Alprostadil (Local)


VA CLASSIFICATION
Primary: HS200
Secondary: CV500; GU900; DX900


Note: For information pertaining to the use of alprostadil for other indications, see Alprostadil (Systemic) . When using phentolamine or papaverine also, see Phentolamine (Intracavernosal) and Papaverine (Intracavernosal) monographs for additional information.

Commonly used brand name(s): Caverject; Edex; Muse; Prostin VR; Prostin VR Pediatric.

Other commonly used names are
PGE 1 and prostaglandin E 1 .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Impotence therapy agent—

diagnostic aid, erectile dysfunction—

diagnostic aid, penile vasculature imaging—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Erectile dysfunction (treatment)—Alprostadil for Injection and alprostadil intraurethral suppositories are indicated {44} {53} and [Alprostadil Injection USP{01}]1 is used to facilitate erections in men with erectile dysfunction {04} {05} {06} {08} {09} {11} {12} {13} {32} {44}. [Low doses of a three-drug combination of alprostadil, papaverine, and phentolamine as an injection are sometimes used to achieve a synergistic action{15}{48} .]1 Erectile dysfunction that is medication-induced or caused by endocrine problems, such as hypogonadism or hyper- or hypothyroidism, should be evaluated and appropriately treated before alprostadil treatment is considered {32} {44}.

Erectile dysfunction (diagnosis) or
Penile vasculature imaging (diagnostic adjunct)—Alprostadil for Injection is indicated {44} and [Alprostadil Injection USP{01}]1 is used by intracavernosal injection as an aid in the evaluation of penile vasculature, alone or prior to angiography, cavernosography, or cavernosometry {14} {32} {44}.

Unaccepted
Use of alprostadil to enhance erections in men who are not impotent is not recommended because of the risk of priapism and permanent damage to penile tissues.

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
    Description: Suppository—Measures 1.4 millimeters (mm) in diameter and 3 mm or 6 mm in length and is located within the stem of its delivery device. A depressable button on the body of the device initiates the suppository's release from the stem. {53}
Molecular weight—
    354.49 {33}

pKa—
    6.3 {34}

Mechanism of action/Effect:

Alprostadil is a prostaglandin, specifically prostaglandin E 1, that is produced endogenously to relax vascular smooth muscle and cause vasodilation. The total prostaglandin concentration occurring naturally in human seminal fluid is 100 to 200 mg per mL and includes prostaglandins E 1 and E 2 {53}.

Impotence therapy agent—When administered by intracavernosal injection or as an intraurethral suppository, alprostadil acts locally to relax the trabecular smooth muscle of the corpora cavernosa and the cavernosal arteries. Swelling, elongation, and rigidity of the penis result when arterial blood rapidly flows into the corpus cavernosum to expand the lacunar spaces. The entrapped blood reduces the venous blood outflow as sinusoids compress against the tunica albuginea. {02} {03} {05} {08} {09} {13} {32} {53}

Adding papaverine and phentolamine to the alprostadil regimen synergistically increases arterial blood flow via separate mechanisms. Papaverine relaxes the sinusoid and the smooth muscle of the helicine arteries, while phentolamine relaxes arterial smooth muscle and blocks the alpha-adrenergic receptors that inhibit an erection. {50} {51}

Absorption:

Suppository—When inserted immediately after urination, residual urine in the urethra dissolves the urethral suppository. Within 10 minutes, alprostadil absorption occurs from the urethral lining, passing to the corpora cavernosa via the corpus spongiosum. {53}

Biotransformation:

Local, rapid {02} {05} {06} {11} {32} within the urethra, prostate, and corpus cavernosum {53}; if any alprostadil is systemically absorbed, it is metabolized by a single pass through the lungs {44} {53}.

Onset of action:

5 to 10 minutes {32} {36} {37} {38}.

Time to peak effect:

Within 20 minutes {06} {16} {32}.

Duration of action:

Injection—1 to 3 hours {08} {16} {32}; dose-related {05} {32}.

Suppository—30 to 60 minutes {53}.


Precautions to Consider

Carcinogenicity

Studies have not been done {01}.

Mutagenicity

Alprostadil is not mutagenic, according to results of the Ames test and alkaline elution assay {01} {48}.

Pregnancy/Reproduction
Fertility—
In an in vitro study of human sperm, an alprostadil concentration of 400 mcg/mL had no effect on sperm motility and viability {53}.

