ACEP News - June 2008 - (Page 8)

PSYCHIATRY ACEP NEWS • J U N E 2 0 0 8 Distinguish Delirium From Dementia With Brief Exams B Y M I C H E L E G. S U L L I VA N Else vier Global Medical Ne ws S A N F R A N C I S C O — Two brief mental state exams can reliably differentiate delirium from dementia in the elderly emergency department patient. Because delirium usually is caused by an organic illness, confusional symptoms may disappear once the underlying problem is treated, said Dr. Allen Yuen, director of emergency medicine at Epworth Hospital, Melbourne. Dementia, the product of a SKELAXIN® (Metaxalone) Tablets DESCRIPTION SKELAXIN® (metaxalone) is available as an 800 mg oval, scored pink tablet. Chemically, metaxalone is 5-[(3,5- dimethylphenoxy) methyl]2-oxazolidinone. The empirical formula is C 12H15NO3, which corresponds to a molecular weight of 221.25. The structural formula is: CH3 progressive disease, is largely untreatable. “Poor differentiation between the confusional states is associated with poor outcomes in the patients, with increased morbidity and mortality, longer hospital stays, and functional decline,” he said at the 12th International Conference on Emergency Medicine. There are three types of confusion in elderly patients, Dr. Yuen said at the meeting, which was hosted by the American College of Emergency Physicians. Delirium is characterized by the sudden onset of symp- toms. Patients may appear either drowsy or agitated. They can exhibit variable shortterm memory, poor attention, disorganized thoughts, and even hallucinations. The causes range from cardiovascular disorders—such as cerebral ischemia, myocardial infarction, and pulmonary embolism—to seemingly innocuous problems like a urinary tract infection, pain, cold, urinary retention, and constipation. Dementia is a state of chronic confusion induced by a long-term neurologic illness such as Alzheimer’s disease. This is proPRECAUTIONS Metaxalone should be administered with great care to patients with pre-existing liver damage. Serial liver function studies should be performed in these patients. False-positive Benedict’s tests, due to an unknown reducing substance, have been noted. A glucose-specific test will differentiate findings. Taking SKELAXIN with food may enhance general CNS depression; elderly patients may be especially susceptible to this CNS effect. (See CLINICAL PHARMACOLOGY: Pharmacokinetics and PRECAUTIONS: Information for Patients section). Information for Patients SKELAXIN may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle, especially when used with alcohol or other CNS depressants. Drug Interactions SKELAXIN may enhance the effects of alcohol, barbiturates and other CNS depressants. Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenic potential of metaxalone has not been determined. Pregnancy Reproduction studies in rats have not revealed evidence of impaired fertility or harm to the fetus due to metaxalone. Post marketing experience has not revealed evidence of fetal injury, but such experience cannot exclude the possibility of infrequent or subtle damage to the human fetus. Safe use of metaxalone has not been established with regard to possible adverse effects upon fetal development. Therefore, metaxalone tablets should not be used in women who are or may become pregnant and particularly during early pregnancy unless in the judgement of the physician the potential benefits outweigh the possible hazards. Nursing Mothers It is not known whether this drug is secreted in human milk. As a general rule, nursing should not be undertaken while a patient is on a drug since many drugs are excreted in human milk. Pediatric Use Safety and effectiveness in children 12 years of age and below have not been established. ADVERSE REACTIONS The most frequent reactions to metaxalone include: CNS: drowsiness, dizziness, headache, and nervousness or “irritability”; Digestive: nausea, vomiting, gastrointestinal upset. Other adverse reactions are: Immune System: hypersensitivity reaction, rash with or without pruritus; Hematologic: leukopenia; hemolytic anemia; Hepatobiliary: jaundice. Though rare, anaphylactoid reactions have been reported with metaxalone. OVERDOSAGE Deaths by deliberate or accidental overdose have occurred with metaxalone, particularly in combination with antidepressants, and have been reported with this class of drug in combination with alcohol. When determining the LD50 in rats and mice, progressive sedation, hypnosis and finally respiratory failure were noted as the dosage increased. In dogs, no LD50 could be determined as the higher doses produced an emetic action in 15 to 30 minutes. Treatment - Gastric lavage and supportive therapy. Consultation with a regional poison control center is recommended. DOSAGE AND ADMINISTRATION The recommended dose for adults and children over 12 years of age is one 800 mg tablet three to four times a day. HOW SUPPLIED SKELAXIN (metaxalone) is available as an 800 mg oval, scored pink tablet inscribed with 8667 on the scored side and “S” on the other. Available in bottles of 100 (NDC 60793-136-01) and in bottles of 500 (NDC 