SPORANOX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SPORANOX (SPORANOX).
Inhibits fungal cytochrome P450 (CYP450)-dependent lanosterol 14α-demethylase, blocking ergosterol synthesis and disrupting fungal cell membrane integrity.
| Metabolism | Primarily metabolized by hepatic CYP3A4 enzyme; metabolites include hydroxy-itraconazole. It is an inhibitor of CYP3A4. |
| Excretion | Itraconazole is extensively metabolized in the liver via CYP3A4 to active metabolites, including hydroxyitraconazole. The parent drug and metabolites are primarily excreted in feces (approximately 54%) and urine (approximately 35%), with less than 1% of the dose excreted unchanged in urine. |
| Half-life | The terminal elimination half-life of itraconazole ranges from 21 to 35 hours for single doses, increasing to approximately 34 to 42 hours at steady state. The half-life of the active metabolite, hydroxyitraconazole, is similar. This long half-life allows for once-daily or twice-daily dosing in most indications. |
| Protein binding | Itraconazole is highly protein-bound (99.8%), primarily to albumin. This high binding restricts distribution into tissues but contributes to its long half-life and extensive tissue penetration. |
| Volume of Distribution | The apparent volume of distribution (Vd/F) for itraconazole is large, approximately 10.7 L/kg, indicating extensive tissue distribution and high lipophilicity. This results in tissue concentrations several times higher than plasma concentrations, particularly in skin, nails, lungs, and adipose tissue. |
| Bioavailability | Oral bioavailability of itraconazole capsules is approximately 55% under fed conditions (especially with a full meal) but is variable (30-70%) and decreases significantly when taken on an empty stomach. The oral solution has higher and more consistent bioavailability (approximately 60-80%) and is better absorbed in the fasted state. Absorption is pH-dependent; therefore, concomitant use of acid-reducing agents reduces absorption. |
| Onset of Action | Oral: Time to peak plasma concentration (Tmax) is 2 to 5 hours. Clinical effect, such as antifungal activity, begins within 24 to 48 hours after the first dose, but therapeutic response may take several days to weeks depending on the infection site and severity. Intravenous: Not available in all formulations; onset is more rapid with IV administration. |
| Duration of Action | The duration of therapeutic effect is prolonged due to the long half-life and high tissue penetration. After discontinuation, therapeutic concentrations persist in tissues (e.g., skin, nails) for weeks to months, supporting pulse dosing regimens for onychomycosis. Clinical duration varies by indication: for dermatophytosis, treatment duration is typically 1 to 4 weeks; for systemic mycoses, months may be required. |
| Molecular Weight | 705.63 |
| Action Class | Fungal ergosterol synthesis inhibitor |
| Brand Substitutes | Itralase 100 Capsule, Canditral 100 Capsule, Syntran Capsule, Itrafree 100mg Capsule, Itromed 100 Capsule, Iycotizol Capsule |
200 mg orally twice daily for 3-7 days; for onychomycosis: 200 mg orally once daily for 12 weeks.
| Dosage form | SOLUTION |
| Renal impairment | No adjustment needed for GFR 15-50 mL/min; avoid use in GFR <15 mL/min. |
| Liver impairment | Child-Pugh A: 100 mg orally once daily; Child-Pugh B or C: avoid use. |
| Pediatric use | 5 mg/kg/day orally in two divided doses for systemic fungal infections; max 400 mg/day. |
| Geriatric use | Start at 100 mg orally once daily; increase cautiously based on response and tolerability. |
| 1st trimester | Contraindicated in first trimester due to dose-related teratogenicity in animal studies and reports of skeletal and soft tissue malformations in humans. Use only for life-threatening infections with no alternative. |
| 2nd trimester | Use only if potential benefit justifies risk to fetus, as there are no adequate well-controlled studies. Has been associated with increased risk of spontaneous abortion. |
| 3rd trimester | Same as second trimester; avoid use near term due to potential for neonatal hypoglycemia from IV formulation excipient (hydroxypropyl-β-cyclodextrin). |
Clinical note
Comprehensive clinical and safety monograph for SPORANOX (SPORANOX).
