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 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 Steven's-Johnson Syndrome, or other hypersensitivities to armodafinil.
Pharmacology
Pharmacodynamics
The mechanism of action of armodafinil is unknown. Armodafinil has pharmacological properties almost identical to those of modafinil - and -. The - and -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 antagonisthaloperidol 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 increase locomotor activity in animals, according to Nuvigil prescribing information from manufacturer Cephalon, armodafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking, and feelings typical of other central nervous system stimulants in humans. Armodafinil, like racemic modafinil, may also possess reinforcing properties, as evidenced by its self-administration in monkeys previously trained to administer cocaine; armodafinil was also partially discriminated as stimulant-like. A Cephalon-founded study in which patients were administered modafinil, methylphenidate, and a placebo found that modafinil produces "psychoactive and euphoric effects and feelings consistent with ."
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 --enantiomer following a single dose of 50 mg Nuvigil or 100 mg Provigil -- and - 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 --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 Tmax is also associated with elevated plasma concentration later in time, food can potentially affect the onset and time course of pharmacologic action of armodafinil.
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
Armodafinil is not directly illegal in Romania, it is not scheduled as a narcotic, it is not included directly in the list of doping agents as modafinil is, but at laboratory testings it will show up as modafinil, being its enantiomer, and so will be prosecuted the same. Sanctions range from a warning to a 4.000 lei fine, and always confiscation of the substance.
Marketing
Brand names
Armodafinil is sold under a wide variety of brand names worldwide:
