Consume and Burn,Medication-induced Photosensitivity

My summer preflight checklist includes CFR 91.03 and the ultraviolet (UV) index. The “UV Index” is my sunscreen application reminder checklist. All pilots and civilians taking medications that induce photosensitivity must also consider checking the UV index.

A total of 393 photosensitizing medications are reported in the literature. This topic could be a chapter in a pharmacology textbook. My discussion will cover the most commonly prescribed medications with a high reported photosensitivity rate. The broad definition of medication-induced photosensitivity is a chemical change in the skin caused by the drug that makes an individual more sensitive to light. When exposed to sunlight, the most common skin manifestations are sunburn, rash, or other reactions that generally would not cause a reaction. In my experience, I have seen second- and third-degree burns that lead to pain, and many hours spent at the clinic to get these burns under control.

There are two different types of photosensitivity, described as photoallergy and phototoxicity. An allergic reaction of the skin causes photoallergy reactions, and photosensitivity is a reaction to direct exposure to the sun or artificial lighting, such as a tanning booth. The offending medications include creams, ointments, oral tablets, capsules, injections, and inhalers.

Sunburns, rash, allergies, itching, and scaling are not the only conditions of medication-induced photosensitivity. Additional complications and conditions due to medication-induced photosensitivity include skin cancer, premature skin aging, eye burns, cataracts, immunity decline, and blood vessel damage.

Two notes of interest are that not everyone taking a photosensitizing medication will get symptoms, and if it does happen once, it may not happen again. I hope to prevent second- or third-degree burns from the sun in patients who are prescribed these photosensitizers.

Pilots on photosensitizing medications may have higher rates of symptoms exacerbated by environmental and occupational exposure to the sun. A recent meta-analysis reported an increased incidence of melanoma in pilots and cabin crew, possibly due to occupational exposures (JAMA Dermatol. 2015 Jan:151:51-58). Airplane windshields are commonly made of polycarbonate plastic or multilayer composite glass. UV-B (short-wavelength UV that causes skin burn) transmission was reported to be less than 1%. UV-A (long-wavelength UV that causes skin aging) ranged from 0.41% to 53.5%, with plastic attenuating more UV radiation than glass (Nakagawara VB, Montgomery RW, Marshall JW. Optical Radiation Transmittance of Aircraft Windscreens and Pilot Vision.Washington, DC: Federal Aviation Administration; 2007). If a pilot is on photosensitizing medications, sunscreen of SPF > 15 should be applied regularly. An addendum to this practice is that if it is sunny or above an overcast cloud deck for extended periods, all pilots should apply sunscreen to block UV rays before the flight.

The pathophysiology of photosensitization commences when a photosensitive medication changes upon absorption of UV radiation or visible light in the skin. Free radical activation leads to molecular changes in cellular components, which may result in a cytotoxic cellular burden and induce a macroscopically visible phototoxic skin reaction (J Dtsch Dermatol Ges, 2021 Jan 2021;19(1): 19-29).

The photosensitizing medications discussed below have substantial proof of photosensitizing effects, with the number of publications greater or equal to 15. All medicines mentioned are YES drugs in the FAA medication database.

Diuretic medications are a category of drug prescribed for patients with hypertension. The effect of diuretic medications is to eliminate excess fluid and sodium. Hydrochlorothiazide (HCTZ) works on a specific area of the nephron called the distal tubule. Sodium chloride is excreted through the kidneys. High sodium levels in the body cause a rise in blood pressure. HCTZ will decrease potassium levels as well. HCTZ is a chronic hypertensive medication, so the risk of photosensitivity is high. HCTZ may also increase the risk of skin cancer due to a photocarcinogenesis effect with regular use. The skin cancers seen are basal cell carcinoma, squamous cell carcinoma, and melanoma. Furosemide (Lasix™) is a very potent diuretic that inhibits the reabsorption of sodium, water, potassium, and chloride and increases diuresis. It is a loop diuretic that works on the ascending Loop of Henle in the kidney. The indication for furosemide is heart failure. Heart failure is the decline of the heart’s pumping function over time. This patient population will accumulate fluid (edema) in their lower extremities and the lungs (pulmonary edema) as the disease progresses. Furosemide is given in IV form if the patient has difficulty breathing from all the water in the lungs. Furosemide is administered until the edema is no longer a concern to the patient.

