Procarbazine and Sertraline: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Procarbazine
No brand names on recordSertraline
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
These two medicines should not be taken together. Procarbazine is a chemotherapy drug that also acts as an MAO inhibitor, which means it slows down how your body breaks down a brain chemical called serotonin. Sertraline (an antidepressant) raises serotonin. Put them together and serotonin can climb too high.
That can cause a dangerous reaction called serotonin syndrome, with symptoms like a racing heart, high blood pressure, fever, sweating, shaking, muscle twitching, and confusion. It can be very serious. The good news is your care team can prevent this by spacing the two drugs apart in time. Please talk to your doctor or pharmacist before starting or stopping either one.
Contraindicated combination. Procarbazine is a weak, nonselective MAOI; sertraline is an SSRI. Combined, they produce additive serotonergic effects, and MAO inhibition blocks serotonin metabolism, risking serotonin syndrome or CNS toxicity (hypertension, tachycardia, hyperthermia, myoclonus, hyperreflexia, diaphoresis, altered mental status). Serious and fatal reactions reported.
- Direction: additive/potentiated serotonergic activity; neither is a prodrug requiring activation.
- Evidence: probable. Onset: can be rapid.
- Management: Do not co-administer. Allow a 14-day washout after stopping an MAOI before starting sertraline, and 14 days after stopping sertraline before starting an MAOI.
What happens
An increased risk of serotonin syndrome (hypertension, tachycardia, hyperthermia, myoclonus, mental status changes) or CNS toxicity
Interaction Deep Dive
Taking sertraline together with an MAOI is contraindicated. If an MAOI used for psychiatric conditions is stopped, allow a minimum of 14 days before starting sertraline. Likewise, once sertraline is discontinued, wait at least 14 days before beginning an MAOI intended for psychiatric disorders1. Giving sertraline and an MAOI inhibitor at the same time, or with overlapping treatment periods, can produce CNS toxicity or serotonin syndrome, a hyperserotonergic condition marked by features such as restlessness, myoclonus, altered mental status, hyperreflexia, diaphoresis, shivering, and tremor. Reactions that are serious and even fatal have been documented 3465.
Why it happens (mechanism)
Additive serotonergic effects; inhibition of serotonin metabolism by monoamine oxidase
How to manage this interaction
The key point: these drugs are not used at the same time. Your care team manages this by separating them:
- If you were on an MAOI (like procarbazine), your team typically waits at least 14 days after stopping it before starting sertraline.
- If you were on sertraline, they typically wait at least 14 days after stopping it before starting an MAOI.
Do not start, stop, or change either medicine on your own. If both have been prescribed, or you are switching between them, contact your prescriber or pharmacist right away so they can plan the safe timing. Seek urgent care for fever, rapid heartbeat, agitation, muscle twitching, or confusion.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) Taking serotonin specific reuptake inhibitors together with monoamine oxidase inhibitors can lead to a toxic response called serotonin syndrome 2.
b) A 26 year old woman who had used isocarboxazid for eight weeks discontinued the drug for 11 days before starting sertraline. Following a single 100 mg dose of sertraline, she grew restless and developed twitching in her legs. She was subsequently brought to the emergency room with diaphoresis, tachycardia, hyperreflexia, and assorted neuromuscular disturbances. She showed no improvement after being treated with diazepam and propranolol. She was then administered two 4 mg doses of cyproheptadine one hour apart, with marked improvement in her symptoms after the second dose 3.
c) A drug interaction was described in a 61 year old woman in whom sertraline 100 mg twice daily was added to a regimen consisting of lithium, phenelzine, thioridazine, and doxepin. Three hours after her first sertraline dose, she was discovered in a semicomatose state, with raised body temperature, elevated pulse, increased respiratory rate, and a blood pressure of 140/110 mmHg. Once taken to the hospital, she was initially misdiagnosed with neuroleptic malignant syndrome (NMS), a diagnosis later revised to serotonin syndrome resulting from an interaction between sertraline and phenelzine. The authors recommend that MAO inhibitor therapy be stopped for at least two weeks before starting a selective serotonin reuptake inhibitor (SSRI) and that, prior to beginning a MAOI, SSRI therapy be halted for at least 5 half-lives of the parent drug and any active metabolites 4.
d) Two case reports pointed to a possible interaction between FLUoxetine and selegiline. One case described a first episode of mania noted roughly 1 month after selegiline was added to fluoxetine therapy. The patient improved 2 months after both medications were stopped, and no additional details were provided. The second case described diaphoresis, vasoconstriction, and cyanosis of the hands that arose in close temporal association with the addition of FLUoxetine and selegiline. Both drugs were discontinued, with relatively rapid resolution of symptoms. Rechallenge with FLUoxetine alone proceeded without incident 5.
Common questions
Can I take Procarbazine and Sertraline together?
Procarbazine (an MAOI) and sertraline should not be used together because of the risk of serotonin syndrome; a 14-day gap is needed when switching between them. Let your doctor or pharmacist plan the timing. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Procarbazine and Sertraline interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Procarbazine and Sertraline interaction managed?
The key point: these drugs are not used at the same time. Your care team manages this by separating them: If you were on an MAOI (like procarbazine), your team typically waits at least 14 days after stopping it before starting sertraline. If you were on sertraline, they typically wait at least 14 days after stopping it before starting an MAOI. Do not start, stop, or change either medicine on your… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Procarbazine or Sertraline need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (6)
- Product Information: ZOLOFT oral tablets, oral solution, sertraline hydrochloride oral tablets, oral solution. Viatris Specialty LLC (per FDA), Morgantown, WV, 2023. DailyMed
- Sternbach H: The serotonin syndrome. Am J Psychiatr 1991; 148:705-713. PubMed
- Lappin RI & Auchincloss EL: Treatment of the serotonin syndrome with cyproheptadine. N Engl J Med 1994; 331:1021-1022. PubMed
- Graber MA, Hoehns TB, & Perry PJ: Sertraline-phenelzine drug interaction: a serotonin syndrome reaction. Ann Pharmacother 1994; 28:732-735. DOI
- Suchowersky O & de Vries JD: Interaction of fluoxetine and selegiline (letter). Can J Psychiatry 1990; 35:571-572. PubMed
- Bhatara VS & Bandettini FC: Possible interaction between sertraline and tranylcypromine. Clin Pharm 1993; 12:222-225.
Keep reading about Procarbazine
Keep reading about Sertraline
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