Itraconazole
Mechanism :
Itraconazole inhibits the cytochrome P-450-dependent synthesis of ergosterol, which is a vital component of fungal cell membranes.
Indication :
- Systemic Fungal infections (off-label)
- Candidiasis (off-label)
- Histoplasmosis (off-label)
- Cystic Fibrosis
Contraindications :
Coadministration of terfenadine, astemizole or cisapride with itraconazole is contraindicated.
Concomitant administration with oral triazolam or with oral midazolam is contraindicated.
Should not be administered to pregnant patients or to women contemplating pregnancy.
Contraindicated in patients who have shown hypersensitivity to the drug or its excipients.
Dosing :
Oral <12 years:
3-5 mg/kg/day in two divided doses and
12-18 years:
200 mg once or twice daily. Max: 600 mg/day.
Duration for 15 days in tinea corporis, tinea cruris and oropharyngeal candidiasis and 30 days for tinea pedis and tines manuum. Duration is one year for histoplasmosis.
Adverse Effect :
Commonly seen adverse reactions are dizziness, abdominal pain, raised hepatic enzymes, nausea, constipation, headache, dyspepsia, menstrual disorders. Allergic reactions including rash, urticaria, pruritus and angioedema have been seen.
Interaction :
Terfenadine: Has led to elevated plasma concentrations of terfenadine, resulting in rare instances of life-threatening cardiac dysrhythmias.
Astemizole: Inhibits the metabolism of astemizole, resulting in elevated plasma concentrations of astemizole which may prolong QT intervals.
Midazolam or Triazolam: Resulted in elevated plasma concentrations of the two drugs. This may potentiate and prolong hypnotic and sedative effects.
Cyclosporine, Tacrolimus or Digoxin: Increased plasma concentrations.
Phenytoin, Rifampin, or H2antagonists: Reduced plasma concentrations of itraconazole were reported.
Anticoagulant: Enhances the anticoagulant effect of coumarin-like drugs. Therefore, prothrombin time should be carefully monitored.
Oral Hypoglycemic Agents: Severe hypoglycemia has been reported in patients concomitantly receiving azole antifungal agents and oral hypoglycemic agents.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in normal renal function. |
| HD | Not dialysed. Dose as in normal renal function |
| HDF/High flux | Not dialysed. Dose as in normal renal function |
| CAV/VVHD | Not dialysed. Dose as in normal renal function |
Hepatic Dose :
Limited data is available on the use of oral itraconazole in patients with hepatic impairment. Very rare cases of serious hepatotoxicity, including some cases of fatal acute liver failure, have been reported with the use of Itraconazole. Liver function monitoring should be considered in patients receiving itraconazole treatment. It is recommended that the prolonged elimination half-life of itraconazole in cirrhotic patients be considered when deciding to initiate therapy with other medications metabolized by CYP3A4.