Questions about Atrial Fibrillation? Get answers from our expert.

Alprostadil

Pronunciation

Class: Vasodilating Agents, Miscellaneous
VA Class: CV900
Chemical Name: (11α,13E,15S)-11,15-Dihydroxy-9-oxo-prost-13-en-1-oic acid
Molecular Formula: C20H34O5
CAS Number: 745-65-3
Brands: Caverject, edex, Muse, Prostin VR Pediatric

Warning(s)

  • Apnea
  • Apnea reported in 10–12% of neonates with congenital heart defects receiving IV or intra-arterial alprostadil;1 3 44 50 53 60 usually occurs during first hour of IV or intra-arterial infusion, particularly in neonates weighing <2 kg at birth.1 3 44 50 53 60

  • Use in neonates only when adequate treatment facilities for assisted ventilation are readily available;1 3 44 50 53 60 monitor respiratory status throughout therapy.1 50

Introduction

Vasodilator and platelet-aggregation inhibitor; a naturally occurring prostaglandin E1.1 5 20 98

Uses for Alprostadil

Erectile Dysfunction

Used to facilitate attainment of a sexually functional erection in males with erectile dysfunction (ED, impotence).98 110 b

Second-line therapy for treatment of ED in patients not responding to psychotherapy/behavioral therapy, vacuum constriction devices, and/or oral, selective phosphodiesterase (PDE) type 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)19 23 65 112 s t u v and in whom attempts at identifying and modifying any drug-related (e.g., certain antihypertensive agents) or other potentially reversible medical causes of ED have proved inadequate.2 19 23 65 112

Selective oral PDE type 5 inhibitor therapy preferred as first-line treatment of ED unless contraindicated.112

Intraurethral therapy generally preferred over intracavernosal vasoactive therapy because it is less invasive; however intracavernosal therapy is most effective nonsurgical treatment for ED.112

Consider intraurethral therapy for patients with inadequate responses to or who are not candidates for selective oral PDE type 5 inhibitor therapy.112

Slideshow: The Rise to Fame: Viagra, PDE5 Inhibitors, and ED

Effective in patients with organic (neurogenic and/or mild to moderate vasculogenic) ED or with psychogenic ED.19 20 24 25 27 34 36 41 45 46 64 67 71

Not recommended for simply enhancing erections in men who are not impotent because of GU risks.64 (See Priapism and also GU Effects, under Cautions.)

Manufacturers state that safety and efficacy of alprostadil in combination with other vasoactive therapy for erectile dysfunction not established and currently not recommended.64 101 b However, American Urological Association (AUA) and other clinicians state that combination therapy with other intracavernosal vasoactive agents increased efficacy and decreased adverse effects relative to alprostadil alone.9 10 11 12 14 15 17 18 21 65 71 90 91 y z Combined therapy with intraurethral alprostadil and vacuum constriction device or oral selective PDE type 5 inhibitor increased efficacy relative to alprostadil alone.112

Adjunct to other vascular testing (e.g., duplex ultrasonography, cavernosometry/cavernosography, angiography, radioisotope penogram) in differential diagnosis of ED and evaluation of hemodynamic status of erectile tissue.5 15 16 17 21 24 27 28 65 66 67 110 b

Ductus Arteriosus-dependent Congenital Heart Disease

Palliative treatment in maintaining patency of ductus arteriosus in neonates with various ductal-dependent congenital heart defects (e.g., pulmonary atresia, pulmonary stenosis, tricuspid atresia, tetralogy of Fallot, interruption of aortic arch, coarctation of the aorta, transposition of great vessels).1 3 29 42 43 44 47 51 56 57 60

Used to provide adequate circulation and oxygenation and prevent or correct resultant acidemia until corrective or palliative surgery can be performed.1 3 42 43 44 47 49 51 52 53 54 55 56 60

Do not use in neonates with respiratory distress syndrome.1 4 42 49 64 (See Respiratory Distress Syndrome under Cautions.)

Alprostadil Dosage and Administration

General

ED

  • Initiate and titrate dosage in medical setting (e.g., clinician’s office);7 23 34 65 98 101 110 112 b patient must remain in this setting until complete detumescence occurs.5 19 32 64 112 b d h

  • Carefully individualize dosage according to patient’s erectile response5 8 12 19 32 34 89 98 99 100 101 107 b toward therapeutic goal of achieving erection satisfactory for intercourse, but persists for ≤1 hour.5 12 34 69 89 97 98 b h (See Priapism under Cautions.)

  • Titrate dosage slowly to lowest possible effective level to avoid priapism.5 12 19 32 101 b Erections persisting >1 hour increase risk of priapism.5 12 34 69 89 97 98 b h (See Priapism under Cautions.)

  • Initiate maintenance home treatment regimens at dosage determined as optimal during titration in medical setting.97 98 b d f Further dosage adjustments may be required.b d f i Dosage determined by clinician in medical setting should not be changed without consulting clinician.b e f i r

Ductus Arteriosus-dependent Congenital Heart Disease

  • Use only by trained personnel in facilities providing pediatric intensive care.1 3 44 50 53 60 Monitor respiratory status of neonate throughout administration; facilities and equipment for assisted ventilation should be readily available.1 50 (See Boxed Warning.)

  • Adjust dosage using lowest possible effective dosage for shortest period necessary to provide desired effects.1

  • If long-term infusion considered (e.g., when surgery deferred in poor-risk neonate), carefully weigh risks of prolonged therapy against anticipated benefits.1 44 47 49 50 54 55 58 59 (See GI Effects, Musculoskeletal Effects, and also Cardiovascular and Cerebrovascular Effects, under Cautions.)

  • In neonates with restricted pulmonary blood flow, monitor measures of improved blood oxygenation.1 3 29 42 43 44 54 56 57 60 70

  • In neonates with restricted systemic blood flow, monitor measures of improved systemic BP and blood pH.1 3 29 43 44 48 51 54 56 57 60

  • Periodically monitor arterial BP via umbilical artery catheter, auscultation, or Doppler transducer.1 50 (See Cardiovascular and Cerebrovascular Effects under Cautions.)

Administration

Administer by continuous IV or intra-arterial infusion to maintain patency of ductus arteriosus in neonates with congenital heart disease.1

Administer by intracavernosal injection for treatment and diagnosis of ED or by intraurethral suppository for treatment of ED.97 98 100 101 b

IV and Intra-arterial Infusion

For solution and drug compatibility information, see Compatibility under Stability.

To maintain patency of ductus arteriosus, administer by continuous IV infusion into a large vein (peripheral or central);1 44 preferred route of administration.1 3 50

Alternatively, administer by controlled intra-arterial infusion through an umbilical1 3 57 70 artery catheter placed at ductal opening or main pulmonary artery.1 44 56 57 70

If flushing occurs during intra-arterial infusion, reposition catheter or convert to IV infusion.1 3 50 54 55

A controlled-infusion device (e.g., an electronic volumetric controller, volumetric IV infusion pump) or other apparatus to ensure precise control of the flow rate should be used; inadvertent rapid administration could result in toxicity (e.g., apnea).1 50 60 70 (See Boxed Warning.)

