Alprostadil
Pronunciation
(al PROS ta dill)
U.S. Brand Names
Caverject®; Caverject® Impulse™; Edex®; Muse®; Prostin VR Pediatric®
Synonyms
PGE1; Prostaglandin E1
Generic Available
Yes
Canadian Brand Names
Caverject®; Muse® Pellet; Prostin® VR
Use
Prostin VR Pediatric®: Temporary maintenance of patency of ductus arteriosus in neonates with ductal-dependent congenital heart disease until surgery can be performed. These defects include cyanotic (eg, pulmonary atresia, pulmonary stenosis, tricuspid atresia, Fallot's tetralogy, transposition of the great vessels) and acyanotic (eg, interruption of aortic arch, coarctation of aorta, hypoplastic left ventricle) heart disease
Caverject®: Treatment of erectile dysfunction of vasculogenic, psychogenic, or neurogenic etiology; adjunct in the diagnosis of erectile dysfunction
Edex®, Muse®: Treatment of erectile dysfunction of vasculogenic, psychogenic, or neurogenic etiology
Use - Unlabeled/Investigational
Investigational: Treatment of pulmonary hypertension in infants and children with congenital heart defects with left-to-right shunts
Pregnancy Risk Factor
X/C (Muse®)
Pregnancy Implications
Alprostadil is embryotoxic in animal studies. It is not indicated for use in women. The manufacturer of Muse® recommends a condom barrier when being used during sexual intercourse with a pregnant women.
Lactation
Not indicated for use in women
Contraindications
Hypersensitivity to alprostadil or any component of the formulation; hyaline membrane disease or persistent fetal circulation and when a dominant left-to-right shunt is present; respiratory distress syndrome; conditions predisposing patients to priapism (sickle cell anemia, multiple myeloma, leukemia); patients with anatomical deformation of the penis, penile implants; use in men for whom sexual activity is inadvisable or contraindicated; pregnancy
Warnings/Precautions
Use cautiously in neonates with bleeding tendencies; apnea may occur in 10% to 12% of neonates with congenital heart defects, especially in those weighing <2 kg at birth; apnea usually appears during the first hour of drug infusion.
When used in erectile dysfunction: priapism may occur; patient must be instructed to report to physician or seek immediate medical assistance if an erection persists greater than 4 hours. Treat immediately to avoid penile tissue damage and permanent loss of potency; discontinue therapy if signs of penile fibrosis develop (penile angulation, cavernosal fibrosis, or Peyronie's disease). When used in erectile dysfunction (Muse®), syncope occurring within 1 hour of administration, has been reported; the potential for drug-drug interactions may occur when Muse® is prescribed concomitantly with antihypertensives; some lowering of blood pressure may occur without symptoms, and swelling of leg veins, leg pain, perineal pain, and rapid pulse have been reported in <2% of patients during in-clinic titration and home treatment.
Adverse Reactions
Intraurethral:
>10%: Genitourinary: Penile pain, urethral burning
2% to 10%:
Central nervous system: Headache, dizziness, pain
Genitourinary: Vaginal itching (female partner), testicular pain, urethral bleeding (minor)
<2%: Tachycardia, perineal pain, leg pain
Intracavernosal injection:
>10%: Genitourinary: Penile pain
1% to 10%:
Cardiovascular: Hypertension
Central nervous system: Headache, dizziness
Genitourinary: Prolonged erection (>4 hours, 4%), penile fibrosis, penis disorder, penile rash, penile edema
Local: Injection site hematoma and/or bruising
<1%: Balanitis, injection site hemorrhage, priapism (0.4%)
Intravenous:
>10%:
Cardiovascular: Flushing
Central nervous system: Fever
Respiratory: Apnea
1% to 10%:
Cardiovascular: Bradycardia, hyper-/hypotension, tachycardia, cardiac arrest, edema
Central nervous system: Seizures, headache, dizziness
Endocrine & metabolic: Hypokalemia
Gastrointestinal: Diarrhea
Hematologic: Disseminated intravascular coagulation
Neuromuscular & skeletal: Back pain
Respiratory: Upper respiratory infection, flu syndrome, sinusitis, nasal congestion, cough
Miscellaneous: Sepsis, localized pain in structures other than the injection site
<1%: Anemia, anuria, bleeding, bradypnea, bronchial wheezing, cerebral bleeding, CHF, gastric regurgitation, hematuria, hyperbilirubinemia, hyperemia, hyperextension of neck, hyperirritability, hyperkalemia, hypoglycemia, hypothermia, jitteriness, lethargy, peritonitis, second degree heart block, shock, stiffness, supraventricular tachycardia, thrombocytopenia, ventricular fibrillation
Overdosage/Toxicology
Symptoms of overdose when treating patent ductus arteriosus include apnea, bradycardia, hypotension, and flushing. If hypotension or pyrexia occurs, the infusion rate should be reduced until symptoms subside. Apnea or bradycardia requires drug discontinuation. If intracavernous overdose occurs, supervise until systemic effects have resolved or until penile detumescence has occurred.
Drug Interactions
Risk of hypotension and syncope may be increased with antihypertensives.
