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At least 19 recordsLinked to original sources
PubMed2007

Effectiveness of risk management plans: a case study of pemoline using pharmacy claims data.

PURPOSE: To assess the effectiveness of a pharmaceutical risk management plan using pemoline as a case study and pharmacy claims as the data source. METHODS: Prescription claims from a continuously enrolled US population (September 1, 2000-September 30, 2002) from Caremark, a pharmacy benefit manager, were evaluated for patients with one or more pemoline claims. Patients were categorized using pemoline as second-line or first-line therapy depending on presence or absence of other central nervous system (CNS) stimulants prescriptions 90 days prior to the first pemoline claim. Logistic regression was performed to compare second-line and first-line usage with regard to patient age, gender and prescribing physician specialty and region of practice. RESULTS: Of 1,279,296 prescription claims for CNS stimulants, 17,256 (1.3%) were for pemoline. Nine hundred thirteen patients received pemoline and had 90 days or more prior enrollment. Overall, 10% of patients receiving pemoline received it as second-line therapy (95%CI: 8-12%). After adjusting for age, gender, specialty, and region, the odds of receiving pemoline as second-line therapy were significantly greater in pediatrics relative to adults (OR = 2.82, 95%CI: 1.58-5.03), and among those whose prescribers were psychiatrists versus primary care physicians (OR = 2.48, 95%CI: 1.37-4.50). Children treated by a psychiatrist had the greatest likelihood for use as second-line therapy (36%, 95%CI: 19-56%). CONCLUSIONS: Among patients who received pemoline, concordance with second-line therapy recommendations was low, even among the primary target audience of children. These results in a large geographically diverse patient population are consistent with an earlier regional study.

Adolescent↗
PubMed2001

Pemoline hepatotoxicity and postmarketing surveillance.

OBJECTIVE: To review the numerous reports of hepatotoxic adverse drug reactions (ADRs) ascribed to pemoline that were sent to the U.S. Food and Drug Administration (FDA) between 1975 and 1996 and to describe the medical community's lack of awareness of these reports. METHOD: All ADR reports from 1975 through 1996 wherein pemoline was the suspect agent were obtained from the FDA MedWatch Internet site, and some details of nine pemoline-related deaths in youths were obtained directly from the FDA. The published literature on this subject was fully reviewed. RESULTS: (1) In premarketing clinical trials with pemoline in the early 1970s, hepatic abnormalities were noted in enzyme levels (1%-3% of youths receiving maintenance treatment), during rechallenges (6 of 6), and in biopsies (2 of 2). (2) Between 1975 and 1989, 12 cases of jaundice and 6 deaths in youths ascribed to pemoline hepatotoxicity were reported to the FDA. (3) The first medical literature report of a serious ADR ascribed to pemoline was in a 1989 letter to the editor. (4) Physicians generally only became aware of serious pemoline hepatotoxicity in December 1996. (5) Pemoline use increased until 1997. CONCLUSION: Limitations in postmarketing surveillance and public reporting in the United States, particularly in the 1980s, largely accounted for delays in an appropriate response to pemoline hepatotoxicity.

Adolescent↗
PubMed1995

Abnormal auditory P300 topography in attention deficit disorder predicts poor response to pemoline.

P300 is a cognitive evoked potential that evaluates attention and information processing. This study uses auditory and visual P300 topography to develop a classification of attention deficit disorder (ADD), and to find predictors of treatment response to the stimulant pemoline. Forty-five ADD children ages 6 to 15 were administered auditory and visual P300 using 31 scalp electrodes. They were compared with 39 normals. Patients were treated with pemoline, and good and poor responders compared. There were no P300 differences between normals and ADD patients. Good and poor responders to pemoline were clinically identical. Poor pemoline responders had smaller right fronto-central auditory P300 amplitudes than good responders. The ratio of right fronto-central to parietal auditory P300 amplitude, had a sensitivity of 0.70 and specificity of 0.76, as a test for good pemoline response. A ratio greater than 0.5 predicted good response to pemoline, while a ratio less than 0.5 predicted poor response. Treatment with pemoline produced no P300 changes. We conclude that P300 topography classifies ADD into group 1 with normal P300 topography and good response to pemoline, and group 2 with small right fronto-central auditory P300 amplitudes and poor response to pemoline.

