API Itraconazole

Itraconazole More Info

OVERVIEW

Itraconazole is a synthetic triazole antifungal drug belonging to the azole antifungal class. This pharmaceutical compound functions as a broad-spectrum antimycotic agent with efficacy against various fungal species. The drug was originally developed by Janssen Pharmaceutica Institute and is available under several commercial brand names.

CHEMICAL PROPERTIES

The systematic chemical name for Itraconazole is (±)-4-[4-[4-[4-. The molecular formula is C₃₅H₃₈Cl₂N₈O₄ with a molecular weight of 705.63 g/mol. The CAS registry number is 84625-61-6. The compound appears as a white powder with a melting point of 166°C. Itraconazole demonstrates heat sensitivity and is soluble in DMSO at approximately 4 mg/mL.

ALTERNATIVE NAMES AND BRAND NAMES

Itraconazole is commercially known by various trade names including Sporanox, Tolsura, Itrizole, Onmel, and Triasporin. The compound carries ATC code J02AC02 in the Anatomical Therapeutic Chemical Classification System. Additional manufacturer codes include R-51211.

MECHANISM OF ACTION

Itraconazole works by inhibiting cytochrome P-450-dependent enzymes that are required for ergosterol synthesis in fungal cells. By disrupting ergosterol production, the compound alters the permeability of the fungal cell membrane, thereby preventing fungal growth and survival. This mechanism is structurally related to ketoconazole but exhibits broader spectrum activity.

THERAPEUTIC INDICATIONS

Itraconazole is indicated for the treatment of various fungal infections including blastomycosis, histoplasmosis, aspergillosis, sporotrichosis, candidiasis, onychomycosis, coccidioidomycosis, oral thrush, vaginal candidiasis, skin fungal infections, nail infections, and pulmonary fungal infections. The medication is effective against both immunocompromised and non-immunocompromised patients. It is also used to prevent recurrent fungal infections in HIV/AIDS patients and to prevent fungal infections in neutropenic patients. Additionally, itraconazole has demonstrated activity against hedgehog signaling pathways and has shown inhibition of medulloblastoma growth in animal models.

PHARMACOKINETICS

Itraconazole is well absorbed when taken with food, demonstrating an absolute oral bioavailability of approximately 55%. The compound has a volume of distribution of 796 ± 185 L and is extensively protein-bound at 98.8%. Metabolism occurs primarily in the liver through the CYP3A4 isoenzyme, forming hydroxyitraconazole as the major active metabolite. The elimination half-life is approximately 21 hours. Studies have estimated the hepatic first-pass effect to be 18.5% in rat models.

DOSAGE AND ADMINISTRATION

Common dosage forms include capsules (100 mg) and oral solution (10 mg/mL or 2 mg/mL). The recommended starting dose is typically 200 mg once daily, taken with food. For treatment-resistant cases or progressing infections, the dose may be increased in 100 mg increments up to a maximum of 400 mg daily. In severe situations, a loading dose protocol may be employed during the initial three days of therapy. For oral solution administration used to treat throat infections, the recommended technique involves swishing 10 mL of the solution in the mouth for several seconds before swallowing.

CONTRAINDICATIONS AND PRECAUTIONS

Co-administration with terfenadine, astemizole, cisapride, quinidine, pimozide, dofetilide, levacetylmethadol, methadone, felodipine, lovastatin, oral midazolam, nisoldipine, simvastatin, triazolam, or ergot alkaloids is contraindicated. Itraconazole should not be administered to patients with evidence of ventricular dysfunction or history of congestive heart failure. Patients with hypersensitivity to other azoles are contraindicated from using this medication. Antacids or stomach medicines require a 2-hour gap before or after taking itraconazole.

SIDE EFFECTS AND ADVERSE REACTIONS

Common side effects include nausea, diarrhea, abdominal pain, headache, dizziness, dyspepsia, and skin rashes. Unusual taste in the mouth may also occur. Serious adverse effects include liver problems indicated by yellowing of skin or eyes, pale stools, dark urine, fever, hives, and difficulty swallowing. Rare but severe reactions such as Stevens-Johnson syndrome have been reported. Signs or symptoms of congestive heart failure require immediate discontinuation of therapy. Patients experiencing severe allergic reactions such as hives, severe skin rash, tingling in arms or legs, difficult breathing, or swelling of face, lips, tongue, or throat require emergency medical attention.

STORAGE AND HANDLING

Products should be stored in their original container, tightly closed and out of reach of children. Capsules and tablets should be kept in cool, dry places away from direct sunlight. Different brands and dosage forms of itraconazole are not interchangeable without doctor supervision. Sporanox oral liquid works differently than Sporanox capsules even at the same milligram dose.

SPECIAL POPULATIONS

Itraconazole is classified as pregnancy category C by the FDA, indicating potential risks to fetal development including maternal toxicity, embryotoxicity, and teratogenicity. The medication passes into breast milk and is not recommended for use in breastfeeding women. Safety and effectiveness in children have not been fully established. Caution is advised for patients with liver or kidney disease, cystic fibrosis, lung problems, or weak immune systems.