Dilution

Alprostadil for injection concentrate must be diluted prior to IV or intra-arterial infusion.1

Add 1 mL of alprostadil concentrate to 0.9% sodium chloride or 5% dextrose injection to provide solution containing 2–20 mcg/mL of drug, depending on controlled-infusion device employed and needs of neonate.1 64

When using a device with a volumetric infusion chamber, add appropriate volume of diluent to chamber first and then add 1 mL of drug concentrate to diluent.1

Dilution of Alprostadil Concentrate for Injectiona

Add 1 vial (volume of 500 mcg/mL concentrate)

to Compatible IV Solution (volume of solution)

to Make (final dilution concentration)

1 mL

250 mL

2 mcg/mL

1 mL

100 mL

5 mcg/mL

1 mL

50 mL

10 mcg/mL

1 mL

25 mL

20 mcg/mL

Rate of Administration

Sample infusion rates to deliver a dosage of 0.1 mcg/kg of body weight per minute can be obtained from the following table: a

Infusion Rates to Provide Dosage of 0.1 mcg/kg per Minute

Final Dilution Concentration

Infusion rate

2 mcg/mL

0.05 mL/minute per kg of body weight

5 mcg/mL

0.02 mL/minute per kg of body weight

10 mcg/mL

0.01 mL/minute per kg of body weight

20 mcg/mL

0.005 mL/minute per kg of body weight

Decrease rate of infusion immediately if clinically important decrease in arterial BP, fever, or hypotension occurs.1 3 50 (See Cardiovascular and Cerebrovascular Effects under Cautions.) Once symptoms subside, increase rate cautiously, if necessary.1 3 50

Intracavernosal Administration

Administer by intracavernosal injection into the penis.22 24 27 67 69 71 83 89 101 e i r

Vary injection site to minimize adverse effects related to repeated local injection.8 89 111 b e r

Prior to administration using Caverject impulse dual-chambered syringe system, set dose to be delivered by slowly turning the end of the plunger rod clockwise until the number visible in the dose window matches the appropriate dose of the drug (in mcg).111

Reconstituted solutions of alprostadil for intracavernosal injection are intended for single-use only.2 28 101 110 Properly dispose of single-use delivery device and any remaining solution following use.110 111

Reconstitution

Caverject: Reconstitute vial labeled as containing 20 or 40 mcg of alprostadil powder with 1 mL of bacteriostatic or sterile water for injection (with benzyl alcohol) supplied by manufacturer, to provide a solution containing 20.5 or 41.1 mcg/mL, respectively, and delivering 20 or 40 mcg/mL.b (See Pediatric Use under Cautions.) Use a 3 mL syringe with a 27- to 30-gauge, 0.5-inch needle.b Swirl contents of vial gently until clear solution obtained.e Withdraw desired dose of reconstituted solution into same syringe prior to administration.e

Caverject impulse dual-chambered syringe system: Reconstitute by turning plunger rod clockwise until rod meets resistance110 111 to force diluent (sterile bacteriostatic water for injection) into chamber containing sterile powder.111 Mix contents of syringe thoroughly by turning device upside down several times until solution is clear.110 111

edex dual-chambered system: Place cartridge containing alprostadil lyophilized powder into edex injection devicer and push plunger of device until 2 gray rubber stoppers touch to force diluent (1.075 mL of 0.9% sodium chloride injection) into upper chamber containing drug powder.d r Gently move injection device back and forth until solution is clear.r Do not use if cartridge is damaged or cake of drug powder is substantially <(3/8) inch in thickness.101

Intracavernosal Injection Technique

Hold head (glans) of penis (if uncircumcised, pull back foreskin initially) between thumb and forefinger, and stretch lengthwise along thigh while sitting upright or slightly reclined.22 24 27 67 69 71 83 89 101 e i r Inject into a corpus cavernosum of the penis (underneath the tunica albuginea along dorsolateral aspect of proximal third of penis) using a steady motion.22 24 27 64 67 69 71 83 89 101 110 111 e i r Avoid blood vessels, corpus spongiosum, subcutaneous tissue, urethra, and dorsal neural vascular structures as injection sites.5 7 8 28 34 83 b d e h i

Inject dose slowly (over 5–10 seconds);22 27 64 71 83 101 110 111 r apply pressure to injection site with alcohol swab for 5 minutes (or until bleeding stops) after needle is withdrawn.7 22 25 67 71 83 89 101 111 e r If bleeding continues or recurs, abstain from intercourse.r (See Hematologic Effects under Cautions.)

If solution does not inject easily or if a burning pain at injection site occurs, reposition needle by moving needle slightly or partially withdrawing needle until solution can be injected easily and painlessly.i r

If needle bends severely at anytime during reconstitution or injection, discard needle, and replace with new unused needle.e

Rate of Administration

Inject slowly (over 5–10 seconds).22 27 64 71 83 101 110 111 r

Intraurethral Administration

Administer intraurethrally as a suppository.97 98 99 100 104 105 106

Urinate immediately prior to administration and gently shake penis to remove excess urine.97 100 105 106 Microsuppository (medicated pellet) is designed to dissolve in small quantity of urine remaining in urethra after urination.99

Insert intraurethral suppository according to manufacturer’s instructions.97 100 After insertion, inspect applicator to confirm that urethral suppository is no longer in applicator tip.100 If some residual medication is left in applicator, repeat insertion procedure.100 Urination or dribbling immediately following intraurethral administration may result in loss of drug from urethral area.100

After insertion of suppository, hold penis upright, and stretch to its full length.100 Roll penis firmly between hands for ≥10 seconds to ensure that drug distributes adequately along walls of urethra.100 If a burning sensation occurs, roll penis for additional 30–60 seconds or until burning subsides.100

After administration, increase blood flow to penis by sitting, standing, or walking for 10 minutes.100 106 Lying down (especially on back) immediately after administration may reduce penile blood flow and subsequent development of erection.100 106 During sexual activity, use positions that favor blood flow into penis.100

Dosage

Pediatric Patients

Ductus Arteriosus-dependent Congenital Heart Disease
IV and Intra-arterial Infusion

Neonates: Initially, 0.1 mcg/kg per minute.1 3 a However, adequate clinical response reported with 0.05 mcg/kg per minute1 70 in some neonates.3 43 49 57 58 60 70 95 96

If response inadequate, may increase dosage gradually to ≤0.4 mcg/kg per minute.1 3 57 60 a However, dosages >0.1 mcg/kg per minute generally have not produced additional benefit.1 3 57 60 a

After therapeutic response achieved, reduce infusion rate to provide the lowest possible dosage that maintains response; progressively taper dosage from 0.1 down to 0.05 to 0.025 to 0.01 mcg/kg per minute until lowest effective dose reached.1 3

Continue therapy until surgical repair is complete, usually ≤24–48 hours after initiation.3 44

If complications occur, consider lower infusion rate or discontinuance of infusion.1 60 (See IV and Intra-arterial Infusion: Rate of Administration under Dosage and Administration.)

If apnea or bradycardia occurs, discontinue infusion and initiate appropriate treatment.1 50 In some cases, reinitiate infusion cautiously if continued therapy considered necessary.1 3 42 50 64

Adults

ED
Initiation and Titration for ED of Neurogenic, Vasculogenic, Psychogenic, or Mixed Etiology
Intraurethral Suppository

Initially, 125 or 250 mcg.98 105 If no response, increase subsequent doses in a stepwise manner to 500 mcg or 1 mg, as needed, on separate occasions.98 107 Use ≤2 urethral suppositories within 24 hours.98 100 104

Initiation and Titration for ED of Pure Neurogenic Etiology
Intracavernosal Injection

Caverject vials and single-use, dual-chambered injection device: Initially, 1.25 mcg.89 110 b If no response, double second dose to 2.5 mcg after ≤1 hour.64 110 b Do not administer >2 doses within 24 hours.64 110 x If additional dosage titration required, administer 5 mcg during next 24 hours.110 b Increase subsequent dosage in 5-mcg increments, with each incremental increase separated by ≥24 hours, until optimum response achieved.110 b (See General: ED, under Dosage and Administration.)

edex reusable dual-chambered injection device: Initially, 1.25 mcg.d If no response, double second dose to 2.5 mcg after ≤1 hour; if still no response, increase to 5 mcg after ≤1 hour.d z Increase subsequent dosage in 5-mcg increments, until optimum response achieved.d z (See General: ED, under Dosage and Administration.) If a partial response observed at any point in dosage titration, wait ≥1 day before resuming dose titration.d z

Initiation and Titration for ED of Vasculogenic, Psychogenic, or Mixed Etiology
Intracavernosal Injection

Caverject vials and single-use, dual-chambered injection devices: Initially, 2.5 mcg.8 110 b If partial response observed, double dose to 5 mcg after ≤1 hour.110 b If no response, increase second dose to 7.5 mcg after ≤1 hour.110 b Administer ≤2 doses within ≤24 hours.110 x If additional titration required, increase dosage in increments of 5–10 mcg at intervals of ≥24 hours until optimum response achieved.110 b z (See General: ED, under Dosage and Administration.)

edex reusable dual-chambered injection device: Initially, 2.5 mcg.d If no response, increase second dose to 7.5 mcg after ≤1 hour, followed by increments of 5–10 mcg at intervals of ≤1 hour until a response occurs.d z If partial response observed with 2.5 mcg, wait ≥24 hours before doubling dose to 5 mcg, followed by increments of 5–10 mcg at intervals of ≥24 hours until optimum response achieved.d z (See General: ED, under Dosage and Administration.)

