Peyronie's Disease Agents
Collagenase clostridium histolyticum (CCH; Xiaflex) is the only FDA-approved medication for Peyronie's disease (PD). Treatment should address the patient's functional difficulty and goals; a smaller curvature measurement is not by itself proof of restored intercourse, improved erections or relief of distress. See the clinical PD page for assessment and treatment selection.[1][2]
The 2026 EAU guideline and the Fifth ICSM recommendations (published December 2025/January 2026) update the context around the still-current 2015 AUA PD guideline. Recommendations and drug availability differ; do not treat an old permissive recommendation as current US availability or FDA approval.[2][3][4]
Collagenase clostridium histolyticum
Indication and selection
The US indication is an adult man with a palpable plaque and curvature at least 30° at treatment initiation. The label does not itself impose the narrower AUA selection criteria of stable disease, greater than 30° and less than 90°, and erections sufficient for intercourse with or without medication.[1][2]
IMPRESS excluded ventral curvature, isolated hourglass deformity and calcification that interfered with injection. A ventral curve is not synonymous with a plaque involving the urethra: urethral involvement is a label contraindication, whereas ventral curvature was a trial exclusion. Use outside the pivotal population requires explicit discussion of the more limited evidence. CCH targets plaque collagen; it is not an established treatment for ED or penile pain.[1][2]
US labeled preparation and course
| Item | Instruction |
|---|---|
| Dose | 0.58 mg into the plaque responsible for the curvature |
| Reconstitution | Add 0.39 mL of the supplied diluent; inject 0.25 mL of the reconstituted solution. The whole vial contains 0.9 mg and is not the labeled PD dose. |
| Cycle | Two injections 1–3 days apart, then clinician modeling 1–3 days after the second injection |
| Interval/course | About 6 weeks between cycles, up to 4 cycles / 8 injections |
| Stopping | Omit subsequent cycles if curvature becomes less than 15° or further treatment is clinically inappropriate; safety of more than one course is unknown. |
| Delivery | REMS-certified prescriber and healthcare site; follow the complete current preparation/injection instructions. |
These are label instructions, not a requirement that every patient complete eight injections.[1]
Injection and modeling considerations
Identify the target at maximal concavity during erection, then inject the plaque with the penis flaccid. The label describes a 27-gauge, half-inch needle entering from the plaque's side and advancing transversely without passing through it. Avoid the urethra, nerves, vessels and corpora; never direct the needle perpendicularly beneath the plaque. Deposit the dose within the plaque during withdrawal. This summary does not replace REMS training.[1]
Clinician modeling is followed by taught, gentle home exercises: flaccid stretching three times daily and gentle straightening during spontaneous erections, without pain. Do not use a vacuum erection device during Xiaflex treatment under the US label. Published traction/VED combination protocols are not all the labeled regimen; timing and force need a specific specialist plan.[1]
No sexual activity between the two injections. Wait at least 4 weeks after the second injection of each cycle, and until pain and swelling have resolved. A popping sensation with sudden detumescence, marked bruising/swelling, severe pain, hematuria or voiding difficulty warrants prompt assessment for corporal rupture or other serious injury.[1]
Safety
The boxed warning concerns corporal rupture and serious penile injury. In pooled controlled/uncontrolled clinical experience, confirmed rupture occurred in 5/1,044 (0.5%), another 9/1,044 (0.9%) had findings in which rupture could not be excluded, and severe penile hematoma occurred in 39/1,044 (3.7%). These categories and denominators should not be combined with the separate randomized-trial adverse-event table.[1]
- Contraindications: plaque involving the urethra; prior hypersensitivity to Xiaflex or therapeutic collagenase.
- Bleeding: abnormal-coagulation patients were excluded from trials except low-dose aspirin (up to 150 mg/day). The label recommends avoiding use with coagulation disorders/concomitant anticoagulants other than low-dose aspirin; safety with anticoagulants within the preceding 7 days is unknown. This is not an instruction to stop prescribed anticoagulation without an individualized plan.
