Tadalafil and palpebral edema.

To the Editor: Tadalafil is a selective and reversible type 5 phosphodiesterase (5PDE) inhibitor. Therefore, its effect is greater on 5PDE than on other phosphodiesterases. It is indicated in the treatment of erectile dysfunction but still requires sexual stimulation to be effective. Tadalafil has a longer elimination half-life than sildenafil (17.5 versus 3.7 hours, respectively) and provides an efficient erection up to 36 hours after ingestion of the drug. To our knowledge, only rare and short-lasting side effects have been reported, most frequently headaches, dyspepsia, dizzy spells, hot flushes, blocked nose, back and muscle pain, and, more rarely, eye pain, conjunctival hyperemia, and eyelid edema. (1) To the best of our knowledge, this is the first case of palpebral edema probably related to the ingestion of tadalafil.

A 56-year-old male with a history including generalized psoriasis, insulin-dependent diabetes, severe obesity (body mass index, 38.3) and chronic smoking, consulted for sudden and recurrent edemas of the lower eyelids occurring mainly in the morning. These edemas were white, nonpruriginous, and accompanied by conjunctive hyperemia. The patient did not complain of any visual disturbance or of any other concomitant symptoms. Except psoriasis, the clinical examination was normal. There was no known history of allergy or atopic profile, and no recent modification had occurred in the patient's environment. His usual treatment over many years included insulin pump, metformin, lisinopril, acetylsalicylic acid, and atenolol. Only one drug, tadalafil, had been introduced the day before the appearance of the edemas. The patient had taken tadalafil, and the following morning bilateral eyelid edemas occurred and regressed spontaneously within 72 hours. One week later, a second intake of tadalafil induced the recurrence of the same symptoms.

In the literature, tadalafil appears to be associated with the appearance of palpebral edemas but, to our knowledge, no clinical case has ever been reported. The scrupulous questioning of the patient, the clinical examination, and the para-clinical results allowed us to rule out other causes of palpebral edema such as allergy, a contact eczema, and angioedema. Infections (infectious mononucleosis, trichinosis, and so forth) as well as hepatic, cardiac, or immunologic (lupus, dermatomyositis) causes were also ruled out by complementary examinations. The hypothesis of a diabetic nephropathy was also eliminated and, during questioning, the patient denied the long-term use of psychotropic drugs. Moreover, the chronological elements observed in this case consist of a 12-hour delay between drug intake and the onset of the palpebral edemas, a total regression and no reoccurrence of these symptoms during the period without any tadalafil intake, and the recurrence of the same adverse effect when the patient provoked a fortuitous rechallenge. This leads us to consider tadalafil as a probable causative agent for these rapidly occurring and short-lasting palpebral edemas.

It has been demonstrated in animals that inhibitors of PDE3 and PDE4 can provoke vascular lesions. These lesions could induce excessive vasodilatation and a reduction in blood flow and may be responsible for local cell ischemia (endothelial and smooth muscle). The cell damage could provoke a modification in vascular permeability and escalate the formation of tissue edemas. (2) Moreover, the peculiar anatomic structure of the eyelid, which limits the exchange of liquids and the resorption of such transudates, could intensify this drug-induced local iatrogenic side effect.

The existence of palpebral edemas recently described with another molecule should draw the attention of clinicians to the role of some drugs in the occurrence of this type of adverse effect. (3)

References

1. Padma-Nathan H, Mc Murray JG, Pullman WE, et al. On-demand IC351 (Cialis) enhances erectile function in patients with erectile dysfunction. Int J Impot Res 2001;13:2-9.

2. Slim RM, Robertson DG, Albassam M, et al. Effect of dexamethasone on the metabonomics profile associated with phosphodiesterase inhibitor-induced vascular lesions in rats. Toxicol Appl Pharmacol 2002;183:108-116.

3. Esmaeli B, Prieto VG, Buttler CE, et al. Severe periorbital edema secondary to ST1571 (Gleevec). Cancer 2002;95:881-887.

Marie-Lorraine Chandeclerc, MD

Samuel Martin, MD

Nadine Petitpain, MD

Annick Barbaud, MD

Jean-Luc Schmutz, MD

Department of Dermatology

Fournier Hospital

Nancy, France