altered gait or balance, excessive sedation, seizures,
unusual movements, anxiety, abnormal thoughts, confusion, personality changes);
chest pain, palpitations, rapid heartbeat, or severe dizziness; unresolved
urinary retention or changes in urinary pattern; altered menstrual pattern,
change in libido, swelling or pain in breasts (male or female); vision changes,
skin rash, irritation, or changes in color of skin (gray-blue); or worsening of
condition. Pregnancy/breast-feeding precautions: Inform prescriber if
you are or intend to be pregnant. Breast-feeding is not
recommended. |

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Nursing
Implications |
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Avoid contact of oral solution or injection with skin (contact
dermatitis) |

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Dosage Forms |
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Capsule, as hydrochloride, sustained action: 30 mg, 75 mg, 150 mg, 200 mg,
300 mg
Concentrate, oral, as hydrochloride: 30 mg/mL (120 mL); 100 mg/mL (60 mL, 240
mL)
Injection, as hydrochloride: 25 mg/mL (1 mL, 2 mL, 10 mL)
Suppository, rectal, as base: 25 mg, 100 mg
Syrup, as hydrochloride: 10 mg/5 mL (120 mL)
Tablet, as hydrochloride: 10 mg, 25 mg, 50 mg, 100 mg, 200 mg
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References |
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American Academy of Pediatrics Committee on Drugs,
"Reappraisal of Lytic Cocktail/Demerol®,
Phenergan®, and Thorazine® (DPT) for
the Sedation of Children," Pediatrics, 1995, 95(4):598-602.
Fernandes CM, "Parenteral Chlorpromazine and a Meningitis Headache," J
Emerg Med, 1995, 13(4):577-9.
Gez E, Ben-Yosef R, Catane R, et al,
"Chlorpromazine and Dexamethasone Versus High-Dose Metoclopramide and Dexamethasone in Patients Receiving Cancer Chemotherapy, Particularly Cis-Platinum: A Prospective Randomized Crossover Study,"
Oncology, 1989, 46(3):150-4.
Gez E, Brufman G, Kaufman B, et al,
"Methylprednisolone and Chlorpromazine in Patients Receiving Cancer Chemotherapy: A Prospective Nonrandomized Study,"
J Chemother, 1989, 1(2):140-3.
Knight ME and Roberts RJ,
"Phenothiazine and Butyrophenone Intoxication in Children," Pediatr Clin
North Am, 1986, 33(2):299-309.
Lipka LJ, Lathers CM, and Roberts J,
"Does Chlorpromazine Produce Cardiac Arrhythmia Via the Central Nervous System,"
J Clin Pharmacol, 1988, 28(11):968-83.
Mitchell AC and Brown KW, "Chlorpromazine-Induced Retinopathy," Br J
Psychiatry, 1995, 166(6):822-3.
Oshika T,
"Ocular Adverse Effects of Neuropsychiatric Agents. Incidence and Management,"
Drug Saf, 1995, 12(4):256-63.
Peabody CA, Warner MD, Whiteford HA, et al,
"Neuroleptics and the Elderly," J Am Geriatr Soc, 1987, 35(3):233-8.
Relling MV, Mulhern RK, Fairclough D, et al,
"Chlorpromazine With and Without Lorazepam as Antiemetic Therapy in Children Receiving Uniform Chemotherapy,"
J Pediatr, 1993, 123(5):811-6.
Risse SC and Barnes R,
"Pharmacologic Treatment of Agitation Associated With Dementia," J Am Geriatr
Soc, 1986, 34(5):368-76.
Rosenberg MR and Green M,
"Neuroleptic Malignant Syndrome: Review of Response to Therapy," Arch Intern
Med, 1989, 149(9):1927-31.
Saab GA, Shamseddine A, and Habbal Z,
"Prolonged Chlorpromazine Infusion as Antiemetic in Patients on Daily Cisplating Infusion. A Pilot Study,"
Am J Clin Oncol, 1988, 11(4):470-3.
Saltz BL, Woerner MG, Kane JM, et al,
"Prospective Study of Tardive Dyskinesia Incidence in the Elderly," JAMA,
1991, 266(17):2402-6.
Seifert RD, "Therapeutic Drug Monitoring: Psychotropic Drugs," J Pharm
Pract, 1984, 6:403-16. |

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