Pemoline dosing

Pemoline is less potent than the other available stimulants. It is started at 18.75 mg each morning and is increased in increments of 18.75 mg every week or two. The maximum dose is 112.5mg/day, though some patients do require higher doses. Because pemoline is less potent than other stimulants, it is more likely to be ineffective even at its higher doses. When pemoline does not relieve the symptoms of ADHD, patients should be changed to a different stimulant. 

Although side effects of other stimulants respond to dose reduction or change in time of administration, PEM use can be associated with serious, irreversible liver damage. Postmarketing surveillance revealed abnormalities in liver function tests in 44 children receiving PEM acutely or chronically (Berkovitch et ah, 1995). Even more disturbing, 13 children on PEM experienced total liver failure—11 resulting in death or transplant within 4 weeks of failure. This exceeds the rate in the normal population by 4 to 17 times. Pemoline, therefore, is reserved for alternative treatment only if the patient fails to tolerate all three stimulants (MPH, DEX, and AMP) and subsequent trials of an-... 

Pelham, W.E., Swanson, J., Furman, M., and Schwindt, H. (1995) Pemoline effects of children with ADHD a time-reponse by dose-response analysis on classroom measures./ Am Acad Child Adolesc Psychiatry 34 1504-1513. 

Methylphenidate and D-amphetamine are both short-acting compounds, with an onset of action within 30 to 60 minutes and a peak clinical effect seen usually between 1 and 2 hours after administration, lasting 2 to 5 hours. Therefore, multiple daily administrations are required for a consistent daytime response. The amphetamine compound Adderall, the sustained-release preparations of methylphenidate and dextroamphetamine, and pemoline are all intermediate-acting compounds with an onset of action within 60 minutes and a peak clinical effect seen usually between 1 and 3 hours after administration and maintained for up to 8 hours (8 hours with metadate C.D. and Ritalin LA 12 hours with Concerta), allowing for a single dose for the entire school day. Adderall XR is a 12 hour preparation. 

A frequently used test to assess the effect of psychostimulants is the CPT. Methylphenidate at doses of around 0.3mg/kg usually improves performance, Le. reduces the number of errors, on the CPT whereas the effects of d-amphetamine (at doses between 5 and 20 mg) and pemoline (10 60mg) appear to be less reliable (Riccio et al., 2001). The stimulating effect of caffeine in various areas of performance is of shorter duration than that of... 

The starting dose of pemoline for children weighing less than 35 kg is 37.5 mg in the morning for heavier children, the starting doses is 56.25 mg. Each week the dose can be escalated in 18.75-mg increments to a maximum of 112.5 and 150 mg in lighter and heavier children, respectively ( 74). 

The usual starting dose for the treatment of ADHD in children over 5 years of age is 37.5 mg/ day, increased gradually by 18.75 mg/week until the desired response is reached. The usual therapeutic dose range is from 56.25 to 75 mg/day, with a maximum dose of 112 mg/day (57). Since pemoline is not approved for the treatment of narcolepsy, dosage recommendations for this indication are not readily available however, in the subsequent section, dosage information can be extrapolated from a small number of sleep deprivation studies. 

Information on pemoline s tolerance and toxicity is not available. However, as with almost any drag, there is a chance of psychological and/or physical dependence with excessive doses and/or long-term misuse (57). In comparison to methylphenidate and amphetamine, pemoline has the least potential for abuse (39). Benowitz (41) suggests that approximately 3 mg/kg pemoline should be considered life-threatening. Treatment for overdose is similar to what has been recommended for methylphenidate and amphetamine. In cases of overdose, the administration of chlorpromazine has been found useful for decreasing the amount of CNS overstimulation (57). 

In summary, the literature suggests pemoline could be useful for sustaining alertness and performance over short periods of sleep deprivation (24 hr). In fact, there are some indications that pemoline is more efficacious for this purpose than methylphenidate, although the drug may have a slower onset of action. Pemoline seems to affect reaction time more so than accuracy in various performance tasks, and it exerts no substantial effect on mood. One study raised the possibility that multiple doses may actually produce performance decrements in some tasks after the second day of continuous wakefulness, and this issue remains unresolved. In light of this fact and the fact that pemoline has been associated with hepatic failure, pemoline should not be considered for the maintenance of wakefulness in sleep-deprived people. 

Kelly TL, Ryman DH, Schlangen K, Gomez SA, Elsmore, TF. The effects of a single dose of pemoline on performance and mood during sleep deprivation. Milit... 

Kelly TL, Babkoff H, Matteson L, Gomez S, Naitoh P. The effect of moderate doses of methylphenidate and pemoline on the maintenance of performance speed during 64 hours of sleep deviation (abstr). Sleep Res 1990 19 67. 

EDS is usually treated using amphetamine-like CNS stimulants or modaflnil, a novel wake-promoting compound unrelated to amphetamines. The most commonly used amphetamine-like compounds aremethamphetamine, D-amphetamine, methylpheni-date, pemoline, and mazindol. The most important pharmacological property of these compounds is to release catecholamines, i.e., dopamine and norepinephrine. Amphetamine-like compounds also share the property of blocking the reuptake and the degradation of these monoamines (monoamine oxidase inhibition at high doses). All these properties presynaptically enhance dopamine transmission, which are likely to contribute to the EEG arousal effects of amphetamines. 

Disposition in the Body. Slowly absorbed after oral administration. About 50% of a dose is excreted in the urine as unchanged drug in 48 hours and about 4% as 5-phenyloxazolidine-2,4-dione the remainder is excreted in the urine as conjugated pemoline and unidentified polar metabolites mandelic acid is also a metabolite of pemoline. Less than 1% of a dose is eliminated in the faeces. 

A critical part of the assessment must be to determine the patient s impairment at various times throughout the day to ensure that medication coverage overlaps with the time when the patient is most likely to benefit. As with all medication trials, it is important to start with a low dose of medication and keep increasing it slowly until the optimal risk-to-benefit ratio has been determined. Stimulant medication (methylphenidate, mixed amphetamine salts, and pemoline) and atomoxetine (a non-stimulant selective norepinephrine reuptake inhibitor, approved by the FDA for adult ADHD) are the first-line treatments of adult ADHD. Pemoline is not recommended as first-line treatment due to the risk of hepatoxicity. Stimulant drugs used to treat adults with ADHD are considered safe and effective, and have been well studied. There are several new long-acting formulations of... 

Caffeine is the most popular psychoactive stimulant. This xanthine alkaloid occurs in coffee, tea, and cola beverages. At a modest dose of 100-200 mg, it enhances wakefulness and reduces fatigue. However, intake of higher quantities (>500 mg/day) can cause addiction. Other psychostimulant substances include deanol, pemoline, and their derivatives. These substances have limited clinical apphcation. The structures of caffeine. 

Methylphenidate (15) and magnesium pemoline (16) were more effective than placebo in mildly depressed outpatients however, psychiatric patients did not respond well to these stimulants.In a study dealing with a group of "neurophysiologic immature" inpatient children, minimal doses of methylphenidate produced favorable improvement in five of eight children.S3... 

Magnesium pemoline some doses were given 2 weeks pre-irradiation. Phenylhydrazine hydrochloride (CgH NHNH- HCl) when administered 5-8 days before Irradiation stimulation of erythropolesls and an Increase In stem cells may explain the protective effect. 

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