Guidance on minimising photosensitivity / phototoxicity reactions between medication and sunlight. (v2 – October 2013)

Everyone should be protected from excess exposure to the sun by avoiding the sun at midday and covering up – to include wearing a hat and utilising appropriate sunscreen. Some medicines can sensitise patients to greater reaction to sunlight. These patients should be even more cautious in avoiding direct exposure to the sun, and they should always use a high factor sunscreen.

How likely are photosensitising reactions to occur? The table below identifies drugs that are known to have the potential to cause photosensitising reactions. Some of them, (mostly newer ones), have been evaluated regarding the likelihood of occurrence. In these cases the following words have been used to specify how many patients are likely to be affected: • very common: more than 1 in 10 • common: more than 1 in 100, but less then 1 in 10 • uncommon: more than 1 in 1000, but less than 1 in 100 • rare: more than 1 in 10000, but less than 1 in 1000 • very rare: less than 1 in 10000

Please note, however, that these data mostly stem from voluntary reporting systems, which may be biased and inaccurate 1. This means that drugs for which no data exist cannot be assumed to be less likely to cause a reaction when the patient is exposed to sunlight. Where data are more reliable, drugs are required to carry a cautionary label: “Avoid exposure of skin to direct sunlight or sun lamps”.

Which drugs are involved? Major drug groups that can be expected to cause photosensitivity are: phenothiazine- based antipsychotics (chlorpromazine, thioridazine)2, sulfonamides, tetracyclines (such as doxycycline) 2, and quinolone antibacterials. Some diuretics, amiodarone 2 and some anti-inflammatory drugs have also been associated with these types of reaction 1.

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What is the worst that could happen? The following reactions can occur in response to drugs: phototoxicity, photoallergy, planus lichenoid reaction, pseudoporphyria, and subacute cutaneous lupus erythematosus 3. Phototoxic reactions usually present as an exaggerated response minutes to hours after exposure to the sun, whereas photoallergic reactions manifest after 24 to 48 hours, usually as a pruritic eczematous eruption 4. Mortality is rare and generally only occurs in individuals exposed to large doses of psoralens, (a specialist drug used to treat psoriasis not listed in the table below), and large amounts of sunlight. Even so, drug-induced photosensitivity can cause significant morbidity in some individuals, who must severely limit their exposure to natural or artificial sunlight, (e.g. in persistent light reactivity after photoallergy).

It has also been suggested that prolonged exposure to photosensitising drugs has carcinogenic potential 3. In most patients, however, the prognosis is excellent, once the offending agent has been removed, although complete resolution of the photosensitivity may take several weeks, or even several months with some compounds.

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DRUG CLASS GROUP DRUGS FREQUENCY- IF REPORTED ACE inhibitors 5 Losartan 6 Not known 6 2 and ARBs 6 Valsartan Reports Lisinopril 6 Not known Quinapril Reports 2 Captopril 5 Very rare 6 Fosinopril 6 Reports 1 Enalapril 6 One case report 2; part of complex syndrome 6 Ramipril 6 One case report 2; very rare 6 Antibiotics Quinolones 2,5 Moxifloxacin 6 Ciprofloxacin 6 Rare 6 Levofloxacin 6 Very rare Nalidixic acid BNF cautionary label Ofloxacin 6 Very rare, BNF cautionary label 5,6 Sulphonamides Co-trimoxazole Very rare Tetracyclines 5 Azithromycin6 Uncommon Lymecycline 6 Not known Oxytetracycline 6 Not known Demeclocycline BNF cautionary label Doxycycline Common, BNF cautionary label Minocycline Rare. Reports 6 Tetracycline Reports; unknown 6 Others Gentamicin Isoniazid 1 Reports Nitrofurantoin Trimethoprim 5,6 Antidepressants Tricyclics 5 Amoxapine Amitriptyline 6 6 Clomipramine 2,6 - Common Desipramine Doxepin 6 Reports Imipramine 2,6 Lofepramine 6 Nortriptyline 6 Others St John’s Wort Venlafaxine 2,5,6 Reports Phenelzine 2 SSRIs 2,5 Citalopram Uncommon 6 Escitalopram Fluoxetine Rare 6 Fluvoxamine Rare 6 Paroxetine Very rare 6 Sertraline Rare reports 6 Antidiabetics Sulfonylureas 6 Glimepiride 6 Not known 6 2 (oral) Glibenclamide Reports Gliclazide 6 Glipizide 6 Rare 5 Antiepileptics Carbamazepine 2 very rare 5,6 Lamotrigine Phenobarbital 6 reports Phenytoin Itraconazole 2,5,6 Antifungals Reports Terbinafine Very rare 6, rare 5 Voriconazole 2 Common 5 Antihistamines 5 Chlorpheniramine 6 Cyproheptadine Reports Diphenhydramine (2) Loratadine

