Alcoholic hepatitis (severe) (Maddrey Discriminant Function [MDF] score ≥32, especially when corticosteroids contraindicated) (off-label use): Oral: 400 mg 3 times daily for 4 weeks (AASLD [O’Shea 2010], ACG [Singal 2018]).
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) (Guyatt 2012).
Venous leg ulcer (off-label use): Oral: 400 mg 3 times daily (with compression therapy) (Jull 2012; Robson 2006).
Manufacturer's labeling:
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling. However, exposure to one of pentoxifylline’s the active metabolites (metabolite V) is increased with renal impairment; use with caution.
CrCl <30 mL/minute: 400 mg once daily.
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: supplemental postdialysis dose is not necessary.
Peritoneal dialysis: 400 mg every 24 hours.
There are no dosage adjustments provided in the manufacturer's labeling. However, pentoxifylline exposure is increased with hepatic impairment; use with caution.
(For additional information see "Pentoxifylline: Pediatric drug information")
Kawasaki disease; adjunctive: Limited data available, efficacy results variable (Nash 1996); AHA recommendations do not address pentoxifylline for the treatment of Kawasaki disease (AHA [McCrindle 2017]): 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 (Best 2003; Furukawa 1994); 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 (Furukawa 1994).
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.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release, Oral:
Generic: 400 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release, Oral:
Generic: 400 mg
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.
Oral: Administer with food or antacids to decrease GI upset. Do not crush, break, or chew extended or controlled release tablet, swallow whole.
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) (Guyatt, 2012).
Alcoholic hepatitis (severe); Venous leg ulcers (with compression therapy)
Pentoxifylline may be confused with tamoxifen
TRENtal may be confused with Bentyl, TEGretol, Trandate
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:
• Elderly: Use with caution in the elderly due to the potential for cardiac, hepatic, or renal impairment.
Substrate of CYP1A2 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
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.
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 and its metabolites are present in breast milk.
Five breastfeeding 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 to 1.13 at 4 hours (Witter 1985). Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother.
May be taken with meals.
Renal function; hemoglobin/hematocrit (especially in high risk patients)
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%)
Renal function impairment: In patients with mild to moderate renal impairment, AUC0-tss and Cmax of the active Metabolite V increased 2.4- and 2.1-fold, respectively. In patients with severe renal impairment, the AUC0-tss and Cmax of active Metabolite V increased 12.9- and 10.6-fold, respectively. Twice daily administration increased the exposure to metabolite V only slightly in both groups.
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.
Geriatric: Pentoxifylline: Increased AUC and decreased elimination rate (60 to 68 years of age).
Tablet, controlled release (Pentoxifylline ER Oral)
400 mg (per each): $1.14 - $1.50
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