Page 1

November 2010

www.TheUrologyNurse.com

VOL 2, NO 6 • SUPPLEMENT

S U P P L E M E N T

Reports from the

Society of Urologic Nurses and Associates (SUNA) 2010 In Recognition of Urology Nurses and Associates Week

Brought to you by Watson, the manufacturer of

©2010 Novellus Healthcare Communications, LLC


Urology Nurses and Associates Week

We Celebrate

Your Commitment to Caring

Watson would like to say thank you to the urologic healthcare professionals who provide unique and challenging care every day. During the week of November 1-7, Watson will join the Society of Urologic Nurses and Associates (SUNA) to celebrate urologic healthcare professionals everywhere. At Watson, we share your commitment to urologic health. Our therapeutic portfolio includes products for 3 of the top 5 urologic conditions—BPH,* prostate cancer, and OAB.† By specializing in treatment options that continue to change the landscape of urology, Watson is helping people live better.

*

Benign prostatic hyperplasia Overactive bladder

© 2010, Watson Pharma, Inc., Morristown, NJ 07960. All rights reserved. 06877 9/10


TABLE OF CONTENTS

Directors, Client Services Mark Timko mark@novellushc.com Russell Hennessey Russell@novellushc.com

4

Conference Highlights: Society of Urologic Nurses and Associates

Jack Iannaccone jack@novellushc.com Editorial Director Kristin Lee Siyahian Copy Editor Bjarne Hansen

4 5 6

A Prescription for Everyday Ethics

Senior Production Manager Alaina Pede Business Manager Blanche Marchitto Executive Administrator Andrea Boylston

Physical Therapy for Pelvic Floor Dysfunction

Editorial Contact Telephone: 732-992-1891 Fax: 732-656-7938 Novellus Healthcare Communications, LLC 241 Forsgate Drive, Suite 205D Monroe Township, NJ 08831

Benign Prostatic Hyperplasia: Evaluation; Treatment Options

11

A SUNA Debate: Should We Really be Using PSA?

13

Simple Intervention Boosts Sperm Cryopreservation in Men With Cancer

14

Anejaculation Common After Radiotherapy for Prostate Cancer

EDITORIAL CORRESPONDENCE should be addressed to EDITORIAL DIRECTOR, Novellus Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205D, Monroe Township, NJ 08831. E-mail: kristin@novellushc.com. POSTMASTER: CORRESPONDENCE REGARDING SUBSCRIPTIONS OR CHANGE OF ADDRESS should be directed to CIRCULATION DIRECTOR, Novellus Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205D, Monroe Township, NJ 08831. YEARLY SUBSCRIPTION RATES: One year: $99.00 USD; Two years: $149.00 USD; Three years: $199.00 USD. Correspondence regarding permission to reprint all or part of any article published in this journal should be addressed to REPRINT PERMISSIONS DEPARTMENT, Novellus Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205D, Monroe Township, NJ 08831. The ideas and opinions expressed in The Urology Nurse®-NP/PA do not necessarily reflect those of the Editorial Board, the Editorial Director, or the Publisher. Publication of an advertisement or other product mention in The Urology Nurse®-NP/PA should not be construed as an endorsement of the product or the manufacturer’s claims. Readers are encouraged to contact the manufacturer with questions about the features or limitations of the products mentioned. Neither the Editorial Board nor the Publisher assumes any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this periodical. Please convey any errors to the Editorial Director. The Urology Nurse®-NP/PA: ISSN# applied for.

The Urology Nurse®-NP/PA is published by Novellus Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205D, Monroe Township, NJ 08831. Telephone: 732992-1891. Fax: 732-656-7938. Copyright ©2010 by Novellus Healthcare Communications, LLC. All rights reserved. The Urology Nurse®-NP/PA is a registered trademark of Novellus Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the Publisher. Printed in the United States of America.

Novellus Healthcare Communications

3


CONFERENCE HIGHLIGHTS: SUNA 2010

Conference Highlights: Society of Urologic Nurses and Associates (SUNA) October 8-11, 2010, Boston, MA Introduction

Meeting for the 41st annual conference, over 400 SUNA members gathered to hear the latest data regarding medication, and to review, and in some cases train in, advanced techniques for the diagnosis and management of urologic dysfunctions. Reviewed in this Urology Nurse – NP/NA newsletter are four presentations representing a range of interests, from the ethics of every day nursing decisions to physical therapy to improve symptoms of incontinence to the effective management of benign prostate hyperplasia. Also included are highlights from a SUNA debate regarding the medical utility of widespread PSA screening.

A Prescription for Everyday Ethics The fine art of knowing, and doing, what must be done Laughter is a common response to keynote addresses, but tears, far less so. This might be especially true given a topic such as “Ethics in Today’s Healthcare Environment: Why Being Ethical Matters.” However, Jack A. Gilbert, EdD, FACHE, quickly set the tone by asserting that ethics are at the core of the human condition and that “it’s not just about work, it’s about our lives.” It’s about the courage it takes to speak up, even in those small moments when something just does not seem quite right. It’s about what happens in those moments when you choose to either say something or just quietly walk away. To put the issue in perspective, Gilbert related the history of the healthcare giant Johnson & Johnson (J&J), a highly successful business that began life with, at its core, a hierarchical code of ethics: The welfare of customer comes first; profits of shareholders last. With this credo as the organizing principle, J&J has thrived for over 100 years. That is, until recently. J&J has experienced a series of setbacks, the last one occurring this past September, when the recall of the analgesic Motrin prompted a congressional investigation. “Just because you have something in place [the credo] it doesn’t mean that is still has life. It has to be regenerated.” What J&J

4

November 2010

fell victim to, said Gilbert, is what he termed “ethical erosion,” which is in essence the acceptance of that which is just a little bit wrong. Once a little wrong is accepted, a great big wrong may well be in your future. Consider the workaround: There is a protocol in place, but there’s simply no time – you’re being commanded, driven by the so-called “tyranny of the urgent,” but the work must be done, so just this once you make an exception, and procedure is ignored. “Well-meaning people in wellmeaning organizations are susceptible to ethical erosion,” said Gilbert. The problem is that it sets a precedent.

