Meta Information
ID:doras
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:
requirement
Nature:
temporal
Temporal spacing:
Hours before target:
0.5
Hours after target:
null
Description:
Dual Orexin Receptor Antagonists (DORAs) are hypnotics designed to initiate and maintain sleep; they should only be taken when you can dedicate at least 7-8 hours to sleep.
Actionable advice:
It should be taken within 30 minutes of going to bed, and only when at least 7 hours are available for sleep.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
BELSOMRA® (suvorexant) is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
informational_none
Target id:
/class/cns-depressants
Target name:
CNS Depressants
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining DORAs with other central nervous system depressants causes additive effects, leading to excessive sedation, impaired coordination, and potentially dangerous respiratory depression.
Actionable advice:
Co-administration with other CNS depressants, especially alcohol, opioids, and benzodiazepines, should be avoided.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression.
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
avoid
Target id:
/dietary/alcohol-acute
Target name:
Alcohol (Acute Consumption)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Alcohol significantly potentiates the sedative and psychomotor impairing effects of DORAs, greatly increasing the risk of accidents, falls, and respiratory depression.
Actionable advice:
Alcohol should not be consumed on days a DORA is taken.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Patients should be advised not to consume alcohol in combination with BELSOMRA because of additive effects
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
informational_none
Target id:
/class/opioid-agonists
Target name:
Opioid Agonists
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The combination of opioids and DORAs can result in profound sedation, respiratory depression, coma, and death due to additive depressant effects on the central nervous system.
Actionable advice:
Opioids and DORAs should not be used together unless under strict medical supervision.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression.
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
avoid
Target id:
/class/benzodiazepines
Target name:
Benzodiazepines
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining benzodiazepines with DORAs leads to significant additive sedation and impairment, greatly increasing the risk of falls, accidents, and memory issues.
Actionable advice:
Benzodiazepines and DORAs should not be taken together.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression.
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
avoid
Target id:
/class/cyp3a4-strong-inhibitors
Target name:
Strong CYP3A4 Inhibitors
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) block the metabolism of DORAs, leading to dangerously high drug levels, prolonged sedation, and increased side effects.
Actionable advice:
Concomitant use is contraindicated; avoid this combination completely.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Not recommended for use in patients taking strong CYP3A inhibitors
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
avoid
Target id:
/class/cyp3a4-moderate-inhibitors
Target name:
Moderate CYP3A4 Inhibitors
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Moderate CYP3A4 inhibitors (e.g., diltiazem, fluconazole) slow the metabolism of DORAs, increasing drug concentrations and the risk of adverse effects like next-day drowsiness.
Actionable advice:
A dose reduction of the DORA is typically required; consult your doctor before combining.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
When used with moderate CYP3A inhibitors, the recommended dosage of BELSOMRA is 5 mg taken no more than once per night
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
adjust_with_prescriber
Target id:
/class/broad-spectrum-inducers
Target name:
Strong or Moderate CYP3A4 Inducers
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin) accelerate the metabolism of DORAs, drastically reducing their blood levels and rendering them ineffective for treating insomnia.
Actionable advice:
DORAs should not be used with strong or moderate CYP3A4 inducers.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Suvorexant exposure can be substantially decreased when co-administered with strong CYP3A inducers (e.g., rifampin, carbamazepine and phenytoin). The efficacy of BELSOMRA may be reduced
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
avoid
Target id:
/intervention/saint-johns-wort
Target name:
Saint John's Wort
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
St. John's Wort is a potent inducer of the CYP3A4 enzyme, which will significantly speed up the breakdown of the DORA, making it ineffective.
Actionable advice:
Saint John's Wort should not be taken while using a DORA.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Strong CYP3A inducers: rifampin, carbamazepine, St. John’s wort
Label source:
FDA label: Lemborexant (Dayvigo)
Action type:
avoid
Target id:
/dietary/grapefruit-pomelo
Target name:
Grapefruit or Grapefruit Juice
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Grapefruit is a moderate inhibitor of CYP3A4 in the gut, which can increase the absorption and blood levels of DORAs, enhancing side effects.
Actionable advice:
Grapefruit or its juice is best avoided while taking a DORA.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
avoid
Target id:
/dietary/high-fat-meal
Target name:
High-Fat Meal
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
1
Description:
Taking a DORA with or shortly after a high-fat meal can significantly delay its absorption, resulting in a slower onset of sleep.
Actionable advice:
It is best taken on an empty stomach or at least 1-2 hours after a meal for the fastest effect.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Ingestion of BELSOMRA with a high-fat meal resulted in no meaningful change in AUC or Cmax but a delay in Tmax of approximately 1.5 hours
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
separate
Target id:
/procedure/driving-operating-machinery
Target name:
Driving or Operating Heavy Machinery
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
8
Hours after target:
0
Description:
DORAs can cause next-day impairment in alertness and motor coordination, even if you feel fully awake.
