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Class: Hemorrheologic Agents
VA Class: CV900
Molecular Formula: C13H18N4O3
CAS Number: 6493-05-6
Brands: Pentoxil, TRENtal

Medically reviewed by Last updated on Jul 2, 2018.


Hemorrheologic agent; a synthetic xanthine derivative.1 2 3 4

Uses for Pentoxifylline

Peripheral Vascular Disease

Used for the symptomatic treatment of intermittent claudication associated with peripheral vascular disease (i.e., chronic occlusive arterial disease of the extremities).1 2 4 6 7 8 9 13 14 16 18 21 27 32 52 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 120 121 May improve function of the extremities and symptoms of the disease1 2 4 6 7 8 9 13 14 16 18 21 27 32 52 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 103 120 121 (e.g., improvement in walking distance and duration;2 4 6 7 8 13 14 27 32 35 52 57 59 60 61 62 63 64 65 68 69 71 119 120 121 reductions in severity and occurrence of paresthesia6 7 8 57 59 62 63 64 68 121 and trophic ulcers6 7 8 109 110 121 ). Does not affect other symptoms associated with claudication such as cramping, tiredness, tightness, and pain during exercise.57 59 62 63 64 68 Pentoxifylline should not replace more definitive therapy for peripheral vascular disease such as smoking cessation, weight loss, exercise therapy,18 103 107 108 121 or surgical bypass or removal of arterial obstructions when indicated.1

Cerebrovascular Disease

Also has been used for the management of acute73 76 81 83 121 and chronic cerebrovascular insufficiency73 74 75 77 78 79 80 81 82 83 84 85 86 87 121 . Improves psychopathologic symptoms74 81 87 121 (e.g., those associated with aging, stroke, TIAs), including memory loss, disorientation, constructional apraxia, impaired practical reasoning, motor impairment, and dizziness.74 81 87 Reduces the incidence of recurrence of TIAs.87 121

Male Infertility

Used in a limited number of patients for the treatment of male fertility disorders, including asthenospermia90 92 121 and idiopathic oligospermia.91 92 121 Increases the duration of activity of ejaculated spermatozoa.90 95

Pentoxifylline Dosage and Administration



Administer orally, preferably with meals.1

An aluminum and magnesium hydroxides antacid can be administered concomitantly to reduce intolerable GI effects.117



Peripheral Vascular Disease

400 mg 3 times daily.1 2 4 8 13 18 59 60 61 63 64 65 68 69 71 Continue for at least 8 weeks to determine efficacy.1 Reduce dosage to 400 mg twice daily if adverse GI and/or CNS effects develop.1 Discontinue if adverse effects persist at this lower dosage.1 Efficacy was demonstrated in clinical studies of 6-months duration.1

Cautions for Pentoxifylline


  • History of intolerance to pentoxyphylline or to xanthine derivatives such as caffeine, theophylline, or theobromine.1

  • Recent cerebral and/or retinal hemorrhage.1


General Precautions

Cardiovascular Effects

Other manifestations of arteriosclerotic disease may be exhibited frequently in patients with chronic occlusive arterial disease.1 Angina, hypotension, and arrhythmia reported occasionally in patients with concomitant coronary artery and/or cerebrovascular disease; consider the possibility that such effects may occur.1

Hematologic Effects

Periodic examination for signs of bleeding (e.g., hemoglobin and hematocrit determinations) recommended in patients who have risk factors potentially complicated by hemorrhage (e.g., recent surgery, peptic ulceration, cerebral and/or retinal bleeding).1

Specific Populations


Category C.1


Distributed into milk.1 102 104 Discontinue nursing or the drug, taking into account the importance of the drug to the woman.1

Pediatric Use

Safety and efficacy not established.a

Common Adverse Effects

Dyspepsia, nausea, dizziness.1

Interactions for Pentoxifylline

Specific Drugs





Potential pharmacokinetic interaction (reduced bioavailability of several metabolites)117

