Caverject 20 mcg
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Caverject (ka-ver-jekt) is used to treat men who can not achieve and/or maintain an erection. Caverject Sterile Powder, which contains alprostadil (al-pros-ta-dil), is available by prescription only and should be used only as directed by your doctor. Your doctor may also use Caverject to help establish the cause of your impotency (or erectile dysfunction).
In response to visual or physical sexual stimulation, the nerves, arteries and veins in your penis act together to create an erection. The nerves cause the smooth muscle of the penis to relax and the blood vessels to expand. The blood becomes trapped in the penis and this allows your penis to become hard and erect.
When Caverject is injected into the blood-filled spaces of the penis (corpora cavernosa; kor-po-rah ka-ver-no-sa) it relaxes the smooth muscle of the penis. This allows more blood to flow into the penis and gives you an erection.
When to Use Caverject
You can use Caverject anytime before sexual intercourse. Caverject is injected into a specific area of the penis and should produce an erection in 5 to 20 minutes. Using the dose recommended by your doctor, you should have an erection lasting up to 1 hour. You may use Caverject for as long as your doctor decides is necessary. Do not use Caverject more than once a day, and not more than 3 times a week, with at least 24 hours between each use.
The Best Dose for You
Impotence can have a variety of causes that will be assessed by your doctor. The right dose of Caverject will depend on the nature of your impotence. Also, some people are more sensitive to the effects of Caverject than others. Your doctor must therefore find the best dose for you. To do this, your doctor will give you an initial injection, then slowly increase the dose for the next injections until the lowest dose for an effective erection is found. The maximum daily dose should not be greater than 60 µg.
Home Use of Caverject
After your doctor has assessed the correct dose, you will receive your first few injections in the doctor's office so you (or your partner) can receive training on how to inject yourself safely and hygienically. Once your doctor is assured that you (or your partner) are comfortable with the procedure (and can properly use sterile technique) home therapy can be started.
Caverject is supplied with everything you need, including complete instructions, plus diagrams, to help you.
During treatment, you may need your dose adjusted. Never increase or decrease the dose yourself without consulting your doctor. In fact, it is important to visit your doctor regularly, at least every 3 months during therapy, to ensure Caverject is working safely and effectively.
Who Should Not Use Caverject
Caverject should not be used if you have an allergy to any of its ingredients (lactose monohydrate, sodium citrate dihydrate, benzyl alcohol), or if you have a medical condition such as sickle cell anemia or trait, or certain cancers (e.g., multiple myeloma or leukemia) which might make you prone to painful and excessively long erections known as priapism (pri-ah-pizm).
Caverject should not be used by men who have been advised by their doctor to avoid sexual activity.
Do not use Caverject if you have a penile implant or a deformed penis (e.g., angulation, fibrosis, Peyronie's disease). Check with your doctor if you are not sure if you have or had any of these conditions.
Caverject is for use in men only, and should not be used in women or children. Caverject is only for use in treating impotence; do not use Caverject for other conditions.
Protect Yourself and Others
Always keep medications out of the reach of children. Do not save outdated medicine or medicine no longer needed. Do not use if solution is cloudy, colored or contains particles.
Caverject will not protect you from sexually transmitted diseases (including the human immunodeficiency virus, HIV). An injection of Caverject may cause a small amount of bleeding at the injection site. If you are infected with a blood-borne disease, even a little bleeding may increase the risk of passing blood-borne diseases to your partner(s). Take protective measures at all times.
What You Should Know Before Using Caverject
Substances like Caverject act on the blood vessels and may (when injected directly into the corpora cavernosa of the penis) lead to erections that last a long time and which may be painful and tender (priapism). An erection lasting longer than 3 hours is not a “normal” length of time for the penis to stay rigid. If this occurs, you have probably overdosed. Report this to your doctor immediately. Treat as a medical emergency.
If you are taking medication to prevent blood clotting, (such as warfarin or heparin) you may experience bruising at the injection site. To help prevent this, press down on the injection site with your thumb and hold for 5 minutes.
Discuss with your doctor the use of other medications (both prescription and nonprescription) while taking Caverject.
