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Special Alerts
Antipsychotics (Conventional and Atypical): Association With an Increased Risk of Mortality in Elderly Patients Treated for Dementia-Related Psychosis - June 2008
The Food and Drug Administration (FDA) is notifying healthcare professionals that conventional antipsychotics (eg, haloperidol, fluphenazine) will now carry a similar boxed warning as atypical antipsychotics (eg, risperidone, aripiprazole) concerning an increased risk of mortality in elderly patients treated for dementia-related psychosis. Atypical antipsychotics received the boxed warning in April 2005 after study data from seven placebo-controlled trials indicated an increased risk of death in patients treated with certain atypicals for dementia-related behavioral disorders.
The FDA requirement to extend the warning to conventional antipsychotics was prompted by two recently published observational studies. Both studies revealed an increased risk of mortality in elderly patients treated with these medications. One of the two studies was a retrospective cohort study which examined 37,241 patients, ?65 years of age, treated with antipsychotics. Of these patients, 12,882 received a conventional antipsychotic compared to 24,359 patients who received an atypical antipsychotic. All-cause mortality within the first 180 days of use was compared between the two groups. The results showed that the risk of death in patients who received a conventional-type antipsychotic was comparable to (and may be greater than) the risk of death in patients receiving an atypical. The second study was also a retrospective cohort study; it involved 27,259 matched pairs of patients, ?66 years of age, diagnosed with dementia. Risk of death was compared in patients who received an atypical antipsychotic versus no antipsychotic, and in patients who received a conventional antipsychotic versus an atypical antipsychotic. An increased risk of death was observed in the groups receiving an atypical antipsychotic compared to no antipsychotic and also in patients receiving a conventional antipsychotic compared to patients receiving an atypical antipsychotic. This effect was seen at 30 days and persisted at 180 days, and was seen in both community-dwelling and long-term care facility patients.
The FDA believes that considering all the available evidence, conventional antipsychotics at least share a similar increased risk of death that has been observed with the use of atypical antipsychotics in elderly patients with dementia-related psychosis. The FDA is reminding practitioners that antipsychotic medications are not approved for the treatment of dementia-related psychosis. Elderly patients treated with antipsychotics, conventional or atypical, are at an increased risk of death. Practitioners prescribing antipsychotics to elderly patients for this purpose should inform the patient and their caregivers of this risk prior to prescribing.
Additional information may be found at http://www.fda.gov/medwatch/safety/2008/safety08.htm#Antipsychotics
References:
Gill SS, Bronskill SE, Normand SL, et al, “Antipsychotic Drug Use and Mortality in Older Adults With Dementia,” Ann Intern Med, 2007, 146(11):775-86.
Schneeweiss S, Setoguchi S, Brookhart A, et al, “Risk of Death Associated With the Use of Conventional Versus Atypical Antipsychotic Drugs Among Elderly Patients,” CMAJ, 2007, 176(5): 627-32.
Medication Safety Issues
Sound-alike/look-alike issues:
ChlorproMAZINE may be confused with chlordiazePOXIDE, chlorproPAMIDE, clomiPRAMINE, prochlorperazine, promethazine
Thorazine® may be confused with thiamine, thioridazine
Pronunciation
(klor PROE ma zeen)
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Control of mania; treatment of schizophrenia; control of 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
Use: Unlabeled/Investigational
Management of psychotic disorders; behavioral symptoms associated with dementia (elderly); psychosis/agitation related to Alzheimer's dementia
Pregnancy Risk Factor
C
Lactation
Enters breast milk/not recommended (AAP rates “of concern”)
Breast-Feeding Considerations
Drowsiness and lethargy have been reported in nursing infants; galactorrhea has been reported in mother.
Contraindications
Hypersensitivity to chlorpromazine or any component of the formulation (cross-reactivity between phenothiazines may occur); severe CNS depression; coma
Warnings/Precautions
Concerns related to adverse effects:
• Altered cardiac conduction: May alter cardiac conduction (life-threatening arrhythmias have occurred with therapeutic doses of phenothiazines).
• Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. Relative to other neuroleptics, chlorpromazine has a moderate potency of cholinergic blockade.
• Esophageal dysmotility/aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; use with caution in patients at risk of pneumonia (ie, Alzheimer's disease).
• Extrapyramidal symptoms: May cause extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is low-moderate relative to other neuroleptics).
• Hypotension: Significant hypotension may occur, particularly with parenteral administration.
