Drug-Induced Photosensitivity

DRUG-INDUCED PHOTOSENSITIVITY
Drug-induced photosensitivity: cutaneous adverse events due to exposure to a drug and either ultraviolet (UV) or visible radiation. Reactions can be classified as either photoallergic or phototoxic drug eruptions, though distinguishing between the two reactions can be difficult and usually does not affect management. The following criteria must be met to be considered as a photosensitive drug eruption: • Occurs only in the context of radiation • Drug or one of its metabolites must be present in the skin at the time of exposure to radiation • Drug and/or its metabolites must be able to absorb either visible or UV radiation
		Photoallergic drug eruption	Phototoxic drug eruption
Description		Immune-mediated mechanism of action. Response is not dose-related. Occurs after repeated exposure to the drug	More frequent and result from direct cellular damage. May be dose-dependent. Reaction can be seen with initial exposure to the drug
Incidence		Low	High
Pathophysiology		Type IV hypersensitivity reaction	Direct tissue injury
Onset		>24hrs	<24hrs
Clinical appearance		Eczematous	Exaggerated sunburn reaction with erythema, itching, and burning
Localization		May spread outside exposed areas	Only exposed areas
Pigmentary changes		Unusual	Frequent
Histology		Epidermal spongiosis, exocytosis of lymphocytes and a perivascular inflammatory infiltrate	Necrotic keratinocytes, predominantly lymphocytic and neutrophilic dermal infiltrate
PHOTOSENSITIZING DRUGS¹
Generic	Brand	Type of Reaction	Notes
ANTIMICROBIALS
Antibiotics: Beta-Lactams
cefotaxime	—	Photodistributed telangiectasia
ceftazidime	Fortaz, Tazicef	Increased susceptibility to sunburn
Antibiotics: Fluoroquinolones
ciprofloxacin	Cipro	Mild phototoxic potential. Photo-induced purpura have been reported. Persistent sequalae from phototoxicity in lung-transplant recipient on long-term immunosuppressive therapy	Typically a return to baseline 1wk after drug discontinuation
levofloxacin	—	Mild phototoxic potential. Photo-induced purpura have been reported.
moxifloxacin	Avelox	More photostable and least phototoxic
ofloxacin	—	Moderate to severe sunburn reactions
Antibiotics: Tetracyclines
doxycycline²	Doryx, Vibramycin	Mild sunburn-like reactions with erythema and burning in sun-exposed areas; photodermatitis; solar urticaria, actinic granuloma, lichenoid reactions, nail dystrophy with photo-induced onycholysis, dyschromia. Nail effects can be delayed in presentation up to 2wks following sun exposure	Severe doxycycline-induced photo-onycholysis can occur at doses as low as 20mg/day in children
minocycline	Minocin, Solodyn		Generally not considered to be significant cause
tetracycline²	—
Antibiotics: Others
dapsone	—	Phototoxic and photoallergic drug eruptions
trimethoprim	—	Photosensitivity
Antifungals
griseofulvin	—		Not a potent photosensitizer. UVA implicated in photosensitivity
itraconazole	Sporanox, Tolsura	Photosensitivity in predominantly phototoxic pattern. Erythema, edema, vesicles in sun-exposed areas	Side effects reported following 5-day course oral therapy for candidiasis
ketoconazole	—	Photodermatitis
terbinafine	—	Solar urticaria
voriconazole²	Vfend	Classic phototoxicity patterns, cheilitis, pseudoporphyria, photo-onycholysis	Second most commonly reported culprit in phototoxicity reactions. More likely in patients receiving long-term prophylactic therapy. Photosensitive eruptions occur months after drug initiation. Acute photodermatitis usually resolves upon discontinuation, however, photoaging and development of melanoma and squamous cell carcinoma in previously affected areas have been reported (esp. in children).
Antimalarials
atovaquone/ proguanil	Malarone	Blisters and skin sloughing on sun-exposed areas	Occurred within hours of exposure and resolved within days of discontinuation. Confirmed by photopatch testing.
chloroquine	—	Drug-induced photodermatoses	Also used for photoprotective effects in photosensitivity conditions (eg, polymorphous light eruption, SLE). Occur within days to weeks of starting drug and resolve after discontinuation.
