Pentoxifylline, also known as oxpentifylline, is a

xanthine Xanthine ( or ; archaically xanthic acid; systematic name 3,7-dihydropurine-2,6-dione) is a purine base found in most human body tissues and fluids, as well as in other organisms. Several stimulants are derived from xanthine, including caffein ...

derivative used as a drug to treat muscle pain in people with peripheral artery disease. It is

generic Generic or generics may refer to: In business * Generic term, a common name used for a range or class of similar things not protected by trademark * Generic brand, a brand for a product that does not have an associated brand or trademark, other ...

and sold under many brand names worldwide.Drugs.co
drugs.com international listings for Pentoxifylline
Page accessed Feb 1, 206

Medical uses

Its primary use in medicine is to reduce pain, cramping, numbness, or weakness in the arms or legs which occurs due to

intermittent claudication Intermittent claudication, also known as vascular claudication, is a symptom that describes muscle pain on mild exertion (ache, cramp, numbness or sense of fatigue), classically in the calf muscle, which occurs during exercise, such as walking, an ...

, a form of muscle pain resulting from peripheral artery diseases. This is its only FDA, MHRA and TGA-labelled indication. However, pentoxifylline is also recommended for

off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...

use as an adjunct to compression bandaging for the treatment of chronic venous leg ulcers by the

Scottish Intercollegiate Guidelines Network Healthcare Improvement Scotland (HIS) is the national healthcare improvement organisation for Scotland. It is a public body which is part of the Scottish National Health Service, created in April 2011. History NHS Quality Improvement Scotland (N ...

(SIGN) as this has been shown to improve healing rates. Pentoxifylline has been tested for use in

sarcoidosis Sarcoidosis (also known as ''Besnier-Boeck-Schaumann disease'') is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly af ...

patients as an alternative or compliment to prednisone and other steroids, as the drug can inhibit excess levels of TNF-a, which is associated with granuloma formation. Pentoxifylline has also been used to treat immunologic reactions to

leprosy Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria '' Mycobacterium leprae'' or '' Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve d ...

with some success. Pentoxifylline has also been shown to be of benefit in alcoholic hepatitis, with some studies demonstrating a reduction in risk of

hepatorenal syndrome Hepatorenal syndrome (often abbreviated HRS) is a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure. HRS is usually fatal unless a liver transpl ...

. Pentoxifylline has been used to improve

sperm Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, ...

quality and motility for in vitro fertilization and as safe oral drug in the treatment of male

infertility Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal st ...

and

erectile dysfunction Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of ma ...

An interesting off-label indication of pentoxifylline is the supportive treatment of distal

diabetic neuropathy Diabetic neuropathy is various types of nerve damage associated with diabetes mellitus. Symptoms depend on the site of nerve damage and can include motor changes such as weakness; sensory symptoms such as numbness, tingling, or pain; or autonomic c ...

, where it can be added, for example, to thioctic acid or gabapentin. Theoretically, it can (among other things) act prophylactically against ulcerative changes of the lower limbs associated with chronically decompensated diabetes. Patients with measurable impairment in arterial supply are more likely to benefit from adjunctive treatment with pentoxifylline. The administration of higher doses of pentoxifylline in hospitalization for complications of distal diabetic neuropathy is usually conditioned by the joint agreement of the neurologist with the physicians of internal medicine (diabetology and angiology).

Adverse effects

Common side effects are belching, bloating, stomach discomfort or upset, nausea, vomiting,

indigestion Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier t ...

, dizziness, and flushing. Uncommon and rare side effects include angina, palpitations, hypersensitivity, itchiness, rash,

hives Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-last ...

, bleeding, hallucinations, arrhythmias, and aseptic meningitis. Contraindications include intolerance to pentoxifylline or other xanthine derivatives, recent retinal or cerebral haemorrhage, and risk factors for haemorrhage.

Mechanism

Like other methylated xanthine derivatives, pentoxifylline is a competitive nonselective

phosphodiesterase inhibitor A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), thereby preventing the inactivation of the intracellular second messengers, cyclic adenosine monophosphate (cAMP) and c ...

which raises intracellular

cAMP Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...

, activates

PKA PKA may refer to: * Professionally known as: ** Pen name ** Stage persona * p''K''a, the symbol for the acid dissociation constant at logarithmic scale * Protein kinase A, a class of cAMP-dependent enzymes * Pi Kappa Alpha, the North-American so ...

, inhibits TNF and leukotriene synthesis, and reduces inflammation and innate immunity. In addition, pentoxifylline improves red blood cell deformability (known as a haemorrheologic effect), reduces blood viscosity and decreases the potential for platelet aggregation and blood clot formation. Pentoxifylline is also an antagonist at

adenosine Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9- glycosidic bond. Adenosine is one of the four nucleoside building ...

2 receptors.

Research

There is some evidence that pentoxifylline can lower the levels of some biomarkers in non-alcoholic steatohepatitis but evidence is insufficient to determine if the drug is safe and effective for this use. Animal studies have been conducted exploring the use of pentoxifylline for

and

hearing loss Hearing loss is a partial or total inability to hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to acquire spoken l ...

. Human studies have been conducted for Peyronie's disease. Pentoxifylline, in combination with tocopherol and clodronate, has been found to heal refractory osteoradionecrosis of the jaw, and to be prophylactic against osteoradionecrosis. In a Cochrane systematic review on the use of pentoxifylline for intermittent claudication in 2015, the following was concluded "The quality of included studies was generally low, and very large variability between studies was noted in reported findings including duration of trials, doses of pentoxifylline and distances participants could walk at the start of trials. Most included studies did not report on randomisation techniques or how treatment allocation was concealed, did not provide adequate information to permit judgement of selective reporting and did not report blinding of outcome assessors. Given all these factors, the role of pentoxifylline in intermittent claudication remains uncertain, although this medication was generally well tolerated by participants".

References

External links