There is no apparent injectable treatment using multiple drug ingredients or “cocktail” for erectile dysfunction. In addition, there are no data on the efficacy and safety of these combinations.
What You Should Do if You Experience a Prolonged Erection
If you have an erection lasting longer than 2 hours, try to reduce the erection using methods suggested by your doctor. Do not wait, it is easier to reduce the erection if you treat it earlier rather than later. Erections that last more than 6 hours can cause serious and permanent damage.
If your penis is still hard after 3 hours, see your doctor immediately or go to emergency. Write on a piece of paper the name of the drug, the dose and the time you took it and bring this with you to emergency.
Adverse Reactions from Using Caverject
The most common adverse effect is mild to moderate pain in the penis after injection or during an erection. About one-third of patients experience this effect. Other patients may experience a “burning sensation”, “discomfort” or “tension” in the penis.
Occasionally you may have blood blisters (hematoma, ecchymosis) at the site of injection. These relate to improper injection technique rather than the effects of Caverject. If this occurs, ask your doctor to re-instruct you. Pressing down on the injection site will help avoid blood blisters.
Other local adverse effects include: fibrosis (formation of scar tissue in the penile tissues), irritation, sensitivity, penile rash and penile edema (fluid in the tissues).
Rarely occurring are: pain in the testicles or at the base of the penis, erythema (redness of the skin), penile lumps, tenderness, abnormal ejaculation, curved erections, balanitis (inflammation of the tip of the penis) and itching, swelling, inflammation or bleeding at the injection site, urethral bleeding and injuries resulting from poor injection technique.
Rare whole-body effects include: changes in blood pressure, irregular heartbeat, increased pulse rate, dizziness, headache, faintness.
Call your doctor if you notice any of the above or if you experience anything not listed here. Tell your doctor if you have a condition or are taking a medicine that interferes with blood clotting.
Guide to the Correct Use of Caverject (see package insert for illustrations)
The information provided below only applies to the self-injection of Caverject. Do not use these methods for taking any other medication.
This guide does not replace the advice of your doctor. If you have any questions, please ask your doctor.
A case of Caverject has enough drug for 1 injection. The number of cases you need will depend on the length of your therapy.
Caverject Case Supplies
Each blue plastic case contains the following:
One vial of Caverject sterile powder in strengths of 20 µg. Ensure you have the correct strength Caverject vial for your dosage.
One prefilled syringe containing bacteriostatic water. This is sterile water containing a preservative and is used to dissolve Caverject. This solution does not contain active drug. You will use this syringe after attaching the needle, to inject the drug into your penis.
A 27 gauge, 0.5-inch needle. Keep the plastic cover on the needle until ready to inject.
Two alcohol swabs. It is important to use the swabs to provide hygienic conditions and prevent infection.
Storage and Handling
You can store unused vials of Caverject Sterile Powder between 2 to 30°C. Do not freeze.
Do not use vials after the expiry date listed on the label.
Once dissolved, the Caverject solution must be used immediately. Do not freeze solution.
Use contents of each vial only once. Throw out unused solution. See “Disposal of Used Materials” at the end of this guide.
Important: Failure to comply with the following antiseptic measures may lead to infection.
To ensure sterile conditions, never contaminate the needle. The disposable needle and syringe require no sterilization steps if the package is intact.
Do not reuse needles or syringes. Do not give used needles or syringes to others.
Self-injection Method: Preparing Caverject
Wash your hands thoroughly with soap and water.
Pull back on tabs of needle package to expose open end of needle. Do not let this end touch any surface.
Hold syringe tip upwards and remove rubber end cover. Continue to hold syringe upright in one hand. With free hand, pick up needle by covered end.
With needle cover still on, attach open end of needle to syringe tip by pushing down and twisting into place. Make sure the needle fits tightly.
Remove the plastic cap from the vial.
Wipe the rubber stopper of the vial, using one of the swabs provided. Discard the used swab (the second swab is needed later).
Handle the syringe by the barrel only. Remove needle cover carefully from the syringe. Do not allow needle to touch any surface.
