Updated CSP, alprostadil, UK/H/PSUR/0020/002, 24 July 2012
Annex I : CSP
4.3Contraindications
Alprostadil is contraindicated in the following patients:
- patients who have a known hypersensitivity to the drug or any of theconstituents
- patients who have conditions that might predispose them to priapism, such assickle cell anemia or trait, multiple myeloma, or leukemia
- patients with anatomical deformation of the penis, such as angulation,cavernosal fibrosis, or Peyronie's disease
- patients with penile implants
- patients for whom sexual activity is inadvisable or contraindicated
4.4Special warnings and precautions for use
Underlying treatable medical causes of erectile dysfunction should be diagnosedand treated prior to initiation of therapy with alprostadil.
Priapism (erection lasting over six hours) may occur following intracavernosaladministration of alprostadil. Treatment of priapism should not be delayed morethan 6 hours (please refer to Section 4.9 Overdose).
To minimize the risk, select the lowest effective dose and instruct patient toimmediately report to his prescribing physician, or, if unavailable, seek immediatemedical assistance for any erection that persist longer than 4 hours. Treatment ofpriapism should be according to established medical practice.
Painful erection is more likely to occur in patients with anatomical deformationsof the penis, such as angulation, phimosis, cavernosal fibrosis, Peyronie's diseaseor plaques.
Penile fibrosis, including angulation, cavernosal fibrosis, fibrotic nodules and
Peyronie's disease may occur following the intracavernosal administration of
alprostadil. The occurrence of fibrosis may increase with increased duration ofuse.
Regular follow-up of patients, with careful examination of the penis, is stronglyrecommended to detect signs of penile fibrosis or Peyronie's disease.
Treatment with alprostadil should be discontinued in patients who develop penileangulation, cavernosal fibrosis, or Peyronie's disease.
In some patients, injection of alprostadil can induce a small amount of bleeding atthe site of injection. In patients infected with blood born diseases, this couldincrease the transmission of such diseases to their partner.
Patients on anticoagulants such as warfarin or heparin may have increasedpropensity for bleeding after the intracavernosal injection.
Alprostadil should be used with caution in patients who have experiencedtransient ischaemic attacks or those with unstable cardiovascular disorders.
Alprostadil is not intended for co-administration with any other agent for thetreatment of erectile dysfunction (see also 4.5).
The potential for abuse of alprostadil should be considered in patients with ahistory of psychiatric disorder or addiction.
Sexual stimulation and intercourse can lead to cardiac and pulmonary events inpatients with coronary heart disease, congestive heart failure or pulmonarydisease. These patients when using alprostadil should engage in sexual activitywith caution.
Reconstituted solutions of alprostadil are intended for single use only. Theinjection delivery system/syringe and any remaining solution should be properlydiscarded.
Alprostadil Sterile Powder and solvent (Dual Chamber) contains benzyl alcohol,which may cause hypersensitivity reactions.
4.5Interaction with other medicinal products and other forms of interaction
The effects of combinations of alprostadil with other treatments for erectile dysfunction (e.g. sildenafil) or other drugs inducing erection (e.g. papaverine) have not been formally studied. Such agents should not be used in combination with alprostadil due to the potential for inducing prolonged erections.
Sympathomimetics may reduce the effect of alprostadil. Alprostadil may enhance the effects of antihypertensives, vasodilative agents, anticoagulants and platelet aggregation inhibitors.
4.6Pregnancy and lactation
Not applicable.
4.7Effects on ability to drive and use machines
Alprostadil would not be expected to have an influence on the ability to drive oroperate machines.
4.8Undesirable effects
The most frequent adverse effects following an intracavernous injection was pain in the penis. Thirty percent of patients reported pain at least once. Pain was associated with 11% of the injections administered. In most cases pain was assessed as mild or moderate. Three per cent of patients discontinued treatment because of pain.
Penile fibrosis, including angulation, fibrotic nodules, and Peyronie’s disease, was reported in 3% of clinical trial patients overall. In one self-injection study in which the duration of use was up to 18 months, the incidence of penile fibrosis was higher, approximately 8%.
Haematoma and ecchymosis at the injection site, which is related with the injection technique rather than the effect of alprostadil, was reported by 3% and 2% of patients, respectively.
Prolonged erection (an erection for 4 - 6 h) developed in 4% of patients. Priapism (a painful erection for more than 6 hours) occurred in 0.4%. In most cases it disappeared spontaneously.
Adverse drug reactions reported during clinical trials and post marketing experience are presented in the following table:
Adverse drug reactions reported during clinical trials and post marketingexperience are presented in the table below, frequencies are very common(≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100).
4.9Overdose
Overdosage was not observed in clinical trials with alprostadil. If intracavernous overdose of Caverject Dual Chamber 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 epinephrine 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 epinephrine 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.