Meta Information
ID:modafinil
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/circadian/sleep
Target name:
Going to Sleep
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
12
Hours after target:
null
Description:
Modafinil is a long-acting wakefulness-promoting agent with a half-life of 12-15 hours, which directly interferes with the ability to fall asleep if taken too close to bedtime.
Actionable advice:
A dose should be taken early in the morning to avoid disrupting nighttime sleep.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
200 mg once a day in the morning
Label source:
FDA label: Modafinil (Provigil) — Dosage and Administration (2.1)
Action type:
avoid
Target id:
/class/estrogens
Target name:
Hormonal Contraceptives (Oral, Patch, Implant)
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Modafinil strongly induces the CYP3A4 enzyme, which significantly accelerates the breakdown of hormonal contraceptives, potentially leading to contraceptive failure and unintended pregnancy.
Actionable advice:
A reliable non-hormonal backup method of contraception should be used during and for one month after stopping modafinil.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Caution patients regarding the potential increased risk of pregnancy when using steroidal contraceptives (including depot or implantable contraceptives) with modafinil and for one month after discontinuation of therapy.
Label source:
FDA label: Modafinil
Action type:
informational_none
Target id:
/class/maois
Target name:
Monoamine Oxidase Inhibitors (MAOIs)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The combination of modafinil with MAOIs can lead to a dangerous increase in blood pressure (hypertensive crisis) due to excessive sympathomimetic effects.
Actionable advice:
Modafinil should not be used with MAOIs or within 14 days of stopping an MAOI.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Caution should be used when concomitantly administering MAO inhibitors and PROVIGIL
Label source:
FDA label: Modafinil (Provigil) — Drug Interactions: MAO Inhibitors
Action type:
avoid
Target id:
/class/cyp3a4-substrates
Target name:
Medications Metabolized by CYP3A4
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Modafinil is a moderate inducer of the CYP3A4 enzyme, which accelerates the breakdown of many medications (e.g., certain statins, benzodiazepines, immunosuppressants), reducing their effectiveness.
Actionable advice:
Modafinil induces CYP3A4 and can lower levels of some drugs, including hormonal contraceptives and certain statins. Use backup contraception and have your prescriber check affected medications.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
clearance of drugs that are substrates for CYP3A4/5
Label source:
FDA label: Modafinil (Provigil) — Drug Interactions: Effects on CYP3A4/5 Substrates
Action type:
informational_none
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Modafinil use during pregnancy may be associated with an increased risk of congenital malformations, including cardiac anomalies and orofacial clefts.
Actionable advice:
Modafinil should not be used during pregnancy or when planning to become pregnant.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Based on animal data, may cause fetal harm.
Label source:
FDA label: Modafinil
Action type:
avoid
Target id:
/condition/cardiovascular-disease
Target name:
History of Heart Problems (e.g., Arrhythmia, Uncontrolled Hypertension)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Modafinil can increase heart rate and blood pressure, which may pose a significant risk for individuals with pre-existing cardiovascular conditions.
Actionable advice:
Use should be avoided in patients with a history of arrhythmia, uncontrolled high blood pressure, or other significant heart conditions.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Known Cardiovascular Disease
Label source:
FDA label: Modafinil (Provigil) — Warnings and Precautions (5.7) Known Cardiovascular Disease
Action type:
avoid
Target id:
/condition/hepatic-impairment
Target name:
Severe Liver Impairment
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The liver is the primary site of modafinil metabolism; severe impairment can lead to significantly increased drug levels and a higher risk of side effects.
Actionable advice:
The dose should be reduced, typically by half, in individuals with severe hepatic impairment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In patients with severe hepatic impairment, the dosage of PROVIGIL should be reduced to one-half
Label source:
FDA label: Modafinil (Provigil) — Dosage (2.3) Severe Hepatic Impairment
Action type:
adjust_with_prescriber
Target id:
/class/cyp2c19-substrates
Target name:
Medications Metabolized by CYP2C19
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Modafinil inhibits the CYP2C19 enzyme, which can slow the breakdown of certain drugs (e.g., omeprazole, phenytoin, diazepam), increasing their levels and risk of side effects.
Actionable advice:
It is worth watching out for increased side effects of co-administered drugs, and dose adjustments may be needed.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Elimination of drugs that are substrates for CYP2C19
Label source:
FDA label: Modafinil (Provigil) — Drug Interactions: Effects on CYP2C19 Substrates
Action type:
adjust_with_prescriber
Target id:
/class/anticoagulants-antiplatelets
Target name:
Warfarin
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Modafinil may weakly inhibit CYP2C9, potentially slowing the metabolism of warfarin and increasing its anticoagulant effect, which raises the risk of bleeding.
Actionable advice:
INR (blood clotting time) is best monitored closely when starting, stopping, or changing the dose of modafinil.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
COUMADIN or adverse reactions pertaining to bleeding. 7.2 CYP450 Interactions CYP450 isozymes involved in the metabolism of warfarin include CYP2C9, 2C19, 2C8, 2C18, 1A2, and 3A4.
Label source:
FDA label: Warfarin (target-side evidence)
Action type:
monitor
Target id:
/class/stimulants
Target name:
Other Stimulant Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining modafinil with other stimulants (e.g., amphetamines, methylphenidate) can lead to additive effects, increasing the risk of anxiety, insomnia, heart palpitations, and high blood pressure.
