Modafinil 200 mg Tablet, 30-count — NDC 23155-862-03 (Billing 23155-0862-03)
This is a package of 30 tablets of Modafinil 200 mg Tablet from Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc., marketed since Feb 2024 and currently FDA-listed; retail pharmacies pay about $0.3436 per tablet (NADAC). It is the main listing for this product, which comes in 4 package sizes.
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 041478
- GCN: 26102
- HICL (First Databank): 010865
- AHFS class code: 28:20.80.00
- RxCUI (RxNorm): 205324
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Sympathomimetic-like Agent class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
- It helps adults stay awake when they have excessive sleepiness from narcolepsy, obstructive sleep apnea, or shift work disorder. In sleep apnea, it treats the sleepiness but not th...
- Take it once a day by mouth. For narcolepsy or sleep apnea, take it in the morning. For shift work disorder, take it about an hour before your shift starts. Follow your prescriptio...
- Common ones are headache, nausea, nervousness, anxiety, trouble sleeping, dizziness, and diarrhea. Most are mild to moderate. Let me know if they bother you or don't go away.
- Yes. Stop the medicine and get help if you see any rash, or swelling of your face, lips, or throat. Also call if you notice new depression, mania, or odd thinking, or if you get ch...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Modafinil — tap one for details:
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.344 | $10.31 / 30 tablets |
| Medicaid paysCMS SDUD · 12 mo | $0.6658 | $19.97 / 30 tablets |
| Medicare drug plans payPart D · Q2 2026 | $0.5456 | $16.37 / 30 tablets |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q4 2025
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Marketing end | Status |
|---|---|---|---|---|---|---|
| 23155-0862-01 23155-862-01 | 100 TABLET in 1 BOTTLE | — | — | 2024-02-21 | — | Active |
| 23155-0862-03 You're viewing this Main listing | 30 TABLET in 1 BOTTLE | $0.3436 / ea | $10.31 | 2024-02-21 | — | Active |
| 23155-0862-05 23155-862-05 | 500 TABLET in 1 BOTTLE | — | — | 2024-02-21 | — | Active |
| 23155-0862-09 23155-862-09 | 90 TABLET in 1 BOTTLE | $0.3436 / ea | $30.93 | 2024-02-21 | — | Active |
You're viewing the smallest of 4 pack sizes for this product.
This pack has the lowest per-ea cost of the 2 priced pack sizes ($0.3436 NADAC).
In Medicaid, this is the most-dispensed pack of this product — about 93% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in this package?
How does this package differ from NDC 23155-0862-09?
What NDC number is used to bill for this package of Modafinil 200 mg Tablet?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Modafinil 200 mg 00904-6792-04 | Major | 30 tablets | $0.344 | AB | Availability likely | — |
| Modafinil 200 mgthis 23155-0862-03 | Heritage | 30 tablets | $0.344 | AB | Availability likely | — |
| Modafinil 200 mg 50268-0571-12 | AvPAK | 20 tablets | $0.344 | AB | Availability likely | — |
| Modafinil 200 mg 60505-2527-01 | Apotex | 100 tablets | $0.344 | AB | Availability likely | — |
| Modafinil 200 mg 65862-0602-01 | Aurobindo | 100 tablets | $0.344 | — | Availability likely | — |
| Modafinil 200 mg 68084-0721-21 | American | 30 tablets | $0.344 | AB | Availability likely | — |
| Modafinil 200 mg 69452-0343-13 | Bionpharma | 30 tablets | $0.344 | AB | Availability likely | — |
| Modafinil 200 mg 72578-0006-01 | Viona | 100 tablets | $0.344 | AB | Availability likely | — |
| Modafinil 200 mg 55253-0802-30 | CIMA | 30 tablets | $0.356 | AB | Discontinued | +3% |
| Modafinil 200 mg 60505-4852-03 | Apotex | 30 tablets | $80.349 | — | Availability likely | +23283% |
| Modafinil 200 mg 63459-0201-30 | Cephalon, | 30 tablets | $80.349 | — | Availability likely | +23283% |
| Modafinil 200 mg 23155-0605-01 | Heritage | 100 tablets | — | AB | FDA listed | — |
| modafinil 200 mg 43353-0925-30 | Aphena | 30 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 46708-0386-10 | Alembic | 100 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 51407-0961-30 | Golden | 30 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 57237-0155-01 | Rising | 100 tablets | — | AB | FDA listed | — |
| Provigil 200 mg 60429-0010-30 | Golden | 30 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 62332-0386-10 | Alembic | 100 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 63629-7315-01 | Bryant | 30 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 68788-8280-03 | Preferred | 30 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 68788-8653-03 | Preferred | 30 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 70771-1052-01 | Zydus | 100 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 71205-0544-30 | Proficient | 30 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 71335-1173-01 | Bryant | 30 tablets | — | AB | Discontinued | — |
| Modafinil 200 mg 71335-2258-00 | Bryant | 100 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 71335-2501-00 | Bryant | 100 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 71610-0685-30 | Aphena | 30 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 71610-0873-30 | Aphena | 30 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 71610-0989-30 | Aphena | 30 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 71610-0991-30 | Aphena | 30 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 82804-0126-30 | Proficient | 30 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 87063-0309-01 | ASCLEMED | 100 tablets | — | AB | FDA listed | — |
| Modafinil 200 mg 87063-0307-01 | ASCLEMED | 100 tablets | — | AB | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Oct 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII M28OL1HH48
Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII FZ989GH94E
Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
5 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Modafinil tablets are indicated to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (OSA), or shift work disorder (SWD). Limitations of Use In OSA, modafinil tablets are indicated to treat excessive sleepiness and not as treatment for the underlying obstruction. If continuous positive airway pressure (CPAP) is the treatment of choice for a patient, a maximal effort to treat with CPAP for an adequate period of time should be made prior to initiating and during treatment with modafinil tablets for excessive sleepiness.
Modafinil tablets are indicated to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (OSA), or shift work disorder (SWD). Limitations of Use In OSA, modafinil tablets are indicated to treat excessive sleepiness and not astreatment for the underlying obstruction.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION The recommended dosage of modafinil tablets for each indication are as follows: Narcolepsy or OSA: 200 mg once a day in the morning. (2.1) SWD: 200 mg once a day, taken approximately one hour prior to start of the work shift (2.2) Severe Hepatic Impairment: reduce dose to half the recommended dose. (2.3, 12.3) Geriatric Patients: consider lower dose. (2.4, 12.3)
2.1Dosage in Narcolepsy and Obstructive Sleep Apnea (OSA) The recommended dosage of modafinil tablets for patients with narcolepsy or OSA is 200 mg taken orally once a day as a single dose in the morning. Doses up to 400 mg/day, given as a single dose, have been well tolerated, but there is no consistent evidence that this dose confers additional benefit beyond that of the 200 mg/day dose [see Clinical Pharmacology (12.3) and Clinical Studies (14.1 , 14.2 )].