It’s about the courage it takes to speak up, even in those small moments when something just doesn’t seem quite right. Illustrating this point is a recent study of medical errors: Imagine the shape of a pyramid constructed from the bottom up by mishaps of escalating seriousness; sentinel events, being the lowest in number, are represented as the peak of the pyramid, with harmful events just below, and nonharmful events – being the most common, in which things went just a little bit wrong – serving as the pyramid’s base. Having drilled down to discover the root cause of

sentinel events, what the study found was that error started out small – at the base. Gilbert extended this conclusion by suggesting that the very ground on which the pyramid sits represents the event of the workaround, the moment where nothing actually went wrong, yet still managed to spark the genesis of a serious, life-threatening lapse in procedure. Is the solution medical perfection? No. But on a day-to-day basis it’s about where to draw the line. And it shouldn’t be comparative; it’s about what is non-negotiable behavior for the individual. “Common practice is not ethical practice,” said Gilbert. “Just because someone else does it doesn’t make it right.” Gilbert has actually heard complacency defended as being relative to the industry as a whole. “I have an actual fear that I will see a billboard someday and it will say ‘We hurt fewer people than our competition.’ ” Ethical Wisdom “If ethical erosion is subtle, I suggest something equally subtle to oppose it – ethical wisdom.” By this Gilbert means the innate awareness of right and wrong. Though indeed subtle, and perhaps vague, these gut feelings have generated real data. Recall the 100,000 Lives Campaign sponsored by the Institute for Healthcare Improvement, a national effort to reduce preventable deaths. Reporting to rapid response teams, nurses, and even family members of patients, were encouraged to speak up when they felt something was wrong


CONFERENCE HIGHLIGHTS: SUNA 2010

with the patient, or patient care, even if the concern could not be readily identified. Eighteen months after the program’s initiation, an estimated 122,000 lives were saved in the 3100 participating hospitals. Gilbert credits this accomplishment to the nurse’s innate sense of what is the right thing to do. The sense exists for wrong action, as well as inaction. Yet, in everyday life, communicating this sense is problematic. “Even the simplest conversation can be difficult to have,” said Gilbert. If you’re in a meeting and you’re uncomfortable with what’s being said… Do you stick your neck out? Do you risk censure, or possibly a friendship? You might even doubt that inner sense, thinking, Well, what do I really know? “It’s not easy,” Gilbert acknowledged, “it’s about trusting yourself.” It’s also about having faith in a collective wisdom. “I’m not saying everyone has it in equal measure, but there’s enough to go around.” Talk to your peers. What you sense, what you feel, someone else is feeling. Where this leads critically depends on what Gilbert describes as the existing ethical culture experienced in the workplace, and here is where the topic becomes concrete. The Action Items of Ethical Culture These five qualities create and sustain the body of ethical culture: Mindfulness Acknowledge your gut feelings. Remain aware. Voice If you see something, say something. Does this carry risks? Certainly. Yet, it calls into question the very reasons why someone enters the healthcare profession: to be of service; to help those who can’t help themselves; to put the needs of the patient first. Respect Striving to understand others rather than fighting to be understood. Truly, deeply, listening to the ideas of others will often reveal two things: 1) There is more than one way to skin a cat, and 2) You have allies you never dreamed of.

Figure 1. Ethical Erosion and Ethical Wisdom Will Impact the Health of Ethical Pathways

Intentions: Vision, Mission, Values, Strategy, Goals

Ethical Erosion

Ethical Pathways

Ethical Wisdom

Performance: Safety, Quality of Care, Financial Health, Satisfaction, Retention, Reputation

© New Page Consulting, Inc. All rights reserved.

Tenacity Stick to your guns. This is not as dreary as it sounds. When you spend your day doing what you value, the personal rewards are clear – it’s energizing. Legacy Meaning, work toward an ethical bequest, a lasting institutional integrity, in whatever small way you can.

“In working toward this ethical culture, we may not finish, we may not see the grand ending, but we will pass it on.”

“In working toward this ethical culture, we may not finish, we may not see the grand ending, but we will pass it on,” said Gilbert. “The small moments in which we chose to say something or not, those are the moments in which cathedrals are built.” ❖

Physical Therapy for Pelvic Floor Dysfunction Your patients want a return of function; PTs want to see your patients

To this final point Dr Gilbert used the example of one of the grandest cathedrals in the world, Notre Dame, Paris. Construction of this extraordinary building, using architectural methods without precedent, began in 1160 and was completed in 1345. No one who conceived of the structure, and only a very few who participated in its creation ever saw the completed cathedral, yet, day by day, in individual small measures, artisans came to work and did their part.

“Physical therapy (PT) is not just about doing Kegels.” So began Laurie Knox, PT, York Hospital, York, ME. In fact, PT for your patients with pelvic floor (PF) dysfunction may involve a range of muscle training techniques from Kegels, certainly, to electrical stimulation, biofeedback, the use of weights or, in some cases, a simple change in behavior. To choose among them one must first recognize the highly specific needs of the individual before designing a treatment plan. Briefly, the PF consists of the urogenital triangle (first, second, and third layer); the anal triangle; bony boundaries; and the pelvic diaphragm. The overall function of the PF is the support of organs: the sphinc-

Novellus Healthcare Communications

5


CONFERENCE HIGHLIGHTS: SUNA 2010

teric closing off of all openings (the focus of this discussion), and sexual function (dysfunction of which may cause painful intercourse, not discussed here). And then, there are muscles; “Muscles are muscles no matter where they are in the body, and there are a lot of them in the pelvic floor.” The pelvic diaphragm consists of two paired muscles, the levator ani, and the coccygeus, which close the inferior outlet of the pelvis, while both supporting the PF and elevating it to help release feces. Other muscles include the piriformis muscle and the obturator internus. “These two are very important from the PT perspective,” said Knox, “because these muscles are very tight in a lot of people but are critical to normal function.” PF dysfunctions include: urinary incontinence (stress, urge, mixed); fecal incontinence; overactive bladder; pelvic organ prolapse; pelvic pain; and sexual dysfunction. “Nearly all patients walk through the door with the chief complaint of loss of function,” said Knox. “Very few say, ‘Ms Knox, I have a dysfunction of my pelvic floor’. It’s the functional component that’s important to the patient.”

