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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
(LOKS a peen)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of psychotic disorders
Use: Unlabeled/Investigational
Psychosis/agitation related to Alzheimer's dementia
Pregnancy Considerations
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
Excretion in breast milk unknown/not recommended
Contraindications
Hypersensitivity to loxapine or any component of the formulation; severe drug-induced CNS depression; coma
Canadian labeling: Additional contraindication (not in U.S. labeling): Circulatory collapse
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 antipsychotics. Avoid use in patients with underlying QT prolongation, in those taking medicines that prolong the QT interval, or cause polymorphic ventricular tachycardia; monitor ECG closely for dose-related QT effects.
• 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 antipsychotics, loxapine has a low 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. Risk of tardive dyskinesia may be increased in elderly patients; antipsychotics may also mask signs/symptoms of tardive dyskinesia. Consider therapy discontinuation with signs/symptoms of tardive dyskinesia. Increased incidence of EPS has been observed with I.M. administration compared to oral administration.
• Hyperprolactinemia: Use associated with increased prolactin levels; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown.
• Neuroleptic malignant syndrome (NMS): NMS has been associated with use of antipsychotic agents; monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability. Discontinue treatment immediately with onset of NMS; recurrence has been reported in patients rechallenged with antipsychotic therapy.
• 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: May be sedating, use with caution in disorders where CNS depression is a feature; 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 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. Loxapine 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: Canadian labeling recommends avoiding use in severe hepatic disease.
• 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.
• 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, particularly elderly women.
Dosage forms specific issues:
• Appropriate use: Injection (Canadian availability; not available in U.S.): Reserve injection for patients unable to tolerate oral administration; convert to oral dosage form with symptom control and ability to tolerate oral administration.
Adverse Reactions
Frequency not defined.
Cardiovascular: ECG changes, edema, facial flushing, hyper-/hypotension, orthostatic hypotension, tachycardia, syncope
Central nervous system: Agitation, altered central temperature regulation, confusion, dizziness, drowsiness, extrapyramidal reactions (akathisia, akinesia, dystonia, pseudoparkinsonism, tardive dyskinesia), faintness, headache, hyperpyrexia, insomnia, lightheadedness, neuroleptic malignant syndrome (NMS), sedation, seizure, slurred speech, tension
Dermatologic: Alopecia, dermatitis, photosensitivity, pruritus, rash, seborrhea
Endocrine & metabolic: Amenorrhea, galactorrhea, gynecomastia, hyperprolactinemia, impotence, menstrual irregularity, polydipsia
Gastrointestinal: Adynamic ileus, constipation, nausea, vomiting, weight gain/loss, xerostomia
Genitourinary: Priapism (rare), urinary retention
Hematologic: Agranulocytosis, leukopenia, thrombocytopenia
Hepatic: ALT increased, AST increased, hepatitis, jaundice
Neuromuscular & skeletal: Gait instability, muscle twitching, numbness, paresthesia, weakness
Ocular: Blurred vision, ptosis
Respiratory: Dyspnea, nasal congestion
Metabolism/Transport Effects
None known.
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
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
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Levocabastine (Nasal); Paliperidone. 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
Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
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
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. 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
LORazepam: Loxapine may enhance the adverse/toxic effect of LORazepam. Specifically, prolonged stupor, respiratory depression, and/or hypotension. 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
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. 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
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
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy
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
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
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 kava kava, gotu kola, valerian, St John's wort (may increase CNS depression).
Storage
Capsules: Store at 20°C to 25°C (68°Fto 77°F).
Canadian products (not available in U.S.): Injection solution, oral solution, tablets: Store at 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Loxapine is a dibenzoxazepine antipsychotic which blocks postsynaptic mesolimbic D1 and D2 receptors in the brain, and also possesses serotonin 5-HT2 blocking activity
Pharmacodynamics/Kinetics
Onset of action: Oral, I.M.: Within 30 minutes
Peak effect: 1.5-3 hours
Duration: ~12 hours
Absorption: Oral, I.M.: Rapid and complete
Metabolism: Hepatic to glucuronide conjugates
Half-life elimination: Biphasic: Initial: 5 hours; Terminal: 19 hours
Excretion: Urine (56% to 70%, as metabolites); feces (as metabolites)
Dosage
Oral:
Adults: Initial: 10 mg twice daily (up to 50 mg/day may be considered in severely disturbed patients), increase dose until psychotic symptoms are controlled; usual maintenance: 60-100 mg/day in divided doses 2-4 times/day; satisfactory response often observed with doses of 20-60 mg/day (maximum: 250 mg/day).Therapy should be maintained at lowest effective dose.
