ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد ایتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Pentoxifylline: Pediatric drug information

Pentoxifylline: Pediatric drug information
(For additional information see "Pentoxifylline: Drug information" and see "Pentoxifylline: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Therapeutic Category
  • Blood Viscosity Reducer Agent
Dosing: Pediatric

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).

Dosing: Kidney Impairment: Pediatric

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.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling; use with caution.

Dosing: Adult

(For additional information see "Pentoxifylline: Drug information")

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).

Dosing: Kidney Impairment: Adult

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.

Dosing: Hepatic Impairment: Adult

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

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Extended Release, Oral:

Generic: 400 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Extended Release, Oral:

Generic: 400 mg

Administration: Pediatric

Oral: Administer with food or antacids to decrease GI upset. Do not crush, break, or chew extended or controlled release tablet, swallow whole.

Administration: Adult

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.

Storage/Stability

Store between 20°C to 25°C (68°F to 77°F); protect from light.

Use

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.

Medication Safety Issues
Sound-alike/look-alike issues:

Pentoxifylline may be confused with tamoxifen

TRENtal may be confused with Bentyl, TEGretol, Trandate

Adverse Reactions

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

Contraindications

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)

Warnings/Precautions

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.

Metabolism/Transport Effects

Substrate of CYP1A2 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

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 Interactions

Food may decrease rate but not extent of absorption. Pentoxifylline peak serum levels may be decreased if taken with food.

Dietary Considerations

May be taken with meals.

Reproductive Considerations

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).

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies.

Mechanism of Action

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.

Pharmacokinetics (Adult data unless noted)

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%)

Pharmacokinetics: Additional Considerations

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).

Extemporaneous Preparations

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.
Pricing: US

Tablet, controlled release (Pentoxifylline ER Oral)

400 mg (per each): $1.14 - $1.50

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Agapurin (HU, PK, UA, VN);
  • Angiopurin (HU);
  • Artelife (MX);
  • Cental (TW);
  • Cerator (HK, MY, TH);
  • Chinotal (HU);
  • Circulaid (JO);
  • Clem (PY);
  • Dartelin (HR);
  • Duplat (CR, DO, GT, HN, MX, NI, PA, SV);
  • Elorgan (ES);
  • Fixoten (MX);
  • Flexital CR (TH);
  • Fylin (TW);
  • Hemovas (ES);
  • Ipentol (TW, VN);
  • Kentadin (MX);
  • Latren (UA);
  • Nelorpin (ES);
  • Oxiflux (RO);
  • Oxopurin 400 SR (IL);
  • Penphylline (TW);
  • Pental (EG);
  • Pentamon (HR);
  • Pentilin (HR, LV);
  • Pentoflux (FR);
  • Pentohexal (PL);
  • Pentolin (BD);
  • Pentox (EG, PH);
  • Pentox von ct (LU);
  • Pentoxal (PH);
  • Pentoxi (CH);
  • Pentoxifilina (CO);
  • Pentoxifyllin AL (HU);
  • Pentoxifyllin Pharmavit (HU);
  • Pentoxifyllin-B (HU);
  • Pentoxifyllin-ratiopharm (LU);
  • Pentoxin (FI);
  • Pentoxin SR (KR);
  • Pentoxine (JO, QA);
  • Pentyllin (AE, CY, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE);
  • Perencal (KR);
  • Peridane (MX);
  • Pexal (BM, BZ, GY, SR);
  • Pexol (PE);
  • Platof (ID);
  • Profiben (MX);
  • Qiquan (CN);
  • Rentylin (LU);
  • Sufisal (CR, DO, GT, HN, MX, NI, PA, SV);
  • Tarontal (GR, ID, TR);
  • Torental (BE, LU);
  • Toxipen (PH);
  • Trenfyl (ID);
  • Trenlin (HK);
  • Trenlin SR (SG);
  • Trental (AE, AR, AT, AU, BB, BD, BG, BM, BO, BR, BS, BZ, CO, CU, CY, CZ, DE, DK, EC, EE, EG, FI, GB, GY, HK, HR, HU, ID, IL, IN, IQ, IR, IS, IT, JM, JO, JP, KR, KW, LB, LT, LV, LY, MT, MX, MY, NL, NO, NZ, OM, PE, PH, PK, PR, PT, PY, QA, RU, SA, SE, SG, SI, SK, SR, SY, TH, TR, TT, TW, UA, UY, VE, YE);
  • Trental SR (BH, EG);
  • Trental-400 (LK);
  • Vantoxyl (CR, DO, GT, HN, MX, NI, PA, SV);
  • Vasolax (BD);
  • Vasonit (AT, RO, UA);
  • Vasonit Retard (LV);
  • Vasopentox (PE);
  • Vasotal (EG);
  • Xipen (MX)