- Other important reactions: anaphylaxis, acute post-injection back pain and syncope/presyncope. Postmarketing penile hematoma has occasionally led to skin/soft-tissue necrosis requiring surgery. Lie down if presyncopal and report serious symptoms promptly.[1]
Pivotal benefit and clinically meaningful outcomes
IMPRESS I/II randomized 832 men; the label's efficacy population comprised 612 with required curvature and PDQ data. At 52 weeks, mean curvature improved by 35.0% vs 17.8% in trial 1 and 33.2% vs 21.8% in trial 2. Both groups received modeling. These are changes from baseline; the drug's added benefit is smaller than the treated-group change.[1]
The 2023 Cochrane review estimated the longer-term between-group difference at 6.9° (95% CI 4.16–9.64°) favoring CCH, below its prespecified 12° threshold for clinical importance. That judgment depends on the chosen threshold and the patient's goals; it does not mean zero statistical effect. Treatment-related adverse events increased (RR 2.32, 95% CI 1.98–2.72). Evidence for intercourse outcomes was absent in this comparison.[5]
Later cycles and long-term follow-up
| Study | Finding and limit |
|---|---|
| Ziegelmann 2023, post hoc IMPRESS analysis | Of those not meeting a 20% response after cycle 1, 60.8% met it by cycle 4. This supports discussing further cycles in suitable patients; it was not randomization to stopping versus continuing and does not override label stopping rules.[6] |
| Goldstein 2020, five-year follow-up | 280 enrolled, 204 completed follow-up; year-5 curvature analysis included 180. An additional mean 4.3° improvement was observed without further CCH. Selected follow-up and attrition limit generalization; this is not five-year randomized evidence.[7] |
| Goldstein 2020, calcification subgroups | Stippled/non-injection-obstructing calcification groups had initial improvements that persisted. Calcification does not imply no possible response; dense calcification preventing injection is a different problem.[8] |
Lipshultz's subgroup analysis found statistically significant comparisons in some strata but not others. A nonsignificant small subgroup is not proof of no treatment effect, nor does it establish that erectile dysfunction or any calcification categorically precludes benefit.[9]
Mechanical adjuncts and surgery comparisons
Alom's 2019 nonrandomized registry analyzed 113 completers with objective data from 287 men with traction-use information. CCH plus RestoreX was associated with greater curvature and length changes than CCH alone or other devices. Selection, adherence and a single-center design limit causal inference; this does not prove that every other traction device is ineffective.[10]
A 2023 randomized trial assigned 40 men to CCH or surgery, both with traction and sildenafil; 38 had 3-month data. Surgery achieved greater curvature correction (84% vs 54%); the CCH arm had greater preserved/gained length and fewer reported adverse events. This small, short trial illustrates tradeoffs rather than a universally superior treatment.[11]
For device details see penile traction therapy. Historical economic models are not current patient prices: obtain actual drug, administration and insurance estimates. CCH remains available in the US through REMS; EAU notes withdrawal from the European market.[1][3]
Interferon α-2b
The 2015 AUA allowed intralesional interferon (Conditional, Grade C), with counseling about flu-like symptoms, sinusitis and swelling. The 2026 EAU no longer recommends it, citing limited evidence and withdrawal from US/European markets in 2021. It should not be presented as a readily available default alternative or the proven best option for ventral plaques.[2][3]
Older placebo-controlled results suggested curvature improvement, but reports by Hellstrom and Kendirci describe the same trial, not two independent replications. Cochrane rated the evidence very uncertain. The absence of ruptures in small series does not establish “no rupture risk.”[5]
Verapamil and nicardipine
Intralesional verapamil is off-label. AUA2015 does have a formal Conditional Grade C recommendation allowing it, while emphasizing weak/conflicting evidence; the older statement that AUA issued no recommendation was incorrect. EAU2026 finds the evidence insufficient to support injected calcium-channel blockers. ICSM2024 offers a conditional verapamil option. These are real guideline differences, not an established equal alternative to CCH.[2][3][4]
Study protocols vary widely. Uncontrolled reductions in pain or curvature do not isolate drug effects from natural history, injection or modeling. Neither verapamil nor nicardipine has robust evidence of a clinically important advantage over placebo. Local bruising and pain, dizziness and nausea require counseling; “no systemic effects” or “no rupture risk” is too absolute.[2][3][5]
Oral agents
Pain and concomitant erectile dysfunction
NSAIDs can treat active-phase pain when otherwise appropriate. PDE5 inhibitors can treat coexisting ED or difficulty with penetration; see the PDE5 hub for doses and contraindications. A retrospective tadalafil study (191 men) reported less short-term curvature progression among men choosing treatment, but this does not establish disease modification. ICSM concludes oral drugs have little established effect on significant deformity reduction.[3][4][12]
Agents without a supported routine role
| Agent | Evidence and practical interpretation |
|---|---|
| Vitamin E, tamoxifen, procarbazine, omega-3, vitamin E plus L-carnitine | AUA recommends against offering these for PD. Preclinical antifibrotic mechanisms and changes in uncontrolled series do not overturn that conclusion.[2] |
| Pentoxifylline, colchicine, CoQ10 | AUA's “Other Treatments” means insufficient evidence even for a conditional recommendation, not endorsement as inexpensive adjuncts. Cochrane excluded specified studies for data-integrity concerns; this should not be generalized into accusations about all studies or investigators.[2][5] |
| POTABA | One trial randomized 103 men with early noncalcified disease, but emphasized 75 completers. The plaque/composite response signal did not establish reversal of existing curvature; attrition and low-certainty outcomes limit routine use.[13] |
Tamoxifen has clinically important harms despite attractive laboratory mechanisms. In a 64-patient male breast-cancer cohort, sexual dysfunction occurred in 14 and 13 stopped treatment for toxicity, including four thromboembolic events. Those rates are not PD-specific estimates, but illustrate why an unproven indication should not inherit a presumption of safety.[14]
Emerging injections
Hyaluronic acid
EAU2026 weakly recommends intralesional HA for acute-phase pain and/or curvature, while explicitly acknowledging limited evidence and the lack of placebo-controlled data. This does not establish FDA approval for PD, nor superiority for erectile function. Different products and injection-plus-device regimens cannot be assumed equivalent.[3]
Older network rankings rely on sparse, heterogeneous direct and indirect comparisons. They do not establish a clinically important, reproducible advantage of HA over the other agents for erections.
