Apnea is experienced by about 10% to 12% of neonates with congenital heart defects treated with alprostadil pediatric sterile solution. Apnea is most often seen in neonates weighing less than 2 kg at birth and usually appears during the first hour of drug infusion. Therefore, monitor respiratory status throughout treatment, and use alprostadil pediatric injection where ventilatory assistance is immediately available.
Erectile dysfunction:
Intracavernous (Caverject, Caverject Impulse, Edex): Individualize dose by careful titration; doses >40 mcg (Edex) or >60 mcg (Caverject) are not recommended: Initial dose must be titrated in health care provider setting. Patient must stay in the health care setting 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; doses should be titrated to the lowest effective dose; increasing the dose or concentration in the treatment of impotence results in increasing pain and discomfort.
Initial dose titration: According to the prescribing information for Caverject and Caverject Impulse, no more than 2 doses should be given within a 24-hour period during the initial titration.
Vasculogenic, psychogenic, or mixed etiology: Initiate dosage titration at 2.5 mcg.
If there is a partial response, increase dose by 2.5 mcg to a dose of 5 mcg and then, in increments of 5 to 10 mcg (depending on erectile response) until the dose that produces an erection suitable for intercourse and not exceeding a duration of 1 hour is reached.
If there is no response to the initial 2.5 mcg dose, the second dose may be increased to 7.5 mcg and administered within 1 hour, followed by increments of 5 to 10 mcg (Edex).
If there is a response, then there should be at least a 24-hour interval before the next dose is given.
Neurogenic etiology (eg, spinal cord injury): Note: Caverject powder must be used to prepare a 1.25 mcg dose: Initiate dosage titration at 1.25 mcg; if there is a partial response, may increase to a dose of 2.5 mcg within 1 hour and if necessary, to a dose of 5 mcg; may increase further in increments of 5 mcg until the dose is reached that produces an erection suitable for intercourse and not exceeding a duration of 1 hour.
Maintenance: Once an 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
Intraurethral (Muse Pellet):
Initial: 125 to 250 mcg; dose may be increased or decreased on separate occasions in a stepwise manner until the patient achieves an erection that is sufficient for sexual intercourse.
Maintenance: Administer as needed to achieve an erection; duration of action is about 30 to 60 minutes; use only two systems per 24-hour period.
Raynaud phenomenon (off-label use):
IV: 60 mcg over 3 hours once daily for 5 or 6 consecutive days followed by maintenance dosing of 60 mcg over 3 hours once every 30 days (Bartolone 1999; Marasini 2004) or 40 mcg (at a rate of 3 to 5 ng/kg/minute) twice daily for ≥7 days and repeated every 3 to 4 weeks (Lamprecht 1998).
Dosage adjus tment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Alprostadil: Pediatric drug information")
Ductus arteriosus patency, maintenance: Infants: Continuous IV infusion: Initial: 0.05 to 0.1 mcg/kg/minute; once therapeutic response is achieved, reduce rate to lowest effective dosage; with unsatisfactory response, increase rate gradually; usual maintenance: 0.01 to 0.4 mcg/kg/minute. Note: Therapeutic response is indicated by an increase in systemic blood pressure and pH in those with restricted systemic blood flow and acidosis, or by an increase in oxygenation (pO2) in those with restricted pulmonary blood flow.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
Use lowest effective dose. In clinical studies with Edex, higher minimally effective doses and a higher rate of lack of effect were noted. Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Kit, Intracavernosal:
Caverject Impulse: 10 mcg, 20 mcg [contains benzyl alcohol, lactose]
Edex: 10 mcg, 20 mcg, 40 mcg [pyrogen free; contains lactose]
Pellet, Urethral:
Muse: 125 mcg (1 ea [DSC], 6 ea [DSC]); 250 mcg (1 ea, 6 ea); 500 mcg (1 ea, 6 ea); 1000 mcg (1 ea, 6 ea)
Solution, Injection:
Prostin VR: 500 mcg/mL (1 mL) [contains alcohol, usp]
Generic: 500 mcg/mL (1 mL)
Solution Reconstituted, Intracavernosal:
Caverject: 40 mcg (1 ea) [contains benzyl alcohol, lactose]
Solution Reconstituted, Intracavernosal [preservative free]:
Caverject: 20 mcg (1 ea) [contains lactose]
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Kit, Intracavernosal:
Caverject: 20 mcg [contains benzyl alcohol, lactose]
Pellet, Urethral:
Muse: 250 mcg (1 ea); 500 mcg (1 ea); 1000 mcg (1 ea)
Solution, Injection:
Prostin VR: 500 mcg/mL (1 mL) [contains alcohol, usp]
Solution Reconstituted, Intracavernosal:
Caverject: 20 mcg (1 ea) [contains lactose]
Intracavernous: Erectile dysfunction:
Caverject: Wipe the intended injection site with an alcohol swab prior to injection. Use a 1/2 inch, 29- or 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. Compress the site of injection with an alcohol swab or sterile gauze for 5 minutes after administration.
