Pentoxifylline (Trental) - Indication, Dose, Side effects

Pentoxifylline (Trental) is a methyl-xanthine derivative that has anti-inflammatory properties and reduces blood viscosity by increasing the fibrinolytic activity and reducing fibrinogen levels [Ref]. It makes the red cells more resistant to deformity when crossing the smaller blood vessels.

Pentoxifylline 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).
  • Off Label Use of Pentoxifylline in Adults:

    • Severe Alcoholic hepatitis;
    • Venous leg ulcers (with compression therapy)

Pentoxifylline Dose in Adults

Pentoxifylline Dose in the treatment of Severe Alcoholic hepatitis:

(Maddrey Discriminant Function [MDF] score ≥32, especially when corticosteroids contraindicated) (off-label):

  • Oral: 400 mg 3 times a day for 4 weeks (AASLD).

Intermittent claudication:

  • Oral: 400 mg 3 times a day; maximal therapeutic benefit may take 2 to 4 weeks to develop;
  • recommended maintaining therapy for a minimum of 8 weeks.
  • May reduce to 400 mg twice a day if GI or CNS side effects occur;
  • discontinue if side effects persist.


  • Use for the treatment of intermittent claudication refractory to exercise therapy (and smoking cessation) has been discouraged by The American College of Chest Physicians.

Pentoxifylline Dose in the treatment of venous leg ulcers (off-label):

  • Oral: 400 mg 3 times a day (with compression therapy).

Pentoxifylline Dose in Childrens

Pentoxifylline Dose as adjunctive therapy in the treatment of Kawasaki disease:

  • Infants ≥2 months and Children:

    • Oral: at 20 mg/kg/day in 3 divided doses in combination with standard IV immunoglobulin and aspirin therapy;
    • specific role in disease management undefined;
    • data suggests use in patients with high serum concentrations of TNF may be appropriate.

Pregnancy Risk Factor C

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

Pentoxifylline use during breastfeeding:

  • Pentoxifylline and its metabolites are excreted into breast milk.
  • Five nursing women (~6 weeks postpartum) were given a single dose of pentoxifylline 400 mg and maternal milk and serum samples were measured 2 and 4 hours later.
  • The mean M/P ratio of pentoxifylline was 0.87 at 4 hours; actual milk concentrations ranged from below the limit of detection to 67.4 ng/mL.
  • Three metabolites were also measured in breast milk, with mean M/P ratios ranging from 0.54-1.13 at 4 hours.
  • Due to the potential for serious side effects in the nursing infant, the drug manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.

Pentoxifylline Dose in Kidney Disease:

  • Manufacturer's labeling:

    • CrCl ≥30 mL/minute:

      • There are no dosage adjustments provided in the drug manufacturer's labeling.
      • However, exposure to one of the pentoxifylline’s active metabolites (metabolite V) is increased with renal impairment; use with caution.
    • CrCl <30 mL/minute:

      • 400 mg once a day.
  • The following guidelines have been used by some clinicians:

    • Aronoff 2007:

      • 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:

        • A supplemental post-dialysis dose is not necessary.
      • Peritoneal dialysis:

        • 400 mg every 24 hours.

Pentoxifylline Dose in Liver Disease:

  • There are no dosage adjustments provided in the drug manufacturer's labeling.
  • However, pentoxifylline exposure is increased with hepatic impairment;
  • Use with caution.

Side Effects of Pentoxifylline (Trental):

  • Gastrointestinal:

    • Nausea
    • Vomiting

Contraindications to Pentoxifylline (Trental):

  • Patients previously showing 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 US labeling):

  • Acute MI,
  • severe coronary artery disease when myocardial stimulation might prove harmful,
  • peptic ulcers (current or recent)

Warnings and Precautions

  • Anaphylaxis and anaphylactoid reactions:

    • Discontinue at the first sign of anaphylaxis or anaphylactoid reaction.
  • Hepatic impairment:

    • caution needs to be taken in patients with mild to moderate hepatic impairment; the bioavailability of pentoxifylline and metabolite is increased.
    • Has not been studied in patients with severe hepatic disease.
  • Renal impairment:

    • Use with caution in a patient with renal impairment; bioavailability of active metabolite V may be increased.

Pentoxifylline: Drug Interaction

Risk Factor C (Monitor therapy)

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.)

Pentoxifylline may enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Blood Pressure Lowering Agents

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


May increase the serum concentration of Pentoxifylline.

Ciprofloxacin (Systemic)

May increase the serum concentration of Pentoxifylline.

CYP1A2 Inhibitors (Strong)

May increase the serum concentration of Pentoxifylline.


Pentoxifylline may enhance the anticoagulant effect of Heparin.

Heparins (Low Molecular Weight)

Pentoxifylline may enhance the anticoagulant effect of Heparins (Low Molecular Weight).

Theophylline Derivatives

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

Vitamin K Antagonists (eg, warfarin)

Pentoxifylline may enhance the anticoagulant effect of Vitamin K Antagonists.

Risk Factor X (Avoid combination)

Ketorolac (Nasal)

May enhance the adverse/toxic effect of Pentoxifylline. Specifically, the risk of bleeding may be increased.

Ketorolac (Systemic)

May enhance the adverse/toxic effect of Pentoxifylline. Specifically, the risk of bleeding may be increased with this combination.

Monitoring Parameters:

  • Renal function;
  • hemoglobin/hematocrit (especially in high risk patients)

How to administer Pentoxifylline (Trental)?

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

Mechanism of action of Pentoxifylline (Trental):

  • 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.

The onset of action:

  • 2 to 4 weeks with multiple doses


  • Well absorbed


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

Half-life elimination:

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

Time to peak serum concentration:

  • 2 to 4 hours


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

International Brand Names of Pentoxifylline:

  • Agapurin
  • Angiopurin
  • Artal
  • Artelife
  • Cental
  • Cerator
  • Ceretal
  • Chinotal
  • Circulaid
  • Clem
  • Dartelin
  • Duplat
  • Elorgan
  • Fixoten
  • Flexital CR
  • Fylin
  • Hemovas
  • Ipentol
  • Kentadin
  • Latren
  • Nelorpin
  • Oxiflux
  • Oxopurin 400 SR
  • Penphylline
  • Pental
  • Pentamon
  • Pentilin
  • Pentolin
  • Pentox
  • Pentox von ct
  • Pentoxal
  • Pentoxi
  • Pentoxifilina
  • Pentoxifyllin AL
  • Pentoxifyllin Pharmavit
  • Pentoxifyllin-B
  • Pentoxifyllin-ratiopharm
  • Pentoxin SR
  • Pentoxine
  • Pentyllin
  • Perencal
  • Peridane
  • Pexal
  • Pexol
  • Platof
  • Profiben
  • Qiquan
  • Rentylin
  • Sufisal
  • Tarontal
  • Torental
  • Trenfyl
  • Trenlin
  • Trenlin SR
  • Trental
  • Trental SR
  • Trental-400
  • Vantoxyl
  • Vasolax
  • Vasonit
  • Vasonit Retard
  • Vasopentox
  • Vasotal
  • Xipen

Pentoxifylline Brand Names in Pakistan:

Pentoxifylline Injection 100 mg/5ml

Agapurin Neo Medix


Pentoxifylline 400 mg Tablets

Agapurin Neo Medix


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