Intraurethral Alprostadil

MUSE is an alprostadil urethral suppository approved in the United States for erectile dysfunction (ED).^[1][20] FDA now lists every MUSE strength as discontinued (see The delivery system).^[1][20] It offers a needle-free option, usually with lower efficacy than intracavernosal treatment. Treatment choice should reflect effectiveness, adverse effects, access and preference; MUSE may be used before every oral option has failed. The AUA recommends informing men about intraurethral alprostadil, including benefits and burdens , and performing an in-office test before use ; the US MUSE label likewise calls for supervised dose titration.^[1][2] EAU 2026 recommends topical or intraurethral alprostadil as alternative first-line therapy for well-informed patients who are unsuitable for or do not want oral vasoactive therapy, do not want intracavernosal injections, or prefer a less invasive treatment ; its discussion notes lower efficacy than intracavernosal therapy.^[3] It suits men in whom PDE5 inhibitors are contraindicated or ineffective, and men or partners who prefer to avoid oral drugs or injections.^[2]

For related treatments, see Intracavernosal injection agents, PDE5 inhibitors, and Testosterone replacement. MUSE pellets, topical alprostadil cream and injectable alprostadil are different formulations; their instructions and evidence are not interchangeable.

Mechanism and formulation

Alprostadil is prostaglandin E1 (PGE1), chemically identical to the endogenous compound. It relaxes cavernosal smooth muscle and promotes arterial inflow and corporal veno-occlusion. Drug absorbed from the urethral mucosa reaches the erectile bodies through communicating vessels between the corpus spongiosum and the corpora cavernosa. In the label's Doppler studies, a 500-microgram intraurethral dose increased cavernosal artery diameter and produced a 5- to 10-fold rise in peak systolic velocity.^[1]

Absorption is rapid (about 80% of a dose within 10 minutes), and peripheral venous alprostadil is low or undetectable, which is why systemic drug interactions are minimal and systemic effects are mainly those of local absorption and hypotension.^[1] Urethral delivery is far less efficient than injection. In a crossover comparison, the most-used doses were 1000 micrograms for MUSE (mean 922.5 micrograms) and 40 micrograms for intracavernosal alprostadil (mean 26.1 micrograms).^[6]

The delivery system

The MUSE pellet is a micro-suppository of alprostadil in polyethylene glycol 1450, 1.4 mm in diameter and 3 or 6 mm long, seated in the tip of a translucent hollow applicator. The components are medical-grade polypropylene and each system is sealed in its own foil pouch. The pellet dissolves in the urethra and does not require an injection.^[1]

The last US label (revised May 2024) lists 250, 500 and 1000 microgram systems. Historical trials and some non-US guidance used a 125-microgram dose; the last US label listed other strengths.^[1][3] MUSE is no longer marketed in the United States. The final DailyMed label (version 21, effective May 15, 2024) gives marketing end dates of December 31, 2022 for the 250-microgram system and April 30, 2023 for the 500- and 1000-microgram systems.^[1] Drugs@FDA and the Orange Book list all four approved strengths under NDA 020700 (125, 250, 500 and 1000 micrograms) as discontinued.^[20] For patients who hold supply or obtain MUSE elsewhere, the label remains the dosing and safety reference.

US dosing and administration

Decision	US label (May 2024)
Initial dose	250 micrograms under medical supervision
Titration	Adjust stepwise on separate occasions to the lowest dose sufficient for intercourse; monitor symptoms of hypotension and demonstrate correct technique
Maximum frequency	Two single-dose systems in 24 hours; the US label does not specify an additional seven-dose weekly ceiling
Expected response	Usually begins within 5–10 minutes and lasts approximately 30–60 minutes, with individual variation
Storage	Unopened pouches refrigerated at 2–8°C; room temperature 20–25°C for up to 14 days before use; do not expose above 30°C

