Drug Interactions

MIDAZOLAM Drug Interactions

Also known as: Midazolam

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.MIDAZOLAM has 10 documented drug interactions in our database, including 4 contraindicated, 6 major, 0 moderate, and 0 minor interactions.

4

Contraindicated

6

Major

0

Moderate

0

Minor

BUPRENORPHINE(BUPRENORPHINE)
Contraindicated

The combination significantly increases the risk of severe respiratory depression, profound sedation, coma, and death. Patients may experience decreased respiratory rate, hypoventilation, hypoxia, hypotension, and impaired mental status. The onset of these effects can be rapid and life-threatening.

Mechanism

Both buprenorphine, an opioid partial agonist, and midazolam, a benzodiazepine, are central nervous system (CNS) depressants. Their co-administration leads to an additive depressant effect on the CNS, primarily by enhancing GABAergic neurotransmission (benzodiazepines) and inhibiting neuronal activity via opioid receptors (buprenorphine). This synergistic depression significantly impairs respiratory drive and consciousness.

Clinical Management

Concomitant use of buprenorphine and midazolam is generally contraindicated due to the high risk of severe adverse events, as highlighted by an FDA Black Box Warning. If co-administration is absolutely unavoidable, it should be reserved for patients for whom alternative treatment options are inadequate, and only under close medical supervision with immediate availability of resuscitative equipment and naloxone. Doses of both drugs should be reduced, and patients must be continuously monitored for respiratory depression and sedation.

Evidence: established
Onset: rapid
Source: LLM-generatedCompare these drugs
TRAMADOL HYDROCHLORIDE(TRAMADOL HYDROCHLORIDE)
Contraindicated

Concomitant use can cause severe respiratory depression, profound sedation, hypotension, psychomotor impairment, coma, and death. Patients may exhibit decreased level of consciousness, bradycardia, hypoventilation, and cyanosis.

Mechanism

Both tramadol (an opioid analgesic) and midazolam (a benzodiazepine) are central nervous system (CNS) depressants. Their coadministration leads to additive pharmacodynamic effects, significantly enhancing GABAergic inhibition and mu-opioid receptor agonism, resulting in profound CNS and respiratory depression.

Clinical Management

The coadministration of tramadol and midazolam is contraindicated due to the high risk of severe adverse outcomes, including respiratory depression and death. If no alternative treatments are available and coadministration is deemed absolutely necessary, prescribe the lowest effective doses and shortest durations, monitor patients closely for respiratory depression and sedation, and provide naloxone and flumazenil availability.

Evidence: established
Onset: rapid
Source: LLM-generatedCompare these drugs
METHADONE(Methadone Hydrochloride)
Contraindicated

The combination significantly increases the risk of profound sedation, respiratory depression, coma, and death. Patients may experience decreased level of consciousness, hypoventilation, hypoxia, and hypotension. These effects can be rapid in onset and life-threatening.

Mechanism

Methadone, an opioid agonist, primarily acts on mu-opioid receptors, causing central nervous system (CNS) depression, including respiratory depression. Midazolam, a benzodiazepine, enhances the effect of the inhibitory neurotransmitter GABA at GABA-A receptors, leading to further CNS depression. The synergistic CNS depressant effects of both drugs significantly increase the risk of severe adverse outcomes.

Clinical Management

Concomitant use is generally contraindicated. If co-administration is unavoidable, use the lowest effective doses and shortest possible duration, and monitor patients closely for respiratory depression and sedation. Consider naloxone for opioid overdose and flumazenil for benzodiazepine overdose, but be aware of potential withdrawal and seizure risks.

Evidence: established
Onset: rapid
Source: LLM-generatedCompare these drugs
TAPENTADOL HYDROCHLORIDE(Tapentadol Hydrochloride)
Contraindicated

The concurrent use of tapentadol and midazolam significantly increases the risk of severe adverse outcomes including profound sedation, respiratory depression, coma, and death. Patients may exhibit decreased level of consciousness, hypoventilation, bradycardia, and hypotension.

Mechanism

Both tapentadol, an opioid analgesic, and midazolam, a benzodiazepine, are central nervous system (CNS) depressants. Their co-administration leads to an additive depressant effect on the CNS, primarily impacting the brainstem respiratory centers and leading to profound sedation and respiratory depression.

Clinical Management

Concomitant use of tapentadol and midazolam is contraindicated due to the high risk of respiratory depression and death. If co-administration is unavoidable, the lowest effective doses should be used for the shortest possible duration, and patients must be closely monitored for signs of respiratory depression and sedation. Naloxone should be readily available.

Evidence: established
Onset: rapid
Source: LLM-generatedCompare these drugs
FENTANYL(FENTANYL)
Major

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.

Clinical Management

Avoid concomitant use of fentanyl and midazolam whenever possible due to the high risk of severe adverse effects. If co-administration is unavoidable, use the lowest effective doses for the shortest duration possible, and closely monitor patients for signs of respiratory depression and sedation. Have naloxone and flumazenil readily available, and educate patients and caregivers on the risks and symptoms of overdose.

Evidence: established
Onset: rapid
Source: LLM-generatedCompare these drugs
OXYCODONE(Oxycodone Hydrochloride)
Major

The combination of oxycodone and midazolam can lead to profound sedation, respiratory depression (decreased respiratory rate and depth), coma, and death. Patients may exhibit dizziness, confusion, psychomotor impairment, and hypotension. These effects are dose-dependent and can be life-threatening.

