metabolism. Avoid or Use Alternate Drug. Avoid coadministration of zanubrutinib (a CYP3A4 substrate) with moderate CYP3A4 inhibitors. If unavoidable, increase zanubrutinib dose to 320 mg PO BID. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib. ziconotideMonitor Closely (1)ziconotide increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.ziprasidoneMonitor Closely (1)ziprasidone increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)armodafinil will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.zolpidemMinor (1)armodafinil will decrease the level or effect of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.zonisamideMinor (1)armodafinil will decrease the level or effect of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. >10% Headache (14-23%) 1-10% Nausea (6-9%) Dry mouth (2-7%) Dizziness (5%) Anxiety (4%) Diarrhea (4%) Insomnia (4%) Rash (1-4%) Depression (1-3%) Dyspepsia (2%) Fatigue (2%) Palpitations (2%) Agitation (1%) Anorexia (1%) Attention disturbances (1%) Contact dermatitis (1%) Dyspnea (1%) Hyperhidrosis (1%) Nervousness (1%) Paresthesia (1%) Pyrexia (1%) <1% Angioedema Dysphagia Bronchospasm Reversible psychosis Postmarketing Reports Aggression Mouth Sores Persistent sleepiness Contraindications Hypersensitivity to modafinil, armodafinil, or other ingredients Cautions Not recommended in patients with angina, cardiac ischemia, recent history of myocardial infarction, left ventricular hypertrophy, or mitral valve prolapse Use caution in patients with history of left ventricular hypertrophy/mitral valve prolapse who have had mitral valve prolapse syndrome when previously receiving CNS stimulants; consider increased monitoring Use caution in severe hepatic impairment and the elderly History of depression, psychosis, mania; consider discontinuing armodafinil if psychiatric symptoms develop May reduce effectiveness of steroidal contraceptives 1 month after discontinuation of drug therapy If used adjunctively with continuous positive airway pressure (CPAP), periodic assessment of CPAP compliance is necessary Serious rash requiring hospitalization and discontinuation of treatment has been reported; discontinue at first sign of serious rash Discontinue therapy if symptoms suggest angioedema or anaphylaxis Skin and mouth sores, blistering, and ulceration reported Persistent sleepiness Patients with abnormal levels of sleepiness who receive therapy should be advised that their level of wakefulness may not return to normal Patients with excessive sleepiness, should be frequently reassessed for their degree of sleepiness and, if appropriate, advised to avoid driving or any other potentially dangerous activity Prescribers should be aware that patients may not acknowledge sleepiness or drowsiness until directly questioned about drowsiness or sleepiness during specific activities Dermatologic reactions Rare cases of serious or life-threatening rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), reported in adults and children in worldwide post-marketing experience There are no factors, including duration of therapy, known to predict risk of occurrence or severity of rash associated with therapy; discontinue therapy at first sign of rash, skin or mouth sores, or blistering or ulceration, unless rash is clearly not drug-related Discontinuation of treatment may not prevent rash from becoming life-threatening or permanently disabling or disfiguring Multiorgan hypersensitivity DRESS, also known as multi-organ hypersensitivity, has been reported; important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident If multi-organ hypersensitivity reaction suspected, discontinue therapy; although there are no case reports to indicate cross-sensitivity with other drugs that produce this syndrome, the experience with drugs associated with multi-organ hypersensitivity would indicate this to be a possibility Cardiovascular events Cardiovascular adverse reactions, including chest pain, palpitations, dyspnea and transient ischemic T-wave changes on ECG reported in association with mitral valve prolapse or left ventricular hypertrophy Recommended that medication not be used in patients with a history of left ventricular hypertrophy or in patients with mitral valve prolapse who have experienced the mitral valve prolapse syndrome when previously receiving CNS stimulants Findings suggestive of mitral valve prolapse syndrome include but are not limited to ischemic ECG changes, chest pain, or arrhythmia; if new onset of any of these findings occurs, consider cardiac evaluation Increased monitoring of heart rate and blood pressure may be appropriate in patients on therapy; exercise caution when prescribing therapy to patients with known cardiovascular disease Drug interaction overview CYP3A4/5 substrates Modafinil moderately induces CYP3A4/5, which may result in lower systemic exposure of CYP3A4/5 substrates (eg, hormonal contraceptives, cyclosporine, midazolam, triazolam) Dose adjustment of substrate may be required CYP2C19 substrates Modafinil weakly inhibits CYP2C19, which may result in higher systemic exposure of CYP2C19 substrates (eg, phenytoin, diazepam, propranolol, omeprazole, clomipramine) Individuals deficient in CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19 (eg, TCAs, SSRIs), may be increased by coadministration Dose adjustments of these drugs and other drugs that are substrates for CYP2C19 may be necessary if modafinil is coadministered Warfarin Modafinil appeared to produce a concentration-related suppression of CYP2C9 activity, therefore suggesting potential