“People are shocked when they come to PT and we tell them they are going to undergo an internal digital exam.” Getting to Know You They don’t call them “physical terrorists” for nothing, so it’s important that you tell your patients that at the initial PT evaluation, internal examination of the PF is common practice. “People are shocked when they come to PT and we tell them they are going to undergo an internal digital exam.” The full evaluation will involve taking a history (which may reveal a problem unrelated to the PF), a musculoskeletal exam (including body posture and gait, which demonstrate how the body is being used), connective tissue exam (surgical scars may restrict movement of the PF), and (take a deep breath) a PF exam. Also performed is

6

November 2010

a rectal exam to assess contractile strength and coccygeal mobility. After evaluation comes the treatment plan. To illustrate the potential of PT in this setting, the example of stress incontinence was chosen. “There are four possible approaches here,” explained Knox. 1) Body awareness. The patients are encouraged to consciously contract the PF during activities that induce localized pressure, eg, contracting the PF before they lift a box, and holding that tension for the duration of the lift. 2) Strength training. Kegels. The patients are taught to perform regular strength training over time. Diligence is required; results will take weeks. 3) Indirect Training. The PF can be trained indirectly by contraction of the internal abdominal muscles, especially the transverses. In a sense, this is training the PF through the back door. 4) Functional training. Patients are asked to contract their PF during different activities; walking, yard work, house work, and the like. Critical to three of these approaches is the ability to isolate and activate the PF muscles. A study from 1991 estimated that 30% of patients were unable to contract their PF on the first visit. This strongly suggests the need for, if not requires, repeated follow-up. Should the patient have this initial difficulty, several options are available, including direct electrical stimulation and biofeedback. “E-stim is not very pleasant,” warned Knox, “but if you hit the motor point unit, the pelvic floor will contract. It’s very effective in helping patients find their way.” And e-stim devices can be used in the home. On the other hand, biofeedback, generally office-based, is popular with patients, aids in locating the PF, and can be extremely useful in situations where the patient needs to learn to relax. Where the Boys Are Data indicate that urinary incontinence is common after prostatectomy. Though the clinical evidence for PT in this setting is not robust, the rationale for its use is that PF contraction increases the strength of the

external urethral sphincter resulting in hypertrophy of the striatum muscle, thereby increasing mechanical pressure on the urethra. “The issue is not if it works, but whether PTs ever get to see these guys,” said Knox. Another issue is when these men should be seen. “By the time they’ve had their surgery, and then they’re incontinent, and then you send them down, these guys are devastated. The last thing they want is to come and see me so that I can teach them how to do a pelvic floor muscle contraction.”

“The last thing they want is to come and see me so that I can teach them how to do a pelvic floor muscle contraction.” Knox strongly advocates sending prostatectomy candidates to PT before the procedure. “It’s much easier to teach them while they’re functional.” If they continue to exercise preoperatively, they will be in much better shape postoperatively. At this point a question was raised about whether preoperative conditioning would be covered by insurance. Knox did not specifically know but suspected that it would be, given that cancer benefits are more generous compared with other disease states. “What I can tell you is that it’s worthwhile. Males who are incontinent postoperatively are extremely compliant with PF training.” ❖

Benign Prostatic Hyperplasia: Evaluation; Treatment Options A review of current trends in the management of BPH The population is aging. There are currently 37 million men older than 50 years in the United States, and an estimated 50% of these individuals have histologic, benign prostate hyperplasia (BPH). A detailed understanding of the condition – diagnosis, progression, and treatment options – will be


CONFERENCE HIGHLIGHTS: SUNA 2010

critical to effectively manage a rapidly expanding patient population. Key to this understanding is that BPH is progressive. “By the age of 70 years, 80%-90% of all men will have developed BPH,” said Dr Bhalchandra Parulkar, assistant professor of urology, University of Massachusetts Medical School, Worcester. That doesn’t mean this same segment of the population all have an enlarged prostate, or, for that matter, a noticeable urinary obstruction. “If you take a needle biopsy and look at the pathology slide you will see BPH – the term is used as a synonym for having an enlarged prostate, but that’s not really true. BPH is a histological diagnosis.” Those who have histological BPH do not always have an enlarged prostate; this is an important distinction when considering a diagnosis or potential treatment options. When a physician or nurse performs a digital rectal examination (DRE), that person is feeling the outside of the prostate; however, the symptoms of BPH are produced from within. “For some individuals the capsule enclosing the prostate is tight. When the prostate starts growing the capsule prevents it from expanding, therefore, it grows inwards.” This produces the same symptoms as those seen with an enlarged prostate, but without the physical size. In general, this discussion is framed by the consideration of an enlarged prostate, defined as a prostate of ≥30 mL in volume. At 30 mL and above, prostate size slowly starts making greater demands of the bladder, eventually resulting in hypertrophy of the muscles. The muscles then contract more frequently, thereby creating the combined problems of a weak urine stream, because of a blocked urethra, and irritative symptoms such as frequency, urgency, and urge incontinence. “Hesitancy is a classic and common symptom of enlarged prostate, however, storage symptoms are the most bothersome,” said Parulkar. Most men don’t mind taking some extra time to establish a urine stream, but frequency, urgency, or nocturia can have a significant impact on quality of life. Putting Your Finger on the Problem “If the diagnosis of BPH was simple, every primary care MD would treat it. But there

Figure 2. Natural History of BPH

Hyperplasia

Increased Urethral Resistance

Decreased Bladder Storage

Increased Detrusor Pressure

LUTS Urg./Freq./Nocturia

are many other conditions that mimic prostate symptoms.” These include prostate cancer, bladder cancer, prostatitis, urinary tract infections, renal dysfunction, diabetes, urethral narrowing, and interstitial cystitis. All these possibilities must be ruled out, but first, when the patient presents, there must be a consideration of risk. “On a patient’s first visit I consider these factors for BPH progression: age over 50, prostate exceeding 30 mL in volume, PSA ≥1.4 ng/mL, an AUA-SI score over 7, and weak urinary flow.”