• Neuroleptic malignant syndrome (NMS): May be associated with NMS; monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability (risk may be increased in patients with Parkinson's disease or Lewy body dementia).
• Orthostatic hypotension: May cause orthostatic hypotension; use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).
• Pigmentary retinopathy: May be associated with pigmentary retinopathy.
• Sedation: Highly sedating which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Temperature regulation: Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects.
Disease-related concerns:
• Bone marrow suppression: Use with caution in patients with bone marrow suppression; blood dyscrasias have occurred. Use only if benefits outweigh risk.
• Cardiovascular disease: Use with caution in patients with severe cardiovascular disease.
• Glaucoma: Use with caution in patients with narrow-angle glaucoma; condition may be exacerbated by cholinergic blockade. Screening is recommended.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; condition may be exacerbated by cholinergic blockade.
• Parkinson's disease: Use with caution in patients with Parkinson's disease; they may be more sensitive to adverse effects.
• Prolactin-dependent tumors: Use with caution in patients with breast cancer or other prolactin-dependent tumors; elevates prolactin levels.
• Renal impairment: Use with caution in patients with renal impairment.
• Respiratory disease: Use with caution in patients with respiratory disease.
• Seizure disorder: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold.
Concurrent drug therapy issues:
• Antiemetic effects: May mask toxicity of other drugs or conditions (eg, intestinal obstruction, Reye's syndrome, brain tumor) due to antiemetic effects.
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations:
• Elderly: Use with caution in the elderly; increased risk for developing tardive dyskinesia.
Dosage form specific issues:
• Sulfites: Injection contains sulfites.
Adverse Reactions
Frequency not defined.
Cardiovascular: Postural hypotension, tachycardia, dizziness, nonspecific QT changes
Central nervous system: Drowsiness, dystonias, akathisia, pseudoparkinsonism, tardive dyskinesia, neuroleptic malignant syndrome, seizure
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
Metabolism/Transport Effects
Substrate of CYP1A2 (minor), 2D6 (major), 3A4 (minor); Inhibits CYP2D6 (strong), 2E1 (weak)
Drug Interactions
Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotics. Severe extrapyramidal symptoms have occurred in some patients. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Amphetamines: Antipsychotics may diminish the stimulatory effect of Amphetamines. Risk C: Monitor therapy
Analgesics (Opioid): Antipsychotic Agents (Phenothiazines) may enhance the hypotensive effect of Analgesics (Opioid). Risk C: Monitor therapy
Antacids: May decrease the absorption of Antipsychotic Agents (Phenothiazines). Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Antimalarial Agents: May increase the serum concentration of Antipsychotic Agents (Phenothiazines). Risk C: Monitor therapy
Anti-Parkinson 's Agents (Dopamine Agonist): Antipsychotics (Typical) may diminish the therapeutic effect of Anti-Parkinson 's Agents (Dopamine Agonist). Risk D: Consider therapy modification
Beta-Blockers: Antipsychotic Agents (Phenothiazines) may enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. Exceptions: Atenolol; Levobunolol; Metipranolol; Nadolol. Risk C: Monitor therapy
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
CYP2D6 Substrates: CYP2D6 Inhibitors (Strong) may decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Haloperidol: May enhance the QTc-prolonging effect of ChlorproMAZINE. ChlorproMAZINE may decrease the metabolism of Haloperidol. Risk D: Consider therapy modification
Lithium formulations: May enhance the neurotoxic effect of Antipsychotics. Lithium formulations may decrease the serum concentration of Antipsychotics. Specifically noted with chlorpromazine. Risk C: Monitor therapy
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Thioridazine: CYP2D6 Inhibitors may decrease the metabolism of Thioridazine. Risk X: Avoid combination
Tramadol: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Tramadol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Risk C: Monitor therapy
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase CNS depression).
Herb/Nutraceutical: Avoid St John's wort (may decrease chlorpromazine levels, increase photosensitization, or enhance sedative effect). Avoid dong quai (may enhance photosensitization). Avoid kava kava, gotu kola, valerian (may increase CNS depression).
Storage
Injection: 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.
Reconstitution
Dilute injection (1 mg/mL) with NS for I.V. administration.
Compatibility
Stable in dextran 6% in dextrose, dextran 6% in NS, D5LR, D51/4NS, D51/2NS, D5NS, D5W, D10W, LR, 1/2NS, NS.
