CAVERJECT Powder for solution for injection Ref.[6147] Active ingredients: Alprostadil

Caverject is administered by direct intracavernous injection. A half inch, 27 to 30 gauge needle is generally recommended. The dose of Caverject should be individualised for each patient by careful titration under supervision by a physician.

The intracavernosal injection must be done under sterile conditions. The site of injection is usually along the dorsolateral aspect of the proximal third of the penis. Visible veins should be avoided. Both the side of the penis that is injected and the site of injection must be alternated; prior to the injection, the injection site must be cleansed with an alcohol swab.

To reconstitute Caverject using the prefilled diluent syringe: flip off the plastic cap from the vial, and use one of the swabs to wipe the rubber cap. Fit the 22 gauge needle to the syringe.

Inject the 1 ml of diluent into the vial, and shake to dissolve the powder entirely. Withdraw slightly more than the required dose of Caverject solution, remove the 22 gauge needle, and fit the 30 gauge needle. Adjust volume to the required dose for injection. Following administration, any unused contents of the vial or syringe should be discarded.

As an aid to aetiologic diagnosis.

Subjects without evidence of neurological dysfunction

20 micrograms alprostadil to be injected into the corpus cavernosum and massaged through the penis. Should an ensuing erection persist for more than one hour detumescent therapy (please refer to Section 4.9) should be employed prior to the subject leaving the clinic to prevent a risk of priapism.

Over 80% of subjects may be expected to respond to a single 20 micrograms dose of alprostadil. At the time of discharge from the clinic, the erection should have subsided entirely and the penis must be in a completely flaccid state.

Subjects with evidence of neurological dysfunction

These patients can be expected to respond to lower doses of alprostadil. In subjects with erectile dysfunction caused by neurologic disease/trauma the dose for diagnostic testing must not exceed 10 micrograms and an initial dose of 5 micrograms is likely to be appropriate. Should an ensuing erection persist for more than one hour detumescent therapy (please refer to Section 4.9) should be employed prior to the subject leaving the clinic to prevent a risk of priapism. At the time of discharge from the clinic, the erection should have subsided entirely and the penis must be in a completely flaccid state.

Treatment

The initial dose of alprostadil in patients with erectile dysfunction of neurogenic origin secondary to spinal cord injury is 1.25 micrograms, with a second dose of 2.5 micrograms, a third of 5 micrograms, and subsequent incremental increases of 5 micrograms until an optimal dose is achieved. For erectile dysfunction of vasculogenic, psychogenic, or mixed aetiology, the initial dose is 2.5 micrograms. The second dose should be 5 micrograms if there is a partial response, and 7.5 micrograms if there is no response. Subsequent incremental increases of 5-10 micrograms should be given until an optimal dose is achieved. If there is no response to the administered dose, then the next higher dose may be given within 1 hour. If there is a response, there should be at least a 1-day interval before the next dose is given. The usual maximum recommended frequency of injection is no more than once daily and no more than three times weekly.

The first injections of alprostadil must be done by medically trained personnel. After proper training and instruction, alprostadil may be injected at home. If self-administration is planned, the physician should make an assessment of the patient’s skill and competence with the procedure. It is recommended that patients are regularly monitored (e.g. every 3 months) particularly in the initial stages of self injection therapy when dose adjustments may be needed.

The dose that is selected for self-injection treatment should provide the patient with an erection that is satisfactory for sexual intercourse. It is recommended that the dose administered produces a duration of the erection not exceeding one hour. If the duration is longer, the dose should be reduced. The majority of patients achieve a satisfactory response with doses in the range of 5 to 20 micrograms. Doses of greater than 60 micrograms of alprostadil are not recommended. The lowest effective dose should be used.

The pharmacotoxic signs of alprostadil are similar in all animal species and include depression, soft stools or diarrhoea and rapid breathing. In animals, the lowest acute LD₅₀ was 12 mg/kg which is 12,000 times greater than the maximum recommended human dose of 60 micrograms.

In man, prolonged erection and/or priapism are known to occur following intracavernous administration of vasoactive substances, including alprostadil. Patients should be instructed to report to a physician any erection lasting for a prolonged time period, such as 4 hours or longer.

Overdosage was not observed in clinical trials with alprostadil. If intracavernous overdose of alprostadil occurs, the patient should be placed 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.

The treatment of priapism (prolonged erection) should not be delayed more than 6 hours. Initial therapy should be by penile aspiration. Using aseptic technique, insert a 19-21 gauge butterfly needle into the corpus cavernosum and aspirate 20-50 ml of blood. This may detumesce the penis. If necessary, the procedure may be repeated on the opposite side of the penis until a total of up to 100 ml blood has been aspirated. If still unsuccessful, intracavernous injection of alpha-adrenergic medication is recommended. Although the usual contra-indication to intrapenile administration of a vasoconstrictor does not apply in the treatment of priapism, caution is advised when this option is exercised. Blood pressure and pulse should be continuously monitored during the procedure. Extreme caution is required in patients with coronary heart disease, uncontrolled hypertension, cerebral ischaemia, and in subjects taking monoamine oxidase inhibitors. In the latter case, facilities should be available to manage a hypertensive crisis. A 200 microgram/ml solution of phenylephrine should be prepared, and 0.5 to 1.0 ml of the solution injected every 5 to 10 minutes. Alternatively, a 20 microgram/ml solution of adrenaline should be used. If necessary, this may be followed by further aspiration of blood through the same butterfly needle. The maximum dose of phenylephrine should be 1 mg, or adrenaline 100 micrograms (5 ml of the solution). As an alternative metaraminol may be used, but it should be noted that fatal hypertensive crises have been reported. If this still fails to resolve the priapism, urgent surgical referral for further management, which may include a shunt procedure, is required.

Shelf life: 2 years.

Reconstituted solutions should be used immediately and not stored.

Do not store above 25°C. Reconstituted solutions are intended for single use only, they should be used immediately and not stored.

Single pack containing a 5 ml clear, colourless, glass vial of Caverject 20 micrograms powder with a bromobutyl rubber stopper and an aluminium overseal with polypropylene flip-off cap.

Packs also each contain a syringe of solvent, a sterile 22G and a 30G needle plus a preinjection swab.

The presence of benzyl alcohol in the reconstitution vehicle decreases the degree of binding to package surfaces. Therefore, a more consistent product delivery is produced when Bacteriostatic Water for Injection containing benzyl alcohol is used.

Use immediately after reconstitution.