Pentoxifylline (known in Australia as Oxpentifylline) has the most common brand name, Trental. It is a prescription drug that belongs to the class of drugs called xanthine derivatives. Pentoxifylline’s most common use is to enhance peripheral and cerebral blood circulation.
Mechanisms of Action in ME
Many studies attest to Pentoxifylline’s ability to treat Raynaud’s phenomenon. It achieves improved circulation in vivo through several mechanisms including by improving the flexibility of red blood cells which in turn allows the red blood cells to navigate with greater ease through the capillaries. Pentoxifylline also improves platelet deaggregation which subsequently aids circulation through blood vessels. In addition it reduces the viscosity of blood. As a consequence of the aforementioned mechanisms of action of Pentoxifylline, it is useful in providing oxygen through the means of circulation to the peripheries of the body. SPECT scans have demonstrated that ME patients invariably have impaired blood circulation.
Pentoxifylline has several other possible mechanisms of action in ME other than enhancing circulation. It has the ability to reduce the cytokine IL-2 which is often high in ME patients. Dr. Klimas has stated that “In CFS, the Th2 is upregulated with pro inflammatory TNF-alpha and IL-2.” In Osler’s Web, Hillary Johnson writes, “Abnormally high levels of IL-2 have consistently been found in CFS patients by researchers. The IL-2 levels exceed those found in MS patients, AIDS patients and Lymphoma patients.”
Pentoxifylline may also reduce NF Kappa B which is also high in ME patients. Maes et al. 2007 (http://www.ncbi.nlm.nih.gov/pubmed/17693979) have written that “stimulated production of NF Kappa Beta were significantly higher in CFS patients than in controls. There were significant and positive correlations between the production of NF Kappa Beta and the severity of illness…..It is suggested that CFS patients should be treated with antioxidants, which inhibit the production of NF Kappa Beta.”
The final inflammatory pathway that Pentoxifylline may downregulate is the cytokine TNF-alpha. Moss et al. 1999 (http://www.ncbi.nlm.nih.gov/pubmed/10535608) concluded that “our results suggest a significant increase serum TNF-alpha in patients with CFS compared to non-CFS controls….the clinical testing of TNF-alpha blockers and other anti-inflammatory agents for the treatment of this disease is warranted.”
Pentoxifylline also has a degree of anti-viral activity with Amvros’eva et al. 1993 (http://www.ncbi.nlm.nih.gov/pubmed/8284924) demonstrating its efficacy against 8 viruses. Pentoxifylline was most effective against the herpes simplex virus including a strain that acyclovir was ineffective against, as well as the vaccinia virus, rotavirus and tick-borne encephalitis virus. The authors concluded that Pentoxifylline was an “effective broad spectrum virus inhibitor.”
Pentoxifylline also has the potential ability to inhibit retroviral infection. Several papers have shown that it can (in vitro) inhibit HIV replication and a further study has revealed that Pentoxifylline can reduce the HIV plasma levels in asymptomatic patients. It is sometimes used as a secondary treatment for AIDS.
The most common dosage of Pentoxifylline (for diseases other than ME, due to a lack of ME-Pentoxifylline studies) is 400mg taken three times a day at regular intervals for a total daily dosage of 1200mg. Studies have shown that doses of Pentoxifylline at higher than 400mg 3xday do not improve its efficacy however increase the risk of side effects. Due to many ME patients having sensitivities to drugs, a lower initial dosage may be beneficial to reduce the severity of any potential side effects. It is recommended by several sources that Pentoxifylline should be taken at 8 hour intervals in order to maintain a consistent level of the drug in the bloodstream. These sources also recommended that Pentoxifylline is taken with food.
Side Effects and Contraindications
Pentoxifylline is a xanthine derivative (in some respects similar to caffeine) and therefore should not be taken by those patients who cannot tolerate stimulants. Pentoxifylline should also be avoided by those with a peptic ulcer or those with a risk of haemorrhaging. Dr Claudia Zein, a Pentoxifylline researcher has stated that the drug has an “established safety profile” although this comment was not in relation to ME as Pentoxifylline has not been trialled on ME patients in a published study to date. Many studies have tested Pentoxifylline’s safety profile for a variety of conditions with all studies read by me having a similar conclusion. An example of these studies is by Crowder et al. (http://ang.sagepub.com/content/40/9/795.short) who administered the drug to geriatric patients and concluded that Pentoxifylline was “safe and well tolerated” at the 1200mg per day dose.
Drugs.com lists the incidence of side effects of Pentoxifylline http://www.drugs.com/sfx/pentoxifylline-side-effects.html (see extended release capsules, as these are the type commercially available.) In terms of Pentoxifylline and ME patients, a potential negative involves its potential to replicate the cytomegalovirus which some ME patients may have.
Pentoxifylline is a potentially useful drug in the treatment of ME due to its ability to improve cerebral and peripheral circulation. Its anti-inflammatory effects, achieved through down regulating IL-2, NF Kappa B and TNF-alpha may be beneficial to ME patients. Pentoxifylline also has a degree of anti-viral and immunomodulatory ability.