These are product-specific instructions.^[1] EAU guidance describes a 500-microgram starting strategy, supported partly by an older open randomized trial; that is different from the US label's starting dose.^[3][4][1] In Ekman's trial, 166 men were randomized and 142 were included in efficacy analysis; a 500-microgram start improved early response but produced more penile pain during the first four weeks.^[4]

Doses needed in practice are high. In the pivotal trials, about 10%, 20%, 30% and 40% of randomized men were titrated to 125, 250, 500 and 1000 micrograms, respectively.^[1] In a retrospective clinic series (n = 270), the effective dose was 500 micrograms in 49.2% and 1000 micrograms in 42.2% of successful users.^[13] The AUA notes that higher doses bring more adverse events, so the lowest dose expected to work should be used, and it requires in-office instruction and dose titration before the medication is prescribed for home use.^[2]

Administration checklist

The US Instructions for Use (May 2024) provide the complete illustrated technique. The main steps are:^[1]

1. Urinate immediately beforehand; insert within 10 minutes of urination. Wash and dry hands.
2. Open the pouch, remove the protective cover without operating the button, and verify that the pellet is present. Avoid touching the stem and tip.
3. Gently stretch the penis to its full length and straighten the urethra. Insert to the applicator collar without force; withdraw slightly and reposition if there is discomfort or pulling.
4. Push the button until it stops (it moves only slightly), hold for five seconds, then release and gently move the applicator side to side to detach the pellet. Excessive pressure can scratch the urethral lining and cause bleeding.^[1]
5. Withdraw while keeping the penis upright and inspect the tip. If the pellet remains, follow the label's reinsertion steps.
6. With the penis upright and stretched, roll it between the hands for at least 10 seconds. Replace the cover and discard the single-use applicator.

Teaching pearls that patients most often miss:

• Urinate first. Residual urine in the urethra helps the pellet dissolve and disperse along the urethra.^[2]
• Straighten and hold the penis upright during insertion; the AUA describes placing the stem about 3 cm into the urethra, and the label instructs insertion to the applicator collar.^[1][2]
• Roll, then move. Rolling the penis between the hands disperses the medication. The AUA also advises walking or standing for about 10 minutes afterward to aid blood flow.^[2]
• Expect a warm, sensitive penis for a few hours; the label calls this normal.^[1]
• Use the dose chosen in the office and no more than two systems in 24 hours; change the dose only as the prescriber instructs.^[1]

Do not substitute older or another country's instructions for the supplied product leaflet. Check comfort, dexterity and vision during teaching, particularly after reconstruction or with altered sensation.

What efficacy estimates actually mean

Pivotal placebo-controlled trial

Padma-Nathan and colleagues enrolled 1,511 men. Of these, 996 (65.9%) achieved an intercourse-sufficient erection during clinic titration. Men responding in clinic entered the randomized home phase; among those reporting at least one home treatment, 299/461 (64.9%) receiving alprostadil versus 93/500 (18.6%) receiving placebo reported successful intercourse at least once over three months.^[5]

Among active-treatment men who reported intercourse at least once during the three-month home phase, about seven of ten MUSE administrations were followed by intercourse.^[1][5]

The AUA review found in-office positive-test rates of 20%–65.9% and intercourse success rates of 29.5%–78.1% across heterogeneous studies. Its approximately 73% per-dose result combined intercourse, orgasm or a 10-minute intercourse-sufficient erection; it was not an intercourse-only endpoint.^[2]

Clinical-practice experience

Outside the pivotal trials, results are more modest and more variable:

