Armodafinil Technical Information
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.1 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.
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.
Armodafinil (150 mg or 250 mg) has been assessed in several 12-week placebo-controlled trials (see Table).2-5 In daytime maintenance of wakefulness tests, patients with narcolepsy or obstructive sleep apnoea stayed awake up to 4.5 minutes longer with armodafinil than with placebo.2-4 In night-time multiple sleep latency tests, patients with excessive sleepiness due to shift work disorder stayed awake on average 2.7 minutes longer with armodafinil than with placebo.5
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.6
Rashes have been reported with armodafinil, including a fatal case of Stevens-Johnson syndrome. The drug should be stopped immediately if a rash develops.
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.
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, prescriber should be aware of its potential for abuse.