Drug-Induced Photosensitivity

Full update August 2019

Drug-induced photosensitivity reactions can vary in presentation and are usually either phototoxic or photoallergic, although it is often not possible to determine which.1-3 Photoallergy is a rare, immunological response, which is not dose-related and occurs after repeat exposure to a drug. Photoallergy occurs when light causes a drug to act as a hapten, triggering a hypersensitivity response which often manifests as a pruritic and eczematous rash.1,4-6 Phototoxic reactions are chemically induced reactions which occur when the drug absorbs UVA light and causes cellular damage. This reaction can be seen with initial exposure to a drug, may be dose-dependent, and doesn’t demonstrate cross-sensitivity. It usually has rapid onset and manifests as an exaggerated sunburn. This reaction will be seen only on skin areas exposed to the sun.1,4-6 The best way to manage drug-induced photosensitivity is prevention. Patients taking these drugs should be counseled to minimize sun exposure and to use broad-spectrum sunscreens when sun exposure cannot be avoided. We have a patient education handout to help patients choose and use sunscreens correctly, Staying Safe in the Sun. When appropriate, taking a medication at bedtime instead of in the morning may be useful as a preventive strategy.2 If a reaction does occur, the offending agent should typically be stopped (if not possible, lowering the dose may help) and a topical or oral corticosteroid can be used for treatment.1,3 It may take weeks to months for reactions to fade.7

The following table lists drugs that have been associated with photosensitivity. Reactions can be difficult to predict. The most common reported medication classes to cause photosensitivity are antimicrobials, NSAIDs, and cardiovascular drugs. It is important to note that many of the drugs listed were included based on information from case reports. Due to factors such as underreporting, it is not possible to estimate the true incidence of photosensitivity with individual agents.1,3 As such, this table may not be all-inclusive. Drugs that are considered more potent photosensitizers are indicated in bold type.1,4

Drug Class

Specific Agentsa

Comments

ANTIBIOTICS

Fluoroquinolones

ciprofloxacin

levofloxacin

moxifloxacin

nalidixic acid

ofloxacin

Fluoroquinolones seem to cause reactions to varying degrees, dependent on their chemical structure. For example, ciprofloxacin and levofloxacin appear to have less risk of photosensitivity.7

The reaction with fluoroquinolones may present as a sunburn or as increased skin fragility and blistering.3,7

Tetracyclines

demeclocycline

doxycycline

tetracycline

Reaction with doxycycline is dose-dependent.1,7

Minocycline is not typically considered to be a significant cause of photosensitivity.1,7

Other Antibiotics

ceftazidime

cefotaxime

dapsone

gentamicin

isoniazid

nitrofurantoin

pyrazinamide

sulfamethoxazole

sulfisoxazole

trimethoprim

Sulfonamides are associated with photosensitivity in 5% to 10% of treated patients.8

ANTICONVULSANTS

carbamazepine

lamotrigine

phenobarbital

phenytoin

None

ANTIDEPRESSANTS

Tricyclics1,4

amitriptyline

amoxapine

clomipramine

desipramine

doxepin

imipramine

nortriptyline

protriptyline

trimipramine

None

Selective Serotonin Reuptake Inhibitors (SSRIs)1

citalopram

escitalopram

fluoxetine

 

fluvoxamine

paroxetine

sertraline

SSRIs are not considered to be potent photosensitizers.1

Other Antidepressants1,2,11

mirtazapine

phenelzine

venlafaxine

Some antidepressants within the same classes (e.g., the serotonin noradrenaline reuptake inhibitors [SNRIs] duloxetine and desvenlafaxine) do not appear to cause photosensitivity.7

ANTIFUNGALS1,4,7

griseofulvin

itraconazole

ketoconazole

terbinafine

voriconazole

Voriconazole may increase the risk of melanoma and non-melanoma skin cancers.3

Reports of reactions with voriconazole typically involve long-term use.1

Fluconazole has not been reported to cause photosensitivity.1

ANTIHISTAMINES1,4

cyproheptadine

brompheniramine

diphenhydramine

promethazine

Reactions have been seen with both topical and systemic administration of antihistamines.