hydroxychloroquine	Plaquenil	Drug-induced photodermatoses
quinine	Qualaquin	Photoallergic and phototoxic reactions. Photosensitive dermatosis (edematous, eczematous, lichenoid); photo-onycholysis	Routinely confirmed by photopatch testing
Antiretrovirals
efavirenz	Sustiva	Photosensitive eruptions (eg, polymorphous light eruption, porphyria cutanea tarda, actinic prurigo, chronic actinic dermatitis, photosensitive granuloma annulare, lichenoid photoeruption)	Photosensitive eruptions can occur in HIV patients, independent of drug
tenofovir	Vemlidy, Viread
Antituberculosis
isoniazid	—	Photosensitive dermatoses, lichenoid eruption	Confirmed by photopatch and re-challenge testing
pyrazinamide	—	Photosensitive dermatoses	Confirmed by re-challenge testing
CARDIOVASCULAR AGENTS
Antihypertensives: ACE Inhibitors
enalapril	Vasotec	Photosensitivity
quinapril	Accupril
ramipril	Altace
Antihypertensives: Angiotensin Receptor Blockers
candesartan	Atacand	Photosensitivity
irbesartan	Avapro
losartan	Cozaar
olmesartan	Benicar
telmisartan	Micardis
valsartan	Diovan
Antihypertensives: Diuretics
furosemide	Lasix	Bullous eruptions (mimicking Brunsting-Perry-type presentation of localized bullous pemphigoid)
hydrochlorothiazide²	—	Exaggerated sunburn reactions, eczematous lesions in photodistributed pattern, lichenoid eruptions, photoleukomelanoderma	Chronic eczematous photosensitivity reported lasting months to years after discontinuation
indapamide	—	Photo-onycholysis
triamterene	Dyrenium	Photosensitivity	Confirmed by photopatch testing
Antihypertensives: Calcium Channel Blockers
amlodipine	Norvasc	Photodistributed facial telangiectasia	May cross react with nifedipine
diltiazem	Cardizem	Photodistributed hyperpigmentation, photosensitive dermatitis
nifedipine	Procardia	Photodistributed facial telangiectasia, photodermatitis	May cross react with amlodipine
Antihypertensives: Others
methyldopa	—	Photosensitivity
Antiarrhythmics
amiodarone²	—	Burning/tingling sensation in sun-exposed skin followed by development of erythema and eczema, pseudoporphyria; blue-grey hyperpigmentation on sun-exposed areas	Hyperpigmentation seen in long-term, high-dose therapy. Resolves within months of discontinuation; pigmentation fades over 1-2yrs.
amiodarone²	Nexterone
dronedarone	Multaq	Photosensitivity	Significantly less phototoxic than amiodarone
quinidine	—	Eczematous dermatitis, lichenoid eruption, livedoid purpuric eruption, photoallergic reaction
Cholesterol-Lowering Agents
atorvastatin	Lipitor	Edematous erythema on sun-exposed areas
fenofibrate	Tricor	Eczematous photosensitivity, lichenoid photosensitivity
pravastatin	—	Photodistributed erythema multiforme
simvastatin	Zocor	Persistent photodistributed dermatitis, photodistributed erythema multiforme
CHEMOTHERAPY
bicalutamide	Casodex	Photosensitivity	Seen in patients with prostate cancer
capecitabine	Xeloda	Photodistributed lichenoid eruptions	Less photosensitizing than fluorouracil. Alternative treatment for those unable to tolerate fluorouracil
crizotinib	Xalkori	Phototoxicity
dacarbazine	—	Photosensitive eruptions	Can switch to temozolomide if unable to tolerate
doxorubicin	Doxil	Photosensitivity
epirubicin	Ellence	Bullous eruption
erlotinib	Tarceva	Photosensitivity
fluorouracil	—	Photosensitive eruptions, enhanced sunburn reactions, photodistributed hyperpigmentation, polymorphous light eruption-like reactions
flutamide	—	Photosensitivity	Seen in patients with prostate cancer
hydroxyurea	Droxia, Hydrea	Photodistributed dermatitis, photodistributed granulomatous rash	Seen in patients with chronic myeloid leukemia
imatinib	Gleevec	Exaggerated sunburn reactions, photo-induced dermatitis, pseudoporphyria	Seen in patients treated for chronic myelogenous leukemia. Dermatitis may resolve upon drug withdrawal and recur upon rechallenge
paclitaxel	Abraxane	Photodistributed erythema multiforme, onycholysis	Photosensitive reactions also reported for nab-paclitaxel
vandetanib	Caprelsa	Photodistributed erythematous, vesiculobullous eruption, erythema multiforme-like lesions, pigmentation in photo-exposed areas	Seen in patients treated for thyroid, lung, and hepatocellular carcinoma
vemurafenib²	Zelboraf	Phototoxicity	Common culprit
vinblastine	—	Photosensitivity
NSAIDS
celecoxib	Celebrex	Photoallergic reactions and pseudoporphyria
diclofenac	Arthrotec	Photo-onycholysis
indomethacin	Indocin	Pseudoporphyria, erythema multiforme, lichenoid eruptions
meclofenamate	—
nabumetone	—
naproxen²	Aleve	Pseudoporphyria, erythema multiforme, lichenoid eruptions	Most photosensitizing potential
oxaprozin	Daypro	Pseudoporphyria, erythema multiforme, lichenoid eruptions
piroxicam²	Feldene	Vesiculobullous, eczematous, lichenoid reactions
sulindac	—	Pseudoporphyria, erythema multiforme, lichenoid eruptions
PSYCHOTROPIC AGENTS
Antidepressants
citalopram	Celexa	Photodistributed hyperpigmentation
clomipramine	Anafranil	Photoallergy
escitalopram	Lexapro	Erythroderma on sun-exposed areas
fluoxetine	Prozac	Erythema, blisters
fluvoxamine	—	Photosensitivity
imipramine	Tofranil	Photodistributed erythema, blue-grey hyperpigmentation in photodistributed areas	Hyperpigmentation seen in long-term use
paroxetine	Paxil	Photosensitivity, photodistributed granuloma annulare
phenelzine	Nardil	Clinical photosensitivity
sertraline	Zoloft	Macular erythematous photoallergic reaction
venlafaxine	Effexor XR	Photodistributed telangiectasia
Antipsychotics
aripiprazole	Abilify	Photo-onycholysis
chlorpromazine²	—	Exaggerated sunburn reactions, lichenoid reactions, bullous eruptions; photodistributed slate-grey to violaceous hyperpigmentation	Hyperpigmentation seen in long-term, high-dose therapy. Routinely confirmed by photopatch testing.