60793-136-05). Store at Controlled Room Temperature, between 15°C and 30°C (59°F and 86°F). Rx Only Prescribing Information as of April 2007. gressive and irreversible. Short-term memory is impaired, and the patient may not be able to perform simple tasks when asked. Language may be impaired. Family members may report aggression or personality changes. Acute or chronic confusion occurs when a treatable illness, such as infection, brings on acute delirium in a patient with dementia. A combination of the Confusion Assessment Method (CAM) and the MiniMental State Exam (MMSE) is highly effective in differentiating the types of confusion, Dr. Yuen said. “A positive CAM and an MMSE score of more than 25 are strongly predictive of delirium,” he said. CAM has sensitivity of 95%-100% and a specificity of up to 95% for diagnosing delirium in the elderly. It relies on observations both by family members or caretakers and clinicians to assess four symp- O CH2 CH O CH2 NH C O CH3 Metaxalone is a white to almost white, odorless crystalline powder freely soluble in chloroform, soluble in methanol and in 96% ethanol, but practically insoluble in ether or water. Each tablet contains 800 mg metaxalone and the following inactive ingredients: alginic acid, ammonium calcium alginate, B-Rose Liquid, corn starch and magnesium stearate. CLINICAL PHARMACOLOGY Mechanism of Action: The mechanism of action of metaxalone in humans has not been established, but may be due to general central nervous system depression. Metaxalone has no direct action on the contractile mechanism of striated muscle, the motor end plate or the nerve fiber. Pharmacokinetics: The pharmacokinetics of metaxalone have been evaluated in healthy adult volunteers after single dose administration of SKELAXIN under fasted and fed conditions at doses ranging from 400 mg to 800 mg. Absorption Peak plasma concentrations of metaxalone occur approximately 3 hours after a 400 mg oral dose under fasted conditions. Thereafter, metaxalone concentrations decline log-linearly with a terminal half-life of 9.0 ± 4.8 hours. Doubling the dose of SKELAXIN from 400 mg to 800 mg results in a roughly proportional increase in metaxalone exposure as indicated by peak plasma concentrations (Cmax) and area under the curve (AUC). Dose proportionality at doses above 800 mg has not been studied. The absolute bioavailability of metaxalone is not known. The single-dose pharmacokinetic parameters of metaxalone in two groups of healthy volunteers are shown in Table 1. Table 1: Mean (%CV) Metaxalone Pharmacokinetic Parameters Dose (mg) 4001 8002 Distribution, Metabolism, and Excretion Although plasma protein binding and absolute bioavailability of metaxalone are not known, the apparent volume of distribution (V/F ~ 800 L) and lipophilicity (log P = 2.42) of metaxalone suggest that the drug is extensively distributed in the tissues. Metaxalone is metabolized by the liver and excreted in the urine as unidentified metabolites. Pharmacokinetics in Special Populations Age: The effects of age on the pharmacokinetics of metaxalone were determined following single administration of two 400 mg tablets (800 mg) under fasted and fed conditions. The results were analyzed separately, as well as in combination with the results from three other studies. Using the combined data, the results indicate that the pharmacokinetics of metaxalone are significantly more affected by age under fasted conditions than under fed conditions, with bioavailability under fasted conditions increasing with age. The bioavailability of metaxalone under fasted and fed conditions in three groups of healthy volunteers of varying age is shown in Table 2. Table 2: Mean (%CV) Pharmacokinetics Parameters Following Single Administration of Two 400 mg SKELAXIN Tablets (800 mg) under Fasted and Fed Conditions Younger Volunteers Older Volunteers Age (years) 25.6 ± 8.7 39.3 ± 10.8 71.5 ± 5.0 N 59 21 23 Food Fasted Fed Fasted Fed Fasted Fed Cmax 1816 3510 2719 2915 3168 3680 (ng/mL) (43) (41) (46) (55) (43) (59) Tmax (h) AUC0-t (ng⋅h/mL) AUC∞ (ng⋅h/mL) 3.0 (39) 14531 (47) 15045 (46) 4.9 (48) 20683 (41) 20833 (41) 3.0 8.7 2.6 6.5 (40) (91) (30) (67) 19836 20482 23797 24340 (40) (37) (45) (48) 20490 20815 24194 24704 (39) (37) (44) (47) THE CONFUSION ASSESSMENT METHOD HAS A SENSITIVITY OF 95%-100% AND A SPECIFICITY OF UP TO 95% FOR DIAGNOSING DELIRIUM IN THE ELDERLY. toms: acute confusional onset, inattention, disorganized thinking, and altered level of consciousness. The diagnosis of delirium by CAM requires the presence of both the first and second feature and at least one of the other two. The MMSE, while not considered a diagnostic tool, does identify patients with cognitive impairment suggestive of dementia. The screen measures orient http://www.kingpharm.com http://www.kingpharm.com http://www.kingpharm.com http://www.skelaxin.com

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ACEP News - June 2008 Contents News - Time to Move Tricks of the Trade - Revealing Tips Focus On - Dengue Fever Practice Trends - EMTALA Results

ACEP News - June 2008

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