Maintenance (Self-administration)
Intraurethral Suppository

Initially, self-administer dose determined as optimal during titration in a medical setting (e.g., physician’s office);97 98 administer ≤2 urethral suppositories within a 24-hour period.98 100 104

Intracavernosal Injection

Initially, self-administer dose determined as optimal during titration in a medical setting (e.g., physician’s office); administer no more frequently than 3 times weekly with >1 day elapsing between each dose.2 34 101 b d e h i r

If required, adjust dosage only after consultation with a clinician (not independently by the patient), following the same initial titration guidelines.2 b e f i r

Diagnostic Use
Intracavernosal Injection

Adjunct to other vascular testing: Use single dose that produces firm erection.86 110 b

Prescribing Limits

Pediatric Patients

Ductus Arteriosus-dependent Congenital Heart Disease
IV or Intra-arterial Infusion

Maximum: ≤0.4 mcg/kg per minute.1 3 57 60 a

Adults

ED
Initiation and Titration
Intraurethral Suppository

Maximum 2 suppositories within 24 hours.98 100 104

Intracavernosal Injection

Caverject vials and single-use, dual-chambered injection devices: Generally, maximum 60–65 mcg.26 32 35 36 41 64 110 b Administer maximum 2 injections within 24 hours.h x

edex reusable dual-chambered injection device: Dosages >40 mcg not evaluated.d If a response occurs, allow >1 day interval between doses.d

Maintenance (Self-administration)
Intraurethral Suppository

Maximum 2 urethral suppositories within a 24-hour period.98 100 104

Intracavernosal Injection

Maximum frequency ≤3 injections weekly with ≥1 day elapsing between each dose.34 101 110 b z

Cautions for Alprostadil

Contraindications

  • Intraurethral suppository or intracavernosal injection: Conditions predisposing to priapism (e.g., sickle cell anemia or trait, multiple myeloma, leukemia, thrombocythemia, polycythemia, propensity to develop venous thrombosis, hyperviscosity syndrome).8 19 32 64 76 89 97 98 100 b d

  • Intraurethral suppository or intracavernosal injection: Anatomic deformation of penis (e.g., angulation, cavernosal fibrosis, Peyronie’s disease).8 19 32 64 76 89 97 98 100 b d

  • Intraurethral suppository or intracavernosal injection: Men for whom sexual activity is inadvisable (e.g., underlying cardiovascular status).8 19 32 64 76 89 97 98 100 b h y (See Assessment of Patients with Erectile Dysfunction under Cautions.)

  • Intraurethral suppository or intracavernosal injection: Women and children, including neonates.d h

  • Intraurethral suppository or intracavernosal injection: Use with penile implants.101 b d

  • Intraurethral suppository: Certain GU tract disorders (e.g., urethral stricture or obstruction, balanitis, acute or chronic urethritis, severe hypospadias and curvature, anuria).97 98 99 100 105

  • Intraurethral suppository: Use with indwelling urethral catheter.97 98 99 100 105

  • Intraurethral suppository: Unprotected sexual intercourse with pregnant women.98 100 104 (See Pregnancy under Cautions.)

  • Known hypersensitivity to alprostadil or other prostaglandins.98 d

Warnings/Precautions

Warnings

Apnea

Risk of respiratory depression and apnea in neonates with congenital heart defects.1 3 44 50 53 60 (See Boxed Warning.)

GI Effects

Risk of gastric outlet obstruction secondary to antral hyperplasia in neonates receiving alprostadil injection for arteriosus-dependent congenital heart disease; associated with prolonged therapy (e.g., cumulative dose and duration of therapy).1 3 44 47 49 50 52 54 55 58 59 95

Closely monitor neonates receiving recommended dosages for >120 hours for evidence of antral hyperplasia and gastric outlet obstruction.1 59 During prolonged therapy, carefully weigh possible risk of gastric outlet obstruction against potential benefits.1 3 44 47 49 50 52 54 55 58 59 95

Priapism

Possible prolonged erection (persisting for 4–6 hours) or priapism (erection persisting for >6 hours).98 112 b d

May result in penile tissue damage and permanent loss of potency if not treated immediately110 d r (e.g., aspiration of cavernosal blood, intracavernosal injection of an α-adrenergic agonist or dopamine).6 7 8 11 12 19 20 23 46 67 83 89 98 113 b

Minimize risk of prolonged erection by slowly titrating to lowest possible effective dosage.110 b d Consider decreased dosage or discontinuance in patients who develop priapism or prolonged erection.98 (See General: ED, under Dosage and Administration.)

Cardiovascular and Cerebrovascular Effects

Risk of symptomatic hypotension and syncope in patients using intraurethral alprostadil;110 d monitor patients during dosage initiation and titration for manifestations of such effects.98 100

Hypotension and/or dizziness reported following intracavernosal administration; may result from increased peripheral blood levels of prostaglandin E1, especially in patients with significant corpora cavernosa venous leakage.110 d

Possible hypotension and bradycardia in neonates receiving IV or intra-arterial therapy.1 3 50 If bradycardia occurs, discontinue infusion and institute appropriate therapy;1 50 (See Dosage: Pediatric Patients under Dosage and Administration) if hypotension occurs, reduce infusion rate and institute appropriate therapy, if necessary.1 3 50 (See IV and Intra-arterial Infusion: Rate of Administration under Dosage and Administration.)

Morphologic changes in ductal and pulmonary arteries observed in infants receiving short- or long-term IV or intra-arterial therapy at usual recommended dosages.a

General Precautions

Respiratory Distress Syndrome

Do not use in neonates with respiratory distress syndrome;1 4 42 49 64 closure of ductus arteriosus is necessary to prevent overload of pulmonary circulation in such neonates.4 42 49 55

Prior to initiating therapy in neonates, make a differential diagnosis between neonatal respiratory distress syndrome (hyaline membrane disease) and cyanotic heart disease (restricted pulmonary blood flow).1 If full diagnostic facilities not readily available, use cyanosis (evidenced by PO2 <40 mm Hg) and radiographic evidence of restricted pulmonary blood flow as indicators of cyanotic heart disease.1

GU Effects

Penile fibrosis, including Peyronie’s disease, reported following intracavernosal administration.110 b d

Examine patients (e.g., every 3 months) for any changes in penis and assess therapeutic benefit.34 41 110 b d Discontinue therapy in any patient who develops penile angulation, cavernosal fibrosis, or Peyronie’s disease during therapy.89 110 b d

Assessment of Patients with Erectile Dysfunction

Thorough medical history and physical examination recommended to diagnose erectile dysfunction, determine potential underlying causes, exclude potentially reversible or treatable causes, identify underlying disorders that might preclude use, and identify appropriate treatment.65 110 b d l (See Contraindications under Cautions.)

Examine cardiac fitness of patient prior to treatment initiation, particularly in patients with underlying cardiovascular disease.l v y (See Contraindications under Cautions.)

Sexual Preference

No experience with use in homosexual men or for sexual activities other than vaginal intercourse.l

Concomitant Therapy

Safety and efficacy of combination therapy with other treatments for erectile dysfunction not established; combined use not recommended by manufacturer.64 101 110 b d (See Erectile Dysfunction under Uses.)

Increased propensity for bleeding with intracavernosal use in patients receiving concurrent anticoagulants (e.g., heparin, warfarin).b d h (See Specific Drugs under Interactions.)