clozapine	Clozaril	Photosensitivity, vasculitis, erythema multiforme, skin pigmentation
haloperidol	Haldol	Photosensitive dermatitis
olanzapine	Zyprexa	Photo-onycholysis
risperidone	Risperdal	Photosensitivity
thioridazine²	—	Photodistributed slate-grey to violaceous hyperpigmentation	Seen in long-term, high-dose therapy
Anxiolytics
alprazolam	Xanax	Pruritic erythema in sun-exposed areas
chlordiazepoxide	—	Photo-induced eczematous eruption
OTHERS
carbamazepine	Tegretol	Photosensitive eczematous eruptions, lichenoid eruptions	Carbamazepine-induced facial burns occured in one patient due to prolonged use of a photocopier
clopidogrel	Plavix	Lichenoid photodistributed eruption
diphenhydramine	Benadryl	Photosensitivity
eculizumab	Soliris	Photosensitivity
esomeprazole	Nexium	Photosensitive dermatitis	Resolved upon discontinuation
ethinyl estradiol	—	Photosensitive eruptions, erythematous vesicular eruptions
glyburide	Diabeta, Glynase	Eczematous photodermatitis
isotretinoin	Absorica, Amnesteem		No clinical or experimental evidence confirming isotretinoin-induced photosensitivity
leflunomide	Arava	Photosensitivity
mesalamine	Lialda, Pentasa
mesna	Mesnex
metformin	—	Erythematous and eczematous photosensitivity eruptions
pantoprazole	Protonix	Photosensitivity
pirfenidone	Esbriet	Exfoliative erythema, photoleukomelanoderma
ranitidine	—	Papulosquamous eruption on sun-exposed skin	Normalization upon discontinuation. No recurrence upon re-initiation
sitagliptin	Januvia	Prolonged photosensitive eruption
tocilizumab	Actemra	Photosensitivity
PREVENTION AND MANAGEMENT
• Caution patients of the potential reaction for drugs considered to be potent photosensitizers; monitor. • Emphasize sun avoidance and sun protection upon treatment initiation. • Discontinue offending drug once diagnosis of drug-induced photosensitivity is made. Implement secondary preventive measures (eg, sun avoidance esp. during peak daylight hours, use of sun protective clothing and sunscreens with both UVA and UVB protection) if drug discontinuation is not possible. • Administer medication in the evening if appropriate. • Use of topical or systemic corticosteroids may be helpful to treat drug-induced photosensitive eruptions in symptomatic patients.
NOTES
Key: ACE = angiotensin-converting enzyme; SLE = systemic lupus erythematosus ¹ Drugs that have been reported in medical literature to cause clinical photosensitivity are listed. Most of this literature consist of case reports and case series. Due to underreporting, it is difficult to ascertain the true incidence of photosensitivity reactions. Topically administered drugs that cause photosensitivity have been excluded, as well as drugs that cause photosensitivity as part of their desired mechanism of action. ² Considered to be potent and common causes of photosensitivity. Not an inclusive list of medications and/or official indications. Please see drug monograph at www.eMPR.com and/or contact company for full drug labeling.
REFERENCES
Adapted from Blakely KM, Drucker AM, Rosen CF. Drug-Induced Photosensitivity – An Update: Culprit Drugs, Prevention and Management. Drug Safety. 2019; 42:827-847. https://doi.org/10.1007/s40264-019-00806-5. (Rev. 11/2022)

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