aminolevulinic acid topical (Rx)

Adverse effects are for all grades unless otherwise specified

>10%

Ameluz

• Erythema (92%)
• Pain/burning (92%)
• Irritation (72%)
• Edema (35%)
• Pruritus (34%)
• Exfoliation (19%)
• Scab (19%)
• Induration (12%)
• Vesicles (12%)

Levulan Kerastick

• Face

  • Scaling/crusting (1-71%)
  • Itching (1-25%)
  • Hypo/hyperpigmentation (22%)
  • Erosion (1-14%)

• Scalp

  • Scaling/crusting (2-64%)
  • Hypo/hyperpigmentation (36%)
  • Itching (7-14%)
  • Skin disorder NOS (12%)

• Upper extremities

  • Erythema (100%)
  • Stinging/burning (96%)
  • Scaling and dryness (87%)
  • Hyperpigmentation (73%)
  • Edema (56%)
  • Hypopigmentation (50%)
  • Oozing/vesiculation/crusting (41%)

1-10%

Ameluz

• Paresthesia (9%)
• Hyperalgesia (5%)
• Discomfort (3%)
• Erosion (3%)
• Discharge (2%)
• Bleeding (1%)
• Pustules (1%)

Levulan Kerastick

• Face

  • Wheal/flare (1-7%)
  • Skin disorder NOS (5%)
  • Ulceration (4%)
  • Bleeding/hemorrhage (4%)
  • Vesiculation (4%)
  • Pustules (4%)
  • Dysesthesia (2%)
  • Scabbing (1-2%)
  • Excoriation (1%)
  • Oozing (1%)
  • Pain (1%)
  • Tenderness (1%)
  • Edema (1%)

• Scalp

  • Vesiculation (5%)
  • Tenderness (2%)
  • Ulceration (2%)
  • Bleeding/hemorrhage (2%)
  • Erosion (2%)
  • Wheal/flare (2%)

Postmarketing Reports

Skin and subcutaneous tissue disorders: Erythema, swelling, application site inflammation, skin discoloration; increased photosensitivity, allergic dermatitis

Eye disorders: Eye irritation, diplopia, ocular hyperemia, photophobia, and blurred vision

Coagulation defects

Transient amnestic episodes

Dysaesthesia

Fatigue

Contraindications

Hypersensitivity to porphyrins

Hypersensitivity to any gel components, which includes soybean phosphatidylcholine

Porphyria; drug may cause uncontrolled phototoxic effects

Known photodermatoses of varying pathology and frequency (eg, metabolic disorders [aminoaciduria], idiopathic or immunological disorders [polymorphic light reaction], genetic disorders [xeroderma pigmentosum], and diseases precipitated or aggravated by exposure to sun light [lupus erythematoides or pemphigus erythematoides])

Levulan Kerastick

• Cutaneous photosensitivity at wavelengths of 400-450 nm

Cautions

Ameluz

• Transient amnestic episodes reported during postmarketing use of topical gel in combination with photodynamic therapy
• BF-RhodoLED lamp may cause eye irritation, glare, or injury; protective eye equipment must be used by patient, healthcare providers and any person present during the illumination period
• Has not been tested on patients with inherited or acquired coagulation disorders; special care should be taken to avoid bleeding during lesion preparation
• Eyelid edema and mucous membrane irritation reported; rinse eyes with water in case of accidental contact
• Several cases of hypersensitivity reported during postmarketing use prior to PDT illumination; if allergic reactions occur, clean the area of skin where product was applied and institute appropriate therapy; inform patients and their caregivers that therapy may cause hypersensitivity, potentially including severe courses (anaphylaxis)

Levulan Kerastick

• Topical solution contains alcohol and is intended for topical use only; irritation may occur if applied to eyes or mucus membranes; do not apply to eyes or to mucous membranes; excessive irritation may be experienced if this product is applied under occlusion >3 hr
• Treatment site will become photosensitive and patients should avoid exposure of photosensitive treatment sites to sunlight or bright indoor light (e.g., examination lamps, operating room lamps, tanning beds, or lights at close proximity) for 40 hours; exposure may result in a stinging and/or burning sensation and may cause erythema and/or edema of the lesions; before exposure to sunlight, patients should protect treated lesions from sun by wearing a wide-brimmed hat or similar head covering of light-opaque material, and/or a long-sleeved shirt and/or gloves; because of potential for skin to become photosensitized, the topical solution should be used by a qualified health professional to apply drug to no more than 5mm of perilesional skin surrounding the target actinic keratosis lesions
• Safety and efficacy not established on patients with inherited or acquired coagulation defects