Actionable advice:
Driving and other hazardous activities should be avoided until it is clear how the medication affects a person the next day.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
patients using the 20 mg dose of BELSOMRA should be cautioned against next-day driving and other activities requiring full mental alertness
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
informational_none
Target id:
/condition/narcolepsy
Target name:
Narcolepsy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
DORAs work by blocking the orexin system, which is already deficient in narcolepsy, and may worsen symptoms like cataplexy (sudden muscle weakness).
Actionable advice:
Use of DORAs is contraindicated in patients with narcolepsy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
BELSOMRA is contraindicated in patients with narcolepsy
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
avoid
Target id:
/condition/hepatic-impairment
Target name:
Liver Impairment
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The liver is responsible for metabolizing DORAs; severe liver disease can lead to dangerously high drug levels and prolonged sedation.
Actionable advice:
Dose adjustment is needed for moderate impairment; avoid use in severe liver impairment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Patients with severe hepatic impairment: Not recommended
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
avoid
Target id:
/condition/geriatric
Target name:
Older Adults (Geriatric)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Older adults are more susceptible to the side effects of DORAs, including drowsiness, dizziness, and impaired balance, which increases the risk of falls and injury.
Actionable advice:
This is best used with caution and typically at a lower starting dose in older adults.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Of the total number of patients treated with BELSOMRA (n=1784) in controlled clinical safety and efficacy studies, 829 patients were 65 years and over
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
informational_none
Target id:
/condition/depression-suicidal-ideation
Target name:
Depression or History of Suicidal Thoughts
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
All sedative-hypnotics, including DORAs, carry a warning for potentially worsening depression or causing abnormal thinking and behavioral changes.
Actionable advice:
It is worth watching out for any new or worsening mood changes, and it is important to report them to a doctor immediately.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Worsening of Depression/Suicidal Ideation: Worsening of depression or suicidal thinking may occur. Risk increases with dose. Immediately evaluate any new behavioral changes
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
monitor
Target id:
/condition/asthma-copd
Target name:
Compromised Respiratory Function (e.g., COPD, Sleep Apnea)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
While generally having less respiratory depressant effect than older hypnotics, DORAs should be used with caution in patients with conditions like severe COPD or obstructive sleep apnea.
Actionable advice:
This is best used with caution and under medical supervision in those with a respiratory condition.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Compromised Respiratory Function: Effect on respiratory function should be considered
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
informational_none
Target id:
/intervention/cannabis
Target name:
Cannabis (THC or CBD)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Cannabis products, particularly those containing THC or high-dose CBD, have CNS depressant effects that are additive with DORAs, increasing sedation and impairment.
Actionable advice:
Cannabis products are best avoided on the same day a DORA is taken.
Validation status:
validated_via_expert_review
Evidence tier:
tier_c
Evidence basis:
expert_review_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression.
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
avoid
Target id:
/intervention/digoxin
Target name:
Digoxin
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Some DORAs (e.g., suvorexant) can inhibit the P-glycoprotein (P-gp) transporter, potentially increasing the concentration of digoxin, a heart medication with a narrow therapeutic index.
Actionable advice:
If taking with digoxin, your doctor may need to monitor digoxin levels more closely.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Concomitant administration of BELSOMRA with digoxin slightly increased digoxin levels due to inhibition of intestinal P-gp. Digoxin concentrations should be monitored
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
monitor
Target id:
/intervention/melatonin
Target name:
Melatonin
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
While working through different mechanisms, combining melatonin with a DORA can result in additive sedative effects and increase the risk of next-day grogginess.
Actionable advice:
Melatonin and a DORA are generally best not taken on the same night unless directed by a physician.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
The use of BELSOMRA with other drugs to treat insomnia is not recommended
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
avoid
Target id:
/intervention/valerian-root
Target name:
Valerian Root
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining with other substances that have sedative properties, like Valerian Root, can lead to additive drowsiness and next-day impairment.
Actionable advice:
Other sleep-promoting supplements are generally best avoided to prevent excessive sedation.
Validation status:
validated_via_expert_review
Evidence tier:
tier_c
Evidence basis:
expert_review_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The use of BELSOMRA with other drugs to treat insomnia is not recommended
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
avoid
Target id:
/class/p-glycoprotein-substrates
Target name:
P-glycoprotein (P-gp) Substrates
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Some DORAs are weak inhibitors of the P-gp drug transporter, which could slightly increase levels of P-gp substrates like dabigatran or fexofenadine.
Actionable advice:
P-gp substrate drugs may have slightly increased effects, though this is generally not clinically significant.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
In vitro metabolism studies demonstrate that suvorexant has the potential to inhibit CYP3A and intestinal P-gp
Label source:
FDA label: Suvorexant (Belsomra)
Action type:
informational_none
Class Id
dual-orexin-receptor-antagonists-doras