DrugindexOnline^{2nd edition}

Pronouncation: (pen-TOX-IH-fill-in)
Class: Hemorrheologic agent

Trade Names:
Trental
- Tablets, controlled-release 400 mg

Nu-Pentoxifylline (Canada)
Pentoxifylline (Canada)

Mechanism of Action

Pharmacology

Improves blood flow by decreasing blood viscosity.

Pharmacokinetics

Absorption

Pentoxifylline is almost completely absorbed. Food delays absorption and increases C _max by 28% and AUC by 13%. T _max is 1 hr (parent drug and metabolites) and 2 to 4 hr (controlled–release).

Distribution

Extensive first-pass metabolism. Protein binding to erythrocyte membrane. Both parent drug and metabolites distribute into breast milk.

Metabolism

Undergoes first-pass effect and, in the liver, some metabolites are active with 5 to 8 times the plasma levels of the parent drug.

Elimination

Urine (as metabolites), fecal (less than 4%). The plasma t _{1/ 2} is 0.4 to 0.8 hr (parent drug) and 1 to 1.6 hr (metabolites).

Onset

2 to 4 wk (multiple doses).

Special Populations

Elderly

Increases AUC and decreases elimination rate (60 to 68 yr).

Indications and Usage

Intermittent claudication on basis of chronic occlusive arterial disease of limbs.

Unlabeled Uses

Treatment of psychopathological symptoms in patients with cerebrovascular insufficiency; treatment of diabetic angiopathies; reduction of incidence of stroke in patients with recurrent TIAs.

Contraindications

Intolerance to methylxanthines (ie, caffeine, theophylline); recent cerebral or retinal hemorrhage.

Dosage and Administration

Adults

PO 400 mg tid with meals for greater than or equal to 8 wk. If GI and CNS side effects occur, decrease to 400 mg bid. If side effects persist, discontinue.

Storage/Stability

Store at room temperature in a tightly closed, light-resistant container.

Drug Interactions

Antihypertensives

Small decreases in blood pressure possible with patients receiving pentoxifylline while using antihypertensive drugs. Monitor blood pressure. If indicated, reduce dosage of the antihypertensive.

Cimetidine

Effects of pentoxifylline may be increased.

Theophylline

Concomitant administration with pentoxifylline leads to increased theophylline levels and possible toxicity in some patients. Monitor and adjust closely.

Warfarin

Bleeding and prolonged prothrombin time possible in patients.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Angina; edema; hypotension; dyspnea; arrhythmia; tachycardia.

CNS

Dizziness; insomnia; headache; tremor; anxiety; confusion.

Dermatologic

Brittle fingernails; pruritus; rash; flushing; urticaria.

EENT

Blurred vision; conjunctivitis; nose-bleed; bad taste; excessive salivation; sore throat.

GI

Dyspepsia; nausea; vomiting; belching; flatus; bloating; dry mouth.

Hepatic

Hepatitis; jaundice.

Hematologic

Leukopenia; pancytopenia; purpura; thrombocytopenia; decreased serum fibrinogen.

Respiratory

Flu-like symptoms; laryngitis.

Precautions

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy for children less than 18 yr not established.

Renal Function

Drug may accumulate, producing toxicity; lower dose may be necessary.

Hemorrhage

Periodically examine patients with risk of hemorrhage for bleeding.

Overdosage

Symptoms

Symptoms appear to be dose related. They usually occur 4 to 5 hr after ingestion and last approximately 12 hr. Symptoms include flushing, hypotension, nervousness, agitation, tremors, convulsions, somnolence, loss of consciousness, fever, and agitation. Transient (less than 24 hr) bradycardia with first- or second-degree atrioventricular block may be seen.

Patient Information

• Explain that improvement in symptoms may take 2 to 4 wk to notice and up to 8 wk for max relief.
• Explain importance of follow-up lab work for patients with high risk of bleeding or taking anticoagulant.
• In patients with occlusive peripheral vasospastic disorders, emphasize use of self-help measures to augment drug therapy (eg, exercise, weight control, no smoking).
• Review specifics of good foot care, including bathing of feet daily in lukewarm water and drying thoroughly, applying lanolin to feet after bathing, use of lambs wool between toes and feet, avoidance of extremes in temperature, wearing of clean cotton socks daily.
• Instruct patient to report the following symptoms to health care provider: dizziness, chest pain, fainting, excessive bruising, abnormal bleeding.
• Advise patient that drug may cause dizziness, and to use caution while driving or performing other tasks requiring mental alertness.