Holding the syringe with needle pointing upward, push plunger to the 1-cc (mL) line marked on the syringe. (This will remove a slight amount of overfill in the syringe.)
Pierce needle through the centre portion of the vial's rubber cap. Push down plunger and inject entire contents of syringe (bacteriostatic [bak-te-reo-stat-ik] water) into the vial.
Carefully hold syringe and vial as a unit, and gently swirl the two (do not shake) until the powder dissolves completely. Do not use if the resulting solution is cloudy or colored, or if it contains particles.
To withdraw the medication, turn the vial (and syringe) upside down. Keep tip of needle below the level of the fluid. Then slowly withdraw syringe plunger until the amount of solution is level with the line recommended by your doctor.
If there are air bubbles in the syringe, tap syringe gently to remove them, or inject the solution back into the vial and slowly withdraw again.
Remove needle from bottle and carefully replace needle cover. Do not puncture the vial more than once, you could contaminate the solution.
The medication must be injected into either of two areas of the corpora cavernosa (spongy tissue of penis). The corpora cavernosa run down both sides of the penis.
Follow these instructions carefully to ensure you inject the medication correctly:
Perform the self-injection while sitting in an upright or slightly reclining position and under good lighting.
Only use the injection areas described above. Do not inject the very top or underside of your penis. Change the injection site each time you use Caverject. (i.e., choose the right side for this injection, use the left side next time, and so on.) Within either area, the injection point should also be changed each time.
Grasp the head of your penis with your thumb and forefinger. Stretch your penis tautly and hold it firmly against your thigh so that it does not slip. In uncircumcised men, the foreskin must be pulled back to assure proper placement of the injection.
Clean the injection area thoroughly with a new alcohol swab. Put swab to one side; you will need to use it again.
Hold syringe between thumb and index finger. Do not put your thumb on the plunger. With syringe at a right angle (90°) to your penis, insert needle to penetrate the skin at the injection site. This is a sensitive area, so expect a little discomfort. Avoid any area where veins are clearly visible.
Once the needle pierces the skin and resistance is felt, push needle firmly forward until a distinct “give” is felt and insert the needle all the way in with a steady, continuous motion.
Move your thumb or forefinger to the top of plunger and press down. Inject the entire contents of the syringe using a slow, steady motion.
Withdraw the needle from your penis and replace needle cover. Squeeze both sides of your penis immediately, and apply pressure with the alcohol swab to the injection site for about 3 minutes. If bleeding occurs, maintain pressure until the bleeding stops.
As long as you use your doctor's recommended dose, expect an erection to occur within 5 to 20 minutes after an injection.
A standard treatment goal is to produce an erection lasting up to an hour. If an erection is extremely painful (or persists after 3 hours) or if you have other adverse effects that concern you, consult your doctor immediately.
Information for the Patient
Absorption: The absolute bioavailability of alprostadil following intracavernosal injection has not been determined.
Distribution: Following a 20 µg intracavernosal injection of alprostadil, mean peripheral plasma concentrations of alprostadil were 89 pg/mL and 102 pg/mL at 30 and 60 minutes post-injection respectively, which were not significantly greater than baseline levels of endogenous alprostadil at 96 pg/mL. Alprostadil is bound primarily to plasma albumin (81%) and to a lesser degree to α-globulin IV-4 fraction (55%). No significant binding could be demonstrated with erythrocytes or white cells.
Metabolism: Alprostadil is rapidly converted to compounds which are further metabolized prior to excretion. In man, a single pass through the lung effectively metabolizes approximately 80% of the available PGE1 primarily by beta- and omega-oxidation. Therefore, any alprostadil which may enter the systemic circulation following intracavernosal injection is rapidly metabolized. However, pulmonary clearance of PGE1 can be affected by disease states such as acute respiratory distress syndrome (ARDS), with a resultant reduction in the pulmonary extraction ratio.
After intracavernosal administration of 20 µg of alprostadil, peripheral levels of the primary metabolite 15-oxo-13,14-dihydro-PGE1 increased, reaching a peak at 30 minutes and falling to pre-dose levels by 60 minutes post-injection.
