Pentoxifylline: What is it? Uses, Metabolism, Administration and Effects

It is a medication that decreases the viscosity of the blood and is used to treat the symptoms of intermittent claudication due to peripheral vascular disease (PVD).

Pentoxifylline is a derivative of Xanthine. It is extensively metabolized by red blood cells and in the liver but does not affect the levels of cytochrome P450 activity.

It has not been associated with elevated serum enzymes during therapy, but in several reports of isolated cases, it has been linked to a clinically apparent liver injury.

Although Pentoxifylline has been reported to cause such a condition, most cases have been mild and self-limiting. Several have occurred in patients with a history of intolerance to caffeine and Xanthine derivatives. Therefore, patients with hypersensitivity to Xanthine should avoid using this medication.

Class of drug: Cardiovascular drug. Intermittent claudication agent. It is derived from Xanthine.


This medication improves the symptoms of a particular blood flow problem in the legs or arms. It can decrease muscle pain and cramping during exercise, including walking.

Pentoxifylline belongs to a class of medications known as hemorheological agents. It works by helping blood flow more quickly through the narrow arteries.


This increases the amount of oxygen the blood can supply when the muscles need more (such as during exercise), thus increasing the distance of travel and duration.


It should be taken orally with food, usually three times a day or as directed by the doctor or pharmacist.

It should not be crushed or chewed since doing so can release all the medication at once, thus increasing the risk of side effects.

Also, tablets should not be separated unless they have a scoring line and the doctor or pharmacist indicates it is done. Swallow the whole or divided tablet without crushing or chewing.

The dose is based on the medical condition and response to treatment. Using the medication regularly helps you get the most benefit from it.

It is essential to continue taking it even if it feels good. It should not be stopped without consulting the doctor.

The improvement in symptoms can occur from 2 to 4 weeks, but Pentoxifylline can take up to 8 weeks to get the full benefit.

If your condition persists or worsens, notify your doctor.

The recommended dose and dose adjustment

The recommended initial dose is 400 mg, twice a day after meals. The usual dose is 400 mg two or three times a day. A maximum of 400 mg three times a day should not be exceeded.

It can take up to two months to get complete results.

Clinical use

Pentoxifylline is indicated for the symptomatic treatment of:

  • Patients with peripheral vascular disorders:  In such patients, it can alleviate the signs and symptoms of altered blood flow, such as intermittent claudication or trophic ulcers.

Storage and stability

  • Store at room temperature (15 to 30 ° C).
  • Protect from light.
  • Protect from moisture and excessive heat.


Pentoxifylline, a synthetic derivative of dimethylxanthine, structurally related to theophylline and caffeine, is used in the treatment of peripheral vascular diseases and the treatment of cerebrovascular insufficiency, sickle cell disease, and diabetic neuropathy.

Metabolism and elimination route

After oral administration, the aqueous solution of Pentoxifylline is almost completely absorbed. He suffers the first-pass metabolism, and several metabolites appear in the plasma shortly after administration; Maximum plasma levels are reached within 2 hours.

The excretion of the drug is almost urinary; The main biotransformation product is Metabolite V. Essentially, no original prescription is found in the urine.

Despite the variations in the levels of the original compound and its metabolites in the plasma, the urinary recovery of the metabolite V is constant and proportional to the dose. Less than 4% of the administered dose is recovered in the stool.

Interactions with other drugs

Using Pentoxifylline in conjunction with the following drugs can generate different reactions:

  • Abciximab: may increase antiplatelet activities.
  • Abiraterone: the serum concentration of Pentoxifylline may be increased when combined with Abiraterone.
  • Acebutolol: Pentoxifylline may increase the hypotensive activities of Acebutolol.
  • Acenocoumarol: May increase anticoagulant activities.
  • Acetylsalicylic acid: Pentoxifylline may increase the antiplatelet activities of acetylsalicylic acid.
  • Aliskiren: increases hypotensive activities.
  • Aloxiprine: The risk or severity of side effects may be increased when Pentoxifylline is combined with Aloxiprine.
  • Alprenolol: used in conjunction with Pentoxifylline can increase hypotensive activities.
  • Acenocoumarol: may increase anticoagulant activities.
  • Alprostadil: increases antiplatelet activities.
  • Alteplase: Pentoxifylline may increase the anticoagulant activities of Alteplase.

