Levulan Kerastick

Photosensitizing Agents
Sensitizers used in Photodynamic and Radiation Therapy

Administration restricted to neurosurgeons that have completed a distributor-provided training program on fluorescence use during surgery.
Use with a standard surgical operating microscope adapted with a blue light emitting light source (power density 40 to 80 mW/cm2) and ancillary excitation and emission filters to visualized fluorescence excitation in the wavelength of 375 to 440 nm and for observation from 620 to 710 nm. Filters transmit porphyrin fluorescence as red-violet, as well as a fraction of backscattered blue excitation light necessary for distinguishing nonfluorescing tissue.

Reconstitution:
Determine number of vials needed to achieve intended dose using the following equation: Number of Vials = Body Weight (kg)/75 kg per vial. Dose may require reconstitution of more than 1 vial; round up to the nearest whole vial.
Completely removed the white cap and aluminum crimp seal from each vial. Remove and retain the rubber stopper from each vial.
Using an appropriate volumetric measuring device, add 50 mL of drinking water to each vial containing 1,500 mg of the drug. Reconstituted solution contains 30 mg aminolevulinic acid/mL and is clear and colorless to slightly yellowish.
Gently swirl the vial to complete dissolution.
Storage: If not used immediately, replace stopper and store reconstituted solution for up to 24 hours at room temperature.
 
Oral Solution:
Calculate volume of reconstituted solution to be administered using the following equation: Administration Volume (mL) = Body Weight (kg) x Dose (20 mg/kg)/Solution Concentration (30 mg/mL).
Transfer entire contents of the prepared vial(s) into an appropriate dosing container (e.g., oral medicine bottle); ensure all of the contents are transferred.
Using a disposable volumetric syringe, remove the calculated administration volume from the dosing container and transfer to a separate oral dosing container. Discard unneeded volume of solution.
Administer by mouth 3 hours (range 2 to 4 hours) prior to induction of anesthesia.

Avoid applying to the periorbital or mucosal surfaces. If accidental exposure occurs, thoroughly rinse the area with water. Do not ingest.
Administration must only be performed by qualified health care professionals. It is not intended for application by patients. Use without subsequent illumination is not recommended.
Photodynamic therapy is a 2-step process consisting of application of aminolevulinic acid to the lesions followed by illumination with a specific blue (BLU-U) or red (BF-RhodoLED) light illuminator.
 
Preparation of the 20% Topical Solution:
Manual Preparation:
While holding the Levulan Kerastick so that the applicator tip is pointing up, crush the bottom ampule containing the vehicle solution by applying finger pressure to position A on the cardboard sleeve.
Crush the top ampule containing the aminolevulinic acid powder by applying finger pressure to position B on the cardboard sleeve. Continue crushing the applicator downward, applying finger pressure to position A.
Holding the Levulan Kerastick between the thumb and forefinger, point the applicator cap away from the face, shake the Levulan Kerastick gently for at least 30 seconds to completely dissolve the drug powder in the vehicle. Do not press on end cap while shaking.
After mixing the solution, remove the applicator cap. The dry applicator tip should be dabbed with a gauze pad until uniformly wet with the solution.
Use immediately following preparation of the solution. Application of the solution must be completed within 2 hours of preparation.
 
Kerastick Krusher Preparation:
Open the Kerastick Krusher and insert one Levulan Kerastick into the base with the Kerastick label "A" aligned with the Krusher "A". With the cap at the open end, firmly seat the Kerastick against the closed end of the Krusher.
Close and firmly press the top and bottom handles together until a distinct crushing sound is made.
Remove the Kerastick from the Krusher and mix the solution.
Holding the Levulan Kerastick between the thumb and forefinger, point the applicator cap away from the face, shake the Levulan Kerastick gently for at least 30 seconds to completely dissolve the drug powder in the vehicle. Do not press on end cap while shaking.
After mixing the solution, remove the applicator cap. The dry applicator tip should be dabbed with a gauze pad until uniformly wet with the solution.
Use immediately following preparation of the solution. Application of the solution must be completed within 2 hours of preparation.
 