And keep a sharp eye out – once a prostate progresses beyond 60 grams, most of the simple treatments options are off the table. Diagnostic workup will include a DRE, labs for creatinine, urinary analysis for infection, and PSA. Further tests may include a urine flow study, postvoid residue via ultrasound, and, if needed, urodynamics and cystoscopy. A voiding diary may also be requested to establish functional bladder capacity, as well to inform in cases where the chief complaint is nocturia. Finally, the patient is asked to complete the international prostate symptom score to establish the severity of the given complaint; scores range from mild to severe. Consider a patient who is young (55 years) who has presented with a mild urolog-

ic complaint but has a 30-gram prostate. “You can bet that with time that prostate is going to grow and cause more problems,” said Parulkar. This is particularly true if there is an older close relative with BPH. He suggested that a good urologic physician or nurse would anticipate worsening symptoms and recommend preventive treatment. What if you chose a less aggressive approach? Remember, BPH is progressive. Data indicate that men older than 60 years with enlarged prostates and obstructive symptoms have a 39% lifetime risk of requiring surgery. Further, if left untreated, 1 in 6 patients with an enlarged prostate, urologic symptoms, and a PSA ≥1.4 experience acute urinary retention or BPH-related surgery within 4 years of diagnosis. “You must get a baseline PSA,” advised Parulkar. “It’s a good predictor of BPH progression.” The higher the PSA, the faster the growth. And keep a sharp eye out – once a prostate progresses beyond 60 grams, most of the simple treatments options are off the table. But it is worth noting that the prostate doesn’t grow quickly on a yearly basis. Treatment Options Alpha-blockers Alpha receptors are present on the prostate and related blood vessels; receptor antagonism results in loss of local muscle tone. “If tone is lost, the urethra expands, the bladder neck expands, and this creates a wider passage for the urine to flow. Alpha-blockers do not reduce the prostate size but effectively achieve symptom relief – “and that’s what the patient came to you for,” said

Novellus Healthcare Communications

7


IN THE TREATMENT OF SYMPTOMATIC BPH*

RAPID RELIEF THAT KEEPS HIM GOING

Rapid BPH symptom relief starts in 3 to 4 days1,2 • A majority of patients achieved at least a 3-point improvement in IPSS† total score3 • Significant improvements in total IPSS at all time points studied (P<0.0001)1,2

*RAPAFLO® is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). RAPAFLO® is not indicated for the treatment of hypertension. †

International Prostate Symptom Score

References: 1. RAPAFLO® (silodosin) Capsules full Prescribing Information. 2. Marks LS, Gittelman MC, Hill LA, et al. Rapid efficacy of the highly selective α1A-adrenoceptor antagonist silodosin in men with signs and symptoms of benign prostatic hyperplasia: pooled results of 2 phase 3 studies. J Urol. 2009;181:26342640. 3. Data on file, Watson Laboratories, Inc. 4. Marks LS, Gittelman MC, Hill LA, et al. Silodosin in the treatment of the signs and symptoms of benign prostatic hyperplasia: a 9-month open-label extension study. Urology. 2009;74:1318-1322. 5. Marks LS. Reply to editorial comment. Urology. 2009;74:1323-1324. Models are for illustrative purposes only. © 2010, Watson Pharma, Inc., Morristown, NJ 07960. All rights reserved.

06317 1/10


• Significant improvement in total IPSS and irritative and obstructive IPSS subscores3,4 – Patients continuing RAPAFLO® therapy experienced additional improvements in IPSS scores over the 9-month uncontrolled, open-label period3,4 ®

– Patients continuing RAPAFLO therapy experienced an ~9-point overall reduction in IPSS total score over 52 weeks5

Convenient dosing regimen

Changes in IPSS Over 52 Weeks5‡ Continuing RAPAFLO® 21

Baseline

n=206 -2.0

Mean Change in IPSS from Baseline to Week 52

Sustained relief for up to 1 year

-4.0

-6.0

-8.0

• One 8-mg capsule taken once daily with a meal1

12

RAPAFLO® 8 mg #30 SIG: 1 CAP PO DAILY WITH A MEAL

-10.0 ‡

Patients received RAPAFLO® for 12 weeks in the double-blind controlled trials and for 40 weeks in the uncontrolled, open-label phase.

Important Safety Information RAPAFLO® is contraindicated in patients with severe renal impairment (CCr <30 mL/min), severe hepatic impairment (ChildPugh score ≥10), and with use of strong CYP3A4 inhibitors. Postural hypotension with or without symptoms (eg, dizziness) may develop when beginning treatment with RAPAFLO®. As with all alpha-blockers, there is a potential for syncope. Patients should be warned of the possible occurrences of such events and should avoid situations where injury could result. RAPAFLO® should be used with caution in patients with moderate renal impairment. Patients should be assessed to rule out the presence of prostate cancer prior to starting treatment with RAPAFLO®. Patients planning cataract surgery should inform their ophthalmologist that they are taking RAPAFLO®. The most common side effects are retrograde ejaculation, dizziness, diarrhea, orthostatic hypotension, headache, nasopharyngitis, and nasal congestion. Please see brief summary of full Prescribing Information on adjacent page.

