Meda Health Sales

MUSE 500 microgram urethral stick.

Each urethral stick contains 500 micrograms alprostadil.

For a full list of excipients, see section 6.1.

Urethral Stick.

MUSE is a sterile, single-use transurethral system for the delivery of alprostadil to the male urethra. Alprostadil is suspended in macrogol and is formed into a urethral stick (1.4 mm in diameter by 6 mm in length) which is contained in the tip of the polypropylene applicator.

Treatment of erectile dysfunction of primarily organic etiology.

Adjunct to other tests in the diagnosis and management of erectile dysfunction.

Use in Adults

Treatment of erectile dysfunction

Initiation of therapy: a medical professional should instruct each patient on the correct use of MUSE. The recommended starting dose is 250 micrograms.

Dosage may be increased in a stepwise manner (from 500 to 1000 micrograms), or decreased (to 125 micrograms) under medical supervision until the patient achieves a satisfactory response. After an assessment of the patient's skill and competence with the procedure, the chosen dose may then be prescribed for home use.

It is important for the patient to urinate before administration since a moist urethra makes administration of MUSE easier and is essential to dissolve the drug. To administer MUSE, remove the protective cover from the MUSE applicator, stretch the penis upward to its full length, and insert the applicator stem into the urethra. Depress the applicator button to release the medication from the applicator and remove the applicator from the urethra, (rocking the applicator gently prior to removal will ensure that the medication is separated from the applicator stem). Roll the penis between the hands for at least 10 seconds to ensure that the medication is adequately distributed along the wall of the urethra. If the patient feels a burning sensation it may help to roll the penis for an additional 30 to 60 seconds or until the burning subsides. The erection will develop within 5-10 minutes after administration and lasts approximately 30-60 minutes. After administration of MUSE, it is important to sit, or preferably, stand or walk for about 10 minutes while the erection is developing. More detailed information is given in the patient information leaflet. During home use, periodic checks of efficacy and safety are recommended.

Not more than 2 doses are recommended to be used in any 24-hour period, and not more than 7 doses are recommended to be used in a 7-day period. The prescribed dosage should not be exceeded.

Adjunct to other tests in the diagnosis and management of erectile dysfunction

MUSE can be used as an adjunct in evaluating penile vascular function using Doppler duplex ultrasonography. It has been shown that a 500 microgram dose of MUSE has a comparable effect on penile arterial dilatation and peak systolic velocity flow to 10 microgram of alprostadil given by intracavernosal injection. At the time of discharge from the clinic, the erection should have subsided.

Use in the elderly

No adjustment for age is required.

MUSE is contraindicated in men with any of the following conditions:

Hypersensitivity to the active substance or to any of the excipients.

Abnormal penile anatomy (stenosis of the distal urethra, severe hypospadia or severe curvature), balanitis, acute or chronic urethritis.

Conditions with an increased risk of priapism (sickle cell anaemia or trait, thrombocythaemia, polycythaemia, multiple myeloma; predisposition to venous thrombosis), or a history of recurrent priapism.

MUSE should not be used in men for whom sexual activity is inadvisable, as in men with unstable cardiovascular or unstable cerebrovascular conditions.

MUSE should not be used if the female partner is or may be pregnant unless the couple uses a condom barrier.

MUSE is contraindicated in women and children.

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

Incorrect insertion of MUSE may cause urethral abrasion and minor urethral bleeding. Patients on anticoagulants or with bleeding disorders may have an increased risk of urethral bleeding.

Patients should be asked to report promptly to their treating physician any erections lasting 4 hours or longer. For treatment: see section 4.9. Overdose. In clinical trials of MUSE, priapism (rigid erections lasting 6 hours) and prolonged erection (rigid erection lasting 4 hours and <6 hours) were reported infrequently (<0.1% and 0.3% of patients, respectively). Nevertheless, these events are a potential risk of pharmacologic therapy. It may be necessary to reduce the dose or discontinue treatment in any patient who develops priapism.

Patients and their partners should be advised that MUSE offers no protection from transmission of sexually transmitted diseases. They should be counselled about the protective measures that are necessary to guard against the spread of sexually transmitted agents, including the human immunodeficiency virus (HIV). The use of MUSE will not affect the integrity of condoms. Since MUSE may add small amounts of alprostadil to the naturally occurring PGE₁ already present in the semen, it is recommended that adequate contraception is used if the woman is of child-bearing potential.

Systemic interactions are unlikely because of the low levels of alprostadil in the peripheral venous circulation, however the presence of medication affecting erectile function may influence the response to MUSE. Decongestants and appetite suppressants may diminish the effect of MUSE. Patients on anticoagulants or with bleeding disorders may have an increased risk of urethral bleeding. Insufficient data exists concerning the concomitant use of MUSE with vasoactive medications. There is the potential that this combination may increase the risk of hypotensive symptoms; this effect may be more common in the elderly.

