What is prostaglandin E1 (PGE1) and how is it used clinically?

What is PGE1 (Prostaglandin E1)?

Prostaglandin E1 (PGE1), also known as alprostadil, is a synthetic vasodilator prostaglandin that causes smooth muscle relaxation and inhibits platelet aggregation by activating adenylyl cyclase and increasing cyclic adenosine monophosphate (cAMP) levels. 1, 2

Mechanism of Action

PGE1 works through multiple pathways:

• Vascular effects: Causes direct relaxation of smooth muscle cells in blood vessels and cavernous bodies 3, 4
• Platelet inhibition: Prevents platelet aggregation and reduces low-density lipoprotein entry into vascular walls 3
• Neurotransmitter modulation: Attenuates presynaptic noradrenaline release 2, 3
• Erectile function: Induces erection by relaxing trabecular smooth muscle and dilating cavernosal arteries, leading to expansion of lacunar spaces and compression of venules against the tunica albuginea (corporal veno-occlusive mechanism) 2

Clinical Applications

Erectile Dysfunction (FDA-Approved)

Intracavernous injection therapy with alprostadil is the most effective non-surgical treatment for erectile dysfunction, with response rates exceeding 70%. 1, 3, 5

• Initial dosing: The first dose must be administered under direct healthcare provider supervision to establish effective dosing (typically 10-20 mcg), monitor for priapism, and teach proper injection technique 1, 6, 2
• Hypotension risk: Approximately 3% of patients experience hypotension, particularly after the first dose 1, 7
• Priapism risk: Occurs in only 0.35% of patients with PGE1 compared to 6% with papaverine/phentolamine combinations 3
• Common side effects: Pain at injection site or during erection (16.8%), hematoma/ecchymosis (1.5%), and prolonged erection/priapism (1.3%) 5

Intraurethral alprostadil suppositories are a less invasive alternative but less effective than intracavernous injection 1

Peripheral Arterial Disease (Not FDA-Approved in US)

For intermittent claudication, oral vasodilator prostaglandins including PGE1 are NOT recommended as they are not effective medications to improve walking distance (ACC/AHA Class III recommendation, Level of Evidence: A). 1

• Intravenous PGE1 administered once or twice daily for 4-8 weeks showed some improvement in pain-free walking distance in trials, but daily IV administration is impractical for most patients 1

Critical Limb Ischemia

Parenteral administration of PGE-1 for 7-28 days may be considered to reduce ischemic pain and facilitate ulcer healing in patients with critical limb ischemia who are not candidates for revascularization, but efficacy is likely limited to a small percentage of patients (ACC/AHA Class IIb recommendation, Level of Evidence: A). 1

• Dosing: 60-80 micrograms over 2-4 hours per day for 7-28 days 1
• Efficacy: The largest trial (1560 patients) showed statistically significant but marginal improvement in ischemic pain and ulcer healing at 6 months, with no significant reductions in amputation or mortality risk 1
• Common adverse effects: Headache, flushing, and gastrointestinal distress 1

Congenital Heart Disease (Neonatal Use)

PGE1 maintains ductal patency in critical congenital heart disease 8

• Standard dosing: 0.05 µg/kg/minute, though lower doses (0.01 µg/kg/minute) have proven safe and effective in 83% of patients 8
• Respiratory depression: Occurs in 28% of patients, with mechanical ventilation needed in 8%, primarily in premature infants 8
• Prolonged use caution: Necrotizing vasculitis and pulmonary vascular changes have been reported with prolonged PGE1 administration in infants 9

Erythromelalgia

Intravenous iloprost (a synthetic prostacyclin analogue similar to PGE1) significantly reduces symptoms and sympathetic dysfunction in erythromelalgia, though oral misoprostol (a synthetic oral PGE1 analogue at 0.4-0.8 mg daily) should generally be considered first due to easier administration. 1

Pharmacokinetics

• Metabolism: Approximately 80% metabolized in one pass through the lungs, primarily by beta- and omega-oxidation 2
• Excretion: Almost 90% excreted in urine within 24 hours as metabolites 2
• Protein binding: 81% bound to albumin, 55% to α-globulin IV-4 fraction 2
• Systemic absorption: Following intracavernous injection of 20 mcg, peripheral plasma concentrations remain near baseline endogenous levels 2

Critical Safety Considerations

For Erectile Dysfunction Use

• Never prescribe for home use without in-office dose titration and supervised technique demonstration 6
• Maximum frequency: Once per 24-hour period 6
• Priapism protocol: Patients must seek immediate medical attention for erections lasting more than 4 hours; intracavernosal phenylephrine is the recommended initial treatment 6
• Cardiovascular monitoring: Blood pressure monitoring is mandatory during initial administration, especially in patients with pre-existing cardiovascular disease 7

Contraindications

• Sickle cell anemia, severe coagulopathy, schizophrenia or severe psychiatric disorder, poor manual dexterity, severe venous incompetence, or severe systemic disease 5

Long-Term Monitoring

• Monitor for penile fibrosis (incidence ranges from <1% to 23.3% depending on examination rigor) and angulation with extended use 10, 5
• If fibrosis develops, over half of cases improve spontaneously; watchful waiting with 3-month follow-up intervals is recommended 10