Actionable advice:
Co-administration is best avoided unless specifically prescribed and monitored by a healthcare provider.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Physicians should follow patients closely, especially those with a history of drug
Label source:
FDA label: Modafinil (Provigil) — Drug Abuse and Dependence: stimulant abuse
Action type:
avoid
Target id:
/dietary/alcohol-acute
Target name:
Alcohol (Acute Consumption)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The interaction between modafinil and alcohol is not well studied, but it may lead to unpredictable effects, impaired judgment, or an increased risk of adverse reactions.
Actionable advice:
It is generally recommended to avoid consuming alcohol while taking modafinil.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Alcohol Advise patients that the use of modafinil in combination with alcohol has not been studied.
Label source:
FDA label: Modafinil
Action type:
avoid
Target id:
/condition/bipolar-disorder
Target name:
Bipolar Disorder or History of Psychosis
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Modafinil can induce or exacerbate mania, delusions, hallucinations, and suicidal ideation in susceptible individuals.
Actionable advice:
This is best used with extreme caution and close monitoring in patients with a history of psychosis, depression, or mania.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Caution should be exercised when modafinil is given to patients with a history of psychosis, depression, or mania.
Label source:
FDA label: Modafinil
Action type:
monitor
Target id:
/condition/seizure-disorder
Target name:
Seizure Disorder / Epilepsy
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Modafinil may lower the seizure threshold, potentially increasing the risk of seizures in susceptible individuals or interfering with anticonvulsant medications.
Actionable advice:
This is best used with caution in individuals with a history of seizures.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
informational_none
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is not known if modafinil passes into breast milk, but due to its stimulant properties, there is a potential for adverse effects like irritability and poor sleep in the nursing infant.
Actionable advice:
Use should be avoided while breastfeeding due to potential risks to the infant.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Because many drugs are excreted in human milk, caution should be exercised when modafinil is administered to a nursing woman.
Label source:
FDA label: Modafinil
Action type:
informational_none
Target id:
/circadian/wake
Target name:
Waking Up
Severity:
moderate
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
null
Hours after target:
1
Description:
Taking modafinil upon waking aligns its peak effects with the desired period of wakefulness and minimizes impact on subsequent nighttime sleep.
Actionable advice:
A dose is best taken within one hour of waking up for optimal effect.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
200 mg once a day in the morning
Label source:
FDA label: Modafinil (Provigil) — Dosage and Administration (2.1)
Action type:
informational_none
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
1
Description:
Taking modafinil with food, especially a high-fat meal, can delay its absorption and the onset of its effects by approximately one hour, but does not reduce its overall effectiveness.
Actionable advice:
For the fastest onset of action, it is best taken on an empty stomach.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Food has no effect on overall PROVIGIL bioavailability
Label source:
FDA label: Modafinil (Provigil) — Clinical Pharmacology: Food effect
Action type:
separate
Target id:
/intervention/caffeine
Target name:
Caffeine
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Caffeine has additive stimulant effects with modafinil, which can increase the likelihood of side effects like jitteriness, anxiety, and increased heart rate.
Actionable advice:
Caffeine intake is worth keeping in mind, and reducing it may help if increased side effects occur.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
At these doses, caffeine was associated with the highest percentage of subjectively reported side-effects while modafinil did not differ significantly from placebo.
Label source:
PubMed: Journal of sleep research (2008)
Source url:
Exact phrase from label:
In sleep-deprived individuals, modafinil improves mood, fatigue, sleepiness and cognition to a similar extent as caffeine but has a longer duration of action.
Label source:
PubMed: Drugs (2008)
Source url:
Exact phrase from label:
Caffeine, an adenosine A1 and A2a receptor antagonist, is a widely consumed stimulant and also used for the treatment of hypersomnia; however, the wake-promoting potency of caffeine is often not strong enough, and high doses may induce side effects.
Label source:
PubMed: Sleep (2010)
Action type:
informational_none
Target id:
/class/cyp1a2-substrates
Target name:
Medications Metabolized by CYP1A2
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Modafinil is a weak inducer of the CYP1A2 enzyme, which could slightly increase the metabolism and decrease the effectiveness of drugs like theophylline or caffeine.
Actionable advice:
A mild reduction in effect may occur for drugs metabolized by CYP1A2.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
modafinil is a weak inducer of CYP1A2
Label source:
FDA label: Modafinil (Provigil) — Drug Interactions: CYP1A2 weak induction
Action type:
informational_none
Target id:
/class/tricyclic-antidepressants
Target name:
Tricyclic Antidepressants (e.g., Clomipramine, Desipramine)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Modafinil may increase levels of certain TCAs by inhibiting their metabolism, leading to a higher risk of side effects like dry mouth, constipation, and cardiac issues.
Actionable advice:
It is worth watching out for TCA side effects, and a dose reduction may be warranted if used concurrently.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Modafinil on CYP2C19 Substrates Elimination of drugs that are substrates for CYP2C19 (e.g., phenytoin, diazepam, propranolol, omeprazole, and clomipramine) may be prolonged by modafinil via inhibition of metabolic enzymes, with resultant higher systemic exposure.
Label source:
FDA label: Modafinil
Action type:
adjust_with_prescriber