There is limited information available in the literature concerning the concomitant use of MUSE and sildenafil for the treatment of erectile dysfunction. No conclusions can be drawn, however, regarding the safety or efficacy of this combination.

The use of MUSE in patients with penile implants has been reported in a limited number of cases in the literature. However no conclusions can be drawn regarding the safety or efficacy of this combination.

MUSE may add small amounts of alprostadil to the naturally occurring PGE₁ already present in the semen. A condom barrier should therefore be used during sexual intercourse if the female partner is pregnant to avoid irritation of the vagina and guard against any risk to the foetus.

Patients should be cautioned to avoid activities, such as driving or hazardous tasks, where injury could result if hypotension or syncope were to occur after MUSE administration. In patients experiencing hypotension and/or syncope, these events have usually occurred during initial titration and within one hour of drug administration.

The most frequently reported adverse events in treatment with MUSE are presented in the table below. (Very common > 1/10; Common > 1/100, <1/10; Uncommon >1/1000, <1/100; Rare >1/10000, <1/1000; Very rare <1/10000)

Vaginal burning/itching was reported by approximately 6% of partners of patients on active treatment. This may be due to resuming sexual intercourse or due to the use of MUSE.

Overdosage has not been reported with MUSE.

Symptomatic hypotension, persistent penile pain and in rare instances, priapism may occur with alprostadil overdosage. Patients should be kept under medical supervision until systemic or local symptoms have resolved.

Should a prolonged erection lasting 4 or more hours occur, the patient should be advised to seek medical help. The following actions can be taken:

• The patient should be supine or lying on his side. Apply an ice pack alternately for two minutes to each upper inner thigh (this may cause a reflex opening of the venous valves). If there is no response after 10 minutes, discontinue treatment.

• If this treatment is ineffective and a rigid erection has lasted for more than 6 hours, penile aspiration should be performed. 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.

• If still unsuccessful, intracavernous injection of α-adrenergic medication is recommended. Although the usual contraindication 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 5-10 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 (5ml 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, the patient should immediately be referred for surgical management.

ATC Code: G04B E01 (Drugs used in erectile dysfunction).

Alprostadil is chemically identical to prostaglandin E₁, the actions of which include vasodilatation of blood vessels in the erectile tissues of the corpora cavernosa and increase in cavernosal artery blood flow, causing penile rigidity.

Approximately 80% of the alprostadil delivered by MUSE is absorbed through the urethral mucosa within 10 minutes.

The half-life is less than 10 minutes and peripheral venous plasma concentrations are low or undetectable. Alprostadil is rapidly metabolised, both locally and in the pulmonary capillary bed; metabolites are excreted in the urine (90% within 24 hours) and the faeces. There is no evidence of tissue retention of alprostadil or its metabolites.

In rats, high doses of prostaglandin E₁ increased foetal resorption, presumably due to maternal stress. High concentrations of alprostadil (400 microgram/ml) had no effect on human sperm motility or viability in vitro. In rabbits, there was no foetal damage or effect on reproductive function at the maximum tested intravaginal dose of 4mg.

In the majority of in vitro and in vivo genotoxicity test systems in which alprostadil has been evaluated it produced negative results. These tests include the bacterial reversion test using Salmonella typhimurium, unscheduled DNA synthesis in rat primary hepatocytes, forward mutation assay at the hprt locus in cultured ovary cells from Chinese hamsters, alkaline elution test, sister chromatid exchange assay (all in vitro tests) and the micronucleus test in both mice and rats (in vivo tests). In two other in vitro tests, the mouse lymphoma forward mutation assay and the Chinese hamster ovary chromosomal aberration assay, alprostadil produced borderline positive and positive evidence, respectively, for chromosomal damage. In view of the number of negative in vitro results and the lack of evidence for genotoxicity in two in vivo tests, it is considered that the positive results obtained in these two in vitro tests are of doubtful biological significance. Overall the presently available evidence cannot fully exclude the risk of genotoxic activity in humans.

Macrogol 1450

Not applicable.

2 years.

From a microbiological point of view, the product should be used immediately after opening the foil pouch.

Store at 2°- 8°C (in a refrigerator). Store in the original package.

Unopened pouches may be kept out of the refrigerator by the patient, at a temperature below 30°C, for up to 14 days prior to use.

MUSE is supplied as cartons of 1, 2, 3, 6 or 10 foil pouches, with each pouch containing one delivery system. Not all pack sizes may be marketed.

The pouches are composed of aluminium foil/laminate. The applicators are made from radiation-resistant medicalgrade polypropylene.

No special requirements.

Meda Health Sales Ireland Limited

Unit 34/35, Block A

Dunboyne Business Park

Dunboyne

Co. Meath

Ireland

PA 1332/4/3

First date of authorisation: 05 February 1999

Last date of authorisation: 07 October 2007

November 2011