Trofentyl Drug Interactions

Effect of other drugs on fentanyl.
Central Nervous System (CNS) depressants: The use of opioid premedication, barbiturates, benzodiazepines, neuroleptics, general anaesthetics and other non-selective CNS depressants (e.g. alcohol) may enhance or prolong the respiratory depression of fentanyl.
When patients have received other CNS-depressants, the dose of fentanyl required may be less than usual. Concomitant use with fentanyl in spontaneously breathing patients may increase the risk of respiratory depression, profound sedation, coma, and death.
The pharmacological effects of fentanyl citrate can be reversed by naloxone.
Antipsychotics: Droperidol: The concomitant use of droperidol can result in a higher incidence of hypotension.
Antihypertensive: Clonidine : Co-administration of clonidine may enhance fentanyl effects and especially prolong fentanyl-induced respiratory depression.
Cytochrome P450 3A4 (CYP3A4) inhibitors: Fentanyl, a high clearance drug, is rapidly and extensively metabolised mainly by CYP3A4. When IV fentanyl is used, the concomitant use of a CYP3A4 inhibitor may result in a decrease in fentanyl clearance. With single-dose IV fentanyl administration, the period of risk for respiratory depression may be prolonged, which may require special patient care and longer observation. With multiple-dose fentanyl administration, the risk for acute and/or delayed respiratory depression may be increased, and a dose reduction of fentanyl may be required to avoid accumulation of fentanyl.
Oral ritonavir (a potent CYP3A4 inhibitor) reduced the clearance of a single IV fentanyl dose by two thirds, although peak plasma concentrations of IV fentanyl were not affected. However itraconazole (another potent CYP3A4 inhibitor) at 200 mg/day given orally for 4 days had no significant effect on the pharmacokinetics of a single dose of IV fentanyl.
Co-administration of fluconazole or voriconazole (moderate CYP3A4 inhibitors) and fentanyl may result in an increased exposure and/or prolonged exposure to fentanyl.
Bradycardia and possibly cardiac arrest can occur when fentanyl is combined with non-vagolytic muscle relaxants (e.g. vecuronium).
Serotonergic Drugs: Coadministration of fentanyl with a serotonergic agent, such as a Selective Serotonin Re-uptake Inhibitor (SSRI) or a Serotonin Norepinephrine Re-uptake Inhibitor (SNRI) or a Monoamine Oxidase Inhibitor (MAOI), may increase the risk of serotonin syndrome, a potentially life-threatening condition.
Effect of fentanyl on other drugs: Following the administration of fentanyl, the dose of other CNS depressant drugs should be reduced. This is particularly important after surgery, because profound analgesia is accompanied by marked respiratory depression, which can persist or recur in the postoperative period. Administration of a CNS depressant, such as a benzodiazepine, during this period may disproportionally increase the risk for respiratory depression.
Plasma concentrations of etomidate increased considerably (by a factor 2-3) when combined with fentanyl. The total plasma clearance and volume of distribution of etomidate is decreased by a factor of 2 to 3 without a change in half-life when administered with fentanyl.
Simultaneous administration of fentanyl and intravenous midazolam results in an increase in the terminal plasma half-life and a reduction in the plasma clearance of midazolam. When these drugs are co-administered with fentanyl their dose may need to be reduced.