From the Guidelines
Itraconazole is contraindicated in patients with heart failure and hepatotoxicity, and its use requires careful monitoring of hepatic function tests, especially in patients with pre-existing liver disease or those receiving concomitant hepatotoxic drugs. The most common adverse reactions associated with itraconazole include headache and gastrointestinal upset 1. Itraconazole should be taken with food and in an acidic pH environment to optimize absorption. The recommended dosage is 200 mg per day for 12 weeks continuously, or alternatively as ‘pulse therapy’ at a dose of 400 mg per day for 1 week per month, with two pulses for fingernails and three pulses for toenails 1.
Key Considerations
- Contraindications: heart failure, hepatotoxicity
- Common adverse reactions: headache, gastrointestinal upset
- Monitoring requirements: hepatic function tests, especially in patients with pre-existing liver disease or those receiving concomitant hepatotoxic drugs
- Dosage and administration: 200 mg per day for 12 weeks continuously, or alternatively as ‘pulse therapy’ at a dose of 400 mg per day for 1 week per month, with two pulses for fingernails and three pulses for toenails
Important Interactions
Itraconazole is extensively metabolized by the liver and is a potent inhibitor of the CYP3A4 enzyme system, which metabolizes many commonly prescribed medications, and therefore, its use with certain medications should be avoided or carefully monitored 1.
Special Populations
Pregnant women should avoid itraconazole as it is teratogenic, and patients with liver disease should use itraconazole cautiously with dose adjustments 1.
From the FDA Drug Label
ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. SPORANOX ® has been associated with rare cases of serious hepatotoxicity, including liver failure and death.
Table 3: Summary of Adverse Events Reported by ≥2% of SPORANOX ®Treated Patients in U. S. Clinical Trials (Total)
Gastrointestinal disorders Nausea1110115 Diarrhea1110104 Vomiting7681 Abdominal pain6477 Constipation2210
Postmarketing Experience Adverse drug reactions that have been first identified during postmarketing experience with SPORANOX ® (all formulations) are listed in Table 4 below.
Gastrointestinal Disorders:Pancreatitis Hepatobiliary Disorders: Serious hepatotoxicity (including some cases of fatal acute liver failure), hepatitis, reversible increases in hepatic enzymes
BOXED WARNING Congestive Heart Failure, Cardiac Effects and Drug Interactions Congestive Heart Failure and Cardiac Effects If signs or symptoms of congestive heart failure occur during administration of SPORANOX ®(itraconazole) Oral Solution, continued SPORANOX ® use should be reassessed.
Coadministration of a number of CYP3A4 substrates are contraindicated with SPORANOX ®. Some examples of drugs that are contraindicated for coadministration with SPORANOX ® Oral Solution are: methadone, disopyramide, dofetilide, dronedarone, quinidine, isavuconazole, ergot alkaloids (such as dihydroergotamine, ergometrine (ergonovine), ergotamine, methylergometrine (methylergonovine)), irinotecan, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisoldipine, ivabradine, ranolazine, eplerenone, cisapride, naloxegol, lomitapide, lovastatin, simvastatin, avanafil, ticagrelor, finerenone, voclosporin.
Itraconazole Side Effects:
- Gastrointestinal disorders: nausea, diarrhea, vomiting, abdominal pain, constipation
- Hepatobiliary disorders: serious hepatotoxicity, liver failure, death
- Postmarketing experience: pancreatitis, serious hepatotoxicity, hepatitis, reversible increases in hepatic enzymes
Itraconazole Contraindications:
- Coadministration with certain CYP3A4 substrates, such as:
From the Research
Itraconazole Side Effects
- The most common side effects of itraconazole therapy are hepatotoxicity (7.0%), nausea/vomiting (6.6%), and diarrhoea (6.2%) 3.
- Approximately one-quarter of patients with histoplasmosis receiving long-term itraconazole therapy experience at least one side effect 3.
- The median time to side effect is 45 days, and about two-thirds of patients with side effects undergo a therapeutic intervention, such as dose reduction or discontinuation of itraconazole 3.
Itraconazole Contraindications
- Itraconazole is associated with congestive heart failure, and its labelling has been changed to alert physicians to this new finding 4.
- Patients with a history of congestive heart failure should be cautious when using itraconazole, as it may exacerbate the condition 4.
Special Considerations
- Itraconazole has a broad-spectrum of activity and is available in both an intravenous and oral form, making long-term use in chronic mycoses practical 5.
- However, pharmacokinetic variability and clinically important drug interactions make therapeutic drug monitoring (TDM) of itraconazole an important consideration 5.
- TDM can help minimize the risk of side effects and ensure optimal treatment outcomes 5.