Armodafinil in the treatment of excessive sleepiness

Figures & data

Figure 1 Structure of (A) R-modafinil and (B) S-modafinil. Armodafinil comprises only R-modafinil, while racemic modafinil comprises a mixture of both R- and S-modafinil.

Table 1 Pharmacokinetic parameters of armodafinil and modafinil

Parameters	Armodafinil 200 mg (mean ± SD)	Modafinil 200 mg (mean ± SD)
Cmax(μg/mL)	5.44 ± 1.64	4.61 ± 0.73
AUClast (μg·h/mL)	88.2 ± 29.6	66.5 ± 14.4
AUC∞ (μg·h/mL)	95.8 ± 28.0	68.5 ± 15.3
tmax (h)a	1.8	2.5
t1/2β (h)	13.0 ± 2.6	13.6 ± 2.0

Note:

a Median values.

Reprinted with permission from Darwish M, Kirby M, Hellriegel ET, Robertson P Jr. Armodafinil and modafinil have substantially different pharmacokinetic profiles despite having the same terminal half lives: analysis of data from three randomized, single-dose, pharmacokinetic studies. Clin Drug investig. 2009;29(9):613–623.⁶⁶ Copyright © 2009 wolters Kluwer

Abbreviations: AUC_last, area under the plasma drug concentration vs time curve from time zero to the time of the last measurable concentration; AUC_∞, area under the plasma drug concentration vs time curve from time zero to infinity; C_max, maximum plasma drug concentration; SD, standard deviation; t_1/2β, terminal elimination half-life; t_max, time to reach C_max

Table 2 Wakefulness-promoting effects of armodafinil in the treatment of ES associated with OSA, SWD, and narcolepsy

Study/indication	Patients (n)	Treatment	Wakefulness
OSA
Hirshkowitz et al^Citation38	259		MWT
		Armodafinil (150 mg/day)	+2.3 min
		Placebo	−1.3 min (P < 0.001)
Roth et al^Citation39	395		MWT
		Armodafinil (150/250 mg/day)	+1.9 min
		Placebo	−1.7 min (P < 0.001)
Roth et al^Citation40	658		MWT
		Armodafinil (150/250 mg/day)	+2.0 min
		Placebo	−1.5 min (P < 0.0001)
SWD
Czeisler et al^Citation46	245		MSLT
		Armodafinil (150 mg/day)	+3.1 min
		Placebo (given 30–60 min before the shift)	+0.4 min (P < 0.001)
Narcolepsy
Harsh et al^Citation55	194		MWT
		Armodafinil (150/250 mg/day)	09:00–15:00: +1.9 min
			15:00–19:00: +1.6 min
		Placebo	09:00–15:00: −1.9 min (P < 0.01 vs armodafinil combined)
			15:00–19:00: −1.2 min (P < 0.05 vs armodafinil combined)

Abbreviations: ES, excessive sleepiness; MSLT, Multiple Sleep Latency Test; MWT, Maintenance of wakefulness Test; OSA, obstructive sleep apnea; SWD, shift-work disorder.

Table 3 The most commonly reported adverse events (≥5% of patients) occurring in patients with OSA, narcolepsy, or SWD treated with armodafinil (150 or 250 mg/day)^40,46,55

Indications	Adverse events	Incidence (%)
		Armodafinil (150/250 mg)	Placebo
OSA		(n = 391)	(n = 260)
	Headache	17	8
	Nausea	6	4
	insomnia	6	1
	Dizziness	5	2
	Anxiety	5	<1
Narcolepsy		(n = 131)	(n = 63)
	Headache	22	11
	Nausea	11	0
	Dizziness	5	0
SWD		(n = 123)	(n = 122)
	Headache	12	10
	Nausea	7	3
	Nasopharyngitis	6	3
	Anxiety	5	2

Abbreviations: OSA, obstructive sleep apnea; SWD, shift-work disorder.

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