Pharmaniaga Fentanyl Drug Interactions

Agents like barbiturates, benzodiazepines, neuroleptics, volatile anaesthetics containing halogens or other medicaments that have a non-selective depressant effect on the central nervous system (i. e. alcohol), may augment the respiratory depression caused by opioids.
When such medicaments have been administered to patients, the required dose of fentanyl will be lower than usual. This should also result in lowering the dose of other medicaments which have a depressant effect on the central nervous system, when these agents are administered after fentanyl is given.
With higher doses of fentanyl the concomitant application of nitrous oxide or even small doses of diazepam can lead to an impairment of cardiovascular function.
The combined application of fentanyl and midazolam can lead to a decrease in blood pressure.
Simultaneous application of droperidol can lead to a fall in blood pressure, but in some cases a rise in blood pressure was also observed.
The pulmonary arterial pressure can be decreased. Furthermore, shivering, restlessness and postoperative episodes of hallucinations may occur.
In patients with preceding medication with MAO inhibitors within the last 14 days before opioid administration, life-threatening interactions with pethidine on the central nervous system (i.e. agitation, muscle rigidity, hyperpyrexia, convulsions), and the respiratory and circulatory system (i.e. circulatory depression, hypotension, haemodynamic instability and coma) have been observed and cannot be ruled out with fentanyl.
MAO-inhibitors also block the enzymes which metabolise centrally active substances (sedatives, antihistamines, opioids, etc.). As a consequence an intensive and prolonged effect of fentanyl may occur, including respiratory depression.
A preceding administration of cimetidine may lead to increased plasma levels of fentanyl.
Co-administration of clonidine may enhance fentanyl effects and especially prolong fentanyl-induced ventilatory depression.
Vecuronium can cause haemodynamic depression when combined with fentanyl. Significant decreases in heart rate, mean arterial pressure, and cardiac output may occur which are not dependent on the dose of vecuronium.
Bradycardia may develop during the combined application of atracurium and fentanyl.
Fentanyl effects are enhanced and prolonged when combined with baclofen.
Anticonvulsants like carbamazepine, phenytoin, primidone are potent enzyme inducing agents which increase the metabolism of fentanyl by the liver so that fentanyl is cleared from the body more quickly. A marked increase in the fentanyl requirements should be anticipated in any patient on long-term treatment with these anticonvulsants, but not with sodium valproate.
Fentanyl, a high clearance drug, is rapidly and extensively metabolized mainly by CYP3A4. Itraconazole (a potent CYP3A4 inhibitor) at 200 mg/day given orally for 4 days had no significant effect on the pharmacokinetics of IV fentanyl. Oral ritonavir (one of the most potent CYP3A4 inhibitors) reduced the clearance of IV fentanyl by two thirds; however peak plasma concentrations after a single dose of IV fentanyl were not affected. When fentanyl is used in a single dose, the concomitant use of potent CYP3A4 inhibitors such as ritonavir requires special patient care and observation. Although clinical data are lacking, in vitro data suggest that other potent cytochrome P450 3A4 enzyme inhibitors (e.g. fluconazole, ketoconazole, erythromycin, diltiazem and cimetidine) may inhibit the metabolism of fentanyl.
Incompatibilities: This medicinal product must not be diluted with other solutions for parenteral use other than those mentioned in Recommended Dosage.
Compatibility must be checked before administration, if intended to be mixed with other drugs. Fentanyl citrate is reported to be physically incompatible with pentobarbital sodium, methohexital sodium, thiopental sodium and nafcilline.