ANTIMALARIALS1,7

atovaquone/proguanil

chloroquine

hydroxychloroquine

mefloquine

pyrimethamine

quinidine

quinine

None

ANTIPLATELETS1

Clopidogrel

None

ANTIPSYCHOTICS

Phenothiazines1,4

chlorpromazine

fluphenazine

perphenazine

prochlorperazine

promethazine

thioridazine

trifluoperazine

Chlorpromazine is one of the most frequently reported drugs associated with phototoxicity.9

Other Antipsychotics1

aripiprazole

clozapine

haloperidol

olanzapine

risperidone

thiothixene

Atypical antipsychotic drugs appear to be less photosensitizing than phenothiazines.7

ANTIRETROVIRALS1,7

efavirenz

tenofovir

Photosensitive reactions can occur in patients with HIV in the absence of medications, making it difficult to associate photosensitivity with HIV medications.7

CARDIOVASCULAR AGENTS

Antihypertensives1,4,7

amlodipine

captopril

diltiazem

enalapril

fosinopril

hydralazine

methyldopa

nifedipine

olmesartan

quinapril

ramipril

valsartan

None

Statins1,4

atorvastatin

pravastatin

simvastatin

Photosensitivity is not a common reaction of statins.7

Other Cardiovascular Agents1,4

amiodarone

disopyramide

fenofibrate

quinidine

Incidence with amiodarone of 10% to 50% has been seen.1,2 Phototoxicity has rarely been reported with dronedarone.11,12

Reactions with amiodarone may take months to resolve after discontinuation of the drug.1 The reaction can present as prickling or burning during exposure to UV radiation, immediate erythema, edema or urticaria with higher doses, and possibly delayed erythema, hyperpigmentation, or blue-grey pigmentation.3,7

CHEMOTHERAPY AGENTS1,4

bicalutamide

capecitabine

crizotinib

dacarbazine

epirubicin

fluorouracil

flutamide

hydroxyurea

imatinib

methotrexate

paclitaxel

procarbazine

vandetanib

vemurafenib

vinblastine

Capecitabine (fluorouracil prodrug) may be less photosensitizing than fluorouracil. Capecitabine may be a possible alternative for patients not able to tolerate photosensitivity reactions with fluorouracil.7

Vincristine is an analog of vinblastine; however, it does not appear to cause photosensitivity.7

Vemurafenib causes photosensitivity reactions in 35% to 65% of patients.7

DIETARY SUPPLEMENTS AND VITAMINS10

bergamot

bitter orange

chlorella

dong quai

gossypol

haronga

St. John’s wort
vitamin B6
(pyridoxine)

Limited reporting of adverse reactions with supplements makes this listing incomplete.

Citrus fruits (e.g., bergamot, lemon, lime) contain psoralens which can cause photosensitivity reactions with topical use or exposure.10,14

Also see our Natural Medicines chart (in the “Tools” section) for more sensitizers.

DIURETICS

Thiazides1,4

chlorthalidone

chlorothiazide

hydrochlorothiazide

methyclothiazide

metolazone

The reaction with thiazide diuretics may present as dermatitis or a sunburn-type reaction.3

Other Diuretics1,4

acetazolamide

amiloride

ethacrynic acid

furosemide

spironolactone

triamterene

Furosemide reactions typically include bullous eruptions.7

HORMONAL AGENTS1,4

ethinyl estradiol

corticosteroids

Photosensitivity has been reported with both oral and topical (patch) ethinyl estradiol contraceptives.7

HYPOGLYCEMIC AGENTS1,4

chlorpropamide

gliclazide

glimepiride

glipizide

glyburide

metformin

tolazamide

tolbutamide

None

IMMUNOSUPPRESSANTS4

azathioprine

Immunosuppressive therapy with azathioprine is associated with an increased risk of skin cancer in patients with kidney transplants.4

MISCELLANEOUS7

esomeprazole

pantoprazole

pirfenidone

ranitidine

A case of esomeprazole photosensitivity resolved on discontinuation of the drug and did not recur when ranitidine was initiated.7

