Muse Information
Muse () Description
Muse () (alprostadil) is a single-use, medicated transurethral system for the delivery of alprostadil to the male urethra. Alprostadil is suspended in polyethylene glycol 1450 (as excipient) and is formed into a medicated pellet (micro-suppository measuring 1.4 mm in diameter by 3 mm or 6 mm in length) that resides in the tip of a translucent hollow applicator. Muse () is administered by inserting the applicator stem into the urethra after urination. The pellet containing alprostadil is delivered by depressing the applicator button . The components of the delivery system are constructed of medical grade polypropylene. Each Muse () system is packaged in an individual foil pouch.
The active ingredient in Muse () is alprostadil, which is chemically identical to the naturally occurring eicosanoid, prostaglandin E (PGE). The chemical name for alprostadil is prost-13-en-1-oic acid, 11,15-dihydroxy-9-oxo-(11α,13E,15S)-(1R,2R,3R)-3-hydroxy-2-[(E)-(3S)-3-hydroxy-1-octenyl]-5-oxo-cyclopentane heptanoic acid, and the molecular weight is 354.49. The empirical formula is CHO. The structural formula of alprostadil is represented below:
Alprostadil is a white to off-white crystalline powder with a melting point between 115° and 116°C. Its solubility at 35°C is 8000 mcg per 100 mL double-distilled water. The inactive ingredient in Muse () is polyethylene glycol 1450, USP. There are no other active agents or excipients in Muse () .
Muse () is available in 4 dosage strengths: 125 mcg, 250 mcg, 500 mcg, and 1000 mcg.
Muse () Clinical Pharmacology
Mechanism of Action:
In human studies using Doppler duplex ultrasonography, intraurethral administration of 500 mcg of Muse () resulted in an increase in cavernosal artery diameter and a 5- to 10-fold increase in peak systolic flow velocities. These results suggest that intraurethral alprostadil is absorbed from the urethra, transported throughout the erectile bodies by communicating vessels between the corpus spongiosum and corpora cavernosa, and able to induce vasodilation of the targeted vascular beds.
The vasodilatory effects of alprostadil on the cavernosal arteries and the trabecular smooth muscle of the corpora cavernosa result in rapid arterial inflow and expansion of the lacunar spaces within the corpora. As the expanded corporal sinusoids are compressed against the tunica albuginea, venous outflow through subtunical vessels is impeded and penile rigidity develops. This process is referred to as the corporal veno-occlusive mechanism.
The most notable systemic effects of alprostadil are vasodilation, inhibition of platelet aggregation, and stimulation of intestinal and uterine smooth muscle. Intravenous doses of 1 to 10 micrograms per kilogram of body weight lower blood pressure in mammals by decreasing peripheral resistance. Reflex increases in cardiac output and heart rate may accompany these effects.
Muse () Clinical Trials
The Muse () system was evaluated in 7 placebo-controlled trials of various design in over 2500 patients with a history of erectile dysfunction of various etiologies. These trials assessed erectile function in the clinic and sexual intercourse in outpatient settings. In studies of sexual performance, patients were screened in the clinic, generally using doses of 125 mcg to 1000 mcg, for a satisfactory erectile response, then sent home with the selected dose or placebo for evaluation of sexual performance. Not all patients beginning titration had a successful dose and some patients could not tolerate Muse () , principally because of penile pain, so that the success rates in the studies described below must be understood to represent response rates only in patients who were successfully titrated.
In 2 identical multicenter, double-blind, placebo-controlled, parallel-group studies, 1511 monogamous and heterosexual patients with a mean 4-year history of erectile dysfunction and at least a 3-month history of no erections adequate for sexual intercourse without medical assistance, were enrolled and began dose titration in the clinic with doses between 125 mcg and 1000 mcg. 996 patients (66%) completed dose titration, achieved an erection sufficient for intercourse, and were randomized equally to placebo or active treatment and followed during at-home treatment for up to 3 months. 874 patients and partners completed 3 months of follow-up. About 10%, 20%, 30%, and 40% of patients were titrated to 125 mcg, 250 mcg, 500 mcg, and 1000 mcg, respectively. Couples on active therapy were more likely to have at least 1 successful sexual intercourse (65% vs. 19%) than were couples on placebo. Among patients who reported successful intercourse at least once with active treatment, approximately 7 of 10 Muse () systems resulted in successful sexual intercourse. Results were similar in patients with erectile dysfunction stemming from surgery or trauma, diabetes, vascular disease, or other etiologies, and were similar in Caucasians and non-Caucasians. In administrations resulting in sexual intercourse, the duration of erections sufficient for penetration was 6 minutes on placebo and 16 minutes on active drug. Successful therapy with Muse () was associated with improvement in the quality of life measures of “emotional well-being” for patients and “relationship with partner” for both patients and their female partners.
Muse () Indications And Usage
Muse () is indicated for the treatment of erectile dysfunction. Studies that established benefit demonstrated improvements in success rates for sexual intercourse compared with similarly administered placebo.