Sperm number, motility, and morphology were not affected in a study of dogs given intraurethral doses greater than 3000 mcg a day for 13 weeks, a dose corresponding to 3.5 times the maximum recommended human dose (MRHD) when adjusted for body surface area {53}.

Pregnancy—
Adequate and well-controlled studies in humans have not been done. Despite lack of reported problems, males using the suppositories who have sexual intercourse with pregnant women should use condoms for barrier protection to prevent maternal and fetal exposure to alprostadil. Since alprostadil's effects in early pregnancy are unknown, couples should use adequate contraception if the female partner could become pregnant. {53}

Studies of female animals indirectly exposed to the intraurethral suppository or intracavernosal injection by mating with male animals have not been done; however, direct intravaginal administration of 4000 mcg a day in pregnant rabbits (a dose corresponding to 12.5 times the MRHD) did not cause harmful effects in their fetuses. {53} Other direct routes of administration to females using doses much larger than those used for erectile dysfunction have shown embryo and maternal toxicities in pregnant animals {53}.

Suppository—FDA Pregnancy Category C {53}.

Note: An FDA category has not been assigned for the injection dosage forms.


Geriatrics


Studies in healthy men 56 years of age and older have shown results similar to those seen in younger patients, although some older men required slightly higher maintenance doses when arterial occlusive disease was present. Older patients are likely to differ from younger patients in the course and etiology of their erectile dysfunction. {17} {49}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Sympathomimetic agents, alpha-adrenergic, especially epinephrine{08} , metaraminol{06} , and phenylephrine    (sympathomimetic agents reverse the vasodilating effect of alprostadil; phenylephrine and epinephrine may be used to treat priapism or overdose)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Abnormalities of the penis, such as{44}
Anatomical deformity
Angulation of the penis
Cavernosal fibrosis
Hypospadia, severe
Peyronie's disease
Urethral stricture    (patients who have an anatomical deformity, angulation of the penis, cavernosal fibrosis, or Peyronie's disease are at increased risk of developing problems when using parenteral or intraurethral dosage forms of alprostadil {44})

    (use of urethral suppositories is not recommended in patients with urethral stricture or severe hypospadia {53})


» Balanitis or
» Urethritis    (use of urethral suppositories is not recommended because infection or inflammation may worsen, and abrasions or minor bleeding from penis may be more likely to occur {53})


Risk-benefit should be considered when the following medical problems exist
» Coagulation defects, severe{32}    (risk of bleeding may be increased because alprostadil inhibits platelet aggregation; may be especially problematic when an improperly administered suppository or injection causes either a urethral abrasion or a contusion)


» Leukemia{44} or
» Myeloma, multiple{44} or
» Polycythemia{53} or
» Priapism, history of{18} or
» Sickle cell disease{18}{32} or
» Thrombocythemia{53}    (increased risk of priapism, especially if hyperviscosity of blood or venous thrombosis results from these predisposing conditions {53})


Sensitivity to alprostadil{53}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Palpation of penis{19}{32}    (recommended at regular intervals by both the patient and the physician to check for developing fibrosis or curvature {32})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
    
Hypotension (faintness; lightheadedness)—incidence of 2%, more likely for injectable doses greater than 20 mcg{48}
    
prolonged erection (erection continuing for 4 to 6 hours)—incidence of 0.3%{48}
    
priapism (erection continuing for more than 6 hours{06}{08}{20}{32}{35}{36}{53} with severe and continuing pain of the penis)—incidence of less than 0.1%{48}
    
testicular pain or edema{53} (swelling of testes)—incidence of less than 1% with use of injection{48} and incidence of 5% with use of suppositories{53}

Note: Prolonged erection can resolve spontaneously; at times it will require treatment, especially if priapism develops. Priapism usually is due to excessive dosage.

For injection only
    
Fibrosis of penis (curving of penis with pain during erection)—incidence 5.2%{48}


Signs and symptoms of systemic absorption—associated with excessive doses
    
Dizziness {53}
    
faintness
    
hypertension, reflexive {48}
    
prostatic disorders (pelvic pain){53}
    
rapid pulse
    
respiratory infection {53}(flu-like symptoms)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Pain at site of administration{05}{10}{11}{12}{13}{32}{53}
    
penile pain during erection —incidences of 32% with use of suppository and 11% with use of injection{05}{06}{11}{18}{22}{32}{53}

For injection only
    
Bleeding at injection site, transient

For suppositories only
    
Bleeding or spotting from urethra —incidence of 5%{53}
    
stinging of urethra —incidence of 12%{53}


Note: When males used the suppository dosage form, 5.8% of female partners reported vaginal itching or stinging. These symptoms may partially result from an associated lack of recent sexual activity for these women {53}.


