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(pen toks IF i lin)

Index Terms

  • Oxpentifylline
  • Trental

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet Extended Release, Oral:

TRENtal: 400 mg [DSC] [contains benzyl alcohol]

Generic: 400 mg

Brand Names: U.S.

  • TRENtal [DSC]

Pharmacologic Category

  • Blood Viscosity Reducer Agent


Pentoxifylline increases blood flow to the affected microcirculation. Although the precise mechanism of action is not well-defined, blood viscosity is lowered, erythrocyte flexibility is increased, leukocyte deformability is increased, and neutrophil adhesion and activation are decreased. Overall, tissue oxygenation is significantly increased.


Well absorbed


Hepatic to multiple metabolites; undergoes extensive first-pass effect; Pentoxifylline undergoes reduction to metabolite I (active), and oxidation to form metabolite V (active) (Ward 1987); Note: Plasma concentrations of M-1 and M-V are 5 and 8 times greater, respectively, than pentoxifylline


Urine (0% as unchanged, 50% to 80% as M-V metabolite, 20% as other metabolites); feces (<4%)

Onset of Action

2 to 4 weeks with multiple doses

Time to Peak

Serum: 2 to 4 hours

Half-Life Elimination

Parent drug: 24 to 48 minutes; Metabolites: 60 to 96 minutes

Special Populations: Renal Function Impairment

In patients with mild to moderate renal impairment, AUC0-tss and Cmax of the active Metabolite V increased 2.4- and 2.1-fold, respectively. In patients with severe renal impairment, the AUC0-tss and Cmax of active Metabolite V increased 12.9- and 10.6-fold, respectively. Twice daily administration increased the exposure to metabolite V only slightly in both groups.

Special Populations: Hepatic Function Impairment

Following a single dose of pentoxifylline, the AUC increased 6.5-fold and the Cmax increased 7.5-fold in patients with mild to moderate hepatic impairment, The AUC and Cmax of active Metabolite I also increased 6.9- and 8.2-fold, respectively. Studies were not conducted in patients with severe hepatic failure.

Special Populations: Elderly

Pentoxifylline: Increased AUC and decreased elimination rate (60 to 68 years of age).

Use: Labeled Indications

Intermittent claudication: Treatment of intermittent claudication on the basis of chronic occlusive arterial disease of the limbs.

Limitations of use: May improve function and symptoms, but not intended to replace more definitive therapy. Note: The American College of Chest Physicians (ACCP) discourages the use of pentoxifylline for the treatment of intermittent claudication refractory to exercise therapy (and smoking cessation) (Guyatt, 2012).

Use: Unlabeled

Severe alcoholic hepatitis; venous leg ulcers (with compression therapy)


Patients previously exhibiting intolerance to pentoxifylline, xanthines (eg, caffeine, theophylline), or any component of the formulation; recent cerebral and/or retinal hemorrhage

Canadian labeling: Additional contraindications (not in U.S. labeling): Acute MI, severe coronary artery disease when myocardial stimulation might prove harmful, peptic ulcers (current or recent)

Dosing: Adult

Intermittent claudication: Oral: 400 mg 3 times daily; maximal therapeutic benefit may take 2 to 4 weeks to develop; recommended to maintain therapy for at least 8 weeks. May reduce to 400 mg twice daily if GI or CNS side effects occur; discontinue if side effects persist.

Note: Use for the treatment of intermittent claudication refractory to exercise therapy (and smoking cessation) has been discouraged by The American College of Chest Physicians (ACCP) (Guyatt, 2012).

Severe alcoholic hepatitis (Maddrey Discriminant Function [MDF] score ≥32, especially when corticosteroids contraindicated) (off-label use): Oral: 400 mg 3 times daily for 4 weeks (O’Shea, 2010)

Venous leg ulcer (off-label use): Oral: 400 mg 3 times daily (with compression therapy) (Jull, 2002; Robson, 2006)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

Manufacturer's labeling: CrCl <30 mL/minute: 400 mg once daily

The following guidelines have been used by some clinicians:

Aronoff, 2007: Adults:

CrCl >50 mL/minute: 400 mg every 8 to 12 hours

CrCl 10-50 mL/minute: 400 mg every 12 to 24 hours

CrCl <10 mL minute: 400 mg every 24 hours

Hemodialysis: supplemental postdialysis dose is not necessary.