Excretion: The major route of elimination of the metabolites of alprostadil is through the kidney. Urinary excretion of an i.v. dose is essentially complete (90%) within 24 hours of administration. The remainder of the dose is excreted in the feces. There is no evidence to suggest any tissue retention of PGE1 or its metabolites after an i.v. administration.
Pharmacokinetics in Special Populations: Geriatrics: The potential effect of age on the pharmacokinetics of alprostadil has not been formally evaluated. In patients with ARDS, the mean (±SD) pulmonary extraction of alprostadil was 72%±15% in 11 elderly patients aged 65 years or older (mean 71±6 years) and 65%±20% in 6 young patients aged 35 years or younger (mean 28±5 years).
Children: Plasma alprostadil concentrations were evaluated in 10 neonates (gestational age 34 weeks in 2 infants and 38 to 40 weeks in 8 infants) receiving steady-state i.v. infusions of alprostadil to treat underlying cardiac malformations. Alprostadil infusion rates ranged from 5 to 50 ng/kg/min (median 45 ng/kg/min), with resultant plasma concentrations in the range of 22 to 530 pg/mL (median 56 pg/mL). The individual clearance of alprostadil in neonates is highly variable as reflected by the wide range of plasma concentrations observed.
Gender: The influence of gender on the pharmacokinetics of alprostadil has not been formally studied. Two studies evaluated pulmonary extraction in 23 patients with ARDS following i.v. administration of alprostadil. The 17 males had a pulmonary extraction of 66% compared to 69% in the 6 female patients, suggesting no gender influence.
Race: The influence of race on the pharmacokinetics of alprostadil has not been formally studied.
Renal and Hepatic Insufficiency: The effects of renal and hepatic insufficiency on the pharmacokinetics of alprostadil have not been formally studied. Since systemic clearance of alprostadil is primarily by first-pass metabolism through the lungs, it is not expected that altered renal or hepatic function will have a major influence on the pharmacokinetics of alprostadil.
Pulmonary Disease: In one study, pulmonary extraction of alprostadil given i.v. was found to be reduced by 15% in patients with ARDS (66%) compared to patients with normal respiratory function (78%). In a second study of 14 patients with ARDS or at risk of developing ARDS, the mean extraction efficiency of alprostadil was 67% ranging from subnormal (11%) to normal (90%).
For the intracavernosal treatment of erectile dysfunction due to neurogenic, vasculogenic, psychogenic, or mixed etiology. Intracavernosal alprostadil may also be useful as an adjunct to diagnostic tests in the diagnosis of erectile dysfunction.
The potential for pharmacokinetic drug-drug interactions between alprostadil and other agents has not been formally studied.
Underlying treatable medical causes of erectile dysfunction must be diagnosed and treated prior to initiating therapy with alprostadil.
The results of clinical studies with alprostadil indicate an overall incidence of penile fibrosis, including Peyronie's disease, of 3% (55/1 861). In one long-term (up to 18 months duration) self-injection study, the incidence of fibrosis reported was 7.8% (53/683). Regular follow-up of patients, with careful examination of the penis, is strongly recommended to detect signs of penile fibrosis. Treatment with alprostadil should be discontinued in patients who develop penile angulation, cavernosal fibrosis or Peyronie's disease.
Patients on anticoagulants such as warfarin or heparin may have an increased propensity for bleeding after intracavernosal injection.
An injection of alprostadil can induce a small amount of bleeding at the injection site (see Adverse Effects—hematoma, ecchymosis, hemorrhage). In patients infected with blood-borne diseases, this may increase the transmission of blood-borne diseases between partners.
The safety and efficacy of combinations of alprostadil and other vasoactive agents have not been systematically studied. Therefore, the use of such combinations is not recommended.
Patients using a self-injection program of therapy should receive proper instruction in both intracavernosal injection and aseptic technique (see Information for the Patient). Physicians should ensure that patients are able to demonstrate competence and skill with the injection procedure prior to initiating self-injection.