Incidence rare
For injection only
    
Ecchymosis or hematoma at site of injection{05}{32} (bruising or localized blood clot in penis at site of injection)—incidence of 3%, usually due to incorrect injection technique{48}






Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Alprostadil (Local) and, when also using papaverine and phentolamine, Advice for the Patient, Phentolamine and Papaverine (Intracavernosal).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to alprostadil
Other medical problems, especially abnormalities of the penis, balanitis, severe coagulation defects, leukemia, multiple myeloma, polycythemia, history of priapism, sickle cell disease, thrombocythemia, or urethritis

Proper use of this medication
» Reading patient package insert, although patient information may not be available for all products

For injection dosage forms
» Recognizing that different injection products have different mixing procedures

Proper preparation
Washing hands with soap and water; wiping tops of bottles but not needle with alcohol swab, then discarding the swab; attaching needle to the syringe if needed without taking the cap off needle

To mix
For Caverject—Adding plunger to the syringe; mixing alprostadil powder for injection with 1 mL of the diluent, Bacteriostatic Water for Injection USP, included in the packaging as a prefilled syringe or separate vial

For Edex—Adding plunger to the syringe; mixing alprostadil powder for injection with 1.2 mL of the diluent, Sodium Chloride Injection USP, included in the packaging as a prefilled syringe

For Prostin VR or Prostin VR Pediatric—Getting exact mixing instructions from the physician or pharmacist, and following them carefully if told to mix two solutions

Proper administration
» Checking that final solution is clear before measuring dose; not using if injection is cloudy, colored, or contains solids

» Drawing the correct dose into syringe; removing air bubbles; rechecking dose

» After cleansing injection site with alcohol swab, giving injection by keeping needle at a 90-degree angle to the penis while inserting and injecting slowly over 5 to 10 seconds and directly into corpus cavernosum at sides or midshaft of penis; avoiding subcutaneous administration {32} and injection into arteries or veins or injection at top or head of penis or at base of penis near the scrotum; if inadvertently injected subcutaneously (as evidenced by pain at injection site), stopping injection and withdrawing and repositioning needle

» After removing and recapping needle, applying gentle pressure at the injection site for 5 minutes to prevent bruising {32}; massaging penis as directed by physician to distribute medication

» Varying site of injection {32}

» Throwing away any unused mixture remaining in syringe; not reusing needles

For suppository dosage forms

Proper administration
» Urinating just prior to insertion; residual urine in urethra helps to dissolve the suppository

» Removing delivery device and cap from applicator stem; inserting delivery stem into urethra after lengthening and stretching penis upward; withdrawing and reinserting delivery device if discomfort or pulling sensation is felt

After depressing button to release suppository, holding delivery device still for 5 seconds, then rocking delivery device gently from side to side; after removing delivery device, inspecting the device for complete suppository release and, if needed, repeating process to insert any remaining suppository

Rolling penis between hands for 10 seconds to distribute the suppository within the walls of the urethra; continuing motion for relief if stinging occurs

Sitting, standing, or walking for 10 minutes while erection is developing to promote blood flow to the penis for a proper erection

For injection and suppository dosage forms
Effect begins in about 5 to 10 minutes {32} {36} {37} {38} {53}; attempting intercourse within 10 to 30 minutes after administration {37}. Erection may continue after ejaculation {53}
»
Proper disposal
For suppository delivery device—Replacing cap on device; placing in foil pouch; throwing away

For syringes and needles from injection—Using plastic case with locking device that comes with some packaging, or using a heavy plastic container; cutting or breaking needle before disposing; alternatively, giving to a health care professional for disposal

» Proper dosing

» Proper storage

Precautions while using this medication
» Not using medication with a penile implant unless advised by physician

» Compliance with therapy; importance of not exceeding prescribed dosage and frequency of use; risk of priapism, tissue ischemia, and permanent damage with overdose {24}

» Telling physician immediately if erection persists longer than 4 hours or becomes painful

