Armodafinil (armodafinil)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Armodafinil, the R-enantiomer of racemic modafinil, is a wakefulness-promoting agent.
Armodafinil is a non-amphetamine wakefulness-promoting agent. The drug is theR-enantiomer of modafinil, which is a racemic compound containing equal amounts of the R- and S- isomers. Both armodafinil and modafinil are benzhydrylsulfinylacetamides.
Armodafinil is the longer-lasting R-isomer of modafinil, having a half-life approximately 3-4 times longer than that of S-modafinil. In vitro and animal studies have shown that armodafinil and modafinil have similar pharmacologic actions.
The exact mechanism by which armodafinil and modafinil promote wakefulness is not known, but may involve activation of certain arousal centers of the brain (e.g., hypothalamus, prefrontal cortex, anterior cingulate cortex). Armodafinil and modafinil have wake-promoting effects similar to sympathomimetic agents (e.g., amphetamine, methylphenidate); however, their pharmacologic profile is not identical to such agents. Additionally, modafinil produces effects commonly described with other CNS stimulants in humans, including psychoactive and euphoric effects and alterations in mood, perception, thinking, and feelings.
Armodafinil is an indirect dopamine receptor agonist, and has been shown in in vitro studies to bind to the dopamine transporter and inhibit dopamine reuptake. Such inhibitory effects have been associated with increased extracellular dopamine concentrations in animal models. The stimulant effects of modafinil can be attenuated by the alpha1-adrenergic receptor antagonist prazosin, but modafinil is inactive in other assay systems known to be responsive to alpha1-adrenergic receptor agonists.
The active component of Nuvigil(R) is armodafinil, which is the longer-acting enantiomer (R-enantiomer) of modafinil. Armodafinil is readily absorbed following oral administration, with peak plasma concentrations occurring at approximately 2 hours in the fasted state. The effect of food on the overall bioavailability of armodafinil appears minimal, but time to achieve peak concentrations may be delayed by approximately 2-4 hours in the fed state.
Armodafinil exhibits linear pharmacokinetics following administration of single or multiple oral doses of the drug over the dosage range of 50-400 mg. Steady-state plasma concentrations of armodafinil are achieved within 7 days of daily administration, and the mean elimination half-life of the drug is approximately 15 hours. Peak plasma concentrations and total exposure of armodafinil at steady state are approximately 37% and 70% higher, respectively, following 200 mg of armodafinil compared to 200 mg of modafinil, which is due to the more rapid clearance of the S-enantiomer compared to the R-enantiomer.
Although the plasma protein binding of armodafinil is not known, modafinil is 60% bound to plasma proteins, predominantly albumin. Interactions with highly-protein bound drugs are expected to be minimal. Armodafinil undergoes hydrolytic deamidation, S-oxidation, and aromatic ring hydroxylation, with subsequent glucuronide conjugation of the hydroxylated products.
The 2 principal metabolites (R-modafinil acid and modafinil sulfone) of armodafinil or modafinil do not appear to contribute to the CNS-activating properties of the parent compounds. Although the metabolic fate of armodafinil has not been specifically studied, racemic modafinil is mainly eliminated via metabolism, predominantly in the liver, with 80% of the drug excreted in urine and 1% in feces, mainly as metabolites. Pharmacokinetic analyses indicate gender has no impact on armodafinil pharmacokinetics.
It is not known whether race/ethnicity affects the pharmacokinetics of armodafinil.
USES: Armodafinil reduces extreme sleepiness due to narcolepsy and other sleep disorders, such as periods of stopped breathing during sleep (obstructive sleep apnea). It is also used to help you stay awake during work hours if you have a work schedule that keeps you from having a normal sleep routine (shift work sleep disorder). This medication does not cure these sleep disorders and may not get rid of all your sleepiness.
Armodafinil does not take the place of getting enough sleep. It should not be used to treat tiredness or hold off sleep in people who do not have a sleep disorder. It is not known how armodafinil works to keep you awake.