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Antimalarials Malarone Unknown 6 Chloroquine and 6 hydroxychloroquine Rare 5 Mefloquine Pyrimethamine reports 1,2 Quinine 5,6 Antineoplastics Azathioprine 6 Reports 1 Reports 2 Hydroxyurea () 5 - Imatinib 5 - Common 5 6 6 - Uncommon 6 Reports 2 5,6 Common – but not real photosensitivity 2 Vinblastine One case report 2 Antipsychotics 5 Sulpiride 6 6 Butyrophenones Haloperidol Reports 1 rare 5 Phenothiazines 2 Chlorpromazine 5,6 BNF cautionary label Fluphenazine 6 Pipotiazine 6 Prochlorperazine 1,6 Reports Promethazine 1 Trifluoperazine 6 Flupentixol 2,6 Thioxanthenes Reports Zuclopenthixol 6 Atypical Aripiprazole 6 Frequency not known 6 2 5,6 antipsychotics Olanzapine Uncommon Clozapine 2 Reports

Alprazolam 2 Anxiolytics Reports Chlordiazepoxide Diuretics Acetazolamide Reports 1 rare 5,6 Amiloride Reports 1 Bendroflumethiazide 5,6 Uncommon Bumetanide 5 Reports Hydrochlorothiazide 5 Common Indapamide 2,5,6 Reports Furosemide 2,5,6 Reports Spironolactone 6 Reports 1 Triamterene 2 Reports 1,2 rare 5 NSAIDs 5 Indometacin 6 2,6 Rare Diclofenac 5,6 BNF cautionary label Ibuprofen 2,6 Uncommon Ketoprofen 6 Reports Mefenamic acid 6 Reports 1 Naproxen 2,6 Very rare Piroxicam 2,6 Reports 2,5 Isotretinoin 6 Very rare, BNF cautionary label Acitretin BNF cautionary label BNF cautionary label Adapalene Other drugs Aciclovir Common 6 6 Alendronate Rare 2,5 Amiodarone Very common, BNF cautionary label Atorvastatin 2 Reports Auranofin BNF cautionary label Calcipotriol 6 Very rare

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Clopidogrel (2) Reports Coal tar 5 Reports Corticosteroids Reports 1 Dapsone 2 One report Diltiazem 2,5 Uncommon; not known 6 Disopyramide Reports 1 Fibrates 2 Reports. Uncommon 5 Hydralazine Reports 1 Leflunomide 2 Reports Mesalazine 2 Reports Metoprolol 6 Very rare Nifedipine 2,5 and other CCBs, including 1 5 Reports - rare amlodipine 6 and felodipine 6 Oral contraceptives (oestrogens and Reports progestagens) 2 Oxybutinin 6 Reports Oxycodone 6 Rare Para-amino-benzoic Reports acid (preservative) Pimecrolimus topical BNF cautionary label Pravastatin 2 Reports Proton pump inhibitors 6 omeprazole, Rare lansoprazole Quinidine 2 Reports Ranitidine 2 Reports Simvastatin Reports 1 Sodium aurothiomalate BNF cautionary label Sulfasalazine Reports 1 – uncommon 5 Tacrolimus BNF cautionary label; uncommon 6 Vardenafil 6 Rare Voriconazole BNF cautionary label Zaleplon 6 Uncommon

With groups of drugs please assume that all members cause photosensitivity unless stated otherwise.

Please note that this list is not exhaustive. Consult your local pharmacy team or Medicines Information department for specific information

References: 1. Moore DE. Drug-Induced Cutaneous Photosensitivity. Drug Safety 2002; 25 (5): p. 345- 372. Available from http://www.ncbi.nlm.nih.gov/pubmed/12020173?dopt=Abstract (accessed 18 march 2013) 2. Drucker AM, Rosen CF. Drug-Induced Photosensitivity. Drug Safety 2011; 34(10):821-837. Accessed 21 st August 2013. 3. Zhang, A., Y., Craig, A., E. 2007. Drug-Induced Hypersensitivity. [Online] (Updated 19 March 2007) Available at: http://emedicine.medscape.com/article/1049648-print [accessed 29 April 2009] 4. MedicinesComplete © Pharmaceutical Press. 2013. Martindale: The Complete Drug Reference. [Online] Drug-induced photosensitivity (Latest modification 4-Feb-2008) Available at: http://www.medicinescomplete.com [Accessed 18 March 2013]. 5. BNF. Online edition. Individual monographs. 6. Datapharm Communications Ltd. 2013. electronic Medicines Compendium. [Online] Available at: http://emc.medicines.org.uk Individual monographs. [first accessed 18 March 2013].

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Principal authors: Josef Elias – Clinical Pharmacist Gus Fernandez – Clinical & MI Pharmacist

Supported by: Jed Hewitt – Chief Pharmacist (Governance & Professional Practice)

Guidance issued: March 2010

Review & update: October 2013

Date of next review: October 2015

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