A Case of Progressive Cholestatic Drug-Induced Liver Injury Due to Terbinafine.

INTRODUCTION: Terbinafine is commonly prescribed for onychomycosis. It rarely leads to severe, prolonged cholestatic drug-induced liver injury. Clinicians should remain vigilant for this complication. CASE PRESENTATION: A 62-year-old woman was started on terbinafine and developed mixed hepatocellular and cholestatic drug-induced liver injury, confirmed on liver biopsy. The injury became predominantly cholestatic. Unfortunately, she developed coagulopathy with elevated international normalized ratio and progressive drug-induced liver injury with severely elevated alkaline phosphatase and total bilirubin, requiring repeat liver biopsy. Fortunately, she did not develop acute liver failure. DISCUSSION: Prior case reports and series have documented severe cholestatic drug-induced liver injury (although with lesser degree of bilirubin elevation) due to terbinafine, which has very rarely been associated with acute liver failure, need for liver transplantation, and/or death. CONCLUSIONS: Non-acetaminophen drug-induced liver injury is idiosyncratic. Complications including acute liver failure and vanishing bile duct syndrome can be slow to develop, so monitoring for them is important over longitudinal follow-up.

Olive oil and clove oil-based nanoemulsion for topical delivery of terbinafine hydrochloride: in vitro and ex vivo evaluation.

In this article, formulation studies for terbinafine hydrochloride nanoemulsions, prepared by high-energy ultrasonication technique, are described. Pseudo-ternary phase diagram was constructed in order to find out the optimal ratios of oil and surfactant/co-solvent mixture for nanoemulsion production. Clove and olive oils were selected as oil phase. Based on the droplet size evaluation, maximum nanoemulsion region were determined for formulation development. Further characterization included polydispersity index (PDI), zeta potential, Fourier transform infrared (FT-IR) spectroscopy, morphology, pH, viscosity, refractive index, ex vivo skin permeation, skin irritation, and histopathological examination. Droplet sizes of optimized formulations were in colloidal range. PDI values below 0.35 indicated considerably homogeneous nanoemulsions. Zeta potential values were from 13.2 to 18.1 mV indicating good stability, which was also confirmed by dispersion stability studies. Ex vivo permeation studies revealed almost total skin permeation of terbinafine hydrochloride from the nanoemulsions (96-98%) in 6 hours whereas commercial product reached only 57% permeation at the same time. Maximum drug amounts were seen in epidermis and dermis layers. Skin irritation and histopathological examination demonstrated dermatologically safe formulations. In conclusion, olive oil and clove oil-based nanoemulsion systems have potential to serve as promising carriers for topical terbinafine hydrochloride delivery.

Terbinafine-induced lichenoid drug eruption: case report and review of terbinafine-associated cutaneous adverse events.

Terbinafine is an antifungal agent used in the treatment of hair, nail, and skin dermatophyte infections. Skin side effects to terbinafine are not common. Lichenoid drug eruption is a medication-related adverse cutaneous event; the lesion morphology and pathology mimic lichen planus. A woman with onychomycosis developed a lichenoid drug eruption one week after starting terbinafine. The features of her dermatosis and the characteristics of two additional men who also experienced terbinafine-induced lichenoid drug eruption are discussed. They were receiving a daily terbinafine dosage of either 125mg or 250mg to treat onychomycosis or tinea cruris. The lichenoid drug eruption presented as diffuse or symmetric lesions within one to two weeks after starting terbinafine treatment. The extremities, chest, abdomen, and/or trunk were common sites. Less frequent locations were the lips, nails, palms, soles, and suprapubic region; lesions did not occur on the oral or genital mucosa. The eruption resolved after discontinuation of the medication (with or without treatment using topical corticosteroids, systemic corticosteroids, or both). In addition, more frequently occurring terbinafine-associated cutaneous adverse events (such as urticaria, erythematous eruptions, pruritus, acute generalized exanthematous pustulosis, subacute cutaneous lupus erythematosus, and papulosquamous conditions) are reviewed.

Acute generalized exanthematous pustulosis due to terbinafine.

Acute generalized exanthematous pustulosis is a rare adverse cutaneous reaction characterized by the rapid appearance of numerous pustules arising on edematous, erythematous skin. It is commonly accompanied by fever and leukocytosis and usually resolves with discontinuation of the offending agent. Herein, acute generalized exanthematous pustulosis induced by terbinafine is described, followed by a brief review of the literature.