Sertraline with Oxycodone Interaction Details

Brand Names Associated with Sertraline

Brand Names Associated with Oxycodone

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 13, 2023

Interaction Effect

Increased oxycodone exposure and an increased risk of serotonin syndrome

Interaction Summary

Coadministration of sertraline, a CYP2D6 inhibitor, and oxycodone may result in prolonged or increased opioid effects. These effects may be more pronounced when sertraline is added after stable dose of oxycodone is achieved. Because both sertraline and oxycodone both affect the serotonergic neurotransmitter system, coadministration may also result in serotonin syndrome. If concomitant use of oxycodone and sertraline is clinically required, monitor patients frequently for signs of sedation, respiratory depression and serotonin syndrome, especially during treatment initiation and dosage adjustment. Consider dosage reduction of oxycodone until stable plasma concentrations are achieved. Discontinue oxycodone if serotonin syndrome is suspected. If sertraline is discontinued, monitor for signs of opioid withdrawal and consider increasing the oxycodone dosage until stable drug effects are achieved. Strongly consider prescribing naloxone for the emergency treatment of opioid overdose. Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Coadministration of oxycodone and sertraline has resulted in the development of symptoms suggestive of serotonin syndrome .

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Coadministration of sertraline, a CYP2D6 inhibitor, and oxycodone may result in prolonged or increased opioid effects. These effects may be more pronounced when sertraline is added after stable dose of oxycodone is achieved. Because both sertraline and oxycodone both affect the serotonergic neurotransmitter system, coadministration may also result in serotonin syndrome. If concomitant use of oxycodone and sertraline is clinically required, monitor patients frequently for signs of sedation, respiratory depression and serotonin syndrome, especially during treatment initiation and dosage adjustment. Consider dosage reduction of oxycodone until stable plasma concentrations are achieved. Discontinue oxycodone if serotonin syndrome is suspected. If sertraline is discontinued, monitor for signs of opioid withdrawal and consider increasing the oxycodone dosage until stable drug effects are achieved. Strongly consider prescribing naloxone for the emergency treatment of opioid overdose.

Mechanism Of Interaction

Inhibition of CYP2D6-mediated oxycodone metabolism; additive serotonergic effects

Literature Reports

A) Symptoms of serotonin syndrome developed in an 86-year-old woman following concurrent administration of oxycodone and sertraline. The woman was hospitalized subsequent to a fall which resulted in a sacral fracture. Prior to hospitalization, medications included extended-release oxycodone 10 mg twice daily and sertraline 150 mg once daily. The oxycodone dose was increased to 20 mg twice daily for pain control and following a brief hospital stay, she was transferred to a long-term care facility for rehabilitation. Within days, she appeared agitated and had markedly increased muscle tone in lower extremities, truncal ataxia, and coarse tremors, with myoclonic jerks, in both her feet. Subsequently, sertraline was rapidly tapered off and the oxycodone dose was decreased which resolved the myoclonus, rigidity, and tremors within 2 days. It was postulated that the increase in opiate dose may have precipitated the serotonin syndrome in this patient .

B) A 34-year-old bone marrow transplant male patient experienced visual hallucinations and tremors following concurrent use of sertraline and high-dose oxycodone. Three days prior to presentation, the patient had been discharged from the hospital, following extensive evaluation (including a bone marrow biopsy) and treatment of pneumonia. Discharge medications comprised of sertraline 50 mg once daily, oxycodone 10 mg as needed (average daily dose 10 to 20 mg/day), and cyclosporine 75 mg (total daily dose). Additional medications included methylprednisolone, omeprazole, folinic acid, acyclovir, fluconazole, and trimethoprim/sulfamethoxazole. Within 48 hours after discharge, the patient consumed a total of 200 mg oxycodone over 48 hours for severe biopsy-site related pain and during this interval, he experienced severe tremors and visual hallucinations. Since the patient had experienced similar tremors with initiation of cyclosporine therapy 1 year ago and his current cyclosporine level was 467 ng/mL (388.31 nanomol/L), cyclosporine was believed to be the offending agent, with contribution from the narcotic usage. Both cyclosporine and oxycodone were discontinued and hydromorphone (maximum 6 mg/day) was initiated for pain control. However, 72 hours later, severe tremor and visual hallucinations, to a lesser degree, persisted and the cyclosporine level had decreased to 128 ng/mL (106.4 nanomol/L). It was postulated that increased oxycodone doses in combination with sertraline use may have precipitated an increase in central serotonin. Subsequently, sertraline was discontinued and oral cyproheptadine 8 mg was administered, which resolved the hallucinations and lessened the tremor after 12 hours .

C) Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs .

Sertraline Overview

• 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.

Oxycodone Overview

• Oxycodone is used to relieve moderate to severe pain. Oxycodone extended-release tablets and extended-release capsules are used to relieve severe pain in people who are expected to need pain medication around the clock for a long time and who cannot be treated with other medications. Oxycodone extended-release tablets and extended-release capsules should not be used to treat pain that can be controlled by medication that is taken as needed. Oxycodone extended-release tablets, extended-release capsules, and concentrated solution should only be used to treat people who are tolerant (used to the effects of the medication) to opioid medications because they have taken this type of medication for at least one week. Oxycodone is in a class of medications called opiate (narcotic) analgesics. It works by changing the way the brain and nervous system respond to pain.

• Oxycodone is also available in combination with acetaminophen (Oxycet, Percocet, Roxicet, Xartemis XR, others); aspirin (Percodan); and ibuprofen. This monograph only includes information about the use of oxycodone alone. If you are taking an oxycodone combination product, be sure to read information about all the ingredients in the product you are taking and ask your doctor or pharmacist for more information.

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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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.