ITRANOX

What it is

ITRANOX contains itraconazole 100 mg in hard gelatin capsule form.

Approved indications —

Superficial dermatomycoses not responding to topical treatment. — Fungal keratitis which has failed to respond to topical treatment or where the disease is either progressing rapidly or is immediately sight threatening. — Pityriasis versicolor not responding to any other treatment. — Vulvovaginal candidiasis not responding to topical treatment. — Oral candidiasis in immunocompromised patients. — Onychomycosis caused by dermatophytes. — Systemic aspergillosis, histoplasmosis, and lymphocutaneous/cutaneous sporotrichosis; and treatment and maintenance therapy in AIDS patients with disseminated or chronic pulmonary histoplasmosis infection. — Oropharyngeal and/or oesophageal candidiasis when first line systemic antifungal therapy is inappropriate or has proven ineffective. — Non-invasive candidiasis in non-neutropenic patients when first-line systemic antifungal therapy is inappropriate or has proven ineffective.

Dosing overview

ITRANOX capsules must be taken immediately after a meal for maximal absorption. The capsules must be swallowed whole. For systemic mycoses, dosing varies according to the infection: aspergillosis requires 200 mg once daily (increased to 200 mg twice daily in invasive or disseminated disease) for 2 to 5 months; histoplasmosis requires 200 mg once or twice daily for 8 months with maintenance therapy of 200 mg once daily continued as necessary in AIDS patients; lymphocutaneous/cutaneous sporotrichosis requires 100 mg once daily (with some patients requiring 200 mg daily) for 3 months; and candidiasis requires 100 to 200 mg once daily for 3 weeks to 7 months.

Key safety warnings

Isolated cases of peripheral neuropathy have been reported, predominantly during long-term treatment with ITRANOX. If neuropathy occurs that may be attributable to ITRANOX, treatment should be discontinued. Life-threatening cardiac dysrhythmias and/or sudden death have occurred in patients using drugs such as methadone, pimozide or quinidine concomitantly with itraconazole and/or other CYP3A4 inhibitors. ITRANOX has been shown to have a negative inotropic effect and has been associated with reports of congestive heart failure. Heart failure was more frequently reported among spontaneous reports of 400 mg total daily dose than among those of lower total daily doses, suggesting that the risk of heart failure might increase with the total daily dose of ITRANOX. ITRANOX should not be used in patients with evidence of ventricular dysfunction such as congestive heart failure or with a history of congestive heart failure unless the benefit clearly outweighs the risk. The risk-benefit assessment should consider factors such as the severity of the indication, the dosing regimen, and individual risk factors for heart failure, which include cardiac disease such as ischaemic and valvular disease, significant pulmonary disease such as chronic obstructive pulmonary disease, and renal failure and other oedematous disorders. Rare cases of cholestatic jaundice and very rare cases of hepatitis have been reported. Very rare cases of serious hepatotoxicity, including some cases of fatal acute liver failure, have occurred with the use of ITRANOX. Most of these cases involved patients who had pre-existing liver disease, were treated for systemic indications, had significant other medical conditions and/or were taking other hepatotoxic drugs. Liver function monitoring should be considered in patients receiving ITRANOX treatment. Patients should be instructed to promptly report to their physician signs and symptoms suggestive of hepatitis such as anorexia, nausea, vomiting, fatigue, abdominal pain or dark urine. In these patients treatment should be stopped immediately and liver function testing should be conducted. Transient or permanent hearing loss has been reported in patients receiving treatment with ITRANOX. The hearing loss usually resolves when treatment is stopped, but can persist in some patients. Several cases of hypokalaemia have been reported. Serum potassium should be monitored in patients at risk during high-dose ITRANOX therapy.

Contraindications

ITRANOX is contraindicated in patients with a known hypersensitivity to the drug or its excipients. ITRANOX should not be administered to patients with evidence of ventricular dysfunction such as congestive heart failure or a history of congestive heart failure except for the treatment of life-threatening or other serious infections. ITRANOX is contraindicated in pregnant women except for the treatment of life-threatening cases of systemic mycoses, where the potential benefits outweigh the potential harm to the foetus. Highly effective contraceptive precautions should be taken by women of childbearing potential throughout ITRANOX therapy, and continued for two months following the completion of ITRANOX therapy. Co-administration of the following drugs is contraindicated with ITRANOX: terfenadine, astemizole, aliskiren, bepridil, felodipine, lercanidipine, domperidone, disopyramide, dronedarone, methadone, lurasidone, quetiapine, dabigatran, ticagrelor, apixaban, rivaroxaban, halofantrine, isavuconazole, naloxegol, lomitapide, avanafil, darifenacin, dapoxetine, eliglustat, irinotecan, venetoclax (in patients with chronic lymphocytic leukaemia during dose initiation/titration/ramp-up phase), ivabradine, ranolazine, eplerenone, sildenafil (pulmonary hypertension), ombitasvir/paritaprevir/ritonavir (with or without dasabuvir), nisoldipine, mizolastine, cisapride, dofetilide, levacetylmethadol, quinidine, pimozide, sertindole, simvastatin and lovastatin, oral midazolam, triazolam and ergot alkaloids such as dihydroergotamine, ergometrine, ergotamine, eletriptan and methylergometrine, fesoterodine (in subjects with moderate to severe renal or hepatic impairment), solifenacin (in subjects with severe renal or moderate to severe hepatic impairment), vardenafil (in patients older than 75 years), colchicine (in subjects with renal or hepatic impairment), vorapaxar, edoxaban, and telithromycin (in subjects with severe renal or hepatic impairment).

PBS listing

ITRANOX 100 mg capsules are listed on the PBS with one item under streamlined restrictions at an ex-manufacturer price of A$97.22.

Regulatory history

ITRANOX itraconazole 100 mg capsules were first registered on the Australian Register of Therapeutic Goods (ARTG 244432) on 9 August 2016.