for CYP2C9 inhibition; caution if drugs that have a narrow therapeutic index Consider more frequent monitoring of prothrombin times/INR MAO inhibitors Other CNS stimulants may induce severe cardiovascular reactions; avoid coadministration Pregnancy Limited available data in pregnant women are insufficient to inform about drug associated risk of adverse pregnancy outcomes; intrauterine growth restriction and spontaneous abortion reported in association with armodafinil and modafinil; although the pharmacology of armodafinil not identical to that of sympathomimetic amines, armodafinil shares some pharmacologic properties with this class; sympathomimetics have been associated with intrauterine growth restriction and spontaneous abortions 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 Lactation There are no data on presence of armodafinil or metabolite in human milk, effects on breastfed infant, or effect of this drug on milk production; modafinil was present in rat milk when animals were dosed during the lactation period; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for armodafinil and any potential adverse effects on breastfed child from armodafinil or from underlying maternal conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Unknown; not sympathomimetic (R-enantiomer of modafinil); may increase dopamine levels in the brain by binding to the dopamine transporter and inhibiting dopamine reuptake Absorption Peak plasma time: 2 hr Distribution Protein bound: 60% Vd: 42 L Metabolism Hepatic; primarily amide hydrolysis; also sulfone formation by CYP3A4/5 Enzymes induced: CYP1A2, possibly CYP3A4 in a concentration-related manner Enzymes inhibited: CYP2C19 Pharmacokinetics Half-life: 15 hr Excretion: Urine (80%) BRAND FORM. UNIT PRICE PILL IMAGE Nuvigil oral- 250 mg tabletNuvigil oral- 200 mg tabletNuvigil oral- 50 mg tabletNuvigil oral- 150 mg tabletarmodafinil oral- 250 mg tabletarmodafinil oral- 150 mg tabletarmodafinil oral- 200 mg tabletarmodafinil oral- 250 mg tabletarmodafinil oral- 250 mg tabletarmodafinil oral- 50 mg tabletarmodafinil oral- 250 mg tabletarmodafinil oral- 150 mg tabletarmodafinil oral- 150 mg tabletarmodafinil oral- 50 mg tabletarmodafinil oral- 250 mg tabletarmodafinil oral- 150 mg tabletarmodafinil oral- 50 mg tabletCopyright © 2010 First DataBank, Inc.Print Patient Educationarmodafinil oral ARMODAFINIL - ORAL (AR-moe-DAF-i-nil) COMMON BRAND NAME(S): Nuvigil 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. HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using armodafinil and each time you get a refill. If you have any questions, ask your doctor or pharmacist.For narcolepsy and obstructive sleep apnea, take this medication by mouth as directed by your doctor, usually once daily in the morning. If you are using armodafinil for shift work sleep disorder, take it as directed by your doctor, usually once a day 1 hour before you start your work shift. You may take this medication with or without food, but armodafinil may take longer to work if you take it with food.If you are using this drug for sleep apnea, continue your other treatment (such as the CPAP machine, mouth device) unless your doctor tells you to stop.The dosage is based on your medical condition and response to treatment. Take this medication regularly to get the most benefit from it.If you suddenly stop using this medication, you may have withdrawal symptoms (such as shaking, sweating, chills, nausea, vomiting, confusion). To help prevent withdrawal, your doctor may lower your dose slowly. Withdrawal is more likely if you have used armodafinil for a long time or in high doses. Tell your doctor or pharmacist right away if you have withdrawal.When this medication is used for a long time, it may not work as well. Talk with your doctor if this medication stops working well.Though it helps many people, this medication may sometimes cause addiction. This risk may be higher if you have a substance use disorder (such as overuse of or addiction to drugs/alcohol). Take this medication exactly as prescribed to lower the risk of addiction. Ask your doctor or pharmacist for more details.Tell your doctor if your condition does not improve or if it worsens. SIDE EFFECTS: Headache, nausea, dry mouth, nervousness, dizziness, or difficulty sleeping may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: fast/pounding/irregular heartbeat, mental/mood changes (such as agitation, confusion, depression, hallucinations, rare thoughts of suicide).Get medical help right away if you have any very serious side effects, including: chest pain.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: fever, swollen lymph nodes, rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345. PRECAUTIONS: Before taking armodafinil, tell your doctor or pharmacist if you are allergic to it; or to modafinil; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: heart problems (such as enlarged heart, mitral valve problem, chest pain, heart attack, irregular heartbeat), heart problems after taking stimulant drugs such as amphetamines (including chest pain, irregular heartbeat), high blood pressure, liver problems, mental/mood disorders (such as depression, mania, psychosis), personal or family history of a substance use disorder (such as overuse of or addiction to drugs/alcohol).Sleep disorders may reduce your ability to react quickly. Though armodafinil helps keep you awake, you still may not be able to safely do things that require quick reactions (such as driving). This drug may also make you dizzy. Alcohol or marijuana