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

Prolonged erection and/or priapism may occur following intracavernosal administration of alprostadil. To minimize the risk, select the lowest effective dose. Patients should be instructed to report immediately to a physician, or if unavailable to seek immediate medical assistance for any erection lasting for a prolonged time period, such as 4 hours. Treatment of priapism should not be delayed more than 6 hours (please refer to Section 4.9) and should be according to established medical practice.

Painful erection is more likely to occur in patients with anatomical deformations of the penis, such as angulation, phimosis, cavernosal fibrosis, Peyronie’s disease or 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 of use. Regular follow-up of patients, with careful examination of the penis, is strongly recommended to detect signs of penile fibrosis or Peyronie’s disease. 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 increased propensity for bleeding after the intracavernosal injection.

Underlying treatable medical causes of erectile dysfunction should be diagnosed and treated prior to initiation of therapy with alprostadil.

Use of intracavernosal alprostadil offers no protection from the transmission of sexually transmitted diseases. Individuals who use alprostadil should be counselled about the protective measures that are necessary to guard against the spread of sexually transmitted diseases, including the human immunodeficiency virus (HIV). In some patients, injection of alprostadil can induce a small amount of bleeding at the site of injection. In patients infected with blood-borne diseases, this could increase the transmission of such diseases to their partner.

Alprostadil should be used with caution in patients with cardiovascular and cerebrovascular risk factors. Alprostadil should be used with caution in patients who have experienced transient ischaemic attacks or those with unstable cardiovascular disorders.

Sexual stimulation and intercourse can lead to cardiac and pulmonary events in patients with coronary heart disease, congestive heart failure or pulmonary disease. These patients when using alprostadil should engage in sexual activity with caution.

Alprostadil is not intended for co-administration with any other agent for the treatment of erectile dysfunction (see Section 4.5).

The potential for abuse of alprostadil should be considered in patients with a history of psychiatric disorder or addiction.

Caverject uses a superfine needle for administration. As with all superfine needles, the possibility of needle breakage exists.

Needle breakage, with a portion of the needle remaining in the penis, has been reported and, in some cases, required hospitalisation and surgical removal.

Careful patient instruction in proper handling and injection techniques may minimise the potential for needle breakage.

The patient should be instructed that, if the needle is bent, it must not be used; they should also not attempt to straighten a bent needle. They should remove the needle from the syringe, discard it, and attach a new, unused sterile needle to the syringe.

Reconstituted solutions of alprostadil are intended for single use only, they should be used immediately and not stored. The syringe and any remaining solution should be properly discarded.

The solvent contains benzyl alcohol, which may cause hypersensitivity reactions and has been associated with serious adverse events, including the “gasping syndrome”, and death in paediatric patients. 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 capacity to detoxify the chemical. Premature and low-birth weight infants may be more likely to develop toxicity.

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.

Not applicable.

High doses of alprostadil (0.5 to 2.0 mg/kg subcutaneously) had an adverse effect on the reproductive potential of male rats, although this was not seen with lower doses (0.05 to 0.2 mg/kg). Alprostadil did not affect rat spermatogenesis at doses 200 times greater than the proposed human intrapenile dose.

Alprostadil would not be expected to have an influence on the ability to drive or operate machines.

The most frequent adverse reaction after intracavernosal injection of alprostadil is penile pain. Thirty percent of the patients reported penile pain at least once; however, this event was associated with only 11% of the administered injections. In the majority of the cases, penile pain was rated mild or moderate in intensity. 3% of patients discontinued treatment because of penile pain.

Prolonged erection (defined as an erection that lasts for 4 to 6 hours) after intracavernosal administration of alprostadil was reported in 4% of patients. The frequency of priapism (defined as an erection that lasts 6 hours or longer) was 0.4%. In the majority of cases, spontaneous detumescence occurred.

Penile fibrosis, including angulation, fibrotic nodules and Peyronie’s disease was reported in 3% of clinical trial patients overall, however, 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 site of injection, which is related to the injection technique rather than to the effects of alprostadil, occurred in 3% and 2% of patients, respectively. Penile oedema or rash was reported by 1% of alprostadil treated patients.

Adverse drug reactions reported during clinical trials and post marketing experience 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); not known (cannot be estimated from the available data). The adverse drug reactions are listed in order of decreasing medical seriousness within each frequency category and system organ class.

Infections and Infestations

Uncommon: Fungal infection, Common cold

Nervous System Disorders

Uncommon: Presyncope, Hypoaesthesia, Hyperaesthesia

Not known: Cerebrovascular accident

Eye Disorders

Uncommon: Mydriasis

Cardiac Disorders

Uncommon: Supraventricular extrasystoles

Not known: Myocardial ischaemia

Vascular Disorders

Uncommon: Venous haemorrhage, Hypotension, Vasodilatation, Peripheral vascular disorder, Vein disorder

Gastrointestinal Disorders

Uncommon: Nausea, Dry mouth

Skin and Subcutaneous Tissue Disorders

Uncommon: Erythema, Rash, Hyperhidrosis, Pruritus

Musculoskeletal and Connective Tissue Disorders

Common: Muscle spasms

Renal and Urinary Disorders

Uncommon: Urethral haemorrhage, Haematuria, Dysuria, Pollakiuria, Micturition urgency

Reproductive System and Breast Disorders

Very common: Penile pain

Common: Peyronie’s disease, Penis disorder, Erection increased

Uncommon: Priapism, Pelvic pain, Testicular mass, Spermatocele, Testicular swelling, Testicular oedema, Testicular disorder, Scrotal pain, Scrotal erythema, Scrotal oedema, Testicular pain, Scrotal disorder, Painful erection, Balanitis, Phimosis, Erectile dysfunction, Ejaculation disorder

General Disorders and Administration Site Conditions

Common: Injection site haematoma, Haematoma, Ecchymosis

Uncommon: Haemorrhage, Injection site haemorrhage, Inflammation, Injection site inflammation, Injection site warmth, Injection site oedema, Injection site swelling, Injection site pain, Injection site irritation, Asthenia, Injection site anaesthesia, Oedema, Oedema peripheral, Injection site pruritus

Investigations

Uncommon: Blood creatinine increased, Blood pressure decreased, Heart rate increased

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

Caverject is not intended to be mixed or coadministered with any other products.