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Viewpoints in dermatology • Correspondence Sclerosing lymphangitis of the penis after ergosterol biosynthetic pathway. Azoles may inhibit CYP- coadministration of tadalafil and fluconazole mediated metabolism and may be responsible for inducingtoxicity of other co-administered drugs by decreasing their clearance. In particular, fluconazole has been shown tomarkedly Multi-drug treatment is a common practice in patients with multiple disorders. Up to 2.8% of hospital admissions are SLP is a benign pathology of the superficial dorsal penile due to drug–drug interactions resulting in adverse drug vein, characterized by development within 24–48 h of a firm cord-like swelling of the coronal sulcus. There may be mild to A 50-year-old man presented with a 3-week history of moderate pain, tenderness and discomfort on erection, or discomfort in the genital area and a lesion that had also there may be no symptoms. Although many causes have appeared on his penis after sexual intercourse.
been proposed, the pathogenesis of penile SLP is unclear.
On physical examination, a painless, tender, flesh- We recently described a case of SLP after tadalafil use, and coloured, subcutaneous cord-like structure was found in suggested, as a possible explanation, an existing anatomical the coronal sulcus. There were no genitourinary symptoms variation of the venous arcade in addition to mechanical or regional lymphadenopathy. Laboratory investigations, compression by the corpora cavernosa produced by tadalafil- including complete blood count, urinalysis, and serological induced prolonged overexpansion.4 We therefore believe that testing for syphilis and human immunodeficiency virus, pharmacokinetic interaction tadalafil-fluconazole could have produced SLP by increasing the plasma concentration The patientÕs medical history showed that 2 years previ- of tadalafil and intensifying its pharmacological response.
ously, he had been prescribed sildenafil citrate (100 mg to be Although both tadalafil and sildenafil undergo signifi- taken 2 hours before intercourse; ViagraÒ; Pfizer Inc., New cant intestinal and hepatic CYP3A4-mediated first-pass York, NY, USA) then switched to tadalafil 20 mg (CialisÒ; Eli metabolism, the major metabolite of tadalifil (methylcate- Lilly & Co., Indiana, IN, USA) a year later, without experi- chol glucuronide) is 13 000 times less potent than tadalafil encing adverse effects. Because of onychomycosis of hands itself against PDE-5.2 In contrast, sildenafil is a substrate and feet, he was also being treated with fluconazole (ElazorÒ; not only of CYP3A4 but also of CYP2C9. Furthermore, one Sigma-Tau SpA, Rome, Italy) 300 mg ⁄ day once weekly. He circulating metabolite of sildenafil may contribute to had also taken fluconazole years earlier because of tinea approximately 20% of the net pharmacological effect of corporis, without any adverse events. The penile lesion had the drug.5 This may explain why our patient never appeared approximately 24 h after the third day of fluco- experienced such reactions while taking both fluconazole nazole treatment, when the patient was also taking tadalafil.
A diagnosis of sclerosing lymphangitis of the penis (SLP) Although a causal connection with SLP can only be was made, and sexual and pharmacological abstinence presumed, this case underlines the importance of care in were recommended. At follow-up 4 weeks later, all symp- prescribing azoles with other CYP-inhibitors or substrates, and taking into consideration drug–drug interactions, espe- Erectile dysfunction (ED) is a medical condition affecting cially with drugs that are not often declared by patients.
millions of men worldwide. Tadalafil is a widely prescribedoral agent acting on the corpora cavernosa by inhibiting a specific cyclic-guanidine monophosphate phosphodiesterase Institute of Dermatology, Azienda Ospedaliera Universitaria G.
(PDE-5), which results in raised cytosolic calcium concen- Martino, Via Consolare Valeria, Gazzi 98125, Messina, Italy; and tration and smooth-muscle contraction, consequently pro- *Department of Clinical Experimental Medicine and Pharmacology, and moting erection. Tadalafil is metabolized predominantly by IRCCS Centro Neurolesi ‘Bonino-Pulejo’, University of Messina, the hepatic cytochrome P450 3A4 (CYP3A4) isoenzyme.2 Fluconazole is used to treat a variety of fungal infections and inhibits fungal cytochrome P450, responsible for the Conflict of interest: none declared.
Accepted for publication 19 May 2008 conversion of lanosterol to 14a-demethyllanosterol in the Ó 2009 The Author(s)Journal compilation Ó 2009 British Association of Dermatologists • Clinical and Experimental Dermatology, 34, e225–e226 activities in human liver microsomes. Biol Pharm Bull 2005; 1 Shapiro LE, Shear NH. Drug-drug interactions: how scared 4 Guarneri C, Guarneri F. MondorÕs phlebitis after using should we be? CMAJ 1999; 161: 1266–7.
tadalafil. Br J Dermatol 2007; 157: 209–10.
2 Kim S, Narayanan S, Song JC. Tadalafil. An oral selective 5 Warrington JS, Shader RI, von Moltke LL et al. In vitro phosphodiesterase 5 inhibitor for treatment of erectile dys- biotransformation of sildenafil (Viagra); identification of function. Formulary 2002; 37: 289–96.
human cytochromes and potential drug interactions.
3 Niwa T, Shiraga T, Takagi A. Effect of antifungal drugs on Drug Metab Dispos 2000; 28: 392–7.
cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A4 Journal compilation Ó 2009 British Association of Dermatologists • Clinical and Experimental Dermatology, 34, e225–e226

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