Pharmacokinetic interactions: The metabolism of budesonide is primarily mediated by the enzyme CYP3A4. Potent inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone and HIV protease inhibitors) are likely to markedly increase plasma levels of budesonide and concomitant use should be avoided. If this is not possible the time interval between administration of the inhibitor and budesonide should be as long as possible (see Precautions). In patients using potent CYP3A4 inhibitors, Symbicort maintenance and reliever therapy is not recommended.
The potent CYP3A4 inhibitor ketoconazole, 200 mg once daily, increased plasma levels of concomitantly orally administered budesonide (single dose of 3 mg) on average six-fold. When ketoconazole was administered 12 hours after budesonide the concentration was on average increased only three-fold showing that separation of the administration times can reduce the increase in plasma levels. Limited data about this interaction for high-dose inhaled budesonide indicates that marked increase in plasma levels (on average four-fold) may occur if itraconazole, 200 mg once daily, is administered concomitantly with inhaled budesonide (single dose of 1000 μg).
Pharmacodynamic interactions: Beta-adrenergic blockers can weaken or inhibit the effect of formoterol. Symbicort should therefore not be given together with beta-adrenergic blockers (including eye drops) unless there are compelling reasons.
Concomitant treatment with quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine) and tricyclic anti-depressants can prolong the QTc-interval and increase the risk of ventricular arrhythmias.
In addition, L-Dopa, L-thyroxine, oxytocin and alcohol can impair cardiac tolerance towards β2 sympathomimetics.
Concomitant treatment with monoamine oxidase inhibitors including agents with similar properties such as furazolidone and procarbazine may precipitate hypertensive reactions.
There is an elevated risk of arrhythmias in patients receiving concomitant anaesthesia with halogenated hydrocarbons.
Concomitant use of other beta-adrenergic drugs can have a potentially additive bronchodilating effect.
Hypokalaemia may increase the disposition towards arrhythmias in patients who are treated with digitalis glycosides.
Hypokalaemia may result from beta2-agonist therapy and may be potentiated by concomitant treatment with xanthine derivatives, corticosteroids and diuretics (see Precautions).
Budesonide and formoterol have not been observed to interact with any other drugs used in the treatment of asthma.
Peadiatric population: Interaction studies have only been performed in adults.