What is the use of Pentoxifylline (PTX)?

From the Guidelines

Pentoxifylline is not recommended for the treatment of claudication due to its lack of effectiveness, as evidenced by a multicenter RCT and a Cochrane review of 24 studies with 3,377 participants 1.

Key Points

• The 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease recommends against the use of pentoxifylline for claudication treatment, citing a Class III: No Benefit recommendation with a Level of Evidence B-R 1.
• A Cochrane review of 24 studies found large variability in study design and results, leading to unclear effectiveness of pentoxifylline for claudication treatment, despite it being generally well tolerated 1.
• A multicenter RCT comparing pentoxifylline, cilostazol, or placebo in patients with moderate-to-severe claudication showed no difference between pentoxifylline and placebo in maximal walking distance, the primary endpoint 1.

Considerations

• Patients with claudication should focus on evidence-based treatments such as smoking cessation, regular exercise, and appropriate diet modifications.
• Alternative medications like cilostazol may be considered for claudication treatment, depending on individual patient needs and medical history.
• Pentoxifylline's anti-inflammatory properties and potential off-label uses should not overshadow its lack of efficacy in treating claudication, as supported by the most recent and highest quality evidence 1.

From the FDA Drug Label

Pentoxifylline Extended-Release Tablets are indicated for the treatment of patients with intermittent claudication on the basis of chronic occlusive arterial disease of the limbs. The FDA drug label does not answer the question.

From the Research

Overview of Pentoxyphilline

• Pentoxyphilline is a drug used to treat intermittent claudication, a symptom of peripheral arterial disease (PAD) characterized by high morbidity and mortality 2, 3, 4.
• The mechanism of action of pentoxyphilline involves decreasing blood viscosity, improving erythrocyte flexibility, and promoting microcirculatory flow and tissue oxygen concentration 2, 3, 4.

Efficacy of Pentoxyphilline

• Studies have shown that pentoxyphilline may improve pain-free walking distance (PFWD) and total walking distance (TWD) in patients with intermittent claudication, but the results are variable and the quality of the evidence is generally low 2, 3, 4.
• The difference in percentage improvement in TWD for pentoxyphilline over placebo ranged from 1.2% to 155.9%, and in PFWD from -33.8% to 73.9% 2, 3, 4.
• There is no statistically significant difference in ankle-brachial pressure index (ABI) between the pentoxyphilline and placebo groups 2, 3, 4.

Safety and Tolerability of Pentoxyphilline

• Pentoxyphilline is generally well tolerated, with the most commonly reported side effects consisting of gastrointestinal symptoms such as nausea 2, 3, 4.
• The recommended dose of pentoxyphilline is 400 mg three times daily with meals 5.

Comparison with Other Treatments

• Pentoxyphilline is one of two drugs approved by the US FDA for the management of intermittent claudication, the other being cilostazol 5, 6.
• Cilostazol is a potent, reversible, phosphodiesterase III inhibitor that has been shown to increase pain-free walking time and total distance walked 5, 6.
• Other drugs, such as ginkgo biloba, naftidrofuryl, and buflomedil, may also relieve the symptoms of intermittent claudication, but the evidence is limited 5.