2.2Dosage in Shift Work Disorder (SWD) The recommended dosage of modafinil tablets for patients with SWD is 200 mg taken orally once a day as a single dose approximately 1 hour prior to the start of their work shift.
2.3Dosage Modifications in Patients with Severe Hepatic Impairment In patients with severe hepatic impairment, the dosage of modafinil tablets should be reduced to one-half of that recommended for patients with normal hepatic function [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ].
2.4Use in Geriatric Patients Consideration should be given to the use of lower doses and close monitoring in geriatric patients [see Use in Specific Populations (8.5)] .
2.1Dosage in Narcolepsy and Obstructive Sleep Apnea (OSA) The recommended dosage of modafinil tablets for patients with narcolepsy or OSA is 200 mg taken orally once a day as a single dose in the morning. Doses up to 400 mg/day, given as a single dose, have been well tolerated, but there is no consistent evidence that this dose confers additional benefit beyond that of the 200 mg/day dose [see Clinical Pharmacology (12.3) and Clinical Studies (14.1 , 14.2 )].
2.2Dosage in Shift Work Disorder (SWD) The recommended dosage of modafinil tablets for patients with SWD is 200 mg taken orally once a day as a single dose approximately 1 hour prior to the start of their work shift.
2.3Dosage Modifications in Patients with Severe Hepatic Impairment In patients with severe hepatic impairment, the dosage of modafinil tablets should be reduced to one-half of that recommended for patients with normal hepatic function [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ].
2.4Use in Geriatric Patients Consideration should be given to the use of lower doses and close monitoring in geriatric patients [see Use in Specific Populations (8.5)] .
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Modafinil Tablets, USP 100mg–White to off white capsule shaped uncoated tablets debossed with AC 132 on one side and plain on other side. Modafinil Tablets, USP 200 mg – White to off white round shaped uncoated tablet scored on the one side with AC above and 133 below and plain on other side. Tablets: 100 mg and 200 mg
⛔ Contraindications ▾
4 CONTRAINDICATIONS Modafinil tablets are contraindicated in patients with known hypersensitivity to modafinil or armodafinil or its inactive ingredients [see Warnings and Precautions (5.1, 5.2 , 5.3) ]. Modafinil tablets are contraindicated in patients with known hypersensitivity to modafinil or armodafinil.
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Serious Rash, including Stevens - Johnson Syndrome: Discontinue Modafinil tablets at the first sign of rash, unless the rash is clearly not drug-related. (5.1) Angioedema and Anaphylaxis Reactions: If suspected, discontinue modafinil tablets. (5.2) Multi-organ Hypersensitivity Reactions: If suspected, discontinue modafinil tablets.
(5.3) Persistent Sleepiness: Assess patients frequently for degree of sleepiness and, if appropriate, advise patients to avoid driving or engaging in any other potentially dangerous activity. (5.4) Psychiatric Symptoms: Use caution in patients with a history of psychosis, depression, or mania. Consider discontinuing modafinil tablets if psychiatric symptoms develop.
(5.5) Known Cardiovascular Disease: Consider increased monitoring. (5.7)
5.1Serious Rash, including Stevens - Johnson Syndrome Serious rash requiring hospitalization and discontinuation of treatment has been reported in association with the use of modafinil. In clinical trials of modafinil, the incidence of rash resulting in discontinuation was approximately 0.8% (13 per 1,585) in pediatric patients (age <17 years); these rashes included 1 case of possible Stevens - Johnson Syndrome (SJS) and 1 case of apparent multi-organ hypersensitivity reaction. Several of the cases were associated with fever and other abnormalities (e.g., vomiting, leukopenia).
The median time to rash that resulted in discontinuation was 13 days. No such cases were observed among 380 pediatric patients who received placebo. Modafinil tablets are not approved for use in pediatric patients for any indication [see Use in Specific Populations (8.4) ].
Rare cases of serious or life-threatening rash, including SJS, Toxic Epidermal Necrolysis (TEN), and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) have been reported in adults and children in worldwide postmarketing experience. The reporting rate of TEN and SJS associated with modafinil use, which is generally accepted to be an underestimate due to underreporting, exceeds the background incidence rate. Estimates of the background incidence rate for these serious skin reactions in the general population range between 1 to 2 cases per million-person years.
There are no factors that are known to predict the risk of occurrence or the severity of rash associated with modafinil tablets. Nearly all cases of serious rash associated with modafinil occurred within 1 to 5 weeks after treatment initiation. However, isolated cases have been reported after prolonged treatment (e.g., 3 months).
Accordingly, duration of therapy cannot be relied upon as a means to predict the potential risk heralded by the first appearance of a rash. Although benign rashes also occur with modafinil tablets, it is not possible to reliably predict which rashes will prove to be serious. Accordingly, modafinil tablets should be discontinued at the first sign of rash, unless the rash is clearly not drug-related.
Discontinuation of treatment may not prevent a rash from becoming life-threatening or permanently disabling or disfiguring.
5.2Angioedema and Anaphylaxis Reactions Angioedema and hypersensitivity (with rash, dysphagia, and bronchospasm), were observed in patients treated with armodafinil, the R enantiomer of modafinil (which is the racemic mixture). No such cases were observed in modafinil clinical trials. However, angioedema has been reported in postmarketing experience with modafinil.
Patients should be advised to discontinue therapy and immediately report to their physician any signs or symptoms suggesting angioedema or anaphylaxis (e.g., swelling of face, eyes, lips, tongue or larynx; difficulty in swallowing or breathing; hoarseness).
5.3Multi-organ Hypersensitivity Reactions Multi-organ hypersensitivity reactions, including at least one fatality in postmarketing experience, have occurred in close temporal association (median time to detection 13 days: range 4-33) to the initiation of modafinil. Although th… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Serious Rash, including Stevens-Johnson Syndrome [see Warnings and Precautions (5.1) ] Angioedema and Anaphylaxis Reactions [see Warnings and Precautions (5.2) ] Multi-organ Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Persistent Sleepiness [see Warnings and Precautions (5.4) ] Psychiatric Symptoms [see Warnings and Precautions (5.5) ] Effects on Ability to Drive and Use Machinery [see Warnings and Precautions (5.6) ] Cardiovascular Events [see Warnings and Precautions (5.7) ] Most common adverse reactions (≥5%): headache, nausea, nervousness, rhinitis, diarrhea, back pain, anxiety, insomnia, dizziness, and dyspepsia.