Amiodarone (Cordarone™) is an antiarrhythmic agent prescribed for ventricular tachycardia. Ventricular tachycardia is the rapid beating of the ventricles of the heart. For these patients, the initiation of CPR and defibrillation is necessary. Amiodarone’s indication is to prevent the occurrence of future ventricular arrhythmias. Amiodarone’s primary indication is for atrial fibrillation patients. Amiodarone is the safest of the antiarrhythmics prescribed for atrial fibrillation. Amiodarone may cause an increased risk of basal cell carcinoma. Dronedarone (Multaq™) is similar to amiodarone, only without the side effects of pulmonary fibrosis, hypothyroid, hyperthyroid, lenticular opacities, and blue-gray skin discoloration. Anti-inflammatory medications that may cause phototoxicity are among the most common medication classes the general public takes for pain. The non-steroidal anti-inflammatory drugs (NSAIDs) include naproxen sodium (Aleve), ketoprofen (Orudis), and piroxicam (Feldene). Ibuprofen has a lower risk of photosensitivity in patients. NSAIDs have been reported to increase the risk of squamous cell carcinoma. Phototoxicity usually occurs in patients taking NSAIDs chronically. Two highly prescribed antibiotics that increase the risk for photosensitivity are Ciprofloxacin and Doxycycline. The indications for Ciprofloxacin are urinary tract infection, pneumonia, cellulitis, and utilized in patients with a true penicillin allergy. The pilot should not be flying in the first place if they need antibiotics for the mentioned disease states. The half-life of Ciprofloxacin is 4 hours. The pilot should be off Ciprofloxacin for at least 24 hours before a flight to eliminate all of the drug from the body. Ciprofloxacin has been reported to increase the risk of basal cell carcinoma. Indications for Doxycycline are for patients with STDs and respiratory tract infections. Doxycycline will take 72 hours for complete elimination from the body. Statins may cause photosensitivity. Pravastatin (Pravachol), Rosuvastatin (Crestor), and Atorvastatin (Lipitor™) have been added to the list of photosensitive medications after 2005. Statins are prescribed for patients who need to reduce LDL lipids. In multiple studies, statins show reduced mortality and decreased risk of future myocardial infarction events. The obvious remedy is to apply sunscreen when taking photosensitizing medications. I have an oxymoron for you. Some sunscreens have ingredients in their formulations that are photosensitizing. Sunscreen ingredients with photosensitizing effects are 6-Acetoxy-2.4-dimethyle-m-dioxane, benzophenones, cinnamates, oxybenzone, PABA esters, and para-aminobenzoic acid (PABA). Please take a look at the sunscreen ingredients before you purchase. Patient awareness of the ramifications of photosensitizing medications is less than adequate. You are a unique patient if you are aware of and know about the sticker on your vial that reads, “You should AVOID prolonged or excessive exposure to direct /or artificial sunlight while taking this medication.” If you are prescribed a medication with a high rate of photosensitivity, grab your sunscreen with an SPF of 30-50, containing titanium dioxide 8% and zinc oxide 10. Even if you are not on a photosensitizing medication, a preflight ritual application of sunscreen on a sunny day may save you from a severe burn at 3,000 feet and above.
Larry M. Diamond, PharmD, CFII
Larry Diamond has a Doctor of Pharmacy Degree and has been a pharmacist for 37 years. Larry’s pharmacy practice has been as a Clinical Pharmacy Specialist in Cardiology, Orthopedic Surgery Specialist and most recently Clinical Pharmacy Coordinator. He is a CFII, a pilot for 33 years and has been an AOPA member since 1984.

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