Itraconazole

Type of Medication: Antifungal

Indications: Treatment of ABPA in combination with steroids

Side Effects: GI upset ,nausea, abdo pain, dyspepsia, constipation, diarrhoea, headaches, raised liver enzymes, menstrual disorders, rash, pruritus, urticaria, angioedema. hepatitis and cholestasis (especially if treatment exceeds one month), peripheral neuropathy, Steven-Johnson syndrome, on prolonged use hypokalaemia, oedema and hair loss. Itraconazole is predominantly metabolised in the liver. The half-life of itraconazole is prolonged in both cirrhotic patients and individuals with renal insufficiency. A dose adjustment should be considered.Rare reports of heart faliure, caution in those patinets at risk and those patients recieving higher doses and longer treatment courses. Negative inotrope, has been associated with reports of congestive heart failure.

Route of administration: Adult (Oral)

Dose:5mg/kg/day in 2 divided doses (maximum 200 mg bd). Use liquid, capsules are not well absorbed in CF. Plama monitoring maybe required and dosage increased if necessary.

Administration: Itraconazole liquid contains 10mg per ml. Take on empty stomach (no food within 1 hour of taking) swish around mouth and swallow. Take for 4 weeks. Use with prednisolone when treating ABPA. Monitor liver function in patients receiving continuous treatment (more than one month).

Route of administration: Paediatric (Oral)

Dose:5 mg/kg/day in one or two divided doses. Max: 200 mg bd.

Examples of some Drug Interactions 

Interacting drug: Antacids

Reduced absorption of itraconazole.

Interacting drug: Calcium channel blockers

Possible negative inotropic effect could be potentiated.

Interacting drug: Carbamazepine

dose,if co-administered with itraconazole, should be reduced if necessary.

Interacting drug: Ciclosporin,Tacrolimus,Sirolimus

increased plasma concentration .Dosage,if co-administered with itraconazole, may need to be reduced, Avoid concomitant use with sirolimus.

Interacting drug: Cisapride

Qt interval prologation. Avoid.

Interacting drug: Digoxin

increased plasma digoxin concentration.

Interacting drug: High dose inhaled steroids

there have been reports of adrenal suppression following the use of inhaled steroids and itraconazole

Interacting drug: Macrolides – clarithromycin and erythromycin

May increase plasma concentation of itraconazole.

Interacting drug: Methylprednisolone

increased plasma concentration of methylprednisolone.

Interacting drug: Midazolam

dose, if co-administered with itraconazole, should be reduced if necessary.

Interacting drug: Phenytoin

Reduced plasma concentration of itraconazole

Interacting drug: proton pump inhibitors

reduced absorption of itraconazole

Interacting drug: quinidine

plasma levels of quinidine elevated:increased risk of ventricular arrythmias.

Interacting drug: ranitidine and cimetidine

reduced absorption of itraconazole

Interacting drug: Rifampicin

Reduced plasma concentration of itraconazole

Interacting drug: sildenafil, tadalafil, vardenafil

increased plasma concentrations, dosage reduction may be required (sildenafil) or avoid concomitant use (vardenafil).

Interacting drug: simvastatin, atorvastatin

increased risk of myopathy;avoid concomitant use.

Interacting drug: Tolterodine

avoidance of itraconazole advised by manufacturer of tolterodone

Interacting drug: Warfarin

Effect of warfarin will be accentuated and the dose of warfarin should be reduced if necessary.

Interaction: Ivacaftor

Increases the dose of ivacaftor which must be reduced eg 1 tablet bd twice a week