Alprostadil

Dosage Forms

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, 6 ea); 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: 20 mcg (1 ea)

Caverject: 40 mcg (1 ea) [contains benzyl alcohol, lactose]

Solution Reconstituted, Intracavernosal [preservative free]:

Caverject: 20 mcg (1 ea [DSC]) [contains lactose]

Pharmacology

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)

Pharmacokinetics/Pharmacodynamics

Distribution

Insignificant following penile injection

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

Excretion

Primarily urine (90% as metabolites) within 24 hours; feces

Onset of Action

Erectile dysfunction: 5 to 20 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

Duration of Action

Ductus arteriosus will begin to close within 1 to 2 hours after drug is stopped; Erectile dysfunction: Intended duration <1 hour

Half-Life Elimination

30 seconds to 10 minutes

Protein Binding

Plasma: 81% to albumin

Use in Specific Populations

Special Populations Note

Pulmonary disease: May have reduced capacity to clear the drug.

Use: Labeled Indications

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

Use: Off Label

Raynaud phenomenonc

Evidence from small controlled trials indicate that alprostadil may be beneficial in the management of severe systemic sclerosis–related Raynaud phenomenon, demonstrating a decrease in frequency and severity of attacks

Contraindications

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.

Dosage and Administration

Dosing: Adult

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-labeled use): IV: 60 mcg over 3 hours once daily for 5 consecutive days (loading dose) followed by maintenance dosing of 60 mcg over 3 hours once every 30 days for 2 doses (Marasini 2004) or 60 mcg over 3 hours once daily for 6 consecutive days (Bartolone 1999) or 40 mcg (at a rate of 3 to 5 ng/kg/minute) twice daily for a minimum duration of 7 days and repeated every 3 to 4 weeks (Lamprecht 1998)

Dosing: Geriatric

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.

Dosing: Pediatric

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.

Reconstitution

Caverject Impulse: Provided as a dual-chamber syringe with diluent in one chamber. To mix, hold syringe with needle pointing upward and rotate plunger clockwise until it goes all the way in and stops (do not push on the plunger while trying to rotate it); turn upside down several times to evenly mix solution. Device can be set to deliver specified dose, each device can be set at various increments.

Caverject powder: Use only the supplied diluent for reconstitution (ie, bacteriostatic/sterile water with benzyl alcohol 0.945%).

Edex: Reconstitute with NS; use immediately following reconstitution. Discard any remaining solution in cartridge.

Administration

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.

Storage

Caverject Impulse: Store unreconstituted product at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Following reconstitution, store at 2°C to 25°C (36°F to 77°F) and use within 24 hours (do not freeze). Discard any unused solution.

Caverject powder: Store 20 mcg vials at 20°C to 25°C (68°F to 77°F). Store 40 mcg vials at 2°C to 8°C (36°F to 46°F) until dispensed. After dispensing, stable for up to 3 months at or below 25°C (77°F). Following reconstitution, all strengths should be stored at or below 25°C (77°F); do not refrigerate or freeze; use within 24 hours.

Edex: Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Muse: Store at 2°C to 8°C (36°F to 46°F); may be stored at room temperature (below 30°C [86°F]) for up to 14 days. Do not expose to temperatures >30°C (86°F). Each system is for single use only; discarded after use.

Prostin VR Pediatric: Refrigerate at 2°C to 8°C (36°F to 46°F). Extended storage information at room temperature may be available; contact product manufacturer to obtain current recommendations.

Drug Interactions

Phosphodiesterase 5 Inhibitors: May enhance the adverse/toxic effect of Alprostadil. Avoid combination

Adverse Reactions

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)

Warnings/Precautions

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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.

Monitoring Parameters

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

Pregnancy

Pregnancy Considerations

Alprostadil is not indicated for use in women. The manufacturer of Muse recommends a condom barrier when being used during sexual intercourse with a pregnant woman.

Patient Education

What is this drug used for?

• It is used to treat erectile dysfunction (ED).
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Urethra warming or burning
• Aching in penis or surrounding area
• Penile pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe penile pain
• Erectile redness, lumps, swelling, or curving
• Injection site irritation
• Chest pain
• Fast heartbeat
• Dizziness
• Passing out
• Severe headache
• Shortness of breath
• Bruising
• Bleeding
• Swelling of leg veins
• Erection that lasts more than 4 hours
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.