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    All Other Cardiac Preparations
    Erectile Dysfunction Products

    BOXED WARNING

    Apnea, congenital heart disease, premature neonates, respiratory depression

    Apnea is experienced by approximately 10% to 12% of neonates and infants with congenital heart disease defects treated with intravenous alprostadil. Apnea is most often seen in premature neonates weighing less than 2 kg at birth and usually occurs during the first hour of drug infusion. Respiratory status should be monitored throughout treatment and neonatal use of alprostadil should only be undertaken where ventilatory assistance is immediately available. Alprostadil should be used cautiously in neonates and infants with respiratory depression.

    DEA CLASS

    Rx

    DESCRIPTION

    Prostaglandin E-1 
    Used for erectile dysfunction (ED) and to maintain patency of ductus arteriosus in neonates until surgery
    Erectile dysfunction products include an intraurethral insert (Muse) and intracavernosal injection (Caverject or Edex); other dosage forms under investigation
    Prostin VR Pediatric is an IV form used in neonates; use requires respiratory monitoring due to risk of apnea

    COMMON BRAND NAMES

    Caverject, Caverject Impulse, Edex, Muse, Prostin VR

    HOW SUPPLIED

    Alprostadil/Prostin VR Intravenous Inj Sol: 1mL, 500mcg
    Caverject Intravenous Inj Pwd F/Sol: 20mcg
    Caverject/Caverject Impulse/Edex Intracavernous Inj Pwd F/Sol: 10mcg, 20mcg, 40mcg
    Muse Urethral Supp: 125mcg, 250mcg, 500mcg, 1000mcg

    DOSAGE & INDICATIONS

    For the treatment of neonates with congenital heart defects to maintain the patency of the ductus arteriosus (ductus arteriosus maintenance) until palliative or corrective surgery can be performed.
    Intravenous dosage (Prostin VR Pediatric)
    Neonates

    Initially, 0.05—0.1 mcg/kg/minute IV infusion. The usual maintenance dosage range is 0.01—0.1 mcg/kg/minute IV infusion. Once an adequate response has been achieved, the infusion rate should be reduced to the lowest dosage that will maintain the response. If the initial response if inadequate, the manufacturer reports the rate can be gradually increased to a maximum of 0.4 mcg/kg/minute; however, higher infusion rates do not usually produce greater effects.

    For the treatment of erectile dysfunction (ED).
    NOTE: Per ED guidelines, second-line treatment options for ED treatment include intracavernous injection and intra-urethral therapy. Intracavernous injection therapy is the most effective nonsurgical treatment for ED, with predictable and sustained response. However, it is invasive and caries notable side-effects including priapism and penile fibrosis. Careful dose selection, proper patient education, and continued monitoring by a prescribing physician is warranted for successful non-oral treatment of ED. Follow-up visits for ED patients, regardless of therapy, are necessary to determine whether therapy continues to be effective and whether cardiovascular health has significantly changed.
    For erectile dysfunction due to vasculogenic, psychogenic, or mixed causes or following post-radical prostatectomy†.
    Intracavernous dosage (Caverject injection)
    Adult males

    2.5 mcg initially, injected into the corpus cavernosa, adjusting the dosage by 2.5 mcg increments, to 5 mcg, then by 5 mcg increments according to patient response. Maximum 60 mcg/dose. Do not administer more than 3 times per week, with a minimum of 24 hours between doses.

    Intracavernous dosage (Edex injection)
    Adult males

    2.5 mcg initially, injected into the corpus cavernosa. If there is a partial response, may be increase by 2.5 mcg to 5 mcg and then in 5 to 10 mcg increments according to patient response until the dose producing an erection suitable for intercourse and not more than 1 hour in duration achieved. 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. Patient must remain in physician's office until complete detumescence occurs. If there is no response, the next higher dose may be given within 1 hour. If there is a response, wait at least a 1-day interval before giving the next dose. Do not administer more than 3 times per week, with a minimum of 24 hours between doses.

    Intraurethral dosage (MUSE urethral suppository)
    Adult males

    Therapy should be initiated with 125 mcg or 250 mcg into the urethra as directed. If necessary, the dose should be increased (or decreased) on separate occasions in a stepwise manner until the patient achieves an erection that is sufficient for sexual intercourse. Once dose titration is complete, MUSE should be used as needed. The maximum frequency of use is 2 administrations per 24-hour period.

    For erectile dysfunction due to neurogenic origin.
    Intracavernous dosage (Caverject injection)
    Adult males

    1.25 mcg initially, injected into the corpus cavernosa, adjusting the dosage by 2.5 mcg increments, to 5 mcg, then by 5 mcg increments according to patient response. Maximum 60 mcg/dose. Do not administer more than 3 times per week, with a minimum of 24 hours between doses.

