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Pronunciation
(pen toks IF i lin)
Generic Available (U.S.)
Yes
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Treatment of intermittent claudication on the basis of chronic occlusive arterial disease of the limbs; may improve function and symptoms, but not intended to replace more definitive therapy
Use: Unlabeled/Investigational
Venous leg ulcers (Jull, 2007)
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women.
Lactation
Enters breast milk/not recommended
Contraindications
Hypersensitivity to pentoxifylline, xanthines (eg, caffeine, theophylline), or any component of the formulation; recent cerebral and/or retinal hemorrhage
Warnings/Precautions
Disease-related concerns:
• Renal impairment: Use with caution; active metabolite may accumulate in renal impairment leading to increased risk of adverse effects.
Special populations:
• Elderly: Use with caution in the elderly; due to potential for renal impairment.
• Pediatrics: Safety and efficacy have not been established in children.
Adverse Reactions
1% to 10%: Gastrointestinal: Nausea (2%), vomiting (1%)
<1%, postmarketing, and/or case reports: Anaphylactoid reaction, angioedema, angina, anorexia, anxiety, aplastic anemia, arrhythmia, aseptic meningitis, bloating, blurred vision, brittle fingernails, chest pain, cholecystitis, confusion, conjunctivitis, constipation, depression, dyspnea, earache, edema, epistaxis, eructation, fibrinogen decreased (serum), flatus, flu-like syndrome, hallucinations, hepatitis, hypotension, jaundice, laryngitis, leukemia, leukopenia, liver enzymes increased, malaise, nasal congestion, pancytopenia, pruritus, purpura, rash, scotoma, seizure, sialism, sore throat, taste perversion, tachycardia, thrombocytopenia, tremor, urticaria, weight change, xerostomia
Metabolism/Transport Effects
Inhibits CYP1A2 (weak)
Drug Interactions
Antihypertensives: Pentoxifylline may enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Antiplatelet Agents: Pentoxifylline may enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of Pentoxifylline. Risk C: Monitor therapy
Ciprofloxacin: May enhance the adverse/toxic effect of Pentoxifylline. Risk C: Monitor therapy
Ciprofloxacin (Systemic): May enhance the adverse/toxic effect of Pentoxifylline. Risk C: Monitor therapy
Heparin: Pentoxifylline may enhance the anticoagulant effect of Heparin. Risk C: Monitor therapy
Heparin (Low Molecular Weight): Pentoxifylline may enhance the anticoagulant effect of Heparin (Low Molecular Weight). Risk C: Monitor therapy
Ketorolac: May enhance the adverse/toxic effect of Pentoxifylline. Specifically, the risk of bleeding may be increased with this combination. Risk X: Avoid combination
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. Exceptions: Dyphylline. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Pentoxifylline may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Food may decrease rate but not extent of absorption. Pentoxifylline peak serum levels may be decreased if taken with food.
Storage
Store between 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Reduces blood viscosity via increased leukocyte and erythrocyte deformability and decreased neutrophil adhesion/activation; improves peripheral tissue oxygenation presumably through enhanced blood flow.
Pharmacodynamics/Kinetics
Absorption: Well absorbed
Metabolism: Hepatic to 3-carboxybutyl (M-IV, inactive) and 3-carboxypropyl (M-V, active) and via erythrocytes to 5-hydroxyhexyl (M-I, active); extensive first-pass effect; M-I is further metabolized in the liver
Half-life elimination: Parent drug: 24-48 minutes; Metabolites: 60-96 minutes
Time to peak, serum: 2-4 hours
Excretion: Primarily urine (50% to 80% as M-V, 20% as other metabolites); feces (<4%)
Dosage
Oral:
Adults: 400 mg 3 times/day with meals; maximal therapeutic benefit may take 2-4 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.
Elderly: Dosage adjustment based on creatinine clearance can be considered.
Dosage adjustment in renal impairment: Dosage adjustments are not required by manufacturer; however, consider dosing adjustments based on degree of renal impairment (Paap, 1996):
Moderate renal impairment (Clcr ~60 mL/minute): 400 mg twice daily
Severe renal impairment (Clcr ~20 mL/minute): 400 mg once daily; further reduction may be required; Paap suggests 200 mg once daily, but with current products (extended or controlled release; unscored) may require adaptation to 400 mg once every other day
Administration: Oral
Tablets should be swallowed whole; do not chew, break, or crush. May be administered with food.
Test Interactions
Decreased calcium (S), magnesium (S); false-positive theophylline levels
Dietary Considerations
May be taken with meals.
Patient Education
This may relieve pain of claudication, but additional therapy may be recommended. May cause dizziness, heartburn, nausea, or vomiting. Report chest pain; swelling of lips, mouth, or tongue; persistent headache; respiratory difficulty; rash; or unrelieved nausea or vomiting.
