Injection therapy for Peyronie’s disease: pearls of wisdom
William O. Brant, Amanda Reed-Maldonado, and Tom F. Lue
Additional article information
Peyronie’s disease (Peyronies Disease) is a localized connective tissue disorder of the penis that may result in formation of
plaque, penile deformity, pain,
erectile dysfunction and emotional stress. It can affect the
tunica albuginea, septum, or intracavernous struts leading to curvature, shortening, indentation, or
hourglass deformity of the erect penis. Because it is a localized disease, a focal therapy seems to be the most rational approach. Additionally, patients are understandably hesitant to have surgery on the penis. This commentary summarizes the combined experience of
verapamil and
Xiaflex injection by the authors. Other practitioners use interferon and other medications. We do not use these and therefore have eliminated this from the discussion.
Verapamil injection
Although not FDA approved for use in Peyronies Disease,
verapamil has been used commonly for many years (1-3).
Verapamil is administered as 10 mg in 10
cc of NS, every 2 weeks. Our practice is to perform a penile block, use a 21 g needle to administer the medication, and to give six injections prior to reevaluation of the clinical situation. If there is good improvement but not quite enough, the patient may elect to have another six injections of 20 mg in 10
cc.
Although the number of patients receiving
verapamil has decreased since the FDA approved
Xiaflex, there still is a patient population that seems to benefit from this medication. Unlike
Xiaflex,
verapamil is given in a larger volume. In other studies, injection of saline alone has a good response rate, and it is unclear to us the relative role of the drug itself versus the hydro-distension effect of the large volume of saline.
Cost
Verapamil is substantially cheaper than
Xiaflex, and thus may be used when insurance coverage or other financial considerations prohibit the use of
Xiaflex.
Pain
Although
Xiaflex is not uncomfortable to receive, some patients have significant pain for up to 48 hours after the injection, with rare patients having discomfort beyond this period.
Verapamil is more painful to receive, likely due to the volume of fluid, but is not significantly painful thereafter. It hastens the resolution of Peyronies Disease-related pain. Although many studies have noted that resolution of pain is an eventuality in Peyronies Disease patients, it is often a considerable source of bother in those patients who have it, and resolution of pain as rapidly as possible is a very desirable outcome. We have found that
Xiaflex may be extremely uncomfortable in patients in whom pain is a predominant symptom.
Non-curvature deformities
Verapamil seems to have a superior outcome for deformities that are not purely curvature in nature. These include waists,
hourglass, and areas of instability or hinging. Although the deformity in these cases appears lateral, a lateral
plaque is relatively uncommon and these defects usually are associated with a typical, dorsally located
plaque. Our surgical experience has shown us that the area of indentation is a contracture, rather than an area of underlying corporal
fibrosis. The
dorsal plaque is associated with abnormalities in the intracorporal struts, which causes local contracture. Our theory is that
verapamil and/or the associated hydrodistension allows the struts to expand and thus corrects these types of abnormalities.
Stage of disease
With stable disease and heavy
plaque calcification,
verapamil seems to have much less efficacy than when used in the context of early disease and softer plaques. Overall, we prefer to use
Xiaflex in the context of stable plaques.
Xiaflex (
collagenase clostridium histolyticum) injection
The main difference between
Xiaflex and other injectable therapy is
Xiaflex’s ability to dissolve the collagenous fibrous tissue within the
plaque (4,5). However,
Xiaflex also carries the risks of
hematoma and
penile fracture due to thinning/softening of the
tunica albuginea. The modeling/stretching maneuver to expand/lengthen the contracture following
Xiaflex injection is as important as the injection itself. Clinical trials have clearly shown that the combination of injection plus modeling has the best results in reduction of penile curvature.
