Methylated xanthines or methylxanthines include stimulants such as caffeine, aminophylline and pentoxifylline. Xanthine is a purine base or nitrogenous compound found in most human body tissues and fluids such as urine and blood. Methylated refers to the introduction of a methyl group into a chemical compound.
Most people don’t care about coffee being a methylxanthine, much less about other methylxanthines available out there. Some might have heard of pentoxifylline as a treatment for arterial claudication. Most think of it as a useless drug from the old school. Or maybe that is what they would like us to believe. In Europe it is still used for bad circulation and there are thousands of papers published on pentoxifylline. It is sort of Big Pharma’s wonder drug. It is extremely cheap and has a safety track record of decades.
What is even more intriguing is that scientists don’t know why or how pentoxifylline works, but it seems to be working in a number of debilitating conditions.
From McCarty MF, O’Keefe JH, DiNicolantonio JJ. Pentoxifylline for vascular health: a brief review of the literature. Open Heart 2016;3: e000365. doi:10.1136/openhrt-2015-000365
…a review of the existing literature suggests that pentoxifylline may have potential for slowing the progression of atherosclerosis, stabilising plaque, reducing risk for vascular events, improving the outcome of vascular events, dampening the systemic inflammatory response following cardiopulmonary bypass, providing symptomatic benefit in angina and intermittent claudication, enhancing cerebral blood flow in patients with cerebrovascular disease while slowing progression of vascular dementia, improving prognosis in congestive heart failure, and aiding diabetes control.
All sorts of mechanisms of actions for pentoxifylline are described, but still, it is clear that this drug is not a standard anti-inflammatory or circulation drug. It also decreases fibrotic lesions, making pentoxifylline a cheap alternative in conditions that are very debilitating. From Pentoxifylline – a review of its use in osteoradionecrosis
Pentoxifylline has been used to treat complications related to fibrosis for over 20 years. Formerly used to treat those after radiotherapy such as osteoradionecrosis (ORN), it is now being tried for medication-related osteonecrosis of the jaw (MRONJ), which can occur after prolonged use of bisphosphonates. We review theories on the formation of fibrosis in patients with ORN, discuss the pharmacology of pentoxifylline and vitamin E, and report published outcomes. To our knowledge no prospective randomised controlled trial has investigated the benefits ofthese agents in cases of ORN, but reported outcomes in many published case series are encouraging.
From Pentoxifylline in heart failure: a meta-analysis of clinical trial
A meta-analysis evaluating pentoxifylline versus placebo in HF [heart failure] suggested a significant nearly fourfold decrease in all-cause mortality in the pentoxifylline group.
From Repurposing Pentoxifylline for the Treatment of Fibrosis: An Overview
Recently, the effectiveness of pentoxifylline in the treatment of fibrosis via attenuating and reversing fibrotic lesions has been demonstrated in several clinical trials and animal studies. As a result of the limited availability of antifibrotic agents in the long-term treatment of fibrosis that can attenuate and even reverse fibrotic lesions effectively, it would be of particular importance to consider the potential clinical utility of pentoxifylline in the treatment of fibrosis. Thus, this paper discusses the evolving roles of pentoxifylline in the treatment of different types of fibrosis.
From Successful treatment of generalized granuloma annulare with pentoxifylline
Generalized granuloma annulare has a protracted course with only rare spontaneous resolution. It comprises 8–15% of all the cases. Diabetes has been reported in 21% of generalized granuloma annulare. Laboratory abnormalities such as hyperlipidemia, hypergammaglobulinemia and presence of circulating antinuclear antibodies have been observed. Investigations of our patient did not reveal any of these abnormalities except for high blood sugars. As described earlier, the histopathological changes in our patient were typical of interstitial granuloma annulare, which is the most common pattern reported in generalized granuloma annulare.
Generalized granuloma annulare is poorly responsive to therapy. Because our patient had an unsatisfactory response to multiple treatment options, pentoxifylline was given which showed a striking response.
Pentoxifylline is a phosphodiesterase inhibitor which is commonly used in intermittent claudication. Its dermatological uses include Raynauds phenomenon, livedoid vasculopathy, necrobiosis lipoidica and venous ulcers. Even though the drug has been in use since many decades, novel indications are emerging even in recent times.
Pentoxifylline has been successfully used in generalized granuloma annulare by Rubel et al. and Patrascu et al.
The exact mechanism of action of pentoxifylline in granuloma annulare is not known. We postulate that, in granuloma annulare, pentoxifylline, probably with its TNF alpha blocking action, inhibits macrophage activation, and hence the granulomatous inflammation. Moreover, with its anti-inflammatory action, it may also reduce the vasculitis occurring in granuloma annulare.