For injection dosage forms
If bleeding occurs at injection site, applying pressure; checking with physician if bleeding persists

For suppository dosage forms
» Using a condom when having sexual intercourse with a pregnant female in order to protect the mother and fetus from exposure to alprostadil

» Using contraception when having sexual intercourse with a female of reproductive age


Side/adverse effects
Signs of potential side effects, especially hypotension; prolonged erection; priapism; testicular pain or edema; fibrosis of penis (injection only)

Signs and symptoms of systemic absorption, usually resulting from excessive doses, including dizziness, faintness, reflexive hypertension, prostatic disorders, rapid pulse, or respiratory infection


General Dosing Information
There is no information on administering alprostadil injections or suppositories to patients who also use a penile implant. {44}

Patients receiving alprostadil should be under the supervision of a physician experienced in its use and familiar with proper management of prolonged erection and priapism {32}. Medical personnel usually give the first dose(s) in a clinical setting, titrating the dose carefully according to guidelines. For all responses during the titration process, patient should remain under clinical supervision until complete detumescence occurs. Maintenance doses are usually self-administered.

Dosage adjustment should be made carefully, based on the degree and duration of tumescence achieved with the previous dose {32}. In general, patients with neurogenic erectile dysfunction may be more sensitive to the effects of intracavernosal vasodilators, and may require lower doses {05} {32}.

For injection dosage forms
In one clinical study of 579 patients having erectile dysfunction due to various etiologies, the doses after titration ranged between 5 and 20 mcg for 56% of patients; the mean maintenance dose was 17.8 mcg {44}. In an uncontrolled self-injection study, the mean maintenance dose used after 6 months was 20.7 mcg {44}. Specific to the cause of erectile dysfunction, mean maintenance doses of 12.4 mcg for psychogenic, 15.8 mcg for neurogenic, and 18.5 mcg for vasculogenic erectile dysfunction have been reported by the manufacturer. Other studies have shown similar results {46} {47}.

For treatment of erectile dysfunction, alprostadil {13} is slowly injected (over 5 to 10 seconds) {55} directly into the corpus cavernosum at the sides or midshaft {23} {25} of the penis {32}. A characteristic give should be noticed as the needle penetrates the tunica albuginea and enters the corpus cavernosum. Proper injection technique is necessary to avoid injury. Alprostadil should not be injected into the urethra, arteries, veins, scrotum, upper- or bottom-most part of the penis (top or head of penis or area on the penile shaft near the scrotum), or into the dorsal area of the penis. {31} {32}

Injection sites should be alternated {32}. After completion of the injection, pressure is applied to the injection site to prevent bleeding {32}. The entire length of the corpus cavernosum on the side receiving the injection should be squeezed firmly to distribute the medication. To uniformly distribute the medication within both corpora cavernosa, the other side also can be squeezed.

A low-dose three-drug combination injection (alprostadil, papaverine, and phentolamine) may be more effective and, in some cases, less painful than alprostadil injected alone. A thorough evaluation of comparative studies is still needed {50}. While the doses used in studies vary, an accepted strength is 17.6 mg papaverine, 0.6 mg phentolamine, and 5.9 mcg alprostadil per mL. The amount prescribed for self-injection is titrated according to individual response. {15} {48}

For suppository dosage form
In two placebo-controlled, parallel group studies of 1511 patients with erectile dysfunction, 996 patients (66%) completed the titration process; some patients could not complete the titration process because of accompanying penile pain. Of the 874 patients completing 3 months of treatment, doses for about 10, 20, 30, and 40% of patients were titrated to 125, 250, 500, and 1000 mcg, respectively {53} {54}.

Prior to inserting the intraurethral suppository, the patient should urinate; the residual urine remaining in the urethra will help dissolve the suppository {53} {54}.

The delivery device is inserted into the urethra with ease after the penis is first stretched lengthwise and pressed at top and bottom. After depressing a button to release the suppository into the urethra, the device is held upright and immobile for 5 seconds to help dissolve the suppository. Moving the device and the penis as a unit gently side to side helps to dissolve the suppository and enhances its release from the device. Whenever the patient feels an uncomfortable or pulling sensation, the delivery system should be removed and the procedure repeated if needed. Also, the procedure can be repeated to insert a partial suppository not fully dislodged from the device {53}.

