Griseofulvin in Children: Revisiting the Vintage Drug

Madam, Griseofulvin is a natural spirocyclic polyketide produced mainly by ascomycetes. It is the first systemic antifungal licensed for dermatophytosis in children.[1] Even after several years of its discovery, it remains one of the widely used antifungals due to the cost-effective and safe treatment option for dermatophytosis. In 1939, griseofulvin was first discovered and isolated from Pencillium griseofulvum Dierckx (Synonyms: Pencillium urticae Bain.; Pencillium patulum Bain.) by Oxford et al. In 1959, FDA approved Griseofulvin for the treatment of dermatophytosis and was launched in the market in 1962 for its treatment.[1,2] The structure of Griseofulvin is shown in Figure 1. The molecular formula of griseofulvin is C17H17ClO6.Figure 1: Structure of griseofulvinGriseofulvin has low aqueous solubility and bioavailability. The absorption can be augmented by the administration with a fatty meal, along with a whole milk, coating with polyethylene glycol, and reducing the drug particle size (micronization or ultra-micronization). It has a half-life of 9–21 h and a peak-post dosing levels at 2–4 h. Griseofulvin gets excreted through the sweats and appears in the stratum corneum within 4 h after a single dose administration. Griseofulvin gets accumulated in the keratin-producing tissues and adherently binds to neoformed keratin, making it resistant to fungal penetration.[1,2] Griseofulvin is available either in tablet form or as an oral suspension. It is available in ultramicro-size (125 and 250 mg) and micro-size (250 and 500 mg) forms. Griseofulvin tablets can be pulverized and administered with food. In children who struggle to swallow tablets, oral suspension may be preferred.[2,3] Griseofulvin passes into the dermatophyte through energy-dependent transport processes. It binds to the tubulins and microtubule-associated proteins of the fungi and disrupts the mitotic spindle, thereby inhibiting mitosis at the metaphase of the cell cycle.[1] Griseofulvin is US FDA approved for the management of tinea capitis in children above 2 years of age. However, it is used off-label for the treatment of other superficial dermatophyte infections such as tinea corporis, tinea cruris, tinea faciei, tinea pedis, and tinea imbricata.[3] Griseofulvin has shown good therapeutic effects for tinea capitis in children less than 2 years of age.[4] A network meta-analysis has shown that oral griseofulvin monotherapy is the most efficacious agent for Microsporum genus in terms of clinical and mycological cure.[5] The dosing schedule of griseofulvin for dermatophyte infections in children is summarized in Table 1.Table 1: Griseofulvin treatment regimens for dermatophytosisGriseofulvin has shown good efficacy in reducing the person-to-person transmission of tinea capitis in school-going children.[6] In Israeli refugee children with tinea capitis, 14% of the children showed partial response to a griseofulvin dose of ≤25 mg/kg/day. However, upon increasing the dose to ≥30 mg/kg/day, showed a complete response.[7] In healthy children treated with griseofulvin for a duration of 8 weeks or less, laboratory monitoring is not needed. Liver enzymes, blood urea nitrogen, and serum creatinine should be measured after 8 continuous weeks of griseofulvin use.[8] Griseofulvin is a CYP3A4 and CYP2C9 inducer. Barbiturates reduce the absorption of griseofulvin, thereby decreasing its efficacy. Interactions with warfarin, aspirin, thalidomide, and cyclosporine have been reported.[3] Griseofulvin is a well-tolerated safe drug to use clinically in children. A mild elevation in hepatic transaminases is a relative common finding in pediatric patients treated with griseofulvin for tinea capitis.[8] The systemic adverse effects associated with griseofulvin are mentioned in Table 2. It is a known photosensitizing agent. Hence, patients should be instructed to avoid excessive exposure to direct sunlight, wear protective eyewear and clothing, and use sunscreen.[3,9] The list of cutaneous adverse effects related to griseofulvin use is mentioned in Table 3.Table 2: Systemic adverse effects associated with griseofulvinTable 3: Cutaneous adverse effects associated with griseofulvinThe years of experience with the griseofulvin use in children has demonstrated long-term efficacy and favorable adverse effect profile. Even after 60 years of its use, it still has a vital role in the treatment armamentarium of dermatophyte infections due to alarming emergence of resistance against allylamines and azole group of drugs. Declaration of consent The authors certify that they have obtained all appropriate consent forms, duly signed by the parent(s)/guardian(s) of the patient. In the form, the parent(s)/guardian(s) has/have given his/her/their consent for the images and other clinical information of their child to be reported in the journal. The parents understand that the names and initials of their child/children will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.