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Special Alerts
Antipsychotics: Newborn Extrapyramidal and Withdrawal Symptoms with Third Trimester Exposure (Update)
June 2011
The U.S. Food and Drug Administration (FDA) and Health Canada have updated or are in the process of updating the pregnancy sections of their respective prescribing information for antipsychotics to contain detailed information about nonteratogenic effects following maternal use during pregnancy. Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms; EPS) and withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor. These effects vary in severity and may be self-limiting (subsiding within hours or days) or require hospitalization. In the cases reported to the FDA, concomitant use of other medications (known to precipitate withdrawal symptoms) may have contributed to the effects, although in some cases, antipsychotic medication use was the only contributing factor for the EPS and withdrawal symptoms.
Women who are taking antipsychotics should not stop them if they become pregnant (abrupt discontinuation is not recommended), but should notify their healthcare provider. Women taking antipsychotics who intend to become pregnant should discuss treatment concerns with their healthcare provider. Any adverse effects noted in newborns should be reported in the U.S. to the FDA's Medwatch program (1-800-332-1088 or https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm) or in Canada to Health Canada's Canada Vigilance Program (1-866-234-2345 or http://www.hc-sc.gc.ca/dhp-mps/medeff/index-eng.php).
For additional information, please refer to:
U.S.: http://www.fda.gov/Drugs/DrugSafety/ucm243903.htm#aihp
Canada: http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2011/2011_78-eng.php
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(klor PROE ma zeen)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of psychotic disorders (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
Behavioral symptoms associated with dementia (elderly); psychosis/agitation related to Alzheimer's dementia
Pregnancy Considerations
Embryotoxicity was observed in animal reproduction studies. Jaundice or hyper-/hyporeflexia have been reported in newborn infants following maternal use of phenothiazines. Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms [EPS]) and withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor; these effects may be self-limiting or require hospitalization.
Lactation
Enters breast milk/not recommended (AAP rates “of concern”; AAP 2001 update pending)
Breast-Feeding Considerations
Chlorpromazine and its metabolites have been detected in breast milk; concentrations in the milk do not correlate with those in the mother and may be higher than what is in the maternal plasma.
Contraindications
Hypersensitivity to chlorpromazine or any component of the formulation (cross-reactivity between phenothiazines may occur); severe CNS depression; coma
Warnings/Precautions
Boxed warnings:
• Dementia: See “Disease-related concerns” below.
Concerns related to adverse effects:
• Altered cardiac conduction: May alter cardiac conduction (life-threatening arrhythmias have occurred with therapeutic doses of phenothiazines). May cause QT prolongation and subsequent torsade de pointes; avoid use in patients with diagnosed or suspected congenital long QT syndrome.
• 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.
• Blood dyscrasias: Leukopenia, neutropenia, and agranulocytosis (sometimes fatal) have been reported in clinical trials and postmarketing reports with antipsychotic use; presence of risk factors (eg, pre-existing low WBC or history of drug-induced leuko/neutropenia) should prompt periodic blood count assessment. Discontinue therapy at first signs of blood dyscrasias or if absolute neutrophil count <1000/mm3.
• 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 (EPS): May cause extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia. Risk of dystonia (and possibly other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients.
• Hyperprolactinemia: Use associated with increased prolactin levels; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown.
• 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.
• Ocular effects: May cause pigmentary retinopathy, and lenticular and corneal deposits, particularly with prolonged therapy.
• 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).
• 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:
• Cardiovascular disease: Use with caution in patients with severe cardiovascular disease.
• Dementia: [U.S. Boxed Warning]: Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Chlorpromazine is not approved for the treatment of dementia-related psychosis.
• Glaucoma: Use with caution in patients with narrow-angle glaucoma; condition may be exacerbated by cholinergic blockade.
• 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.
• Renal impairment: Use with caution in patients with renal impairment.
• Respiratory disease: Use with caution in patients with respiratory disease (eg, severe asthma, emphysema) due to potential for CNS effects.
• 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.
• Drugs with QT prolongation potential: Avoid concurrent use with other drugs known to prolong QTc interval.
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations:
• Elderly: Use in patients with dementia is associated with an increased risk of mortality and cerebrovascular accidents; avoid antipsychotic use for behavioral problems associated with dementia unless alternative nonpharmacologic therapies have failed and patient may harm self or others. In addition, may cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults. May be inappropriate in older adults depending on comorbidities (eg, delirium) due to its potent anticholinergic effects (Beers Criteria). Increased risk for developing tardive dyskinesia, particularly in elderly women.