After the delivery device is withdrawn, the patient should roll his penis between his hands for 10 seconds to further distribute the suppository within the walls of the urethra and to ease any stinging sensation. Sitting, standing, or walking for 10 minutes while erection is developing promotes blood flow. {53}

Use of contraception is recommended by the manufacturer if the patient engages in sexual intercourse with a female of reproductive age because potential effects on early pregnancy are not known. Using a condom is recommended when having sexual intercourse with a pregnant female; it provides a barrier and protects the mother and fetus from the effects of alprostadil. {53}

For treatment of prolonged erection or priapism
A prolonged erection should be treated if it persists longer than 4 hours {32}; priapism should be treated promptly {32}. If tumescence is not reversed, interruption of blood flow may result in penile tissue ischemia and permanent tissue damage.

Treatment of adverse effects should be initiated by a physician trained in treating drug-induced tumescence. Depending on the severity, treatment may include:    • Application of ice packs to inner thigh, alternating between thighs, for no more than 10 minutes to shorten the duration of a prolonged erection {53}.
   • Aspiration of intracavernosal blood {32}.
   • Intracavernosal administration of an alpha-adrenergic agonist; phenylephrine is preferred to epinephrine. While monitoring blood pressure, an injection of 0.5 mg/mL Phenylephrine Hydrochloride Injection USP is given, followed by a second dose, if needed, in 15 minutes. {32}
   • Irrigation of the corpus cavernosum with 0.9% Sodium Chloride Irrigation USP or 20 mL of dilute solutions of phenylephrine (20 mg Phenylephrine Hydrochloride Injection USP in 500 mL of 0.9% Sodium Chloride Irrigation USP) or epinephrine (1 mL 1:1000 Epinephrine Injection USP in 1 liter of 0.9% Sodium Chloride Irrigation USP), using a 19-gauge needle to remove clotted blood {31} {48}.
   • Surgery (rarely needed) {32}.



Intraurethral Dosage Forms

ALPROSTADIL SUPPOSITORIES

Usual adult dose
Impotence therapy agent
Initial: Intraurethral, 125 or 250 mcg a day, followed by dose adjustments in stepwise fashion on separate occasions as instructed by a physician {53} {54}.
Maintenance: Intraurethral, an individual dose established by a physician is inserted by the patient between ten and thirty minutes before intercourse. Dosage adjustments require physician consultation. No more than two suppositories should be used within twenty-four hours. {53} {54}


Strength(s) usually available
U.S.—


125 mcg (Rx) [Muse (polyethylene glycol)]{53}


250 mcg (Rx) [Muse (polyethylene glycol)]{53}


500 mcg (Rx) [Muse (polyethylene glycol)]{53}


1000 mcg (Rx) [Muse (polyethylene glycol)]{53}

Canada—
Not commercially available.

Note: The unit-dose packaging includes a suppository and delivery device; six unit-dose packages are contained in one box. {53}


Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F), unless otherwise specified by manufacturer. Protect from freezing. May be stored between 15 and 30 °C (59 and 86 °F) for up to fourteen days {53}.

Auxiliary labeling:
   • Refrigerate.
   • Do not freeze.

Note: Include patient package insert (PPI) when dispensing {53}.




Parenteral Dosage Forms

Note: Bracketed information in the Dosage Forms section refers to uses that are not included in U.S. product labeling.

ALPROSTADIL INJECTION USP

Usual adult dose
[ Impotence therapy agent]1


For patients with erectile dysfunction of penile vasculogenic or mixed etiology:
Initial—Intracavernosal, 2.5 mcg, followed by dosage adjustments as supervised by a physician according to patient response. The proper dose will produce a full erection that begins within five to twenty minutes, and lasts for no more than one hour. If an erection lasts longer than one hour, the dose should be reduced. Further dosing depends on whether the first dose produced a partial or no erectile response. {44}

• For patients partially responding to the first dose, 7.5 mcg can be injected twenty-four hours or longer following the first dose. Until the proper dose is established, further doses scheduled on no more than two consecutive days (twenty-four hours apart) or three times a week can be increased by 5- to 10-mcg increments thereafter until an erection suitable for intercourse is achieved. {44}


• For patients not responding to the first dose, 5 mcg more can be injected within the hour, resulting in a total daily dose of 7.5 mcg. Until proper dose is established, further doses scheduled on no more than two consecutive days (twenty-four hours apart) or three times a week can be increased by 5- to 10-mcg increments. {44}


Maintenance—Intracavernosal, an individual dose established by a physician is injected by the patient ten to thirty minutes before intended intercourse. Alprostadil should not be used more often than three times a week or on more than two consecutive days; at least twenty-four hours should elapse between doses. Dosing adjustments require physician-patient consultation. {44}

Note: For patients using a three-drug regimen, 0.25 mL (17.6 mg papaverine, 0.6 mg phentolamine, and 5.9 mcg alprostadil per mL) is the usual dose achieved after completing the titration process {48}.