For more information, please visit www.rapaflo.com


BRIEF SUMMARY For full Prescribing Information, see package insert. INDICATIONS AND USAGE RAPAFLO, a selective alpha-1 adrenergic receptor antagonist, is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). RAPAFLO is not indicated for the treatment of hypertension. CONTRAINDICATIONS t Severe renal impairment (CCr < 30 mL/min) t Severe hepatic impairment (Child-Pugh score ≥ 10) t Concomitant administration with strong Cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, clarithromycin, itraconazole, ritonavir) [see Drug Interactions] WARNINGS AND PRECAUTIONS Orthostatic Effects Postural hypotension, with or without symptoms (e.g., dizziness) may develop when beginning RAPAFLO treatment. As with other alpha-blockers, there is potential for syncope. Patients should be cautioned about driving, operating machinery, or performing hazardous tasks when initiating therapy [see Adverse Reactions and Use in Specific Populations]. Renal Impairment In a clinical pharmacology study, plasma concentrations (AUC and Cmax) of silodosin were approximately three times higher in subjects with moderate renal impairment compared with subjects with normal renal function, while half-lives of silodosin doubled in duration. The dose of RAPAFLO should be reduced to 4 mg in patients with moderate renal impairment. Exercise caution and monitor such patients for adverse events [see Use in Specific Populations]. RAPAFLO is contraindicated in patients with severe renal impairment [see Contraindications]. Hepatic Impairment RAPAFLO has not been tested in patients with severe hepatic impairment, and therefore, should not be prescribed to such patients [see Contraindications and Use in Specific Populations]. Pharmacokinetic Drug-Drug Interactions In a drug interaction study, co-administration of a single 8 mg dose of RAPAFLO with 400 mg ketoconazole, a strong CYP3A4 inhibitor, caused a 3.8-fold increase in maximum plasma silodosin concentrations and 3.2-fold increase in silodosin exposure (i.e., AUC). Concomitant use of ketoconazole or other strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ritonavir) is therefore contraindicated [see Drug Interactions]. Pharmacodynamic Drug-Drug Interactions The pharmacodynamic interactions between silodosin and other alpha-blockers have not been determined. However, interactions may be expected, and RAPAFLO should not be used in combination with other alpha-blockers [see Drug Interactions]. A specific pharmacodynamic interaction study between silodosin and antihypertensive agents has not been performed. However, patients in the Phase 3 clinical studies taking concomitant antihypertensive medications with RAPAFLO did not experience a significant increase in the incidence of syncope, dizziness, or orthostasis. Nevertheless, exercise caution during concomitant use with antihypertensives and monitor patients for possible adverse events [see Adverse Reactions and Drug Interactions]. Caution is also advised when alpha-adrenergic blocking agents including RAPAFLO are co-administered with PDE5 inhibitors. Alpha-adrenergic blockers and PDE5 inhibitors are both vasodilators that can lower blood pressure. Concomitant use of these two drug classes can potentially cause symptomatic hypotension [see Drug Interactions]. Carcinoma of the Prostate Carcinoma of the prostate and BPH cause many of the same symptoms. These two diseases frequently co-exist. Therefore, patients thought to have BPH should be examined prior to starting therapy with RAPAFLO to rule out the presence of carcinoma of the prostate. Intraoperative Floppy Iris Syndrome Intraoperative Floppy Iris Syndrome has been observed during cataract surgery in some patients on alpha-1 blockers or previously treated with alpha-1 blockers. This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents; progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs; and potential prolapse of the iris toward the phacoemulsification incisions. Patients planning cataract surgery should be told to inform their ophthalmologist that they are taking RAPAFLO [see Adverse Reactions]. Laboratory Test Interactions No laboratory test interactions were observed during clinical evaluations. Treatment with RAPAFLO for up to 52 weeks had no significant effect on prostate-specific antigen (PSA). ADVERSE REACTIONS Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In U.S. clinical trials, 897 patients with BPH were exposed to 8 mg RAPAFLO daily. This includes 486 patients exposed for 6 months and 168 patients exposed for 1 year. The population was 44 to 87 years of age, and predominantly Caucasian. Of these patients, 42.8% were 65 years of age or older and 10.7% were 75 years of age or older. In double-blind, placebo controlled, 12-week clinical trials, 466 patients were administered RAPAFLO and 457 patients were administered placebo. At least one treatment-emergent adverse reaction was reported by 55.2% of RAPAFLO treated patients (36.8% for placebo treated). The majority (72.1%) of adverse reactions for the RAPAFLO treated patients (59.8% for placebo treated) were qualified by the investigator as mild. A total of 6.4% of RAPAFLO treated patients (2.2% for placebo treated) discontinued therapy due to an adverse reaction (treatment-emergent), the most common reaction being retrograde ejaculation (2.8%) for RAPAFLO treated patients. Retrograde ejaculation is reversible upon discontinuation of treatment. Adverse Reactions observed in at least 2% of patients: The incidence of treatment-emergent adverse reactions listed in the following table were derived from two 12-week, multicenter, double-blind, placebo-controlled clinical studies of RAPAFLO 8 mg daily in BPH patients. Adverse reactions that occurred in at least 2% of patients treated with RAPAFLO and more frequently than with placebo are shown in Table 1. Table 1 Adverse Reactions Occurring in ≥ 2% of Patients in 12-week, Placebo-Controlled Clinical Trials Adverse Reactions Retrograde Ejaculation Dizziness Diarrhea Orthostatic Hypotension Headache Nasopharyngitis Nasal Congestion

RAPAFLO N = 466 n (%) 131 (28.1) 15 (3.2) 12 (2.6) 12 (2.6) 11 (2.4) 11 (2.4) 10 (2.1)

Placebo N = 457 n (%) 4 (0.9) 5 (1.1) 6 (1.3) 7 (1.5) 4 (0.9) 10 (2.2) 1 (0.2)

In the two 12-week, placebo-controlled clinical trials, the following adverse events were reported by between 1% and 2% of patients receiving RAPAFLO and occurred more frequently than with placebo: insomnia, PSA increased, sinusitis, abdominal pain, asthenia, and rhinorrhea. One case of syncope in a patient taking prazosin concomitantly and one case of priapism were reported in the RAPAFLO treatment group. In a 9-month open-label safety study of RAPAFLO, one case of Intraoperative Floppy Iris Syndrome (IFIS) was reported. Postmarketing Experience The following adverse reactions have been identified during post approval use of silodosin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Skin and subcutaneous tissue disorders: toxic skin eruption, purpura Hepatobiliary disorders: jaundice, impaired hepatic function associated with increased transaminase values