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid concurrent use (vasodilating effect).
Stability
Caverject® Impulse™: Store at controlled room temperature of 15°C to 30°C (59°F to 86°F). Provided as a duel-chamber syringe with diluent in one chamber. To mix, hold syringe with needle pointing upward and turn plunger clockwise; turn upside down several times to mix. Device can be set to deliver specified dose, each device can be set at various increments. Following reconstitution, use within 24 hours and discard any unused solution.
Caverject® powder: The 5 mcg, 10 mcg, and 20 mcg vials should be stored at or below 25°C (77°F). The 40 mcg vial should be stored at 2°C to 8°C until dispensed. After dispensing, stable for up to 3 months at or below 25°C. Use only the supplied diluent for reconstitution (ie, bacteriostatic/sterile water with benzyl alcohol 0.945%). Following reconstitution, all strengths should be stored at or below 25°C (77°F); do not refrigerate or freeze; use within 24 hours.
Caverject® solution: Prior to dispensing, store frozen at -20°C to -10°C (-4°F to -14°F); once dispensed, may be stored frozen for up to 3 months, or under refrigeration at 2°C to 8°C (36°F to 46°F) for up to 7 days. Do not refreeze. Once removed from foil wrap, solution may be allowed to warm to room temperature prior to use. If not used immediately, solution should be discarded. Shake well prior to use.
Edex®: Store at controlled room temperature of 15°C to 30°C (59°F to 86°F); following reconstitution with NS, use immediately and discard any unused solution.
Muse®: Refrigerate at 2°C to 8°C (36°F to 46°F); may be stored at room temperature for up to 14 days.
Prostin VR Pediatric®: Refrigerate at 2°C to 8°C (36°F to 46°F); prior to infusion, dilute with D5W or NS; use within 24 hours.
Mechanism of Action
Causes vasodilation by means of direct effect on vascular and ductus arteriosus smooth muscle; relaxes trabecular smooth muscle by dilation of cavernosal arteries when injected along the penile shaft, allowing blood flow to and entrapment in the lacunar spaces of the penis (ie, corporeal veno-occlusive mechanism)
Pharmacodynamics/Kinetics
Onset of action: Rapid
Duration: <1 hour
Distribution: Insignificant following penile injection
Protein binding, plasma: 81% to albumin
Metabolism: ~75% by oxidation in one pass via lungs
Half-life elimination: 5-10 minutes
Excretion: Urine (90% as metabolites) within 24 hours
Dosage
Patent ductus arteriosus
(Prostin VR Pediatric®):
I.V. continuous infusion into a large vein, or alternatively through an umbilical artery catheter placed at the ductal opening: 0.05-0.1 mcg/kg/minute with therapeutic response, rate is reduced to lowest effective dosage; with unsatisfactory response, rate is increased gradually; maintenance: 0.01-0.4 mcg/kg/minute
PGE1 is usually given at an infusion rate of 0.1 mcg/kg/minute, but it is often possible to reduce the dosage to
1
/2 or even
1
/10 without losing the therapeutic effect. The mixing schedule is as follows. Infusion rates deliver 0.1 mcg/kg/minute: See table.
Erectile dysfunction:
Alprostadil
Add 1 Ampul
(500 mcg) to: |
Concentration
(mcg/mL) |
Infusion Rate |
mL/min/kg
Needed to Infuse
0.1 mcg/kg/min |
mL/kg/24 h |
|
250 mL |
2 |
0.05 |
72 |
|
100 mL |
5 |
0.02 |
28.8 |
|
50 mL |
10 |
0.01 |
14.4 |
|
25 mL |
20 |
0.005 |
7.2 |
Therapeutic response is indicated by increased pH in those with acidosis or by an increase in oxygenation (PO2) usually evident within 30 minutes
Erectile dysfunction:
Caverject®, Edex®: Intracavernous: Individualize dose by careful titration; doses >40 mcg (Edex®) or >60 mcg (Caverject®) are not recommended: Initial dose must be titrated in physicians office. Patient must stay in the physician's office until complete detumescence occurs; if there is no response, then the next higher dose may be given within 1 hour; if there is still no response, a 1-day interval before giving the next dose is recommended; increasing the dose or concentration in the treatment of impotence results in increasing pain and discomfort
Vasculogenic, psychogenic, or mixed etiology: Initiate dosage titration at 2.5 mcg, increasing by 2.5 mcg to a dose of 5 mcg and then in increments of 5-10 mcg depending on the erectile response until the dose produces an erection suitable for intercourse, not lasting >1 hour; if there is absolutely no response to initial 2.5 mcg dose, the second dose may be increased to 7.5 mcg, followed by increments of 5-10 mcg
Neurogenic etiology (eg, spinal cord injury): Initiate dosage titration at 1.25 mcg, increasing to a dose of 2.5 mcg and then 5 mcg; increase further in increments 5 mcg until the dose is reached that produces an erection suitable for intercourse, not lasting >1 hour
Maintenance: Once appropriate dose has been determined, patient may self-administer injections at a frequency of no more than 3 times/week with at least 24 hours between doses
Muse® Pellet: Intraurethral:
Initial: 125-250 mcg
Maintenance: Administer as needed to achieve an erection; duration of action is about 30-60 minutes; use only two systems per 24-hour period
Elderly: Elderly patients may have a greater frequency of renal dysfunction; lowest effective dose should be used. In clinical studies with Edex®, higher minimally effective doses and a higher rate of lack of effect were noted.