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc. at 1-866-901-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Modafinil tablets has been evaluated for safety in over 3,500 patients, of whom more than 2,000 patients with excessive sleepiness associated with OSA, SWD, and narcolepsy. Most Common Adverse Reactions In placebo-controlled clinical trials, the most common adverse reactions (≥5%) associated with the use of modafinil tablets more frequently than placebo-treated patients were headache, nausea, nervousness, rhinitis, diarrhea, back pain, anxiety, insomnia, dizziness, and dyspepsia.
The adverse reaction profile was similar across these studies. Table 1 presents the adverse reactions that occurred at a rate of 1% or more and were more frequent in modafinil tablets-treated patients than in placebo-treated patients in the placebo-controlled clinical trials. Table 1.
Adverse Reactions in Pooled Placebo-Controlled Trials Adverse Reactions that occurred in ≥1% of modafinil tablets -treated patients (either 200, 300, or 400 mg once daily) and greater incidence than placebo in Narcolepsy, OSA, and SWD Modafinil tablets (%) (n=934) Placebo (%) (n=567) Headache 34 23 Nausea 11 3 Nervousness 7 3 Rhinitis 7 6 Back Pain 6 5 Diarrhea 6 5 Anxiety 5 1 Dizziness 5 4 Dyspepsia 5 4 Insomnia 5 1 Anorexia 4 1 Dry Mouth 4 2 Pharyngitis 4 2 Chest Pain 3 1 Hypertension 3 1 Abnormal Liver Function 2 1 Constipation 2 1 Depression 2 1 Palpitation 2 1 Paresthesia 2 0 Somnolence 2 1 Tachycardia 2 1 Vasodilatation 2 0 Abnormal Vision 1 0 Agitation 1 0 Asthma 1 0 Chills 1 0 Confusion 1 0 Dyskinesia 1 0 Edema 1 0 Emotional Lability 1 0 Eosinophilia 1 0 Epistaxis 1 0 Flatulence 1 0 Hyperkinesia 1 0 Hypertonia 1 0 Mouth Ulceration 1 0 Sweating 1 0 Taste Perversion 1 0 Thirst 1 0 Tremor 1 0 Urine Abnormality 1 0 Vertigo 1 0 Dose-Dependent Adverse Reactions In the placebo-controlled clinical trials which compared doses of 200, 300, and 400 mg/day of modafinil tablets and placebo, the following adverse reactions were dose related: headache and anxiety.
Adverse Reactions Resulting in Discontinuation of Treatment In placebo-controlled clinical trials, 74 of the 934 patients (8%) who received modafinil tablets discontinued due to an adverse reaction compared to 3% of patients that received placebo. The most frequent reasons for discontinuation that occurred at a higher rate for modafinil tablets than placebo patients were headache (2%), nausea, anxiety, dizziness, insomnia, chest pain, and nervousness (each <1%). Laboratory Abnormalities Clinical chemistry, hematology, and urinalysis parameters were monitored in the studies.
Mean plasma levels of gamma glutamyltransferase (GGT) and alkaline phosphatase (AP) were found to be higher following administration of modafinil tablets, but not placebo. Few patients, however, had GGT or AP elevations outside of the normal range. Shifts to higher, but not clinical… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Effects of Modafinil Tablets on CYP3A4/5 Substrates The clearance of drugs that are substrates for CYP3A4/5 (e.g., steroidal contraceptives, cyclosporine, midazolam, and triazolam) may be increased by modafinil tablets via induction of metabolic enzymes, which results in lower systemic exposure. Dosage adjustment of these drugs should be considered when these drugs are used concomitantly with modafinil tablets [see Clinical Pharmacology (12.3) ]. The effectiveness of steroidal contraceptives may be reduced when used with modafinil tablets and for one month after discontinuation of therapy.
Alternative or concomitant methods of contraception are recommended for patients taking steroidal contraceptives (e.g., ethinyl estradiol) when treated concomitantly with modafinil tablets and for one month after discontinuation of modafinil tablets treatment. Blood levels of cyclosporine may be reduced when used with modafinil tablets. Monitoring of circulating cyclosporine concentrations and appropriate dosage adjustment for cyclosporine should be considered when used concomitantly with modafinil tablets.
Effects of Modafinil Tablets on CYP2C19 Substrates Elimination of drugs that are substrates for CYP2C19 (e.g., phenytoin, diazepam, propranolol, omeprazole, and clomipramine) may be prolonged by modafinil tablets via inhibition of metabolic enzymes, with resultant higher systemic exposure. In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of modafinil tablets.
Dose adjustments of these drugs and other drugs that are substrates for CYP2C19 may be necessary when used concomitantly with modafinil tablets [see Clinical Pharmacology (12.3) ]. Warfarin More frequent monitoring of prothrombin times/INR should be considered whenever modafinil tablets are coadministered with warfarin [see Clinical Pharmacology (12.3) ]. Monoamine Oxidase (MAO) Inhibitors Caution should be used when concomitantly administering MAO inhibitors and modafinil tablets.
Steroidal contraceptives (e.g., ethinyl estradiol): Use alternative or concomitant methods of contraception while taking modafinil tablets and for one month after discontinuation of modafinil tablets treatment. (7) Cyclosporine: Blood concentrations of cyclosporine may be reduced. (7) CYP2C19 substrates, such as omeprazole, phenytoin, and diazepam: Exposure of these medications may be increased.
(7)
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm. (8.1)
8.1Pregnancy Pregnancy Category C There are no adequate and well-controlled studies of modafinil in pregnant women. Intrauterine growth restriction and spontaneous abortion have been reported in association with modafinil (a mixture of R-and S-modafinil) and armodafinil (the R-enantiomer of modafinil). Although the pharmacology of modafinil is not identical to that of the sympathomimetic amines, it does share some pharmacologic properties with this class.
Certain of these drugs have been associated with intrauterine growth restriction and spontaneous abortions. Whether the cases reported with modafinil are drug-related is unknown. In studies of modafinil and armodafinil conducted in rats (modafinil, armodafinil) and rabbits (modafinil), developmental toxicity was observed at clinically relevant plasma exposures.
Modafinil tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Modafinil (50, 100, or 200 mg/kg/day) administered orally to pregnant rats throughout organogenesis caused, in the absence of maternal toxicity, an increase in resorptions and an increased incidence of visceral and skeletal variations in the offspring at the highest dose tested. The higher no-effect dose for embryofetal developmental toxicity in rats (100 mg/kg/day) was associated with a plasma modafinil AUC less than that in humans at the recommended human dose (RHD) of modafinil tablets (200 mg/day).
However, in a subsequent study of up to 480 mg/kg/day of modafinil, no adverse effects on embryofetal development were observed. Oral administration of armodafinil (60, 200, or 600 mg/kg/day) to pregnant rats throughout organogenesis resulted in increased incidences of fetal visceral and skeletal variations and decreased fetal body weight at the highest dose tested. The highest no-effect dose for embryofetal developmental toxicity in rats (200 mg/kg/day) was associated with a plasma armodafinil AUC less than that in humans at the RHD of modafinil tablets.