Study	n	Design	Result
Guay 2000	270 (229 followed)	Retrospective, after patient and partner education and office trial	56% success (intercourse in more than 66% of at least two attempts); of failures, 61.4% lacked efficacy and 38.6% had side effects (genital pain or urethral bleeding)[13]
Kim 2000 (Korea)	334	Multicenter, open	59.3% had a score 4–5 erection in clinic; 78.1% of the 228 men in home treatment had intercourse at least once over two months[14]
Ekman 2000	142 analyzed	Randomized open-label	68% reported intercourse at least once in 12 weeks[4]
Khan 2002 (UK)	100	Clinical practice	35% initially successful; only 43% of those still used it at six months[15]
Fulgham 1998	115	Urology practice, manufacturer algorithm	No more than 30% reached a score 4–5 erection in the office at any dose; 41.2% met strict criteria for orthostatic hypotension; 18.6% were still using MUSE at telephone follow-up 2–3 months after the last office test[16]

Set these against the trials: pain, insufficient erections and cost drive discontinuation, and follow-up and patient education substantially affect results.^[13][15][16]

Comparison with injections and continuation

In a randomized crossover study of 111 men, intracavernosal alprostadil produced intercourse-sufficient erections after 82.5% of administrations, compared with 53.0% for MUSE with optional constriction support. Patients and partners more often preferred injections. A separate randomized study of 60 men also favored injections for efficacy, but favored MUSE for comfort and continuation.^[6][7]

Outcome	Intracavernosal alprostadil (alfadex in Shabsigh 2000)	MUSE (optional ACTIS constriction band in Shabsigh 2000)
Shabsigh 2000 (n = 111, crossover): erections sufficient for intercourse, per administration	82.5%	53.0%
At least one sufficient erection	92.6%	61.8%
At least 75% of erections sufficient	75.0%	36.8%
Shokeir 1999 (n = 60; 30 per arm; 20 micrograms injection vs 1 mg MUSE): men reporting intercourse at least once during 3 months of home treatment	26/30 (87%)	16/30 (53%)[7]
Home treatment rated "easy"	40%	90%
Urogenital pain	47%	7%
Withdrawal before 3 months	67%	17%

The Shabsigh authors advised offering injection as first choice when oral therapy fails or is contraindicated; Shokeir concluded that MUSE is less effective but easier and better accepted.^[6][7]

These differing experiences argue against promising that a needle-free route will always be more comfortable or acceptable. Response in a supervised office trial, home usability, partner experience and follow-up are more useful than an isolated efficacy percentage. Long-term discontinuation remains common.^[3][6][7] EAU summarizes intercourse-sufficient erections in 30–65.9% of men, local pain in 29–41%, dizziness with possible hypotension in 1.9–14%, penile fibrosis or priapism in under 1%, urethral bleeding in about 5% and urinary tract infection in 0.2%; these ranges span heterogeneous studies. It also cites about 30% adherence to long-term therapy and efficacy significantly below intracavernous treatment.^[3]

Safety and contraindications

Rare priapism is still an emergency

The US label reports two cases of priapism among 1,511 patients (0.13%). A rigid erection lasting four hours or longer requires urgent medical assessment. See Priapism management.^[1][5]

Risk	Practical implication
Penile/urethral pain and spotting	Common local adverse effects. In the US label's home-treatment table, penile pain occurred in 32%, urethral burning in 12%, and minor bleeding/spotting in 5% of active-treatment patients
Hypotension and syncope	During clinic titration, symptomatic hypotension occurred in about 3% and syncope in 0.4%; supervise titration and prescribe the lowest effective dose
Antihypertensives	Additive hypotension is possible; review baseline pressure, orthostasis and other vasoactive drugs
Anticoagulation or bleeding disorder	Urethral abrasion may cause more bleeding. Assess risk individually; this is not an instruction to stop prescribed anticoagulants automatically
Female partner vaginal burning/itching	Reported in 5.8% of female partners of active-treatment patients versus 0.8% of female partners of placebo patients; the label states that medication versus resumption of intercourse as the cause is uncertain[1]

Rates above come from the product label and reflect its trial populations and observation periods.^[1] During in-clinic titration the label also reports penile pain in 36%, urethral pain in 13% and testicular pain in 5%, mostly mild and transient; dizziness in 4%; minor urethral bleeding or spotting in about 3%; and withdrawal for adverse reactions in about 7%. Fewer than 2% discontinued for adverse reactions during home treatment.^[1] Penile fibrosis was not reported in Ekman's 12-week trial or the post-prostatectomy MUSE subgroup; the US label reports priapism in 2/1,511 men (0.13%). These reports provide no injection comparator for fibrosis or priapism.^[1][4][17] Avoid driving or hazardous activities when dizziness or fainting could cause injury; postmarketing syncope has occurred within an hour of use.

