Guidance on minimising photosensitivity and phototoxicity reactions between medication and sunlight Version 3

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, amiodarone2 and some anti-inflammatory drugs have also been associated with these types of reaction1.

If you require this document in an alternative format, i.e. easy read, large text, audio, Braille or a community language please contact the pharmacy team on 01243 623349 (Text Relay calls welcome)

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 erythematosus3. Phototoxic reactions usually present as an exaggerated sunburn response minutes to hours after exposure to the sun, whereas photoallergic reactions manifest after 24 to 48 hours, usually as a pruritic eczematous eruption4. 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 potential3. 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 inhibitors5 Losartan6 Not known 6 Valsartan6 Reports2 and ARBs 6 Lisinopril As symptom complex 2 6 Quinapril Reports Not known 5 6 Captopril Very rare Fosinopril6 Reports1

Enalapril6 One case report2; part of complex

syndrome6 Perindopril6 Uncommon6 Ramipril6 One case report2; very rare6 Antibiotics Quinolones2,5 Moxifloxacin6 Reports6 Ciprofloxacin6 Rare6 6 Levofloxacin Reports Nalidixic acid BNF cautionary label- Rare Ofloxacin5 Very Rare, BNF cautionary label 5,6 Sulphonamides Co-trimoxazole Very rare Tetracyclines5 Azithromycin6 Uncommon6 6 Lymecycline Not known Oxytetracycline6 Rare Demeclocycline BNF cautionary label- Common Doxycycline Common, BNF cautionary label 6 Minocycline Rare. Reports Tetracycline Reports; unknown6 6 Others Tigecycline Reports Gentamicin Reports1 2 Isoniazid Reports Nitrofurantoin Reports Trimethoprim5,6 Rare6 Tricyclics Amitriptyline6 Frequency not known5 Antidepressants 2,6 6 Clomipramine Frequency not known Doxepin6 Not known5 Imipramine2,6 Reports6 Frequency not known5 Lofepramine6 Reports Nortriptyline5,6 Rare Others St John’s Wort Reports ? Venlafaxine2,5,6 Uncommon 2 Phenelzine Reports SSRIs2,5 Citalopram Uncommon6 2 Escitalopram Unclear Duloxetine6 Rare Fluoxetine Rare6 Fluvoxamine Rare6 Paroxetine Very rare6

Sertraline Frequency not known, reports6 Antidiabetics Sulfonylureas6 Glimepiride6 Not known6 2 (oral) Glibenclamide Reports Gliclazide6 Not known Glipizide6 Not known6 Antiepileptics Carbamazepine2 Very rare5,6 Lamotrigine Phenobarbital6 Reports Phenytoin 2,5,6 Itraconazole 6 Antifungals Reports, Not known

Ketoconazole 6 Not known Terbinafine Very rare5,6 Voriconazole2 Reports6 BNF Cautionary Label- Uncommon

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6 Antihistamines5 Alimemazine 6 Chlorphenamine Cyproheptadine6 Cyclizine6 Reports Desloratadine6 Not known Diphenhydramine(2) 6 Loratadine -Rare Cetirizine6 Not known6 Antimalarials Malarone Unknown6 Chloroquine and 6 hydroxychloroquine Rare5 Mefloquine Pyrimethamine reports 1,2 Quinine5,6 Antineoplastics Azathioprine6 Reports 1 Bortezomib Rare6 Capecitabine Uncommon6 Dasatinib Uncommon6 Doxorubicin6 Reports2 Epirubicin Uncommon6 Hydroxyurea 6 SPC warning to avoid sun exposure (hydroxycarbamide) Idelalisib Potential Risk6 Imatinib5 Common5 Lenalidomide Uncommon6 Paclitaxel6 Uncommon6 Pazopanib Uncommon6 Pentostatin Common6 Pixantrone Reports6 Fluorouracil6 Reports2Uncommon6 Methotrexate5,6 Uncommon Tioguanine Not known6 Vemurafenib Very Common6 Vinblastine One case report2 Antipsychotics5 Sulpiride6 Reports6 6 Butyrophenones Haloperidol Reports 1 rare5 Uncommon6 Phenothiazines2 Chlorpromazine5,6 BNF cautionary label, Not known6 Fluphenazine6 Pericyazine6 Pipotiazine6 Reports Prochlorperazine1,6 Promethazine1 Trifluoperazine6 Levomepromazine Reports Flupentixol2,6 Thioxanthenes Reports Zuclopenthixol6 Atypical Aripiprazole6 Frequency not known6 2 5,6 antipsychotics Olanzapine Uncommon Clozapine2 Reports Anxiolytics Alprazolam Not known6 Chlordiazepoxide Reports2 Diuretics Acetazolamide Reports 1 rare5,6 Amiloride Reports 1 Bendroflumethiazide5,6 Uncommon, Reports6 Bumetanide5 Reports Hydrochlorothiazide5 uncommon Indapamide2,5,6 Not known Furosemide2,5,6 Uncommon Spironolactone6 Reports 16 Triamterene2 Reports 1,2 rare5