Geriatric Considerations
Pentoxifylline's value in the treatment of intermittent claudication is controversial. Walking distance improved statistically in some clinical trials, but the actual distance was minimal when applied to improving physical activity. Dose adjustment in moderate and severe kidney impairment has been recommended based on accumulation of two active metabolites. However, these doses have not been studied for clinical or safety outcomes.
Cardiovascular Considerations
Pentoxifylline may be used in the treatment of peripheral vascular disease; however, its efficacy is not fully established. The role of cytokine modulation with pentoxifylline in patients with heart failure is under investigation.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause anxiety, confusion, depression, dizziness, or rarely agitation
Mental Health: Effects on Psychiatric Treatment
May cause seizures; use with caution with concomitant use of clozapine, which is associated with dose-dependent risk of seizures
Nursing: Physical Assessment/Monitoring
Assess efficacy of therapy objectively.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, controlled release, oral:
TRENtal®: 400 mg
Tablet, extended release, oral: 400 mg
Pricing: U.S. (www.drugstore.com)
Tablet, controlled release (Pentoxifylline CR)
400 mg (100): $24.99
Tablet, controlled release (TRENtal)
400 mg (60): $84.29
Extemporaneously Prepared
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.
Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
References
Aronoff SC, Quinn FJ, Carpenter LS, et al, “Effects of Pentoxifylline on Sputum Neutrophil Elastase and Pulmonary Function in Patients With Cystic Fibrosis: Preliminary Observations,” J Pediatr, 1994, 125(6 Pt 1):992-7.
Berman W Jr, Berman N, Pathak D, et al, “Effects of Pentoxifylline (Trental®) on Blood Flow, Viscosity, and Oxygen Transport in Young Adults With Inoperable Cyanotic Congenital Heart Disease,” Pediatr Cardiol, 1994, 15(2):66-70.
Dolgin J, Abrams B, and Tucker J, “Survival With Massive Pentoxifylline Overdose and High Serum Levels,” Vet Hum Toxicol, 1994, 36:369.
Furukawa S, Matsubara T, Umezawa Y, et al, “Pentoxifylline and Intravenous Gamma Globulin Combination Therapy for Acute Kawasaki Disease,” Eur J Pediatr, 1994, 153(9):663-7.
Garnier R, Riboulet-Delmas G, Chatenet T, et al, “Acute Pentoxifylline in Children,” Ann Pediatr (Paris), 1986, 33(1):62-3.
Hirsh J, Guyatt G, Albers GW, et al, “Executive Summary: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition),” Chest, 2008, 133(6 Suppl):71-109.
Jull A, Arroll B, Paraq V, et al, “Pentoxifylline for Treating Venous Leg Ulcers,” Cochrane Database Syst Rev, 2007, (3):CD001733.
Kearon C, Kahn SR, Agnelli G, et al, “Antithrombotic Therapy for Venous Thromboembolic Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition),” Chest, 2008, 133(6 Suppl):454-45.
Lauterbach R, “Pentoxifylline Treatment of Persistent Pulmonary Hypertension of Newborn,” Eur J Pediatr, 1993, 152(5):460. (I.V. use)
Lauterbach R, Pawlik D, Tomaszczyk B, et al, “Pentoxifylline Treatment of Sepsis of Premature Infants; Preliminary Clinical Observations,” Eur J Pediatr, 1994, 153(9):672-4. (I.V. use)
Luke DR, Rocci ML Jr, and Hoholick C, "Inhibition of Pentoxifylline Clearance by Cimetidine," J Pharm Sci, 1986, 75(2):155-7.
MacDonald MJ, Shahidi NT, Allen DB, et al, “Pentoxifylline in the Treatment of Children With New-Onset Type I Diabetes Mellitus,” JAMA, 1994, 271(1):27-8.
Mauro VF, Mauro LS, and Hageman JH, "Alteration of Pentoxifylline Pharmacokinetics by Cimetidine," Clin Pharmacol, 1988, 28(7):649-54.
Paap CM, Simpson KS, Horton MW, et al, “Multiple-Dose Pharmacokinetics of Pentoxifylline and its Metabolites During Renal Insufficiency,” Ann Pharmacother, 1996, 30(7-8):724-9.
Sznajder IJ, Bentur Y, and Taitelman U, “First and Second Degree Atrioventricular Block in Oxpentifylline Overdose,” Br Med J (Clin Res Ed), 1984, 288(6410):26.
Ward A and Clissold SP, “Pentoxifylline: A Review of Its Pharmacodynamic and Pharmacokinetic Properties and Its Therapeutic Efficacy,” Drugs, 1987, 34(1):50-97.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
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