Y-site administration: Compatible: Amsacrine, cisatracurium, cisplatin, cladribine, cyclophosphamide, cytarabine, docetaxel, doxorubicin, doxorubicin liposome, famotidine, filgrastim, fluconazole, gatifloxacin, gemcitabine, granisetron, heparin, hydrocortisone sodium succinate, ondansetron, potassium chloride, propofol, teniposide, thiotepa, vinorelbine, vitamin B complex with C. Incompatible: Allopurinol, amifostine, amphotericin B cholesteryl sulfate complex, aztreonam, cefepime, etoposide phosphate, fludarabine, furosemide, linezolid, melphalan, methotrexate, paclitaxel, piperacillin/tazobactam, sargramostim. Variable (consult detailed reference): Remifentanil, TPN.
Compatibility in syringe: Compatible: Atropine, benztropine, butorphanol, diphenhydramine, doxapram, droperidol, fentanyl, glycopyrrolate, hydromorphone, hydroxyzine, meperidine, metoclopramide, midazolam, morphine, pentazocine, perphenazine, prochlorperazine edisylate, promazine, promethazine, scopolamine. Incompatible: Cimetidine, dimenhydrinate, heparin, pentobarbital, thiopental. Variable (consult detailed reference): Ranitidine.
Compatibility when admixed: Compatible: Ascorbic acid injection, ethacrynate, netilmicin, theophylline, vitamin B complex with C. Incompatible: Aminophylline, amphotericin B, ampicillin, chloramphenicol, chlorothiazide, floxacillin, furosemide, methohexital, penicillin G potassium, penicillin G sodium, phenobarbital. Variable (consult detailed reference): Pentobarbital.
Mechanism of Action
Chlorpromazine is an aliphatic phenothiazine antipsychotic which 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
Pharmacodynamics/Kinetics
Onset of action: I.M.: 15 minutes; Oral: 30-60 minutes
Absorption: Rapid
Distribution: Vd: 20 L/kg; crosses the placenta; enters breast milk
Protein binding: 92% to 97%
Metabolism: Extensively hepatic to active and inactive metabolites
Bioavailability: 20%
Half-life, biphasic: Initial: 2 hours; Terminal: 30 hours
Excretion: Urine (<1% as unchanged drug) within 24 hours
Dosage
Children ?6 months:
Schizophrenia/psychoses:
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
<5 years (22.7 kg): Maximum: 40 mg/day
5-12 years (22.7-45.5 kg): Maximum: 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
<5 years (22.7 kg): Maximum: 40 mg/day
5-12 years (22.7-45.5 kg): Maximum: 75 mg/day
Adults:
Schizophrenia/psychoses:
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
Elderly: Behavioral symptoms associated with dementia (unlabeled use): 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 comments in renal impairment: Hemodialysis: Not dialyzable (0% to 5%)
Dosing adjustment/comments in hepatic impairment: Avoid use in severe hepatic dysfunction
Administration: I.V.
Direct of intermittent infusion: Infuse 1 mg or portion thereof over 1 minute. Note: Avoid skin contact with solution; may cause contact dermatitis.
Monitoring Parameters
Vital signs; lipid profile, fasting blood glucose/Hgb A1c; BMI; mental status; abnormal involuntary movement scale (AIMS); extrapyramidal symptoms (EPS)
Reference Range
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
Test Interactions
False-positives for phenylketonuria, amylase, uroporphyrins, urobilinogen. May cause false-positive pregnancy test.
Patient Education
Use exactly as directed; do not increase dose or frequency. Do not discontinue this medication without consulting prescriber. Tablets may be taken with food. Do not take within 2 hours of any antacid. Store away from light. Avoid 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, fruit, or 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 become pregnant. Breast-feeding is not recommended.
Geriatric Considerations
Many elderly patients receive antipsychotic medications for inappropriate nonpsychotic behavior. Before initiating antipsychotic medication, the clinician should investigate any possible reversible cause; any stress or stress from any disease can cause acute “confusion” or worsening of baseline nonpsychotic behavior. Most commonly acute changes in behavior are due to increases in drug dose or addition of new drug to regimen; fluid electrolyte loss; infections; and changes in environment.
Any changes in disease status in any organ system can result in behavior changes.