DRUG INTERACTIONS Moderate and Strong CYP3A4 Inhibitors In a clinical metabolic inhibition study, a 3.8-fold increase in silodosin maximum plasma concentrations and 3.2-fold increase in silodosin exposure were observed with concurrent administration of a strong CYP3A4 inhibitor, 400 mg ketoconazole. Use of strong CYP3A4 inhibitors such as itraconazole or ritonavir may cause plasma concentrations of silodosin to increase. Concomitant administration of strong CYP3A4 inhibitors and RAPAFLO is contraindicated [see Contraindications and Warnings and Precautions]. The effect of moderate CYP3A4 inhibitors on the pharmacokinetics of silodosin has not been evaluated. Concomitant administration with moderate CYP3A4 inhibitors (e.g., diltiazem, erythromycin, verapamil) may increase concentration of RAPAFLO. Exercise caution and monitor patients for adverse events when co-administering RAPAFLO with moderate CYP3A4 inhibitors. Strong P-glycoprotein (P-gp) Inhibitors In vitro studies indicated that silodosin is a P-gp substrate. Ketoconazole, a CYP3A4 inhibitor that also inhibits P-gp, caused significant increase in exposure to silodosin. Inhibition of P-gp may lead to increased silodosin concentration. RAPAFLO is therefore not recommended in patients taking strong P-gp inhibitors such as cyclosporine. Alpha-Blockers The pharmacodynamic interactions between silodosin and other alpha-blockers have not been determined. However, interactions may be expected, and RAPAFLO should not be used in combination with other alpha-blockers [see Warnings and Precautions]. Digoxin The effect of co-administration of RAPAFLO and digoxin 0.25 mg/day for 7 days was evaluated in a clinical trial in 16 healthy males, aged 18 to 45 years. Concomitant administration of RAPAFLO and digoxin did not significantly alter the steady state pharmacokinetics of digoxin. No dose adjustment is required. PDE5 Inhibitors Co-administration of RAPAFLO with a single dose of 100 mg sildenafil or 20 mg tadalafil was evaluated in a placebocontrolled clinical study that included 24 healthy male subjects, 45 to 78 years of age. Orthostatic vital signs were monitored in the 12-hour period following concomitant dosing. During this period, the total number of positive orthostatic test results was greater in the group receiving RAPAFLO plus a PDE5 inhibitor compared with RAPAFLO alone. No events of symptomatic orthostasis or dizziness were reported in subjects receiving RAPAFLO with a PDE5 inhibitor. Other Concomitant Drug Therapy Antihypertensives The pharmacodynamic interactions between silodosin and antihypertensives have not been rigorously investigated in a clinical study. However, approximately one-third of the patients in clinical studies used concomitant antihypertensive medications with RAPAFLO. The incidence of dizziness and orthostatic hypotension in these patients was higher than in the general silodosin population (4.6% versus 3.8% and 3.4% versus 3.2%, respectively). Exercise caution during concomitant use with antihypertensives and monitor patients for possible adverse events [see Warnings and Precautions]. Metabolic Interactions In vitro data indicate that silodosin does not have the potential to inhibit or induce cytochrome P450 enzyme systems. Food Interactions The effect of a moderate fat, moderate calorie meal on silodosin pharmacokinetics was variable and decreased silodosin maximum plasma concentration (Cmax) by approximately 18 - 43% and exposure (AUC) by 4 - 49% across three different studies. Safety and efficacy clinical trials for RAPAFLO were always conducted in the presence of food intake. Patients should be instructed to take silodosin with a meal to reduce risk of adverse events. USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category B. RAPAFLO is not indicated for use in women. An embryo/fetal study in rabbits showed decreased maternal body weight at 200 mg/kg/day (approximately 13-25 times the maximum recommended human exposure or MRHE of silodosin via AUC). No statistically significant teratogenicity was observed at this dose. Silodosin was not teratogenic when administered to pregnant rats during organogenesis at 1000 mg/kg/day (estimated to be approximately 20 times the MRHE). No maternal or fetal effects were observed at this dose. Rats and rabbits do not produce glucuronidated silodosin, which is present in human serum at approximately 4 times the level of circulating silodosin and which has similar pharmacological activity to silodosin. No effects on physical or behavioral development of offspring were observed when rats were treated during pregnancy and lactation at up to 300 mg/kg/day. Pediatric Use RAPAFLO is not indicated for use in pediatric patients. Safety and effectiveness in pediatric patients have not been established. Geriatric Use In double-blind, placebo-controlled, 12-week clinical studies of RAPAFLO, 259 (55.6%) were under 65 years of age, 207 (44.4%) patients were 65 years of age and over, while 60 (12.9%) patients were 75 years of age and over. Orthostatic hypotension was reported in 2.3% of RAPAFLO patients < 65 years of age (1.2% for placebo), 2.9% of RAPAFLO patients ≥ 65 years of age (1.9% for placebo), and 5.0% of patients ≥ 75 years of age (0% for placebo). There were otherwise no significant differences in safety or effectiveness between older and younger patients. Renal Impairment The effect of renal impairment on silodosin pharmacokinetics was evaluated in a single dose study of six male patients with moderate renal impairment and seven male subjects with normal renal function. Plasma concentrations of silodosin were approximately three times higher in subjects with moderate renal impairment compared with subjects with normal renal function. RAPAFLO should be reduced to 4 mg per day in patients with moderate renal impairment. Exercise caution and monitor patients for adverse events. RAPAFLO has not been studied in patients with severe renal impairment. RAPAFLO is contraindicated in patients with severe renal impairment [see Contraindications and Warnings and Precautions]. Hepatic Impairment In a study comparing nine male patients with moderate hepatic impairment (Child-Pugh scores 7 to 9), to nine healthy male subjects, the single dose pharmacokinetics of silodosin were not significantly altered in patients with hepatic impairment. No dosing adjustment is required in patients with mild or moderate hepatic impairment. RAPAFLO has not been studied in patients with severe hepatic impairment. RAPAFLO is contraindicated in patients with severe hepatic impairment [see Contraindications and Warnings and Precautions]. OVERDOSAGE RAPAFLO was evaluated at doses of up to 48 mg/day in healthy male subjects. The dose-limiting adverse event was postural hypotension. Should overdose of RAPAFLO lead to hypotension, support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by maintaining the patient in the supine position. If this measure is inadequate, administration of intravenous fluid should be considered. If necessary, vasopressors could be used, and renal function should be monitored and supported as needed. Dialysis is unlikely to be of significant benefit since silodosin is highly (97%) protein bound.

