Drug safety alert: IPC flags adverse drug reaction linked to Itraconazole

This came after preliminary analysis of Adverse Drug Reactions (ADRs) from the Pharmacovigilance Programme of India (PvPI) database.

Itraconazole is an antifungal agent used for the treatment of various fungal infections in immunocompromised and non-immunocompromised patients, such as pulmonary and extrapulmonary blastomycosis, histoplasmosis, and onychomycosis.

Itraconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Itraconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.

Itraconazole is indicated for the treatment of Systemic aspergillosis and candidiasis, cryptococcosis, sporotrichosis, Paracoccidioidomycosis, blastomycosis and other rarely occurring systemic or tropical mycoses.

In addition, the drug is also indicated tfor Empiric therapy of febrile neutropenic patients with suspected fungal infections.

Following the preliminary analysis of Adverse Drug Reactions (ADRs) from the PvPI database, it is reported that Itraconazole can lead to Symmetrical Drug Related Intertriginous and Flexural Exanthema (SDRIFE).

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) or (Baboon syndrome) is a symmetrical erythematous rash on the flexures after systemic exposure to a drug. This is distinct from other cutaneous drug reactions owing to its typical morphology, distribution, and absence of systemic findings. However, real pathogenetic mechanisms of symmetrical drug-related intertriginous and flexural exanthema are still unclear, but it has been suspected to develop as a result of a type IV delayed hypersensitivity immune response.

Now, as per the issued drug safety alert, the following suspected drug is associated with the ADRs as given below:

In light of the above, the Indian Pharmacopoeia Commission, Ministry of Health & Family Welfare, has advised Healthcare Professionals, Patients/Consumers to closely monitor the possibility of the above ADRs associated with the use of above suspected drugs.

Further, the safety alert added, "If such reaction is encountered, please report to the NCC-PvPI, IPC by filling of Suspected Adverse Drug Reactions Reporting Form/Medicines Side Effect Reporting Form for Consumer (http://www.ipc.gov.in), through Android Mobile App "ADR PvPI App" and PvPIHelpline No. 1800-180-3024 (Toll Free)."