Modafinil administered orally to pregnant rabbits throughout organogenesis at doses of up to 100 mg/kg/day had no effect on embryofetal development; however, the doses used were too low to adequately assess the effects of modafinil on embryofetal development. In a subsequent developmental toxicity study evaluating doses of 45, 90, and 180 mg/kg/day in pregnant rabbits, the incidences of fetal structural alterations and embryofetal death were increased at the highest dose. The highest no-effect dose for developmental toxicity (100 mg/kg/day) was associated with a plasma modafinil AUC similar to that in humans at the RHD of modafinil tablets.
Modafinil administration to rats throughout gestation and lactation at oral doses of up to 200 mg/kg/day resulted in decreased viability in the offspring at doses greater than 20 mg/kg/day, a dose resulting in a plasma modafinil AUC less than that in humans at the RHD of modafinil tablets. No effects on postnatal developmental and neurobehavioral parameters were observed in surviving offspring.
8.3Nursing Mothers It is not known whether modafinil or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when modafinil tablets are administered to a nursing woman.
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established. Modafinil tablets are not approved in this population for any indication. Serious skin rashes, including erythema multiforme major (EMM) and Stevens - Johnson Syndrome (SJS) have been associated with modafinil use in pediatric patients [see Warnings and Precautions (5.1) ].
In a controlled 6-week study, 165 pediatric patients (aged 5-17 years) with narcolepsy were treated with modafinil (n=123), or placebo (n=42). There were no statistically significant differences favoring modafinil over placebo in prolonging… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Category C There are no adequate and well-controlled studies of modafinil in pregnant women. Intrauterine growth restriction and spontaneous abortion have been reported in association with modafinil (a mixture of R-and S-modafinil) and armodafinil (the R-enantiomer of modafinil). Although the pharmacology of modafinil is not identical to that of the sympathomimetic amines, it does share some pharmacologic properties with this class.
Certain of these drugs have been associated with intrauterine growth restriction and spontaneous abortions. Whether the cases reported with modafinil are drug-related is unknown. In studies of modafinil and armodafinil conducted in rats (modafinil, armodafinil) and rabbits (modafinil), developmental toxicity was observed at clinically relevant plasma exposures.
Modafinil tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Modafinil (50, 100, or 200 mg/kg/day) administered orally to pregnant rats throughout organogenesis caused, in the absence of maternal toxicity, an increase in resorptions and an increased incidence of visceral and skeletal variations in the offspring at the highest dose tested. The higher no-effect dose for embryofetal developmental toxicity in rats (100 mg/kg/day) was associated with a plasma modafinil AUC less than that in humans at the recommended human dose (RHD) of modafinil tablets (200 mg/day).
However, in a subsequent study of up to 480 mg/kg/day of modafinil, no adverse effects on embryofetal development were observed. Oral administration of armodafinil (60, 200, or 600 mg/kg/day) to pregnant rats throughout organogenesis resulted in increased incidences of fetal visceral and skeletal variations and decreased fetal body weight at the highest dose tested. The highest no-effect dose for embryofetal developmental toxicity in rats (200 mg/kg/day) was associated with a plasma armodafinil AUC less than that in humans at the RHD of modafinil tablets.
Modafinil administered orally to pregnant rabbits throughout organogenesis at doses of up to 100 mg/kg/day had no effect on embryofetal development; however, the doses used were too low to adequately assess the effects of modafinil on embryofetal development. In a subsequent developmental toxicity study evaluating doses of 45, 90, and 180 mg/kg/day in pregnant rabbits, the incidences of fetal structural alterations and embryofetal death were increased at the highest dose. The highest no-effect dose for developmental toxicity (100 mg/kg/day) was associated with a plasma modafinil AUC similar to that in humans at the RHD of modafinil tablets.
Modafinil administration to rats throughout gestation and lactation at oral doses of up to 200 mg/kg/day resulted in decreased viability in the offspring at doses greater than 20 mg/kg/day, a dose resulting in a plasma modafinil AUC less than that in humans at the RHD of modafinil tablets. No effects on postnatal developmental and neurobehavioral parameters were observed in surviving offspring.
🧓 Geriatric Use ▾
8.5Geriatric Use In clinical trials, experience in a limited number of modafinil-treated patients who were greater than 65 years of age showed an incidence of adverse reactions similar to other age groups. In elderly patients, elimination of modafinil and its metabolites may be reduced as a consequence of aging. Therefore, consideration should be given to the use of lower doses and close monitoring in this population [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)].
🆘 Overdosage ▾
10 OVERDOSAGE In clinical trials, a total of 151 protocol-specified doses ranging from 1,000 to 1,600 mg/day (5 to 8 times the recommended daily dose of modafinil tablets) have been administered to 32 subjects, including 13 subjects who received doses of 1,000 or 1,200 mg/day for 7 to 21 consecutive days. In addition, several intentional acute overdoses occurred; the two largest being 4,500 mg and 4,000 mg taken by two subjects participating in foreign depression studies. None of these study subjects experienced any unexpected or life-threatening effects.
Adverse reactions that were reported at these doses included excitation or agitation, insomnia, and slight or moderate elevations in hemodynamic parameters. Other observed high-dose effects in clinical studies have included anxiety, irritability, aggressiveness, confusion, nervousness, tremor, palpitations, sleep disturbances, nausea, diarrhea, and decreased prothrombin time. From postmarketing experience, there have been reports of fatal overdoses involving modafinil alone or in combination with other drugs.
Symptoms most often accompanying modafinil tablets overdose, alone or in combination with other drugs have included insomnia; central nervous system symptoms such as restlessness, disorientation, confusion, agitation, anxiety, excitation, and hallucination; digestive changes such as nausea and diarrhea; and cardiovascular changes such as tachycardia, bradycardia, hypertension, and chest pain. Cases of accidental ingestion/overdose have been reported in children as young as 11 months of age. The highest reported accidental ingestion on a mg/kg basis occurred in a three-year-old boy who ingested 800-1,000 mg (50-63 mg/kg) of modafinil tablets.
The child remained stable. The symptoms associated with overdose in children were similar to those observed in adults. No specific antidote exists for the toxic effects of a modafinil tablets overdose.
Such overdoses should be managed with primarily supportive care, including cardiovascular monitoring.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The mechanism(s) through which modafinil promotes wakefulness is unknown. Modafinil has wake-promoting actions similar to sympathomimetic agents including amphetamine and methylphenidate, although the pharmacologic profile is not identical to that of the sympathomimetic amines. Modafinil-induced wakefulness can be attenuated by the α1- adrenergic receptor antagonist, prazosin; however, modafinil is inactive in other in vitro assay systems known to be responsive to α-adrenergic agonists such as the rat vas deferens preparation.