The US contraindications include:^[1]

• Alprostadil hypersensitivity.
• Urethral stricture, balanitis, severe hypospadias or severe penile curvature, or acute or chronic urethritis.
• Conditions predisposing to priapism or venous thrombosis/hyperviscosity, including sickle cell anemia or trait, thrombocythemia, polycythemia and multiple myeloma.
• A medical condition making sexual activity inadvisable.
• Intercourse with a pregnant partner unless a condom barrier is used.

Use in patients with penile implants has not been studied; this is different from a labeled absolute contraindication. Prior reconstruction and spinal cord injury also require individualized anatomical and safety assessment rather than being automatically classified as label contraindications.^[1]

MUSE provides no contraception or protection against sexually transmitted infections. The label recommends adequate contraception when the partner can become pregnant and specifically requires a condom barrier with a pregnant partner.^[1]

Special populations and combinations

Spinal cord injury and constriction support

The frequently cited Bodner report involved 15 men with spinal cord injury, all previously successful with injections. After hypotension in the first three men, the remaining participants used a constriction ring. Erections remained less rigid than with injections, and the three men trying home MUSE discontinued it. Bodner's small uncontrolled report supports caution and supervised testing of ring-plus-MUSE in spinal cord injury; safety and efficacy across patients remain unestablished.^[8]

Bodner concluded that MUSE in spinal cord injury should always be used after placing a constriction ring, because of hypotension.^[8] If a specialist selects constriction support, teach safe removal and skin monitoring, particularly when sensation is reduced. EAU guidance for constriction rings advises removal within 30 minutes to avoid ischemic injury.^[3]

The ring is also studied more generally. In Ekman's trial, 8% of men reached a sufficient erection only at 1000 micrograms plus a pubic band, and the Shabsigh comparison allowed an optional constriction band with MUSE.^[4][6] The band is intended to keep blood in the corpora and improve rigidity.

After radical prostatectomy

MUSE can provide an assisted erection after prostatectomy when anatomy and safety permit. That differs from proving recovery of spontaneous erectile function.

Costabile's retrospective analysis of the MUSE trials identified 384 men whose erectile dysfunction followed radical prostatectomy (at least 3 months earlier). In this subgroup, 70.3% had an erection sufficient for intercourse in clinic and 57.1% of those on active drug had intercourse at least once at home, an overall success of about 40%. Clinic hypotension was lower than in other organic causes (0.8% vs 4.2%) but urethral pain or burning was higher (18.3% vs 10.4%). No urinary tract infection, fibrosis or priapism occurred.^[17]

In McCullough's open randomized comparison, 139 men started nightly intraurethral alprostadil and 73 started nightly sildenafil; 97 and 59 completed treatment, respectively. No final endpoint differed significantly between groups. Attrition, lack of an untreated control and assessment involving sildenafil after washout limit claims of equivalent rehabilitation efficacy or prevention of irreversible fibrosis.^[9]

Combination therapy and topical cream

Selected refractory patients may receive specialist-directed combinations, since alprostadil (cAMP pathway) and PDE5 inhibitors (cGMP pathway) act by different mechanisms. A review of nine publications on PDE5 inhibitor plus alprostadil (intracavernosal, intraurethral or topical) found improved IIEF scores over either drug alone, including after prostatectomy, without combination side effects causing discontinuation. The ISSM standard of practice grades this as level 3 evidence that a PDE5 inhibitor plus transurethral or intracavernosal therapy outperforms either monotherapy.^[18][19]

