Skip to main content
Log in

Ingenol Mebutate Gel 0.015% and 0.05%

In Actinic Keratosis

  • Adis Drug Profile
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Ingenol mebutate is the main active constituent of sap from the plant Euphorbia peplus, which has traditionally been used as a home remedy for various skin conditions. Ingenol mebutate gel is approved in the US, EU, Australia and Brazil for the topical treatment of actinic keratosis.

A short course of field-directed therapy with topical ingenol mebutate gel was effective in the treatment of actinic keratoses on the face or scalp (ingenol mebutate gel 0.015% once daily for 3 consecutive days) and on the trunk or extremities (ingenol mebutate gel 0.05% once daily for 2 consecutive days), according to the results of four randomized, double-blind, vehicle-controlled, multicentre studies.

Significantly higher complete clearance rates (primary endpoint) and partial clearance rates were seen at day 57 in patients receiving ingenol mebutate gel than in those receiving vehicle gel. Treatment with ingenol mebutate gel was generally associated with sustained clearance of actinic keratoses in the longer term.

Topical ingenol mebutate gel was generally well tolerated in the treatment of patients with actinic keratoses on the face or scalp and on the trunk or extremities. Application-site conditions were the most commonly occurring adverse events.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. de Berker D, McGregor JM, Hughes BR, et al. Guidelines for the management of actinic keratoses. Br J Dermatol 2007 Feb; 156(2): 222–30

    Article  PubMed  Google Scholar 

  2. Del Rosso JQ. Current regimens and guideline implications for the treatment of actinic keratosis: proceedings of a clinical roundtable at the 2011 Winter Clinical Dermatology Conference. Cutis 2011 Jul; 88 Suppl. 1: 1–8

    PubMed  Google Scholar 

  3. Anderson L, Schmieder GJ, Werschler WP, et al. Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis. J Am Acad Dermatol 2009 Jun; 60(6): 934–43

    Article  PubMed  Google Scholar 

  4. Rosen RH, Gupta AK, Tyring SK. Dual mechanism of action of ingenol mebutate gel for topical treatment of actinic keratoses: rapid lesion necrosis followed by lesion-specific immune response. J Am Acad Dermatol 2012 Mar; 66(3): 486–93

    Article  PubMed  CAS  Google Scholar 

  5. Barnaby JWJ, Styles AR, Cockerell CJ. Actinic keratoses: differential diagnosis and treatment. Drugs Aging 1997 Sep; 11(3): 186–205

    Article  PubMed  CAS  Google Scholar 

  6. Ramsay JR, Suhrbier A, Aylward JH, et al. The sap from Euphorbia peplus is effective against human nonmelanoma skin cancers. Br J Dermatol 2011 Mar; 164(3): 633–6

    PubMed  CAS  Google Scholar 

  7. Rizk AM, Hammouda FM, El-Missiry MM, et al. Biologically active diterpene esters from Euphorbia peplus. Phytochem 1985; 24(7): 1605–6

    Article  CAS  Google Scholar 

  8. LEO Pharma, Inc. Picato® (ingenol mebutate) gel, 0.015% and 0.05% for topical use: US prescribing information [online] Available from URL: http://www.leo-pharma.us/Files/Billeder/LEO_local_images/LEO-Pharma.US/Releases/Picato%20PI.pdf [Accessed 2012 Jun 28]

  9. European Medicines Agency. Picato (ingenol mebutate) gel: EU summary of product characteristics [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002275/WC500135327.pdf [Accessed 2012 Dec 3]

  10. Stahlhut M, Chahal H, Lord J, et al. Ingenol mebutate initiates multiple specific cell death pathways in human cancer cells [abstract no. 5517]. J Am Acad Dermatol 2012 Apr; 66 (4 Suppl. 1): AB152

    Google Scholar 

  11. Zibert JR, Eriksson AH, Grue-Sørensen G, et al. Ingenol mebutate penetrates reconstructed human skin in a gradient-dependent manner and clears subclinical skin cancer [abstract no. 5501]. J Am Acad Dermatol Apr; 66 (4 Suppl. 1): AB152

  12. Challacombe JM, Suhrbier A, Parsons PG, et al. Neutrophils are a key component of the antitumor efficacy of topical chemotherapy with ingenol-3-angelate. J Immunol 2006 Dec 1; 177(11): 8123–32

    PubMed  CAS  Google Scholar 

  13. Ogbourne S, Suhrbier A, Jones B, et al. Antitumor activity of 3-ingenyl angelate: plasma membrane and mitochondrial disruption and necrotic cell death. Cancer Res 2004 Apr 15; 64(8): 2833–9