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NSAIDs5 Indometacin6 Reports6 Celecoxib2,6 Rare Dexketoprofen Very Rare6 Diclofenac5,6 BNF cautionary label, Very Rare6 Flurbiprofen Reports6 Ibuprofen2,6 Reports Ketoprofen6 Reports , Not known6 Mefenamic acid6 Reports1 Naproxen2,6 Rare Piroxicam2,6 Infrequent Retinoids2,5 Isotretinoin6 Very rare6, BNF cautionary label Acitretin BNF cautionary label, Uncommon6 Alitretinoin BNF cautionary label Adapalene Other drugs Aciclovir Common6 6 Aceclofenac Very Rare 6 Acemetacin Very Rare Alendronate6 Rare Amiodarone2,5 Very common, BNF cautionary label Aprepitant Rare6 Atorvastatin2 Reports Benzydamine 6 6 Very rare hydrochloride Benzoyl peroxide and 6 Common clindamycin gel Bezafibrate6 Uncommon Bicalutamide6 Rare Botulinum toxin type A Uncommon6 Calcipotriol6 Reports Certolizumab Uncommon6 Ciprofibrate Very rare6 Clopidogrel(2) Reports Coal tar5 Reports Cobimetinib 6 Common hemifumarate Corticosteroids Reports 1 Dacarbazine Uncommon6 Dapsone2 One report Diltiazem2,5 Uncommon; not known6 Disopyramide Reports 1 Dronedarone Uncommon6 Eltrombopag Reports6 Esomeprazole Rare6 Etodolac6 Very Rare Felbinac Reports6 Fenofibrate Uncommon6 Flecainide Not known6 Fosaprepitant Rare6 Hydralazine Reports 1 Interferon alfa-2b Common6 Ketorolac Reports6 Leflunomide2 Reports Levothyroxine6 Reports6 Mercaptopurine Unknown6 Methyl aminolevulinate Uncommon6 Mesalazine2 Reports Metoprolol6 Very rare Nabumetone Uncommon6 Nicotine Reports6 2,5 Nifedipine and other 1 5 Reports - rare CCBs, including

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amlodipine6 and felodipine6 Human normal 6 Reports immunoglobulin Oral contraceptives (oestrogens and Reports progestagens)2 Omalizumab Uncommon6 Oxerutins Very Rare6 Oxybutinin6 Reports, Not known6 Oxycodone6 Common Para-amino-benzoic Reports acid (preservative) Pantoprazole Not known6 Peginterferon alfa-2a Common6 Pirfenidone Very Common6 Pimecrolimus topical BNF cautionary label Pitolisant Rare6 Pravastatin2 Reports Pyrazinamide Reports6 Proton pump inhibitors6 omeprazole, Rare lansoprazole Ranitidine2 Reports Ribavirin Common6 Romiplostim Uncommon6 Safinamide Uncommon6 Simvastatin Reports 1 Rare6 Simeprevir Common6 Sodium BNF cautionary label (irreversible aurothiomalate pigmentation in sun-exposed areas) Sulfasalazine Reports 1 – Frequency not known5,6 Tacrolimus BNF cautionary label; uncommon6 Tazarotene Not known6 Temozolomide Uncommon6 Tenoxicam Not known6 Tiaprofenic Acid Reports6 Tipranavir Reports6 Tolfenamic acid Very Rare6 Torasemide Very Rare6 Trandolapril Rare6 Valaciclovir Common6 Vardenafil6 Rare Verteporfin Common6 Zaleplon5 Uncommon 5-aminolevulinic acid Uncommon6

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. First accessed 21st August 2013. Accessed to review guideline: 20/11/16

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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 20/11/16]. 5. BNF. Online edition. Individual monographs. 6. Datapharm Communications Ltd. 2013. electronic Medicines Compendium. [Online] Available at: http://emc.medicines.org.uk Individual monographs. [Accessed 20/11/16].

Original authors: Josef Elias – Clinical Pharmacist Gus Fernandez – Clinical Pharmacist

Reviewed November 2016 by: Ellie Morton- Rotational Pharmacist Paulina Sajdak Orzechowska- Clinical Pharmacist

Supported by: Reviewed by the Medicine Information Department Western Sussex Hospitals NHS Foundation Trust November 2016

Version 1 issued: March 2010

Version 2 issued: October 2013

Version 3 issued: November 2016

Date of next review: November 2020

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