    Intracavernous dosage (Edex injection)
    Adult males

    1.25 mcg initially, injected into the corpus cavernosa. May increase 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 a dose producing an erection suitable for intercourse and not more than 1 hour in duration achieved. Patient must remain in physician's office until complete detumescence occurs. If there is no response, the next higher dose may be given within 1 hour. If there is a response, wait at least a 1-day interval before the next dose is given. Do not administer more than 3 times per week, with a minimum of 24 hours between doses.

    For the treatment of ED in combination with other vasoactive agents (i.e., papaverine, phentolamine)†.
    Intracavernous dosage (Triple-drug regimen)
    Adults males

    Although alprostadil monotherapy has a high efficacy rate, reaching up to 70%, triple drug therapy with alprostadil, papaverine, and phentolamine has a response rate of up to 92%. Individual dosages are determined by series of trial injections under physician supervision. Limit use to 1 injection in a 24-hour period, given no more than 3 times per week. Triple drug regimen dose ranges: 0.2 to 0.4 mg phentolamine plus 8 to 16 mg papaverine plus 10 to 20 mcg alprostadil per injection.

    MAXIMUM DOSAGE

    Adults

    Dependent on indication for therapy and product prescribed.

    Geriatric

    Dependent on indication for therapy and product prescribed.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Doses > 0.4 mcg/kg/minute IV of Prostin VR Pediatric are not recommended.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Dilution:
    For infusion, dilute 1 mL of the concentrate labeled as containing 500 mcg of alprostadil in 0.9% Sodium Chloride Injection or 5% Dextrose Injection to provide a solution containing 2 to 20 mcg/mL, depending on the controlled-infusion device used and the needs of the neonate. When using a device with a volumetric infusion chamber, the proper amount of diluent should be added to the chamber first and then 1 mL of the concentrate for infusion should be added to the diluent. Care should be taken to avoid direct contact of the concentrate with the wall of the plastic volumetric infusion chamber; the appearance of the chamber may change and a hazy solution may develop.
    The manufacturer recommends that diluted infusion solutions of alprostadil be prepared freshly every 24 hours and that any remaining solution should be discarded.
     
    Continuous intravenous infusion:
    The infusion rate depends on the concentration of the final injection solution and desired dosage.
    Because of the risk of respiratory depression and apnea, respiratory status should be monitored throughout alprostadil administration. Facilities and equipment for assisted ventilation should be readily available. Apnea is most likely to develop during the first hour of the infusion, particularly in neonates weighing less than 2 kg at birth. If apnea or bradycardia occurs, the infusion should be stopped and appropriate therapy initiated. Arterial pressure should also be monitored periodically via umbilical artery catheter, auscultation, or Doppler transducer. The rate of infusion should be decreased immediately if a clinically important decrease in arterial pressure occurs. The infusion rate should also be reduced if fever or hypotension occurs since these may be signs of overdosage; if necessary, the rate may be increased cautiously once fever or hypotension subsides.

    Other Injectable Administration

    Intra-arterial Administration
    Dilution
    For infusion, dilute 1 mL of the concentrate labeled as containing 500 mcg of alprostadil in 0.9% Sodium Chloride Injection or 5% Dextrose Injection to provide a solution containing 2 to 20 mcg/mL, depending on the controlled-infusion device used and the needs of the neonate. When using a device with a volumetric infusion chamber, the proper amount of diluent should be added to the chamber first and then 1 mL of the concentrate for infusion should be added to the diluent. Care should be taken to avoid direct contact of the concentrate with the wall of the plastic volumetric infusion chamber; the appearance of the chamber may change and a hazy solution may develop.
    The manufacturer recommends that diluted infusion solutions of alprostadil be prepared freshly every 24 hours and that any remaining solution should be discarded.
     
    Intra-arterial infusion (i.e. umbilical artery catheter positioned at the ductal opening)
    The infusion rate depends on the concentration of the final injection solution and desired dosage.
    Because of the risk of respiratory depression and apnea, respiratory status should be monitored throughout alprostadil administration. Facilities and equipment for assisted ventilation should be readily available. Apnea is most likely to develop during the first hour of the infusion, particularly in neonates weighing less than 2 kg at birth. If apnea or bradycardia occurs, the infusion should be stopped and appropriate therapy initiated. Arterial pressure should also be monitored periodically via umbilical artery catheter, auscultation, or Doppler transducer. The rate of infusion should be decreased immediately if a clinically important decrease in arterial pressure occurs. The infusion rate should also be reduced if fever or hypotension occurs since these may be signs of overdosage; if necessary, the rate may be increased cautiously once fever or hypotension subsides.
     
