ALPROSTADIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALPROSTADIL (ALPROSTADIL).
Alprostadil is a synthetic prostaglandin E1 (PGE1) that causes vasodilation by binding to prostanoid EP receptors, increasing intracellular cAMP, and relaxing smooth muscle. It also inhibits platelet aggregation.
| Metabolism | Primarily metabolized via oxidation in the lungs, liver, and kidneys. Approximately 80% inactivated by 15-hydroxy dehydrogenase enzyme on first pass through the lungs. |
| Excretion | Primarily via urine (90%) as metabolites; 10% unchanged; minimal fecal excretion. |
| Half-life | 5-10 minutes; rapidly metabolized in the lungs, clinical effect lasts longer due to continuous infusion. |
| Protein binding | 80-90% bound to albumin. |
| Volume of Distribution | 0.3-0.4 L/kg (large, extensive tissue distribution). |
| Bioavailability | IV: 100%; intracavernosal: nearly complete; intra-arterial: high first-pass lung metabolism limits systemic bioavailability. |
| Onset of Action | IV: immediate; intracavernosal: 5-20 minutes; intra-arterial: rapid within minutes. |
| Duration of Action | IV: 30-60 minutes (infusion-dependent); intracavernosal: 30-60 minutes (erection); intra-arterial: 1-2 hours. |
Initial: 20-40 mcg IV bolus over 1-2 seconds; then 30-70 mcg/min continuous IV infusion for erectile dysfunction via intracavernosal injection: 2.5-10 mcg; for patent ductus arteriosus: 0.05-0.1 mcg/kg/min continuous IV infusion.
| Dosage form | INJECTABLE |
| Renal impairment | No specific GFR-based dose modifications established; use with caution in renal impairment due to potential for hypotension. |
| Liver impairment | No specific Child-Pugh based dose modifications established; use with caution in hepatic impairment due to altered metabolism. |
| Pediatric use | For patent ductus arteriosus: initial IV infusion 0.05-0.1 mcg/kg/min; titrate to response; for erectile dysfunction: not typically used in pediatric patients. |
| Geriatric use | Start at lower end of dosing range (e.g., initial IV bolus 20 mcg) due to increased sensitivity and comorbidity; monitor blood pressure closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ALPROSTADIL (ALPROSTADIL).
| Breastfeeding | No data on excretion in human milk; M/P ratio unknown. Due to short half-life and local administration, systemic absorption minimal. Use with caution in breastfeeding. |
| Teratogenic Risk | Alprostadil is not indicated for use in pregnancy; systemic exposure poses risk of uterine hyperstimulation and fetal distress. No adequate human studies; animal studies show embryotoxicity. Avoid in pregnancy unless no safer alternative. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to alprostadil","Conditions predisposing to priapism (e.g., sickle cell anemia, multiple myeloma, leukemia)","Penile implant or anatomical penis deformity (for erectile dysfunction formulations)","Neonates with persistent fetal circulation or respiratory distress syndrome (for intravenous formulation)","In women who are pregnant or breastfeeding (not indicated)"]
| Precautions | ["Risk of priapism (prolonged erection >4 hours) requiring immediate medical attention","Risk of penile fibrosis or angulation with long-term use","Use with caution in patients with bleeding disorders or on anticoagulants due to bleeding risk","Do not use in neonates with respiratory distress syndrome or persistent fetal circulation","Monitor blood pressure during intravenous use due to hypotension risk"] |
| Food/Dietary | No known food interactions. Grapefruit may increase levels via CYP3A4 inhibition, but clinical significance is low for topical/intracavernosal use. |
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| Monitor uterine activity (tocolysis if preterm labor), fetal heart rate during systemic use. For erectile dysfunction, no specific monitoring required. |
| Fertility Effects | No documented adverse effects on fertility. Intraurethral or intracavernous alprostadil does not impair spermatogenesis or endocrine function. |
| Clinical Pearls | Alprostadil causes vasodilation via cAMP increase; watch for hypotension and priapism. For erectile dysfunction, inject into corpus cavernosum, not dorsal vein. For patent ductus arteriosus, monitor respiratory drive as apnea is common in neonates. |
| Patient Advice | Seek immediate medical help if erection lasts more than 4 hours. · Do not use if you have a penile implant or conditions like sickle cell disease. · Avoid driving until you know how this medication affects you. · For injection, rotate injection sites and use within 24hrs of opening vial. · Report any signs of infection at injection site. |