The initial treatment dose is established in the physicians office. The lowest effective dose sufficient to induce an erection lasting up to 1 hour should be used. The patient may expect an erection to occur within 5 to 20 minutes. Patients who require dosage adjustments and are self-injecting alprostadil, should not increase or decrease their dose without the advice of their physician. Generally, patients should not use alprostadil more than once a day and not more than 3 times a week, with at least 24 hours between each use.
Alprostadil is labelled for “single use only”. Patients should discard any unused solution after withdrawing the proper volume for their dose. The vial should not be shaken once reconstituted.
Reconstituted vials of alprostadil which on visual inspection appear cloudy, colored or contain particulate matter, should be discarded.
Patients who experience an erection lasting longer than 2 hours should attempt to detumesce using methods prescribed by their physician.
Patients should be advised on the possible adverse effects associated with the use of alprostadil; the most frequent being mild to moderate penile pain after injection. A patient should report to his physician if he complains of: any penile pain not previously present, an increased intensity of pain, nodules or hard tissue appearing in the penis, or curvature of the erect penis. There is the potential for infection with any type of injection, therefore patients should also report any occurrences of penile redness, swelling, or tenderness. The importance of regular physician visits to assess the continued safety and efficacy of alprostadil treatment should be stressed to the patient.
A potentially serious adverse reaction with intracavernosal therapy is priapism. Accordingly, the patient should be instructed to contact the physician's office immediately or, if unavailable, to seek immediate medical assistance if an erection persists for longer than 3 hours.
In clinical trials, the use of concomitant medicines such as antihypertensives, diuretics, antidiabetic agents (including insulin) or NSAIDs, did not affect the safety or efficacy of alprostadil.
The use of alprostadil intracavernosally does not offer any protection from the spread of sexually transmitted diseases. Individuals using alprostadil should be properly counselled with regards to protective measures to safeguard against the spread of sexually transmitted diseases, including human immunodeficiency virus (HIV) infection.
Patients should be instructed not to reuse or share needles or syringes. The patient should not allow anyone else to use this medicine. Patients should dispose of used needles, syringes, and vials, safely and properly (see Information for the Patient).
A patient administration guide, found in every package, provides a step-by-step method for the proper preparation and administration of alprostadil. Patients should be instructed to carefully follow this guide for self-injection.
Long-term carcinogenicity studies have not been conducted. Reproductive studies in the rat with alprostadil at doses of up to 0.2 mg/kg/day did not adversely affect or alter spermatogenesis, conferring a 200-fold margin of safety at usual human doses. A battery of mutagenicity assays including, bacterial mutation (Ames), alkaline elution, rat micronucleus, sister chromatid exchange, CHO/HGPRT mammalian cell forward gene mutation and unscheduled DNA synthesis (UDS), revealed no potential for mutagenesis.
A one-year irritancy study was conducted in male Cynomolgus monkeys. Three groups of 5 animals received twice weekly intracavernosal injections of either 3 or 8.25 µg alprostadil or vehicle. A further 2 groups of 6 animals were given 8.25 µg alprostadil or vehicle twice weekly, as above, and in addition, multiple doses during weeks 44, 48 and 52. Three monkeys receiving vehicle and 3 monkeys receiving 8.25 µg alprostadil were held for evaluation following a 4-week recovery period. No evidence of alprostadil-related penile or systemic tissue lesions were found. Local irritation noted in control and treated monkeys was considered to be related to the injection procedure itself and any penile lesions found were reversible. After the 4-week recovery period, a regression in histological changes in the penis was observed.
Each case contains: a single dose vial of alprostadil 20 µg sterile powder, 1 mL prefilled syringe of BWFI diluent, a 27-gauge 0.5 inch needle, 2 alcohol swabs and Patient Administration Leaflet. These cases are fitted with a lock designed for safe and convenient disposal of the contents after use. Once reconstituted, each mL contains: alprostadil 20 µg, lactose monohydrate 172 mg, sodium citrate dihydrate 47 µg, benzyl alcohol 8.4 mg, and sterile water for injection q.s. Cartons of 5.