Elderly: Reduced dosing may be indicated due to risks of adverse events associated with high-dose therapy.
I.M. (Canadian availability; not available in the U.S.): Adults: 12.5-50 mg every 4-6 hours or longer; individualize dose early in therapy; some patients respond satisfactorily to twice-daily dosing
Dosage adjustment in renal impairment: There are no dosage adjustments provided in the manufacturer's labeling.
Dosage adjustment in hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling. Canadian labeling does not recommend use in severe hepatic disease.
Administration: Oral
Oral solution (Canadian availability; not available in the U.S.) should be mixed with orange or grapefruit juice prior to administration.
Administration: I.M.
Injection (Canadian availability; not available in the U.S.) is administered by I.M. injection.
Administration: I.V.
Injection (Canadian availability; not available in the U.S.): Do not administer I.V.
Monitoring Parameters
Vital signs, orthostatic blood pressures 3-5 days after initiation of therapy or a dose increase; liver and kidney function, CBC at baseline and then at regular intervals (in patients at risk for blood dyscrasias), lipid profile, fasting blood glucose/Hgb A1c; BMI; mental status, abnormal involuntary movement scale (AIMS), extrapyramidal symptoms (EPS)
Test Interactions
False-positives for phenylketonuria, amylase, uroporphyrins, urobilinogen
Patient Education
It may take 2-3 weeks to achieve desired results. Avoid alcohol. Maintain adequate hydration unless instructed to restrict fluid intake. You may experience excess drowsiness, restlessness, dizziness, blurred vision, nausea, vomiting, constipation, postural hypotension, urinary retention, or decreased perspiration. Report persistent CNS effects (eg, trembling fingers, altered gait or balance, excessive sedation, seizures, unusual movements, anxiety, abnormal thoughts, confusion, personality changes); chest pain, palpitations, or rapid heartbeat; severe dizziness; unresolved urinary retention or changes in urinary pattern; vision changes; skin rash or yellowing of skin; respiratory difficulty; 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.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment:
Xerostomia and changes in salivation (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, the elderly are at greater risk for orthostatic hypotension.
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. Loxapine 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
Loxapine 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”). Loxapine 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
Loxapine is not commonly used. 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.
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 screening results at beginning of therapy and periodically throughout. 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.
Capsule, oral: 5 mg, 10 mg, 25 mg, 50 mg
Loxitane®: 5 mg, 10 mg, 25 mg, 50 mg
Pricing: U.S. (www.drugstore.com)
Capsules (Loxapine Succinate)
5 mg (30): $26.99
50 mg (30): $39.99
Capsules (Loxitane)
5 mg (60): $99.35
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.
Moore TA, “Schizophrenia Treatment Guidelines in the United States,” Clin Schizophr Relat Psychoses, 2011, 5(1):40-9.
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
Risse SC and Barnes R, “Pharmacologic Treatment of Agitation Associated With Dementia,” J Am Geriatr Soc, 1986, 34(5):368-76.
Saltz BL, Woerner MG, Kane JM, et al, “Prospective Study of Tardive Dyskinesia Incidence in the Elderly,” JAMA, 1991, 266(17):2402-6.
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.
Seifert RD, “Therapeutic Drug Monitoring: Psychotropic Drugs,” J Pharm Pract, 1984, 6:403-16.
Tam CW, Olin BR 3d, and Ruiz AE, “Loxapine-Associated Rhabdomyolysis and Acute Renal Failure,” Arch Intern Med, 1980, 140(7):975-6.
International Brand Names
Lexi-Comp.com
Last full review/revision December 2011
Content last modified December 2011
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