Meperidine and Aripiprazole Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Meperidine
Aripiprazole Injection
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.
What happens
Increased risk of respiratory depression, profound sedation, hypotension, coma and death
Interaction Deep Dive
The concomitant use of meperidine with other CNS depressants may result in profound sedation, respiratory depression, hypotension, coma, or death. Reserve concomitant use to clinical settings where alternative treatment options are inadequate. If combination therapy is required, reduce the initial dose of the newly prescribed medication and titrate to clinical response while monitoring for respiratory depression and sedation; use the lowest dose and shortest durations necessary to achieve treatment goals234. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose 3.
Why it happens (mechanism)
Additive CNS depression
Literature reports
3 reports — tap to read
a) The rate of emergency department visits involving non-medical use of concomitant benzodiazepines and opioid analgesics increased significantly over the period from 2004 to 2011, from 11 visits per 100,000 population to 34.2 visits per 100,000 population. Also, deaths from drug overdose involving concomitant benzodiazepines and opioid analgesics (including both prescribed doses and doses greater than prescribed) increased from 0.6 per 100,000 population to 1.7 per 100,000 population. The proportion of opioid overdose deaths for which benzodiazepines were also implicated increased from 18% to 31% 1
b) In a prospective cohort study performed in North Carolina, overdose deaths in patients who were dispensed both opioids and benzodiazepines were 10-fold greater than those dispensed opioids alone (7 per 10,000 person-years vs 0.7 per 10,000 person-years). A case-cohort study in the Veterans Health Administration demonstrated that patients taking opioids with a benzodiazepine prescription history or current benzodiazepine prescriptions had an increased risk of death due to overdose compared with patients taking opioids without a history of benzodiazepine prescription, risk increased 2.33- to 3.86-fold in patient with current or historical prescriptions for benzodiazepines. As daily benzodiazepine doses increased, risk of death due to drug overdose increased as well 1
c) Arterial blood gases were measured to determine the effect of methotrimeprazine in 31 healthy volunteers. Methotrimeprazine, administered alone, caused no significant respiratory depression but was found to potentiate the respiratory depression caused by meperidine. When methotrimeprazine (0.15 mg per kg intravenously) was given alone, PaO2, PaCO2, pH, and base excess remained unchanged. When methotrimeprazine and meperidine were combined, significant increases in PaCO2 and pH reductions were observed, which confirms the potentiation of meperidine-induced respiratory depression by methotrimeprazine 5.
Common questions
Can I take Meperidine and Aripiprazole Injection together?
Increased risk of respiratory depression, profound sedation, hypotension, coma and death Always confirm with your pharmacist or prescriber before making any change.
How serious is the Meperidine and Aripiprazole Injection interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Meperidine or Aripiprazole Injection 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 (5)
- US Food and Drug Administration (FDA): Drug Safety Communications: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. US Food and Drug Administration (FDA). Silver Spring, MD. 2016.
- Product Information: MEPERGAN intramuscular, intravenous injection, meperidine HCl, promethazine HCl intramuscular, intravenous injection. West-Ward Pharmaceuticals Corp (per FDA), Eatontown, NJ, 2023.
- Product Information: DEMEROL(R) oral tablets, oral solution, meperidine HCl oral tablets, oral solution. Validus Pharmaceuticals LLC (per FDA), Parsippany, NJ, 2023. DailyMed
- Product Information: Demerol(TM) intramuscular, subcutaneous, intravenous injection, meperidine HCl intramuscular, subcutaneous, intravenous injection. Hospira Inc (per FDA), Lake Forest, IL, 2022.
- Zsigmond EK & Flynn K: The effect of methotrimeprazine on arterial blood gases in human volunteers. J Clin Pharmacol 1988; 28:1033-1037. PubMed
Keep reading about Meperidine
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