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), CYP2D6 (major), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (moderate), CYP2E1 (weak)
Drug Interactions
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification
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
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. 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: Levocabastine (Nasal); Paliperidone. Risk C: Monitor therapy
Antidepressants (Serotonin Reuptake Inhibitor/Antagonist): Antipsychotic Agents (Phenothiazines) may enhance the adverse/toxic effect of Antidepressants (Serotonin Reuptake Inhibitor/Antagonist). Specifically, this may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Antidepressants (Serotonin Reuptake Inhibitor/Antagonist) may enhance the hypotensive effect of Antipsychotic Agents (Phenothiazines). 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): May diminish the therapeutic effect of Antipsychotics (Typical). Antipsychotics (Typical) may enhance the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Management: Avoid concomitant therapy if possible and monitor for decreased effects of both agents when these combinations cannot be avoided. Atypical antipsychotics such as clozapine and quetiapine may be less likely to reduce the effects of anti-Parkinson's agents. Risk D: Consider therapy modification
ARIPiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy
Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
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
Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin (Systemic): 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. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). 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 (Moderate) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Risk C: Monitor therapy
Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Desmopressin: ChlorproMAZINE may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Divalproex: ChlorproMAZINE may increase the serum concentration of Divalproex. Risk C: Monitor therapy
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Haloperidol: ChlorproMAZINE may enhance the QTc-prolonging effect of Haloperidol. ChlorproMAZINE may increase the serum concentration of Haloperidol. Haloperidol may increase the serum concentration of ChlorproMAZINE. Management: Consider alternatives to combined treatment with these agents. If combined treatment cannot be avoided, monitor for signs and symptoms of prolonged QTc interval (e.g. arrhythmias). Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Indacaterol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
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
Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Methylphenidate: Antipsychotics may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotics. Risk C: Monitor therapy
Metoclopramide: May enhance the adverse/toxic effect of Antipsychotics. Risk X: Avoid combination
Metyrosine: May enhance the adverse/toxic effect of Antipsychotics. Risk C: Monitor therapy
Mifepristone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Management: Avoid use of mifepristone for treatment of hyperglycemia in Cushing's syndrome in patients receiving QT interval prolonging agents. Avoid initiation of QT prolonging agents for 2 weeks following mifepristone discontinuation. Risk X: Avoid combination
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
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
QUEtiapine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Quinagolide: Antipsychotics may diminish the therapeutic effect of Quinagolide. Risk C: Monitor therapy
QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Serotonin Modulators: Antipsychotics may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy
Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the formation of highly potent active metabolites. Management: Consider alternatives with less of an inhibitory effect on CYP2D6 activity when possible. Risk D: Consider therapy modification
Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination
Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotics. Risk C: Monitor therapy
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Toremifene: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Toremifene. The risk for potentially dangerous arrhythmias may be increased. Risk X: Avoid combination
Valproic Acid: ChlorproMAZINE may increase the serum concentration of Valproic Acid. Risk C: Monitor therapy
Vandetanib: QTc-Prolonging Agents may enhance the arrhythmogenic effect of Vandetanib. Risk X: Avoid combination
Vemurafenib: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Vemurafenib. Risk X: Avoid combination
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: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
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, dexmedetomidine, docetaxel, doxorubicin, doxorubicin liposome, famotidine, fenoldopam, filgrastim, fluconazole, gemcitabine, granisetron, heparin, hetastarch in lactate electrolyte injection (Hextend®), hydrocortisone sodium succinate, ondansetron, oxaliplatin, potassium chloride, propofol, teniposide, thiotepa, vinorelbine, vitamin B complex with C. Incompatible: Allopurinol, amifostine, amphotericin B cholesteryl sulfate complex, aztreonam, bivalirudin, cefepime, etoposide phosphate, fludarabine, furosemide, linezolid, melphalan, methotrexate, paclitaxel, pantoprazole, pemetrexed, piperacillin/tazobactam, sargramostim, tigecycline. Variable (consult detailed reference): Remifentanil
Compatibility in syringe: Compatible: Atropine, benztropine, buprenorphine, butorphanol, diphenhydramine, doxapram, droperidol, fentanyl, glycopyrrolate, hydromorphone, meperidine, metoclopramide, midazolam, pentazocine, prochlorperazine edisylate, promethazine, scopolamine. Incompatible: Cimetidine, pantoprazole, pentobarbital, thiopental. Variable (consult detailed reference): Dimenhydrinate, heparin, hydroxyzine, morphine, ranitidine.