Caverject Impulse: Supplied as a disposable, single-dose, dual chamber syringe system. Wipe the intended injection site with an alcohol swab prior to injection. After attaching the provided needle assembly, select dose and inject into the dorsolateral aspect of the proximal third of the penis, avoiding visible veins; alternate side of the penis for injections. Compress the site of injection with an alcohol swab or sterile gauze for 5 minutes after administration.
Edex: Wipe the intended injection site with an alcohol swab prior to injection. 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. Administer over a 5- to 10-second interval. Compress the site of injection with an alcohol swab for 5 minutes after administration.
Intraurethral: Erectile dysfunction:
Muse: Insert immediately after urination. Prior to insertion, remove the product from the foil pouch and remove the protective cover from the applicator stem; ensure medicated pellet is present. While sitting or standing, slowly stretch the penis upward to its full length, with gentle compression from top to bottom of the glans. Slowly insert the Muse stem into the urethra up to the collar. Gently press down on the button at the top of the applicator until it stops; leave applicator in place for 5 seconds. Gently rock the applicator from side to side then remove the applicator while keeping the penis upright. If there is residual medication at the end of the applicator, reinsert the applicator and repeat prior steps. Once the applicator is removed, hold the penis upright and stretched to its full length, and roll firmly between hands for at least 10 seconds. Standing or walking for about 10 minutes after administration will increase blood flow and enhance erection.
IV: Raynaud phenomenon (off-label use): Dilute dose in 250 mL of NS or D5W (Bartolone 1999; Lamprecht 1998). Administer 40 mcg dose at a rate of 3 to 5 ng/kg/minute (Lamprecht 1998) or 60 mcg dose over ~3 hours (Bartolone 1999; Marasini 2004) through a peripheral vein (eg, cubital or forearm vein) (Lamprecht 1998).
Continuous IV infusion: Administer into a large vein or alternatively through an umbilical artery catheter placed at the ductal opening.
Rate of infusion (mL/hour) = dose (mcg/kg/minute) x weight (kg) x 60 minutes/hour divided by concentration (mcg/mL)
IV infusion: 10 mcg/mL or 20 mcg/mL
Patent ductus arteriosus (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.