Administration of the 20% Topical Solution:
BLU-U Photodynamic therapy must occur 3 hours after application of the topical solution to the upper extremities or 14 to 18 hours after application of topical solution to the face or scalp.
The solution may be applied to multiple lesions within the same treatment region; however multiple regions should not be treated simultaneously. Clean and dry target lesions before applying the solution.
Apply the solution directly to the target lesions by dabbing gently with the wet applicator tip. Enough solution should be applied to uniformly wet the lesion surface, including the edges without excess running or dripping. DO NOT apply to the periorbital area or allow solution to contact ocular, mucosal, or perilesional surfaces.
For lesions on the face or scalp: Once the initial application has dried, a second application of the solution should be applied in the same manner. Instruct the patient to wear a wide-brimmed hat or other protective apparel to shade the treated actinic keratoses from sunlight or other bright light sources until the photodynamic light therapy.
For lesions on the upper extremities: Cover the treatment area with low density polyethylene plastic wrap and hold in place with an elastic net dressing. Instruct the patient to wear long-sleeves or other protective apparel to shade the treated actinic keratoses from sunlight or other bright light sources until the photodynamic light therapy. Removed the occlusive dressing immediately prior to light treatment and gently rinse the treated area(s) with water and pat dry before light illumination.
A 1000 second (16 minutes 40 seconds) exposure is required to provide 10 J/cm2 light dose. Refer to the BLU-U Illuminator operating instructions for further information on conducting the light treatment.
If the blue light treatment is interrupted or stopped for any reason, it should not be restarted and the patient should be advised to protect the treated lesions from exposure to sunlight or prolonged or intense light for 40 hours after application of the topical solution.
 
Administration of the 10% Topical Gel:
Prior to applying the gel, wipe lesions with ethanol or isopropanol-soaked cotton pad.
Gently roughen lesion surfaces to remove any scaling or crusting. Take care to avoid bleeding.
Using a glove protected finger-tip or spatula, apply gel approximately 1 mm thick to lesion and approximately 5 mm of the surrounding skin. Apply enough gel to cover the lesion or area of lesions, but ensure a maximum dose of 20 cm2 or 2 g of drug (1 tube) is not exceeded with each treatment.
Allow gel to dry for approximately 10 minutes, and then cover the areas with a light-blocking, occlusive dressing.
After 3 hours, remove the dressing and wipe away any remaining gel.
Immediately after removing the dressing, initiate the photodynamic therapy using the BF-RhodoLED illuminator. During the illumination process, health care providers and the patient must wear suitable eye protection.
Position the BF-RhodoLED lamp head 5 to 8 cm away from the skin surface.
The lamp emits a narrow spectrum (about 635 nm) of red light that delivers an approximate dose of 37 J/cm2 within 10 minutes. The illumination time is automatically calculated; calibration by the operator is not needed.
For larger treatment areas, several illumination steps may be needed. Healthy surrounding skin does not require protection during illumination.
If lesions cannot be illuminated within 3 hours of gel application, the gel should be removed with saline and water. Instruct the patient to protect the application site and surrounding skin from sunlight or prolonged or intense light for 2 days after application of the topical gel.

seizures / Delayed / 1.9-1.9
cerebral edema / Early / 1.0
anaphylactic shock / Rapid / Incidence not known
angioedema / Rapid / Incidence not known

erythema / Early / 0-99.0
edema / Delayed / 35.0-35.0
neurotoxicity / Early / 29.0-29.0
elevated hepatic enzymes / Delayed / 2.9-15.8
skin erosion / Delayed / 2.0-14.0
bleeding / Early / 1.0-9.0
aphasia / Delayed / 8.0-8.0
hyperalgesia / Delayed / 5.0-5.0
skin ulcer / Delayed / 2.0-4.0
hypotension / Rapid / 1.0
contact dermatitis / Delayed / Incidence not known
photophobia / Early / Incidence not known
blurred vision / Early / Incidence not known
memory impairment / Delayed / Incidence not known
confusion / Early / Incidence not known
amnesia / Delayed / Incidence not known
metabolic acidosis / Delayed / Incidence not known

xerosis / Delayed / 87.0-87.0
skin hyperpigmentation / Delayed / 22.0-73.0
skin irritation / Early / 0-72.0
skin hypopigmentation / Delayed / 22.0-50.0
pruritus / Rapid / 14.0-34.0
vesicular rash / Delayed / 4.0-12.0
chills / Rapid / 1.0-9.0
sinusitis / Delayed / 2.0-9.0
paresthesias / Delayed / 9.0-9.0
headache / Early / 1.0-9.0
dysesthesia / Delayed / 2.0-2.0
hypoesthesia / Delayed / 1.1-1.1
petechiae / Delayed / 0.1-1.0
diarrhea / Early / 0-1.0
fever / Early / 1.0
vomiting / Early / 1.0
nausea / Early / 1.0
photosensitivity / Delayed / Incidence not known
fatigue / Early / Incidence not known
ocular irritation / Rapid / Incidence not known
diplopia / Early / Incidence not known
urticaria / Rapid / Incidence not known