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
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: 30-800 mg/day in 1-4 divided doses, initiate at lower doses and titrate as needed; usual dose: 200-600 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
I.V. (refractory to oral or I.M. treatment): 25-50 mg via slow I.V. infusion
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.
Do not administer SubQ (tissue damage and irritation may occur); for direct I.V. injection: Dilute with normal saline to a maximum concentration of 1 mg/mL, administer slow I.V. at a rate not to exceed 0.5 mg/minute in children and 1 mg/minute in adults. For treatment of intractable hiccups the manufacturer recommends diluting 25-50 mg of chlorpromazine in 500-1000 ml of normal saline. To reduce the risk of hypotension, patients receiving I.V. chlorpromazine must remain lying down during and for 30 minutes after the injection. Note: Avoid skin contact with solution; may cause contact dermatitis.
Monitoring Parameters
Vital signs (especially with parenteral use); lipid profile, fasting blood glucose/Hgb A1c; BMI; mental status; abnormal involuntary movement scale (AIMS); extrapyramidal symptoms (EPS); CBC in patients with risk factors for leukopenia/neutropenia
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. May interfere with urine detection of amphetamine/methamphetamine and methadone (false-positives).
Patient Education
Avoid alcohol. Maintain adequate hydration, unless instructed to restrict fluid intake. You may experience excess drowsiness, lightheadedness, dizziness, blurred vision, dry mouth, upset stomach, nausea, vomiting, anorexia, constipation, postural hypotension, urinary retention, ejaculatory dysfunction (reversible), decreased perspiration, or photosensitivity. Report persistent CNS effects (trembling fingers, altered gait or balance, excessive sedation, seizures, unusual movements, anxiety, suicide ideation, 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.
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.
This medication is considered to be potentially inappropriate in this patient population (Beers Criteria: Quality of evidence - moderate; Strength of recommendation - strong).
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, mepivacaine and levonordefrin [Carbocaine® 2% with Neo-Cobefrin®]) be used with caution.
Dental Comment
Chlorpromazine is known to prolong the QT interval. The QT interval is measured as the time and distance between the Q point of the QRS complex and the end of the T wave in the ECG tracing. After adjustment for heart rate, the QT interval is defined as prolonged if it is more than 450 msec in men and 460 msec in women. A long QT syndrome was first described in the 1950s and 60s as a congenital syndrome involving QT interval prolongation and syncope and sudden death. Some of the congenital long QT syndromes were characterized by a peculiar electrocardiographic appearance of the QRS complex involving a premature atria beat followed by a pause, then a subsequent sinus beat showing marked QT prolongation and deformity. This type of cardiac arrhythmia was originally termed “torsade de pointes” (translated from the French as “twisting of the points”). Chlorpromazine is considered as having a risk of causing torsade de pointes. Since 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, a medical consult is suggested.
Mental Health: Comment
Chlorpromazine is a low-potency typical antipsychotic. Older antipsychotic medications (chlorpromazine, haloperidol), which do not meet specific criteria for “atypical” antipsychotics, are often referred to as typical antipsychotics. Compared to newer "atypical" antipsychotics, typical antipsychotics may have a greater propensity to cause extrapyramidal symptoms (EPS).
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.
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.
Coadministration of two or more antipsychotics does not generally improve clinical response and may increase the potential for adverse effects.
In 2008, the FDA issued a warning regarding increased mortality risk with typical and atypical antipsychotic drugs when used in elderly patients with dementia-related psychosis.
Nursing: Physical Assessment/Monitoring
Review ophthalmic exam results. Monitor for suicide ideation and depression at beginning of therapy and periodically with long-term use. I.V./I.M.: Significant hypotension may occur. Initiate at lower doses and taper dosage slowly when discontinuing.
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, oral, as hydrochloride: 10 mg, 25 mg, 50 mg, 100 mg, 200 mg
Pricing: U.S. (www.drugstore.com)
Tablets (ChlorproMAZINE HCl)
10 mg (100): $20.79
25 mg (100): $27.03
50 mg (100): $38.24
100 mg (100): $43.52
200 mg (100): $56.77
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International Brand Names
Lexi-Comp.com
Last full review/revision April 2012
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