Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction
The simultaneous administration of isoflurane and the following products requires strict supervision of the clinical and biological condition of the patient; 
Combinations advised against:
− Beta-sympathomimetics (isoprenaline) and alpha- and beta-sympathomimetics (epinephrine or adrenaline; norepinephrine or noradrenaline): should be used with caution during isoflurane narcosis, due to a potential risk of ventricular arrhythmia.

−   Nonselective MAOI: Risk of crisis and hemodynamic instability during the surgery or medical procedures. Treatment should be stopped 15 days prior to surgery.

Combinations requiring precautions in using:
− Beta-blockers: Concomitant use of beta blockers may exaggerate the cardiovascular effects of inhalational anesthetics, including hypotension and negative inotropic effects. Risk of blockage of the cardiovascular compensation mechanism, as a result of which negative inotropic effects are intensified. The action of beta-blockers can be suppressed during the operation with the use of beta-sympathomimetic agents. In general, any medication with a beta-blocker need not be stopped and an abrupt reduction of the dosage should be avoided.

−   Isoniazid: Risk of potentiating the hepatotoxic effect, with increased formation of toxic metabolites of isoniazid. Treatment with isoniazid should be suspended one week before the operation and should not be resumed until 15 days afterwards.

−   Epinephrine (adrenaline) by sub-cutaneous or gingival injections: risk of serious ventricular arrhythmia as a consequence of increased heart rate, although the myocardial sensitivity with respect to epinephrine is lower with the use of isoflurane than in the case of halothane. Thus, the dosage should be limited to, for example, 0.1 mg epinephrine within 10 minutes or 0.3 mg within one hour in adults. Doses of adrenaline greater than 5 mcg/kg, when administered submucosally, may produce multiple ventricular arrhythmias.

−   Indirect-acting sympathomimetics (amphetamines and their derivatives; psychostimulants, appetite suppressants, ephedrine and its derivatives): risk of perioperative hypertension. In patients undergoing elective surgery, treatment should ideally be discontinued several days before surgery.

−   In the majority of cases where a drug treatment is indispensable, there is no reason to suspend it before general anaesthesia. It suffices to inform the anaesthetist about it.


−   All commonly used muscle relaxants are markedly potentiated by isoflurane, the effect being most profound with non-depolarizing agents.

Thus it is recommended that approximately one third to one half of the usual dose of these substances be administered. The disappearance of the myoneural effect takes longer with isoflurane than with other conventional anaesthetics.
Neostigmine has an effect on the non-depolarising relaxants, but has no effect on the relaxing action of isoflurane itself.

−   Opioids, benzodiazepines and other sedative agents are associated with respiratory depression, and caution should be exercised when concomitantly administered with isoflurane.

−   Calcium antagonists: isoflurane may lead to marked hypotension in patients treated with calcium antagonists, particularly dihydropyridine derivatives.
Caution should be exercised when calcium antagonists are used concomitantly with inhalation anaesthetics due to the risk of additive negative inotropic effect.

MAC (minimum alveolar concentration) is reduced by concomitant administration of N2O in adults (see section 4.2).