Manufactured by: Watson Laboratories, Inc., Corona, CA 92880 USA Distributed by: Watson Pharma, Inc., Morristown, NJ 07962 USA Under license from: Kissei Pharmaceutical Co., Ltd., Nagano, Japan Address medical inquiries to: WATSON Medical Communications, P.O. Box 1953, Morristown, NJ 07962-1953 800-272-5525 For additional information see: www.rapaflo.com or call 1-866-RAPAFLO (727-2356) Rx Only Revised: November 2009 173761-2 S1109


CONFERENCE HIGHLIGHTS: SUNA 2010

Parulkar, adding that patients are encouraged by the rapid onset of action for this class of drugs and their relative inexpensive cost. However, as the prostate continues to grow, symptoms may eventually worsen. The combination of an alpha-blocker with a 5alpha reductase inhibitor may be recommended for patients with very large prostates (well larger than 30 mL). Saw Palmetto Sometimes combined with zinc and selenium. This is an option if a patient has mild symptoms but prefers not to use prescription medication. Some patients do experience symptom relief, however, randomized studies indicate no benefit beyond the placebo effect. 5-Alpha Reductase Inhibitors The rationale for the use of these agents is to prevent the conversion of testosterone to dihydrotestosterone (DHT), which is required for prostate growth. “These drugs decrease DHT but do not eliminate testosterone, so men don’t experience too many significant adverse reactions,” said Parulkar, “and the earlier you use them, the better they will work.” These agents will shrink the prostate, but as mentioned in the context of symptoms without enlargement, this treatment will be ineffective. A further downside: “These drugs take up to 6 months to work. That can be a hard sell to the uncomfortable patient.” There is also this caveat: If your patient is taking these drugs, future PSA values must be doubled.

The rationale for the use of these agents is to prevent the conversion of testosterone to dihydrotestosterone (DHT). Surgical Options Stents. Typically used in nursing homes. Not for use in younger patients. Needle Ablation Radiofrequency. A very precise technique using an endoscope through the urethra that applies heat to the prostate and destroys and collapses target tis-

sue. Patients go home the same day with a catheter. Microwave Therapy. Similar to radiofrequency in that it heats the tissue. This method is rapid, and catheters are generally not required. Laser Vaporization. Also rapid, but not widely available. TURP. The most invasive approach with the greatest chance of complications, short of open prostatectomy. TURP requires hospitalization and use of a general or spinal anesthetic. Recovery time, during which strenuous activity must be avoided, lasts up to 6 weeks. Concluding his review, Dr Parulkar cautioned listeners. “Keep in mind that with all these methods, the potential for prostate cancer still exists. The tissue you’re targeting is internal, oncogenesis occurs at the periphery.” Patients will require continued follow-up. ❖

A SUNA Debate: Should We Really Be Using PSA? Recent data suggest that widespread screening programs are ineffective (maybe) Everyone likes a good debate. However, if the loser in such an argument is the patient, which side does one root for, the good data, or the good intention? The data come from two large, randomized trials recently published. The case for good intentions – generated by the desire to do something to reduce the high rates of incidence for prostate cancer (PCa) – was presented by Silvia Maxwell, ACNP-BC, CUNP, Detroit Medical Center, who advanced her argument by presenting the scope of the problem. “The National Cancer Institute estimates that 217,730 new cases will be diagnosed for 2010, eventually resulting in over 32,000 deaths.” As most healthcare providers know, the sooner a cancer is detected the better the treatment outcome, “and right now, the PSA test is our primary tool in the early detection of these prostate cancers.” And therein lies the debate: the two aforementioned trials, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening

Trial1 and the European Randomized Study of Screening for Prostate Cancer2 investigations, enrolling over 130,000 men combined, did not definitively show that PSA really saves lives on the basis of widespread screening. “The problem,” said Maxwell, “is that, while PSA is specific for prostate, it is not specific for cancer.”

After the introduction of the test there was a marked increase in PCa detection and a 30% decline in PCa-related deaths. First identified as a prostate marker in 1966, PSA was established as a tumor marker in 1979 and approved as a diagnostic test in 1994. After the introduction of the test there was a marked increase in PCa detection and a 30% decline in PCarelated deaths. However, one cannot say that the test was directly responsible for the percentage of the decline, as there were concurrent advances in treatment options. What was apparent was that for that initiation period, PCa was overdiagnosed. “This can be attributed to the fact that there is no universally accepted cutoff PSA threshold (generally held to be around 4 ng/mL).” Further, an elevated PSA may not be related to PCa. Increased PSA levels may be indicative of infection or inflammation, urethral trauma, recent ejaculation, or DRE. Levels may be artificially depressed by the use of antibiotics, the use of finasteride or dutasteride to treat BPH, or the patient’s body mass index (BMI). For BMI ≥35, PSA values are artificially low. Again, to be of relevance, the test needs to aid in the identification of tumors in their early stages. If the cancer remains localized, 5year survival rates are near 100%; for metastatic disease, 5-year survival drops to 32% for whites and 29% for AfricanAmericans. “African-Americans have the highest rates in the world,” said Maxwell. Other risk factors include age ≥65 years; family history; and, of epidemiological interest, <12 years of formal education.

