Pentoxifylline
1-(5-oxohexyl)-3,7-dimethylxanthine
Also known as: Trental · BL-191 · oxpentifylline · pentoxifyllinum · Oxypentifylline
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Audited v13 dosing evidence
Structured calculator evidenceInflammatory/autoimmune dermatologic conditions (extralabel)
- q8-12h
NA
Governing clinical context (4)
- NOTE: The commercially available pentoxifylline product is a 400 mg extended-release tablet. Cutting or crushing the tablets may negate the extended-release characteristics and alter pharmacokinetics but splitting tablets may be necessary to administer or accurately dose. Avoid crushing tablets for small animal use.
- ■ Give this medicine with food.
- ■ Extended-release tablets can be split if necessary to give the appropriate dose. Crushing the tablets may increase the risk for side effects and should be avoided when possible.
- The commercially available tablets should be stored in well-closed containers, protected from light at 20°C to 25°C (68°F -77°F).
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Pentoxifylline is a synthetic methylxanthine derivative (structurally related to theophylline and caffeine) with unique hemorrheologic and immunomodulatory properties.
- Dogs: Primarily used to treat immune-mediated dermatologic conditions with underlying microvascular compromise, such as familial canine dermatomyositis, ear margin seborrhea/necrosis, and cutaneous vasculitis (e.g., Alabama rot). It is also used adjunctively for atopic dermatitis and is being investigated for dilated cardiomyopathy (DCM).
- Horses: Used as adjunctive therapy for cutaneous vasculitis, endotoxemia, navicular disease, and placentitis.
- Cats: Occasionally used alongside prednisolone to decrease vasculitis associated with Feline Infectious Peritonitis (FIP).
Clinical Pearl: Because its effects on tissue remodeling and inflammation take time, clinical benefits in dermatologic conditions may not be seen for 4 to 8 weeks.
Mechanism of action
The exact mechanisms are multifaceted, combining rheological improvement with anti-inflammatory effects:
- Phosphodiesterase (PDE) Inhibition: Inhibits erythrocyte PDE → increases intracellular cAMP → increases erythrocyte flexibility and deformability, allowing red blood cells to navigate compromised microvasculature.
- Blood Viscosity Reduction: Reduces plasma fibrinogen and increases fibrinolytic activity.
- Immunomodulation: PDE inhibition in leukocytes decreases the production of inflammatory cytokines, notably TNF-α, reducing the negative effects of endotoxemia.
- Enzyme Inhibition: In horses, it acts as a potent inhibitor of matrix metalloproteinase-9 (MMP-9) and a modest inhibitor of MMP-2, which may aid in preventing tissue degradation.
Safety & warnings
Contraindications
- Intolerance or hypersensitivity to pentoxifylline or other xanthines (e.g., theophylline, caffeine, theobromine)
- Cerebral hemorrhage
- Hypersensitivity to methylxanthines (e.g., theophylline, caffeine)
- Cerebral or retinal hemorrhage
- Severe hepatic or renal impairment (use with caution)
Adverse effects
- Vomiting
- Inappetence
- Loose stools
- Excitement
- Nervousness
- Dizziness (humans)
- Headache (humans)
- Erythema multiforme (rare in dogs)
- Transient leukocytosis (horses IV)
- Muscle fasciculations (horses IV)
- Sweating on shoulders/flanks (horses IV)
- Mild increases in heart rate (horses IV)
- Anorexia
- Diarrhea
- Restlessness
- Tachycardia
- Tremors
Precautions
Caution in patients with severe hepatic or renal impairment, or those at risk for hemorrhage.
- Pregnancy: FDA Category C. May be teratogenic at high dosages.
- Nursing: Excreted in maternal milk. Use cautiously in nursing patients due to potential tumorigenicity seen in rats.
Drug interactions
May increase hypotensive effect when used concurrently
Controversial in horses; may negate beneficial effects for endotoxemia, though some studies show superior efficacy when used with flunixin
Increased risk for bleeding
Serum levels of theophylline may be increased when used concurrently
Increased risk of bleeding; use together with enhanced monitoring and caution
May increase pentoxifylline levels
Potential for additive hypotensive effects
Monitoring
- Clinical efficacy (resolution of dermatologic or vascular signs)
- Adverse effects (GI upset, CNS signs)
- Clinical response (resolution of skin lesions/improved blood flow)
- Gastrointestinal tolerance
- Signs of bleeding
Pharmacokinetics
Half-life
Absorption
Horses: Rapidly absorbed after PO administration of crushed sustained-release tablets, with wide interpatient variation (bioavailability ~68%). Dogs: Bioavailability is approximately 50% with peak levels occurring 1-3 hours after dosing. Humans: Rapid and almost complete absorption, but undergoes a significant first-pass effect.
Distribution
Distributive characteristics are not fully described, but it is known that the drug enters maternal milk.
Metabolism
Metabolized both in the liver and erythrocytes; all identified metabolites appear to be active.
Elimination
Excreted primarily via urine (inferred from human data).
Overdose
Signs of overdose in humans include flushing, seizures, hypotension, unconsciousness, agitation, fever, somnolence, GI distress, and ECG changes. One patient who ingested 80 mg/kg recovered completely. Overdoses should be treated using standard methods of appropriate gut emptying (emesis/lavage) and supportive therapies.
Available products
Formulations
- Tablets (sustained-release / controlled-release)
- Injection (IV)
- 400 mg tablet (often modified-release)
Human-labeled
- Pentoxifylline Controlled/Extended Release Tablets: 400 mg; Trental® (Hoechst Marion Roussel); generic
- Trental 400 mg modified-release tablets
Regulatory status
Human POM used off-label under the cascade.
Human POM used off-label under the cascade.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Commercially available tablets should be stored in well-closed containers, protected from light at 15-30°C.
Client information
- Administration: Give this medication with food to significantly reduce the chance of stomach upset (vomiting or loss of appetite).
- Patience is Key: For skin and vascular conditions, it may take several weeks (up to 6-8 weeks) to see noticeable improvement. Do not stop the medication early unless directed by your veterinarian.
- Side Effects: Watch for vomiting, diarrhea, or unusual nervousness/excitement. Contact your vet if these occur.
- Expectations: Clients should understand that veterinary experience with this medication is limited and that the risk versus benefit profile is not completely defined.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.