Risk of urethral abrasion resulting in minor bleeding or spotting with improper intraurethral use, particularly in patients receiving anticoagulant therapy.l

Musculoskeletal Effects

Risk of cortical hyperostosis of long bones associated with prolonged IV or intra-arterial therapy in neonates and infants.1 3 44 47 49 50 52 54 55 58 59 95 Cortical hyperostosis regresses with therapy withdrawal;a carefully weigh possible risk of cortical hyperostosis of long bones against potential benefits.1 3 44 47 49 50 52 54 55 58 59 95

Hematologic Effects

Bleeding reported rarely following IV or intra-arterial infusion; carefully weigh risk to benefit of therapy in neonates with bleeding disorders.1 42 44 50 64

Risk of urethral abrasion resulting in minor bleeding or spotting with improper use of intraurethral suppository.98

Risk of hematologic complications (e.g., intracorporeal hematoma, ecchymosis, hemorrhage at the site of injection) with intracavernosal therapy, especially in patients receiving concomitant anticoagulant therapy.7 22 25 67 71 83 89 101 111 e r (See Specific Drugs under Interactions.) If bleeding continues or recurs after applying pressure to injection site, abstain from intercourse.r

Specific Populations

Pregnancy

Category C.l Not indicated for use in women.b d h l (See Advice to Patients.)

Intraurethral suppository: Embryotoxic in animals; use condom during sexual intercourse with pregnant woman.98 100 104 (See Contraindications under Cautions.)

Lactation

Not indicated in women.b d h l

Pediatric Use

Intracavernosal injections or intraurethral suppository not indicated for use in children.b d h l

Safety and efficacy of IV or intra-arterial infusion established in infants and neonates.a

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but decreased sensitivity (e.g., increased dosage requirements) cannot be ruled out.b h z

Common Adverse Effects

IV or intra-arterial infusion: Apnea,a fever,a seizures,a flushing,a bradycardia,a hypotension,a tachycardia.a

Intraurethral suppository: Penile or testicular pain,98 urethral burning,l urethral bleeding and/or spotting,98 100 minor urethral abrasions.98 100

Intracavernosal injection: Penile pain,b prolonged erection,101 b penile fibrosis,b injection site hematoma.b

Interactions for Alprostadil

Specific Drugs

Drug

Interaction

Comments

α-Adrenergic agonists

Possible antagonism of erectile effects6 7 8 11 12 19 20 23 46 64 67 78

Anorexigenic agents

Possible antagonism of erectile effectsf

Anticoagulants, oral

Increased risk of bleeding after intracavernosal or intraurethral usea d h

Pharmacokinetic interaction unlikelyd

Intraurethral suppository: Consider risk-benefit ratio with concomitant usel

Antidiabetic agents

Pharmacokinetic or pharmacodynamic interaction unlikelyd

Antihypertensive agents

Possible increased risk of hypotension with intraurethral usel

Intraurethral suppository: Use concurrently with cautionl

Cardiac glycosides

Pharmacokinetic or pharmacodynamic interaction unlikelya d

Decongestants

Possible antagonism of erectile effectsf

Diuretics

Pharmacokinetic or pharmacodynamic interaction unlikelya d

Heparin

Prolongation of PT, thrombin time, and partial thromboplastin timed

Potential for bleedingd h l

Intracavernosal injections: Use concomitantly with cautiond

Intraurethral suppository: Consider risk-benefit ratio with concomitant usel

NSAIAs

Safety and efficacy of alprostadil not affected by concomitant used

Alprostadil Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability about 98% following intracavernosal injection.d

Approximately 80% absorbed ≤10 minutes following intraurethral administration.l

Onset

Erection usually occurs within 2–25 minutes after intracavernosal injection.6 8 10 12 16 17 19 21 23 24 27 28 34 35 36 37 45 46 62 65 67 69 98 101 b d h

Erection usually occurs within 5–10 minutes after intraurethral administration.98 101

Duration

Erection may persist approximately 1 hour up to several hours following intracavernosal injection.6 8 10 12 16 17 19 21 23 24 27 28 34 35 36 37 45 46 62 65 67 69 d h z

Erection may persist approximately 30–60 minutes following intraurethral administration.98

Special Populations

In patients with hepatic impairment receiving alprostadil IV infusion, increased peak blood concentrations of drug and metabolites compared with healthy individuals.d

In patients with renal impairment receiving alprostadil IV infusion, decreased peak blood concentrations of drug and increased peak blood concentrations of metabolites compared with healthy individuals.d

Distribution

Extent

Following intraurethral administration, distributed from mucosal cells of urethra into corpus spongiosum, corpus cavernosum, and pelvic venous circulation.97 98 105 Some drug may distribute from corpus spongiosum directly into pelvic venous circulation bypassing corpus cavernosum.105 l

Following intracavernosal administration, no appreciable binding to erythrocytes or WBCs.b h

Plasma Protein Binding

93%.d

Elimination

Metabolism

Following intracavernosal or intraurethral administration, principally metabolized locally in corpus cavernosum or urethra via oxidation and reduction.105 l z Portion of drug released into systemic circulation and metabolized by lungs.d h l z

Following systemic administration, rapidly and extensively metabolized principally in the lungs via β- and ω-oxidation.1 20 22 24 26 27 28 34 44 54 55 67 94 a d h z

Elimination Route

Following IV administration, excreted principally in urine (88–90%) as metabolites and in feces (10–12%).a b d h l z

Half-life

Intraurethral suppository: 30 seconds to 10 minutes, depending on body compartment measured and physiologic status of individual.l

Intracavernosal injection: 9–11 minutes in healthy individuals.d

Special Populations

In patients with hepatic or renal impairment receiving alprostadil IV infusion, terminal half-lives of drug and metabolites unaffected.d

Stability

Storage

Parenteral

Powder for Injection

edex: 25°C (may be exposed to 15–30°C).d r Do not freeze; protect from excessive heat.r Use reconstituted solution immediately; discard unused solution.d r

Caverject With 20-mcg vials, ≤25°C.b e Do not freeze; protect from excessive heat.e With 40 mcg vials, 2–8°C until dispensed;b thereafter ≤25°C for 3 months or expiration date, whichever comes first.b e Do not freeze; protect from excessive heat.e Use reconstituted solutions within 24 hours when stored at ≤25°C; do not refrigerate or freeze.b e

Caverject impulse: 25°C (may be exposed to 15–30°C).110 Do not freeze; protect from excessive heat.i Use reconstituted solutions within 24 hours when stored at ≤25°C; discard unused solution.110 i

Intraurethral Suppository

Refrigerate at 2–8°C; protect from light and excessive heat (temperatures >30°C).l Store in unopened foil pouches until use.l l May be stored at <30°C for ≤14 days prior to use.l

Injection Concentrate for Infusion

2–8°C.1

Discard unused diluted solutions after 24 hours.1 44

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in water

Sodium chloride 0.9%

Drug Compatibility
Y-Site CompatibilityHID

Compatible

Ampicillin sodium

Cefazolin sodium

Cefotaxime sodium

Chlorothiazide sodium

Dobutamine HCl

Dopamine HCl

Fentanyl citrate

Gentamicin sulfate

Methylprednisolone sodium succinate

Sodium nitroprusside

Tobramycin sulfate

Vancomycin HCl

Vecuronium bromide

Incompatible

Levofloxacin

Actions

  • Ductus Arteriosus-dependent Congenital Heart Disease
  • Dilates constricted ductus arteriosus in neonates with cyanotic congenital heart disease.1 3 43 56 58

  • In neonates with restricted pulmonary blood flow, increases pulmonary blood flow through combined maintenance of patency of ductus arteriosus and dilation of pulmonary vascular bed.43 44 55 56 58 60 70 Temporarily increases arterial oxygen partial pressure (PaO2) and oxygen saturation.1 3 43 56 58

  • In neonates with restricted systemic blood flow, prevents or corrects acidemia and increases cardiac output, systemic BP, femoral pulse volume, and renal blood flow and function (urine production).1 3 29 43 44 51 56 57 60

  • In neonates with coarctation of aorta, decreases gradient of descending to ascending aortic BP.1 3 29 43 44 51 56 57 60

  • In neonates with interruption of aortic arch, decreases gradient of pulmonary artery to descending aortic BP.1 3 29 43 44 51 56 57 60

  • Erectile Dysfunction
  • Interacts with specific membrane-bound receptors that stimulate adenylate cyclase and elevates intracellular concentrations of cyclic adenosine-3’,5’-monophosphate (AMP), leading to activation of protein kinase and resultant smooth muscle relaxation.6 8 12 97 z

