Sertraline with Fosphenytoin Interaction Details
Brand Names Associated with Sertraline
- Sertraline
- Zoloft®
Brand Names Associated with Fosphenytoin
- Cerebyx®
- Fosphenytoin Injection
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 08, 2023
Interaction Effect
Increased risk of phenytoin toxicity, reduced efficacy of sertraline and an increased risk of QT interval prolongation
Interaction Summary
The concomitant use of phenytoin, a CYP2C9 and CYP2C19 substrate and potent CYP-enzyme inducer, and sertraline may increase the risk of phenytoin toxicity and reduce sertraline efficacy. Coadministration of phenytoin with sertraline has resulted in elevated serum phenytoin levels in 2 elderly patients . To achieve optimal clinical outcomes, consider phenytoin and sertraline dose adjustments when phenytoin is added to or withdrawn from a patient's regimen. Phenytoin serum drug level monitoring is suggested when initiating or titrating sertraline. Reduce phenytoin dosage if needed. Also, the risk of QTc prolongation and/or ventricular arrhythmias is increased with concomitant use of other drugs which prolong the QTc interval. Avoid the concomitant use of drugs known to prolong the QTc interval .
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Avoid the concomitant use of drugs known to prolong the QTc interval. The risk of QTc prolongation and/or ventricular arrhythmias is increased with concomitant use of other drugs which prolong the QTc interval. Use caution with coadministration of phenytoin and sertraline, as concurrent use may increase the risk of phenytoin toxicity and reduce sertraline efficacy. Consider phenytoin and sertraline dose adjustments when phenytoin is added to or withdrawn from a patient's regimen. Phenytoin serum drug level monitoring is suggested when initiating or titrating sertraline. Reduce phenytoin dosage if needed .
Mechanism Of Interaction
Inhibition of CYP-mediated phenytoin metabolism by sertraline; induction of CYP-mediated sertraline metabolism by phenytoin; additive QT interval prolongation
Literature Reports
A) Two elderly patients developed elevated serum phenytoin concentrations during coadministration with sertraline. Patient 1, a 78-year old man, was taking phenytoin 300 mg per day in addition to several other medications. After sertraline 25 mg every night was added to his regimen for depression, serum phenytoin levels increased from 5.2 mcg/mL to 12.3 mcg/mL. After serial increases in the sertraline dose to 75 mg per day, the patient's serum phenytoin level rose to 30.9 mcg/mL. Phenytoin was discontinued but was later successfully restarted at a dose of 200 mg per day. Sertraline 100 mg per day was also administered without further adverse effects. Patient 2, an 85-year old man, developed increased serum phenytoin levels (from 15.6 mcg/mL to 20 mcg/mL) after the addition of sertraline 25 mg every other day to phenytoin 260 mg per day. The authors recommend checking serum phenytoin concentrations within one week after starting sertraline therapy or initiating a change in sertraline dose .
B) Sertraline is known to be a moderate to weak inhibitor of the CYP2D6 isoenzyme and is suspected of inhibiting the CYP2C9 and CYP3A4 hepatic isoenzymes. The metabolism of phenytoin may involve the CYP2D6 and CYP2C9 hepatic isoenzymes .
Sertraline Overview
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Sertraline is used to treat depression, obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), panic attacks (sudden, unexpected attacks of extreme fear and worry about these attacks), posttraumatic stress disorder (disturbing psychological symptoms that develop after a frightening experience), and social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life). It is also used to relieve the symptoms of premenstrual dysphoric disorder, including mood swings, irritability, bloating, and breast tenderness. Sertraline is in a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amounts of serotonin, a natural substance in the brain that helps maintain mental balance.
Fosphenytoin Overview
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Fosphenytoin injection is used to treat primary generalized tonic-clonic seizures (formerly known as a grand mal seizure; seizure that involves the entire body) and to treat and prevent seizures that may begin during or after surgery to the brain or nervous system. Fosphenytoin injection may also be used to control certain type of seizures in people who cannot take oral phenytoin. Fosphenytoin is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in the brain.
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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.