Interaction not clinically important; concomitant administration may reduce intolerable GI effects117

Antiarrhythmic agents

Interaction not observeda

Anticoagulants, oral (warfarin)

Possible bleeding an/or prolonged PT1

Determine prothrombin time more frequently during concomitant therapy1

Antidiabetic agents

Interaction not observed1

Antihypertensive agents

Possible additive antihypertensive effect1

Periodic monitoring of systemic blood pressure recommended;1 if required, reduce antihypertensive dosage 1

β-Adrenergic blocking agents

Interaction not observed1

Cardiac Glycosides

Interaction not observed1


Interaction not observed1

Platelet-aggregation inhibitors

Possible bleeding and/or prolonged PT


Possible increased theophylline levels and possible theophylline toxicitya

Closely monitor and adjust theophylline dosage as needed1

Pentoxifylline Pharmacokinetics



Rapidly and almost completely absorbed following oral administration,1 2 3 4 53 54 55 with peak plasma concentrations usually attained within 1 hour.1

Mean absolute bioavailability is 33% in healthy men.122


Symptomatic relief may occur within 2–4 weeks following initiation of therapy.1 The therapeutic effects result principally from an action on newly formed erythrocytes rather than on circulating mature erythrocytes.3 Allow at least 8 weeks to determine full therapeutic efficacy.1


Food increases mean peak plasma concentrations and mean AUC.a

Special Populations

Peak plasma concentrations and mean absolute bioavailability were substantially increased, and time to peak concentration was prolonged in adults with hepatic cirrhosis.122

Increased AUC in patients 60–68 years of age, compared to younger adults.1



Not known whether pentoxifylline or its metabolites cross the placenta.102 103 Pentoxifylline and its metabolites are distributed into milk.102 104



Extensively metabolized in erythrocytes and the liver to active metabolites3 4 53 , principally via reduction, oxidation, and demethylation.3 4 53 55

Elimination Route

Eliminated in urine (95%) 3 4 53 55 and feces (4%), principally as metabolites.1 3 4 53 55


0.4–0.8 hours.1 53 55

Special Populations

Prolonged elimination in adults with hepatic cirrhosis.122

Decreased elimination rate in patients 60–68 years of age, compared with younger adults.1





Tight, light-resistant containers at 15–30°C.1

Actions and Spectrum

  • Increases erythrocyte flexibility (deformability)1 2 3 4 6 7 8 9 10 11 12 13 18 19 20 21 and reduces the viscosity of whole blood, which decreases total systemic vascular resistance,3 4 improves blood flow,1 2 3 18 and increases tissue oxygenation1 2 3 4 6 7 8 9 10 11 12 13 14 15 in patients with peripheral vascular disease.1 2 3 4 6 7 16 17 20 21

  • Affects the electrolyte balance of erythrocytes which may improve erythrocyte flexibility and blood flow.6 7 29

  • May improve poststenotic blood flow in relatively poorly perfused tissue.6 7 26 27 30 31 32 Improves resting blood flow and reactive hyperemia.26 31 Increases peak flow of reactive hyperemia in the extremities indicating an increase in reserve blood flow which is associated with some increase in walking distance.31

  • Improves regional and hemispheric cerebral blood flow, particularly in ischemic areas where microcirculation is impaired.73 74 75 76 77 78 79 81 82 83 84 85 86 87 Increases oxygen and glucose supply, eliminates or reduces perivascular edema, and enhances cellular function in some patients with cerebrovascular insufficiency.77 82 87 121

Advice to Patients

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information. (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name



Dosage Forms


Brand Names



Tablets, extended-release, film-coated

400 mg*

Pentoxifylline Extended-release Tablets

Biovail, Clonmel, Impax, Mylan, Pliva, Purepac, Teva, Torpharm, Watson



TRENtal (with povidone)


AHFS DI Essentials™. © Copyright 2019, Selected Revisions July 1, 2006. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.


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