Each single-dose vial contains: alprostadil 20 µg sterile powder. Packs of 5.
The unreconstituted lyophilized sterile powder (20 µg vials) should be stored between 2 to 30°C.
Patients with a known hypersensitivity to the drug. Patients who have any condition that may predispose them to priapism such as sickle cell anemia or trait, multiple myeloma or leukemia. Patients with anatomical deformations of the penis, such as angulation, cavernosal fibrosis, Peyronie's disease. Patients with penile implants.
Caverject should not be used in women or children and is not for use in newborns.
Alprostadil should not be used in men for whom sexual activity is inadvisable or contraindicated.
Prolonged erection (4 to 6 hours) and/or priapism (>6 hours) are known to occur following intracavernosal administration of vasoactive substances, including alprostadil. In clinical studies, prolonged erection occurred in 4% of patients and 0.4% experienced priapism.
The patient should be instructed to immediately report to his physician, or if unavailable, to seek immediate medical assistance for an erection persisting more than 3 hours. Treatment of prolonged erection/priapism should be according to established medical practice (see Overdose, Symptoms and Treatment). If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result.
In the majority of cases, spontaneous detumescence occurred. To minimize the chances of prolonged erection or priapism, alprostadil should be titrated slowly to the lowest effective dose (see Dosage).
Local Adverse Events: The following local adverse events (see Table 1) were reported from controlled and uncontrolled clinical trials, including an uncontrolled 18-month safety study.
Table 1: Caverject
|Local Event |
(Reported in ≥1% of Patients)
|No. (%) of Patients |
|Pain after injection||580||(31)|
|Pain at the injection site||370||(20)|
|Prolonged erection (4-6 h)||82||(4)|
|Injection site hematoma||63||(3)|
|Injection site ecchymosis||32||(2)|
b. Includes numbness, yeast infection, irritation, sensitivity, phimosis, pruritus, erythema, venous leak, penile skin tear, strange feeling in penis, burning sensation in penis and itch at tip of penis.
Penile Pain: Penile pain after intracavernosal administration of alprostadil was reported at least once by 37% of patients in clinical studies of up to 18 months in duration. The intensity of pain was rated mild or moderate in the majority of cases. Three percent of patients discontinued treatment because of penile pain. The frequency of penile pain was 2% in 294 patients who received 1 to 3 injections of placebo.
Prolonged Erection/Priapism: In clinical trials, prolonged erection was defined as an erection that lasted for 4 to 6 hours; priapism was defined as an erection that lasted 6 hours or longer (see Warnings).
Hematoma/Ecchymosis: The frequency of hematoma and ecchymosis was 3 and 2%, respectively. In most cases, hematoma/ecchymosis was judged to be a complication of a faulty injection technique. Accordingly, proper instruction of the patient in self-injection is of importance to minimize the potential of hematoma/ecchymosis (see Dosage).
Local events observed in <1% of the patients include: balanitis, lack of efficacy, injection site hemorrhage, injection site inflammation, injection site itching, injection site reaction, injection site swelling, injection site edema, trauma, urethral bleeding, urethral disorder, penile hematoma, penile warmth, priapism (>6 h), numbness, yeast infection, irritation, sensitivity, phimosis, pruritus, erythema, venous leak, painful erection and abnormal ejaculation.
Systemic Adverse Events: The following systemic adverse event information (see Table 2) was derived from controlled and uncontrolled studies, including an uncontrolled 18-month safety study.
Table 2: Caverject
| Systemic Eventa by Body Systemb |
(Reported in ≥1% of Patients)c
|No. (%) of Patients |
|Body as a Whole||245||(13)|
|Upper respiratory infection||76||(4)|
|Localized abdominal pain||10||(<1)|
|Urinary tract infection||16||(<1)|
|Skin and Appendages||49||(3)|
b. Number (%) patients reporting a drug-related event within body system, with patients reporting more than one event within the body system counted only once.
c. No significant adverse events were reported by 294 patients who received 1 to 3 injections of placebo.
d. Includes injuries, fractures, abrasions, lacerations, dislocations.
e. Includes pain in various anatomical structures other than injection site.
f. Includes prostatitis, pain, hypertrophy, enlargement.
