Healthcare Professionals - Learn About Transdermal Verapamil 15% Gel For Fibrotic Tissue Disorders

What is Transdermal Verapamil 15% Gel?

Transdermal Verapamil 15% Gel is a painless, non-invasive, treatment for fibrotic tissue disorders such as Peyronie's disease, plantar fibromatosis, and Dupuytren's disease that was developed and patented by PDLabs. Since 1998, PDLabs Transdermal Verapamil 15% Gel has been prescribed for over 13,000 patients. It is a prescription, compounded medication that is applied directly to the skin twice a day and is not FDA approved. Verapamil belongs to the class of medications known as calcium channel blockers. The gel has been designed to carry the verapamil through the skin and deliver it to the lesion. The proprietary formula allows for minimal absorption into the blood, while maximizing the concentration of verapamil in the lesion and surrounding tissue.

Proposed Mechanism of Action

As with many medications, the exact mechanism of action of Transdermal Verapamil 15% Gel is not entirely understood. It is proposed that two different processes are taking place. The first allows for the progression of the lesion to be slowed or stopped and second for the lesion to actually be reduced, which allows for the symptoms of the condition to be reduced or eliminated. Both of these processes are effected by verapamil's ability as a calcium channel blocker to block calcium.

Cells known as fibroblasts are responsible for the production of the primary components of the lesion such as collagen, fibronectin and glycosaminoglycans. Research has shown that the process by which these components are released out of the fibroblast requires calcium. [1] It has been found that calcium channel blockers have the ability to decrease the production of collagen and fibronectin and their release from the fibroblast. [2] A study has also shown that the large increase of Peyronie's fibroblasts is markedly impaired by verapamil, even at low doses. [3] This research is the basis of why it is thought that using Transdermal Verapamil 15% Gel in the inflammatory or early stages of these fibrotic tissue disorders, may prevent the condition from being as severe as it might have been without any treatment.

Fibroblasts are also responsible for the production of collagenase, which is responsible for remodeling the excess collagen that makes up the lesion. Research has demonstrated that calcium channel blockers such as verapamil have the ability to increase the activity of collagenase, which enhances the remodeling of scars in burn victims. [4] It was also found in experiments with bovine fibroblasts that exposure to verapamil increased collagenase activity. [5] Peyronie's disease, plantar fibromatosis, and Dupuytren's disease are thought to be similar to other wound disorders such as keloids and hypertrophic scars. Research on the use of verapamil in keloids has suggested that it may increase procollagenase production, meaning that verapamil may be capable of increasing collagen breakdown. [6] Although this research was not done on fibroblasts from Peyronie's disease, plantar fibromatosis, or Dupuytren's disease, it is theorized that fibroblasts from these lesions will respond in a similar way. This theory is supported by objectively measured improvements in Peyronie's disease plaque and plantar fibromatosis in clinical studies with Transdermal Verapamil 15% Gel. The increase in collagenase activity after exposing the fibroblasts to verapamil, helps to explain how Transdermal Verapamil 15% Gel can remodel an already formed and stable lesion into more healthy and elastic tissue. The remodeling of the tissue and return of the elasticity allows for the symptoms of the condition to be reduced or eliminated.

The illustration below shows the two proposed mechanisms of action, magnified to the level of the fibroblast.

Peyronie's Disease | Plantar Fibromatosis | Dupuytren's Disease

Proposed mechanism of action for Peyronie's disease illustration
Proposed mechanism of action for plantar fibromatosis illustration
Proposed mechanism of action for Dupuytren's disease illustration
[1] Kelly RB. Pathways of protein secretion in eukaryotes.. Science. 1985;230:25. MEDLINE
[2] Aggeler J, Frish SM, Werb Z. Changes in cell shape correlate with collagenase gene expression in rabbit synovial fibroblasts.. J. Cell Biol. 1984;98:1662. MEDLINE
[3] Anderson MS, Shankey TV, Lubrano T, Mulhall JP. Inhibition of Peyronie's plaque fibroblast proliferation by biologic agents. Int J Impot Res. 2000;12:S25.
[4] Lee RC, Doong H, Jellema AF. The response of burn scars to intralesional verapamil. Arch Surg. 1994;129:107. MEDLINE
[5] Lee RC, Ping JA. Calcium antagonist retard extracellular matrix production in connective tissue equivalent. J Surg Res. 1990;49:463. MEDLINE
[6] Doong H, Dissanayake S, Gowrishankar TR, LaBarbera MC, Lee RC. The 1996 Lindberg Award. Calcium antagonists alter cell shape and induce procollagenase synthesis in keloid and normal human dermal fibroblasts. J Burn Care Rehabil. 1996;17:497. MEDLINE