Action mechanisms

There are many hypotheses about the mechanism of action of Pentoxifylline and its cellular and molecular effects, based on studies in humans and animals.

This includes the effects on immune modulation, the impact of tumor necrosis factor, hemorheological effects, and antifibrinolytic effects, together with the impact on endothelial cells and adhesion molecules.

It can be said that Pentoxifylline inhibits the phosphodiesterase of the erythrocytes, which increases the CAMP activity of the erythrocytes. Subsequently, the erythrocyte membrane becomes more resistant to deformity.

Along with erythrocyte activity, Pentoxifylline also decreases blood viscosity by reducing plasma concentrations of fibrinogen and increasing fibrinolytic activity.


Anti-inflammatory effects

It is known that Pentoxifylline is an essential inflammatory mediator with a broad field of activity predominantly produced by mononuclear cells.

This is also an active inhibitor of TNF, and there is evidence that it may influence other inflammatory cytokines.

Antifibrinolytic effects

Pentoxifylline increases the collagenases of fibroblasts and decreases the production of collagen, fibronectin, and mucopolysaccharides. These effects could be attributed to its anti-inflammatory properties.

Hemorrheological effects

Pentoxifylline affects almost all factors responsible for blood viscosity and is among the first known drugs with hemorrhagic activity.

The main hemorrhagic effects of Pentoxifylline are caused by the increased deformability of red blood cells and the decrease in blood viscosity.

It leads to the inhibition of thromboxane and the increase in prostacyclin synthesis. The hypercoagulability states improve due to the decrease in the aggregation and adhesion of the platelets.

The increase of plasminogen activator and anti-thrombin infers the possibility of a more significant role of polymorphonuclear leukocytes in the viscosity of whole blood.

Therefore, Pentoxifylline can be considered an almost complete rheological drug.

Other effects

It leads to a broad field-effect against cell proliferation and inflammation. It also reduces the expression of adhesion molecules such as intercellular adhesion molecule I (ICAM-I) in keratinocytes and E-selectin in endothelial cells.

Use in dermatology

Pentoxifylline is a methyl-xanthine derivative with many anti-inflammatory effects. It is effective for many dermatological and non-dermatological conditions.

It has been used both as a primary and adjuvant drug and is a safe and relatively cost-effective alternative medicine.

Note: The use and efficacy of Pentoxifylline for various dermatological conditions have been demonstrated in several studies over a long period. However, the United States Food and Drug Administration (FDA) has approved its use only for intermittent claudication.

Pentoxifylline has found a place in the treatment of a variety of dermatological conditions such as:

Peripheral vascular diseases

Pentoxifylline has been used throughout the world to treat intermittent claudication, and in 1984 the United States FDA approved its use for intermittent claudication.

Several studies have demonstrated the therapeutic efficacy of Pentoxifylline in a significant percentage of patients with peripheral vascular disease. However, use in intermittent claudication remains the main indication.

Intravenous Pentoxifylline may be beneficial in acute ischemic lesions in systemic sclerosis.

Vasculopathies and vasculitis

Due to its multiple effects on various blood cells and its anti-inflammatory effects, Pentoxifylline could be a helpful drug in treating vascular diseases.

Diseases and venous ulcers in the legs

This medication is also used to treat venous leg diseases and ulcers, especially in patients who can not tolerate compression therapy.

Pigmented purpuric dermatoses

Successful treatment with Pentoxifylline causes a decrease in the intercellular adhesion molecule I in endothelial cells and around extensive dermal lesions.

