Meta Information
ID:dual-orexin-receptor-antagonists-doras
Name:
Schema Version:AIM-2.0
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:
Take within 30 minutes of going to bed, and only if you have at least 7 hours available for sleep.
Target id:
/class/cns-depressants
Target name:
CNS Depressants
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
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:
Avoid co-administration with other CNS depressants, especially alcohol, opioids, and benzodiazepines.
Target id:
/dietary/alcohol-acute
Target name:
Alcohol
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Alcohol significantly potentiates the sedative and psychomotor impairing effects of DORAs, greatly increasing the risk of accidents, falls, and respiratory depression.
Actionable advice:
Do not consume any alcohol on days you take a DORA.
Target id:
/class/opioid-agonists
Target name:
Opioid Agonists
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
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:
Avoid using opioids and DORAs together unless under strict medical supervision.
Target id:
/class/benzodiazepines
Target name:
Benzodiazepines
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Combining benzodiazepines with DORAs leads to significant additive sedation and impairment, greatly increasing the risk of falls, accidents, and memory issues.
Actionable advice:
Avoid taking benzodiazepines and DORAs together.
Target id:
/class/cyp3a4-strong-inhibitors
Target name:
Strong CYP3A4 Inhibitors
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
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.
Target id:
/class/cyp3a4-moderate-inhibitors
Target name:
Moderate CYP3A4 Inhibitors
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
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.
Target id:
/class/broad-spectrum-inducers
Target name:
Strong or Moderate CYP3A4 Inducers
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
null
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:
Avoid using DORAs with strong or moderate CYP3A4 inducers.
Target id:
/intervention/saint-johns-wort
Target name:
Saint John's Wort
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
null
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:
Do not take Saint John's Wort while using a DORA.
Target id:
/dietary/grapefruit-pomelo
Target name:
Grapefruit or Grapefruit Juice
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
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:
Avoid consuming grapefruit or its juice while taking a DORA.
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:
Take on an empty stomach or at least 1-2 hours after a meal for the fastest effect.
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:
Do not drive or engage in other hazardous activities until you know how the medication affects you the next day.
Target id:
/condition/narcolepsy
Target name:
Narcolepsy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
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.
Target id:
/condition/hepatic-impairment
Target name:
Liver Impairment
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
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.
Target id:
/condition/geriatric
Target name:
Older Adults (Geriatric)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
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:
Use with caution and typically at a lower starting dose in older adults.
Target id:
/condition/depression-suicidal-ideation
Target name:
Depression or History of Suicidal Thoughts
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
All sedative-hypnotics, including DORAs, carry a warning for potentially worsening depression or causing abnormal thinking and behavioral changes.
Actionable advice:
Monitor for any new or worsening mood changes and report them to your doctor immediately.
Target id:
/condition/asthma-copd
Target name:
Compromised Respiratory Function (e.g., COPD, Sleep Apnea)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
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:
Use with caution and under medical supervision if you have a respiratory condition.
Target id:
/intervention/cannabis
Target name:
Cannabis (THC or CBD)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
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:
Avoid using cannabis products on the same day you take a DORA.
Target id:
/intervention/digoxin
Target name:
Digoxin
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
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.
Target id:
/intervention/melatonin
Target name:
Melatonin
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
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:
Avoid taking melatonin and a DORA on the same night unless directed by a physician.
Target id:
/intervention/valerian-root
Target name:
Valerian Root
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Combining with other substances that have sedative properties, like Valerian Root, can lead to additive drowsiness and next-day impairment.
Actionable advice:
Avoid combining with other sleep-promoting supplements to prevent excessive sedation.
Target id:
/class/p-glycoprotein-substrates
Target name:
P-glycoprotein (P-gp) Substrates
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
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:
Be aware of the potential for slightly increased effects of P-gp substrate drugs, though this is generally not clinically significant.