Alprostadil

( PGE ₁ ; Prostaglandin E ₁ ) Pronunciation: (al-PRAHST-uh-dill)Class: Impotence agent, Patent ductus arteriosus agent

Trade Names:Caverject- Powder for injection, lyophilized 6.15 mcg (5 mcg/mL)- Powder for injection, lyophilized 11.9 mcg (10 mcg/mL)- Powder for injection, lyophilized 23.2 mcg (20 mcg/mL)

Trade Names:Edex- Powder for injection, lyophilized 6.225 mcg (5 mcg/mL)- Powder for injection, lyophilized 12.45 mcg (10 mcg/mL)- Powder for injection, lyophilized 24.9 mcg (20 mcg/mL)- Powder for injection, lyophilized 49.8 mcg (40 mcg/mL)

Trade Names:Muse- Pellet 125 mcg- Pellet 250 mcg- Pellet 500 mcg- Pellet 1,000 mcg

Trade Names:Prostin VR Pediatric- Injection 500 mcg/mL (in 1 mL dehydrated alcohol)

Prostin VR (Canada)

Pharmacology

Relaxes smooth muscle of ductus arteriosus. Produces vasodilation, inhibits platelet aggregation and stimulates intestinal and uterine smooth muscle. Induces erection by relaxation of trabecular smooth muscle and by dilation of cavernosal arteries.

Pharmacokinetics

Absorption

Urethral suppository

About 80% absorbed within 10 min.

Distribution

About 81% bound to albumin and about 55% bound to alpha-globulin IV-4.

Metabolism

About 80% metabolized in one pass through the lungs.

Urethral suppository

Also rapidly metabolized locally by enzymatic oxidation.

Elimination

Metabolites excreted by kidneys; about 90% of IV dose excreted in urine within 24 h and remainder is excreted in feces. T _1/2 is 0.5 to 10 min.

Special Populations

Pulmonary disease

May have reduced capacity to clear the drug.

Indications and Usage

Palliative therapy to maintain patency of ductus arteriosus temporarily, until surgery can be performed, in newborns who have congenital heart defects (eg, pulmonary stenosis, tricuspid atresia) and who depend on patent ductus for survival. Treatment of erectile dysfunction caused by neurogenic, vasculogenic, psychogenic, or mixed etiology. Intracavernosal alprostadil ( Caverject only) may be useful adjunct to other diagnostic tests in the diagnosis of erectile dysfunction.

Contraindications

Standard considerations.

Caverject

Conditions that might predispose patients to priapism (eg, sickle cell anemia or trait, multiple myeloma leukemia); patients with anatomical deformation of the penis (eg, angulation, cavernosal fibrosis, Peyronie disease); patients with penile implants; use in women, children or newborns; use in men for whom sexual activity is inadvisable or contraindicated.

Dosage and Administration

Ductus ArteriosusNewborns

IV 0.01 to 0.4 mcg/kg/min. Drug is infused for shortest time and at lowest effective dose.

Impotence (Erectile Dysfunction of Vasculogenic, Psychogenic, or Mixed Etiology)

Intracavernosal Initiate dose titration at 2.5 mcg. If there is a partial response, the dose may be increased 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 h is reached. If there is no response to the initial 2.5 mcg dose, the second dose may be increased to 7.5 mcg, followed by increments of 5 to 10 mcg. If there is no response, then the next higher dose may be given within 1 h. If there is a response, then there should be a 1-day interval before the next dose is given.

Erectile Dysfunction of Pure Neurogenic Etiology (Spinal Cord Injury)

Initiate dosage titration at 1.25 mcg. The dose may be increased by 1.25 mcg to a dose of 2.5 mcg, followed by an increment of 2.5 mcg to a dose of 5 mcg, and then in 5 mcg increments until the dose that produces an erection suitable for intercourse and not exceeding a duration of 1 h is reached. If there is no response, then the next higher dose may be given within 1 h. If there is a response, then there should be at least 1-day interval before the next dose is given.

Maintenance therapy

The first injections of alprostadil must be done at the health care provider's office by medically trained personnel. Self-injection therapy by the patient can be started only after the patient is properly instructed and well-trained in the self-injection technique. The health care provider should make a careful assessment of the patient's skills and competence with the procedure.

Intraurethral Administer as needed to achieve an erection. The onset of injection is 5 to 10 min after administration. Duration of effect is approximately 30 to 60 min. Titrate dose under the supervision of health care provider.

CaverjectAdjunct to Diagnosis of Erectile Dysfunction Adults

Intracavernosal Monitor patients for occurrence of an erection after an intracavernosal injection of alprostadil. Extensions of this testing are the use of alprostadil as an adjunct to laboratory investigations (eg, duplex or Doppler imaging) to allow visualization and assessment of penile vasculature. For these tests, use a single dose of alprostadil that induces a rigid erection.

General Advice

• Caverject
• Bacteriostatic water for injection or sterile water, both preserved with benzyl alcohol 0.945% w/v, must be used as the diluent for reconstitution.
• After reconstitution, immediately use the solution and do not store or freeze.
• Do not shake the contents of the reconstituted vial.
• Discard vials with precipitates or discoloration.
• The intracavernosal injection must be done under sterile conditions. The site of injection is usually along the dorsolateral aspect of the proximal third of the penis. Avoid visible veins. The side of the penis that is injected and the site of injection must be alternated; the injection site must be cleansed with an alcohol swab.