Muse () Contraindications
Muse () is contraindicated in men with any of the following:
Muse () Warnings
Because of the potential for symptomatic hypotension and syncope, which occurred in 3% and 0.4%, respectively, of patients during in-clinic dosing, Muse () titration should be carried out under medical supervision. During post-marketing surveillance syncope occurring within one hour of administration has been reported. 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.
Muse () Precautions
Patients should be informed that Muse () offers no protection from the transmission of sexually transmitted diseases. Patients and partners who use Muse () need to be counseled about the protective measures that are necessary to guard against the spread of sexually transmitted agents, including the human immunodeficiency virus (HIV).
Although unreported in clinical trials, there is the possibility that an overdosage of Muse () can cause priapism, a painful erection of the penis sustained for hours and unrelieved by sexual intercourse or masturbation. This condition is serious and, if untreated, it can lead to permanent inability to have an erection. Patients who experience a prolonged erection should seek prompt medical attention. Patients should be instructed how to administer Muse () . A patient package insert must be given to each patient at the initiation of Muse () therapy.
Partners of patients using Muse () should be informed that Muse () offers no protection from the transmission of sexually transmitted diseases. Patients and partners who use Muse () should be counseled about the protective measures that are necessary to guard against the spread of sexually transmitted agents, including the human immunodeficiency virus (HIV). Human semen contains PGE, but additional amounts may be present from Muse () administration (see ). Partners who have experienced an extended period of sexual abstinence should be encouraged to seek advice from a health care professional prior to resuming sexual intercourse. The use of a water-based lubricant may facilitate vaginal penetration.
It is recommended that couples using Muse () employ adequate contraception if the female partner is of childbearing potential. There is no information on the effects on early pregnancy of PGE at the levels received by female partners. Muse () has no contraceptive properties. Muse () should not be used if the female partner is pregnant, unless the couple uses a condom barrier.
Long-term carcinogenicity studies of alprostadil have not been conducted. Alprostadil showed no evidence of mutagenicity in vitro in the Ames bacterial reverse mutation test, the unscheduled DNA synthesis assay in rat hepatocytes, or the Chinese hamster ovary forward gene mutation assay; nor was there evidence of mutagenicity in vivo in the mouse micronucleus assay. Alprostadil concentrations increased chromosomal aberrations above control incidence in the in vitro Chinese hamster ovary chromosomal aberration assay.
In dogs, sperm concentration, morphology, and motility were unaffected by daily intraurethral administration of up to 3000 mcg Muse () (alprostadil) for 13 weeks (200 mcg/kg/day or about 3.5 times the maximum recommended daily dose adjusted for body surface area). Alprostadil concentrations of 400 mcg/mL had no effect on human sperm motility or viability in vitro.
Pregnancy:
Muse () Adverse Reactions
996 patients (66% of those who began titration) were studied during the home treatment portion of 2 Phase III placebo-controlled studies. Fewer than 2% of patients discontinued from these studies primarily because of adverse events. The following table summarizes the frequency of adverse events reported by patients using Muse () or placebo.
Other drug-related side effects observed during in-clinic titration and home treatment include swelling of leg veins, leg pain, perineal pain, and rapid pulse, each occurring in
Muse () Overdosage
Overdosage has not been reported with Muse () . Overdosage with Muse () may result in hypotension, persistent penile pain, and possibly priapism (rigid erection lasting ≥6h). Priapism can result in permanent worsening of erectile function. Patients suspected of overdosage who develop these symptoms should be kept under medical supervision until systemic or local symptoms have resolved.
Muse () Dosage And Administration
Muse () is a transurethral delivery system available in 4 dosage strengths: 125 mcg, 250 mcg, 500 mcg, and 1000 mcg. Muse () should be administered as needed to achieve an erection. The onset of effect is within 5–10 minutes after administration. The duration of effect is approximately 30–60 minutes. However, the actual duration will vary from patient to patient. Each patient should be instructed by a medical professional on proper technique for administering Muse () prior to self-administration. The maximum frequency of use is no more than 2 systems per 24-hour period.
Muse () How Supplied
Muse () is supplied in individual foil pouches containing one (1) system per pouch. Muse () is available in unit cartons containing six (6) systems. Muse () is available in the following 4 dosage strengths:
Muse () Storage And Handling
Store unopened foil pouches in a refrigerator at 2°– 8°C (36°– 46°F). Do not expose Muse () to temperatures above 30°C (86°F). Muse () may be kept by the patient at room temperature (below 30°C or 86°F) for up to 14 days prior to use.
Medical information line at VIVUS 1-888-345-Muse () (1-888-345-6873).
Muse () IS A REGISTERED TRADEMARK OF VIVUS, INC. IN THE U.S. AND OTHER COUNTRIES.
VIVUS, Inc.Mountain View, CA 94040http://www.vivus.com
Catalog Number: 05-10-00001BRevised March 2009Code VM116230403
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