Drug interaction reference
This page is a reference summary of published evidence and regulatory documents. It is not a substitute for individual medical advice, and it is not a recommendation to take or avoid any medicine.
Medically reviewed by Dr. Sofia Lindqvist, · Last reviewed 11 August 2026
Last verified 11 August 2026. Next scheduled verification 11 November 2026.
Educational information, not medical advice. This table is not exhaustive and cannot account for individual circumstances. Any interaction question about a specific regimen belongs with a prescriber or pharmacist who can see the full medication list.
On this page
- Modafinil: the three facts that generate the profile
- Drugs modafinil may make less effective
- Drugs modafinil may increase levels of
- Drugs that affect modafinil levels
- Armodafinil
- Solriamfetol
- Pitolisant
- Amphetamines and methylphenidate
- Who should have a full interaction review
- Change log
- Frequently asked questions
Modafinil: the three facts that generate the profile
Modafinil is a substrate of hepatic CYP3A4, a moderate inducer of CYP3A4 and CYP3A5, and a weak inhibitor of CYP2C19. Its interaction profile follows from those three facts.
Induces CYP3A4
Speeds clearance of 3A4 substrates, reducing their effect
Inhibits CYP2C19
Slows clearance of 2C19 substrates, raising their levels
Substrate of CYP3A4
Its own levels move with inducers and inhibitors
Each enzyme relationship predicts a direction of effect, which is why the tables below are grouped by mechanism rather than alphabetically.
Drugs modafinil may make less effective
Via CYP3A4 induction, which speeds their clearance.
| Affected drug | Effect | Clinical significance |
|---|---|---|
| Hormonal contraceptives | Ethinyl estradiol clearance increased around 18 percent | High. Alternative or additional non hormonal contraception recommended during treatment and for one month after, or two months under UK guidance |
| Cyclosporine | Levels reduced around 50 percent | High. Risk of transplant rejection |
| Other CYP3A4 substrates | Variable reduction | Assess case by case |
| CYP1A2 and CYP2B6 substrates | Possible reduction | Lower certainty |
The interaction that matters most
The contraceptive interaction should be read together with the pregnancy contraindications. Reduced contraceptive efficacy and suspected congenital malformations compound one another, and that combination is the single most clinically important interaction on this page.
Drugs modafinil may increase levels of
Via CYP2C19 inhibition and other mechanisms.
| Affected drug | Concern |
|---|---|
| Warfarin | Bleeding risk. INR monitoring warranted |
| Phenytoin | Narrow therapeutic index. Toxicity risk |
| Diazepam and related benzodiazepines | Increased sedation |
| Omeprazole and other proton pump inhibitors | Increased exposure |
| Certain SSRIs and tricyclic antidepressants | Particularly in CYP2C19 poor metabolisers |
| Propranolol | Increased exposure |
Drugs that affect modafinil levels
| Drug class | Effect on modafinil |
|---|---|
| CYP3A4 inducers: rifampin, phenytoin, carbamazepine, St John's Wort, efavirenz | Reduced levels |
| CYP3A4 inhibitors: ketoconazole, itraconazole, erythromycin | Increased levels |
| Non prescription substance | Concern |
|---|---|
| Caffeine | Additive cardiovascular and anxiogenic load. No formal contraindication. Modafinil weakly induces CYP1A2, which may modestly increase caffeine clearance |
| Alcohol | No formal contraindication. Modafinil masks subjective fatigue without reducing impairment, which can lead to misjudgement of one's own state |
| Other stimulants | Additive cardiovascular and psychiatric adverse effect risk |
Armodafinil
The interaction profile is broadly the same as modafinil, which follows from their being the same molecule. All entries above apply.
Solriamfetol
Solriamfetol is minimally metabolised and excreted renally as unchanged drug. Its interaction profile is consequently much simpler than modafinil’s.
| Concern | Detail |
|---|---|
| Renal function | Determines exposure. Dose adjustment driven by kidney function |
| Cardiovascular | Effects on blood pressure and heart rate. Caution with other agents affecting these |
| MAOIs | UNVERIFIED |
| Dopaminergic agents | UNVERIFIED |
The absence of substantial hepatic metabolism makes solriamfetol a consideration where a complex medication list makes CYP mediated interactions a concern.
Pitolisant
| Concern | Detail |
|---|---|
| Antidepressants | Recognised concern. Clinicians have noted possible facilitation of arrhythmias with concurrent antidepressant use, though this has not been well studied. Some prescribers monitor with ECG, and practice varies |
| Cardiac conduction | Pitolisant affects cardiac conduction. Caution with other QT affecting agents |
| Hormonal contraceptives | UNVERIFIED |
| CYP interactions | UNVERIFIED |
Amphetamines and methylphenidate
| Concern | Detail |
|---|---|
| MAOIs | Contraindicated. Risk of hypertensive crisis |
| Serotonergic agents | Serotonin syndrome risk with amphetamines |
| Acidifying and alkalinising agents | Alter amphetamine excretion |
| Antihypertensives | Efficacy may be reduced |
| Other stimulants including caffeine | Additive cardiovascular load |
Who should have a full interaction review
Anyone taking any of the following should have their regimen reviewed before and during treatment with a wakefulness agent or stimulant.
- Hormonal contraception of any kind
- Anticoagulants including warfarin
- Immunosuppressants including cyclosporine
- Anticonvulsants including phenytoin and carbamazepine
- Benzodiazepines
- Antidepressants of any class
- Proton pump inhibitors
- Antiretrovirals
- Beta blockers and other cardiovascular medication
- Any MAOI
Change log
| Date | Change | Source |
|---|---|---|
| 11 August 2026 | Page created | FDA prescribing information, EMA product information |
Does modafinil reduce the effectiveness of hormonal contraception?
Yes. It induces CYP3A4 and increases ethinyl estradiol clearance by around 18 percent. Alternative or additional non hormonal contraception is recommended during treatment and for one month after, or two months under UK guidance.
Which interaction matters most?
The contraceptive one, read together with the pregnancy contraindications. Reduced contraceptive efficacy and suspected congenital malformations compound one another.
Why is solriamfetol's profile simpler?
It is minimally metabolised and excreted renally as unchanged drug, so CYP mediated interactions are largely not in play. Renal function determines exposure instead.
Can modafinil be combined with caffeine or alcohol?
Neither is formally contraindicated. Caffeine adds cardiovascular and anxiogenic load, and modafinil masks subjective fatigue without reducing alcohol related impairment.