Actinic Keratosis

Initial U.S. Approval:  2016

Mechanism of Action:
Photoactivation following topical application of AMELUZ occurs when aminolevulinic acid (prodrug) is metabolized to protoporphyrin IX (PpIX), a photoactive compound which accumulates in the skin. When exposed to red light of a suitable wavelength and energy, PpIX is activated resulting in an excited state of porphyrin molecules. In the presence of oxygen, reactive oxygen species are formed which causes damage to cellular components, and eventually destroys the cells. AMELUZ photodynamic therapy of AK lesions utilizes photoactivation of topically applied AMELUZ resulting from BF-RhodoLED illumination, which provides a red light of narrow spectrum and a light dose of approximately 37 J/cm2.

INDICATIONS AND USAGE:
AMELUZ gel, a porphyrin precursor, in combination with photodynamic therapy using BF-RhodoLED lamp, is indicated for the lesion-directed and field-directed treatment of actinic keratoses of mild-to-moderate severity on the face and scalp (1).

DOSAGE AND ADMINISTRATION
-Administer AMELUZ only by a health care provider (2.1).
-AMELUZ is for topical use only (2.1).
-Photodynamic therapy with AMELUZ involves preparation of lesions, application of the product, occlusion and illumination with BF-RhodoLED (2.2).
-Retreat lesions that have not completely resolved 3 months after the initial treatment (2.2).
-See BF-RhodoLED user manual for detailed lamp safety and operating instructions (2).

HOW SUPPLIED:
DOSAGE FORMS AND STRENGTHS
Gel: 10%

INDICATIONS AND USAGE
Solaraze® (diclofenac sodium) Gel is indicated for the topical treatment of actinic keratoses (AK). Sun avoidance is indicated during therapy.

WARNINGS
As with other NSAIDs, anaphylactoid reactions may occur in patients without prior exposure to diclofenac. Diclofenac sodium should be given with caution to patients with the aspirin triad. The triad typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs.

DOSAGE AND ADMINISTRATION
Solaraze® Gel is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough Solaraze® Gel is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site. The recommended duration of therapy is from 60 days to 90 days. Complete healing of the lesion(s) or optimal therapeutic effect may not be evident for up to 30 days following cessation of therapy. Lesions that do not respond to therapy should be carefully re-evaluated and management reconsidered.

HOW SUPPLIED
Available in tubes of 100 g (NDC 10337-803-01). Each gram of gel contains 30 mg of diclofenac sodium.

Storage: Store at controlled room temperature 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F). Protect from heat. Avoid freezing.

†Voltaren® is a registered trademark of Novartis.
Manufactured by:
Almirall Hermal GmbH
D-21465 Reinbek, Germany
Made in Germany
Manufactured for:
PharmaDerm® A division of Fougera Pharmaceuticals Inc.

Actinic keratoses:
Carac™: Apply thin film to lesions once daily for up to 4 weeks, as tolerated.
Efudex®: Apply to lesions twice daily for 2-4 weeks; complete healing may not be evident for 1-2 months following treatment.
Fluoroplex®: Apply to lesions twice daily for 2-6 weeks
Supplied: Cream, topical:
Carac™: 0.5% (30 g).   Efudex®: 5% (25 g, 40 g).   Fluoroplex®: 1% (30 g).

Drug UPDATES:  TOLAK™- fluorouracil cream
[Drug information  /  PDF]    Click link for the latest monograph
Dosing:  Click (+) next to Dosage and Administration section (drug info link)

Initial U.S. Approval:  2015

Mechanism of Action: There is evidence that the metabolism of fluorouracil in the anabolic pathway blocks the methylation reaction of deoxyuridylic acid to thymidylic acid. In this manner, fluorouracil interferes with the synthesis of DNA and to a lesser extent inhibits the formation of RNA. Since DNA and RNA are essential for cell division and growth, the effect of fluorouracil may be to create a thymine deficiency that provokes unbalanced growth and death of the cell. The effects of DNA and RNA deprivation are most marked on those cells that grow more rapidly and take up fluorouracil at a more rapid rate.

INDICATIONS AND USAGE:  Tolak (fluorouracil) Cream, 4%, is a nucleoside metabolic inhibitor indicated for the topical treatment of actinic keratosis lesions of the face, ears, and scalp

HOW SUPPLIED: Cream: 40 mg of fluorouracil per gram of cream (4%)

Limitations of Use: Efficacy of imiquimod cream was not demonstrated for molluscum contagiosum in children 2 to 12 years of age.

DOSAGE AND ADMINISTRATION:
For topical use only; not for oral, ophthalmic, intra-anal or intravaginal use.

Actinic Keratosis: Once daily to the skin of the affected area (either the entire face or balding scalp) for two 2-week treatment cycles separated by a 2-week no-treatment period.

External Genital Warts: Once daily to the external genital/perianal warts until total clearance or up to 8 weeks.

DOSAGE FORMS AND STRENGTHS:
Cream: 2.5% packets; 3.75% packets or pump.

CONTRAINDICATIONS:
None

WARNINGS AND PRECAUTIONS
Intense local inflammatory reactions can occur (e.g., skin weeping, erosion). Dosing interruption may be required.

Severe local inflammatory reactions of the female external genitalia can lead to severe vulvar swelling. Severe vulvar swelling can lead to urinary retention; dosing should be interrupted or discontinued.

Flu-like systemic signs and symptoms including fatigue, nausea, fever, myalgias, arthralgias, and chills can occur. Dosing interruption may be required.

Avoid concomitant use of ZYCLARA Cream and any other imiquimod cream because of increased risk for adverse reactions.

ADVERSE REACTIONS
Most common adverse reactions (>4%) are local skin reactions (erythema, edema, erosion/ulceration, exudate, scabbing/crusting), headache, application site pain, application site irritation, application site pruritus, fatigue, influenza-like illness, and nausea.

Mechanism of Action: The mechanism of action by which Picato® gel induces cell death in treating AK lesions is unknown.

INDICATIONS AND USAGE:  Picato ® gel is an inducer of cell death indicated for the topical treatment of actinic keratosis.

DOSAGE AND ADMINISTRATION
ABBREVIATED MONOGRAPH - SEE PACKAGE INSERT
For topical use only; not for oral, ophthalmic, or intravaginal use. (2)
Avoid transfer of Picato® to periocular area. (2)
Avoid application near and around the mouth and lips. (2)

For application of up to one contiguous skin area of approximately 25 cm2 (5 cm x 5 cm) using one unit dose tube. (2)
Actinic keratosis on the face or scalp: Apply Picato® gel, 0.015% to the affected area once daily for 3 consecutive days. (2)

Actinic keratosis on the trunk or extremities: Apply Picato® gel, 0.05% to the affected area once daily for 2 consecutive days. (2)

DOSAGE FORMS AND STRENGTHS
Gel containing ingenol mebutate, 0.015% or 0.05%

CONTRAINDICATIONS
Known hypersensitivity to ingenol mebutate or any component of the formulation.

WARNINGS AND PRECAUTIONS:
Eye disorders, including severe eye pain, eyelid edema, eyelid ptosis, periorbital edema can occur after exposure. Avoid contact with the periocular area. If accidental exposure occurs, flush eyes with water and seek medical care.

Local skin reactions can occur including severe reactions (e.g., vesiculation/pustulation, erosion/ulceration). Administration of Picato® gel is not recommended until skin is healed from any previous drug or surgical treatment.