Modafinil is not a direct-or indirect-acting dopamine receptor agonist. However, in vitro, modafinil binds to the dopamine transporter and inhibits dopamine reuptake. This activity has been associated in vivo with increased extracellular dopamine levels in some brain regions of animals.
In genetically engineered mice lacking the dopamine transporter (DAT), modafinil lacked wake-promoting activity, suggesting that this activity was DAT-dependent. However, the wake-promoting effects of modafinil, unlike those of amphetamine, were not antagonized by the dopamine receptor antagonist haloperidol in rats. In addition, alpha-methyl-p-tyrosine, a dopamine synthesis inhibitor, blocks the action of amphetamine, but does not block locomotor activity induced by modafinil.
In the cat, equal wakefulness-promoting doses of methylphenidate and amphetamine increased neuronal activation throughout the brain. Modafinil at an equivalent wakefulness-promoting dose selectively and prominently increased neuronal activation in more discrete regions of the brain. The relationship of this finding in cats to the effects of modafinil in humans is unknown.
In addition to its wake-promoting effects and ability to increase locomotor activity in animals, modafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking, and feelings typical of other CNS stimulants in humans. Modafinil has reinforcing properties, as evidenced by its self-administration in monkeys previously trained to self-administer cocaine; modafinil was also partially discriminated as stimulant-like. The optical enantiomers of modafinil have similar pharmacological actions in animals.
Two major metabolites of modafinil, modafinil acid and modafinil sulfone, do not appear to contribute to the CNS-activating properties of modafinil.
12.3Pharmacokinetics Modafinil is a 1:1 racemic compound, whose enantiomers have different pharmacokinetics (e.g., the half-life of R-modafinil is approximately three times that of S-modafinil in adult humans). The enantiomers do not interconvert. At steady state, total exposure to R-modafinil is approximately three times that for S-modafinil.
The trough concentration (C min,ss ) of circulating modafinil after once daily dosing consists of 90% of R-modafinil and 10% of S-modafinil. The effective elimination half-life of modafinil after multiple doses is about 15 hours. The enantiomers of modafinil exhibit linear kinetics upon multiple dosing of 200-600 mg/day once daily in healthy volunteers.
Apparent steady states of total modafinil and R-modafinil are reached after 2-4 days of dosing. Absorption Modafinil tablet is readily absorbed after oral administration, with peak plasma concentrations occurring at 2-4 hours. The bioavailability of modafinil tablets is approximately equal to that of an aqueous suspension.
The absolute oral bioavailability was not determined due to the aqueous insolubility (<1 mg/mL) of modafinil, which precluded intravenous administration. Food has no effect on overall modafinil tablets bioavailability; however, time to reach peak concentration (t max ) may be delayed by approximately one hour if taken with food. Distribution Modafinil tablets has an apparent volume of distribution of approximately
0.9L/kg. In human plasma, in vitro, modafinil is moderately bound to plasma protein (approximately 60%), mainly to albumin. The potential for… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action The mechanism(s) through which modafinil promotes wakefulness is unknown. Modafinil has wake-promoting actions similar to sympathomimetic agents including amphetamine and methylphenidate, although the pharmacologic profile is not identical to that of the sympathomimetic amines. Modafinil-induced wakefulness can be attenuated by the α1- adrenergic receptor antagonist, prazosin; however, modafinil is inactive in other in vitro assay systems known to be responsive to α-adrenergic agonists such as the rat vas deferens preparation.
Modafinil is not a direct-or indirect-acting dopamine receptor agonist. However, in vitro, modafinil binds to the dopamine transporter and inhibits dopamine reuptake. This activity has been associated in vivo with increased extracellular dopamine levels in some brain regions of animals.
In genetically engineered mice lacking the dopamine transporter (DAT), modafinil lacked wake-promoting activity, suggesting that this activity was DAT-dependent. However, the wake-promoting effects of modafinil, unlike those of amphetamine, were not antagonized by the dopamine receptor antagonist haloperidol in rats. In addition, alpha-methyl-p-tyrosine, a dopamine synthesis inhibitor, blocks the action of amphetamine, but does not block locomotor activity induced by modafinil.
In the cat, equal wakefulness-promoting doses of methylphenidate and amphetamine increased neuronal activation throughout the brain. Modafinil at an equivalent wakefulness-promoting dose selectively and prominently increased neuronal activation in more discrete regions of the brain. The relationship of this finding in cats to the effects of modafinil in humans is unknown.
In addition to its wake-promoting effects and ability to increase locomotor activity in animals, modafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking, and feelings typical of other CNS stimulants in humans. Modafinil has reinforcing properties, as evidenced by its self-administration in monkeys previously trained to self-administer cocaine; modafinil was also partially discriminated as stimulant-like. The optical enantiomers of modafinil have similar pharmacological actions in animals.
Two major metabolites of modafinil, modafinil acid and modafinil sulfone, do not appear to contribute to the CNS-activating properties of modafinil.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Modafinil Tablets, USP are available as follows: 100 mg White to off white capsule shaped uncoated tablets debossed with AC 132 on one side and plain on other side. NDC 23155-604-03 - Bottles of 30 NDC 23155-604-09 - Bottles of 90 NDC 23155-604-01 - Bottles of 100 NDC 23155-604-05 - Bottles of 500 200 mg White to off white round shaped uncoated tablet scored on the one side with AC above and 133 below and plain on other side. NDC 23155-862-03 - Bottles of 30 NDC 23155-862-09 - Bottles of 90 NDC 23155-862-01 - Bottles of 100 NDC 23155-862-05 - Bottles of 500
16.2Storage Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature]. Dispense in a tight container.
16.1How Supplied Modafinil Tablets, USP are available as follows: 100 mg White to off white capsule shaped uncoated tablets debossed with AC 132 on one side and plain on other side. NDC 23155-604-03 - Bottles of 30 NDC 23155-604-09 - Bottles of 90 NDC 23155-604-01 - Bottles of 100 NDC 23155-604-05 - Bottles of 500 200 mg White to off white round shaped uncoated tablet scored on the one side with AC above and 133 below and plain on other side. NDC 23155-862-03 - Bottles of 30 NDC 23155-862-09 - Bottles of 90 NDC 23155-862-01 - Bottles of 100 NDC 23155-862-05 - Bottles of 500
16.2Storage Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature]. Dispense in a tight container.
📋 Description ▾
11 DESCRIPTION Modafinil tablets, USP are wakefulness-promoting agent for oral administration. Modafinil is a racemic compound. The chemical name for modafinil is 2-[(diphenylmethyl)sulfinyl]acetamide.
