Is phototoxicity or photoallergy known side effects of doxycycline, simvastatin, clopidogrel, parac

Fråga: Is phototoxicity or photoallergy known side effects of doxycycline, simvastatin, clopidogrel, paracetamol, sertraline, budesonide, salbutamol, cinnarizine or theophylline?

Could doxycycline remain in the body one week after withdrawal?

The questions concerns a man medicating with the drugs mentioned above (except doxycycline) who, during a trip to Spain, had a severe sunburn after only a brief sun exposition. One week earlier, he had finished a course of doxycycline.

Sammanfattning: Doxycycline is known to cause phototoxicity, but this is unlikely one week after withdrawal. There are a few reported cases of photosensitivity caused by simvastatin and one where sertraline was thought to be the offending drug. There is one case report where cinnarizine was thought to have elicited subacute cutaneous lupus erythematosus with photosensitivity. Simvastatin could possibly precipitate porphyria cutanea tarda, a condition with increased sensitivity to sunlight.

Svar: Phototoxicity is a well-known adverse effect of doxycycline (1). However, with a biological half-life of 18-22 hours, doxycycline should be completely removed from plasma one week after withdrawal.

Theoretically, the substance could remain in the skin longer than in plasma, but no information on such trapping phenomena was found in Medline or standard pharmacological literature. Moreover, no clinical reports of delayed phototoxicity such as the proposed were found.

Photoallergic reactions can relapse several months after drug withdrawal, but only after an initial symptomatic reaction during the treatment period (2). Besides, doxycycline is known to cause phototoxic rather than photoallergic reactions.

There are two published case reports of photosensitivity following exposure to simvastatin (3-4). The first concerns a 50-year-old woman developing erythema and vesicles on sun-exposed areas one week after starting medication with simvastatin (3). She reacted similarly to low doses of UVA light. The second report was of a man intermittently medicating with simvastatin, who developed chronic actinic dermatitis (4). Photopatch testing between treatment periods triggered an eczematoid reaction and after five days of treatment with simvastatin, a lower dose of UV light was sufficient to provoke the reaction. According to the authors, this worsening strongly supports systemic photosensitivity to simvastatin. In Swedis, there are four reports of photo sensitisation where a causal relationship to simvastatin medication has been deemed possible (5). One of the cases includes a positive de- and re-challenge.

In Swedis, there is one report of photosensitivity with a possible causal relationship to sertraline (5). In Micromedex, photosensitivity is listed as an infrequent adverse effect of sertraline (6).

There is one case report of a 32-year-old woman developing photosensitivity during treatment with cinnarizine and thiethylperazine (7). She was diagnosed with subacute cutaneous lupus erythematosus (SCLE), presumably elicited by the medication. Thiethylperazine is known to cause photosensitivity, but since the patient ten years earlier had experienced similar symptoms during monotherapy with cinnarizine, this drug was thought to be involved in the pathogenicity.

No reports of phototoxic or photoallergic reactions to clopidogrel, paracetamol, budenoside, salbutamol or theophylline were found.

An alternative mechanism, by which drugs could cause photosensitivity is by inducing porphyria. Transient hypocholesterolemia seems to be a risk factor for hepatic porphyria, and there is one published case where simvastatin apparently precipitated porphyria cutanea tarda (8). For the other drugs mentioned above, no such reports were found in Swedis, Medline or Drugline. 1 Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999, p. D229-32 2 Kauppinen K, Alanko K, Hannuksela M, Maibach H, editors. Skin reactions to drugs. Boston: CRC Press; 1998, p. 21-2 3 Morimoto K, Kawada A, Hiruma M, Ishibashi A, Banba H: Photosensitivity to simvastatin with an unusual response to photopatch and photo tests. Contact Dermatitis 1995; 33: 274 4 Rodriguez Graados TM, De La Torre C, Cruces MJ, Pineiro G: Chronic actinic dermatitis due to simvastatin. Contact Dermatitis 1998; 38: 294 5 Swedis (The Swedish Drug Information System) 6 Sertraline. Drugdex(R) System; Micromedex, Inc., Englewood, Colorado (Edition expires 3/2001) 7 Toll P, Gonzalez-Castro J, Campo-Voegeli A, Azon A, iranzon P, Lecha M, Herrero C: Subacute cutaneous lupus erythematosus associated with cinnarizine and thiethylperazine therapy. Lupus 1998; 7: 364-366 8 Perrot JL et al. Porphyria cutanea tarda induced by HMG CoA reductase inhibitors: simvastatin, pravastatin. Ann Dermatol Venereol 1994; 121: 817-9 (abstract)