Platelet-rich plasma
Ledesma's 2024 trial update reported 41 randomized, with a preliminary analysis of 28. A within-sequence curvature improvement after crossover does not establish comparative efficacy or prove a delayed mechanism. No adverse events in that small interim sample cannot establish safety for widespread use. The Fifth ICSM consensus finds no convincing evidence supporting PRP/cell-based therapy; EAU emphasizes its limited evidence.[3][4][15]
See platelet-rich plasma for the broader evidence and formulation limitations.
Botulinum toxin and corticosteroids
Evidence is sparse and does not support routine PD treatment. EAU2026 excludes them from detailed treatment discussion because of poor evidence. AUA2015 lists steroid regimens among unproven Other Treatments; it does not contain the previously attributed blanket Clinical Principle against steroid injection. Neither limited historical responses nor proposed scar biology justifies an established treatment protocol.[2][3]
References
1. Xiaflex. Current US prescribing information, including dosage 2.2, contraindications, warnings, clinical studies 14.2 and patient counseling. DailyMed.
2. Nehra A, Alterowitz R, Culkin DJ, et al. Peyronie's disease: AUA guideline. J Urol. 2015;194:745–753. doi:10.1016/j.juro.2015.05.098.
3. EAU. Sexual and Reproductive Health Guidelines (2026), Penile curvature. Current chapter.
4. Chung E, Ziegelmann M, Lin HC, et al. Management of Peyronie's disease: recommendations from the Fifth International Consultation on Sexual Medicine (ICSM 2024). Sex Med Rev. 2026;14:qeaf068. doi:10.1093/sxmrev/qeaf068.
5. Rosenberg JE, Ergun O, Hwang EC, et al. Non-surgical therapies for Peyronie's disease. Cochrane Database Syst Rev. 2023;7:CD012206. doi:10.1002/14651858.CD012206.pub2.
6. Ziegelmann M, Hu Y, Xiang Q, et al. Incremental treatment response by cycle with collagenase clostridium histolyticum for Peyronie's disease: a pooled analysis of two phase 3 trials. Urology. 2023;175:126–131. doi:10.1016/j.urology.2023.02.019.
7. Goldstein I, Lipshultz LI, McLane M, et al. Long-term safety and curvature deformity characterization in patients previously treated with collagenase clostridium histolyticum for Peyronie's disease. J Urol. 2020;203:1191–1197. doi:10.1097/JU.0000000000000743.
8. Goldstein I, McLane MP, Xiang Q, et al. Long-term curvature deformity characterization in men previously treated with collagenase clostridium histolyticum for Peyronie's disease, subgrouped by penile plaque calcification. Urology. 2020;146:145–151. doi:10.1016/j.urology.2020.08.045.
9. Lipshultz LI, Goldstein I, Seftel AD, et al. Clinical efficacy of collagenase clostridium histolyticum in the treatment of Peyronie's disease by subgroup. BJU Int. 2015;116:650–656. doi:10.1111/bju.13096.
10. Alom M, Sharma KL, Toussi A, Kohler T, Trost L. Efficacy of combined collagenase clostridium histolyticum and RestoreX penile traction therapy in men with Peyronie's disease. J Sex Med. 2019;16:891–900. doi:10.1016/j.jsxm.2019.03.007.
11. Green B, Flores A, Warner J, et al. Comparison of collagenase clostridium histolyticum to surgery for the management of Peyronie's disease: a randomized trial. J Urol. 2023;210:791–802. doi:10.1097/JU.0000000000003634.
12. Spirito L, Manfredi C, La Rocca R, et al. Daily low-dose tadalafil may reduce the penile-curvature progression rate in patients with acute Peyronie's disease: a retrospective comparative analysis. Int J Impot Res. 2024;36:129–134. doi:10.1038/s41443-022-00651-8.
13. Weidner W, Hauck EW, Schnitker J, et al. Potassium paraaminobenzoate (POTABA) in the treatment of Peyronie's disease: a prospective, placebo-controlled, randomized study. Eur Urol. 2005;47:530–535. doi:10.1016/j.eururo.2004.12.022.
14. Pemmaraju N, Munsell MF, Hortobagyi GN, Giordano SH. Retrospective review of male breast cancer patients: analysis of tamoxifen-related side-effects. Ann Oncol. 2012;23:1471–1474. doi:10.1093/annonc/mdr459.
15. Ledesma BR, Velasquez DA, Egemba C, et al. A phase 2 randomized, placebo-controlled crossover trial to evaluate safety and efficacy of platelet-rich plasma injections for Peyronie's disease: clinical trial update. Int J Impot Res. 2024;36:813–817. doi:10.1038/s41443-024-00844-3.