NSAIDs1,4

celecoxib

diclofenac

diflunisal

etodolac

indomethacin

ketoprofen

mefenamic acid

nabumetone

naproxen

oxaprozin

piroxicam

sulindac

NSAIDs seem to cause reactions to varying degrees.1

The reaction with NSAIDs can include increased skin fragility and blistering.3

Ibuprofen is not considered a potent photosensitizer, with only rare case reports of reactions.7

RETINOIDS, oral

etretinate

There is controversy concerning whether or not oral retinoids cause photosensitivity. Etretinate does seem to cause photosensitivity, with a reaction of increased susceptibility to sunburn. Isotretinoin does not seem to cause photosensitivity.1,2

RHEUMATOID ARTHRITIS TREATMENTS1,4

gold salts

leflunomide

methotrexate

sulfasalazine

None

SEDATIVES4

alprazolam

chlordiazepoxide

Alprazolam has been reported to cause pruritic erythema on sun-exposed skin.7

TOPICAL AGENTS4

aminolevulinic acid

coal tar

fluorouracil

hexachlorophene

methoxsalen

psoralens

tazarotene

tretinoin

Data are conflicting regarding whether benzoyl peroxide causes photosensitivity, but it should be used with a sunscreen since sunlight may worsen skin irritation.13

a.

It is important to note that many of the drugs listed in this chart were included based on information from case reports. Due to factors such as underreporting, it is not possible to estimate the true incidence of photosensitivity with individual agents. 1,3 As such, this table may not be all-inclusive.

Project Leader in preparation of this clinical resource (350801): Annette Murray, BScPharm

References

  1. Drucker AM, Rosen CF. Drug-induced photosensitivity: culprit drugs, management and prevention. Drug Saf 2011;34:821-37.
  2. Manage drug-induced photosensitivity through prevention and discontinuation of the causative agent once an event has occurred. Drug Ther Perspect 2012;28:20-3.
  3. Dawe RS. Ibbotson SH. Drug-induced photosensitivity. Dermatol Clin 2014;32:363-8.
  4. Moore DE. Drug-induced cutaneous photosensitivity: incidence, mechanism, prevention and management. Drug Saf 2002;25:345-72.
  5. Allen JE. Drug-induced photosensitivity. Clin Pharm 1993;12:580-7.
  6. Morison WL. Clinical practice. Photosensitivity. N Engl J Med 2004;350;1111-7.
  7. Blakely KM, Drucker AM, Rosen CF. Drug-induced photosensitivity – an update: culprit drugs, prevention and management. Drug Saf 2019;827-47.
  8. Gupta S, Singh R, Ashwlayan VD, Hans RK. Drug induced phototoxicity. Pharma Science Monitor 2011;2:117-30.
  9. Kim WB, Shelley AJ, Novice K, et al. Drug-induced phototoxicity: a systematic review. J Am Acad Dermatol 2018;79:1069-75.
  10. Jellin JM, Gregory PJ, et al. Natural Medicines. www.naturalmedicines.com. Accessed on July 11, 2019. © 2001-2019 by Therapeutic Research Center. Terms of Use: https://naturalmedicines.therapeuticresearch.com/terms-of-use.aspx.
  11. Clinical Pharmacology powered by ClinicalKey. Tampa (FL): Elsevier. 2019. http://www.clinicalkey.com. (Accessed July 11, 2019).
  12. Ladizinski B, Elpern DJ. Dronedarone-induced phototoxicity. J Drugs Dermatol 2013;12:946-7.
  13. Federal Register. Classification of benzoyl peroxide as safe and effective and revision of labeling to drug facts format; topical acne drug products for over-the-counter human use; final rule. March 4, 2010. https://www.federalregister.gov/articles/2010/03/04/2010-4424/classification-of-benzoyl-peroxide-as-safe-and-effective-and-revision-of-labeling-to-drug-facts. (Accessed July 11, 2019).
  14. Quaak MS, Martens H, Hassing RJ, et al. The sunny side of lime. J Travel Med 2012;19:327-8.

Cite this document as follows: Clinical Resource, Drug-Induced Photosensitivity. Pharmacist’s Letter/Prescriber’s Letter. August 2019.

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