pentoxifylline
Regulatory sources consulted
Approved indications
- Elorgan (Spain): obliterative peripheral arterial disease; circulatory disorders of arteriosclerotic, diabetic, inflammatory, or functional origin; trophic changes, distal lower-limb ulcers, and gangrene.
- United States: intermittent claudication due to chronic occlusive arterial disease of the limbs. It may improve function and symptoms but does not replace definitive therapy such as bypass surgery or removal of arterial obstruction.
Contraindications
Absolute
- Hypersensitivity or intolerance to pentoxifylline, excipients, or other methylxanthines such as caffeine, theophylline, or theobromine.
- Elorgan: massive bleeding or extensive retinal hemorrhage. United States: recent cerebral or retinal hemorrhage.
Clinical warnings
- Major warning · Discontinue immediately at the first sign of an anaphylactic or anaphylactoid reaction. — CIMA ficha técnica 54635; DailyMed setid cd840a2c-2a0e-4b2b-84ff-a0406bb6fa37
- Major warning · Monitor for bleeding in patients with recent surgery, peptic ulcer, coagulation disorders, or anticoagulant or antiplatelet therapy; monitor hemoglobin, hematocrit, and anticoagulant activity according to risk. — CIMA ficha técnica 54635; DailyMed setid cd840a2c-2a0e-4b2b-84ff-a0406bb6fa37
- Major warning · Close monitoring is required with severe arrhythmias, myocardial infarction, hypotension, severe renal impairment, or severe hepatic impairment; exposure to pentoxifylline or metabolites increases with renal or hepatic dysfunction. — CIMA ficha técnica 54635; DailyMed setid cd840a2c-2a0e-4b2b-84ff-a0406bb6fa37
Drug interactions
- HighVitamin K antagonists and other anticoagulants
Mechanism: Increased anticoagulant activity, prolonged prothrombin time, and bleeding have been reported.
Recommendation: Monitor prothrombin time, INR, anticoagulant activity, and bleeding signs more frequently when starting or changing the dose.
CIMA ficha técnica 54635DailyMed setid cd840a2c-2a0e-4b2b-84ff-a0406bb6fa37
- HighAntiplatelet drugs and NSAIDs
Mechanism: Additive antihemostatic effects increase bleeding risk.
Recommendation: Use cautiously and intensify clinical monitoring for bleeding.
CIMA ficha técnica 54635
- HighTheophylline or aminophyllineR03DA04
Mechanism: Pentoxifylline may increase theophylline levels and toxicity.
Recommendation: Monitor clinical status and theophylline levels; adjust its dose during and after coadministration.
CIMA ficha técnica 54635DailyMed setid cd840a2c-2a0e-4b2b-84ff-a0406bb6fa37
- ModerateCiprofloxacin, fluvoxamine, or other strong CYP1A2 inhibitors
Mechanism: They may increase pentoxifylline exposure and intensify adverse reactions.
Recommendation: Monitor tolerance and adverse effects; adjust treatment according to clinical response.
CIMA ficha técnica 54635DailyMed setid cd840a2c-2a0e-4b2b-84ff-a0406bb6fa37
- ModerateAntihypertensive or antidiabetic drugs
Mechanism: Pentoxifylline may potentiate blood-pressure reduction or glucose-lowering effects.
Recommendation: Monitor blood pressure and glucose; adjust the concomitant medicine if needed.
CIMA ficha técnica 54635
- ModerateCimetidineA02BA01
Mechanism: Cimetidine increases mean steady-state pentoxifylline concentration by approximately 25% and active metabolite I concentration by 30%.
Recommendation: Monitor tolerance and adverse reactions during coadministration.
CIMA ficha técnica 54635DailyMed setid cd840a2c-2a0e-4b2b-84ff-a0406bb6fa37
Adverse events
Common (≥1%)
Dyspepsia (2.8% with extended-release tablets) · Nausea (2.2% with extended-release tablets) · Dizziness (1.9% with extended-release tablets) · Headache (1.2% with extended-release tablets) · Vomiting (1.2% with extended-release tablets)
Rare but serious
Frequency unknown: bleeding · Frequency unknown: anaphylactic reaction or anaphylactic shock · Frequency unknown: angioedema or bronchospasm · Frequency unknown: thrombocytopenia, pancytopenia, or aplastic anemia · Frequency unknown: hepatitis, jaundice, or cholestasis · Frequency unknown: arrhythmia or angina
Pregnancy and lactation
Elorgan is not recommended during pregnancy because experience is insufficient. Pentoxifylline is excreted in small amounts in human milk; during breastfeeding, weigh maternal benefit against possible risks.