    Intracavernous Administration
    Discussion with the patient and his partner about expectations of alprostadil therapy is important. Therapy should be initiated under the supervision of a physician in order to test a patient's responsiveness and to demonstrate proper administration technique. Patient education can minimize the likelihood of local adverse effects associated with faulty administration technique.
    Patient self-injection should only begin after the patient has received and reviewed a copy of the patient instructions provided by the manufacturer and have been instructed carefully and trained well about proper administration techniques. Long-term follow-up to the patient and his partner should also be provided to assist in adjusting to alprostadil therapy.
    Remind patient not to exceed dose limits. The maximum frequency of use is no more than 1 injection per 24-hour period and no more than 3 injections per week.
     
    Reconstitution of CAVERJECT
    Reconstitute by adding 1 mL of the diluent supplied by the manufacturer to a vial labeled as containing 6.15, 11.9, 23.2, or 46.4 mcg of alprostadil to provide a solution containing 5.4 mcg/mL, 10.5 mcg/mL,, 20.5 mcg/mL,, or 41.1 mcg/mL, respectively. (NOTE: The syringe/needle should be in a straight line with the Caverject vial when injecting the diluent into the sterile powder vial and when removing the correct dose for injection from the Caverject vial). The deliverable amount of alprostadil in these dilutions is 5 mcg/mL, 10 mcg/mL, 20 mcg/mL, or 40 mcg/mL, respectively, because some drug is absorbed onto the vial and syringe.
    After adding the diluent but before removing the syringe from the vial, the contents of the vial should be swirled gently until a clear solution is obtained.
    The desired dose can then be withdrawn into the same syringe.
    Storage: Unused reconstituted solution may be stored for up to 24 hours if stored below 25 degrees C (77 degrees F) and not refrigerated or frozen.
     
    Reconstitution of EDEX
    Prepare the injection immediately before use.
    The Edex injection device is used to reconstitute the single-dose dual chamber cartridge. Use the plunger and force the sterile 0.9% Sodium Chloride injection (1.075 mL) in one chamber into the other chamber containing alprostadil.
    After reconstitution, the Edex injection device is used to administer the dose of alprostadil; use only with the cartridges and needles supplied in the Edex cartridge packs.
    Do not administer unless solution is clear. Do not add any drugs or solutions to the injection solution. Discard unused drug solution. The reconstituted injection solution should not be stored.
     
    Intracavernous injection
    Alprostadil intracavernosal injection cartridge devices are designed for one time use. After the single use, the injection device and remaining solution should be discarded. Of note, the needle used for administration of alprostadil solution is a superfine (27- to 30-gauge) needle; with such a fine needle, breakage is possible. Patients should be carefully instructed on proper injection technique to minimize the risk of needle breakage. Needles or syringes should not be shared.
    The head of the penis should be held between the thumb and forefinger and stretched lengthwise along the thigh while sitting upright or slightly reclined. The needle of the syringe is then positioned so that the drug will be injected into a corpus cavernosum underneath the tunica albuginea along the dorsolateral aspect of the proximal third of the penis. Visible veins should be avoided. Blood vessels, corpus spongiosum, subcutaneous tissue, urethra, and dorsal neural vascular structures should be avoided as injection sites.
    Once positioned, the needle of the syringe provided by the manufacturer should be pushed straight into the site using a steady motion until the metal portion of the needle is almost entirely in the penis; the dose should then be injected slowly over 5 to 10 seconds into the chosen corpus cavernosum.
    The syringe should be withdrawn and pressure applied to the injection site with an alcohol swab for 5 minutes (or until bleeding stops) to avoid hematologic complications, especially in patients receiving concomitant anticoagulant therapy. Injection site and side of the penis should be rotated to minimize adverse effects related to repeated local injection.
    Patient should be cautioned against use of severely bent needles, reuse of syringes and needles. Give patient instructions on proper disposal of syringes and needles in the puncture-resistant container provided by the manufacturer.

    Other Administration Route(s)

    Intraurethral Administration
    Alprostadil (MUSE) is administered as a urethral suppository.
    The initial dose titration should be undertaken under the supervision of a physician in order to test a patient's responsiveness, to demonstrate proper administration technique, and to monitor for evid.nce of hypotension.
    The aloprostadil urethral suppository (MUSE) is designed to be self-administered. Clinicians should instruct patient on proper administration technique.
    Remind patient not to exceed recommended dose limits. The maximum frequency of use is no more than 2 urethral suppository systems per 24-hour period.
     