It is thought to work by affecting certain substances in the brain that control the sleep/wake cycle.
Generic name: armodafinil
Pronunciation: (AR-moe-DAF-i-nil)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Armodafinil
Indications
The following indications are listed for Armodafinil:
- Narcolepsy Syndrome
- Sleepiness Due To Obstructive Sleep Apnea
- Sleepiness Due To Shift Work Sleep Disorder
Also known as: Excessive Sleepiness Associated With Osahs, Friedmann's Disease, Gelineau's Syndrome, Hypnolepsy, Narcolepsy, Paroxysmal Sleep, Sleepiness Associated With Hypopnea Syndrome, Sleepiness Associated With Obstructive Sleep Apnea, Sleepiness Associated With Shifting Sleep-Work Schedule, Somnolence From Obstructive Sleep Apnea.
Dosing
No dosing information is available for this tab.
Armodafinil is administered orally. In patients with obstructive sleep apnea (OSA) or narcolepsy, armodafinil usually is administered once daily in the morning. In patients with shift work disorder (SWD), armodafinil should be taken approximately 1 hour prior to the start of their work shift.
The manufacturer makes no specific recommendations regarding administration of armodafinil with regard to meals.
Store armodafinil tablets at 20-25degreesC.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
In vitro and in vivo data have shown that armodafinil is primarily metabolized via amide hydrolysis, and to a lesser extent by cytochrome P-450 (CYP) isoenzymes 3A4/5. In vitro studies indicate that armodafinil is a weak inducer of CYP1A2 and possibly CYP3A, and a reversible inhibitor of CYP2C19. Other CYP activities do not appear to be affected by armodafinil. In vitro studies have also shown that armodafinil is a substrate of the efflux transporter P-glycoprotein, although the impact of this inhibition is not known.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known hypersensitivity to armodafinil, modafinil, or any ingredient in the formulation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in >=5% of patients receiving armodafinil in clinical trials and more frequently than with placebo include headache, nausea, dizziness, and insomnia.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and effectiveness of armodafinil have not been established in pediatric patients. Serious rash has occurred in pediatric patients taking modafinil.
A pregnancy registry is available that monitors pregnancy outcomes in women exposed to armodafinil during pregnancy. Clinicians are encouraged to register patients, or pregnant patients can register themselves, by calling 1-866-404-4106.
Limited data are available to assess the drug-associated risk of adverse developmental outcomes with armodafinil use during pregnancy; however, armodafinil and modafinil have been associated with intrauterine growth restriction and spontaneous abortion. Animal reproductive studies with armodafinil and modafinil in rats and rabbits during the period of organogenesis showed evidence of developmental toxicity (increased embryofetal and offspring mortality, decreased fetal growth) at clinically relevant plasma concentrations.
It is not known whether armodafinil or its metabolites are distributed into human milk, although modafinil has been detected in the milk of lactating rats. The effects of armodafinil or its metabolites on milk production and on the breast-fed infant are not known. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for the drug and the potential for adverse effects on the breast-fed infant from armodafinil and from the underlying maternal condition.
Because elimination of armodafinil and its metabolites may be reduced with age in geriatric patients, consideration should be given to using dosages lower than the usual recommended dosages and closely monitoring in this age group.
Elimination of armodafinil and its metabolites may be reduced in geriatric patients. In a clinical study with armodafinil, systemic exposure was increased by 15% in geriatric patients >=65 years of age, corresponding to a 12% lower oral clearance, when compared to younger adults 18-45 years of age. Peak plasma concentrations and total exposure of the metabolite (armodafinil acid), was increased approximately 61% and 73%, respectively, compared to younger patients; however, exposure of the sulfone metabolite was approximately 20% lower. Systemic exposure of armodafinil was increased by approximately 10% and 27% in patients 65-74 years of age and >=75 years of age, respectively, compared to younger patients. The manufacturer states that this difference is not likely clinically significant, but since there is increased armodafinil exposure in some geriatric patients, the use of lower dosages and close monitoring should be considered.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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