Combining Fentanyl and Midazolam is a major interaction and should generally be avoided without close medical supervision.
The primary clinical effects of this interaction include profound sedation, respiratory depression (ranging from hypoventilation to apnea), hypotension, bradycardia, coma, and death. Patients may exhibit reduced level of consciousness, difficulty arousing, shallow breathing, cyanosis, and decreased oxygen saturation. These effects can be rapid in onset and life-threatening.
Mechanism: Fentanyl, an opioid agonist, primarily acts on mu-opioid receptors in the central nervous system (CNS), leading to dose-dependent CNS depression, including respiratory depression and sedation. Midazolam, a benzodiazepine, enhances the effect of gamma-aminobutyric acid (GABA) at GABA-A receptors, also resulting in CNS depression, anxiolysis, and sedation. The co-administration of these two classes of drugs produces additive and synergistic CNS and respiratory depressant effects.
Fentanyl vs. Midazolam
Compare Fentanyl and Midazolam: mechanism of action, indications, side effects, cost, and which may be right for you.
Quick Comparison
| Category | Fentanyl | Midazolam |
|---|---|---|
| Drug Class | Opioid Analgesics | Benzodiazepines |
| Rx Status | Rx | Rx |
| Generic Available | No | No |
| Typical Cost | $150–$600/month | $500–$1,500/month |
Fentanyl Overview
FENTANYL (brand name: FENTANYL) is a Opioid Analgesics. 1 INDICATIONS AND USAGE Fentanyl transdermal system is indicated for the management of severe and persistent pain in opioid-tolerant patients, that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. Patients considered…
Full Fentanyl guide →Midazolam Overview
Midazolam is a type of medicine called a benzodiazepine that helps calm the body and mind. It is primarily used to make you feel relaxed and drowsy before medical procedures, surgeries, or to help you fall asleep for general anesthesia. It works by slowing down brain activity to reduce anxiety and create a state of peacefulness or forgetfulness.
Full Midazolam guide →How Each Drug Works
Fentanyl
Fentanyl is an opioid agonist. Fentanyl interacts predominately with the opioid mu-receptor. These mu-binding sites are distributed in the human brain, spinal cord, and other tissues.
Approved Uses (Indications)
Fentanyl
Fentanyl transdermal system is indicated for the management of severe and persistent pain in opioid-tolerant patients, that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. Patients considered opioid-tolerant are those who are taking, for one week or longer, at least 60 mg morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another op…
Midazolam
INDICATIONS AND USAGE Midazolam Injection is indicated: intramuscularly or intravenously for preoperative sedation/anxiolysis/amnesia; intravenously as an agent for sedation/anxiolysis/amnesia prior to or during diagnostic, therapeutic or endoscopic procedures, such as bronchoscopy, gastroscopy, cystoscopy, coronary angiography, cardiac catheterization, oncology procedures, radiologic procedures, suture of lacerations and other procedures either alone or in combination with other CNS depressants; intravenously for induction of general anesthesia, before administration of other anesthetic agent…
Side Effects
Fentanyl
Midazolam
Cost Comparison
Fentanyl
$150–$600/month
As a brand-only medication, fentanyl can be expensive. Patients should check for manufacturer coupons or patient assistance programs, and compare prices at different pharmacies using discount cards.
Midazolam
$500–$1,500/month
As Midazolam is a brand-only medication, explore manufacturer patient assistance programs or discount cards like GoodRx to help reduce the high cost. Your insurance plan's coverage will also significantly impact your out-of-pocket expenses.
Compare prices for Fentanyl and Midazolam
Check real-time pharmacy prices before you fill — free, no account needed.
Medical Disclaimer
The information on RxGuide is intended for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician, pharmacist, or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.