For patients with erectile dysfunction of psychogenic or neurogenic etiology:
Initial—Intracavernosal, 1.25 mcg, followed by dosage adjustments as supervised by the physician according to patient response. The proper dose will produce a full erection that begins within five to twenty minutes, and lasts for no more than one hour. If an erection lasts longer than one hour, the dose should be reduced. Further dosing depends on whether the first dose produced a partial or no erectile response. {44}

• For patients partially responding to the first dose, 2.5 mcg can be injected twenty-four hours or longer following the first dose. Until the proper dose is established, further doses scheduled on no more than two consecutive days (twenty-four hours apart) or three times a week can be increased by 5-mcg increments thereafter until an erection suitable for intercourse is achieved {44}.


• For patients not responding to the first dose, 1.25 mcg more can be injected within the hour, resulting in a total daily dose of 2.5 mcg. Until proper dose is established, further doses scheduled on no more than two consecutive days (twenty-four hours apart) or three times a week can be increased by 5-mcg increments. {44}


Maintenance—Intracavernosal, an individual dose established by a physician is injected by the patient ten to thirty minutes before intended intercourse. Alprostadil should not be used more often than three times a week or on more than two consecutive days; at least twenty-four hours should elapse between doses. Dosing adjustments require physician-patient consultation. {44}

Note: For patients using a three-drug regimen, 0.12 mL (17.6 mg papaverine, 0.6 mg phentolamine, and 5.9 mcg alprostadil per mL) is the usual dose achieved after completing the titration process {48}.



Diagnostic aid adjunct (penile vasculature imaging)1 or
Diagnostic aid (erectile dysfunction)1
Intracavernosal, the lowest single dose to cause an erection of firm rigidity {44}.

Note: These patients are more likely to develop priapism that may require penile aspiration {46}.



Usual adult prescribing limits
Impotence therapy agent
60 mcg (0.06 mg) of alprostadil per dose {29}.


Strength(s) usually available
U.S.—


500 mcg (0.5 mg) per mL (Rx) [Prostin VR Pediatric (dehydrated alcohol)]

Canada—


500 mcg (0.5 mg) per mL (Rx) [Prostin VR (dehydrated alcohol )]

Note: Distribution of Prostin VR Pediatric in the U.S. and Prostin VR in Canada is limited to acute-care facilities. As an alternative, compounding from bulk products is being done to make a multidose vial, single-use vials, or prefilled syringes; use of filters and preservatives should be considered as needed. {52}


Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F), unless otherwise specified by manufacturer. Protect from freezing.

Preparation of dosage form:
To prepare a solution of 20 mcg/mL of alprostadil, inject 1 mL of 500 mcg/mL Alprostadil Injection USP and 4 mL of 0.9% Sodium Chloride Injection USP into an empty vial to make a 100 mcg/mL alprostadil intermediate solution. After mixing, inject a 1-mL aliquot of 100 mcg/mL Alprostadil Injection USP into five 5-mL multidose vials. To make a 20 mcg/mL alprostadil solution, add 4 mL of 0.9% Sodium Chloride Injection USP to each vial. This multidose vial may be dispensed or separated into five 1-mL single-use vials or five 1-mL prefilled syringes. {15} {52} Other concentrations may be appropriate {51}.

Stability:
Stability after dilution is unknown {12} {32}.

Auxiliary labeling:
   • Refrigerate.
   • Do not freeze.


ALPROSTADIL FOR INJECTION

Usual adult dose
Impotence therapy agent or
Diagnostic aid adjunct (penile vasculature imaging) or
Diagnostic aid (erectile dysfunction)
See Alprostadil Injection USP .


Usual adult prescribing limits
Impotence therapy agent
See Alprostadil Injection USP .