    Urethral Suppository (MUSE) Administration
    The aloprostadil urethral suppository (MUSE) is designed to be self-administered after proper education and dose titration.
    For urethral insertion only. Do not administer by any other route.
    Key administration points:
    Immediately prior to administration, patient should urinate and gently shake the penis several times to remove excess urine. The medicated pellet has been specially developed to dissolve in the small quantity of urine that remains in the urethra after urination.
    After opening pouch, visually inspect the MUSE system to make sure the pellet is present.
    To straighten the urethra, patient should, while sitting or standing, take several seconds to gently and 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. If any discomfort or a pulling sensation, withdraw the applicator slightly and then gently reinsert.
    To administer suppository, gently and completely push down the button at the top of the applicator until it stops to ensure that the medicated pellet is completely released. The patient should then hold the applicator in this position for 5 seconds, then, gently rock the applicator from side to side in order to separate the medicated pellet from the applicator tip. Be sure to tell patient not to apply too much pressure in order to avoid scratching the lining of the urethra and causing it to bleed.
    Remove applicator while keeping the penis upright. Without touching the stem of the applicator, visually inspect the applicator tip to make sure the pellet is no longer in the applicator. If residual medication is present, gently reinsert into the urethra and repeat.
    After administration, instruct patient to hold the penis upright and stretched to its full length and roll the penis firmly between the hands for at least 10 seconds to ensure that the medication is adequately distributed along the walls of the urethra. If a burning sensation is felt, the patient may continue to roll the penis for an additional 30 to 60 seconds or until the burning subsides. Then, to increase blood flow to the penis and enhance erection, the patient should sit, stand, or walk about for 10 minutes while the erection is developing.
    Instruct patient on proper disposal of unit.

    STORAGE

    Caverject:
    - Protect from freezing
    - Store below 77 degrees F
    Caverject Impulse:
    - Do not freeze
    - Store unreconstituted product at 68 to 77 degrees F; excursions permitted to 59 to 86 degrees F
    Edex:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Reconstituted product should be used immediately. Discard unused portion
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Muse:
    - Product may be used for up to 14 days if kept below 86 degrees F after container is opened
    - Store unopened containers in refrigerator (36 to 46 degrees F)
    Prostin VR:
    - Refrigerate (between 36 and 46 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Any underlying and treatable medical cause for erectile dysfunction should be diagnosed and treated before therapy with alprostadil intracavernosal injection or urethral suppository is initiated.

    Apnea, congenital heart disease, premature neonates, respiratory depression

    Apnea is experienced by approximately 10% to 12% of neonates and infants with congenital heart disease defects treated with intravenous alprostadil. Apnea is most often seen in premature neonates weighing less than 2 kg at birth and usually occurs during the first hour of drug infusion. Respiratory status should be monitored throughout treatment and neonatal use of alprostadil should only be undertaken where ventilatory assistance is immediately available. Alprostadil should be used cautiously in neonates and infants with respiratory depression.

    GI obstruction

    The intravenous administration of alprostadil to neonates may result in GI obstruction secondary to antral hyperplasia. Duration of therapy and the accumulation of the drug appears to be related to this adverse effect. Careful monitoring is recommended in neonates receiving alprostadil for greater than 120 hours. Alprostadil should be administered at the lowest effective dose and for the shortest length of time. The risks of prolonged infusion should be weighed against the potential benefits to the infant.

    Respiratory distress syndrome

    Alprostadil intravenous infusions should not be used in neonates with neonatal respiratory distress syndrome. In these neonates, the ductus arteriosus must close in order to prevent overload of the pulmonary circulation. A differential diagnosis between neonatal respiratory distress syndrome and cyanotic heart disease (restricted pulmonary blood flow) should be made prior to initiating alprostadil therapy.

    Bleeding

    Alprostadil inhibits platelet aggregation and therefore can increase the risk of bleeding. Use intravenous alprostadil cautiously in neonates with bleeding tendencies.

    Cardiac disease, driving or operating machinery, hypotension, syncope

    Alprostadil injection for the maintenance of patency of the ductus arteriosus also causes hypotension; neonates receiving an alprostadil infusion should be carefully monitored for a drop in blood pressure. Alprostadil for the management of erectile dysfunction (ED) should be used cautiously in men with cardiac disease. There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Therefore, treatments for erectile dysfunction generally should not be used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status. Increased peripheral blood levels of PGE1 and its metabolites, especially in those patients with significant corpora cavernosa venous leakage may lead to hypotension and/or dizziness, and very rarely syncope, when using alprostadil for ED treatment. Patients should be monitored for symptoms of hypotension during dosing and the lowest effective dose should be prescribed. The use of other vasoactive substances with alprostadil for ED may increase hypotensive risk and is not advised.   Men should also be cautioned to avoid activities, such as driving or operating machinery, or other hazardous tasks, where injury could result if hypotension or syncope were to occur directly after alprostadil administration.