In the treatment of agitated, demented, elderly patients, authors of meta-analysis of controlled trials of the response to the traditional antipsychotics (phenothiazines, butyrophenones) in controlling agitation have concluded that the use of neuroleptics results in a response rate of 18%. Clearly neuroleptic therapy for behavior control should be limited with frequent attempts to withdraw the agent given for behavior control.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment:
Xerostomia (normal salivary flow resumes upon discontinuation).
Significant hypotension may occur, especially when the drug is administered parenterally. Orthostatic hypotension is due to alpha-receptor blockade; elderly are at greater risk.
Tardive dyskinesia: Prevalence rate may be 40% in elderly; development of the syndrome and the irreversible nature are proportional to duration and total cumulative dose over time. 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.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
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. Chlorpromazine is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, levonordefrin [Neo-Cobefrin®]) be used with caution.
Mental Health: Comment
Chlorpromazine is a low-potency antipsychotic. Older antipsychotic medications (chlorpromazine, haloperidol), which do not meet specific criteria for “atypical” antipsychotics, are often referred to as typical antipsychotics. They are associated with the troubling side effect, EPS. However, it is commonly believed that in order for a drug to treat psychosis, it must block dopamine is some manner.
Common side effects include sedation and neuroleptic effect (reduced initiative, interest in the environment, and display of emotion or affect). All typical antipsychotics are considered to be equally effective if given in equipotent doses. An inverse relationship exists between intrinsic antimuscarinic activity and propensity to cause extrapyramidal side effects. If dystonia or pseudoparkinsonism occurs, antiparkinsonian agents should be considered. If akathisia occurs, beta-blockers (eg, propranolol), benzodiazepines, or antiparkinsonian agents should be considered. Tardive dyskinesia (TD) secondary to typical antipsychotics has an estimated incidence of 3% to 5% per year for the first 5 years of treatment. After this time period, the incidence is estimated to be 2% to 3% per year. Prevalence rates are ?15% to 20%. Female gender and age constitute risk factors for TD. Indeed, prevalence rates have been reported to be as high as 70% in elderly females. No specific treatment exists for TD, however, patients are often initiated on/switched to an atypical antipsychotic because of their lower incidence to cause TD and hopes of suppression.
Typical antipsychotics are usually only indicated for schizophrenia, but are generally effective for mania and psychosis and/or behavioral syndromes secondary to other mental conditions. Nonpsychiatric uses include Tourette's syndrome, Huntington's disease, and occasionally, intractable hiccups, pruritus, nausea, and vomiting.
These drugs are thought to exert their antipsychotic activity by blocking dopamine D2 receptors in the mesolimbic dopaminergic pathway. Side effects are often related to their ability to antagonize dopamine receptors in the nigrostriatal and tuberoinfundibular pathways.
Coadministration of two or more antipsychotics does not generally improve clinical response and may increase the potential for adverse effects.
Nursing: Physical Assessment/Monitoring
Assess other medications patient is taking for effectiveness and interactions. Review ophthalmic exam and monitor laboratory results, therapeutic effectiveness, and adverse reactions at beginning of therapy and periodically with long-term use. I.V./I.M.: Significant hypotension may occur. Initiate at lower doses (see Dosing) and taper dosage slowly when discontinuing. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report. Note: Chlorpromazine may cause false-positive pregnancy test.
Oncology: Emetic Potential
Very low (<10%)
Oncology: Vesicant
No
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as hydrochloride: 25 mg/mL (1 mL, 2 mL)
Tablet, as hydrochloride: 10 mg, 25 mg, 50 mg, 100 mg, 200 mg
Pricing: U.S. (www.drugstore.com)
Tablets (ChlorproMAZINE HCl)
10 mg (60): $16.99
25 mg (60): $17.99
50 mg (60): $17.99
100 mg (60): $15.99
200 mg (60): $26.99
References
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.
“American Academy of Pediatrics Committee on Drugs. The Transfer of Drugs and Other Chemicals Into Human Milk,” Pediatrics, 2001, 108(3):776-89.
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.
Hutcheon AW, Palmer JB, Soukop M, et al, “A Randomized Multicentre Single Blind Comparison of a Cannabinoid Antiemetic (Levonantradol) With Chlorpromazine in Patients Receiving Their First Cytotoxic Chemotherapy,” Eur J Cancer Clin Oncol, 1983, 19(8):1087-90.
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.
Rabins PV, Blacker D, Rovner BW, et al, “Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias,” October, 2007. Available at http://www.psych.org/psych_pract/treatg/pg/prac_guide.cfm
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.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
Content last modified August 2008
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