Version November 2024
Kawasaki disease; adjunctive: Limited data available, efficacy results variable (Ref); AHA recommendations do not address pentoxifylline for the treatment of Kawasaki disease (Ref): Infants ≥2 months and Children: Oral: 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 (Ref); the initial trial (n=22, mean age: 2 years, youngest: 6 months) reported a lower incidence of coronary artery lesions in patient receiving pentoxifylline compared to those who did not; all patients received aspirin and IV gamma globulin therapy (Ref).
Use with caution; monitor for enhanced therapeutic and toxic effects; Note: Pentoxifylline is not eliminated unchanged in the urine; however, the pharmacologically active metabolite (M-V) is; M-V may accumulate in patients with renal impairment and add to pharmacologic and toxic effects. Based on experience in adult patients, dosing adjustment suggested.
There are no dosage adjustments provided in manufacturer's labeling; use with caution.
(For additional information see "Pentoxifylline: Drug information")
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) (Ref).
Venous leg ulcer (off-label use): Oral: 400 mg 3 times daily (with compression therapy) (Ref).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function (expert opinion derived from Aronoff 2007 and Paap 1996):
CrCl ≥60 mL/minute: Oral: No dosage adjustment necessary.
CrCl 30 to <60 mL/minute: Oral: 400 mg twice daily; however, doses up to 1.2 g/day have been reasonably well-tolerated in patients with stage III and IV chronic kidney disease (CKD) (CrCl 15 to 60 mL/minute) (Ref); therefore, increasing the dose to 400 mg 3 times daily may be considered in certain patients based on tolerability (the dose limiting effect is primarily GI intolerance) and potential benefit (Ref).
CrCl <30 mL/minute: Oral: 400 mg once daily; however, doses up to 1.2 g/day have been reasonably well-tolerated in patients with stage III and IV CKD (CrCl 15 to 60 mL/minute) (Ref); therefore, increasing the dose up to 400 mg 2 or 3 times daily may be considered in certain patients with CrCl 15 to 30 mL/minute based on tolerability (the dose-limiting effect is primarily GI intolerance) and potential benefit (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (pentoxifylline and metabolites [>15%/hour]) (Ref):
Oral: 400 mg once daily. When scheduled dose falls on a dialysis day, administer after dialysis. Supplemental postdialysis dosing not required (Ref).
Peritoneal dialysis: Oral: 400 mg once daily (Ref).
CRRT: Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Close monitoring of response and adverse reactions (eg, GI intolerance) due to drug accumulation is important.
Oral: Pentoxifylline is likely to be somewhat cleared by CRRT; dose as for patients with CrCl 30 to <60 mL/minute (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions (eg, GI intolerance) due to drug accumulation is important.
Oral: Pentoxifylline is likely to be somewhat cleared by PIRRT; dose as for patients with CrCl 15 to 30 mL/minute (Ref).
There are no dosage adjustments provided in the manufacturer's labeling. However, pentoxifylline exposure is increased with hepatic impairment; use with caution.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%: Gastrointestinal: Nausea (2%), vomiting (1%)
<1%, postmarketing, and/or case reports: Anaphylactic shock, anaphylactoid reaction, anaphylaxis, angioedema, angina pectoris, anorexia, anxiety, aplastic anemia, aseptic meningitis, bloating, blurred vision, cardiac arrhythmia, chest pain, cholecystitis, confusion, conjunctivitis, constipation, decreased serum fibrinogen, depression, dysgeusia, dyspnea, edema, epistaxis, eructation, flatulence, flu-like symptoms, hallucination, hepatitis, hypotension, increased liver enzymes, jaundice, laryngitis, leukemia, leukopenia, malaise, nail disease (brittle fingernails), nasal congestion, otalgia, pancytopenia, pruritus, purpura, scotoma, seizure, sialorrhea, skin rash, sore throat, tachycardia, thrombocytopenia, tremor, urticaria, weight changes, xerostomia
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 US labeling): Acute MI, severe coronary artery disease when myocardial stimulation might prove harmful, peptic ulcers (current or recent)
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:
• Older adult: Use with caution in the elderly due to the potential for cardiac, hepatic, or renal impairment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release, Oral:
Generic: 400 mg
Yes
Tablet, controlled release (Pentoxifylline ER Oral)
400 mg (per each): $1.14 - $1.50
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release, Oral:
Generic: 400 mg
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.
Oral: Administer with food or antacids to decrease GI upset. Do not crush, break, or chew extended or controlled release tablet, swallow whole.
Oral: Administer with food. Swallow whole; do not chew, crush, or divide.
Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. No alternative formulations are available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, if pentoxifylline extended release is continued, close clinical monitoring is advised in the immediate postoperative phase for the theoretical circumstance of reduced absorption after bariatric surgery.
Store between 20°C to 25°C (68°F to 77°F); protect from light.
Treatment of intermittent claudication on the basis of chronic occlusive arterial disease of the limbs (FDA approved in adults). Note: In adults, may improve function and symptoms, but not intended to replace more definitive therapy. 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). Has also been used as adjunct therapy for treatment of Kawasaki disease.
Pentoxifylline may be confused with tamoxifen
Trental may be confused with Bentyl, Tegretol, Trandate
Substrate of CYP1A2 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): Pentoxifylline may enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Blood Pressure Lowering Agents: Pentoxifylline may enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of Pentoxifylline. Risk C: Monitor therapy
CYP1A2 Inhibitors (Moderate): May increase the serum concentration of Pentoxifylline. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May increase the serum concentration of Pentoxifylline. Risk C: Monitor therapy
Heparin: Pentoxifylline may enhance the anticoagulant effect of Heparin. Risk C: Monitor therapy
Heparins (Low Molecular Weight): Pentoxifylline may enhance the anticoagulant effect of Heparins (Low Molecular Weight). Risk C: Monitor therapy
Ketorolac (Nasal): May enhance the adverse/toxic effect of Pentoxifylline. Specifically, the risk of bleeding may be increased. Risk X: Avoid combination
Ketorolac (Systemic): May enhance the adverse/toxic effect of Pentoxifylline. Specifically, the risk of bleeding may be increased with this combination. Risk X: Avoid combination
Theophylline Derivatives: Pentoxifylline may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Pentoxifylline may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Food may decrease rate but not extent of absorption. Pentoxifylline peak serum levels may be decreased if taken with food.
May be taken with meals.
Pentoxifylline may be used to test sperm viability when evaluating nonfertile males (ASRM 2015). It has also been evaluated for the treatment of infertility due to endometriosis, but use for this purpose is not currently recommended (Lu 2012).
Adverse events have been observed in animal reproduction studies.
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.
Onset of action: 2 to 4 weeks with multiple doses
Absorption: Well absorbed
Metabolism: 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
Half-life elimination: Parent drug: 24 to 48 minutes; Metabolites: 60 to 96 minutes
Time to peak, serum: 2 to 4 hours
Excretion: Urine (0% as unchanged, 50% to 80% as M-V metabolite, 20% as other metabolites); feces (<4%)
Altered kidney function: Following a dose of 400 mg 3 times daily, AUC0-tss and Cmax of metabolite V (active) increased 2.4- and 2.1-fold, respectively, in patients with mild to moderate impairment, and 12.9- and 10.6-fold, respectively, in patients with severe impairment. Following a dose of 400 mg twice daily, AUC0-tss and Cmax of metabolite V (active) is only slightly smaller compared to 3-times-daily dosing in patients with mild to severe impairment.
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.
Older adult: Pentoxifylline: Increased AUC and decreased elimination rate (60 to 68 years of age).
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