Mechanism

Oxycodone, an opioid agonist, binds to mu-opioid receptors in the central nervous system (CNS), causing CNS depression, including respiratory depression and sedation. Midazolam, a benzodiazepine, enhances the effect of the inhibitory neurotransmitter GABA at GABA-A receptors, further leading to CNS depression. The synergistic CNS depressant effects of both drugs significantly increase the risk of severe adverse outcomes.

Clinical Management

Avoid concomitant use of oxycodone and midazolam whenever possible. If co-administration is unavoidable, use the lowest effective doses for the shortest duration possible, and monitor patients closely for respiratory depression and sedation. Consider alternative treatments that do not interact with opioids or benzodiazepines. Educate patients and caregivers about the risks and symptoms of CNS depression.

Evidence: established
Onset: rapid
Source: LLM-generatedCompare these drugs
MORPHINE(Opium Tincture Deodorized)
Major

The primary clinical effects include profound sedation, respiratory depression (reduced respiratory rate and tidal volume), hypotension, and psychomotor impairment. In severe cases, this can progress to coma, respiratory arrest, and death. Patients may also experience increased dizziness, confusion, and ataxia.

Mechanism

Both morphine (an opioid agonist) and midazolam (a benzodiazepine) are central nervous system (CNS) depressants. Their co-administration leads to an additive and synergistic depressant effect on the CNS, particularly affecting the respiratory drive and level of consciousness. This occurs through distinct but complementary pathways: opioids primarily act on mu-opioid receptors, while benzodiazepines potentiate the effects of GABA at GABA-A receptors, both leading to neuronal inhibition.

Clinical Management

Co-administration should generally be avoided due to the significant risks, as highlighted by the FDA Black Box Warning. If absolutely necessary, use the lowest effective doses of both medications, limit duration, and ensure close monitoring for respiratory depression and sedation. Have resuscitation equipment and opioid antagonists (e.g., naloxone) readily available. Consider alternative therapies if possible.

Evidence: established
Onset: rapid
Source: LLM-generatedCompare these drugs
CODEINE SULFATE(Codeine sulfate)
Major

The primary clinical effects include profound sedation, respiratory depression, coma, and death. Patients may exhibit reduced level of consciousness, decreased respiratory rate, hypoxemia, and hypotension.

Mechanism

Codeine is an opioid analgesic, and midazolam is a benzodiazepine. Both drug classes are central nervous system (CNS) depressants. Co-administration leads to additive pharmacodynamic effects, particularly on GABA-A receptors (benzodiazepines) and opioid receptors (codeine), resulting in enhanced CNS depression.

Clinical Management

Avoid concomitant use of codeine and midazolam unless the benefits outweigh the risks, and alternative treatment options are inadequate. If co-administration is necessary, use the lowest effective doses for the shortest duration possible, and closely monitor patients for signs of respiratory depression and sedation. Have naloxone readily available.

Evidence: established
Onset: rapid
Source: LLM-generatedCompare these drugs
HYDROMORPHONE HYDROCHLORIDE(Hydromorphone Hydrochloride)
Major

The combination significantly increases the risk of profound sedation, respiratory depression, coma, and death. Patients may exhibit somnolence, decreased level of consciousness, hypoventilation, hypoxia, and hypotension. This interaction can lead to life-threatening respiratory arrest.

Mechanism

Hydromorphone, an opioid agonist, binds to mu-opioid receptors in the central nervous system (CNS), leading to CNS depression and respiratory depression. Midazolam, a benzodiazepine, enhances the effect of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) at GABA-A receptors, also causing CNS and respiratory depression. The concomitant use of these agents results in an additive and synergistic depressant effect on the CNS and respiratory drive.

Clinical Management

Avoid concomitant use of hydromorphone and midazolam whenever possible. If co-administration is absolutely necessary, use the lowest effective doses for the shortest duration possible, and closely monitor patients for signs of respiratory depression and sedation. Have naloxone readily available and educate patients and caregivers on the risks and symptoms of overdose.

Evidence: established
Onset: rapid
Source: LLM-generatedCompare these drugs
OXYMORPHONE HYDROCHLORIDE(Oxymorphone Hydrochloride)
Major

Concomitant use can lead to profound sedation, respiratory depression, coma, and death. Patients may exhibit decreased level of consciousness, hypoventilation, hypoxia, and hypotension. The interaction can also impair psychomotor function and increase the risk of accidental injury.

Mechanism

Oxymorphone, an opioid agonist, primarily acts on mu-opioid receptors in the central nervous system (CNS), leading to dose-dependent CNS depression, including respiratory depression. Midazolam, a benzodiazepine, enhances the inhibitory effects of gamma-aminobutyric acid (GABA) at GABA-A receptors, also resulting in CNS depression. The synergistic CNS depressant effects of both drugs significantly increase the risk of respiratory depression and profound sedation.

Clinical Management

Avoid concomitant use of oxymorphone and midazolam whenever possible due to the high risk of severe adverse outcomes. If co-administration is absolutely necessary, use the lowest effective doses for the shortest duration possible, and closely monitor patients for respiratory depression and sedation. Have naloxone and flumazenil readily available, and educate patients and caregivers on the risks and symptoms of overdose.

Evidence: established
Onset: rapid
Source: LLM-generatedCompare these drugs

For complete prescribing information:

View full MIDAZOLAM monograph →

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