For country abbreviations used in Lexicomp (show table)
  1. Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007.
  2. 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. [PubMed 7996376]
  3. 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. [PubMed 7997416]
  4. Best BM, Burns JC, DeVincenzo J, et al. Pharmacokinetic and tolerability assessment of a pediatric oral formulation of pentoxifylline in kawasaki disease. Curr Ther Res Clin Exp. 2003;64(2):96-115. [PubMed 24944359]
  5. 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. [PubMed 7957426]
  6. Guyatt GH, Akl EA, Crowther M, et al, “Executive Summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines,” Chest, 2012, 141(2 Suppl):7-47.
  7. Jull AB, Arroll B, Parag V, Waters J. Pentoxifylline for treating venous leg ulcers. Cochrane Database Syst Rev. 2012;12:CD001733. [PubMed 23235582]
  8. Lauterbach R, “Pentoxifylline Treatment of Persistent Pulmonary Hypertension of Newborn,” Eur J Pediatr, 1993, 152(5):460. (I.V. use) [PubMed 8319723]
  9. 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) [PubMed 7957428 ]
  10. Lu D, Song H, Li Y, et al, "Pentoxifylline for Endometriosis," Cochrane Database Syst Rev, 2012, 1:CD007677. [PubMed 22258970]
  11. Luke DR, Rocci ML Jr, and Hoholick C, "Inhibition of Pentoxifylline Clearance by Cimetidine," J Pharm Sci, 1986, 75(2):155-7. [PubMed 3958924]
  12. 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. [PubMed 8258882]
  13. Mauro VF, Mauro LS, and Hageman JH, "Alteration of Pentoxifylline Pharmacokinetics by Cimetidine," Clin Pharmacol, 1988, 28(7):649-54.
  14. McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation. 2017;135(17):e927-e999. [PubMed 28356445]
  15. Nash MC, Wade AM. No evidence for use of pentoxifylline in acute Kawasaki disease. Eur J Pediatr. 1996;155(3):258. [PubMed 8929744]
  16. O’Shea R, Dasarathy S, McCullough A, et al, “Alcoholic Liver Disease,” Hepatology, 2010, 51(1):307-28. [PubMed 20034030]
  17. 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. [PubMed 8826548]
  18. Pentoxifylline [prescribing information]. Bridgewater, NJ: Oceanside Pharmaceuticals; November 2019.
  19. Pentoxifylline SR [product monograph]. Vaughan, Ontario, Canada: AA Pharma Inc; January 2022.
  20. Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile female: a committee opinion. Fertil Steril. 2015;103(6):e44-e50. [PubMed 25936238]
  21. Robson MC, Cooper DM, Aslam R, et al, “Guidelines for the Treatment of Venous Ulcers,” Wound Repair Regen, 2006, 14(6):649-62. [PubMed 17199831]
  22. Singal AK, Bataller R, Ahn J, et al. ACG Clinical Guideline: alcoholic liver disease. Am J Gastroenterol. 2018;113(2):175-194. doi: 10.1038/ajg.2017.469. [PubMed 29336434]
  23. Trental (pentoxifylline) [prescribing information]. Parsippany, NJ: Validus; January 2016.
  24. Ward A and Clissold SP, “Pentoxifylline: A Review of Its Pharmacodynamic and Pharmacokinetic Properties and Its Therapeutic Efficacy,” Drugs, 1987, 34(1):50-97. [PubMed 3308412]
  25. Witter FR and Smith RV, "The Excretion of Pentoxifylline and Its Metabolites Into Human Breast Milk," Am J Obstet Gynecol, 1985, 151(8):1094-7. [PubMed 3985069]
Topic 12694 Version 206.0