| Placental transfer | Itraconazole crosses the placenta with cord blood levels approximately 40% of maternal plasma levels. |
| Breastfeeding | Itraconazole is excreted into breast milk in low concentrations. The amount is unlikely to cause adverse effects in a nursing infant, but caution is advised due to potential for accumulation in premature or low-birth-weight infants. Consider alternative antifungal if possible. |
■ FDA Black Box Warning
Congestive heart failure (CHF): SPORANOX may cause or exacerbate CHF. Do not use for treatment of onychomycosis in patients with evidence of ventricular dysfunction (e.g., CHF history). Discontinue if signs/symptoms of CHF occur.
| Serious Effects |
Pregnancy (first trimester) or women of childbearing potential not using effective contraceptionCongestive heart failure (including history), ventricular dysfunctionKnown hypersensitivity to itraconazole or any excipientsCoadministration with CYP3A4 substrates that prolong QT interval (e.g., astemizole, cisapride, methadone, pimozide, quinidine, terfenadine)Coadministration with HMG-CoA reductase inhibitors metabolized by CYP3A4 (e.g., lovastatin, simvastatin)Coadministration with triazolam, oral midazolamCoadministration with ergot alkaloids (e.g., dihydroergotamine, ergotamine)Coadministration with nisoldipine, ranolazine, eplerenone, felodipine, avanafil, or irinotecan
| Precautions | Hepatotoxicity (rare but severe, including liver failure). Negative inotropic effects leading to CHF. Hearing loss (reversible). Hypokalemia, edema, and pulmonary edema. Prolonged QT interval and arrhythmias. |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L2 (Probably Compatible) |
| Teratogenic Risk | Pregnancy Category C. First trimester: Increased risk of major congenital malformations (e.g., skeletal, cardiac, CNS) based on animal studies; limited human data. Second/third trimester: Potential fetal toxicity (e.g., low birth weight, prematurity) observed in animal studies; use only if benefit outweighs risk. |
| Fetal Monitoring | Monitor liver function tests (LFTs) monthly during treatment. Assess renal function, electrolytes, and CBC periodically. In pregnancy, consider ultrasound for fetal growth and anatomy if high-dose or prolonged therapy. |
| Fertility Effects | Animal studies show no significant impairment of fertility at therapeutic doses. In humans, no well-controlled studies; however, itraconazole may cause transient decreases in testosterone levels, potentially affecting spermatogenesis; clinical relevance unclear. |
| Take capsules with a full meal to enhance absorption; avoid grapefruit and grapefruit juice as they may decrease itraconazole absorption. Oral solution should be taken on an empty stomach. |
| Clinical Pearls | SPORANOX (itraconazole) is a triazole antifungal with ciclopirox-like activity. It is highly protein-bound and extensively metabolized by CYP3A4. Key monitoring includes hepatic function, as elevation of liver enzymes can occur. Absorption is enhanced with acidic gastric pH; thus, avoid concurrent use of antacids, H2 antagonists, or PPIs. It has a long half-life (1-2 days) and is lipophilic, accumulating in tissues. Useful for dermatophyte infections and onychomycosis, but note potential for negative inotropic effects — avoid in patients with ventricular dysfunction. Drug interactions are numerous due to CYP3A4 and P-glycoprotein inhibition. |
| Patient Advice | Take Sporanox capsules with a full meal to improve absorption; for oral solution, take on an empty stomach. · Avoid antacids, histamine H2 blockers (e.g., ranitidine), or proton pump inhibitors (e.g., omeprazole) while on this medication. · Do not use Sporanox if you have had a heart attack, heart failure, or irregular heartbeat. · Report symptoms like yellowing of skin/eyes, dark urine, or fatigue immediately. · Complete the full course of therapy even if symptoms improve. · Inform your doctor of all medications you take, as serious interactions can occur. |