1. Photosensitising medications
some guff
Photosensitising medications
Arlene McGuire
Specialist Clinical Pharmacist
Dermatology and Allergy
Guys and St Thomas’ NHS Foundation Trust.

2. Learning Objectives What is drug induced photosensitivity?
Phototoxic Vs photoallergic reactions
Common Photosensitising drugs
Practice points – drug pharmacology/ elimination time/ half life
Brief Overview Psoralens

3. Photosensitivity An increase in skin reactivity to light.
This can be to ordinary light or a particular band of light (UVA, UVB or visible spectrum)
Can be due to a number of factors:
Disease states (e.g. Lupus)
Drugs
skin type

4. Drug Induced Photosensitivity
Cutaneous reactions due to combined effect chemical & Light
Chemicals absorb light similar to their natural wavelength
Photosensitising drugs are usually activated with wavelengths of UVA or visible light (UVB less of a problem)
Vibration energy transmitted to neighbouring molecules as heat energy.
Results in prickling, burning, erythema, sunburn

5. Drug Induced Photosensitivity
Excessive photoactivation of the chemical in the skin can result in Phototoxic or Photoallergic reactions
Phototoxic reactions (Direct damage to tissue - Energy Transmitted causes)
e.g. Oxygen atoms activated causing cell damage OR chemical binds to DNA & Proteins
Photoallergic (Immune mediated response)
Ultraviolet exposure changes the structure of the drug
Seen by the body's immune system as an invader (antigen).
Immune system initiates an allergic response - cause inflammation of the skin in the light-exposed areas

6. Phototoxic Vs Photoallergic reactions
Phototoxicity
Photoallergy
Incidence
High
Low
Agent
Exposure
Dose related
single exposure
Small amount
More than one
Onset
Minutes to hrs
24hrs to 72hrs
Distribution
Sun exposed skin only
All areas
Clinical characteristics
Sunburn, erythema,
Swelling, blistering
Eczematous, pruritic lesions
Immunological mediated No
Type IV immune reaction

7. Phototoxic Vs Photoallergic reactions
Photoallergy - oral sulfonamide
Phototoxicity - Phenothiazine

8. Phototoxic Vs Photoallergic reactions
Photoallergic reactions occur less commonly than phototoxic reactions
Mostly caused by photosensitising topical agents e.g. para-aminobenzoic acid (PABA) found in some sunscreens, topical salicylate, chlorhexidine.
Although some oral photosensitising medications can cause photoallergic reactions, most cause phototoxic reactions.
A handful of medications can cause both phototoxic and photoallergic reactions.

9. Drugs Causing Phototoxicity
Drug Class
Examples
Antibiotics
Tetracyclines, Quinolones, Sulphonamides
NSAIDS
Ibuprofen, Naproxen, Celecoxib, Ketoprofen
Retinoids
Isotretinoin, Acitretin
Statins
Atorvastatin, Simvastatin (All)
Neuroleptics/ Antihistamines
Chlorpromazine, promethazine, thioridazine, thioxanthines
Antifungals
Terbinafine, Itraconazole, Voriconazole, Griseofluvin
Others
5-Fluorouracil, Paclitaxel, Amiodarone, Diltiazem, Enalapril, Quinidine, PABA, Hydroxychloroquine, coal tar, dapsone, oral contraceptives

10. Drugs Causing Photoallergy
Drug Class
Examples
Hypoglycaemics
Sulphonylureas (Gliclazide)
NSAIDS
Celecoxib, Ketoprofen
Retinoids
Isotretinoin, Acitretin
Statins
Atorvastatin, Simvastatin (All)
Neuroleptics
Chlorpromazine, fluphenazine
Antifungals
Itraconazole, Griseofluvin
Fragrances & Sunscreens
Musk ambrette, 6-Methylcoumarin, Para-aminobenzoic acid, Benzophenones

11. Practice Points Not much published advice!
Some research has shown little increased risk of adverse effects when additional photosensitising medications taken during PUVA
However in practice has been observed.
More risk of adverse events with PUVA than UVB
Accurate medication history – include PRN meds
Can drug be stopped avoided?