Location of injection
Anatomically, the thinnest portions of the
tunica albuginea are on the lateral aspect (3 and 9 o’clock positions) and between the
corpus spongiosum and the cavernosa (6 o’clock position). At this time, the company does not recommend injection to the
ventral plaque for fear of damaging the urethra. After more than 1,000 injections, we feel that the
ventral plaque is not necessarily a contraindication as long as the
plaque is clearly palpable, not calcified, and thick (>0.3 cm by ultrasound measurement). We have also found that
ventral plaques respond, in these situations, as well as
dorsal plaques. The urethra can always be spared as long as the
plaque can be firmly pinched between the thumb and index finger. The injection should be directed to the 5 and 7 o’clock positions not 6 o’clock position. We have seen herniation,
hematoma, and micro-rupture of the lateral tunica after injection of
Xiaflex to the lateral aspect of the penis. Therefore, we do not recommend
Xiaflex injection to lateral aspects of the penis for men with true lateral curvature. We have not injected
Xiaflex to sites of intracavernous or septal
fibrosis and therefore cannot recommend it at this time.
Injection technique
The instruction from the company is to insert the needle to the
plaque and slowly withdraw while injecting
Xiaflex solution. We feel that this may “waste” part of the injected
Xiaflex because it is very difficult to be certain that the needle is still inside the
plaque if one is injecting while withdrawing. Additionally, we have seen higher rates of ecchymosis and swelling, likely due to extravasation of
Xiaflex outside of the
plaque via the needle track. Instead, we prefer to forcefully inject
Xiaflex to the
plaque against the high resistance (Figure 1A,B). We also prefer to inject into at least two sites within the
plaque to avoid rupturing the thin
plaque with the total amount 0.25 mL. Of course, a large and thick
plaque is not a problem with 0.25 mL.
Figure 1
Figure 1
Penile ultrasound 5 minutes after
Xiaflex injection into the
plaque showing increased echogenicity from micro-bubbles in the
plaque in (A) transverse view and (B) longitudinal view.
Since the volume of
Xiaflex is small, it is important to pick the best spot for injection. This can be done in several ways, but we prefer to compare the palpable
plaque with the patient’s erection and choose the site that corresponds to the site of maximum deformity. One author prefers to have the patient mark this site with a permanent marker the day prior to the injection so he has the correspondence of the palpable
plaque, the patient’s subjective view of the area of maximum deformity, and the view of this area as seen on auto-photography. The other authors prefer to inject a vasodilator (most of time with 0.05 mL of phentolamine/papavarine solution) and self-stimulation to induce erection and mark it with a marker before giving the local anesthetic.
Patient taking anticoagulants
Discontinuation of an anticoagulant or antiplatelet medication for 5 days prior to injection is preferred. If contraindicated (e.g., cardiac stents that require aspirin), we teach the patient to apply a loose compressive dressing and change this daily for 2-3 days to prevent excessive ecchymosis.
To operate or not to operate
Bleeding during or after nocturnal erections can present with ecchymosis (bleeding within the subcutaneous tissue) (Figure 2) or
hematoma (blood clots between Buck’s fascia and tunica) (Figure 3). In both conditions, a penile ultrasound to confirm the diagnosis is all that needed (Figure 4). Ultrasound examination of the tunica is operator dependent, and such examinations should only be done if the examiner is comfortable with this. On the other hand, if ecchymosis /
hematoma developed suddenly during or after sexual intercourse,
penile fracture is the most likely diagnosis until proven otherwise. If penile ultrasound confirms a sizeable tunical rupture, surgical repair is recommended.
Figure 2
Figure 2
Ecchymosis of penis and pubic area 3 days after
Xiaflex injection.
Figure 3
Figure 3
Hematoma at dorso-lateral aspect of penis 7 days after
Xiaflex injection.
Figure 4
Figure 4
Penile ultrasound 4 days after
Xiaflex injection in a patient with
hematoma. No obvious rupture/disruption of the
tunica albuginea is noted.
Hourglass deformity or unilateral indentation
If the
plaque is palpable at the
dorsal or
ventral aspect, we have injected
Xiaflex into the
plaque followed by daily stretching with a vacuum erection device with reasonably good results. If only lateral
plaque is palpable, we do not recommend
Xiaflex injection anymore because we have seen
hematoma and herniation after
Xiaflex injection in several cases.
Injection schedule
The package insert recommends two injections 1-3 days apart, followed by daily stretching and manipulation by the patient for 6 weeks. In some patients who developed severe skin edema and ecchymosis, we have waited up to 1 week to give the second injection. In some men with small
plaque, we elected to give one
Xiaflex injection followed by modeling to prevent potential tunical rupture.
