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What is the role of pentoxifylline (Trental) in venous stasis ulcers? Wound Reference is recommending 400 mg TID in addition to compression therapy to promote ulcer healing. Is it commonly used in wound care centers?
Feb 21, 2022 by David L. Dugan, MD
2 replies
Elaine Horibe Song
MD, PhD, MBA
Hi Dr Dugan,

Thank you for your question. Other colleagues might have further input, but here is a quick summary: pentoxifylline is approved by the United States Federal Drug Administration for intermittent claudication but is clinically used as an adjunct for VLUs [1,2] - although its use in the US for management of VLU is probably not as widespread as in other countries.

For long-standing or large VLUs, the Society for Vascular Surgery, American Venous Forum recommends treatment with either pentoxifylline or micronized purified flavonoid fraction used in combination with compression therapy. [GRADE - 1; LEVEL OF EVIDENCE - B] [3]

The use of pentoxifylline as an adjunct for treatment of VLU is supported by evidence derived from several randomized controlled trials (RCTs):
- A 2012 Cochrane systematic review of 12 RCTs (n=864 patients) found that patients with VLUs receiving pentoxifylline with compression were more likely to heal than those receiving placebo and compression (RR 1.56, 95% CI 1.14 to 2.13). Pentoxifylline in the absence of compression appears to be more effective than placebo or no treatment (RR 2.25, 95% CI 1.49 to 3.39).[4]
- A 2021 meta-analysis with 13 RCTs (n=921 individuals) found that compared with placebo, pentoxifylline significantly improved the ulcer healing rate (RR = 1.59, 95%CI 1.22 to 2.07, P < .001) while increased the incidence of gastrointestinal disturbances (RR = 2.29, 95%CI 1.04 to 5.03, P = .04) at the same time. Moreover, pentoxifylline also shortened the mean duration of complete wound healing (P = .007) and shrank ulcer size (P = .02). Currently available evidence suggests that pentoxifylline could help venous leg ulcers heal more quickly and effectively.[5]

Mode of action:
Pentoxifylline and its metabolites improve the flow properties of blood by decreasing its viscosity. Pentoxifylline administration has been shown to produce dose-related hemorrheologic effects, lowering blood viscosity, and improving erythrocyte flexibility.[2]
Pentoxifylline also has a fibrinolytic effect. Systemic abnormalities in fibrinolysis, seen in patients with venous disease, contribute to the “pericapillary fibrin cuff,” which also may act as an additional perfusion barrier to oxygen and nutrients. [2,4] It is hypothesized that the fibrinolytic effect of pentoxifylline affects the pericapillary fibrin cuff, and subsequently increases the healing rate of chronic venous ulcers.[1] The pericapillary fibrin cuff is believed to be an important mechanism in the formation of VLUs. A study showed that pentoxifylline administration induced about a 50% decrease of local elastase in VLUs, indicating a local reduction of neutrophil activation and a decrease in fibrin deposition.[4]

[1] https://www.hmpgloballearningnetwork.com/site/wounds/review/literature-review-pharmacological-agents-improve-venous-leg-ulcer-healing
[2] https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=40ae2d9a-0d95-640d-0640-f76e7e1a13cb
[3] https://www.jvascsurg.org/article/S0741-5214(14)00851-9/fulltext
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061323/
[5] https://pubmed.ncbi.nlm.nih.gov/34779680/
Feb 22, 2022
Elaine Horibe Song
MD, PhD, MBA
Quick case shared by Cathy Milne APRN, MSN, CWOCN-AP: Cathy is treating a patient with mixed arterial venous ulcer who was supposed to undergo surgical bypass, but due to a recent cardiac arrest, the patient is no longer a surgical candidate. She started the patient on adjunct pentoxifylline 3 months ago. It took about 120 days but she is now seeing results and it seems like the ulcer will heal. Cathy notes that to minimize GI side effects, pentoxifylline should be taken with full meals.
Feb 22, 2022
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