Interactions
As ingenol mebutate is not effectively absorbed through the skin and into the bloodstream, interactions with oral drugs are unlikely. Chemistry
The substance is an ester of the diterpene ingenol and angelic acid. A 3-step semisynthesis of ingenol mebutate starting from ingenol was described by a chemical research group in Denmark in 2012. A 14-step synthesis of (+)-ingenol from (+)-3-carene, which is a relatively inexpensive constituent of turpentine, was published in July 2013. Mechanism of action
The mechanism by which ingenol mebutate causes cell death is still not fully understood. One study on squamous cell carcinoma, the precursor of which is actinic keratosis, cultures found that the PKC/MEK/ERK signaling pathway is involved in causing cell death after treatment with ingenol mebutate. In addition, the interleukin decoy receptors IL1R2 and IL13RA2 were induced, resulting in a reduction in the long-term viability of the cells, which could help prevent recurrence. Studies
Results from four multicenter, randomized, double-blind studies have shown that ingenol mebutate gel applied topically, for 2 to the trunk or 3 days to the face or scalp, is effective for field treatment of actinic keratoses.A twelve-month follow-up study was performed on actinic keratosis patients who had been treated with ingenol mebutate, 108 of which had been treated for face or scalp and 71 for trunk or extremities and the study found that of those treated for the face or scalp 46.1% had sustained clearance, and of those treated for the trunk 44.0% had sustained clearance for the period of the study.
However, at the higher dose levels (eight and 16 times the human dose equivalent), liver carcinomas and adenomas, lung adenomas, and adenomas of the Harderian gland occurred. No mutagenic effects were seen in assays. Testicular atrophy was noted in dogs and rats at four and eight times the human exposure, respectively. Limitations of use
It should not be used in patients with type 1 diabetes, diabetic ketoacidosis, pancreatitis, Fredrickson types I and V dyslipidemias, and severe renal impairment. Drug interactions
Juvisync should not be used with: strong CYP3A4 inhibitors, cyclosporine, danazol, gemfibrozil, and other fibrates. Caution should be used and the patient should be monitored if they are taking the following: amiodarone, dronedarone, ranolazine, calcium channel blockers, niacin, digoxin, coumarin anticoagulants, and colchicine. References
External links
"Juvisync". Drug Information Portal. U.S. National Library of Medicine.