Diazepam Rectal and Levorphanol: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Levorphanol
Diazepam Rectal
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
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Concomitant use of levorphanol and CNS depressants may increase the risk of respiratory and CNS depression. Between 2004 and 2011, the number of drug-related overdose deaths, the number of nonmedical use-related emergency department visits involving opioids and benzodiazepines, and the number of opioid overdose deaths in which benzodiazepines played a role increased. Two studies have shown that when opioids and benzodiazepines are co-prescribed, the risk of overdose death increases1. Reserve concomitant use of levorphanol and CNS depressants for when alternatives are inadequate. If concomitant use is necessary, use the lowest dose and shortest duration. Closely monitor for sedation and respiratory depression 2.
Why it happens (mechanism)
Additive CNS depression
Literature reports
2 reports — tap to read
a) From 2004 to 2011, drug-related overdose deaths, either from taking prescribed or greater than prescribed doses, and involving both opioids and benzodiazepines, significantly increased from 0.6 to 1.7 per 100,000 population. During this same time, the number of nonmedical use-related emergency department visits where both opioid analgesics and benzodiazepines were involved significantly increased from 11 to 34.2 per 100,000. Additionally, opioid overdose deaths in which benzodiazepines also played a factor significantly rose from 18% to 31% 1.
b) One study, conducted in North Carolina, found overdose death rates were 10 times higher among patients who were co-prescribed opioids and benzodiazepines than among patients who were prescribed opioids alone (7 vs 0.7 per 10,000 person-years). Another study examined data from the Veterans Health Administration and compared risk of fatal overdose in patients taking opioids with no history of a benzodiazepine prescription, patients taking opioids with a history of benzodiazepine prescription, and patients taking opioids with a current benzodiazepine prescription. The conclusion was patients who had a history of a benzodiazepine prescription and patients with a current benzodiazepine prescription had a significantly increased risk of fatal overdose, 2.33 times and 3.86 times, respectively, versus patients taking opioids with no history of a benzodiazepine prescription. The risk continued to increase as the daily benzodiazepine dose increased 1.
Common questions
Can I take Diazepam Rectal and Levorphanol together?
An increased risk of respiratory and CNS depression Always confirm with your pharmacist or prescriber before making any change.
How serious is the Diazepam Rectal and Levorphanol 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 Diazepam Rectal or Levorphanol 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 (2)
- 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: levorphanol tartrate oral tablets, levorphanol tartrate oral tablets. Sentynl Therapeutics Inc (per DailyMed), Solana Beach, CA, 2016. DailyMed
Keep reading about Levorphanol
Keep reading about Diazepam Rectal
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