The molecular formula is C 15 H 15 NO 2 S and the molecular weight is 273.4. The chemical structure is: Modafinil is a white to off-white, crystalline powder that is practically insoluble in water, sparingly soluble in methanol and slightly soluble in ethanol (96%). Modafinil tablets, USP contain 100 mg or 200 mg of modafinil and the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose and povidone.
Chem Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Allergic Reactions Advise patients to stop taking modafinil tablets and to notify their physician right away if they develop a rash, hives, mouth sores, blisters, peeling skin, trouble swallowing or breathing, or a related allergic phenomenon. Driving and Dangerous Activities Advise patients not to alter their previous behavior with regard to potentially dangerous activities (e.g., driving, operating machinery) or other activities requiring appropriate levels of wakefulness, until and unless treatment with modafinil tablets has been shown to produce levels of wakefulness that permit such activities.
Advise patients that modafinil tablet are not a replacement for sleep. Continuing Previously Prescribed Treatments Inform patients that it may be critical that they continue to take their previously prescribed treatments (e.g., patients with OSA receiving CPAP should continue to do so). Discontinuing Drug Due to Adverse Reactions Advise patients to stop taking modafinil tablets and contact their physician right away if they experience chest pain, rash, depression, anxiety, or signs of psychosis or mania.
Pregnancy Advise patients to notify their physician if they become pregnant or intend to become pregnant during therapy. Caution patients regarding the potential increased risk of pregnancy when using steroidal contraceptives (including depot or implantable contraceptives) with modafinil tablets and for one month after discontinuation of therapy. Nursing Advise patients to notify their physician if they are breastfeeding an infant.
Concomitant Medication Advise patients to inform their physician if they are taking, or plan to take, any prescription or over-the-counter drugs, because of the potential for interactions between modafinil tablets and other drugs. Alcohol Advise patients that the use of modafinil tablets in combination with alcohol has not been studied. Advise patients that it is prudent to avoid alcohol while taking modafinil tablets.
Manufactured by: Sidmak Laboratories (India) Pvt. Ltd. Plot No.
20, Pharma City, Selaqui Industrial Area, Dehradun - 248 197, Uttarakhand, India. Manufactured for: Avet Pharmaceuticals Inc. East Brunswick, NJ 08816.
1-866-901-DRUG (3784) P2081011 Revised: 09/2023 M. L. No.
38/UA/2007 modafinil-spl-avetlogo
💬 Medication Guide ▾
MEDICATION GUIDE Modafinil Tablets, USP C-IV (moe DAF i nil) Read this Medication Guide before you start taking modafinil tablets and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or treatment.
What is the most important information I should know about modafinil tablets? Modafinil tablets may cause serious side effects including a serious rash or a serious allergic reaction that may affect parts of your body such as your liver or blood cells. Any of these may need to be treated in a hospital and may be life-threatening.
Stop taking modafinil tablets and call your doctor right away or get emergency help if you have any of these symptoms: skin rash, hives, sores in your mouth, or your skin blisters and peels swelling of your face, eyes, lips, tongue, or throat trouble swallowing or breathing fever, shortness of breath, swelling of the legs, yellowing of the skin or whites of the eyes, or dark urine. If you have a severe rash with modafinil tablets, stopping the medicine may not keep the rash from becoming life-threatening or causing you to be permanently disabled or disfigured.
Modafinil tablets are not approved for use in children for any medical condition. It is not known if modafinil tablets is safe or effective in children under 17 years of age. What are modafinil tablets?
Modafinil tablets are a prescription medicine used to improve wakefulness in adults who are very sleepy due to one of the following diagnosed sleep disorders: narcolepsy obstructive sleep apnea (OSA). Modafinil tablets are used to treat excessive sleepiness, but not the obstruction or medical condition that is causing OSA. You should talk with your doctor about treatments for OSA before you start taking modafinil tablets and during treatment with modafinil tablets.
Modafinil tablets do not take the place of treatments that your doctor has prescribed for OSA. It is important that you continue to use these treatments as prescribed by your doctor. shift work disorder (SWD) Modafinil tablets will not cure these sleep disorders. Modafinil tablets may help the sleepiness caused by these conditions, but it may not stop all your sleepiness.
Modafinil tablets do not take the place of getting enough sleep. Follow your doctor's advice about good sleep habits and using other treatments. Modafinil tablets are federally controlled substance (C-IV) because it can be abused or lead to dependence.
Keep modafinil tablets in a safe place to prevent misuse and abuse. Selling or giving away modafinil tablets may harm others, and is against the law. Tell your doctor if you have ever abused or been dependent on alcohol, prescription medicines, or street drugs.
Who should not take modafinil tablets? Do not take modafinil tablets if you: are allergic or developed a rash to modafinil or armodafinil (NUVIGIL ® ) or any of the ingredients in modafinil tablets. See the end of this Medication Guide for a complete list of ingredients in modafinil tablets.
What should I tell my doctor before taking modafinil tablets? Tell your doctor about all of your medical conditions including, if you: have a history of mental health problems, including psychosis have heart problems or had a heart attack have high blood pressure. Your blood pressure may need to be checked more often while taking modafinil tablets. have liver or kidney problems have a history of drug or alcohol abuse or addiction are pregnant or planning to become pregnant.
It is not known if modafinil will harm your unborn baby. are breastfeeding. It is not known if modafinil passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take modafinil tablets.
Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Modafinil tablets and many other medicines can interact with each other, sometimes causing side eff… [Excerpted — this section continues on DailyMed.]
🍼 Nursing Mothers ▾
8.3Nursing Mothers It is not known whether modafinil or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when modafinil tablets are administered to a nursing woman.
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established. Modafinil tablets are not approved in this population for any indication. Serious skin rashes, including erythema multiforme major (EMM) and Stevens - Johnson Syndrome (SJS) have been associated with modafinil use in pediatric patients [see Warnings and Precautions (5.1) ].
In a controlled 6-week study, 165 pediatric patients (aged 5-17 years) with narcolepsy were treated with modafinil (n=123), or placebo (n=42). There were no statistically significant differences favoring modafinil over placebo in prolonging sleep latency as measured by MSLT, or in perceptions of sleepiness as determined by the clinical global impression-clinician scale (CGI-C). In the controlled and open-label clinical studies, treatment emergent adverse reactions of the psychiatric and nervous system included Tourette’s syndrome, insomnia, hostility, increased cataplexy, increased hypnagogic hallucinations, and suicidal ideation.
Transient leukopenia, which resolved without medical intervention, was also observed. In the controlled clinical study, 3 of 38 girls, ages 12 or older, treated with modafinil experienced dysmenorrhea compared to 0 of 10 girls who received placebo. There were three 7 to 9 week, double-blind, placebo-controlled, parallel group studies in children and adolescents (aged 6-17 years) with Attention-Deficit Hyperactivity Disorder (ADHD).