Conclusions
If a patient is interested in the most definitive, rapid treatment of a stable Peyronie’s deformity, surgical approaches continue to be the gold standard. However, most of our patients are understandably hesitant to pursue surgery and are willing to undergo the inconvenience of repeated injections to achieve a less invasive approach to their deformities. Our combined experience with over 1,000 patients receiving
verapamil and over 400 patients receiving
Xiaflex has shown us that these medications can be very successful and satisfying, but rely on (I) careful consideration of the patient’s individual characteristics, (II) adherence to good techniques for injecting and (III) patient’s willingness to comply with their at-home physical therapy.
Verapamil is appropriate for less stable disease and in softer plaques, whereas we prefer
Xiaflex for more stable disease and denser plaques. We avoid
Xiaflex in true lateral plaques (which are very uncommon). For technique, a fanning technique is appropriate for
verapamil, administered via a 21 g needle for maximum hydrodistention. For
Xiaflex, the needle should remain within the densest portion of the
plaque, corresponding the point of maximum deformity, in order to minimize extravasation and subsequent ecchymoses. The best results are seen when patients comply with manipulation of the
plaque, via a combination of stretching, gentle bending of the erect penis in the opposite direction of the curve, and massage of the
plaque.
Acknowledgements
None.
Footnotes
Conflicts of Interest: The author TF Lue was a consultant to Auxillium Pharmaceuticals, Inc., the others have no conflicts of interest to declare.
Article information
Transl Androl Urol. 2015 Aug; 4(4): 474–477.
doi: 10.3978/j.issn.2223-4683.2015.08.09
PMCID: PMC4708590
PMID: 26812930
William O. Brant,1 Amanda Reed-Maldonado,2 and Tom F. Luecorresponding author2
1Department of Surgery (Urology), Center for Reconstructive Urology and Men’s Health, University of Utah, Salt Lake City, USA; 2Department of Urology, University of California, San Francisco, USA
corresponding authorCorresponding author.
Correspondence to: Tom F. Lue. Department of Urology, University of California, San Francisco, USA. Email:
[email protected]Received 2015 Aug 15; Accepted 2015 Aug 19.
Copyright 2015 Translational Andrology and Urology. All rights reserved.
See the article "
Collagenase Clostridium Histolyticum: A Review in Peyronie's Disease." in Drugs, volume 75 on page 1405.
See the article "Clinical efficacy, safety and tolerability of
collagenase clostridium histolyticum for the treatment of peyronie disease in 2 large double-blind,
randomized,
placebo controlled phase 3 studies." in J Urol, volume 190 on page 199.
This article has been cited by other articles in PMC.
Articles from Translational Andrology and Urology are provided here courtesy of AME Publications
References
1. Abern MR, Larsen S, Levine LA. Combination of penile
traction, intralesional
verapamil, and oral therapies for Peyronie's disease. J Sex Med 2012;9:288-95. Erratum in J Sex Med 2012;9:945. [PubMed] [Google Scholar]
2. Alizadeh M, Karimi F, Fallah MR. Evaluation of
verapamil efficacy in Peyronie's disease comparing with pentoxifylline. Glob J Health Sci 2014;6:23-30. [PMC free article] [PubMed] [Google Scholar]
3. Chung E, Garcia F, Young LD, et al. A comparative study of the efficacy of intralesional
verapamil versus normal saline injection in a novel Peyronie disease animal model: assessment of immunohistopathological changes and erectile function outcome. J Urol 2013;189:380-4. [PubMed] [Google Scholar]
4. Dhillon S.
Collagenase Clostridium Histolyticum: A Review in Peyronie's Disease. Drugs 2015;75:1405-12. [PubMed] [Google Scholar]
5. Gelbard M, Goldstein I, Hellstrom WJ, et al. Clinical efficacy, safety and tolerability of
collagenase clostridium histolyticum for the treatment of peyronie disease in 2 large double-blind,
randomized,
placebo controlled phase 3 studies. J Urol 2013;190:199-207. [PubMed] [Google Scholar].
So
Verapamil suppose to work on non curvature deformities
Author
Topic: VERAPAMIL Injections results (Positive & Negative) (Read 36409 times)
February 20, 2013, 08:14:20 PM