12. Practice Points
YES: Generally most of drug eliminated 5 x ½ life of the drug and add 2-3 days (NOTE renal/hepatic function may alter this)
Contact medicines information service
Contact specialist pharmacist
Consider Patch test area
If on more than one choose one with longest half life
Cant work out half life for topical treatments- can they be avoided on that day?
NO: May have to avoid PUVA or use test areas.

13. Patch Testing MED – Minimum erythema dose for UVB
MPD – Minimum phototoxic dose for PUVA
Phototoxic test - the MED with the drug is compared with MED without drug.
Photopatch testing for photoallergy a smaller dose than the MED is used because the drug may have phototoxic properties

14. What is Half Life of a drug?
Pharmacokinetics: ADME principles
Help us estimate how a drug processed and eliminated by the body.
Elimination ½ Life = the time required for the concentration of the drug to reach half of its original value.
Caution can be complex to interpret -
Other factors to consider e.g. accumulation in tissues & active metabolites.

15. What is Half Life of a drug?
Generally...
Number ½ lives Elapsed
% Drug Remaining 1 50 2 25 3
12.5 4
6.25 5
3.12

16. Worked Example Patient ES 56 Year old Male
Has been on Doxycycline 100mg OD for a week finishing today, Infective exacerbation COPD.
Known photosensitising drug.
What would you do?

17. Worked Example
Contact local pharmacist/ medicines information centre for wash out period.
Half life Doxycycline is hours*
Patient has normal renal/hepatic function
24 x 5 = 120 hours
So may want to wait at least a week before PUVA dose.

18. Psoralen – A Useful Photosensitising Drug!
Natural chemicals found in Figs, celery, Parsley, citrus fruits
Use dates back to 1400 BC!
In 1974 Term PUVA introduced: Methoxypsoralen used in to increase skin reactivity to UVA ( nm)

19. Psoralen Mechanism of Action
Bonds form between psoralen and DNA in presence of UVA – inhibiting its synthesis.
Inhibits Epidermal Growth factor – Down regulation of hyper proliferation of Keratinocytes
Forms highly active oxygen molecules – cell destructive
Reduce inflammatory markers involved in pathogenesis of psoriasis

20. Psoralen Dosages 8- Methoxypsoralen
10mg tablets: dose 25mg/m2 : 2hours before Tx
5- Methoxypsoralen
20mg tablets : dose 50mg/m2 : 3 hours before Tx
8- Methoxypsoralen is also available as
Gel 0.005% : Bath lotion 1.2%
Peak Effect 1.5 to 4.2 hours
Duration 3 to 8 hours *
(wear protective clothing, sunscreen etc)
* Longer in renal impairment

21. Psoralen Side Effects Hypersensitivity reactions – very rare.
Main side effects
GI intolerance, nausea.
Can Split dose in half and take 30 minutes apart to try and minimize.
Can take with a high fat meal – note this will slow absorption time.
Dizziness also reported – caution driving if effected and potentiated by alcohol or other medications causing dizziness.
Hypersensitivity reactions – very rare.

22. Psoralen Drug Interactions
8-MOP is a potent inhibitor of the hepatic enzyme
Cytochrome P450
Interacts with drugs metabolized by this enzyme e.g. theophylline (low therapeutic index drug) and inducers such as phenytoin
Psoralen has additive effect with other photosensitizers
91% protein bound
Displaces other drugs that are protein bound e.g. potentially warfarin

23. Warfarin & Psoralens
Psoralens can potentially increase warfarin level in blood
Theoretically may increase INR
Patients should be advised to inform their anticoagulation clinic
will need increased
frequency of monitoring.

24. References
The British Association of Dermatologist – Clinical guidelines in Phototherapy
Warwick L Morrison, Sangeets Marwaha, Lisa Beck PUVA – induced phototoxicity:Incidence and causes J Am Acad Dermatol 1997;36:183-5
British Photodermatology Group guidelines for PUVA British journal of dermatology , 246 – 255
Melvin Lee; Robert E Kalb .Systemic therapy for psoriasis Dermatol Nurs. 2008;20(2):
Warwick L Morison, Phototherapy and Photochemotherapy for Skin Disease, Third Edition (Basic and Clinical Dermatology)
Stem RS, Kleinerman RA, Parrish JA, et al. Phototoxic reactions to photoactive drugs in patients treated with PUVA Arch Dermatol 1980;116: