Levulan Kerastick

Preparation and Administration Overview

After mixing, the LEVULAN KERASTICK topical solution 20% is intended for direct application to individual lesions diagnosed as actinic keratoses and not to perilesional skin. This product is not intended for application by patients or unqualified medical personnel.  Application should involve lesions on the scalp, face or upper extremities; multiple lesions can be treated within a treatment region, but multiple treatment regions should not be treated simultaneously.

The recommended treatment frequency is: one application of the LEVULAN KERASTICK topical solution and one dose of illumination per treatment region per 8-week treatment session. Each individual LEVULAN KERASTICK applicator should be used for only one patient.

LEVULAN KERASTICK photodynamic therapy for actinic keratoses is a two-stage process involving application of the LEVULAN KERASTICK topical solution to the target lesions and then illumination with blue light using the BLU-U Blue Light Photodynamic Therapy Illuminator after 3 hours for upper extremity lesions or after 14-18 hours for face or scalp lesions.

If for any reason the patient cannot be given BLU-U Blue Light Photodynamic Therapy Illuminator treatment during the prescribed time after applying LEVULAN KERASTICK topical solution, he or she may nonetheless experience sensations of stinging and/or burning if the photosensitized actinic keratoses are exposed to sunlight or prolonged or intense light at that time. Advise the patient to wear appropriate protective apparel (e.g., wide-brimmed hat, long sleeve shirt, gloves) to shade the treated actinic keratoses from sunlight or other bright light sources until at least 40 hours after the application of LEVULAN KERASTICK topical solution. Advise the patient to reduce light exposure if the sensations of stinging and/or burning are experienced.

LEVULAN KERASTICK photodynamic therapy may be repeated a second time for lesions that have not completely resolved 8 weeks after the initial treatment.

Dosage and Administration Instructions

Step A - Treatment of Actinic Keratoses with LEVULAN KERASTICK Topical Solution

Preparation of Lesions

Actinic keratoses targeted for treatment should be clean and dry prior to application of LEVULAN KERASTICK Topical Solution.

Preparation of LEVULAN KERASTICK topical solution

The LEVULAN KERASTICK applicator consists of a plastic tube containing two sealed glass ampules and an applicator tip. One ampule contains 1.5 mL of solution vehicle. The other ampule contains aminolevulinic acid HCl as a dry solid. LEVULAN KERASTICK topical solution is prepared by crushing the glass ampoules and mixing the contents together.

The LEVULAN KERASTICK topical solution can be prepared either manually, or using the optional KERASTICK KRUSHER™.  These methods are illustrated below.

Figure 1:   Manual Preparation:

1. Hold the LEVULAN KERASTICK applicator with cap point up. Crush the bottom ampule containing the solution vehicle by applying finger pressure to Position A on the cardboard sleeve.
   
2. Crush the top ampule containing the ALA HCl powder by applying finger pressure to Position B on the cardboard sleeve. To ensure both ampules are crushed continue crushing the applicator downward, applying finger pressure to Position A. Shake the LEVULAN KERASTICK applicator gently for at least 30 seconds to completely dissolve the drug powder in the solution vehicle.

Figure 2:  Optional KERASTICK KRUSHER Preparation:

1. Open the KERASTICK KRUSHER and properly position one LEVULAN KERASTICK applicator into the KRUSHER making sure to orient the LEVULAN KERASTICK label “A” with the KRUSHER “A”. Firmly seat the LEVULAN KERASTICK applicator against the closed end of the KRUSHER (cap should be at open end).
   
2. Once positioned properly, close and firmly press the top and bottom handles together until the top and bottom handles touch one another along their length. A distinct crushing sound is made during this process. Ensure KRUSHER handles meet.
   
3. Remove the LEVULAN KERASTICK applicator from the KRUSHER and shake the LEVULAN KERASTICK applicator gently for at least 30 seconds to completely dissolve the drug powder in the solution vehicle.

The LEVULAN KERASTICK topical solution must be used within two (2) hours of activation. If the solution is not completely applied within 2 hours of the activation, discard the applicator. If needed, use a new LEVULAN KERASTICK applicator.

Application of LEVULAN KERASTICK topical solution

Application of LEVULAN KERASTICK topical solution to Face or Scalp Lesions:

Following solution admixture, remove the cap from the LEVULAN KERASTICK applicator. The dry applicator tip should be dabbed on a gauze pad until uniformly wet with 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. Once the initial application has dried, apply again in the same manner.

Do not apply the LEVULAN KERASTICK topical solution to the periorbital area or allow it to contact ocular or mucosal surfaces.

Photosensitization of the treated lesions will take place over the next 14-18 hours. The actinic keratoses should not be washed during this time. The patient should be advised to wear a wide-brimmed hat or other protective apparel to shade the treated actinic keratoses from sunlight or other bright light sources until BLU-U Blue Light Photodynamic Therapy Illuminator treatment. The patient should be advised to reduce light exposure if the sensations of stinging and/or burning are experienced.

At the visit for light illumination before treatment, the actinic keratoses treated with the LEVULAN KERASTICK topical solution should be gently rinsed with water and patted dry.

For Lesions on the Upper Extremities

Following solution mixture, remove the cap from the LEVULAN KERASTICK applicator. The dry applicator tip should be dabbed on a gauze pad until uniformly wet with 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.

Occlude the upper extremity with low density polyethylene plastic wrap and hold in place with an elastic net dressing.

Figure 3: Method of Occlusion for Upper Extremities

The patient should wear a long-sleeved shirt and/or gloves or other protective apparel to shade the treated actinic keratoses from sunlight or other bright light sources until BLU-U Blue Light Photodynamic Therapy Illuminator treatment. Photosensitization of the treated lesions will take place over the next 3 hours. The actinic keratoses should not be washed during this time. Remove the occlusive dressing prior to light treatment and gently rinse the treated area(s) with water and pat dry before light illumination.

Step B - Administration of BLU-U Treatment:

LEVULAN KERASTICK is not intended for use with any device other than the BLU-U Blue Light Photodynamic Therapy Illuminator. Use of LEVULAN KERASTICK without subsequent BLU-U Blue Light Photodynamic Therapy Illuminator illumination is not recommended.

Photoactivation of actinic keratoses treated with LEVULAN KERASTICK topical solution is accomplished with illumination from the BLU-U Blue Light Photodynamic Therapy Illuminator. A 1000 second (16 minutes 40 seconds) exposure is required to provide a 10 J/cm 2light dose. During light treatment, both patients and medical personnel should be provided with blue blocking protective eyewear, as specified in the BLU-U Blue Light Photodynamic Therapy Illuminator Operating Instructions. Please refer to the BLU-U Blue Light Photodynamic Therapy Illuminator Operating Instructions for further information on conducting the light treatment. Patients should be advised that transient stinging and/or burning at the target lesion sites occurs during the period of light exposure.

If blue light treatment with the BLU-U Blue Light Photodynamic Therapy Illuminator 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 at least 40 hours after applying the LEVULAN KERASTICK topical solution.

For patients with facial lesions:

1. The BLU-U Blue Light Photodynamic Therapy Illuminator is positioned so that the base is slightly above the patient’s shoulder, parallel to the patient’s face.
   
2. The BLU-U is positioned around the patient’s head so the entire surface area to be treated lies between 2” and 4” from the BLU-U surface:
   a) The patient’s nose should be no closer than 2” from the surface;
   b) The patient’s forehead and cheeks should be no further than 4” from the surface;
   c) The sides of the patient’s face and the patient’s ears should be no closer than 2” from the BLU-U surface.