Systemic events reported in 1% of patients and judged by investigators to be possibly related to the use of alprostadil include: testicular pain, scrotal disorder, scrotal edema, hematuria, testicular disorder, impaired urination, urinary frequency, pelvic pain, hypotension, vasodilation, peripheral vascular disorder, supraventricular extrasystole, vasovagal reactions, hypesthesia, non-generalized weakness, diaphoresis, rash, non-application site pruritus, skin neoplasm, nausea, dry mouth, increased serum creatinine, leg cramps and mydriasis.
Hemodynamic changes, manifested as decreases in blood pressure and increases in pulse rate, were observed during clinical studies, principally at doses above 20 µg and above 30 µg of alprostadil respectively, and appeared to be dose-dependent. However, these changes were clinically unimportant; only 3 patients discontinued the treatment because of symptomatic hypotension.
Alprostadil had no clinically important effect on serum or urine laboratory tests.
The pharmacotoxic signs of alprostadil are similar in all animal species and include depression, soft stool or diarrhea and rapid breathing. In mice, the lowest acute LD50 was 12 mg/kg which is 12 000 times greater than the maximum recommended human dose of 60 µg.
In man, prolonged erection and/or priapism are known to occur following intracavernosal administration of vasoactive substances. Given the dose-response relationship of alprostadil with erection duration, the therapeutic dose range should be determined individually for each patient by his physician during the initial office instruction. Inadvertent or intentional overdosing is the most common cause of prolonged pharmacological erection. In clinical trials with alprostadil, overdosage was not observed. If intracavernous overdose of alprostadil occurs, the patient should be under medical supervision until any systemic effects have resolved and/or until penile detumescence has occurred. Symptomatic treatment of any systemic symptoms would be appropriate.
Patients should be instructed to report any erections persisting for more than 3 hours to a physician. The treatment of priapism/prolonged erection should be according to established medical practice. Physicians may refer to 2 suggested protocols for detumescence presented below.
Detumescence Protocols: 1. Aspirate 40 to 60 mL from either right or left corpora using vacutainer and holder as for drawing blood. Use landmarks as for intracavernosal injection. Patient will often detumesce while aspirating. Apply ice for 20 minutes post-aspiration if erection remains. If 1) unsuccessful then, 2. Have patient lie in supine position. Dilute 10 mg phenylephrine into 20 mL water for injection (0.05%). With an insulin syringe, inject 0.1 to 0.2 mL (50 to 100 µg) into the corpora every 2 to 5 minutes, until detumescence occurs. The occasional patient may experience very transient bradycardia and hypertension when given phenylephrine injections, therefore monitor patient's blood pressure and pulse every 10 minutes. Patients at risk include those with cardiac arrhythmias and diabetics. Refer to the prescribing information for phenylephrine before use. Do not give to patients on MAOIs. When phenylephrine is used within the first 12 hours of erection, the majority of patients will respond. 3. If the above measures fail to detumesce the patient, a urologist should be consulted as soon as possible, especially if the erection has been present for many hours. If priapism is not treated immediately, penile tissue damage and/or permanent loss of potency may result.
Administration: Alprostadil is administered by direct intracavernosal injection. A 0.5 inch 27- to 30-gauge needle is generally recommended. Alprostadil is injected into either of two corpora cavernosum along the dorso-lateral aspects of the proximal third of the penis. Avoid any area where there are visible veins. The injection site should be changed for each injection (i.e., alternate sides of penis). Within either area, the point of injection should also be changed each time and the injection site must be cleansed with an alcohol swab.
Therapeutic/Effective Dose: Appropriate initial doses and maintenance doses are recommended based on the etiology of the erectile dysfunction. In all cases, the dose should be titrated on an individual basis by the physician, and the lowest effective dose always employed as the therapeutic dose. An effective dose is defined as one which produces an erection sufficient for intercourse with an erection duration not exceeding 1 hour. The following guidelines for dose titration are recommended.
