Drug cross-reactions

If more than one drug is taken during a course of treatment they sometimes cross react with each other. This can lead to a wide variety of problems, some of which need to be addressed by the doctor.

Many of the common cross-reactions are written into the drug data-sheets which are supplied with every drug for the information of the prescribing doctor (some of which - antifungal drugs - are reproduced in the treatment section of the main Aspergillus website).

Amphotericin

Concomitant administration of nephrotoxic drugs or anti-neoplastics should be avoided if at all possible.

The hypokalaemia following amphotericin therapy may potentiate the toxicity of digitalis glycosides or enhance the curariform actions of skeletal muscle relaxants.

Corticosteroids may increase the potassium loss due to amphotericin.

Flucytosine toxicity may be enhanced during concomitant administration, possibly due to an increase in its cellular uptake and/or impairment of its renal excretion.

Acute pulmonary reactions have occasionally been observed in patients given amphotericin during or shortly after leukocyte transfusions. It is advisable to separate these infusions as far as possible and to monitor pulmonary function.

Itraconazole

Drug-interactions Enzyme-inducing drugs such as rifampicin and phenytoin significantly reduce the oral bioavailability of itraconazole. Consequently, monitoring of the itraconazole plasma concentration is advised when enzyme-inducing agents are co-administered.

Itraconazole can inhibit the metabolism of drugs metabolised by the cytochrome 3A family. This can result in an increase and/or a prolongation of their effects, including side effects. Known examples are: - Terfenadine, astemizole and cisapride, resulting in increased plasma levels of these drugs and predisposing to serious arrhythmias. Combination of itraconazoie with terfenadine, astemizole or cisapride is contra-indicated. - Midazolam and triazolam, resulting in increased plasma levels of these drugs.

Combination of itraconazole with oral midazolam or triazolam is contraindicated. If midazolam is administered intravenously (eg as premedication in surgical or investigative procedures) special care should be observed since the sedative effect may be prolonged. -

HMG-CoA reductase inhibitors such as simvastatin. These drugs should not be used during treatment with Sporanox-Pulse. -

Oral anticoagulants, digoxin, Cyclosporin A, systemic methylprednisolone, vinca-alkaioids and possibly tacrolimus. Co-administration of itraconazole and digoxin has led to increased levels of the latter drug. A rise in cyclosporin levels has also been reported in patients treated with high doses of itraconazole for several weeks. Plasma levels of digoxin and cyclosporin should therefore be monitored during concomitant administration of itraconazole and the doses adjusted accordingly. In vitro studies indicate that a similar interaction may occur with tacrolimus. With respect to oral anticoagulants, similar interactions have been reported and it is advisable to monitor prothrombin time and reduce the dosage of oral anticoagulants if necessary. Co-administration of itraconazole and vinca-alkaloids may potentiate the toxic effects of the latter drugs and should this occur, coadministration of these drugs should be reconsidered.

Dihydropyridine calcium channel blockers and quinidine. Patients should be monitored for side effects, e.g. oedema and tinnitus/decreased hearing, respectively. If necessary, the dose of these drugs should be reduced.