    Leukemia, multiple myeloma, polycythemia, priapism, sickle cell disease, thrombocytosis

    The use of alprostadil intracavernosal injection or urethral suppository is contraindicated in patients who are prone to venous thrombosis or who have a hyperviscosity syndrome and are therefore at increased risk of priapism. This includes patients with sickle cell disease or trait, thrombocytosis, polycythemia, leukemia, or multiple myeloma. Prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been associated with administration of drugs for the treatment of erectile dysfunction, including alprostadil. Priapism, if not treated promptly, can result in irreversible damage to the erectile tissue. Men who have an erection lasting 4 hours or greater, whether painful or not, should seek emergency medical attention. Lower dosages or discontinuation of treatment should be considered in patients who develop priapism or prolonged erection.

    Balanitis, hypospadia, penile implants, penile structural abnormality, Peyronie's disease, urethral stricture, urethritis

    The use of alprostadil intracavernosal injection or urethral suppository is contraindicated in men with penile structural abnormality. The intracavernosal injection is specifically contraindicated in patients with penile angulation, cavernosal fibrosis, or Peyronie's disease. The urethral suppository is contraindicated in men with urethral stricture, balanitis, Peyronie's disease, severe hypospadia and curvature, or acute or chronic urethritis. The use of alprostadil in patients with penile implants is also contraindicated and has not been studied. Both of these products are contraindicated in patients for whom sexual intercourse is inadvisable or contraindicated. In addition, there is no experience of using alprostadil in homosexual men and no experience with non-vaginal intercourse.

    Anticoagulant therapy, coagulopathy

    Alprostadil should be used cautiously in male patients with a coagulopathy, known bleeding disorder, or in those receiving anticoagulant therapy. Improper administration of the alprostadil urethral suppository may cause urethral abrasion resulting in minor bleeding or spotting. Patients on anticoagulant therapy or with bleeding disorders may be at increased risk of bleeding. Although patients on anticoagulant therapy have been treated safely with the urethral suppository, the manufacturer recommends that the risk/benefit ratio in these patients be considered prior to prescribing. Patients on anticoagulants may have increased propensity for bleeding after intracavernous injection, so proper adherence to administration technique is important to avoid hematoma or other bleeding. A small amount of bleeding may occur in any male at the site of intracavernous administration. This can increase the transmission of a blood-borne diseases to a sexual partner.

    Geriatric, renal impairment

    Clinical trials for the use of aloprostadil for the treatment of erectile dysfunction (ED) have included geriatric adult males 65 years of age and older. Safety concerns vs. use in younger adult men were not evident based on age alone. Geriatric patients should be dosed and titrated according to the same dosage and administration recommendations as younger adult males, and the lowest possible effective dose should always be used. Alprostadil is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with renal impairment. Because older adult patients are more likely to have decreased renal function or underlying cardiac disease, care should be taken in dose selection and titration, and it may be useful to monitor renal function.

    Contraception requirements, females, labor, pregnancy

    Given the indications for use, alprostadil dosage forms for erectile dysfunction (ED) are not to be used in females or during pregnancy. There is no information on the effects on early pregnancy of prostaglandin E1 (PGE1) at the levels received by female partners via the semen of an aloprostadil-treated male. Prostaglandins generally promote uterine contractions, and exposure to prostaglandins during pregnancy may induce contractions and labor. Animal data report embryotoxic effects when alprostadil was given as a subcutaneous bolus, however, no developmental harm was reported when the drug was given intravaginally. Recommendations for contraception requirements for men using aloprostadil urethral suppositories for erectile dysfunction are available. Aloprostadil urethral suppository should not be used by males for sexual intercourse with a pregnant partner unless the couple uses a condom barrier. All couples using alprostadil urethral suppositories for erectile dysfunction are recommended to employ adequate contraception if the female partner is of childbearing potential. Male individuals who are sexually active should be counseled about the protective measures that are necessary to guard against the spread of sexually transmitted diseases, including the human immunodeficiency virus (HIV). Use of aloprostadil for the treatment of erectile dysfunction (ED) offers no protection from the transmission of sexually transmitted or blood-borne diseases.

    Breast-feeding

    Given the indications for use, alprostadil would not be expected to be used during lactation. Use in the lactating female during breast-feeding is not indicated.

