Armodafinil, sold under the brand name Nuvigil, is a wakefulness-promoting medication which is used to treat excessive daytime sleepiness associated with obstructive sleep apnea, narcolepsy, and shift work disorder.
of armodafinil include headache, nausea, dizziness, and insomnia.
Armodafinil is produced by the pharmaceutical company Cephalon
Medical uses
Armodafinil is currently FDA-approved to treat excessive daytime sleepiness (EDS) associated with obstructive sleep apnea (OSA),
narcolepsy, and shift work sleep disorder (SWSD).
It is commonly used
off-label use to treat attention deficit hyperactivity disorder (ADHD), chronic fatigue syndrome (CFS), and major depressive disorder (MDD), and has been repurposed as an
adjunct therapy for
bipolar disorder.
It has been shown to improve
alertness in air traffic controllers,
however in the United States, wakefulness-promoting medications such as
modafinil (Provigil) and armodafinil (Nuvigil) are not approved by the Federal Aviation Administration (FAA) for civilian controllers or pilots.
Psychiatry
Bipolar disorder
Armodafinil, along with racemic modafinil, has been repurposed as an adjunctive treatment for acute depression in people with
bipolar disorder.
Meta-analytic evidence showed that add-on modafinil and armodafinil were more effective than placebo on response to treatment, clinical remission, and reduction in depressive symptoms, with only minor side effects, but the effect sizes are small and the quality of evidence has to be considered low, limiting the clinical relevance of current evidence. However current dosage for bipolar disorder is 150 mg once daily. Paradoxical tiredness and sleeping is observed in some cases.
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 patients with schizophrenia 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.
Available forms
Armodafinil is available in the form of 50, 150, 200, and 250mg oral tablets.
A 50mg dose of armodafinil is essentially equivalent to at 100mg dose of modafinil in terms of drug levels.
Adverse effects
In placebo-controlled studies, the most commonly observed side effects were
headache,
xerostomia (dry mouth),
nausea,
dizziness, and
insomnia.
Possible side effects also include depression, anxiety, hallucinations, euphoria, extreme increase in activity and talking, anorexia, tremor, thirst, rash, suicidal thoughts, and aggression. Symptoms of an overdose on armodafinil include trouble sleeping, restlessness, confusion, disorientation, feeling excited, mania, hallucinations, nausea, diarrhea, severely increased or decreased heart beat, chest pain, and increased blood pressure.
Serious rashes can develop in rare cases, and require immediate medical attention due to the possibility of Stevens–Johnson syndrome, or other
Hypersensitivity to armodafinil.
Misuse potential
Armodafinil has a low
misuse potential similar to
modafinil.
Interactions
Hypertensive crises have been reported when armodafinil has been taken with monoamine oxidase inhibitors (MAOIs) like
tranylcypromine.
Pharmacology
Pharmacodynamics
The mechanism of action of armodafinil is unknown. Armodafinil (
R-(−)-modafinil) has pharmacological properties almost identical to those of
modafinil (a mixture of
R-(−)- and (
S)-(+)-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 binds
in vitro to the dopamine transporter (DAT) 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, an inhibitor of dopamine synthesis, blocks the action of amphetamine but does not block locomotor activity induced by modafinil.
In addition to its wake-promoting effects and ability to hyperlocomotion in animals, according to Nuvigil prescribing information from manufacturer Cephalon, armodafinil produces psychoactive and euphoria effects, alterations in mood, perception, thinking, and feelings typical of other central nervous system (CNS) in humans.
Like modafinil, armodafinil is an enzyme inhibitor and/or enzyme inducer of certain cytochrome P450 .
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 (modafinil being a 1:1 mixture of (
R)-(−)- and (
S)-(−)- enantiomers) are nearly superimposable. However, the C
max 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.
Chemistry
Armodafinil, or (
R)-(–)-modafinil, is the
enantiopure drug (
R)-(–)-
enantiomer of the
racemic mixture modafinil, while
esmodafinil is the (
S)-(+)-enantiomer.
A number of analogues of armodafinil are known, including adrafinil, flmodafinil, fladrafinil, and others.
Society and culture
Brand names
Armodafinil is sold under a wide variety of brand names worldwide:
Legal status
In Australia, and the United States, Armodafinil is considered to be a Schedule 4 prescription-only medicine or prescription animal remedy.
Schedule 4 is defined as "Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription."
Romania
As of 2021, new laws do not directly include Armodafinil as a doping agent, but they do include Modafinil, as Armodafinil is an enantiomer of Modafinil it will show up on lab tests, but it can be debated if it is or not the same substance.
New laws state that simple possession is not a criminal offence and is punished with a fine and confiscation.
Research
Besides
hypersomnia, armodafinil was under development for the treatment of fatigue, bipolar depression, and
schizophrenia.
However, development for these indications was discontinued.
The drug reached phase 3
for treatment of fatigue prior to the discontinuation of its development for this use in January 2024.
Aside from the preceding indications, armodafinil is currently under development for the treatment of
and, as of January 2024, is in phase 3 trials for this use.
External links
