PENTOXIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PENTOXIL (PENTOXIL).
Pentoxifylline is a xanthine derivative that non-selectively inhibits phosphodiesterase, leading to increased intracellular cAMP and cGMP, thereby reducing blood viscosity and improving erythrocyte flexibility. It also inhibits tumor necrosis factor-alpha (TNF-α) synthesis.
| Metabolism | Hepatic via oxidation and reduction, followed by conjugation; metabolites include metabolites I and V. CYP enzymes may be involved, but specific pathways are not fully characterized. |
| Excretion | Primarily renal (>95%) as unchanged drug and metabolites; biliary/fecal excretion <5%. |
| Half-life | Terminal elimination half-life: 3.5-4 hours (prolonged in renal impairment, up to 10-15 hours in severe impairment). |
| Protein binding | 80-85% (primarily to albumin). |
| Volume of Distribution | 0.8-1.2 L/kg (indicating distribution into total body water and some extravascular compartments). |
| Bioavailability | Oral: ~85% (extensive but saturable first-pass metabolism). |
| Onset of Action | Oral: 2-4 hours (peak plasma concentration); intravenous: immediate (within minutes). |
| Duration of Action | Oral: Up to 8 hours (based on hemodynamic effects); intravenous: 1-4 hours. |
400 mg orally three times daily with meals.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR 10-50 mL/min: 400 mg twice daily. GFR <10 mL/min: 400 mg once daily. |
| Liver impairment | Child-Pugh Class A: 400 mg three times daily. Class B: 400 mg twice daily. Class C: 400 mg once daily. |
| Pediatric use | Not recommended for use in children (safety and efficacy not established). |
| Geriatric use | Elderly patients may have increased risk of bleeding; monitor closely. No specific dose adjustment, but consider renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PENTOXIL (PENTOXIL).
| Breastfeeding | Pentoxifylline and its metabolites are excreted into human breast milk in small amounts. The milk-to-plasma (M/P) ratio is approximately 0.8 (estimated from single-dose data). Based on limited data, the relative infant dose is less than 1% of the maternal weight-adjusted dose, which is generally considered compatible with breastfeeding. However, caution is advised; monitor infant for potential adverse effects such as gastrointestinal upset or irritability. |
| Teratogenic Risk | Pentoxifylline (PENTOXIL) is FDA Pregnancy Category C. In animal studies, pentoxifylline was not teratogenic at doses up to 10 times the maximum human daily dose. However, there are no adequate and well-controlled studies in pregnant women. A slight increase in fetal resorptions was observed in rats at doses 10 times the human dose. In humans, pentoxifylline crosses the placenta. Insufficient data exist to assess risk in the first trimester; potential benefit must outweigh unknown risk. During second and third trimesters, use only if clearly needed due to lack of human data. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to pentoxifylline or other xanthines (caffeine, theophylline, theobromine)","Recent cerebral and/or retinal hemorrhage","History of bleeding disorders such as peptic ulcer, ulcerative colitis, or recent surgery"]
| Precautions | ["May increase bleeding risk; use with caution in patients with coagulation disorders or on anticoagulant therapy.","Avoid in patients with recent hemorrhage, cerebral hemorrhage, or retinal hemorrhage.","May cause gastrointestinal intolerance; consider dose reduction or discontinuation.","Use with caution in severe renal or hepatic impairment."] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate due to potential hypotension and tachycardia. Assess for signs of bleeding (e.g., epistaxis, gingival bleeding) as pentoxifylline has antiplatelet effects. In pregnant women, monitor fetal heart rate and uterine activity if administered near term or during labor due to possible uterine relaxant effects. Periodic complete blood count (CBC) may be warranted for prolonged therapy. |
| Fertility Effects | No well-controlled studies on human fertility. Animal studies: In rats, pentoxifylline did not impair fertility at doses up to 10 times the maximum human daily dose. In males, pentoxifylline has been studied to improve sperm motility in some cases, but effects on fertility in healthy individuals are not clearly established. Caution is advised when used in women attempting conception due to unknown effects on ovulation or implantation. |