  • Induces erection by relaxing trabecular smooth muscle and dilating cavernosal arteries and their branches (i.e., the helicine arterioles of the penis).2 11 15 19 20 21 24 27 28 34 46 64 65 71 98 101 102

  • Increases arterial inflow velocity and venous outflow resistance resulting in penile blood engorgement and erection.15 18 85 98 110

  • Drug may enhance actions of nonadrenergic, noncholinergic, vasodilatory neurotransmitters (e.g., nitric oxide, neuropeptide Y, calcitonin gene-related peptide, vasoactive intestinal polypeptide).6 8 12 20 21 33 46 62

Advice to Patients

Erectile Dysfunction

  • Importance of providing patient a copy of manufacturer’s patient information.5 83 98 100 101 112

  • Importance of informing clinician of history of syncope prior to treatment initiation with intraurethral suppository.100

  • Importance of understanding proper storage, preparation, and administration techniques, including precautions and proper disposal of used needles, injection devices, syringes and unused reconstituted drug solutions.5 10 22 34 67 69 71 83 98 100 101 110 112 d

  • Importance of not storing vials or injection devices in checked airline baggage (storage in passenger compartment permitted) or closed automobile.64 111 e r Importance of avoiding freezing or exposure to temperatures >25°C.64 111 e

  • Importance of contacting a clinician if needle breaks during penile injection.e i r

  • Potential for transmission of sexually transmitted diseases or blood-borne diseases and need to use protective measures to guard against such transmission.110 (See Hematologic Effects under Cautions.)

  • With intraurethral suppository, importance of using a condom when engaging in sexual intercourse with a pregnant woman.98 100 104 (See Contraindications under Cautions.)

  • Importance of contacting clinician regularly for assessment of therapeutic benefit, need for possible dosage adjustment, and of potential adverse effects.34 41 89 101 110

  • Importance of seeking immediate medical attention if erection persists >4 hours.34 78 79 89 98 100 110 112 113 (See Priapism under Cautions.)

  • Importance of informing clinician of penile pain that develops or intensifies during intracavernosal therapy. 110

  • Importance of informing clinician of nodules or hard areas in penis, any sign of infection (e.g., penile erythema, swelling, tenderness) or unusual curvature.110

  • Possible dizziness, hypotension, or syncope with intraurethral suppository; use caution when driving or operating machinery.98 Importance of lying down and immediately raising legs if light-headed feeling, dizziness, feeling of faintness, or rapid pulse experienced.100 Importance of informing a clinician if such symptoms persist.100

  • Importance of informing clinician of existing or contemplated concomitant therapy (e.g., agents interfering with blood clotting, antihypertensive agents), including prescription and OTC drugs, as well as any concomitant illnesses (e.g., conditions interfering with blood clotting).98 110 d r

  • Importance of informing patients of other important precautionary information.d (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Alprostadil

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection concentrate, for IV infusion

500 mcg/mL

Alprostadil Injection

Prostin VR Pediatric

Pfizer

For injection, for intracavernosal use

10 mcg

Caverject impulse (available as disposable prefilled dual-chambered cartridges with bacteriostatic water for injection diluent with benzyl alcohol 4.45 mcg; needle and alcohol swabs)

Pfizer

edex (available in cartridges with one compartment of dual-chamber containing diluent [bacteriostatic 0.9% sodium chloride] and with reusable injection device, needles and alcohol swabs)

Schwarz

20 mcg

Caverject (available as single-dose vials with sterile water for injection diluent with benzyl alcohol 8.4 mcg)

Pfizer

Caverject impulse (available as disposable prefilled dual-chambered cartridges with bacteriostatic water for injection diluent with benzyl alcohol 4.45 mcg; needle and alcohol swabs)

Pfizer

edex (available in cartridges with one compartment of dual-chamber containing diluent [bacteriostatic 0.9% sodium chloride] and with reusable injection device, needles and alcohol swabs)

Schwarz

40 mcg

Caverject (available as single-dose vials with sterile water for injection diluent with benzyl alcohol 8.4 mcg)

Pfizer

edex (available in cartridges with one compartment of dual-chamber containing diluent [bacteriostatic 0.9% sodium chloride] and with reusable injection device, needles, and alcohol swabs)

Schwarz

Urogenital

Suppository

125 mcg

Muse (in a polyethylene glycol vehicle; with applicator)

Vivus

250 mcg

Muse (in a polyethylene glycol vehicle; with applicator)

Vivus

500 mcg

Muse (in a polyethylene glycol vehicle; with applicator)

Vivus

1 mg

Muse (in a polyethylene glycol vehicle; with applicator)

Vivus

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Caverject 20MCG Solution (PFIZER U.S.): 1/$55.99 or 3/$145.97

Caverject 40MCG Solution (PFIZER U.S.): 1/$65.99 or 3/$178.98

Caverject Impulse 20MCG Kit (PFIZER U.S.): 2/$96.99 or 6/$265.96

Edex 10MCG Kit (ACTIENT PHARMACEUTICALS): 1/$92.99 or 3/$255.98

Edex 10MCG Kit (ACTIENT PHARMACEUTICALS): 1/$266.98 or 3/$774.00

Edex 20MCG Kit (ACTIENT PHARMACEUTICALS): 1/$117.99 or 3/$332.96

Edex 20MCG Kit (ACTIENT PHARMACEUTICALS): 1/$324.00 or 2/$636.97

Edex 40MCG Kit (ACTIENT PHARMACEUTICALS): 1/$157.99 or 3/$447.95

Edex 40MCG Kit (ACTIENT PHARMACEUTICALS): 1/$449.98 or 3/$1,315.02

Muse 1000MCG Pellets (MEDA PHARMACEUTICALS): 6/$310.99 or 18/$909.93

Muse 125MCG Pellets (MEDA PHARMACEUTICALS): 6/$240.00 or 18/$699.94

Muse 250MCG Pellets (MEDA PHARMACEUTICALS): 6/$268.98 or 18/$775.94

Muse 500MCG Pellets (MEDA PHARMACEUTICALS): 6/$297.99 or 18/$870.93

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 18, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Pharmacia & Upjohn Company. Prostin VR Pediatric (alprostadil sterile solution) injection prescribing information. Kalamazoo, MI; 1997 Sep.

2. Pharmacia & Upjohn Company. Caverject (alprostadil) for injection for intracavernosal use prescribing information. Kalamazoo, MI; 1999 Feb.

3. Roehl SL, Townsend RJ. Alprostadil (Prostin VR Pediatric Sterile Solution, The Upjohn Company). Drug Intell Clin Pharm. 1982; 16:823-32. [IDIS 159788] [PubMed 6756848]

4. Friedman WF. Diseases of the heart, pericadium, aorta, and pulmonary vascular bed: congenital heart disease in infancy and childhood. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. 4th ed. Philadelphia: W.B. Saunders Company; 1992:887-965.

5. The Upjohn Company. Caverject sterile powder (alprostadil for injection) product information. Kalamazoo, MI; Undated.

6. Martinez-Pineiro L, Lopez-Tello J, Dorrego JMA et al. Preliminary results of a comparative study with intracavernous sodium nitroprusside and prostaglandin E1 in patients with erectile dysfunction. J Urol. 1995; 153:1487-90. [IDIS 345270] [PubMed 7714974]

7. Whitehead ED. Impotence: should primary care physicians give penile injections? Geriatrics. 1995; 50:14. Letter. (IDIS 341817)

8. von Heyden B, Donatucci CF, Marshall GA et al. A prostaglandin E1 dose- response study in man. J Urol. 1993; 150:1825-8. [IDIS 321902] [PubMed 8230515]

9. Govier FE, McClure RD, Weissman RM et al. Experience with triple-drug therapy in a pharmacological erection program. J Urol. 1993; 150:1822-4. [IDIS 321901] [PubMed 8230514]

10. Djamilian M, Stief CG, Kuczyk M et al. Followup results of a combination of calcitonin gene-related peptide and prostaglandin E1 in the treatment of erectile dysfunction. J Urol. 1993; 149:1296-8. [IDIS 313864] [PubMed 8479019]

11. Montorsi F, Guazzoni G, Bergamaschi F et al. Four-drug intracavernous therapy for impotence due to corporeal veno-occlusive dysfunction. J Urol. 1993; 149:1291-5. [IDIS 313863] [PubMed 7683061]