    Benzyl alcohol hypersensitivity, children, infants, neonates

    Given the indications for use for adult male erectile dysfunction, alprostadil intracavernosal injection and urethral suppository are contraindicated for use in children under the age of 18 years, infants, and neonates. Alprostadil intracavernosal injection (e.g., Caverject and Caverject Impulse) contains the preservative benzyl alcohol, which can cause adverse effects in neonates or in patients with a benzyl alcohol hypersensitivity. The preservative has been associated with reports of fatal 'gasping syndrome' in neonates; symptoms include a striking onset of gasping respiration, hypotension, bradycardia, and cardiovascular collapse. The minimum amount of benzyl alcohol at which toxicity may occur is not known. The risk of benzyl alcohol toxicity depends on the quantity administered and the hepatic and renal capacity to detoxify the chemical. Premature and low-birth weight infants may be more likely to develop toxicity.

    ADVERSE REACTIONS

    Severe

    apnea / Delayed / 10.0-12.0
    bradycardia / Rapid / 7.0-7.0
    seizures / Delayed / 4.0-4.0
    phimosis / Delayed / 3.0-3.0
    cardiac arrest / Early / 1.0-1.0
    myocardial infarction / Delayed / 1.0-1.0
    ventricular fibrillation / Early / 0-1.0
    heart failure / Delayed / 0-1.0
    penile edema / Early / 1.0-1.0
    visual impairment / Early / 1.0-1.0
    disseminated intravascular coagulation (DIC) / Delayed / 0-1.0
    anuria / Delayed / 0-1.0
    hyperkalemia / Delayed / 0-1.0

    Moderate

    penile pain / Rapid / 29.0-37.0
    urethral pain / Early / 0-13.0
    hematoma / Early / 3.0-5.0
    hypotension / Rapid / 1.0-3.0
    sinus tachycardia / Rapid / 0-3.0
    penile fibrosis / Delayed / 3.0-3.0
    erythema / Early / 2.0-3.0
    hypertension / Early / 2.0-2.0
    peripheral edema / Delayed / 0-2.0
    hypertriglyceridemia / Delayed / 2.0-2.0
    respiratory depression / Rapid / 0-1.0
    tachypnea / Early / 0-1.0
    wheezing / Rapid / 0-1.0
    bleeding / Early / 0-1.0
    edema / Delayed / 1.0-1.0
    supraventricular tachycardia (SVT) / Early / 0-1.0
    hyperemia / Delayed / 0-1.0
    peripheral vasodilation / Rapid / 0-1.0
    priapism / Early / 0-1.0
    thrombocytopenia / Delayed / 0-1.0
    anemia / Delayed / 0-1.0
    hyperbilirubinemia / Delayed / 0-1.0
    hematuria / Delayed / 0-1.0
    hypercholesterolemia / Delayed / 1.0-1.0
    hypoglycemia / Early / 0-1.0
    hyperglycemia / Delayed / 1.0-1.0
    urinary retention / Early / Incidence not known