Peritoneal dialysis: 400 mg every 24 hours

Paap, 1996: Adults:

Moderate renal impairment (CrCl ~60 mL/minute): 400 mg twice daily.

Severe renal impairment (CrCl ~20 mL/minute): 400 mg once daily; further reduction may be required; Paap suggests 200 mg once daily, but with current products (extended or controlled release; unscored) may require adaptation to 400 mg once every other day.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in manufacturer’s labeling; use with caution.

Extemporaneously Prepared

A 20 mg/mL oral suspension may be made using tablets. Crush ten 400 mg tablets and reduce to a fine powder. Add a small amount of purified water and mix to a uniform paste; mix while adding purified water to almost 200 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 200 mL. Label "shake well" and "refrigerate". Stable 91 days.

Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.


Administer with food. Swallow whole; do not chew, crush, or divide.

Dietary Considerations

May be taken with meals.


Store between 20°C to 25°C (68°F to 77°F); protect from light.

Drug Interactions

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): Pentoxifylline may enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Blood Pressure Lowering Agents: Pentoxifylline may enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Cimetidine: May increase the serum concentration of Pentoxifylline. Monitor therapy

CYP1A2 Inhibitors (Strong): May increase the serum concentration of Pentoxifylline. Monitor therapy

Heparin: Pentoxifylline may enhance the anticoagulant effect of Heparin. Monitor therapy

Heparin (Low Molecular Weight): Pentoxifylline may enhance the anticoagulant effect of Heparin (Low Molecular Weight). Monitor therapy

Ketorolac (Nasal): May enhance the adverse/toxic effect of Pentoxifylline. Specifically, the risk of bleeding may be increased. Avoid combination

Ketorolac (Systemic): May enhance the adverse/toxic effect of Pentoxifylline. Specifically, the risk of bleeding may be increased with this combination. Avoid combination

Theophylline Derivatives: Pentoxifylline may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Pentoxifylline may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Test Interactions

Concomitant administration increases theophylline levels

Adverse Reactions

1% to 10%: Gastrointestinal: Nausea (2%), vomiting (1%)

<1% (Limited to important or life-threatening): Anaphylactic shock, anaphylactoid reaction, anaphylaxis, angioedema, angina pectoris, anorexia, aplastic anemia, aseptic meningitis, blurred vision, cardiac arrhythmia, chest pain, cholecystitis, conjunctivitis, decreased serum fibrinogen, depression, dyspnea, hallucination, hepatitis, hypotension, increased liver enzymes, jaundice, leukemia, leukopenia, pancytopenia, scotoma, seizure, tachycardia, thrombocytopenia


Concerns related to adverse effects:

• Anaphylaxis/anaphylactoid reactions: Discontinue at first sign of anaphylaxis or anaphylactoid reaction.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with mild to moderate hepatic impairment; the bioavailability of pentoxifylline and metabolite I is increased. Has not been studied in patients with severe hepatic disease.

• Renal impairment: Use with caution in patients with renal impairment; bioavailability of active metabolite V may be increased.

Special populations:

• Elderly: Use with caution in the elderly due to the potential for cardiac, hepatic, or renal impairment.

Monitoring Parameters

Renal function; hemoglobin/hematocrit in patients with risk factors for hemorrhage

Pregnancy Risk Factor


Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Information related to use in pregnant women has not been located. Pentoxifylline may be used to test sperm viability when evaluating nonfertile males (ASRM, 2012). It has also been evaluated for the treatment of infertility due to endometriosis, but use for this purpose is not currently recommended (Lu, 2012).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience burping, bloating, dizziness, flatulence, headache, vomiting, or nausea. Have patient report immediately to prescriber angina, arrhythmia, severe dizziness, or passing out (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.