The Garrido-Abad study often cited for adding alprostadil to a PDE5 inhibitor used topical cream, with 170 patients assigned by preference (72 alprostadil alone, 98 combination). IIEF-5 rose from 12.4 to 17.1 with the combination but did not change significantly with alprostadil alone (12.2 to 12.7).^[10]

Topical alprostadil cream (Vitaros/Virirec, 200 or 300 micrograms with a permeation enhancer) is applied to the urethral meatus and is available in some European countries. EAU lists it, like MUSE, as a weak-strength alternative first-line option; adverse effects include penile erythema, burning and pain that usually settle within about two hours.^[3] A 2025 meta-analysis of 11 randomized and 4 non-randomized studies found that both topical and intraurethral alprostadil beat placebo, with heterogeneous, low-quality evidence. Confirm local approval, supply and instructions; topical cream is not an interchangeable substitute for a US urethral suppository or intracavernosal preparation.^[3][11][12]

Comparison across alprostadil formulations

Formulation	Route	Dose range	Main advantages	Main limitations
MUSE	Intraurethral pellet	250, 500 or 1000 micrograms (US label)	Needle-free; no injection-site fibrosis reported in the trials cited here; simple technique	Lower efficacy than injection; penile and urethral pain; hypotension; partner symptoms; high discontinuation[1][6]
Intracavernosal alprostadil	Injection	Typically tens of micrograms	Higher efficacy and patient/partner preference in crossover data	Needle required; penile pain; priapism and fibrosis risk[6][7]
Topical alprostadil cream (Vitaros/Virirec)	Meatal cream	200 or 300 micrograms	No applicator; used alone or with a PDE5 inhibitor	Regional availability; heterogeneous, low-quality evidence[3][10][12]

Practical follow-up

Expect substantial discontinuation. Trial completion was high in a selected, motivated population, but in practice series only a minority kept using MUSE at six months or later, with insufficient efficacy and pain the leading reasons.^{[5][13][15][16]} Schedule a check early to address pain, dose, technique and cost before patients quietly stop.

Reassess actual intercourse success, discomfort, dizziness, technique and partner experience. Adjust the dose with the prescriber, or discuss another treatment if the benefit does not justify the burden. Never increase frequency or combine vasoactive preparations simply because an office dose was inadequate. Route-specific dosing and the emergency plan should accompany every prescription.^[1][2]

See Also

• Intracavernosal injection agents
• PDE5 inhibitors
• Testosterone replacement
• Priapism management
• Erectile dysfunction (clinical)