Erectile dysfunction:
Caverject, Edex, Caverject Impulse: Treatment of erectile dysfunction due to vasculogenic, psychogenic, neurogenic, or mixed etiology; Caverject may be a useful adjunct to other diagnostic tests in the diagnosis of erectile dysfunction
Muse: Treatment of erectile dysfunction
Raynaud phenomenon
Alprostadil may be confused with alPRAZolam
Prostin VR may be confused with Prostin E2 (dinoprostone)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Intraurethral:
>10%: Genitourinary: Penile pain, urethral burning
2% to 10%:
Central nervous system: Dizziness, headache, pain
Genitourinary: Testicular pain, urethral bleeding (minor), vulvovaginal pruritus (female partner)
<2%: Leg pain, perineal pain, tachycardia
Intracavernosal injection:
>10%: Genitourinary: Penile pain
1% to 10%:
Cardiovascular: Hypertension
Central nervous system: Dizziness, headache
Genitourinary: Prolonged erection (>4 hours, 4%), penile disease, penile rash, penile swelling, Peyronie's disease
Local: Bruising at injection site, hematoma at injection site
<1%: Balanitis, injection site hemorrhage, priapism (0.4%)
Intravenous:
>10%:
Cardiovascular: Flushing
Respiratory: Apnea
Miscellaneous: Fever
1% to 10%:
Cardiovascular: Bradycardia, cardiac arrest, edema, hypertension, hypotension, tachycardia
Central nervous system: Dizziness, headache, seizure
Endocrine & metabolic: Hypokalemia
Gastrointestinal: Diarrhea
Hematologic & oncologic: Disseminated intravascular coagulation
Infection: Sepsis
Local: Local pain (in structures other than the injection site)
Neuromuscular & skeletal: Back pain
Respiratory: Cough, flu-like symptoms, nasal congestion, sinusitis, upper respiratory tract infection
<1%: Anemia, anuria, bradypnea, cardiac failure, cerebral hemorrhage, gastroesophageal reflux disease, hematuria, hemorrhage, hyperbilirubinemia, hyperemia, hyperirritability, hyperkalemia, hypoglycemia, hypothermia, jitteriness, lethargy, neck hyperextension, peritonitis, second degree atrioventricular block, shock, stiffness, supraventricular tachycardia, thrombocytopenia, ventricular fibrillation, wheezing (bronchial)
Intracavernous: Hypersensitivity to alprostadil or any component of the formulation; conditions predisposing men to priapism (eg, sickle cell anemia or trait, multiple myeloma, leukemia); men with anatomical deformation or fibrotic conditions of the penis (eg, angulation, cavernosal fibrosis, or Peyronie disease); penile implants
IV: There are no contraindications listed in the US labeling.
Canadian labeling: Cyanotic neonates with persistent circulation; neonates with total anomalous pulmonary venous return below the diaphragm; neonates with polysplenia or asplenia in whom pulmonary atresia is combined with anomalous pulmonary venous return, which may be obstructed
Transurethral: Hypersensitivity to alprostadil or any component of the formulation; urethral stricture, balanitis, severe hypospadias and curvature, and in men with acute or chronic urethritis; men who are prone to venous thrombosis or who have a hyperviscosity syndrome (eg, sickle cell anemia or trait, thrombocythemia, polycythemia, multiple myeloma) predisposing them to priapism; use in men for whom sexual activity is inadvisable; sexual intercourse with a pregnant woman unless a condom barrier is being used
Documentation of allergenic cross-reactivity for prostaglandins is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Concerns related to adverse effects:
• Apnea: [US Boxed Warning]: Prostin VR Pediatric: 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.
• Hypotension/syncope: Intracavernous injections can increase peripheral blood levels of alprostadil, resulting in hypotension. Syncope has also been reported. Avoid use in men with known cavernosal venous leakage. Patients must be cautioned to avoid tasks such as operating machinery or driving following administration where injury could result if hypotension or syncope were to occur.
• Penile fibrosis: May occur when used for erectile dysfunction; discontinue use in men who develop penile angulation or cavernosal fibrosis.
• Priapism/prolonged erection: May occur when used for erectile dysfunction; instruct patient to seek immediate medical assistance if an erection persists ≥4 hours; discontinue therapy if priapism or prolonged erection occurs or if signs of penile fibrosis develop (penile angulation, cavernosal fibrosis, or Peyronie disease). To minimize the chances of prolonged erection or priapism, titrate slowly to the lowest effective dose. Use is contraindicated in men who have conditions that predispose them to priapism (eg, sickle cell anemia or trait, multiple myeloma, leukemia). Underlying causes of erectile dysfunction should be evaluated and treated prior to therapy.