• Prostin VR Pediatric
• Dilute medication with normal saline or D5W only.
• Discard preparation after 24 h and mix new solution.

Storage/Stability

Caverject

Store the 5, 10, and 20 mcg strengths at or below 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). Store the 40 mcg strength at 2° to 8°C (36° to 46°F) until dispensed. After dispensing, the 40 mcg strength may be stored at or below 25°C (77°F) for 3 months or until expiration date, whichever occurs first. Use the reconstituted solution within 24 h when stored at or below 25°C (77°F). Do not refrigerate or freeze.

Muse

Store unopened foil pouches in a refrigerator at 2° to 8°C (36° to 46°F). It may be kept at room temperature (below 30°C; 86°F).

Prostin VR Pediatric

Refrigerate at 2° to 8°C (35° to 46°F).

Drug Interactions

Anticoagulants (eg, heparin, warfarin)

After intracavernosal injection, risk of bleeding may be increased.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Flushing; bradycardia; hypotension; tachycardia; cardiac arrest; edema. Other rare, but serious, cardiovascular effects include CHF; hyperemia; second-degree heart block; shock; spasm of right ventricle infundibulum; supraventricular tachycardia; ventricular fibrillation.

CNS

Fever; seizures; cerebral bleeding.

GI

Diarrhea.

Genitourinary

Urethral pain; urethral burning; urethral bleeding/spotting; testicular pain ( Muse only).

Hematologic

DIC; bleeding.

Respiratory

Apnea.

Miscellaneous

Cortical proliferation of long bones; sepsis; penile pain; prolonged erection; penile fibrosis; injection-site hematoma; penis disorder; injection-site ecchymosis ( Caverject only); back pain; pain; pelvic pain; accidental injury ( Muse only).

Precautions

Warnings Apnea is experienced by about 10% to 12% of neonates with congenital heart defects treated with Prostin VR Pediatric solution. Apnea is most often seen in neonates weighing less than 2 kg at birth and usually appears during the first h of drug infusion. Monitor respiratory status throughout treatment.

Monitor Caverject Exercise careful follow-up of the patient while in the self-injection program. This is especially true for the initial self-injections, since adjustments in the dose of alprostadil may be needed. While on self-injection treatment, it is recommended that the patient visit the prescribing health care provider's office every 3 mo. At that time, assess the efficacy and safety of the therapy and adjust the dosage. Prostin VR Pediatric Monitor respiratory status throughout treatment. Have ventilatory equipment at bedside. Monitor BP during administration. Notify health care provider and decrease or stop infusion if infant develops: increased respiratory distress; bleeding, bruising or hematoma formation; sudden changes in cardiac status (eg, decreased BP, bradycardia, cardiac arrest, cyanosis). Decrease or stop infusion until health care provider gives new orders.

Pregnancy

Category C .

Hemostatic effects

Use cautiously in newborns with bleeding tendencies because alprostadil inhibits platelet aggregation.

Respiratory status

Apnea has occurred in some newborns treated with alprostadil.

Priapism (erection lasting more than 6 h)

Prolonged erection has been known to occur following intracavernosal administration of vasoactive substances, including alprostadil. To minimize the chances of priapism, titrate slowing to the lowest effective dose. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result.

Penile fibrosis

Discontinue treatment in patients who develop penile angulation, cavernosal fibrosis, or Peyronie disease.

Overdosage

Symptoms

Apnea, bradycardia, pyrexia, hypotension, flushing.

Patient Information

• Prostin VR Pediatric
• Explain to parents about infant's congenital heart disease and purpose and expected outcome of treatment.
• Keep parents/family informed of course of treatment; alert them to usual adverse reactions (eg, flushing of skin).
• Promote parent-infant bonding by encouraging parental involvement in infant's care.
• Encourage parents to express their emotions. Show compassion and understanding, and help them to cope.

• Caverject
• Thoroughly instruct and train patient in the self-injection technique before beginning intracavernosal treatment at home. Establish the desired dose in the health care provider's office.
• Inform patient that the established dose should not be changed without consulting the health care provider.
• The patient may expect an erection to occur within 5 to 20 min. A standard treatment goal is to produce an erection lasting no longer than 1 h.
• Instruct patient that alprostadil generally should be used 3 times/wk or less, with at least 24 h between each use.
• Instruct patient to seek immediate medical attention if an erection persists for more than 6 h.
• Patient should report any penile pain that was not previously present or that increased in intensity, as well as the occurrence of nodules or hard tissue in the penis to health care provider as soon as possible.
• Advise patient that the use of intracavernosal alprostadil offers no protection from the transmission of STDs. Counsel individuals who use alprostadil about the protective measures necessary to guard against the spread of STDs, including HIV.
• The injection can induce a small amount of bleeding at the site of injection. In patients infected with blood-borne diseases, this could increase the risk of transmission of blood-borne diseases between partners.

• Intraurethral
• Instruct patient on proper technique for administering alprostadil prior to self-administration.

• Muse
• Instruct patient on the proper technique for administering alprostadil prior to self-administration.
• The max frequency of use is 2 systems or less per 24-h period.

Copyright © 2009 Wolters Kluwer Health.