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 (genetics), base found in most human body tissues and fluids, as well as in other organisms. Several stimulants are derived from xanthine, incl ...

derivative used as a drug to treat muscle pain in people with

peripheral artery disease Peripheral artery disease (PAD) is an abnormal narrowing of arteries other than those that supply the heart or brain. When narrowing occurs in the heart, it is called coronary artery disease, and in the brain, it is called cerebrovascular diseas ...

. 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, and ...

, a form of muscle pain resulting from

s. This is its only

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...

, 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 m ...

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 ( ...

(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 Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...

and other steroids, as the drug can inhibit excess levels of

TNF-a Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...

, which is associated with

granuloma A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious ...

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 damag ...

with some success. Pentoxifylline has also been shown to be of benefit in

alcoholic hepatitis Alcoholic hepatitis is hepatitis (inflammation of the liver) due to excessive intake of alcohol. Patients typically have a history of at least 10 years of heavy alcohol intake, typically 8-10 drinks per day. It is usually found in association wit ...

, 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 transplan ...

. 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, whi ...

quality and motility for

in vitro fertilization In vitro fertilisation (IVF) is a process of fertilisation where an egg is combined with sperm in vitro ("in glass"). The process involves monitoring and stimulating an individual's ovulatory process, removing an ovum or ova (egg or eggs) ...

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 state ...

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 male ...

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 Lipoic acid (LA), also known as α-lipoic acid, alpha-lipoic acid (ALA) and thioctic acid, is an organosulfur compound derived from caprylic acid (octanoic acid). ALA is made in animals normally, and is essential for aerobic metabolism. It is a ...

gabapentin Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diabet ...

. 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 Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...

, 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-lasti ...

, bleeding, hallucinations, arrhythmias, and

aseptic meningitis Aseptic meningitis is the inflammation of the meninges, a membrane covering the brain and spinal cord, in patients whose cerebral spinal fluid test result is negative with routine bacterial cultures. Aseptic meningitis is caused by viruses, myco ...

. 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 cycli ...

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 Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase. Leukotrienes ...

synthesis, and reduces inflammation and

innate immunity The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...

. 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 biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...

in non-alcoholic

steatohepatitis Steatohepatitis is a type of fatty liver disease, characterized by inflammation of the liver with concurrent fat accumulation in liver. Mere deposition of fat in the liver is termed steatosis, and together these constitute fatty liver changes. T ...

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 Hearing, 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 Language ...

. Human studies have been conducted for

Peyronie's disease Peyronie's disease is a connective tissue disorder involving the growth of fibrous plaques in the soft tissue of the penis. Specifically, scar tissue forms in the tunica albuginea, the thick sheath of tissue surrounding the corpora cavernosa, ca ...

. Pentoxifylline, in combination with

tocopherol Tocopherols (; TCP) are a class of organic chemical compounds (more precisely, various methylated phenols), many of which have vitamin E activity. Because the vitamin activity was first identified in 1936 from a dietary fertility factor in rats, i ...

and

clodronate Clodronic acid ( INN) or clodronate disodium ( USAN) is a first generation (non-nitrogenous) bisphosphonate. It is an anti-osteoporotic drug approved for the prevention and treatment of osteoporosis in post-menopausal women and men to reduce verte ...

, has been found to heal refractory

osteoradionecrosis Osteoradionecrosis (ORN) is a serious complication of radiation therapy in cancer treatment where radiated bone becomes necrotic and exposed. ORN occurs most commonly in the mouth during the treatment of head and neck cancer, and can arise over 5 y ...

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