References

1. Meda Pharmaceuticals/Viatris. MUSE (alprostadil) US prescribing information, Patient Information and Instructions for Use, revised May 2024 (DailyMed SPL version 21, effective May 15, 2024, the last version published; product listing shows marketing end dates of 12/31/2022 for 250 micrograms and 4/30/2023 for 500 and 1000 micrograms); accessed September 27, 2026. DailyMed.
2. Burnett AL, Nehra A, Breau RH, et al. Erectile Dysfunction: AUA Guideline. J Urol. 2018;200:633–641. doi:10.1016/j.juro.2018.05.004.
3. European Association of Urology. Guidelines on Sexual and Reproductive Health, Limited Update March 2026, sections 5.6.3.g and 5.6.12. EAU.
4. Ekman P, Sjögren L, Englund G, Persson BE. Optimizing the therapeutic approach of transurethral alprostadil. BJU Int. 2000. doi:10.1046/j.1464-410x.2000.00723.x.
5. Padma-Nathan H, Hellstrom WJ, Kaiser FE, et al. Treatment of men with erectile dysfunction with transurethral alprostadil. N Engl J Med. 1997;336:1–7. doi:10.1056/NEJM199701023360101.
6. Shabsigh R, Padma-Nathan H, Gittleman M, et al. Intracavernous alprostadil alfadex is more efficacious, better tolerated, and preferred over intraurethral alprostadil plus optional actis: a comparative, randomized, crossover, multicenter study. Urology. 2000. doi:10.1016/S0090-4295(99)00442-2.
7. Shokeir AA, Alserafi MA, Mutabagani H. Intracavernosal versus intraurethral alprostadil: a prospective randomized study. BJU Int. 1999. doi:10.1046/j.1464-410x.1999.00021.x.
8. Bodner DR, Haas CA, Krueger B, Seftel AD. Intraurethral alprostadil for treatment of erectile dysfunction in patients with spinal cord injury. Urology. 1999. doi:10.1016/S0090-4295(98)00435-X.
9. McCullough AR, Hellstrom WG, Wang R, et al. Recovery of erectile function after nerve sparing radical prostatectomy and penile rehabilitation with nightly intraurethral alprostadil versus sildenafil citrate. J Urol. 2010. doi:10.1016/j.juro.2010.01.062.
10. Garrido-Abad P, Senra-Bravo I, Manfredi C, et al. Combination therapy with topical alprostadil and phosphodiesterase-5 inhibitors after failure of oral therapy in patients with erectile dysfunction: a prospective, two-arm, open-label, non-randomized study. Int J Impot Res. 2022. doi:10.1038/s41443-020-00400-9.
11. Moncada I, Cuzin B. Clinical efficacy and safety of Vitaros/Virirec (alprostadil cream) for the treatment of erectile dysfunction. Urologia. 2015;82(2):84-92. doi:10.5301/uro.5000116.
12. Papadopoulos I, Tishukov M, Sokolakis I, et al. The effect of topical and intraurethral alprostadil on erectile function: a systematic review and meta-analysis. Andrology. 2025;13(8):2235-2245. doi:10.1111/andr.70025.
13. Guay AT, Perez JB, Velásquez E, et al. Clinical experience with intraurethral alprostadil (MUSE) in the treatment of men with erectile dysfunction. A retrospective study. Eur Urol. 2000;38(6):671-6. doi:10.1159/000020360.
14. Kim SC, Ahn TY, Choi HK, et al. Multicenter study of the treatment of erectile dysfunction with transurethral alprostadil (MUSE) in Korea. Int J Impot Res. 2000;12(2):97-101. doi:10.1038/sj.ijir.3900490.
15. Khan MA, Raistrick M, Mikhailidis DP, Morgan RJ. MUSE: clinical experience. Curr Med Res Opin. 2002;18(2):64-7. doi:10.1185/030079902125000318.
16. Fulgham PF, Cochran JS, Denman JL, et al. Disappointing initial results with transurethral alprostadil for erectile dysfunction in a urology practice setting. J Urol. 1998;160(6 Pt 1):2041-6. doi:10.1016/S0022-5347(01)62238-9.
17. Costabile RA, Spevak M, Fishman IJ, et al. Efficacy and safety of transurethral alprostadil in patients with erectile dysfunction following radical prostatectomy. J Urol. 1998;160(4):1325-8. doi:10.1016/s0022-5347(01)62527-8. PMID 9751346.
18. Moncada I, Martinez-Salamanca J, Ruiz-Castañe E, Romero J. Combination therapy for erectile dysfunction involving a PDE5 inhibitor and alprostadil. Int J Impot Res. 2018;30(5):203-8. doi:10.1038/s41443-018-0046-2.
19. Porst H, Burnett A, Brock G, et al. SOP conservative (medical and mechanical) treatment of erectile dysfunction. J Sex Med. 2013;10(1):130-71. doi:10.1111/jsm.12023.
20. US Food and Drug Administration. Drugs@FDA: MUSE (alprostadil) urethral suppository, NDA 020700 (Viatris), all four strengths listed as discontinued (data updated September 24, 2026); Orange Book data files downloaded September 27, 2026, same four products listed as DISCN. Drugs@FDA.