Armodafinil

Psychiatry

Jet lag

On March 30, 2010, the FDA declined to approve use of Nuvigil to treat jet lag.^[20][21]

Available forms

Armodafinil is available in the form of 50, 150, 200, and 250 mg oral tablets.^[1]

A 50 mg dose of armodafinil is essentially equivalent to at 100 mg dose of modafinil in terms of drug levels.^[8]

Misuse potential

Armodafinil has a low misuse potential similar to modafinil.

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.^[25] 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 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 (CNS) stimulants in humans.^[12] 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 [methylphenidate]."^[12]

Like modafinil, armodafinil is an inhibitor and/or inducer of certain cytochrome P450 enzymes.^[7][26] It moderately induces CYP3A4 and moderately inhibits CYP2C19.^[7][26] In contrast to modafinil however, armodafinil does not induce CYP1A2.^[7][26]

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.

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.^[30] 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."