Armodafinil A Nootropic
Armodafinil is a
psychostimulant that aims to improve wakefulness. It is indicated for
narcolepsy, obstructive sleep apnoea or hypopnea syndrome (added to continuous
positive airways pressure) and for chronic shift work sleep disorder when
non-drug approaches have not worked.
Armodafinil
is related to modafinil, which is already registered in Australia for the same
indications. Modafinil is a 1:1 mixture of R and S isomers whereas
armodafinil consists only of the R isomer. Like modafinil, armodafinil’s exact
mechanism of action is unknown.
The absorption,
metabolism and elimination of armodafinil are very similar to modafinil.
However, after oral administration peak serum concentrations and exposure (area
under the curve) are higher for armodafinil than for modafinil at the same
dose. Armodafinil is not therefore bioequivalent to modafinil and cannot be
directly substituted.
Armodafinil should be
taken once a day in the morning for narcolepsy and obstructive sleep apnoea,
and one hour before starting work for those with shift work sleep disorder. As
with modafinil, the armodafinil dose should be reduced in people with severe
hepatic impairment. Lower doses should also be considered in older people due
to reduced clearance of the drug.
The most common
adverse events with armodafinil were headache, nausea, dizziness and insomnia.
In the trials, 7% of people discontinued the drug because of an adverse event.
Headache was the most common reason, but others included psychiatric symptoms
such as anxiety, agitation, irritability and depression.
In
a 12-month open-label trial in 328 patients with narcolepsy, obstructive sleep
apnoea or shift work disorder, rare but serious adverse events that were
possibly related to armodafinil included chest pain, pulmonary embolism,
myocardial infarction and exacerbation of depression.
The potential drug
interactions with armodafinil are expected to be similar to modafinil.
Armodafinil weakly induces cytochrome P450 (CYP) 3A4 so may reduce
concentrations of drugs that are metabolised by this enzyme such as hormonal
contraceptives, cyclosporin, carbamazepine and midazolam. Armodafinil also
inhibits CYP2C19 and may increase concentrations of CYP2C19 substrates such as
omeprazole, phenytoin, diazepam, propranolol and clomipramine. More frequent
monitoring of INR may be required with co-administered warfarin.
Because of its
interaction with hormone contraceptives, women taking armodafinil should use
alternative contraception. Armodafinil is contraindicated in pregnancy and not
recommended during lactation based on previous animal studies with modafinil
showing fetal effects and excretion in breast milk.
Armodafinil
significantly improved the ability of patients to stay awake for longer than a
placebo. However, this was only by a matter of minutes in sleep latency tests.
Although rare, fatalities relating to armodafinil, including from serious skin
reactions, have occurred. Psychiatric symptoms can also be a problem. As
armodafinil may produce euphoric effects, prescribers should be aware of its
potential for abuse.
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