Ameluz, Gleolan, Levulan Kerastick

Rx

Potent photosensitizer and precursor to protoporphyrin IX (PpIX)
Topical formulation used with photodynamic therapy to treat actinic keratosis of the face, scalp, and upper extremities
Oral formulation used to visualize malignant glioma during surgery

Apply topical solution to lesions on the scalp or face; multiple lesions can be treated within a treatment region, but multiple treatment regions should not be treated simultaneously. Application is then followed by photoactivation via blue light illumination (10 J/cm2) 14 to 18 hours later. The recommended frequency is 1 application of solution and 1 dose of illumination per treatment region per 8-week treatment session. Treated lesions that have not completely resolved after 8 weeks may be treated a second time. NOTE: Levulan Kerastick for Topical Solution is not intended for use with any device other than the BLU-U Blue Light Photodynamic Illuminator.

Apply an approximate 1 mm thick layer of topical gel to lesions on the scalp or face, and to 5 mm of surrounding skin. The maximum dose to be applied with each treatment is 20 cm2 or 2 grams of drug (one tube). Cover the gel with a light-blocking occlusive dressing for 3 hours. After 3 hours, removed the dressing and any excess gel. Immediately initiate photoactivation via BF-RhodoLED red light illumination (37 J/cm2). Patients may undergo retreatment for lesions that do not completely resolved after 3 months.

Apply topical solution to lesions on the upper extremities; multiple lesions can be treated within a treatment region, but multiple treatment regions should not be treated simultaneously. Application is then followed by photoactivation via blue light illumination (10 J/cm2) 3 hours later. The recommended frequency is 1 application of solution and 1 dose of illumination per treatment region per 8-week treatment session. Treated lesions that have not completely resolved after 8 weeks may be treated a second time. NOTE: Levulan Kerastick for Topical Solution is not intended for use with any device other than the BLU-U Blue Light Photodynamic Illuminator.

20 mg/kg PO as a single dose given 3 hours (range 2 to 4 hours) before anesthesia induction.

Various studies describe the use of a topical cream or lotion formulations of aminolevulinic acid and exposure to various light sources in the treatment of basal cell carcinoma, squamous cell carcinoma and Bowen disease. In one study, a 5-aminolevulinic acid 20% lotion was applied to various non-melanoma skin cancers. Twelve hours later the tumors were exposed to red and infrared irradiation. Complete responses were noted in 80—84% of patients with superficial or nodular basal cell carcinoma or superficial squamous cell carcinoma.

60 mg/m2 PO once followed by photoactivation 4 to 6 hours later with a dye laser system providing a light dose of 150 J/cm2.[26023]

60 mg/m2 PO once followed by gastroscopy 24 hours later with the tumors illuminated with a red band light at 100 J/cm2 for 600 seconds.[26024]

†Indicates off-label use

It is unknown if dose adjustments of the oral solution are needed for patients with impaired hepatic function. Specific guidelines for dosage adjustments for the topical products in hepatic impairment are not available; it appears that no dosage adjustments are needed.

