PRODUCT

Itrafun^TM is a formulation of 65 mg Itraconazole which is a broad-spectrum antifungal agent. It is a triazole antimycotic agent that has potent lipophilic and keratophilic characteristics.

PHARMACOKINETICS

Itraconazole’s pharmacokinetics are highly variable, influenced by oral bioavailability. It has non-linear saturable pharmacokinetics, with prolonged terminal clearance and slow accumulation. Itraconazole’s terminal half-life is 24 hours and the time to steady state may be 14 days.

PHARMACODYNAMICS

Itraconazole’s pharmacodynamics in interpreting these results for humans is challenging due to differences in drug exposure measurements.

ABSORPTION

Itraconazole capsules’ absorption is influenced by an acidic environment, making them suitable for food or acidic soft drinks. Oral bioavailability doubles after food, but impaired by gastric acid reduction agents and achlorhydria (conditions in which the production of hydrochloric acid in the stomach is respectively absent or reduced).

METABOLISM

Itraconazole is primarily metabolized by CYP isoenzyme CYP3A4 ( member of the cytochrome P450 superfamily of enzymes), producing hydroxyitraconazole, a biologically active metabolite with comparable antifungal potency, with concentrations double that of the parent compound.

MECHANISM OF ACTION & PHARMACOLOGICAL BENEFITS

Like other azole antifungal medicines, itraconazole works by inhibiting 14-α-demethylase, which impairs the synthesis of sterols in the membranes of fungal cells. Itraconazole is efficacious in vitro against both dermatophytes and non-dermatophyte molds, as well as yeasts such as Malassezia and Candida species.

It is useful in various clinical settings due to its broad spectrum. It has been regarded as a key agent for managing chronic and allergic aspergillosis and treating endemic mycoses worldwide.

DRUG-DRUG INTERACTIONS

Itraconazole’s absorption can be impacted by drug-drug interactions, including antacids, proton pump inhibitors, and H2-antagonists. Itraconazole metabolism can be accelerated by concurrent administration of rifampicin, phenytoin, and carbamazepine, and can prolong the action of benzodiazepines, digoxin, statins, and warfarin.

ADVERSE EFFECTS

It is generally well-tolerated, in some cases it has been linked to adverse events including gastrointestinal symptoms, peripheral oedema, hepatic inflammation, and maculopapular rash.