12. von Heyden B, Donatucci CF, Kaula N et al. Intracavernous pharmacotherapy for impotence: selection of appropriate agent and dose. J Urol. 1993; 149:1288-90. [IDIS 313862] [PubMed 8479018]

13. Porst H. Prostaglandin E1 and the nitric oxide donor linsidomine for erectile failure: a diagnostic comparative study of 40 patients. J Urol. 1993; 149:1280-3. [IDIS 313861] [PubMed 8479015]

14. Allen RP, Engel RM, Smolev JK et al. Objective double-blind evaluation of erectile function with intracorporeal papaverine in combination with phentolamine and/or prostaglandin E1. J Urol. 1992; 148:1181-3. [IDIS 303448] [PubMed 1404632]

15. Meuleman EJH, Bemelmans BLH, Doesburg WH et al. Penile pharmacological duplex ultrasonography: a dose-effect study comparing papaverine, papaverine/phentolamine and prostaglandin E1. J Urol. 1992; 148:63-6. [IDIS 298844] [PubMed 1613884]

16. Donatucci CF, Lue TF. The combined intracavernous injection and stimulation test: diagnostic accuracy. J Urol. 1992; 148:61-2. [IDIS 298843] [PubMed 1613883]

17. Bennett AH, Carpenter AJ, Barada JH. An improved vasoactive drug combination for a pharmacological erection program. J Urol. 1991; 146:1564-5. [IDIS 296354] [PubMed 1719248]

18. Stief CG, Wetterauer U, Schaebsdau FH et al. Calcitonin-gene-related peptide: a possible role in human penile erection and its therapeutic application in impotent patients. J Urol. 1991; 146:1010-4. [IDIS 288810] [PubMed 1895414]

19. Gerber GS, Levine LA. Pharmacological erection program using prostaglandin E1. J Urol. 1991; 146:786-9. [IDIS 287641] [PubMed 1875494]

20. Artoux MJ, McQueen KD. Alprostadil in impotence. DICP. 1991; 25:363-6. [IDIS 280091] [PubMed 1926907]

21. Floth A, Schramek P. Intracavernous injection of prostaglandin E1 in combination with papaverine: enhanced effectiveness in comparison with papaverine plus phentolamine and prostaglandin E1 alone. J Urol. 1991; 145:56-9. [IDIS 276217] [PubMed 1984099]

22. Earle CM, Keogh EJ, Wisniewski ZS et al. Prostaglandin E1 therapy for impotence, comparison with papaverine. J Urol. 1990; 143:57-9. [IDIS 271285] [PubMed 2294263]

23. Whitehead ED, Klyde BJ, Zussman S et al. Treatment alternatives for impotence. Postgrad Med. 1990; 88:139-52. [IDIS 269901] [PubMed 2199954]

24. Hwang TIS, Yang CR, Wang SJ et al. Impotence evaluated by the use of prostaglandin E1. J Urol. 1989; 141:1357-9. [IDIS 255242] [PubMed 2724434]

25. Sarosdy MF, Hudnall CH, Erickson DR et al. A prospective double-blind trial of intracorporeal papaverine versus prostaglandin E1 in the treatment of impotence. J Urol. 1989; 141:551-3. [IDIS 252555] [PubMed 2645420]

26. Lee LM, Stevenson RWD, Szasz G. Prostaglandin E1 versus phentolamine/papaverine for the treatment of erectile impotence: a double-blind comparison. J Urol. 1989; 141: 549-50. [IDIS 252554] [PubMed 2918589]

27. Ishii N, Watanabe H, Irisawa C et al. Intracavernous injection of prostaglandin E1 for the treatment of erectile impotence. J Urol. 1989; 141:323-5. [IDIS 251538] [PubMed 2913354]

28. Stackl W, Hasun R, Marberger M. Intracavernous injection of prostaglandin E1 in impotent men. J Urol. 1988; 140:66-8. [IDIS 243511] [PubMed 3379700]

29. Hiraishi S, Fujino N, Saito K et al. Responsiveness of the ductus arteriosus to prostaglandin E1 assessed by combined cross sectional and pulsed Doppler echocardiography. Br Heart J. 1988; 62:140-7.

30. Godschalk MF, Chen J, Katz PG et al. Treatment of erectile failure with prostaglandin E1: a double-blind, placebo-controlled, dose-response study. J Urol. 1994; 151:1530-2. [IDIS 329635] [PubMed 8189563]

31. Chen J, Godschalk M, Katz PG et al. The lowest effective dose of prostaglandin E1 as treatment for erectile dysfunction. J Urol. 1995; 153:80-1. [IDIS 340107] [PubMed 7966797]

32. Godschalk MF, Chen J, Katz PG et al. Prostaglandin E1 as treatment for erectile failure in elderly men. J Am Geriatr Soc. 1994; 42:1263-5. [IDIS 339613] [PubMed 7983289]

33. Goldstein I. Editorial: Impotence. J Urol. 1994; 151:1533-4. [PubMed 8189564]

34. Linet OI, Neff LL. Intracavernous prostaglandin E1 in erectile dysfunction. Clin Investig. 1994; 72:139-49. [PubMed 8186662]

35. Linet OI, Ogrinc FG. Dose-escalating study with maintenance phase using alprostadil (prostaglandin E1, PGE1) sterile powder in patients with erectile dysfunction. Technical Report No. 9124-93-006. The Upjohn Company: Kalamazoo, MI; 1993 Dec 3.

36. Weber RE, Linet OI, Hansen BA et al. Dose-escalating study using alprostadil (prostaglandin E1, PGE1) sterile powder (S.Po.) in patients with erectile dysfunction of vasculogenic origin. Technical Report No. 9124-93-008. The Upjohn Company: Kalamazoo, MI; 1995 Jan 25.

37. Weber RE, Ogrinc FG, Hansen JP et al. Dose-escalating study using alprostadil sterile powder (prostaglandin E1, PGE1) in patients with erectile dysfunction of neurogenic origin secondary to spinal cord injury. Technical Report No. 9124-93-009. The Upjohn Company: Kalamazoo, MI; 1993 Nov 29.

38. Linet OI, Ogrinc FG, Hansen JP. No-effect and minumum-effective dose- finding study of alprostadil (prostaglandin E1,PGE1) sterile powder (S.Po.) in patients with erectile dysfunction. Technical Report No. 9124-93-003. The Upjohn Company: Kalamazoo, MI; 1993 Dec 1.

39. Linet OI, Ogrinc FG. Long-term safety study with alprostadil sterile powder (alprostadil S.Po.; prostaglandin E1, PGE1) in patients with erectile dysfunction. Technical Report No. 9124-93-007. The Upjohn Company: Kalamazoo, MI; 1993 Dec 10.

40. Linet OI, Ogrinc FG. Dose-escalating study with maintenance phase using alprostadil (prostaglandin E1, PGE1) sterile powder (S.Po.) in elderly patients with erectile dysfunction. Technical Report No. 9124-95-002. The Upjohn Company: Kalamazoo, MI; 1995 Jan 17.

41. Linet OI. Clinical pharmacology of alprostadil. In: Goldstein I, Lue TF, eds. The role of alprostadil in the diagnosis and treatment of erectile dysfunction. Princeton: Excerpta Medica; 1993:28-39.

42. Chessman KH, Alpert BS. Pharmacological manipulation of the ductus arteriosus in neonates. Hosp Pharm. 1988; 23:825-7,830,833-4,841.

43. Freed MD, Heymann MA, Lewis AB et al. Prostaglandin E1 in infants with ductus arteriosus-dependent congenital heart disease. Circulation. 1981; 64:899-905. [IDIS 140039] [PubMed 7285305]

44. Heymann MA, Clyman RI. Evaluation of alprostadil (prostaglandin E1) in the management of congenital heart disease in infancy. Pharmacother. 1982; 2:148-55.