It is unknown if dose adjustments of the oral solution are needed for patients with impaired renal function. Specific guidelines for dosage adjustments for the topical products in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Acetaminophen; Aspirin: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Acitretin: (Moderate) Acitretin may increase the effects of photosensitizing agents used during photodynamic therapy; significantly lower doses of phototherapy are required when acitretin is used because acitretin-induced effects on the stratum corneum can increase the risk of erythema (burning).
Adapalene: (Moderate) Concomitant use of adapalene and photosensitizing agents may cause additive phototoxicity; use together with caution.
Adapalene; Benzoyl Peroxide: (Moderate) Concomitant use of adapalene and photosensitizing agents may cause additive phototoxicity; use together with caution.
Alteplase: (Minor) Agents that decrease clotting, such as thrombolytic agents, could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Aminosalicylate sodium, Aminosalicylic acid: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Aspirin, ASA: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Aspirin, ASA; Caffeine: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Aspirin, ASA; Carisoprodol: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Aspirin, ASA; Dipyridamole: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Aspirin, ASA; Omeprazole: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Aspirin, ASA; Oxycodone: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Bexarotene: (Moderate) Systemic or topical bexarotene may increase the effects of photosensitizing agents used during photodynamic therapy; concurrent use of photosensitizing agents is often recommended against by the specific photodynamic therapy, or doses of the therapy may require adjustment.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Tetracyclines cause photosensitivity and may increase the photosensitizing effects photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation and the use of protective clothing and sunscreens on exposed skin.
Bismuth Subsalicylate: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Tetracyclines cause photosensitivity and may increase the photosensitizing effects photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation and the use of protective clothing and sunscreens on exposed skin. (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Butalbital; Aspirin; Caffeine; Codeine: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Calcium-channel blockers: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Choline Salicylate; Magnesium Salicylate: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Corticosteroids: (Minor) Corticosteroids administered prior to or concomitantly with photosensitizing agents used in photodynamic therapy may decrease the efficacy of the treatment.
Demeclocycline: (Moderate) Tetracyclines cause photosensitivity and may increase the photosensitizing effects photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation and the use of protective clothing and sunscreens on exposed skin.
Doxycycline: (Moderate) Tetracyclines cause photosensitivity and may increase the photosensitizing effects photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation and the use of protective clothing and sunscreens on exposed skin.
Eravacycline: (Moderate) Use photosensitizing agents and eravacycline together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity. Prevention of photosensitivity includes adequate protection from sources of UV radiation and the use of protective clothing and sunscreens on exposed skin.
Griseofulvin: (Moderate) Griseofulvin may induce photosensitivity and may increase the effects of photosensitizing agents.
Halobetasol; Tazarotene: (Moderate) Tazarotene may increase the effects of photosensitizing agents used during photodynamic therapy; concurrent use of photosensitizing agents is often recommended against by the specific photodynamic therapy, or doses of the therapy may require adjustment.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Indapamide: (Moderate) Indapamide may cause photosensitivity and may increase the photosensitization effects of drugs like photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
Mafenide: (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of photosensitizing agents used during photodynamic therapy.
Magnesium Salicylate: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Methenamine; Sodium Salicylate: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Methotrexate: (Major) Methotrexate may increase the photosensitizing effects of photosensitizing agents used for photodynamic therapy.
Minocycline: (Moderate) Tetracyclines cause photosensitivity and may increase the photosensitizing effects photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation and the use of protective clothing and sunscreens on exposed skin.
Nonsteroidal antiinflammatory drugs: (Moderate) Agents that inhibit prostaglandin synthesis such as nonsteroidal antiinflammatory drugs (NSAIDs), could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of NSAIDs before and during photodynamic therapy may be advisable.
Omadacycline: (Moderate) Tetracyclines cause photosensitivity and may increase the photosensitizing effects photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation and the use of protective clothing and sunscreens on exposed skin.
Phenothiazines: (Moderate) Phenothiazines may increase the photosensitizing effects of photosensitizing agents used in photodynamic therapy. Patients should limit ultra-violet exposure.
Platelet Inhibitors: (Minor) Agents, such as platelet inhibitors, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Porfimer: (Major) Avoid coadministration of porfimer with topical photosensitizing agents due to the risk of increased photosensitivity. All patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents may increase the risk of a photosensitivity reaction.
Reteplase, r-PA: (Minor) Agents that decrease clotting, such as thrombolytic agents, could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Salicylates: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Salsalate: (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Sarecycline: (Moderate) Tetracyclines cause photosensitivity and may increase the photosensitizing effects photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation and the use of protective clothing and sunscreens on exposed skin.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
St. John's Wort, Hypericum perforatum: (Major) St. John's wort has been reported to increase the phototoxicity associated with photosensitizing agents used in photodynamic therapy. Although interactions have not been reported, in theory it is possible that additive photosensitizing effects may result from the concomitant use of St. John's wort with other photosensitizing drugs.
Sulfacetamide: (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of photosensitizing agents used during photodynamic therapy.
Sulfacetamide; Sulfur: (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of photosensitizing agents used during photodynamic therapy.
Sulfadiazine: (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of photosensitizing agents used during photodynamic therapy.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of photosensitizing agents used during photodynamic therapy.
Sulfasalazine: (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of photosensitizing agents used during photodynamic therapy.
Sulfonamides: (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of photosensitizing agents used during photodynamic therapy.
Sulfonylureas: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
Tazarotene: (Moderate) Tazarotene may increase the effects of photosensitizing agents used during photodynamic therapy; concurrent use of photosensitizing agents is often recommended against by the specific photodynamic therapy, or doses of the therapy may require adjustment.
Tenecteplase: (Minor) Agents that decrease clotting, such as thrombolytic agents, could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Tetracycline: (Moderate) Tetracyclines cause photosensitivity and may increase the photosensitizing effects photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation and the use of protective clothing and sunscreens on exposed skin.
Tetracyclines: (Moderate) Tetracyclines cause photosensitivity and may increase the photosensitizing effects photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation and the use of protective clothing and sunscreens on exposed skin.
Thiazide diuretics: (Moderate) Thiazide diuretics may cause photosensitivity and may increase the photosensitization effects of photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
Thiothixene: (Moderate) Thiothixene may increase the effects of photosensitizing agents used during photodynamic therapy. Patients receiving phenothiazines should avoid ultra-violet (UV) exposure whenever possible.
Thrombolytic Agents: (Minor) Agents that decrease clotting, such as thrombolytic agents, could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Tretinoin, ATRA: (Moderate) Tretinoin, ATRA may increase the effects of photosensitizing agents used during photodynamic therapy; concurrent use of photosensitizing agents is often recommended against by the specific photodynamic therapy, or doses of the therapy may require adjustment.
Trifarotene: (Moderate) Concomitant use of trifarotene and photosensitizing agents may cause additive phototoxicity; use together with caution. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin and topical photosensitizing agents is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents may increase the risk of a photosensitivity reaction.
Ziprasidone: (Moderate) Medications that may cause additive photosensitization when used with ziprasidone include aminolevulinic acid. Patients should limit sunlight and ultra-violet exposure whenever possible, and use proper UV precautions to protect the skin.