Adolescent↗
PubMed1992

Pharmacodynamics of pemoline in attention deficit disorder with hyperactivity.

The onset, duration, and offset of pemoline action to improve cognitive performance is examined intensively in 25 prepubescent males suffering from attention-deficit disorder with hyperactivity (ADDH). The purpose was to characterize the pharmacodynamics of pemoline in ADDH patients through correlation of plasma pemoline concentration with psychometric measures of memory search efficiency and paired-associates learning, with the physiological effect of pemoline on dopaminergic transmission concurrently measured by analysis of plasma prolactin response. The effect of pemoline on neuroprocessing is apparent within the first 2 hours after administration with an inverse relationship between plasma pemoline and prolactin concentration present at hour one only (r = 0.84; p = 0.005). Pemoline therapy for 3 weeks does not significantly affect area under the curve for pemoline or prolactin nor did the effect on memory search efficiency decrease, suggesting no apparent tolerance.

Attention↗
PubMed2004

A randomized controlled trial of pemoline for attention-deficit/hyperactivity disorder in substance-abusing adolescents.

OBJECTIVE: In adolescents with substance use disorder (SUD), comorbid attention-deficit/hyperactivity disorder (ADHD) is associated with greater severity of substance abuse, conduct problems, and worse treatment outcomes. Although many controlled trials have established the efficacy of psychostimulants, including pemoline, for ADHD in children and adolescents, none have been conducted in adolescents with SUD. This randomized, placebo-controlled trial, conducted between 1996 and 2000, evaluated the safety and efficacy of pemoline on substance abuse and conduct problems. METHOD: Sixty-nine adolescents (aged 13-19) with conduct disorder (CD), SUD, and ADHD were recruited from the community and randomly assigned to a 12-week clinical trial of pemoline (n = 35) or placebo (n = 34), titrated over 4 weeks to a single morning dose of 75 to 112.5 mg as tolerated. RESULTS: Pemoline had greater efficacy than placebo for ADHD as determined by significantly more Clinician's Global Impression-Improvement (CGI-I) ratings of 1 (very much improved) or 2 (much improved) at the study endpoint (n = 69; p <.05). There was also greater reduction in ADHD severity on the parent-rated Conners Hyperactivity-Impulsivity scale in pemoline-treated study completers compared to placebo-treated completers (pemoline, n = 17; placebo, n = 16; p <.01), but no difference between groups in the intent-to-treat analysis (n = 68; p <.13). Substance use did not decline in either group, and there was no difference between groups in baseline to study endpoint change in substance use or CD symptoms. Overall, pemoline was well tolerated, demonstrating a good safety profile and no elevation in liver enzyme levels. CONCLUSIONS: Pemoline was efficacious for ADHD but did not have an impact on CD or substance abuse in the absence of specific treatment for SUD.

Adolescent↗
PubMed1989

Pemoline-induced abnormal involuntary movements.

Plasma pemoline levels were measured in 6- to 12-year-old, severely hyperactive males coincident with onset of abnormal involuntary movements. Acute exposure to pemoline (2 mg/kg orally) was associated with choreoathetoid movements of face, limbs, and trunk in five of 20 subjects in an acute study of pemoline pharmacokinetics. Also reported is a series of four chronically treated patients who developed choreiform movements and dyskinesias after variable periods of exposure from 3 weeks to 3 months with pemoline (1.5-2.0 mg/kg/day). Abnormal movements following acute or chronic exposure to pemoline cleared after pemoline discontinuation. Pemoline pharmacokinetics does not seem to be a primary determinant in the development of abnormal involuntary movements after chronic exposure. Total amount of pemoline absorbed may play a role in the development of choreoathetoid movements following acute exposure.

Attention Deficit Disorder with Hyperactivity↗
PubMed1984

Determination of pemoline in plasma, plasma water, mixed saliva, and urine by high-performance liquid chromatography.