45. Schramek P. Dose-dependent effect and side-effect of prostaglandin E1 in erectile dysfunction. Br J Clin Pharmacol. 1989; 28:567-71. [IDIS 261223] [PubMed 2686740]

46. Waldhauser M, Schramek P. Efficiency and side effects of prostaglandin E1 in the treatment of erectile dysfunction. J Urol. 1988; 140:525-7. [IDIS 247072] [PubMed 3045341]

47. Silove ED. Pharmacological manipulation of the ductus arteriosus. Arc Dis Child. 1986; 61:827-9.

48. Sell JE, Jonas RA, Mayer JE et al. The results of a surgical program for interrupted aortic arch. J Thorac Cardiovasc Surg. 1988; 96:864-77. [IDIS 248604] [PubMed 3193799]

49. Yokota M, Muraoka R, Aoshima M et al. Modified Blalock-Taussig shunt following long-term administration of prostaglandin E1 for ductus-dependent neonates with cyanotic congenital heart disease. J Thorac Cardiovasc Surg. 1985; 90:399-403. [IDIS 204755] [PubMed 4033176]

50. Lewis AB, Freed MD, Heymann MA et al. Side effects of therapy with prostaglandin E1 in infants with critical congenital heart disease. Circulation. 1981; 64:893-8. [IDIS 140038] [PubMed 7285304]

51. Zahka KG, Roland MA, Cutilletta AF et al. Management of aortic arch interruption with prostaglandin E1 infusion and microporous expanded polytetrafluoroethylene grafts. Am J Cardiol. 1980; 46:1001-5. [IDIS 128788] [PubMed 7446413]

52. Freed MD. Evaluation of alprostadil. Pharmacother. 1982; 2:155.

53. Lewis AB. Evaluation of alprostadil. Pharmacother. 1982; 2:155.

54. Buck ML. Prostaglandin E1 treatment of congenital heart disease: use prior to neonatal transport. DICP. 1991; 25:408-9. [IDIS 280097] [PubMed 1926911]

55. Barst RJ, Gersony WM. The pharmacological treatment of patent ductus arteriosus: a review of the evidence. Drugs. 1989; 38:249-66. [PubMed 2670518]

56. Graham TP Jr, Atwood GF, Boucek RJ Jr. Pharmacologic dilatation of the ductus arteriosus with prostaglandin E1 in infants with congenital heart disease. South Med J. 1978; 71:1238-41, 1246. [PubMed 81528]

57. Heymann MA, Berman W, Rudolph AM et al. Dilatation of the ductus arteriosus by prostaglandin E1 in aortic arch abnormalities. Circulation. 1979; 59:169-73. [IDIS 120674] [PubMed 758109]

58. Haworth SG, Sauer U, Bühlmeyer K. Effect of prostaglandin E1 on pulmonary circulation in pulmonary atresia. Br Heart J. 1980; 43:306-14. [IDIS 154226] [PubMed 7437177]

59. Peled N, Dagan O, Babyn P et al. Gastric-outlet obstruction induced by prostaglandin therapy in neonates. N Engl J Med. 1992; 327:505-10. [IDIS 300795] [PubMed 1635565]

60. Hallidie-Smith KA. Prostaglandin E1 in suspected ductus dependent cardiac malformation. Arch Dis Child. 1984; 59:1020-6. [IDIS 194392] [PubMed 6542338]

61. Reviewers’ comments (personal observations) on papaverine.

62. Mahmoud KZ, El Dakhli MR, Fahmi IM et al. Comparative value of prostaglandin E1 and papaverine in treatment of erectile failure: double-blind crossover study among Egyptian patients. J Urol. 1992; 147:623-6. [IDIS 292378] [PubMed 1538443]

63. Pruitt A. The cardiovascular system. In: Behrman RE, Kliegman RM, Nelson WE, et al, eds. Nelson textbook of pediatrics. 14th ed. Philadelphia: W.B. Saunders Company; 1992: 1125-227.

64. The Upjohn Company, Kalamazoo, MI: Personal communication.

65. National Institutes of Health Office of Medical Applications of Research. Consensus Conference: impotence. JAMA. 1993; 270:83-90. [IDIS 316686] [PubMed 8510302]

66. Porst H. Prostaglandin E1 in male impotence—its diagnostic and therapeutic use in 2000 patients. Int J Impotence Res. 1992; 4(Suppl 2):A88.

67. Ravnik-Oblak M, Oblak C, Vodusek DB et al. Intracavernous injection of prostaglandin E1 in impotent diabetic men. Int J Impotence Res. 1990; 2:143-49.

68. Hirsch IH, Bagley DH, Christinzio J. Dosage considerations in the self- administration of PGE-1 for erectile dysfunction. J Urol. 1990; 143(Suppl):305A.

69. Weiske WH. Long-term results in self-injection therapy (SIT) with PGE-1 in 220 patients. Int J Impot Res. 1992; 4(Suppl 2):A87.

70. Benson LN, Olley PM, Patel RG et al. Role of prostaglandin E1 infusion in the management of transposition of the great arteries. Am J Cardiol. 1979; 44:691-6. [PubMed 484498]

71. Montorsi F, Guazzoni G, Bergamaschi F et al. Clinical reliability of multi-drug intracavernous vasoactive pharmacotherapy for diabetic impotence. Acta Diabetol. 1994; 31:1-5. [PubMed 8043890]

72. Matsumoto AM. The testis and male sexual function. In: Wyngaarden JB, Smith LH Jr, Bennett JC, eds. Cecil textbook of medicine. 19th ed. Philadelphia: W.B. Saunders Company; 1992:1333-55.

73. Lindoro J, Castro JC, Cruz F et al. Treatment of priapism. Lancet. 1984; 2:1348. [PubMed 6150362]

74. Anon. Intracavernous injections for impotence. Med Lett Drugs Ther. 1987; 29:95-6. [PubMed 3670212]

75. Robinette MA, Moffat MJ. Intracorporal injection of papaverine and phentolamine in the management of impotence. Br J Urol. 1986; 58:692-5. [PubMed 3801830]

76. Lue TF, Tanagho EA. Physiology of erection and pharmacological management of impotence. J Urol. 1987; 137:829-36. [IDIS 229174] [PubMed 3553617]

77. Anon. Intracavernous injections for impotence. Med Lett Drugs Ther. 1990; 32:116-7. [PubMed 2255296]

78. Krane RJ, Goldstein I, Saenz de Tejada I. Impotence. N Engl J Med. 1989; 321:1648-59. [PubMed 2685600]

79. Kirby RS. Impotence: diagnosis and management of male erectile dysfunction. BMJ. 1994; 308:957-61. [IDIS 328981] [PubMed 8173405]

80. Murray FT, Geisser M, Murphy TC. Evaluation and treatment of erectile dysfunction. Am J Med Sci. 1995; 309:99-109. [IDIS 342934] [PubMed 7847449]

81. Bookstein JJ, Valji K, Parsons L et al. Penile pharmacocavernosography and cavernosometry in the evaluation of impotence. J Urol. 1987; 137:772-6. [IDIS 227803] [PubMed 3560346]

82. Montague DK, Lakin MM, VanderBrug Medendorp S et al. Infusion pharmacocavernosometry and nocturnal penile tumescence findings in men with erectile dysfunction. J Urol. 1991; 145:768-71. [IDIS 280173] [PubMed 2005697]

83. Duffy LM, Sidi AA, Lange PH. Vasoactive intracavernous pharmacotherapy—the nursing role in teaching self-injection therapy. J Urol. 1987; 138:1198-200. [IDIS 247278] [PubMed 3669166]

84. Delcour C, Wespes E, Vandenbosch G et al. Opacification of the glans penis during cavernosography. J Urol. 1988; 139:732-3. [IDIS 251291] [PubMed 3352032]

85. Whitehead ED, Klyde BJ, Zussman S et al. Diagnostic evaluation of impotence. Postgrad Med. 1990; 88:123-36. [IDIS 269900] [PubMed 2199953]

86. Kim SC, Kim KB, Oh CH. Diagnostic value of the radioisotope erection penogram for vasculogenic impotence. J Urol. 1990; 144:888-93. [IDIS 275216] [PubMed 2169002]

87. Petty R. Erectile impotence. Practitioner. 1993; 237:828-31. [IDIS 323448] [PubMed 8255874]

88. Gerstenberg TC, Nordling J, Hald T et al. Standardized evaluation of erectile dysfunction in 95 consecutive patients. J Urol. 1989; 141:857-62. [IDIS 253412] [PubMed 2926880]

89. Bénard F, Lue TF. Self-administration in the pharmacological treatment of impotence. Drugs. 1990; 39:394-8. [PubMed 2184008]

90. Montague DK. Editorial: treatment of erectile dysfunction. J Urol. 1993; 150:1833. [IDIS 321904] [PubMed 8230516]

91. Montague DK. Impotence therapy. J Urol. 1993; 149:1313. [IDIS 313866] [PubMed 8479023]

92. Shabsigh R, Fishman IJ, Quesada ET et al. Evaluation of vasculogenic erectile impotence using penile duplex ultrasonography. J Urol. 1989; 142:1469-74. [IDIS 302304] [PubMed 2685366]

93. Oates CP, Pickard RS, Powell PH et al. The use of duplex ultrasound in the assessment of arterial supply to the penis in vasculogenic impotence. J Urol. 1995; 153:354-7. [IDIS 341556] [PubMed 7815582]

94. Gannaway WL, Hoagland RJ, Inciardi JF et al. Chemical stability of alprostadil (PGE-1) in combination with common injectable medications. Int Pharm Abstr. 1990; 27:323.