Size(s) usually available:
U.S.—


5 mcg (0.005 mg) (Rx) [Caverject (benzyl alcohol 8.4 mg) (lactose 172 mg) (sodium citrate 47 mg {44})]


10 mcg (0.01 mg) (Rx) [Caverject (benzyl alcohol 8.4 mg) (lactose 172 mg) (sodium citrate 47 mg {44})] [Edex (alpha-cyclodextrin ) (lactose anhydrous 56.3 mg){55}]


20 mcg (0.02 mg) (Rx) [Caverject (benzyl alcohol 8.4 mg) (lactose 172 mg) (sodium citrate 47 mg {44})] [Edex (alpha-cyclodextrin ) (lactose anhydrous 56.3 mg){55}]


40 mcg (0.04 mg) (Rx) [Edex (alpha-cyclodextrin) (lactose anhydrous 56.3 mg){55}]

Canada—


10 mcg (0.01 mg) (Rx) [Caverject (benzyl alcohol 8.4 mg) (lactose 172 mg) (sodium citrate 47 mg {45})]


20 mcg (0.02 mg) (Rx) [Caverject (benzyl alcohol 8.4 mg) (lactose 172 mg) (sodium citrate 47 mg {45})]

Note: For the prefilled syringe—The 5-, 10-, and 20-mcg strengths of Caverject and all strengths of Edex include in their packaging a single-use vial containing sterile alprostadil powder, prefilled diluent syringe and needle (22-gauge, 11/2-inch needle {44}; or 27- {44} {55} or 30-gauge {55}, 1/2-inch needle), separate syringe plunger, and alcohol swabs {44} {55}. Needle may {44} or may not {55} be attached to the syringe.
For the single-use vials—The 10- and 20-mcg strengths of Caverject include in their packaging a single-use vial containing sterile alprostadil powder, a vial of diluent, and a preassembled 3-cc, 27-gauge {45}, 1/2-inch syringe {45}.
For each product—Six unit-dose packages are contained in one box {45} {55}.


Packaging and storage:
Store between 15 and 25 °C (59 and 77 °F). Protect from freezing. {44} {55}

Preparation of dosage form:
Alprostadil for Injection is prepared by adding diluent to a vial of sterile alprostadil powder. The diluent is packaged as a prefilled syringe or in a separate vial. Solution is mixed, then drawn using the same syringe. {44}

For Caverject: Add 1 mL of diluent (Bacteriostatic Water for Injection USP containing benzyl alcohol) to a vial of sterile alprostadil powder {44}.

For Edex: Add 1.2 mL of diluent (Sodium Chloride Injection USP) to a vial of sterile alprostadil powder {55}.

Stability:
Stability of the medication after dilution is unknown. The manufacturer recommends that the reconstituted solution be used immediately {44} {55}.

Auxiliary labeling:
   • Store in a cool, dry place.
   • Do not freeze.

Note: Include patient package insert (PPI) for Alprostadil for Injection when dispensing {44} {45}.




Revised: 09/26/2000



References
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  1. Virag R. Human penile erection: an extensive study of the effects of vasoactive compounds on the cavernous tissue and the penile arteries [abstract 311]. J Urol 1985; 133(Pt 2): 191A.
  1. Virag R, Adaikan PG. Effects of prostaglandin E1 on penile erection and erectile failure [letter]. J Urol 1987 May; 137: 1010.
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  1. Panel comments, 1990 revision.
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  1. Manufacturer comment, 6/30/89.
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  1. Personal communication, 11/13/91.
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  1. Diagnostic and Therapeutic Assessment (DATA). Vasoactive intracavernous pharmacotherapy for impotence: intracavernous injection of prostaglandin E1. JAMA 1991; 265(24): 3321-3.
  1. Reviewer comment, 4/92.
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  1. Panel comment, 5/96.
  1. Wu CCJ, Xue Z-Y, Apichat K, et al. The use of alprostadil sterile powder in a home self-injection study of Asian men with erectile dysfunction. Clin Ther 1996: 18(2): 256-64.
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  1. Muse package insert (Vivus—US), Rev 11/96, Rec 12/96.
  1. Padma H, Hellstrom WJG, Kaiser FE, et al. Treatment of men with erectile dysfunction with transurethral alprostadil. N Engl J Med 1997 Jan; 336(1): 1-7.
  1. Edex package insert (Schwarz—US), Rev 6/96, Rec 7/97.
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