A new determination method of pemoline in plasma, plasma water, mixed saliva, and urine using high-performance liquid chromatography was developed. The detection limit of pemoline using 0.2 ml of the sample was 0.02 microgram/ml in plasma, plasma water, saliva, and urine. The recoveries of pemoline added to plasma, saliva, and urine (each 6 micrograms/ml) were more than 98%. The coefficients of variation of within-run and between-run precisions for 5 concentrations of pemoline in plasma were less than 5 and 6%, respectively. The elimination half-lives of pemoline obtained from the plasma concentration-time curves after a single oral administration of pemoline in two subjects were 6.7 and 10.3 h. Mean values of the ratio between saliva and plasma total concentration in two subjects were 0.55 and 0.64, and mean values of plasma protein binding percent were 35.7 and 25.2%, respectively. The saliva concentrations were in proportion to the plasma unbound pemoline concentrations at simultaneous samplings, and the ratios between saliva and plasma unbound concentration were about 0.9 in two subjects. Usefulness of saliva in the estimation of plasma protein-unbound pemoline concentration was noted.

Adult↗
PubMed1995

Pemoline-associated fulminant liver failure: testing the evidence for causation.

BACKGROUND: Pemoline is a central nervous system stimulant used in treating children with attention deficit-hyperactivity disorder. Hepatotoxicity has been commonly reported in association with pemoline; however, only two reports of cases of fatal liver failure have been published. OBJECTIVES: We report on a 14-year-old boy who received concomitant pemoline and methylphenidate in whom fulminant liver failure occurred and for whom liver transplantation failed. Other causes of fulminant liver failure were ruled out, and the liver biopsy was suggestive of drug toxicity. We estimated the probability that these three cases represent an increased risk of fulminant liver failure associated with pemoline. RESULTS: Based on the three known cases of fatal liver failure associated with pemoline use, we calculated that a child receiving pemoline has a relative risk of development of fulminant liver failure of 45.3 (95% confidence interval, 4.1 to 510). This highly significant association (p < 0.001) suggests causation. CONCLUSIONS: Because pemoline has been widely used in recent years, further studies are needed to better quantify this risk in children with attention deficit-hyperactivity disorder.

Adolescent↗
PubMed1989

Methylphenidate and pemoline do not cause depletion of rat brain monoamine markers similar to that observed with methamphetamine.

Methylphenidate (Ritalin) and pemoline (Cylert) are central nervous system stimulants which are widely prescribed for attention deficit and other psychiatric disorders. Several other related stimulants, including amphetamine and methamphetamine, have been shown to cause long lasting decreases in monoamine markers in rat brain, characteristic of axonal degeneration. To assess the neurotoxic potential of methylphenidate and pemoline, we compared the effects of multiple injections (sc, bid for up to 4 days) of methylphenidate (21 and 50 mg/kg) and pemoline (20 and 70 mg/kg) with methamphetamine (5 and 15 mg/kg) on rat brain norepinephrine, dopamine, and serotonin levels and transport sites. While decreases were observed in all brain monoamine markers measured in rats treated with methamphetamine, no changes were observed in animals treated with methylphenidate as compared to saline-treated controls. Pemoline failed to induce significant changes in the level of monoamine transport sites; however, a wide array of changes were observed in the levels of 5-hydroxyindoleacetic acid, dopamine, and norepinephrine in various brain areas after a 3-day treatment regimen with a high dose (70 mg/kg) of pemoline. The lack of changes in monoamine transport sites following the repeated administration of high doses of methylphenidate and pemoline suggests that these drugs do not affect axonal integrity. However, the pattern of changes observed in the levels of monoamines after pemoline treatment may have relevance to the self-injurious behavior seen in these animals.

Animals↗
PubMed1982

Pharmacologic control of pemoline induced self-injurious behavior in rats.