95. Sone K, Tashiro M, Fujinaga T et al. Long-term low-dose prostaglandin E1 administration. J Pediatr. 1980; 97:866-7. [IDIS 127917] [PubMed 7431186]

96. Henry GW, Hurwitz RA, Girod DA et al. Prostaglandin treatment of infants with cyanotic congenital heart disease. J Pediatr. 1980; 96:158.

97. Padma-Nathan H, Hellstrom WJG, Kaiser FE et al. Treatment of men with erectile dysfunction with transurethral alprostadil. N Engl J Med. 1997; 336:1-7. [IDIS 377143] [PubMed 8970933]

98. Vivus. Muse (alprostadil) urethral suppository prescribing information. Menlo Park, CA; 1997 Aug.

99. Hellstrom WJG, Bennett AH, Gesundheit N et al. A double-blind, placebo-controlled evaluation of the erectile response to transurethral alprostadil. Urol. 1996; 48:851-6. [PubMed 8973666]

100. Vivus. Muse (alprostadil) urethral suppository patient information. Menlo Park, CA. 1997 Aug.

101. Schwarz Pharma. edex (alprostadil) sterile powder for injection prescribing information. Milwaukee, WI; 1998 Jun.

102. Pharmacia & Upjohn. Caverject (alprostadil) aqueous injection prescribing information. Kalamazoo, MI; 1999 Mar.

103. Pharmacia & Upjohn. Caverject (alprostadil) aqueous injection patient information. Kalamazoo, MI; 1998 June.

104. Anon. Intraurethral alprostadil for impotence. Med Lett Drugs Ther. 1997; 39:32. [PubMed 9121395]

105. Peterson CA, Bennett AH, Hellstrom WJG et al. Erectile response to transurethral alprostadil, prazosin and alprostadil-prazosin combinations. J Urol. 1998; 159:1523-8. [IDIS 405162] [PubMed 9554347]

106. Werthman P, Rajfer J. MUSE therapy: preliminary clinical observations. Urology. 1997; 50:809-11. [PubMed 9372900]

107. Porst H. Transurethral alprostadil with MUSE (medicated urethral system for erection) vs intracavernous alprostadil — a comparative study in 103 patients with erectile dysfunction. Int J Impot Res. 1997; 9:187-92. [PubMed 9442415]

108. GensiaSicor Pharmaceuticals. Alprostadil injection prescribing information. Irvine, CA; 1998 Jul.

109. Bedford Laboratories. Alprostadil injection prescribing information. Bedford, OH; 1999 Jan.

110. Pharmacia & Upjohn Company. Caverject Impulse (alprostadil) dual chamber system for intracavernosal use prescribing information. Kalamazoo, MI; 2002 Jun.

111. Pharmacia & Upjohn Company. Caverject impulse (alprostadil) dual chamber system for intracavernosal use patient information. Kalamazoo, MI; 2002 Jun.

112. Erectile Dysfunction Guideline Update Panel, American Urological Association Education and Research. Management of erectile dysfunction: An update. 2005. Available from website. Accessed 2005 Oct. 20.

113. Erectile Dysfunction Guideline Update Panel, American Urological Association Education and Research. Priapism: Guideline on the management of priapism. 2003. Available from website. Accessed 2005 Oct. 20.

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:21-2.

a. Pharmacia & Upjohn Company. Prostin VR Pediatric (alprostadil sterile solution) injection prescribing information. Kalamazoo, MI; 2002 Aug.

b. Pharmacia & Upjohn Company. Caverject (alprostadil) for injection for intracavernosal use prescribing information. New York, NY; 2006 Sep.

d. Schwarz Pharma. edex (alprostadil) sterile powder and diluent in cartridges for injection prescribing information. Milwaukee, WI; 2006 Jan.

e. Pharmacia & Upjohn Company. Caverject (alprostadil) for injection for intracavernosal use patient instruction. Kalamazoo, MI; 2006 Sep.

f. Vivus. Muse (alprostadil) urethral suppository patient information. Mountain View, CA. 2006 Jan.

h. Pharmacia & Upjohn Company. Caverject impulse (alprostadil) (alprostadil) dual chamber system for intracavernosal use prescribing information. Kalamazoo, MI; 2003 Sep.

i. Pharmacia & Upjohn Company. Caverject impulse (alprostadil) dual chamber system for intracavernosal use patient instructions. Kalamazoo, MI; 2003 Sep.

l. Vivus. Muse (alprostadil) urethral suppository prescribing information. Mountain View, CA; 2003 Aug.

m. American Academy of Pediatrics Committee on Fetus and Newborn and Committee on Drugs. Benzyl alcohol: toxic agent in neonatal units. Pediatrics. 1983; 72:356 8. [IDIS 175725] [PubMed 6889041]

n. Anon. Benzyl alcohol may be toxic to newborns. FDA Drug Bull. 1982; 12(2):10 11.

o. Centers for Disease Control. Neonatal deaths associated with use of benzyl alcohol. MMWR. 1982; 31:290 1. [IDIS 150868] [PubMed 6810084]

p. Menon PA, Thach BT, Smith CH et al. Benzyl alcohol toxicity in a neonatal intensive care unit: incidence, symptomatology, and mortality. Am J Perinatol. 1984; 1:288 92. [PubMed 6440575]

q. Anderson CW, Ng KJ, Andresen B et al. Benzyl alcohol poisoning in a premature newborn infant. Am J Obstet Gynecol. 1984; 148:344 6. [IDIS 181207] [PubMed 6695984]

r. Schwarz Pharma. edex (alprostadil) sterile powder and diluent in cartridges for injection patient information. Milwaukee, WI; 2006 Jan.

s. The Process of Care Consensus Panel. Position paper: the process of care model for evaluation and treatment of erectile dysfunction. Int J Impot Res. 1999; 11:59-70. [PubMed 10356665]

t. Canadian Urological Association Guidelines Committee. Erectile dysfunction practice guidelines. Can J Urol. 2002; 9:1583-7. [PubMed 12243654]

u. Mancini M, Raina R, Agarwal A et al. Sildenafil citrate vs intracavernous alprostadil for patients with arteriogenic erectile dysfunction; a randomised placebo controlled study. Int J Impot Res. 2004; 16:8-12. [PubMed 14963465]

v. Wespes E, Amar E, Hatzichtistou D et al. Guidelines on erectile dysfunction. Arnhem: European Association of Urology, 2005 Mar. Available from website. Accessed 2007 Jul 31.

w. Nandwani R, Goutlay Y. Possible interaction between sildenafil and HIV combination therapy. Lancet. 1999; 353:840.

x. Pfizer, New York, NY: Personal communication.

y. Erectile Dysfunction Guideline Update Panel, American Urological Association Education and Research. Management of erectile dysfunction: An update. 2006. Available from website. Accessed 2007 Jul 12.

z. Lea AP, Bryson HM, Balfour JA. Intracavernous alprostadil: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in erectile dysfunction. Drugs Aging. 1996; 8:56-74. [PubMed 8785470]

Hide
(web2)