Ameluz Topical Gel: 10%
Gleolan Oral Pwd F/Recon: 1500mg
Levulan Kerastick Topical Sol: 20%

Oral solution, 20 mg/kg PO; 20% topical solution, 1 application and 1 dose of illumination per treatment site every 8 weeks; 10% topical gel, 20 cm2 or 2 g (1 tube) with each treatment.

Oral solution, 20 mg/kg PO; 20% topical solution, 1 application and 1 dose of illumination per treatment site every 8 weeks; 10% topical gel, 20 cm2 or 2 g (1 tube) with each treatment.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

In the body, aminolevulinic acid (ALA) is formed from succinyl-CoA and glycine under the influence of the enzyme gamma-aminolevulinate synthetase. This is the initial step of porphyrin and heme synthesis. After multiple steps, protoporphyrin IX is formed. Protoporphyrin IX (PpIX) is a photosensitizer that is converted to heme by ferrochelatase through addition of iron to the PpIX nucleus. The synthesis of ALA is the rate limiting step of heme synthesis and is tightly controlled by negative feedback inhibition of delta-aminolevulinate synthetase by intracellular heme concentrations. By providing an exogenous source of ALA, the negative feedback mechanism is bypassed and PpIX accumulates in the cell. Malignant and premalignant cells seem to accumulate more ALA than do the normal surrounding cells; this effect may be due to several features of the malignant cells. In some malignant cells the activity of ferrochelatase is low and leads to the accumulation of PpIX. The increased permeability of skin tumors also contributes to selective accumulation of PpIX since ALA is hydrophilic and does not easily penetrate intact skin.
 
After application, ALA converts to PpIX and photosensitization occurs in the treated cells. When exposed to light of appropriate wavelength and energy and in the presence of oxygen, the accumulated PpIX produces a cytotoxic photodynamic reaction. The absorption of light by PpIX results in an excited state of the porphyrin molecule. Subsequent spin transfer of electrons from PpIX to molecular oxygen generates oxygen free radicals, which can further react to form superoxide and hydroxyl free radicals. These free radicals cause cytotoxic effects by damaging plasma and intracellular membranes. Damage to treated cells is noted within hours. A necrotic reaction and associated inflammatory responses evolve over several days. Cell damage is characterized by cessation of normal cellular movement and formation of multiple membrane blebs. Blebs are balloon-like protrusions from the cell membrane and indicate severe membrane damage. After bleb formation, the cell dies. The efficacy of topical ALA-photodynamic treatment of actinic keratosis varies with the site treated. Actinic keratosis on the face, scalp, or neck responded to a greater degree than those on the forearm or dorsum of the hand.
 