Administration of oral Pemoline produces long lasting amphetamine-type stereotyped behavior and persistent self-biting behavior in rats. The effects of haloperidol, pimozide, diazepam, and serotonin depletion by pretreatment with p-chlorophenylalanine (PCPA) or chronic pretreatment with p-chloroamphetamine (PCA) on abnormal behavior produced by pemoline were studied. Diazepam consistently increased the duration of stereotyped behavior. It also reduced licking/biting and self-biting but the latter effects were not consistent. Pretreatment with PCA had negligible effects on stereotyped behavior. Pretreatment with PCPA dramatically increased locomotion and rearing without affecting the other components of stereotypy--stereotyped head movements, licking/biting, and self-biting. Haloperidol (0.2 and 0.3 mg/kg) produced a dose related normalization of pemoline induced behaviors, including elimination of self-biting. Pimozide (0.5, 0.8 and 1.3 mg/kg) had little or no effect on behaviors such as locomotions, rears, licking/biting, or stereotyped head movements but eliminated self-biting at 1.3 mg/kg. These data suggest that pemoline, like amphetamine, produces stereotyped behavior through central dopaminergic mechanisms. Dopaminergic mechanisms also appear to be involved in pemoline induced self-biting. pemoline is apparently pharmacologically and behaviorally very similar to amphetamine. Pemoline may provide a useful animal model for syndromes characterized by self-injurious behavior and other repetitive behaviors.

Amphetamines↗
PubMed1999

Controlled trial of high doses of pemoline for adults with attention-deficit/hyperactivity disorder.

Despite the increasing awareness of attention-deficit/hyperactivity disorder (ADHD) in adults, there are a limited number of controlled pharmacologic studies of this disorder. Because the stimulant medication magnesium pemoline (Cylert, Abbott Laboratories, Abbott Park, IL) has been found effective in treating ADHD in pediatric groups, we tested its efficacy in adults with ADHD using higher daily doses than those previously studied. We conducted a 10-week, double-blind, placebo-controlled, crossover design study of pemoline at a target daily dose of 3 mg/kg per day in 35 adult patients with DSM-III-R and -IV ADHD. We used standardized structured psychiatric instruments for diagnosis. To measure improvement, we used separate assessments of ADHD, depressive, and anxiety symptoms at baseline and at each biweekly visit. ADHD outcome was determined using the ADHD symptom checklist and Clinical Global Impression scales of Severity and Improvement. Of the 35 adults with ADHD who were randomized in the trial, 27 (77%) completed the protocol. Treatment with pemoline in the final week of the 4-week active phase was best tolerated at doses substantially lower than the target dose of 3 mg/kg per day (mean dose, 2.2 mg/kg per day; mean+/-SD, 148+/-95 mg). Pemoline was significantly better at reducing ADHD symptoms compared with placebo (z = 2.4,p < 0.02). Using a predefined 30% reduction in symptoms as an indication of improvement, 50% of pemoline-treated subjects and 17% of subjects in the placebo group were considered positive responders (chi2 = 7.1, p = 0.008). These results indicate that pemoline is moderately effective in the treatment of ADHD in adults. Although robust doses were targeted, most adults preferred more moderate dosing (120-160 mg/day). Given the limited efficacy, tolerability, and concerns of hepatic dysfunction, pemoline should be considered as second-line medication for treating ADHD in adults.

Adult↗
PubMed1997

Pemoline alters dopamine modulation of synaptic responses of neostriatal neurons in vitro.