Pregnancy

Ameluz: No available data

Levulan Kerastick: Limited available data with topical solution use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes

Lactation

Unknown if distributed in human breast milk

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Aminolevulinic acid is a precursor of photoactive porphyrins, which accumulate in the skin lesions where the product has been applied and are subsequently illuminated with a photodynamic lamp

When exposed to the light, the accumulated photoactive porphyrins produce a photodynamic reaction, resulting in a cytotoxic process dependent on the simultaneous presence of oxygen, which as a result generates a singlet oxygen; the singlet oxygen can then react to form superoxide and hydroxyl radicals

Absorption

Ameluz

• Plasma concentration: After occlusion for 3 hr, up to 2.5-fold increase of aminolevulinic acid plasma concentrations observed
• Peak plasma time: 3 hr
• Peak plasma concentration: 27.19 ng/mL
• AUC: 142.83 ng·hr/mL

Levulan Kerastick

• Peak plasma time: 2 hr
• Peak plasma concentration: 249.9 ng/mL
• AUC: 669.9 ng·hr/mL

Excretion

Levulan Kerastick

• Half-life: 5.7 hr

Topical Administration

Topical product should be only applied by physician or qualified medical personnel

For topical use only; not for ophthalmic, oral, or intravaginal use

Photodynamic therapy is a multistep process

Ameluz

• One session of photodynamic therapy should be administered for single lesions or an entire field affected by multiple lesions
• Evaluate 3 months after treatment
• Non- or partially responding lesions should be retreated in a second session

• Step 1: Lesion preparation

  • Before applying gel, carefully wipe all lesions with an ethanol or isopropanol-soaked cotton pad to ensure degreasing of the skin
  • Thereafter, gently roughen all lesion surfaces; take care to avoid bleeding

• Step 2: Gel application

  • Using gloved protected fingertips or spatula, apply gel ~1 mm thick to lesion(s) and include ~5 mm of the surrounding skin; if multiple lesions, cover the entire area (not to exceed 20 cm² and no more than 2 g (ie, 1 tube) for a session
  • The gel can be administered to healthy skin around the lesions, whereas application near the eyes, nostrils, mouth, ears or mucosa should be avoided (keep a distance of 1 cm)
  • Avoid direct contact of gel with the eyes or mucous membrane; if accidentally exposed, rinse with water

• Step 3: Occlude for 3 hours

  • Allow gel to dry for ~10 minutes, before an occlusive light-tight dressing is placed over the treatment site
  • Following 3 hr of incubation, the dressing should be removed and the remnant gel wiped off

• Illumination with red light

  • Immediately after cleaning the lesions, the entire treatment area will be illuminated with a red light source with a narrow spectrum around 635 nm that delivers a light dose of approximately 37 J/cm² within 10 minutes
  • During illumination the lamp should be fixed at the distance from the skin surface that is indicated in the user manual
  • Position the lamp head 5-8 cm from the skin’s surface; when an area of 8 x 18 cm is illuminated, the effective treatment area is 6 x16 cm
  • Larger areas can be illuminated in several steps
  • If for any reason, the lesions cannot be illuminated within 3 hr after application, rinse off the gel with saline and water
  • For 2 days, protect the lesion sites and surrounding skin from sunlight or prolonged or intense light

Levulan Kerastick

• Prepare solution by crushing the bottom ampule (diluent) and then the top ampule (powder) of the stick to; shake gently for 30 sec
• 1 application per site per 8 week session
• Apply to affected area; allow to dry
• Do not apply solution to the periorbital area or allow it to contact ocular or mucosal surfaces
• For upper extremities: Occlude upper extremity with low density polyethylene plastic wrap and hold in place with an elastic net dressing
• Follow application with blue light (400-450 nm) photodynamic blue light treatment 14-18 hr later
• May treat a second time lesions that did not completely healed after 8 hr
• At light illumination visit before treatment, gently rinse treated area with water and patted dry

Storage

Ameluz

• Unopened gels: Store refrigerated between 2-8°C (36-46°F); excursions permitted to 15-30°C (59-86°F)
• Opened gels: Refrigerate at 2-8°C (36-46°F) if the tube is tightly closed for up to 12 wk

Levulan Kerastick

• Unused applicators: Store between 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)
• Prepared solutions: Must be used within 2 hr of dissolution