    Mild

    injection site reaction / Rapid / 2.0-15.0
    fever / Early / 14.0-14.0
    flushing / Rapid / 10.0-10.0
    vaginal irritation / Early / 5.8-5.8
    testicular pain / Early / 1.0-5.0
    dizziness / Early / 1.0-4.0
    ecchymosis / Delayed / 2.0-4.0
    pruritus / Rapid / 3.0-3.0
    headache / Early / 2.0-3.0
    back pain / Delayed / 1.0-2.0
    rhinitis / Early / 2.0-2.0
    perineal pain / Early / 0-2.0
    diarrhea / Early / 2.0-2.0
    irritability / Delayed / 0-1.0
    lethargy / Early / 0-1.0
    hypothermia / Delayed / 0-1.0
    syncope / Early / 0-1.0
    mydriasis / Early / 0-1.0
    muscle cramps / Delayed / 0-1.0
    nausea / Early / 0-1.0
    gastroesophageal reflux / Delayed / 0-1.0
    xerostomia / Early / 0-1.0
    rash (unspecified) / Early / 0-1.0
    diaphoresis / Early / 0-1.0
    hypoesthesia / Delayed / 0-1.0
    weakness / Early / 0-1.0
    urinary urgency / Early / Incidence not known
    increased urinary frequency / Early / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Angiotensin II receptor antagonists: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as angiotensin II receptor antagonists (angiotensin receptor blockers, or ARBs), may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Angiotensin-converting enzyme inhibitors: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as angiotensin-converting enzyme inhibitors (ACE inhibitors), may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Atenolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Atenolol; Chlorthalidone: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Bendroflumethiazide; Nadolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Beta-blockers: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Betaxolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Bisoprolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Brimonidine; Timolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Calcium-channel blockers: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, like calcium channel blockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Carteolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Carvedilol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Central-acting adrenergic agents: (Minor) The concomitant use of systemic alprostadil injection and central-acting antihypertensive agents may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Dorzolamide; Timolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Doxazosin: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as doxazosin, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Eplerenone: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as eplerenone, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Epoprostenol: (Minor) Systemic alprostadil and epoprostenol are both prostaglandins that reduce blood pressure, and would not be commonly prescribed together at the same time. The concomitant use of systemic alprostadil injection and epoprostenol would be expected to cause additive hypotension. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Esmolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Heparin: (Moderate) Caution is advised with the concomitant administration of alprostadil injection for dilation of the ductus arteriosis and heparin infusions. Coadministration resulted in a 140% increase in partial thromboplastin time and a 120% increase in thrombin time in a study of 12 healthy volunteers receiving alprostadil 90 mcg infusion over 3 hours and heparin 5000 units. Monitor patients for increased bleeding if these agents are used together.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Hydrochlorothiazide, HCTZ; Propranolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Ibuprofen lysine: (Severe) As ibuprofen lysine is used for the pharmacologic closure of patent ductus arteriosus (PDA), do not administer to patients who require alprostadil injection for dilation of the ductus arteriosus for oxygenation and perfusion. Alprostadil injection for pediatric use (Prostin VR) has been used with the standard therapy for neonates with restricted pulmonary or systemic blood flow which includes antibiotics (e.g., penicillin and gentamicin), vasopressors (e.g., dopamine, isoproterenol), cardiac glycosides, and diuretics (e.g., furosemide).
    Iloprost: (Minor) Systemic alprostadil and epoprostenol are both prostaglandins that reduce blood pressure, and would not be commonly prescribed together at the same time. The concomitant use of systemic alprostadil injection and epoprostenol would be expected to cause additive hypotension. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Labetalol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Levobetaxolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Levobunolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Loop diuretics: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as loop diuretics, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Metoprolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Nadolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Nebivolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Nebivolol; Valsartan: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Penbutolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Phenoxybenzamine: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as phenoxybenzamine, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Pindolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Potassium-sparing diuretics: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as spironolactone or other potassium-sparing diuretics, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Prazosin: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as prazosin, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Propranolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Reserpine: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as reserpine, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Sotalol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Terazosin: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as terazosin, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Thiazide diuretics: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as thiazide diuretics, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Timolol: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Treprostinil: (Minor) Systemic alprostadil and treprostinil are both prostaglandins that reduce blood pressure, and would not be commonly prescribed together at the same time. The concomitant use of systemic alprostadil injection and treprostinil would be expected to cause additive hypotension. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Vasodilators: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as the vasodilators, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.

    PREGNANCY AND LACTATION

    Pregnancy

    Given the indications for use, alprostadil dosage forms for erectile dysfunction (ED) are not to be used in females or during pregnancy. There is no information on the effects on early pregnancy of prostaglandin E1 (PGE1) at the levels received by female partners via the semen of an aloprostadil-treated male. Prostaglandins generally promote uterine contractions, and exposure to prostaglandins during pregnancy may induce contractions and labor. Animal data report embryotoxic effects when alprostadil was given as a subcutaneous bolus, however, no developmental harm was reported when the drug was given intravaginally. Recommendations for contraception requirements for men using aloprostadil urethral suppositories for erectile dysfunction are available. Aloprostadil urethral suppository should not be used by males for sexual intercourse with a pregnant partner unless the couple uses a condom barrier. All couples using alprostadil urethral suppositories for erectile dysfunction are recommended to employ adequate contraception if the female partner is of childbearing potential. Male individuals who are sexually active should be counseled about the protective measures that are necessary to guard against the spread of sexually transmitted diseases, including the human immunodeficiency virus (HIV). Use of aloprostadil for the treatment of erectile dysfunction (ED) offers no protection from the transmission of sexually transmitted or blood-borne diseases.