Disease related concerns:
• Cardiovascular disease: Treatment for erectile dysfunction should not be used in men whom sexual activity is inadvisable because of underlying cardiovascular status.
Special populations:
• Neonates: Prostin VR Pediatric: Use with caution in neonates with bleeding tendencies.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.
Other warnings/precautions:
• Administration: Muse: Urethral abrasion resulting in minor bleeding or spotting may occur from improper administration.
• Needle breakage: Caverject and Caverject Impulse: A superfine needle is used for administration. Needle breakage (a portion of the needle remaining in the penis) has been reported; hospitalization and surgical removal may be necessary.
• Patency of ductus arteriosus: Appropriate use: Prostin VR Pediatric: Infuse for the shortest time at the lowest dose consistent with good patient care. Use for >120 hours has been associated with antral hyperplasia and gastric outlet obstruction.
Alprostadil should not be used in neonates with respiratory distress syndrome; full diagnostic workup should be done to differentiate between respiratory distress syndrome and cyanotic heart disease. Cortical proliferation of long bones has been associated with long-term infusions of alprostadil; most cases of bone changes occurred 4 to 6 weeks after starting alprostadil, but has occurred as early as 9 days. In a study of 86 infants awaiting cardiac transplant, the incidence of hyperostosis was 42% at <30 days of alprostadil infusion, 87% at 30 to 60 days and 100% at >60 days. Cortical hyperostosis usually resolves over 6 to 12 months after stopping alprostadil (Kaufman 1996; Woo 1994).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Phosphodiesterase 5 Inhibitors: May enhance the adverse/toxic effect of Alprostadil. Risk X: Avoid combination
Muse is contraindicated in males having sexual intercourse with a pregnant woman unless a condom barrier is being used.
Alprostadil is not indicated for use in women.
Alprostadil is not indicated for use in women.
Blood pressure, respiratory rate, heart rate, temperature, degree of penile pain, duration of erection, adequate detumescence after dosing, signs of infection, signs of penile fibrosis
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)
Onset of action: Erectile dysfunction: 5 to 20 minutes
Duration: Ductus arteriosus will begin to close within 1 to 2 hours after drug is stopped; Erectile dysfunction: Intended duration <1 hour
Distribution: Insignificant following penile injection
Protein binding, plasma: 81% to albumin
Metabolism: IV: ~70% to 80% by oxidation during a single pass through the lungs; metabolite (13,14 dihydro-PGE1) is active and has been identified in neonates
Half-life elimination: 30 seconds to 10 minutes
Time to peak:
Acyanotic congenital heart disease: Usual: 1.5 to 3 hours; Range: 15 minutes to 11 hours.
Cyanotic congenital heart disease: Usual: ~30 minutes
Erectile dysfunction: Intracavernosal 30 to 60 minutes; Transurethral: ~16 minutes
Excretion: Primarily urine (90% as metabolites) within 24 hours; feces
Pulmonary disease: May have reduced capacity to clear the drug.
Kit (Caverject Impulse Intracavernosal)
10 mcg (per each): $96.67
20 mcg (per each): $124.49
Kit (Edex Intracavernosal)
10 mcg (per each): $182.11
20 mcg (per each): $235.27
40 mcg (per each): $321.28
Pellet (Muse Urethral)
250 mcg (per each): $81.78
500 mcg (per each): $87.53
1000 mcg (per each): $94.51
Solution (Alprostadil Injection)
500 mcg/mL (per mL): $130.01
Solution (Prostin VR Injection)
500 mcg/mL (per mL): $158.01
Solution (reconstituted) (Caverject Intracavernosal)
20 mcg (per each): $123.53
40 mcg (per each): $162.95
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