Armodafinil

Pronunciation: AR-moe-DAF-i-nil
Class: Analeptic

Trade Names

Nuvigil
- Tablets, oral 50 mg
- Tablets, oral 150 mg
- Tablets, oral 250 mg

Pharmacology

Wakefulness-promoting agent; however, the precise mechanism(s) is unknown.

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Pharmacokinetics

Absorption

Readily absorbed. T _max is approximately 2 h. Steady state is reached within 7 days of dosing. Food delays T _max approximately 2 to 4 h.

Distribution

Apparent Vd is approximately 42 L and protein binding is approximately 60%, primarily to albumin.

Metabolism

Primary site is hepatic via hydrolytic deamidation (with sulfone formation by CYP3A4/5), S-oxidation, and aromatic ring hydroxylation, with subsequent glucuronide conjugation of the hydroxylated products.

Elimination

Approximately 80% (urine) and 1% (feces) are excreted in 11 days. Elimination half-life is approximately 15 h. Oral Cl is approximately 33 mL/min.

Special Populations

Severe chronic renal failure (CrCl 20 mL/min or less) increased exposure to modafinil acid 9-fold.

In patients with severe hepatic impairment, Cl of modafinil was decreased by about 60% and the steady-state concentration was doubled.

Decrease of approximately 20% in oral Cl in patients with a mean age of 63 y, which is not likely to be clinically important.

Population pharmacokinetic analysis suggests no gender effect on the pharmacokinetics of armodafinil.

The influence of race on the pharmacokinetics of modafinil has not been studied.

Indications and Usage

Improve wakefulness in patients with excessive sleepiness associated with obstructive sleep apnea (OSA), narcolepsy, and shift work sleep disorder.

Contraindications

Hypersensitivity to modafinil or armodafinil or any component of the product.

Dosage and Administration

PO 150 or 250 mg as a single dose in the morning.

PO 150 mg daily approximately 1 h prior to the start of work shift.

PO Consider using lower doses.

PO Reduce dose in severe hepatic impairment.

General Advice

• Consider dosage adjustment for concomitant medications that are substrates for CYP3A4, such as triazolam and cyclosporine.
• Drugs that are largely eliminated via CYP2C19 metabolism, such as diazepam, propranolol, phenytoin (also via CYP2C9), or S-mephenytoin, may have prolonged elimination when coadministered with modafinil and may require dosage reduction and monitoring for toxicity.

Storage/Stability

Store between 68° and 77°F.

Drug Interactions

Avoid concomitant use.

Modafinil absorption may be delayed approximately 1 h; the same effect may be applicable to armodafinil.

Plasma concentration may be elevated by armodafinil, increasing the risk of adverse reactions. Dosage reduction of these agents may be necessary.

Plasma concentrations may be reduced by armodafinil, decreasing efficacy. Dosage adjustments may be needed.

Food may delay the armodafinil T _max by approximately 2 to 4 h. Because the delay in T _max is associated with elevated plasma concentrations later in time, food can potentially affect the onset and time course of the pharmacologic action of armodafinil.

The efficacy of hormonal contraceptives may be reduced during and for 1 mo after armodafinil coadministration. Use of alternative or concomitant methods of contraception are recommended during and for 1 mo after coadministration with armodafinil.

Use caution when administering MAOIs and armodafinil.

Armodafinil concentrations may be reduced, decreasing efficacy. Monitor the clinical response and adjust treatment as needed.

Armodafinil concentrations may be elevated, increasing the risk of adverse reactions. Monitor the clinical response and adjust treatment as needed.

Possible decrease in armodafinil levels due to prazosin; larger doses of armodafinil may be needed.

A pharmacodynamic interaction cannot be ruled out. Monitor PT and INR more frequently when armodafinil is administered with warfarin.

Adverse Reactions

Cardiovascular

Palpitations (2%); increased heart rate (1%).

CNS

Headache (23%); insomnia (6%); dizziness (5%); anxiety (4%); depression (3%); fatigue (2%); agitation, attention disturbance, depressed mood, migraine, nervousness, paresthesia, tremor (1%).

Dermatologic

Rash (4%); contact dermatitis, hyperhidrosis (1%).

GI

Nausea (9%); dry mouth (7%); diarrhea (4%); dyspepsia, upper abdominal pain (2%); anorexia, constipation, decreased appetite, loose stools, vomiting (1%).

Lab Tests

Increased GGT (1%); increased alkaline phosphatase.

Miscellaneous

Dyspnea, influenza-like illness, pain, polyuria, pyrexia, seasonal allergy, thirst (1%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established in patients younger than 17 y. Serious rash, including erythema multiforme major and Stevens-Johnson syndrome, has been associated with armodafinil use in pediatric patients.

Elderly

Because elimination of armodafinil and its metabolites may be reduced, consider using a lower dose.

Hypersensitivity

Rare cases of angioedema, anaphylactoid reactions, and multiorgan hypersensitivity have been reported.

Hepatic Function

Dosage reduction is recommended in severe hepatic impairment.

Hazardous Tasks

May alter judgment, motor skills, or thinking.

CV effects

Not recommended for use in patients with history of left ventricular hypertrophy or mitral valve prolapse who have experienced the mitral valve prolapse syndrome when receiving CNS stimulants. Use with caution in patients with a recent history of MI or unstable angina.

Dermatologic effects

Serious rash, which may be life-threatening or require hospitalization (eg, Stevens-Johnson syndrome, drug rash with eosinophilia, TEN), may occur.

Drug abuse

Because of psychoactive and euphoric effects, armodafinil has potential for abuse.

Wakefulness

May not return to normal.

Psychiatric effects

Psychiatric adverse reactions, including aggression, delusions, hallucinations, mania, and suicidal ideation, some resulting in hospitalization, may occur. Exercise caution when modafinil is given to patients with a history of psychosis, depression, or mania.

Overdosage

Symptoms

Aggressiveness, agitation, anxiety, confusion, decreased PT, diarrhea, excitation, insomnia, irritability, nausea, nervousness, palpitations, sleep disturbances, slight to moderate elevations in hemodynamic parameters, tremor.

Patient Information

• Advise patients to read the Medication Guide before starting therapy and with each refill.
• Advise patients that armodafinil is not a replacement for sleep.
• Advise patients to continue to take previously prescribed treatments (eg, continuous positive airway pressure for patient with OSA) as instructed by their health care provider.
• Caution patients not to alter previous behavior with regard to potentially dangerous activities (eg, driving, operating machinery) or other activities requiring appropriate levels of wakefulness until, and unless, treatment with armodafinil has been shown to produce levels of wakefulness that permit such activities.
• Inform patients that it is prudent to avoid alcohol while taking armodafinil.
• Advise patients to notify their health care provider if they experience anxiety, chest pain, depression, or signs of psychosis or mania.
• Advise patients to stop taking armodafinil and immediately notify their health care provider if blisters, mouth sores, peeling skin, trouble breathing or swallowing, rash, hives, or other symptoms of anaphylaxis, angioedema, or other allergic reactions occur.
• Advise patients to notify their health care provider if they become pregnant, intend to become pregnant during therapy, or are breast-feeding. Advise women using hormonal contraception (oral, depot, or implantable) to use alternative or concomitant methods of contraception with and for 1 mo following discontinuation of therapy.
• Advise patients to inform their health care providers if they are taking, or planning to take, any prescription or nonprescription drugs because of the potential for interactions between armodafinil and other drugs.

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