Two of the studies were flexible-dose studies (up to 425 mg/day), and the third was a fixed-dose study (340 mg/day for patients <30 kg and 425 mg/day for patients ≥30 kg). Although these studies showed statistically significant differences favoring modafinil over placebo in reducing ADHD symptoms as measured by the ADHD-RS (school version), there were 3 cases of serious rash including one case of possible SJS among 933 patients exposed to modafinil in this program. Modafinil is not approved for use in treating ADHD.
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Modafinil is a 1:1 racemic compound, whose enantiomers have different pharmacokinetics (e.g., the half-life of R-modafinil is approximately three times that of S-modafinil in adult humans). The enantiomers do not interconvert. At steady state, total exposure to R-modafinil is approximately three times that for S-modafinil.
The trough concentration (C min,ss ) of circulating modafinil after once daily dosing consists of 90% of R-modafinil and 10% of S-modafinil. The effective elimination half-life of modafinil after multiple doses is about 15 hours. The enantiomers of modafinil exhibit linear kinetics upon multiple dosing of 200-600 mg/day once daily in healthy volunteers.
Apparent steady states of total modafinil and R-modafinil are reached after 2-4 days of dosing. Absorption Modafinil tablet is readily absorbed after oral administration, with peak plasma concentrations occurring at 2-4 hours. The bioavailability of modafinil tablets is approximately equal to that of an aqueous suspension.
The absolute oral bioavailability was not determined due to the aqueous insolubility (<1 mg/mL) of modafinil, which precluded intravenous administration. Food has no effect on overall modafinil tablets bioavailability; however, time to reach peak concentration (t max ) may be delayed by approximately one hour if taken with food. Distribution Modafinil tablets has an apparent volume of distribution of approximately
0.9L/kg. In human plasma, in vitro, modafinil is moderately bound to plasma protein (approximately 60%), mainly to albumin. The potential for interactions of modafinil tablets with highly protein-bound drugs is considered to be minimal.
Metabolism and Elimination The major route of elimination is metabolism (approximately 90%), primarily by the liver, with subsequent renal elimination of the metabolites. Urine alkalinization has no effect on the elimination of modafinil. Metabolism occurs through hydrolytic deamidation, S-oxidation, aromatic ring hydroxylation, and glucuronide conjugation.
Less than 10% of an administered dose is excreted as the parent compound. In a clinical study using radiolabeled modafinil, a total of 81% of the administered radioactivity was recovered in 11 days post-dose, predominantly in the urine (80% vs. 1.0% in the feces).
The largest fraction of the drug in urine was modafinil acid, but at least six other metabolites were present in lower concentrations. Only two metabolites reach appreciable concentrations in plasma, i.e., modafinil acid and modafinil sulfone. In preclinical models, modafinil acid, modafinil sulfone, 2-[(diphenylmethyl) sulfonyl] acetic acid and 4-hydroxy modafinil, were inactive or did not appear to mediate the arousal effects of modafinil.
In adults, decreases in trough levels of modafinil have sometimes been observed after multiple weeks of dosing, suggesting auto-induction, but the magnitude of the decreases and the inconsistency of their occurrence suggest that their clinical significance is minimal. Significant accumulation of modafinil sulfone has been observed after multiple doses due to its long elimination half-life of 40 hours. Auto-induction of metabolizing enzymes, most importantly cytochrome P-450 CYP3A4, has also been observed in vitro after incubation of primary cultures of human hepatocytes with modafinil and in vivo after extended administration of modafinil at 400 mg/day.
Specific Populations Age A slight decrease (approximately 20%) in the oral clearance (CL/F) of modafinil was observed in a single dose study at 200 mg in 12 subjects with a mean age of 63 years (range 53 – 72 years), but the change was considered not likely to be clinically significant. In a multiple dose study (300 mg/day) in 12 patients with a mean age of 82 years (range 67 – 87 years), the mean levels of modafinil in plasma were approximately two times those historically obtained in matched younger subjects. Due to potential effects from the multiple concomitant medications… [Excerpted — this section continues on DailyMed.]
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Narcolepsy The effectiveness of modafinil tablets in improving wakefulness in adult patients with excessive sleepiness associated with narcolepsy was established in two US 9-week, multi-center, placebo-controlled, parallel-group, double-blind studies of outpatients who met the criteria for narcolepsy. A total of 558 patients were randomized to receive modafinil tablets 200 or 400 mg/day, or placebo. The criteria for narcolepsy include either: 1) recurrent daytime naps or lapses into sleep that occur almost daily for at least three months, plus sudden bilateral loss of postural muscle tone in association with intense emotion (cataplexy); or 2) a complaint of excessive sleepiness or sudden muscle weakness with associated features: sleep paralysis, hypnagogic hallucinations, automatic behaviors, disrupted major sleep episode; and polysomnography demonstrating one of the following: sleep latency less than 10 minutes or rapid eye movement (REM) sleep latency less than 20 minutes.
For entry into these studies, all patients were required to have objectively documented excessive daytime sleepiness, via a Multiple Sleep Latency Test (MSLT) with two or more sleep onset REM periods and the absence of any other clinically significant active medical or psychiatric disorder. The MSLT, an objective polysomnographic assessment of the patient’s ability to fall asleep in an unstimulating environment, measured latency (in minutes) to sleep onset averaged over 4 test sessions at 2-hour intervals. For each test session, the subject was told to lie quietly and attempt to sleep.
Each test session was terminated after 20 minutes if no sleep occurred or 15 minutes after sleep onset. In both studies, the primary measures of effectiveness were: 1) sleep latency, as assessed by the Maintenance of Wakefulness Test (MWT); and 2) the change in the patient’s overall disease status, as measured by the Clinical Global Impression of Change (CGI-C). For a successful trial, both measures had to show statistically significant improvement.
The MWT measures latency (in minutes) to sleep onset averaged over 4 test sessions at 2 hour intervals following nocturnal polysomnography. For each test session, the subject was asked to attempt to remain awake without using extraordinary measures. Each test session was terminated after 20 minutes if no sleep occurred or 10 minutes after sleep onset.
The CGI-C is a 7-point scale, centered at No Change, and ranging from Very Much Worse to Very Much Improved . Patients were rated by evaluators who had no access to any data about the patients other than a measure of their baseline severity. Evaluators were not given any specific guidance about the criteria they were to apply when rating patients.
Both studies demonstrated improvement in objective and subjective measures of excessive daytime sleepiness for both the 200 mg and 400 mg doses compared to placebo. Patients treated with modafinil tablets showed a statistically significantly enhanced ability to remain awake on the MWT at each dose compared to placebo at final visit (Table 2). A statistically significantly greater number of patients treated with modafinil tablets at each dose showed improvement in overall clinical condition as rated by the CGI-C scale at final visit (Table 3).
Nighttime sleep measured with polysomnography was not affected by the use of modafinil tablets.