Pemoline, a central stimulant, administered systemically at high doses (300 mg/kg) reliably produces self-biting behavior in rats. Pemoline-induced self-biting shares many similarities with self-injury seen in certain human disorders. Recent evidence has shown that alterations in neostriatal neurochemistry accompany the self-biting behavior seen in the rat. The present study used intracellular electrophysiological techniques to reveal changes in neostriatal cellular physiology in slices from rats which had displayed self-injury. Depolarizing postsynaptic potentials (DPSPs) were examined in neostriatal slices from rats that received pemoline and had been engaging in self-injurious behavior and from two control populations: rats that received the same concentration of pemoline and did not engage in self-biting, and rats that received vehicle alone (peanut oil). Data were acquired in standard artificial cerebral spinal fluid. DPSPs were evoked by cortical electrical stimulation in the slice. In neurons from rats that received the vehicle or that had received pemoline but had not engaged in self-injury, dopamine (DA, 20 microM) application produced a significant decrease in the size of the cortically evoked neostriatal DPSP. In contrast, DA application produced an increase in DPSP size in neurons from rats which had received pemoline and had engaged in self-injury. Bath application of a combination of D1 and D2 receptor agonists best replicated the enhancing effect of DA. Furthermore, the enhancement could be blocked by pretreatment with the competitive N-methyl-d-aspartate receptor antagonist, 2-amino-5-phosphonopentanoic acid. The results indicate that alterations in neostriatal DA-glutamate interactions accompany pemoline injections which produce self-injurious behavior.

Animals↗
PubMed2002

Pemoline ingestion in children: a report of five cases and review of the literature.

The authors describe five pediatric cases of excessive pemoline ingestion. Based on their experience compared with previously reported cases in the literature, they describe the clinical presentation and rational treatment recommendations for acute pemoline ingestion. Overall, patients experienced a relatively benign clinical course following pemoline ingestion. Symptoms of pemoline ingestion appear to be primarily an accentuation of the drug's pharmacological effects on the central nervous and cardiovascular systems with sinus tachycardia, hypertension, hyperactivity, choreoathetoid movements, and hallucinations being most commonly observed. These findings are consistent with previously reported cases. Possible rhabdomyolysis manifested by evaluation of serum CPK was also observed in 3 of 4 patients in whom this laboratory parameter was measured and appears to be a common finding in acute pemoline poisoning. After acute ingestion, symptoms occurred within 6 hours, lasting up to 48 hours in all patients. Gastric lavage and/or activated charcoal would be effective decontamination measures, whereas ipecac-induced emesis should be avoided after massive ingestion due to the possibility of seizures. Aggressive use of a benzodiazepine appears a reasonable first choice to treat associated involuntary movements, tremor, hyperactivity, irritability, and agitation. Phenothiazines or butyrophenones may also be used especially for serious life-threatening symptoms, including hypertensive crisis and severe hyperthermia, although these serious complications of stimulant overdose have not been reported after pemoline ingestion. If a patient should experience pemoline-induced hypertensive crisis, individual dose titration of labetalol or sodium nitroprusside would appear reasonable pharmacologic approaches for rapid stabilization of blood pressure.

Adolescent↗
PubMed1995

Fatigue therapy in multiple sclerosis: results of a double-blind, randomized, parallel trial of amantadine, pemoline, and placebo.

OBJECTIVE: To determine the relative efficacy of amantadine, pemoline, and placebo in treatment of multiple sclerosis (MS)-related fatigue. BACKGROUND: Fatigue is a complication of MS. Both pemoline and amantadine have been used to treat MS fatigue, but their relative efficacy is not known. METHODS: Amantadine, pemoline, and placebo were compared in a randomized, double-blind, placebo-controlled study using a parallel-group design. Ninety-three ambulatory MS patients completed the study. Primary outcome measures were the fatigue severity scale (FSS); the MS-specific fatigue scale (MS-FS); and subjective response determined by verbal self-report. Secondary outcome measures consisted of assessments of sleep, depression, and vitality. Repeated-measures analysis of variance with planned post-hoc contrasts and Fisher's exact test were used to compare treatment response. RESULTS: Amantadine-treated patients showed a significantly greater reduction in fatigue, as measured by the MS-FS, than did patients treated with placebo (p = 0.04). By verbal report at the end of the study, 79% of patients treated with amantadine versus 52% treated with placebo and 32% treated with pemoline preferred drug therapy compared with no treatment (p = 0.03). No significant differences in any primary outcome measures were noted between pemoline and placebo. Neither amantadine nor pemoline affected sleep or depression relative to placebo. CONCLUSION: Amantadine was significantly better than placebo in treating fatigue in MS patients, whereas pemoline was not. The benefit of amantadine was not due to changes in sleep, depression, or neurologic disability.

Adolescent↗