Desvenlafaxine with Pitolisant Interaction Details
Brand Names Associated with Desvenlafaxine
- Desvenlafaxine
- Pristiq®
Brand Names Associated with Pitolisant
- Pitolisant
- Wakix®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 27, 2023
Interaction Effect
Increased CYP2D6 substrate exposure and an increased risk of CYP2D6 substrate-related adverse events
Interaction Summary
Coadministration of desvenlafaxine with a CYP2D6 substrate may result in higher concentrations of the CYP2D6 substrate. When desvenlafaxine 100 mg daily was coadministered with a single 50 mg dose of desipramine, a CYP2D6 substrate, desipramine Cmax and AUC did not increase significantly; however, when concurrent desvenlafaxine was increased to 400 mg/day (unapproved dosage), the desipramine Cmax increased by about 50% and AUC increased by approximately 90%. Therefore, no dose adjustment of the CYP2D6 substrate is needed when coadministering desvenlafaxine 100 mg daily or less; when using a CYP2D6 substrate with desvenlafaxine 400 mg daily (unapproved dosing), reduce the CYP2D6 substrate dose by one-half and increase the CYP2D6 substrate to the original dose if concurrent desvenlafaxine 400 mg is discontinued.
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Coadministration of desvenlafaxine (a weak CYP2D6 inhibitor) with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate at desvenlafaxine doses greater than 100 mg/day. Coadministering desvenlafaxine 100 mg/day or less with a CYP2D6 substrate does not require dose adjustment. Reduce the CYP2D6 substrate dose by one-half if used concurrently with desvenlafaxine 400 mg/day (unapproved dosage), and increase the CYP2D6 substrate to the original dose if concurrent desvenlafaxine 400 mg is discontinued.
Mechanism Of Interaction
Inhibition of CYP2D6-mediated metabolism by desvenlafaxine
Literature Reports
A) Coadministration of desipramine (a CYP2D6 substrate) 50 mg with desvenlafaxine 400 mg/day (unapproved dosing) in a clinical study resulted in an increase of approximately 50% for the Cmax and 90% for the AUC of desipramine. The differences in desipramine metabolism were not considered clinically relevant when the dose of desvenlafaxine was 100 mg/day (25% increase in Cmax and 17% in AUC) .
Desvenlafaxine Overview
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Desvenlafaxine is used to treat depression. Desvenlafaxine is in a class of medications called selective serotonin and norepinephrine reuptake inhibitors (SNRIs). It works by increasing the amounts of serotonin and norepinephrine, natural substances in the brain that help maintain mental balance.
Pitolisant Overview
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Pitolisant is used to treat excessive daytime sleepiness caused by narcolepsy (a condition that causes excessive daytime sleepiness) and to treat cataplexy (episodes of muscle weakness that begin suddenly and last for a short time) in adults with narcolepsy. Pitolisant is in a class of medications called H3 blockers. It works by changing the amounts of certain natural substances in the area of the brain that controls sleep and wakefulness.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.