Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel, External:
Picato: 0.015% (3 ea); 0.05% (2 ea) [contains benzyl alcohol, isopropyl alcohol]
Pharmacology
Mechanism of Action
Ingenol mebutate appears to induce primary necrosis of actinic keratosis with a subsequent neutrophil-mediated inflammatory response with antibody-dependent cytotoxicity of residual disease cells; killing residual disease cells may prevent future relapse (Ramsay 2011; Siller 2010).
Pharmacokinetics/Pharmacodynamics
Absorption
Absorption through the skin is minimal (with proper use); expected systemic exposure is <0.1 ng/mL.
Use: Labeled Indications
Actinic keratosis: Topical treatment of actinic keratosis
Contraindications
Hypersensitivity to ingenol mebutate or any component of the formulation.
Dosage and Administration
Dosing: Adult
Actinic keratosis: Topical:
Face or scalp: Apply 0.015% gel once daily to affected area for 3 consecutive days; patients not achieving clearance or that experience recurrence after achieving clearance ≥8 weeks after initial treatment may benefit from a second treatment course.
Trunk or extremities: Apply 0.05% gel once daily to affected area for 2 consecutive days
Dosing: Geriatric
Refer to adult dosing.
Administration
Apply topically to one contiguous affected area of skin using one unit-dose tube; one unit-dose tube will cover ~5 cm x 5 cm (~25 cm2 or ~2 inch x 2 inch). Spread evenly then allow gel to dry for 15 minutes. Do not cover with bandages or occlusive dressings. Wash hands immediately after applying and avoid transferring gel to any other areas. Avoid washing or touching the treatment area for at least 6 hours, and following this period of time, patients may wash the area with a mild soap. Not for oral, ophthalmic, or intravaginal use. Avoid application near or around the mouth and lips. Avoid transfer of gel to the periocular area.
Storage
Store in a refrigerator at 2°C to 8°C (36°F to 46°F); excursions are permitted to 0°C to 15°C (32°F to 59°F); do not freeze. Discard tubes after single use.
Drug Interactions
There are no known significant interactions.
Adverse Reactions
Percentages represent face/scalp and trunk/extremities incidences unless otherwise specified.
>10%:
Dermatologic: Erythema (92% to 94%), desquamation (≤90%), exfoliation of skin (≤90%), crusted skin (74% to 80%), swelling of skin (face/scalp: 79%; trunk/extremities: 64%), localized vesiculation (face/scalp: ≤56%; trunk/extremities: ≤44%), pustules (face/scalp: ≤56%; trunk/extremities: ≤44%), dermal ulcer (≤32%), skin erosion (≤32%), application site pain (face/scalp: 15%, trunk/extremities: 2%)
1% to 10%:
Central nervous system: Headache (face/scalp: 2%)
Dermatologic: Application site pruritus (8%), application site irritation (trunk/extremities: 4%), skin infection (face/scalp: 3%; at application site)
Ophthalmic: Periorbital edema (face/scalp: 3%)
Respiratory: Nasopharyngitis (trunk/extremities: 2%)
Frequency not defined:
Ophthalmic: Conjunctivitis, eyelid edema, eye pain
<1%, postmarketing, and/or case reports: Anaphylaxis, conjunctivitis (chemical-induced), corneal injury (burn), eye injury (FDA Safety Alert, August 21, 2015), herpes zoster, pigmentation alteration (application site), scarring (application site), severe hypersensitivity (includes allergic contact dermatitis)
Warnings/Precautions
Concerns related to adverse effects:
- Dermatologic reactions: Severe reactions including erythema, crusting, swelling, vesiculation/pustulation, and erosion/ulceration can occur.
- Hypersensitivity: Cases of hypersensitivity, including anaphylaxis and allergic contact dermatitis, have been reported. If anaphylaxis or other clinically significant hypersensitivity reaction occurs, discontinue immediately and manage as appropriate.
- Ocular: Avoid treatment in the periocular area. Severe eye pain, chemical conjunctivitis, corneal burning, eyelid edema, eyelid ptosis, and periorbital edema can occur after exposure. Patients should wash their hands immediately after applying and avoid transferring to the eye area. If accidental exposure occurs, patient should flush area with water and contact health care provider.
Other warnings/precautions:
- Appropriate use: Apply to intact and nonirritated skin only. Instruct patients to wash hands well after applying and to avoid contact with the periocular area during and after application. Avoid touching the treated area for 6 hours after application. If inadvertent exposure to other area(s) occurs, flush the area with water and seek medical care as soon as possible. Avoid inadvertent transfer to other individuals. Administration of ingenol mebutate gel is not recommended until the skin is healed from any previous drug or surgical treatment. For topical use only; not for oral, ophthalmic, or intravaginal use.
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were observed in some animal reproduction studies following IV administration of ingenol mebutate. Absorption is limited in humans following topical application.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience skin discoloration, skin crusting, scaling, flaking, redness, or edema; headache; stuffy nose; or sore throat. Have patient report immediately to prescriber signs of skin infection, skin ulcers, severe skin reaction or irritation, dizziness, or passing out (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