    MECHANISM OF ACTION

    For the treatment of erectile dysfunction (ED), alprostadil relaxes the smooth muscles of the corpus cavernosum; however, the exact mechanism of action is unknown. It appears that the effects are due to increasing the intracellular concentrations of cyclic AMP. Alprostadil interacts with specific membrane-bound receptors that stimulate adenylate cyclase and elevate intracellular cyclic AMP, leading to activation of protein kinase and resultant smooth muscle relaxation. This action is in contrast to papaverine which inhibits oxidative phosphorylation mediated inactivation of cyclic AMP and interferes with calcium mobilization during muscle contraction. Alprostadil may also antagonize the vasoconstrictive actions of norepinephrine by preventing the neuronal release of norepinephrine and may enhance the actions of nonadrenergic, noncholinergic vasodilatory neurotransmitters. In treating ED, alprostadil induces erection by relaxing trabecular smooth muscle and dilating cavernosal arteries and their branches. Dilation of the cavernosal arteries is accompanied by increased arterial inflow velocity and increased venous outflow resistance. As a result, the lacunar spaces expand and blood becomes entrapped secondary to compression of venules against the tunica albuginea. To achieve adequate tumescence and rigidity, the tunica albuginea must be sufficiently stiff to compress the venules penetrating it and thus block venous outflow. This process is also referred to as the corporal veno-occlusive mechanism. Alprostadil does not directly affect ejaculation or orgasm.
     
    In the treatment of ductus arteriosus-dependent congenital heart defects, alprostadil maintains ductal patency by relaxing the smooth muscles of the ductus arteriosus. Alprostadil is only effective if given prior to complete anatomic closure of the ductus arteriosus. Administration of alprostadil to neonates with cyanotic congenital heart defects (restricted pulmonary blood flow) results in an increase in pulmonary blood flow and/or increase in mixing between the systemic and pulmonary circulation which leads to a temporary increase in arterial oxygen partial pressure (PaO2) and oxygen saturation. The response of the cyanotic neonate to alprostadil therapy is also inversely related to pretreatment PO2. The greatest response appears to be in those neonates with low pretreatment PaO2 (< 20 torr), narrowing ductus arteriosus, and who are 4 days old or younger. Neonates with PaO2 values of 40 torr or more usually have little response to alprostadil.
     
    In neonates with restricted systemic blood flow, administration of alprostadil can result in prevention or correction of acidemia, increased cardiac output with increased systemic blood pressure, increased femoral pulse volume, increased renal blood flow and function, decreased gradient of descending to ascending aortic blood pressures (in neonates with coarctation of the aorta), and/or decreased ratio of pulmonary artery pressure to descending aortic pressure (in neonates with interruption of the aortic arch). Unlike in cyanotic neonates, the efficacy of alprostadil in acyanotic neonates does not depend on age or pretreatment PaO2.

    PHARMACOKINETICS

    Alprostadil is administered by intravenous infusion, intracavernosal injection, or via an urethral suppository. Once in the systemic circulation, alprostadil is bound primarily to albumin (81%). No significant binding to erythrocytes or white blood cells occurs. Alprostadil is completely metabolized in the lung to several metabolites with a first-pass pulmonary elimination of 60% to 90% of PGE1. The main metabolites (15-keto-PGE1, 15-keto-PGE0, and PGE0) are primarily excreted in the urine (88%) and feces (12%) over 72 hours; total excretion is essentially complete within 24 hours after administration. The terminal half-life of PGE1 is approximately 9 to 11 minutes.

    Intravenous Route

    Intravenous administration of alprostadil requires a continuous infusion of the drug because approximately 80% of the dose is metabolized in one pass through the lungs, mostly by beta- and omega-oxidation. There is no evidence of tissue retention of alprostadil or its metabolites following IV administration.

    Other Route(s)

    Intracavernosal Route
    After intracavernosal administration, minimal systemic absorption occurs. After intracavernous injection of 20 mcg of alprostadil, peak concentrations of 16.8 +/- 18.9 pg/mL were reached within 2 to 5 minutes and decreased to endogenous plasma levels within 2 hours. The absolute bioavailability estimated from systemic exposure was 98% as compared to the same dose given by short-term IV infusion. Any alprostadil absorbed by the intracavernous route is rapidly metabolized in the lungs. After intracavernous injection of 20 mcg of alprostadil, terminal half-lives of 15-keto-PGE0 and PGE0 were 40.9 +/- 16.5 minutes and 63.2 +/- 31.1 minutes, respectively. Following intracavernosal administration, erection usually occurs within 5 to 20 minutes and may last for about 1 to several hours. Tolerance to the beneficial vascular effects does not appear to occur.
     
    Intraurethral Route
    After intraurethral administration, minimal systemic absorption occurs. Any alprostadil absorbed by this route is rapidly metabolized. Alprostadil given via the urethra is delivered directly to the urethral lining for transfer via the corpus spongiosum to the corpora cavernosa. The onset of effect is within 5 to 10 minutes after urethral administration and the duration of effect is approximately 30 to 60 minutes and will vary from patient to patient.