Pentoxifylline is inexpensive, readily available and has no severe side effects, and should be considered for use in Schamberg disease.

Aftosis and Behçet’s disease

It has been discovered that Pentoxifylline is effective in recurrent oral and genital fantasies. These beneficial effects may be due to their anti-inflammatory properties and to the correction of the lack of strength of the erythrocyte deformability.


Pentoxifylline rapidly improves the systemic symptoms of the type II leprosy reaction and could be an alternative (although less effective) to thalidomide and a good option for patients with HIV.

Acquired immunodeficiency syndrome and papular pruritic HIV / AIDS rash.

This drug can be considered a safe and effective treatment for pruritus in patients infected with HIV. However, more controlled studies are required to authenticate it.

This could be due to the inhibitory effect of Pentoxifylline on the tumor necrosis factor-alpha, which increases in many patients with AIDS.


It suppresses the transcription of the gene TNF-α (tumor necrosis factor-alpha), potentiates the expression of inducible nitric oxide, and decreases the migration and adhesion of leukocytes.

TNF-α seems to play a significant role in this disease’s pathogenesis. Pentoxifylline has been proposed to treat cutaneous and mucocutaneous leishmaniasis, which significantly reduces the healing time and avoids the need for additional courses of pentavalent antimony.


Pentoxifylline counteracts the unwanted effects of cyclosporine on red blood cells. The abnormal metabolism of triglycerides is standard in psoriatic patients.

This medication possibly reduces triglycerides in the serum, so it seems sensible to use it to reduce such side effects.


It can almost wholly disable the spontaneous production of TNF-α from alveolar macrophages of patients with sarcoidosis.

Fibrosis is induced by radiation and burns.

Pentoxifylline reduces collagen biosynthesis induced by TGF-beta. Treating radiation-induced fibrosis with Pentoxifylline and vitamin E can be a practicable and cost-effective regimen, especially for inoperable patients.

Reactions of irritative and allergic hypersensitivity

Several studies in animals suggest a possible role of the pharmacological intervention with Pentoxifylline to treat contact dermatitis.

Other uses

It can also be beneficial in other diseases such as:

  • Kimura disease with oral ulcers.
  • You generalized ring granuloma.
  • Sweet’s syndrome.
  • Pénfigo vulgar.

Non-Dermatological Uses

  • Conservative treatment of neuropathic lesions.
  • Prevention of strokes.
  • Management of sickle cell disease.
  • Nausea and headaches in altitude sickness in the mountains.
  • Acute alcoholic and nonalcoholic steatohepatitis.
  • Alcoholic liver disease
  • Treatment of endometriosis.
  • Stimulation of various parameters of sperm movement.
  • The penetrability of cervical mucus in patients with Astenozoospermia.

All this presumably through its ability to inhibit TNF.


It would help if you were not allergic to products that contain caffeine, theobromine, theophylline, or any other drug.

Do not ingest it if you have any kidney disease or are pregnant, planning pregnancy, or breastfeeding, because Pentoxifylline is excreted in breast milk and may cause adverse effects in the infant.

Avoid driving a car or operating machinery when using Pentoxifylline.

Laboratory and medical tests (such as blood counts and blood pressure) should be performed continuously to monitor your progress or detect side effects.

Lifestyle changes that can help reduce the symptoms of intermittent claudication include:

  • Give up smoking.
  • Exercise regularly
  • Lose weight.

Ask your doctor about changes in lifestyle that may benefit you.

Before taking Pentoxifylline, tell your doctor if you are allergic to it, caffeine or theophylline, or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems.

Aspirin may increase the risk of bleeding when used with this medication. However, if your doctor told you to take a low dose of aspirin to prevent a heart attack or stroke, you should continue taking it unless your doctor tells you otherwise.

Side effects

  • Sickness.
  • Vomiting
  • Gases.
  • Eructation and dizziness.
  • Severe rare side effect: chest pain.

But, in general, Pentoxifylline is a very safe medicine and is generally well tolerated.