Recent literature (PubMed)
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The α-Klotho protein (henceforth denoted Klotho) has antiaging properties, as first observed in mice homozygous for a hypomorphic Klotho gene (kl/kl). These mice have a shortened lifespan, stunted growth, renal disease, hyperphosphatemia, hypercalcemia, vascular calcification, cardiac hypertrophy, hypertension, pulmonary disease, cognitive impairment, multi-organ atrophy and fibrosis. Overexpression of Klotho has opposite effects, extending lifespan. In humans, Klotho levels decline with age, chronic kidney disease, diabetes, Alzheimer's disease and other conditions. Low Klotho levels correlate with an increase in the death rate from all causes. Klotho acts either as an obligate coreceptor for fibroblast growth factor 23 (FGF23), or as a soluble pleiotropic endocrine hormone (s-Klotho). It is mainly produced in the kidneys, but also in the brain, pancreas and other tissues. On renal tubular-cell membranes, it associates with FGF receptors to bind FGF23. Produced in bones, FGF23 regulates renal excretion of phosphate (phosphaturic effect) and vitamin D metabolism. Lack of Klotho or FGF23 results in hyperphosphatemia and hypervitaminosis D. With age, human renal function often deteriorates, lowering Klotho levels. This appears to promote age-related pathology. Remarkably, Klotho inhibits four pathways that have been linked to aging in various ways: Transforming growth factor β (TGF-β), insulin-like growth factor 1 (IGF-1), Wnt and NF-κB. These can induce cellular senescence, apoptosis, inflammation, immune dysfunction, fibrosis and neoplasia. Furthermore, Klotho increases cell-protective antioxidant enzymes through Nrf2 and FoxO. In accord, preclinical Klotho therapy ameliorated renal, cardiovascular, diabetes-related and neurodegenerative diseases, as well as cancer. s-Klotho protein injection was effective, but requires further investigation. Several drugs enhance circulating Klotho levels, and some cross the blood-brain barrier to potentially act in the brain. In c
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Diabetic kidney disease (DKD) is a major cause of chronic kidney disease (CKD), and it heightens the risk of cardiovascular incidents. The pathogenesis of DKD is thought to involve hemodynamic, inflammatory, and metabolic factors that converge on the fibrotic pathway. Genetic predisposition and unhealthy lifestyle practices both play a significant role in the development and progression of DKD. In spite of the recent emergence of angiotensin receptors blockers (ARBs)/angiotensin converting enzyme inhibitor (ACEI), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid receptors antagonists (NS-MRAs), current therapies still fail to effectively arrest the progression of DKD. Glucagon-like peptide 1 receptor agonists (GLP-1RAs), a promising class of agents, possess the potential to act as renal protectors, effectively slowing the progression of DKD. Other agents, including pentoxifylline (PTF), selonsertib, and baricitinib hold great promise as potential therapies for DKD due to their anti-inflammatory and antifibrotic properties. Multidisciplinary treatment, encompassing lifestyle modifications and drug therapy, can effectively decelerate the progression of DKD. Based on the treatment of heart failure, it is recommended to use multiple drugs in combination rather than a single-use drug for the treatment of DKD. Unearthing the mechanisms underlying DKD is urgent to optimize the management of DKD. Inflammatory and fibrotic factors (including IL-1, MCP-1, MMP-9, CTGF, TNF-a and TGF-β1), along with lncRNAs, not only serve as diagnostic biomarkers, but also hold promise as therapeutic targets. In this review, we delve into the potential mechanisms and the current therapies of DKD. We also explore the additional value of combing these therapies to develop novel treatment strategies. Drawing from the current understanding of DKD pathogenesis, we propose HIF inhibitors, AGE inhibitors, and epigenetic modifications as promising therapeutic targe
Keloids are an aberrant fibroproliferative response to wound healing of the skin, leading to scar tissue that expands above and beyond the original cutaneous injury. Keloids can be difficult to treat because of their tendency to recur after treatments, including after excision. There is a myriad of treatment modalities used, which can be used as monotherapy or in combination with surgical excision or other treatment methods. This review covers many treatment approaches including surgical excision, compression, silicone sheets, steroid-impregnated tape, imiquimod, intralesional injections, cryotherapy, laser, radiation, pentoxifylline, and dupilumab.