Armodafinil
Armodafinil is the enantiopure of the wakefulness-promoting agent modafinil (Provigil), and is indicated to improve wakefulness in adult patients with excessive sleepiness associated with obstructive sleep apnea (OSA), narcolepsy, or shift work disorder (SWD).
Research has shown that armodafinil significantly improves driving simulator performance in patients with SWD. Armodafinil and was approved by the U.S. Food and Drug Administration (FDA) in June 2007.
Mechanism of effect
Unknown; may increase dopamine levels in the brain by binding to the dopamine transporter and inhibiting dopamine reuptake.
Pharmacodynamic
Not Available
Pharmacokinetics
Absorption
Peak plasma time: 2 hr
Distribution
Protein bound: 60%
Vd: 42 L
Metabolism
Hepatic; primarily amide hydrolysis; also sulfone formation by CYP3A4/5
Elimination
Half-life: 15 hr
Excretion: Urine (80%)
Drug contraindications
Hypersensitivity to this drug or componentsSide effects
depression , Anxiety , Insomnia , Diarrhea , Headache , nausea , dry mouth , rash , vertigo , palpitations , anorexia , tiredness , Restlessness , shortness of breath , indigestionInteractions
Ranolazine , Axitinib , Zolpidem , escitalopram , Entrectinib , atovaquone/proguanil , Triphasic , Gefitinib , Cannabidiol , Sarecycline , AbametapirAlerts
Concerns related to adverse effects:
CNS effects: May impair the ability to engage in potentially hazardous activities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery, driving).
Dermatologic effects (severe): Serious and life-threatening rashes including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported. In modafinil clinical trials, rashes were more likely to occur in children; serious, postmarketing reactions have occurred with modafinil and armodafinil in adults and children. Most cases have been reported within the first 8 weeks of initiating therapy; however, rare cases have occurred after prolonged therapy. No risk factors have been identified to predict occurrence or severity of these reactions. Patients should be advised to discontinue use at first sign of rash, skin or mouth sores.
Disease-related concerns:
Cardiovascular disease: Use is not recommended in patients with a history of left ventricular hypertrophy or patients with mitral valve prolapse who have developed mitral valve prolapse syndrome with previous CNS stimulant use. Patients with these conditions may also experience chest pain, palpitations, dyspnea, and transient ischemic T-wave changes on ECG. Due to limited experience use caution in patients with history of myocardial infarction (MI) or angina. Increased blood pressure monitoring may be required, and new or additional antihypertensive therapy may be needed.
Hepatic impairment: Use with caution in patients with hepatic impairment; dosage reduction is recommended with severe dysfunction.
Psychiatric disorders: Use caution in patients with a history of psychosis, depression, or mania. Armodafinil has been shown to worsen the symptoms of these diseases (eg, mania, hallucinations, suicidal thoughts). Discontinue therapy if psychiatric symptoms develop.
Sleep disorders: The degree of sleepiness should be reassessed frequently; some patients may not return to a normal level of wakefulness. Patients with excessive sleepiness should be advised to avoid driving or any other potentially dangerous activity. Use >12 weeks has not been studied; patient should be reevaluated to determine effectiveness if use exceeds 12 weeks.
Tourette syndrome/tics: Use with caution in patients with Tourette syndrome and other tic disorders. Stimulants may exacerbate tics (motor and phonic) and Tourette syndrome; however, evidence demonstrating increased tics is limited. Evaluate for tics and Tourette syndrome prior to therapy initiation.
Special populations:
Elderly: Use reduced doses in elderly patients; concentrations of armodafinil are significantly higher in patients >65 years of age.
Other warnings/precautions:
Abuse potential: Use with caution in patients with a history of drug abuse; potential for drug dependency exists.
Points of recommendation
Patients should stop taking armodafinil and call doctor if they have a skin rash, no matter how mild. Other signs of a severe reaction include fever, swelling in face or tongue, mouth sores, trouble breathing, swelling in legs, yellowing of skin or eyes.
Effectiveness of hormonal contraceptives may be reduced up to for one month after discontinuation of therapy; advise women who using a hormonal method of contraception to use additional barrier method or alternative non-hormonal method of contraception during treatment and for one month after discontinuation of treatment.
Ask a Pharmacist