The excited state porphyrin molecule can also decay back to its ground state with the release of energy in the form of fluorescence. The photodynamic diagnostic uses of ALA utilize the release of fluorescence to detect dysplastic or malignant tissue. The 20% topical solution is administered prior to photodynamic therapy (PDT) using a specific blue light illuminator (BLU-U), while the 10% topical gel is given before PDT using a specific red light illuminator (BF-RhodoLED). Both formulations are indicated for the treatment of actinic keratosis. Peak fluorescence is reached in 11 +/- 1 hours for actinic keratosis and 12 +/- 1 hours for perilesional skin. The fluorescence of ALA-derived PpIX in normal and malignant skin increases with time after topical ALA application and depends upon the concentration of ALA (2% to 40%), amounts of preparations (30 to 50 mg/cm2), and application time. In general, topical application of ALA alone for less than 4 hours produces PpIX only at the site of application. Generalized photosensitization may occur if ALA is administered for longer periods of time (e.g., up to 14 hours) or if it is combined with vehicles that enhance skin penetration. Time-dependent changes in surface fluorescence have been used to determine PpIX accumulation and clearance in actinic keratosis and perilesional skin following drug application. The mean clearance of fluorescence from lesions is 30 +/- 10 hours and 28 +/- 6 hours for perilesional skin.
 
Orally administered aminolevulinic acid is indicated as an adjunct for visualization of malignant tissue during glioma surgery. Exposing the drug to a blue emitting light source (power density 40 to 80 mW/cm2) results in red fluorescence of tumor tissue when viewed at wavelengths of 620 to 710 nm through an operating microscope with filters for excitation light of wavelength 375 to 440 nm. Tissue lacking sufficient PpIX concentrations appears blue. The relationship between the timing of the dose and the drug plasma concentration at the time of visualization with fluorescence intensity in brain tissue is unknown.

Aminolevulinic acid is administered orally and topically. In vitro data suggests the mean protein binding of aminolevulinic acid as 12%. Aminolevulinic acid is metabolized to protoporphyrin IX (PpIX); however, the fraction of the administered dose that is metabolized to PpIX is unknown. On average, plasma exposure of PpIX is less than 6% of that of aminolevulinic acid. The parent drug is excreted in the urine, with 34 +/- 8% (range 27% to 57%) being excreted within the first 12 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters: none

The absolute bioavailability of oral aminolevulinic acid is approximately 100% (range 78.5% to 131.2%). Maximum plasma concentrations of the parent drug and the PpIX metabolite are achieved at 0.8 hour (range 0.5 to 1 hour) and 4 hours (range 1.2 to 7.8 hours), respectively. The mean half-life of aminolevulinic acid after the recommended oral dose is 0.9 +/- 1.2 hours (range 0.8 to 1.3 hours). The mean elimination half-life of the metabolite (PpIX) is 3.6 +/- 1.8 hours (range 1.2 to 7.8 hours).

Two pharmacokinetic studies have been conducted in patients with minimally to moderately thick actinic keratoses of the upper extremities. Patients were administered a single dose comprised of 2 topical application of 20% solution (each containing 354 mg aminolevulinic acid) applied directly to lesions and occluded for 3 hours. In the first study, the baseline-corrected mean maximum concentration (Cmax) of aminolevulinic acid (ALA) was 249.9 +/- 694.5 ng/mL and the median time to reach Cmax was 2 hours post dose. The mean exposure (AUC) was 669.9 +/- 1,610 ng x hour/mL, and the median elimination half-life was 5.7 +/- 3.9 hours. In the second study, the baseline-corrected mean of Cmax for ALA and protoporphyrin IX (PpIX) was 95.6 +/- 120.6 ng/mL and 0.95 +/- 0.71 ng/mL, respectively. The median Tmax for ALA and PpIX was 2 hours and 12 hours post dose, respectively. The mean AUC of ALA was 261.1 +/- 229.3 ng x hour/mL. The mean elimination half-live of ALA was 8.5 +/- 6.7 hours.

There are no available data on aminolevulinic acid use during human pregnancy to inform a drug-associated risk. Administration to pregnant rabbits during organogenesis at doses 3-times the maximum recommended human oral dose resulted in no adverse developmental effects. Systemic absorption of aminolevulinic acid is negligible after topical administration under maximal clinical use conditions; it is not expected that maternal use of topical aminolevulinic acid will result in fetal exposure to the drug.

There are no data on the presence of aminolevulinic acid in human or animal breast milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for aminolevulinic acid and any potential adverse effects on the breast-fed infant from aminolevulinic acid. To decrease exposure to aminolevulinic acid to the breast-feeding infant, advise a lactating woman to pump and discard breast milk for 24 hours (i.e., 5 to 6 half-lives) after oral administration of aminolevulinic acid. Breast-feeding is not expected to result in exposure of the child to topical aminolevulinic acid due to negligible systemic absorption under maximal clinical use conditions.