Armodafinil is the enantiopure of the wakefulness-promoting agent, or
eugeroic, modafinil. It consists of just the-(R)-enantiomer of the racemic
modafinil. Armodafinil is produced by the pharmaceutical company Cephalon Inc.
and was approved by the U.S. Food and Drug Administration in June 2007.
Although they have similar half-lives, armodafinil reaches its peak
concentration in the blood later after administration than modafinil does,
which may make it more effective at improving wakefulness in patients with
excessive daytime sleepiness. Medical uses
Armodafinil is currently FDA-approved to treat excessive daytime sleepiness
associated with obstructive sleep apnea, narcolepsy, and shift work disorder. It
is commonly used off-label to treat attention deficit hyperactivity
disorder, chronic fatigue syndrome, and major depressive disorder. It has been
shown to improve vigilance in air traffic controllers.
= Sleep disorders= Armodafinil is approved by the U.S. FDA
for the treatment of narcolepsy and shift work sleep disorder, and as an
adjuvant therapy for obstructive sleep apnea. For narcolepsy and obstructive
sleep apnea, armodafinil is taken as a once daily 150 mg or 250 mg dose in the
morning. For shift work sleep disorder, 150 mg of armodafinil are taken one hour
prior to starting work. Slow dose titration is needed to mitigate some
side effects. = Investigational=
Schizophrenia In June, 2010, it was revealed that a
phase II study of armodafinil as an adjunctive therapy in adults with
schizophrenia had failed to meet the primary endpoints, and the clinical
program was subsequently terminated. However, a study published later that
year showed that schizophrenic patients treated with armodafinil showed fewer of
the negative symptoms of schizophrenia. Jet lag
On March 30, 2010, the FDA declined to approve use of Nuvigil to treat jet lag.
Adverse effects In placebo-controlled studies, the most
commonly observed side effects were headache, xerostomia, nausea, dizziness,
and insomnia. Possible side effects include
depression, anxiety, hallucinations, euphoria, extreme increase in activity
and talking, anorexia, tremor, thirst, rash, suicidal thoughts, and aggression.
Symptoms of an overdose on modafinil include trouble sleeping, restlessness,
confusion, disorientation, feeling excited, mania, hallucinations, nausea,
diarrhea, severely increased or decreased heart beat, chest pain, and
increased blood pressure. Pharmacology
= Pharmacodynamics= The mechanism of action of armodafinil
is unknown. Armodafinil has pharmacological properties almost
identical to those of modafinil. The R- and S- enantiomers have similar
pharmacological action in animals. Armodafinil has wake-promoting actions
similar to sympathomimetic agents including amphetamine and
methylphenidate, although its pharmacologic profile is not identical
to that of the sympathomimetic amines. Armodafinil is an indirect dopamine
receptor agonist; it binds in vitro to the dopamine transporter and inhibits
dopamine reuptake. For modafinil, this activity has been associated in vivo
with increased extracellular dopamine levels. In genetically engineered mice
lacking the dopamine transporter, modafinil lacked wake-promoting
activity, suggesting that this activity was DAT-dependent. However, the
wake-promoting effects of modafinil, unlike those of amphetamine, were not
antagonized by the dopamine receptor antagonist haloperidol in rats. In
addition, alpha-methyl-p-tyrosine, a dopamine synthesis inhibitor, blocks the
action of amphetamine but does not block locomotor activity induced by modafinil.
In addition to its wake-promoting effects and ability to increase
locomotor activity in animals, armodafinil produces psychoactive and
euphoric effects, alterations in mood, perception, thinking, and feelings
typical of other central nervous system stimulants in humans. Modafinil has
reinforcing properties, as evidenced by its self-administration in monkeys
previously trained to administer cocaine; armodafinil was also partially
discriminated as stimulant-like. Armodafinil has been shown to have a
similar abuse potential to methylphenidate in an inpatient study
with experienced drug users. Armodafinil produced psychoactive and euphoric
effects consistent with other CNS stimulants. An independent study in
which patients were administered modafinil, methylphenidate, and a
placebo found that modafinil produces the same level of extracellular dopamine
produced by methylphenidate. = Pharmacokinetics=
Armodafinil exhibits linear time-independent kinetics following
single and multiple oral dose administration. Increase in systemic
exposure is proportional over the dose range of 50–400 mg. No time-dependent
change in kinetics was observed through 12 weeks of dosing. Apparent steady
state for armodafinil was reached within 7 days of dosing. At steady state, the
systemic exposure for armodafinil is 1.8 times the exposure observed after a
single dose. The concentration-time profiles of the R-enantiomer following a
single dose of 50 mg Nuvigil or 100 mg Provigil are nearly superimposable.
However, the Cmax of armodafinil at steady state was 37% higher following
administration of 200 mg Nuvigil than the corresponding value of modafinil
following administration of 200 mg Provigil due to the more rapid clearance
of the S-enantiomer. Absorption
Armodafinil is readily absorbed after oral administration. The absolute oral
bioavailability was not determined due to the aqueous insolubility of
armodafinil, which precluded intravenous administration. Peak plasma
concentrations are attained at approximately 2 hours in the fasted
state. Food effect on the overall bioavailability of armodafinil is
considered minimal; however, time to reach peak concentration may be delayed
2–4 hours in the fed state. Since the delay in t max is also associated with
elevated plasma concentration later in time, food can potentially affect the
onset and time course of pharmacologic action of armodafinil.
Society and culture = Brand names=
Armodafinil is sold under a wide variety of brand names worldwide.
R-Modawake - India Artvigil - India
Waklert - India See also
Adrafinil Ampakine
CRL-40,941 Fluorenol
Modafinil References
External links NUVIGIL.com - official site
Medication Guide for Patients Full Prescribing Information