Initial Titration in Physician's Office: Erectile Dysfunction of Vasculogenic, Psychogenic or Mixed Etiology: Dosage titration should be initiated at 2.5 µg of alprostadil. If there is a partial response, the dose may be increased by 2.5 µg to a dose of 5 µg and then in increments of 5 to 10 µg, depending upon erectile response, until the effective dose is reached (see Therapeutic/Effective Dose). If there is no response to the initial 2.5 µg dose, the second dose may be increased to 7.5 µg, followed by increments of 5 to 10 µg. The patient must remain in the physician's office until complete detumescence is achieved. If there is no response, then the next higher dose may be given within 1 hour. If there is a response, then there should be at least a 24-hour interval before the next dose is given.
Erectile Dysfunction of Pure Neurogenic Etiology: Dosage titration should be initiated at 1.25 µg of alprostadil. The dose may be increased by 1.25 µg to a dose of 2.5 µg, followed by an increment of 2.5 µg to a dose of 5 µg and then in 5 µg increments until the effective dose is reached (see Therapeutic/Effective Dose). The patient must remain in the physician's office until complete detumescence is achieved. If there is no response, then the next higher dose may be given within 1 hour. If there is a response, then there should be at least a 24-hour interval before the next dose is given.
In one clinical study involving 579 patients, the majority of patients (56%) were titrated to doses of >5 µg but ≤ 20 µg. The mean dose at the end of the titration phase was 17.8 µg of alprostadil.
Maintenance Therapy: The initial injection of alprostadil must be delivered by a medically trained health care professional. Before beginning a self-injection program of therapy, the physician must ensure that the patient (or his partner) aptly demonstrates skill and competence with the injection procedure, and uses appropriate sterile technique. A patient package insert is available to patients for referral (see Information for the Patient).
The dose selected for self-injection therapy is established during dose titration in the physician's office. The correct dose is the lowest effective dose. The dose should be reduced if the erection persists for longer than 1 hour; however, the physician should take into consideration the patient's preferences when defining the dose for self-injection. An erection lasting >3 hours is to be treated as a medical emergency. A physician should be consulted for any dose adjustments, if required. The dose should be adjusted in accordance with the titration guidelines described above. Regular follow-up visits, at least every 3 months, are recommended in order to assess the safety and efficacy of the therapy.
Maximum Recommended Dose Limits: Daily dose should not exceed 60 µg. Not more than once daily and not more than 3 times weekly, with at least 24 hours between each dose. Do not inject alprostadil into an erect penis.
There is no evidence that tolerance to the effects of alprostadil develops with continued use. The long-term use of alprostadil has been documented for up to 6 months in an uncontrolled self-injection study. The mean dose after 6 months was 20.7 µg.
A vial of Caverject delivers 1 dose only. Instructions for proper disposal of the syringe, needle and vial should be followed (see Information for the Patient).
Diagnostic Dose: Pharmacologic Testing: An initial dose of 2.5 µg is employed with subsequent upward titration in 2.5 µg increments. Patients are monitored for the occurrence of an erection following an intracavernosal injection of alprostadil.
Adjunct to Laboratory Investigations: A single dose of alprostadil sufficient to induce a rigid erection is used. For use with Doppler imaging/Duplex Ultrasonography, 133Xenon washout tests, Radionuclide Phallography and Penile Arteriography for the visualization and assessment of the penile vasculature.
Reconstituted Solutions: See Table 3. Alprostadil is reconstituted with the addition of 1 mL bacteriostatic water for injection (BWFI). Vial content after reconstitution is approximately 1.13 mL which allows 1.0 mL to be delivered to the patient. An excess of alprostadil is added to compensate for loss due to adsorption to the vial and syringe. The resultant solution contains 20 µg/mL of alprostadil, 172 mg/mL lactose, 47 µg/mL sodium citrate, and 8.4 mg/mL benzyl alcohol. Once reconstituted, no additional substances should be injected into the vial.
Once reconstituted, the alprostadil solution must be used immediately. Do not freeze the reconstituted solution. A solution which appears cloudy, colored or contains particles should be discarded.