For patients with scalp lesions:

1. The knobs on either side of the BLU-U are loosened and the BLU-U is rotated to a horizontal position.
   
2. The BLU-U is positioned around the patient’s head so the entire surface area to be treated lies between 2” and 4” from the BLU-U surface:
   a) The patient’s scalp should be no closer than 2” from the surface;
   b) The patient’s scalp should be no further than 4” from the surface;
   c) The sides of the patient’s face and the patient’s ears should be no closer than 2” from the BLU-U surface.
   

For patients with upper extremity lesions:

1. The knobs on either side of the BLU-U Blue Light Photodynamic Therapy Illuminator are loosened and the light is rotated to a horizontal position.
   
2. The BLU-U Blue Light Photodynamic Therapy Illuminator is positioned around the upper extremity so the entire surface area to be treated lies between 2” and 4” from the BLU-U surface.  A table may be used to support the upper extremities during light treatment.

Pregnancy

Risk Summary

Limited available data with LEVULAN KERASTICK topical solution use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. Animal developmental toxicology studies were not conducted with aminolevulinic acid.  LEVULAN KERASTICK solution has low systemic absorption following topical administration, and the risk of maternal use resulting in fetal exposure to the drug is unknown [see Clinical Pharmacology (12.3)].

The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Lactation

Risk Summary

There are no data on the presence of LEVULAN KERASTICK topical solution in either human or animal milk, the effects on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LEVULAN KERASTICK topical solution and any potential adverse effects on the breastfeeding child from LEVULAN KERASTICK topical solution or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness in pediatric patients below the age of 18 have not been established. Actinic keratosis is not a disease generally seen in the pediatric population.

Geriatric Use

Of the 512 subjects in Phase 3 clinical trials of LEVULAN KERASTICK topical solution, 63% (321/512) were 65 years old and over, while 24% (123/512) were 75 years old and over.  No overall differences in safety or substantial differences in effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

Transient Amnestic Episodes

Transient amnestic episodes have been reported during postmarketing use of LEVULAN KERASTICK in combination with BLU-U Blue Light Photodynamic Therapy Illuminator. Inform patients and their caregivers that LEVULAN KERASTICK in combination with PDT may cause transient amnestic episodes. Advise them to contact the healthcare provider if the patient develops amnesia after treatment.

Photosensitivity

After LEVULAN KERASTICK topical solution has been applied, the treatment site will become photosensitive and patients should avoid exposure of the 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.

Therefore, before exposure to sunlight, patients should protect treated lesions from the sun by wearing a wide-brimmed hat or similar head covering of light-opaque material, and/or a long-sleeved shirt and/or gloves. Sunscreens will not protect against photosensitivity reactions caused by visible light. It has not been determined if perspiration can spread the LEVULAN KERASTICK topical solution outside the treatment site to the eye or surrounding skin.

Application of LEVULAN KERASTICK topical solution to perilesional areas of photodamaged skin of the face, scalp or upper extremities may result in photosensitization. Upon exposure to activating light from the BLU-U, such photosensitized skin may produce a stinging and/or burning sensation and may become erythematous and/or edematous in a manner similar to that of actinic keratoses treated with LEVULAN KERASTICK Photodynamic Therapy.  Because of the potential for skin to become photosensitized, the LEVULAN KERASTICK 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.

If for any reason the patient cannot return for blue light treatment during the prescribed period after applying LEVULAN KERASTICK topical solution, the patient should call the doctor. The patient should also continue to avoid exposure of the photosensitized lesions to sunlight or prolonged or intense light for at least 40 hours. If stinging and/or burning is noted, exposure to light should be reduced.

Irritation

The LEVULAN KERASTICK topical solution contains alcohol and is intended for topical use only. Irritation may be experienced if this product is applied to eyes or mucous membranes.  Do not apply to the eyes or to mucous membranes. Excessive irritation may be experienced if this product is applied under occlusion longer than 3 hours.

Coagulation Defects

The LEVULAN KERASTICK for topical solution has not been tested on patients with inherited or acquired coagulation defects.