    Article  PubMed  CAS  Google Scholar 

  14. Hampson P, Kavanagh D, Smith E, et al. The anti-tumor agent, ingenol-3-angelate (PEP005), promotes the recruitment of cytotoxic neutrophils by activation of vascular endothelial cells in a PKC-δ dependent manner. Cancer Immunol Immunother 2012 Aug; 57(8): 1241–51

    Article  Google Scholar 

  15. Kedei N, Lundberg DJ, Toth A, et al. Characterization of the interaction of ingenol 3-angelate with protein kinase C. Cancer Res 2004 May 1; 64(9): 3243–55

    Article  PubMed  CAS  Google Scholar 

  16. Ersvaer E, Kittang AO, Hampson P, et al. The protein kinase C agonist PEP005 (ingenol 3-angelate) in the treatment of human cancer: a balance between efficacy and toxicity. Toxins 2010 Jan; 2(1): 174–94

    Article  PubMed  CAS  Google Scholar 

  17. Li L, Shukla S, Lee A, et al. The skin cancer chemotherapeutic agent ingenol-3-angelate (PEP005) is a substrate for the epidermal multidrug transporter (ABCB1) and targets tumor vasculature. Cancer Res 2010 Jun 1; 70(11): 4509–19

    Article  PubMed  CAS  Google Scholar 

  18. Cozzi S-J, Ogbourne SM, James C, et al. Ingenol mebutate field-directed treatment of UVB-damaged skin reduces lesion formation and removes mutant p53 patches. J Invest Dermatol 2012 Apr; 132(4): 1263–71

    Article  PubMed  CAS  Google Scholar 

  19. Peplin. A study to evaluate the pharmacokinetics of PEP005 (ingenol mebutate) gel, 0.05%, when applied in a maximal use setting to the dorsal aspect of the forearm in patients with actinic keratosis [ClinicalTrials.gov identifier NCT00852137]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials/gov [Accessed 2012 Jun 28]

  20. Siller G, Gebauer K, Welburn P, et al. PEP005 (ingenol mebutate) gel, a novel agent for the treatment of actinic keratosis: results of a randomized, double-blind, vehicle-controlled, multicentre, phase IIa study. Australas J Dermatol 2009 Feb; 50(1): 16–22

    Article  PubMed  Google Scholar 

  21. Spencer J. Multicenter, randomized, double-blind, vehicle-controlled, dose-ranging study to evaluate the efficacy and safety of PEP005 (ingenol mebutate) gel 0.005%, 0.01%, and 0.015% when used to treat actinic keratoses on the head [abstract no. P2913]. J Am Acad Dermatol 2010 Mar; 62 (3 Suppl. 1): AB105

    Google Scholar 

  22. Lebwohl M, Swanson N, Anderson LL, et al. Ingenol mebutate gel for actinic keratosis. N Engl J Med 2012 Mar 15; 366(11): 1010–9

    Article  PubMed  CAS  Google Scholar 

  23. Berman B, Marmur E, Larsson T, et al. Three-day topical treatment with ingenol mebutate gel 0.015% for actinic keratoses on the face and scalp: analysis of data pooled from two trials [poster no. 5623]. 70th Annual Meeting of the American Academy of Dermatology; 2012 Mar 16–20; San Diego (CA)

  24. Anderson LL, Schmieder GJ, Xu Z, et al. Two-day topical treatment with ingenol mebutate gel 0.05% for actinic keratoses on the trunk and extremities: analysis of data pooled from two trials [poster no. 5640]. 70th Annual Meeting of the American Academy of Dermatology; 2012 Mar 16–20; San Diego (CA)

  25. Stein Gold L, Melgaard A, Larsson T. Long-term follow-up studies of ingenol mebutate gel for the treatment of actinic keratosis [abstract no. 5620]. J Am Acad Dermatol 2012 Apr; 66 (4 Suppl. 1): AB154. Plus poster presented at the 70th Annual Meeting of the American Academy of Dermatology; 2012 Mar 16–20; San Diego (CA)

    Google Scholar 

  26. Peplin. A multi-center study to evaluate the safety and efficacy of PEP005 (ingenol mebutate) gel, when used to treat actinic keratoses on non-head locations (trunk and extremities) [ClinicalTrials.gov identifier NCT00917306]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials/gov [Accessed 2012 Jul 16]

  27. Lebwohl M, Swanson N, Kobayashi K, et al. Local skin responses associated with ingenol mebutate gel for the treatment of actinic keratosis: two analyses of pooled data [poster no. 4997]. 70th Annual Meeting of the American Academy of Dermatology; 2012 Mar 16–20; San Diego (CA)

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gillian M. Keating.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Keating, G.M. Ingenol Mebutate Gel 0.015% and 0.05%. Drugs 72, 2397–2405 (2012). https://doi.org/10.2165/11470090-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11470090-000000000-00000

Keywords

Navigation