14.2Obstructive Sleep Apnea (OSA) The effectiveness of modafinil tablets in improving wakefulness in patients with excessive sleepiness associated with OSA was established in two multi-center, placebo-controlled clinical studies of patients who met the criteria for OSA.The criterial include either: 1) excessive sleepiness or insomnia, plus frequent episodes of impaired breathing during sleep, and associated features such as loud snoring, morning headaches and dry mouth upon awakening; or 2) excessive sleepiness or insomnia and polysomnography demonstrating one of the following: mor… [Excerpted — this section continues on DailyMed.]
🔒 Drug Abuse and Dependence ▾
9 DRUG ABUSE AND DEPENDENCE
9.1Controlled Substance Modafinil tablets contains modafinil, a Schedule IV controlled substance.
9.2Abuse In humans, modafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking, and feelings typical of other CNS stimulants. In in vitro binding studies, modafinil binds to the dopamine reuptake site and causes an increase in extracellular dopamine, but no increase in dopamine release. Modafinil is reinforcing, as evidenced by its self-administration in monkeys previously trained to self-administer cocaine.
In some studies, modafinil was also partially discriminated as stimulant-like. Physicians should follow patients closely, especially those with a history of drug and/or stimulant (e.g., methylphenidate, amphetamine, or cocaine) abuse. Patients should be observed for signs of misuse or abuse (e.g., incrementation of doses or drug-seeking behavior).
The abuse potential of modafinil (200, 400, and 800 mg) was assessed relative to methylphenidate (45 and 90 mg) in an inpatient study in individuals experienced with drugs of abuse. Results from this clinical study demonstrated that modafinil produced psychoactive and euphoric effects and feelings consistent with other scheduled CNS stimulants (methylphenidate).
9.3Dependence In one placebo-controlled clinical trial, the effects of modafinil withdrawal were monitored following 9 weeks of modafinil use. There were no reported withdrawal symptoms with modafinil during 14 days of observation, although sleepiness returned in narcoleptic patients.
9.1Controlled Substance Modafinil tablets contains modafinil, a Schedule IV controlled substance.
9.2Abuse In humans, modafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking, and feelings typical of other CNS stimulants. In in vitro binding studies, modafinil binds to the dopamine reuptake site and causes an increase in extracellular dopamine, but no increase in dopamine release. Modafinil is reinforcing, as evidenced by its self-administration in monkeys previously trained to self-administer cocaine.
In some studies, modafinil was also partially discriminated as stimulant-like. Physicians should follow patients closely, especially those with a history of drug and/or stimulant (e.g., methylphenidate, amphetamine, or cocaine) abuse. Patients should be observed for signs of misuse or abuse (e.g., incrementation of doses or drug-seeking behavior).
The abuse potential of modafinil (200, 400, and 800 mg) was assessed relative to methylphenidate (45 and 90 mg) in an inpatient study in individuals experienced with drugs of abuse. Results from this clinical study demonstrated that modafinil produced psychoactive and euphoric effects and feelings consistent with other scheduled CNS stimulants (methylphenidate).
9.3Dependence In one placebo-controlled clinical trial, the effects of modafinil withdrawal were monitored following 9 weeks of modafinil use. There were no reported withdrawal symptoms with modafinil during 14 days of observation, although sleepiness returned in narcoleptic patients.
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Carcinogenicity studies were conducted in which modafinil (a mixture of R-and S-modafinil) was administered in the diet to mice for 78 weeks and to rats for 104 weeks at doses of 6, 30, and 60 mg/kg/day. The highest doses studied were associated with plasma modafinil exposures (AUC) less than that in humans at the recommended human dose (RHD) of modafinil tablets (200 mg/day). There was no evidence of tumorigenesis associated with modafinil administration in these studies.
However, the mouse study was inadequate because the high dose was not a maximum tolerated dose (MTD). In a mouse carcinogenicity study in which armodafinil (the R-enantiomer of modafinil) was administered at oral doses of up to 300 mg/kg/day in males and 100 mg/kg/day in females for approximately 2 years, no tumorigenic effects were observed. The highest doses studied, which were considered MTDs, were associated with plasma armodafinil exposures less than (females) or 2 times (males) that in humans at the RHD of modafinil tablets.
Mutagenesis Modafinil was negative in a series of in vitro (i.e., bacterial reverse mutation, mouse lymphoma tk, chromosomal aberration in human lymphocytes, cell transformation in BALB/3T3 mouse embryo cells) or in vivo (mouse bone marrow micronucleus) assays. Impairment of Fertility Oral administration of modafinil (doses of up to 480 mg/kg/day) to male and female rats prior to and throughout mating, and continuing in females through day 7 of gestation produced an increase in the time to mate at the highest dose; no effects were observed on other fertility or reproductive parameters.
The no-effect dose of 240 mg/kg/day was associated with a plasma modafinil AUC less than that in humans at the RHD of modafinil tablets.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Carcinogenicity studies were conducted in which modafinil (a mixture of R-and S-modafinil) was administered in the diet to mice for 78 weeks and to rats for 104 weeks at doses of 6, 30, and 60 mg/kg/day. The highest doses studied were associated with plasma modafinil exposures (AUC) less than that in humans at the recommended human dose (RHD) of modafinil tablets (200 mg/day). There was no evidence of tumorigenesis associated with modafinil administration in these studies.
However, the mouse study was inadequate because the high dose was not a maximum tolerated dose (MTD). In a mouse carcinogenicity study in which armodafinil (the R-enantiomer of modafinil) was administered at oral doses of up to 300 mg/kg/day in males and 100 mg/kg/day in females for approximately 2 years, no tumorigenic effects were observed. The highest doses studied, which were considered MTDs, were associated with plasma armodafinil exposures less than (females) or 2 times (males) that in humans at the RHD of modafinil tablets.
Mutagenesis Modafinil was negative in a series of in vitro (i.e., bacterial reverse mutation, mouse lymphoma tk, chromosomal aberration in human lymphocytes, cell transformation in BALB/3T3 mouse embryo cells) or in vivo (mouse bone marrow micronucleus) assays. Impairment of Fertility Oral administration of modafinil (doses of up to 480 mg/kg/day) to male and female rats prior to and throughout mating, and continuing in females through day 7 of gestation produced an increase in the time to mate at the highest dose; no effects were observed on other fertility or reproductive parameters.
The no-effect dose of 240 mg/kg/day was associated with a plasma modafinil AUC less than that in humans at the RHD of modafinil tablets.
📄 Package Label / Principal Display Panel ▾
modafinil-spl-100mg30s modafinil-spl-100mg90s modafinil-200mg30s modafinil-spl-200mg90s spl-modafinil-200mg-30s spl-modafinil-200mg-90s spl-modafinil-200mg-100s spl-modafinil-200mg-500s