With its favorable toxicity profile and familiarity among dermatologists, pentoxifylline may be a good choice for this difficult to treat and distressing condition. We report this case as resolution of lesions of granuloma annulare with pentoxifylline has rarely been reported.
As an anecdotal side note, I have a patient with debilitating venous ulcers which have required daily wound dressing with various ointments and oxygenated fatty acids. I started him on pentoxifylline and within days, there was finally a positive progression of the ulcers after months of stagnation. The underlying tissues looked healthier and with better circulation.
From Treatment of vascular inner ear disease with pentoxifylline: a 4-week, controlled, randomized trial
The efficacy of pentoxifylline (PXF) in vascular inner ear disease (VIED) was studied comparing PXF and placebo in a 4-week study; 60 patients with unilateral loss of hearing, vertigo, dizziness, tinnitus (analyzed with an analogue scale line), and cochlear flow reduction were included. The aim of the study was to study the effect of PXF (1800 mg/day) in VIED considering clinical outcome and cochlear flow. All patients completed the study. Improvement in cochlear flow (p<0.05) and a decrease in score in both groups were observed. The cochlear flow increase was 287.5% in the PXF group vs 168% in the placebo group (119.5% difference; p<0.02). There was a difference in score decrease (44.1% larger) in the PXF group (p<0.05). PXF was more effective considering flow and symptoms.
I’m guilty of ignoring pentoxifylline throughout most of my life until I accompanied my Godmother to Swiss Medica Clinic in Belgrade. I was surprised to hear that she was going to receive pentoxifylline infusions. One of the doctors at the clinic told me as a matter of fact that it was due to the bad circulation. Amazing that something as simple as that could help. In my mind it was only for intermittent claudication and that was that. Networking works!
Pentoxifylline is also used as a painkiller. It has had results as a topical agent in combination with other things such as capsaicin. Better than taking opioids! From Novel Treatment of Radicular Pain With a Multi-Mechanistic Combination Topical Agent: A Case Series and Literature Review
Pharmacologic treatment of radicular pain with oral medications is limited by adverse effects and concern for dependence. While topical formulations have been explored in pain research, there is no published literature evaluating the efficacy in radicular pain. We present the first three cases of radicular pain successfully treated with a topical formulation of diclofenac, ibuprofen, baclofen, cyclobenzaprine, bupivacaine, gabapentin, and pentoxifylline.
Doctors forget it exists, specially when pharma-sponsored education only emphasize opioids and biological agents that costs thousands per vial. Comparatively speaking, pentoxiphylline is Big Pharma’s cheapest and good drug. Typically, most will not hear about its potential beneficial effect in quite a number of conditions including neuropathic pain. Pentoxifylline’s safety track record and beneficial effects should make it a first line of therapy before mind numbing pain killer drugs are considered.
I think it’s important to keep an open mind because pentoxifylline’s potential benefit might be due to a potentiation of effects when it is taken with adjunct therapy such as vitamins or antioxidants. Pentoxifylline works in various levels and other drugs that act on those same pathways can cost over a thousand euros per vial.
Granted, safety track record for a Big Pharma drug doesn’t mean zero reports of adverse effects. But I wouldn’t jump into conclusions or discard it based on some odd report that might have been due, in part, to other factors. I wouldn’t discard it either based on my experience with pentoxifylline in the public health care system. Sometimes I was biased to think that all the drugs people take are related to their current problems. That is not necessarily an opened minded approach. It is important to go through the studies with an open mind. What if pentoxifylline is something that could make the difference in a person’s life, even when it is combined with other efforts?
My Godmother benefited from pentoxifylline, some of the positive effects were corroborated when she was at home after the initial experience at the clinic. Other than the positive effects on the circulation of the lower limbs, there was also a significant reduction in her tinnitus and in her jaw problem that she’s dealt with for 40 years. Her neuropathic pain from a traumatic herniated disc was finally gone with pentoxifylline. Her brother has used it for COPD and he is feeling much better. A friend also saw an improvement in her vasculitis and another friend saw a relief in his hidradenitis suppurativa.
I myself didn’t care about pentoxifylline before, it was only after hearing people I care about deriving a positive effect from this drug that I got very curious as to what might be happening there.
I wouldn’t throw the baby with the bathwater, not all drugs are bad. Take a look at pubmed and see when, where and why pentoxifylline is prescribed.Share
About the Author:A countryside family medicine doctor and former heart surgeon in service of the Hippocratic Oath.