Administration
Erectile dysfunction: Use a
1
/2 inch, 27- to 30-gauge needle. Inject into the dorsolateral aspect of the proximal third of the penis, avoiding visible veins; alternate side of the penis for injections.
Monitoring Parameters
Arterial pressure, respiratory rate, heart rate, temperature, degree of penile pain, length of erection, signs of infection
Patient Education
Use only as directed, no more than 3 times/week, allowing 24 hours between injections. Avoid alcohol. Store in refrigerator and dilute with supplied diluent immediately before use. Use alternate sides of penis with each injection. Dispose of syringes and needle and single dose vials in a safe manner (do not share medication, syringes, or needles). Note that the risk of transmitting blood-borne disease is increased with use of alprostadil injections since a small amount of bleeding at injection site is possible. Stop using and contact prescriber immediately if signs of priapism occur, erections last more than 4 hours, or you experience moderate to severe penile pain. Report penile problems (eg, nodules, new penile pain, rash, bruising, numbness, swelling, signs of infection, abnormal ejaculations); cardiac symptoms (hypo- or hypertension, chest pain, palpitations, irregular heartbeat); flushing, fever, flu-like symptoms; respiratory difficulty or wheezing; or other adverse reactions. Refer to prescriber every 3 months to ensure proper technique and for dosage evaluation.
Pregnancy precautions:
Consult prescriber about use of barrier contraceptives. Do not give blood while taking this medication and for 1 month following discontinuance.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness; rarely may produce irritability
Mental Health: Effects on Psychiatric Treatment
May cause seizures; use caution with clozapine and bupropion
Dosage Forms
[DSC] = Discontinued product
Injection, powder for reconstitution:
Caverject®: 10 mcg, 20 mcg, 40 mcg [contains lactose; diluent contains benzyl alcohol]
Caverject® Impulse™: 10 mcg, 20 mcg [prefilled injection system; contains lactose; diluent contains benzyl alcohol]
Edex®: 10 mcg, 20 mcg, 40 mcg [contains lactose; diluent contains benzyl alcohol; also packaged in kits containing diluent, syringe, and alcohol swab]
Injection, solution: 500 mcg/mL (1 mL)
Caverject® [DSC]: 20 mcg/mL (2 mL)
Prostin VR Pediatric®: 500 mcg/mL (1 mL) [contains dehydrated alcohol]
Pellet, urethral (Muse®): 125 mcg, 250 mcg, 500 mcg, 1000 mcg
References
Peled N, Dagan O, Babyn P, et al, "Gastric-Outlet Obstruction Induced by Prostaglandin Therapy in Neonates,"
N Engl J Med
, 1992, 327(8):505-10.
Weesner KM, "Hemodynamic Effects of Prostaglandin E1 in Patients With Congenital Heart Disease and Pulmonary Hypertension,"
Cathet Cardiovasc Diagn
, 1991, 24(1):10-5.
Williams G, Abbou CC, Amar ET, et al, "The Effect of Transurethral Alprostadil on the Quality of Life of Men With Erectile Dysfunction, and Their Partners. MUSE Study Group,"
Br J Urol
, 1998, 82(6):847-54.
Woo K, Emery J, and Peabody J, "Cortical Hyperostosis: A Complication of Prolonged Prostaglandin Infusion in Infants Awaiting Cardiac Transplantation,"
Pediatrics
, 1994, 93(3):417-20.
International Brand Names
Alprostadil Pharmacia® (ES); Alprostan® (CZ); Alprostapint® (AT, CZ, HU, IL, PL); Alprostar® (IT); Aplicav® (BR); Bondil® (NO, SE); Cardiobron® (AR); Caverject® (AR, AT, AU, BE, BG, CA, CH, CL, CO, CR, CZ, DE, DK, ES, FI, FR, GB, GT, HN, HR, HU, ID, IE, IL, IT, LU, MX, NL, NO, NZ, PA, PL, PT, RO, RU, SE, SG, SI, SV, TH, ZA); Caverject Dual® (FI, SE); Edex® (FR, PL, RU); Eglandin® (SG); Karon® (CZ); Minprog® (AT, DE); Muse® (AU, CH, DK, FI, GB, ID, IE, IL, MX, NL, RO, ZA); Muse® Pellet (CA); Prolisina VR® (AR); Prostandin® (JP); Prostavasin® (AR, AT, CZ, DE, HU, IT, LU, PL); Prostine VR® (AU, FR, IN, PL); Prostin VR® (AU, BE); Prostin® VR (CA); Prostin VR® (CH, CL, CO, CZ, GB, HR, HU, IL, IN, IT, NZ, PL, PT, SI, TH); Prostivas® (DK, FI, NO, SE); Sugiran® (ES); Vazaprostan® (RU); Viridal® (DE, GB, IE, IT)
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