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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