What is Pentoxyphylline (Trental)?

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From the Guidelines

Pentoxifylline is not recommended for the treatment of claudication due to its lack of effectiveness, as stated in the 2017 AHA/ACC guideline 1. The guideline assigns a Class III: No Benefit recommendation with a Level of Evidence B-R, indicating that pentoxifylline is not effective for treating claudication 1. This recommendation is based on a Cochrane review of 24 studies with 3,377 participants, which showed large variability in study design and results, making the review's effectiveness unclear 1. Additionally, a multicenter RCT comparing pentoxifylline, cilostazol, or placebo for patients with moderate-to-severe claudication found no difference between pentoxifylline and placebo in the primary endpoint of maximal walking distance 1.

Some older guidelines, such as the 2013 ACCF/AHA guideline, suggest that pentoxifylline may be considered as second-line alternative therapy to cilostazol to improve walking distance in patients with intermittent claudication 1. However, this recommendation is based on a lower level of evidence (Level of Evidence: A) and is not supported by more recent guidelines 1. The clinical effectiveness of pentoxifylline as therapy for claudication is marginal and not well established, with a Level of Evidence: C 1.

In terms of dosage, the typical dosage of pentoxifylline is 400 mg taken orally three times daily with meals 1. Pentoxifylline works by decreasing blood viscosity and improving red blood cell flexibility, which enhances microcirculation in affected areas 1. It also has anti-inflammatory properties that may contribute to its effectiveness 1. Common side effects include nausea, dizziness, headache, and stomach discomfort, which can often be minimized by taking the medication with food 1. Patients with recent cerebral or retinal hemorrhage should avoid pentoxifylline, and those with kidney or liver impairment may require dose adjustments 1.

Given the lack of effectiveness of pentoxifylline in treating claudication, as stated in the most recent guideline 1, it is not recommended as a treatment option for patients with intermittent claudication. Instead, other treatments such as smoking cessation, regular exercise, and appropriate diet modifications should be prioritized as part of a comprehensive treatment approach 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Pentoxyphilli e

  • Pentoxyphilline, also known as pentoxifylline, is a medication used to treat intermittent claudication, a symptom of peripheral arterial occlusive disease (PAD) 2.
  • The mechanism of action of pentoxifylline is poorly understood, but it is thought to involve improving red blood cell deformability, reducing fibrinogen concentration, platelet adhesiveness, and whole blood viscosity 3.
  • Pentoxifylline has been shown to increase pain-free walking distance and total walking distance in patients with intermittent claudication, although the evidence is not consistent across all studies 4, 2.
  • The recommended dose of pentoxifylline is 400 mg three times daily with meals 3.
  • Pentoxifylline is generally well tolerated, but it can cause side effects such as headache, palpitations, and diarrhea 5, 2.

Comparison with Cilostazol

  • Cilostazol is another medication approved for the treatment of intermittent claudication, and it has been compared to pentoxifylline in several studies 4, 6, 5.
  • Cilostazol has been shown to be more effective than pentoxifylline in improving walking distance in patients with intermittent claudication 6, 5.
  • However, pentoxifylline may still have a place in the treatment of intermittent claudication, particularly as a complementary treatment to lifestyle changes, exercise, and secondary prevention measures 2.

Efficacy and Safety

  • The efficacy of pentoxifylline in treating intermittent claudication is uncertain due to the poor quality of published studies and the large degree of heterogeneity in the interventions and results 2.
  • Pentoxifylline is generally well tolerated, but it can cause side effects such as headache, palpitations, and diarrhea 5, 2.
  • The safety and efficacy of pentoxifylline should be assessed on an individual basis, taking into account the patient's medical history, lifestyle, and other treatments 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Pentoxifylline for intermittent claudication.

The Cochrane database of systematic reviews, 2012

Research

Treatment of intermittent claudication with pentoxifylline and cilostazol.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2001

Research

Cilostazol for intermittent claudication.

The Cochrane database of systematic reviews, 2014

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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