Novellus Healthcare Communications

11


CONFERENCE HIGHLIGHTS: SUNA 2010

So, yes, PCa is a serious healthcare issue, but is the information PSA is giving us worth all the biopsies? “I do believe that over the years many men have been overtreated,” Maxwell admitted, and that more discussion needs to be had with men about what the score means. “A value of 2 or 2.5 indicates a very slow-growing tumor of very little eventual risk.” This is particularly true for the elderly. Con: The Data Clearly Show That the Import of PSA Is Not Clear Susan Quallich, ANP-BC, NP-C, CUNO, Division of Sexual and Reproductive Medicine, Department of Urology, University of Michigan, was not quite as circumspect in her arguments. “There is no agreed consensus about how to assess a defined group, or way to treat people who have elevated PSA.” Issues include: who should be screened, how screening should be offered, how often, and how to advise patients about results. Its value as an all-comer, population-based screen is unclear even to the experts. Consider the guidelines: American Urological Association – yes to screening, but only for the well counseled; World Health Organization – no to screening until large randomized trials show benefit; European Association of Urology – no to widespread screening based on insufficient evidence of benefit. “It has been said that widespread screening for PSA has created a pseudo epidem-

12

November 2010

ic,” asserted Quallich, adding that, “We don’t have really good evidence for benefit, but we have a lot of evidence for harm.” It has even lead one Harvard epidemiologist to go on record saying that PSA screening “…is a disaster of contemporary medicine.”3

Issues include: who should be screened, how screening should be offered, how often, and how to advise patients about results. The term “disaster” is relative, but that PSA can have a negative impact is finite. Since its introduction, PSA has all but doubled the chance that an individual man will be diagnosed with PCa – in 1980 it was 1 in 11, today it is 1 in 6. This is largely an increase in local detection, not metastasis, not the life-threatening cancers. “We see men with elevated PSA but don’t really know what to do with that information. Even before biopsy, this information alone increases anxiety.” Studies have shown that just the idea that someone might have cancer has a negative impact on health. Patients may experience depression, anxiety, voiding problems, and bowel problems; and with PCa treatment, which may or may not have been necessary; erectile dysfunction;

bowel dysfunction, and incontinence. It’s noteworthy that 50% of men with an elevated PSA never have clinical symptoms. “Ultimately you can make the argument with PSA screening that we’re violating the idea that we do no harm.” And we haven’t even begun to discuss the cost. Finally, the minute a PSA threshold for concern seems to be established, new data provide nothing but confusion. “One of the most interesting findings to come out in the last 8-12 months is that obesity causes a PSA to be lower than it would actually be,” said Quallich. This is really significant. We have all heard about the obesity epidemic – with widespread screening, what are we to do with these numbers? A comment from the audience sidestepped the debate regarding the wisdom of widespread screening to say that PSA velocity, not merely a single measure, was highly informative for the individual. This idea framed the debate: value to the individual patient versus service to the population at large. ❖ References 1. Andriole GL, Crawford ED, Grubb RL 3rd, et al. Mortality results from a randomized prostatecancer screening trial. N Engl J Med. 2009; 360:1310-1319. 2. Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320-1328. 3. Adami HO. The prostate cancer pseudo-epidemic. Acta Oncol. 2010;49:298-304.


NEWS FROM THE UROLOGY NURSE

Simple Intervention Boosts Sperm Cryopreservation in Men With Cancer BY JILL STEIN

An hour-long lecture by a fertility specialist during oncology grand rounds dramatically improves the rate of pretreatment sperm cryopreservation in young men with cancer, according to data presented at the American Urological Association 2010 Annual Scientific Meeting. The researchers found that educating oncologists by a urologist specializing in male infertility increased sperm cryopreservation in male cancer 4-fold. “Even though our study was observational, our results highlight the importance of educating our colleagues in the oncology world about this resource,” Daniel H. Williams IV, MD, Assistant Professor of Urology and Director of Male Reproductive Medicine and Microsurgery, University of Wisconsin, Madison, said in an interview with The OB/GYN and Infertility Nurse. Dr Williams’ team compared sperm cryopreservation rates before and after the lecture, which focused on the risks of cancer treatment–induced male infertility, advances in assisted reproductive technology, and the local availability of sperm cryopreservation. The dramatic increase in sperm cryopreservation seen 1 month after a single lecture was maintained at follow-up several months later. Because of therapeutic advances, pediatric and adult cancer survivors are living “well into” their reproductive years, Dr

Williams pointed out. However, most cancer treatment regimens have adverse effects on testicular function and male reproductive potential, and posttreatment fecundity is difficult to predict.

“Cancer treatments now focus not only on survival but on quality of life, and fertility and fertility potential is a large component of quality of life after cancer treatment.” —Daniel H. Williams IV, MD “Sperm cryopreservation provides an opportunity to preserve a man’s fertility before cancer treatment,” Dr Williams said. The American Society of Clinical Oncology has recommended that oncologists routinely discuss the potential for infertility along with fertility preservation options with patients before cancer therapy and refer interested patients to reproductive specialists. In addition, the guidelines recommend that semen cryopreservation be adopted as standard practice. In contrast, epidemiologic studies indicate that most young male cancer patients are not advised to bank sperm before their

cancer treatment. Surveys have consistently identified a lack of information as the main reason for the low sperm cryopreservation rate. About 40 healthcare practitioners attended the lecture. Attendees were mostly pediatric and adult oncologists but also included oncology nurses and other staff. In the 24-month period before the lecture, only 1 patient with cancer per month banked his sperm. After the lecture, the rate increased significantly, to 3.7 patients with cancer per month over the subsequent 7 months (P<.001). Most of the change was comprised of a nearly 6-fold increase in the number of patients with nontesticular cancer, from 0.42 to 2.42 per month (P<.001). “With improvements in cancer therapies, young men of reproductive age who develop cancers – lymphomas, leukemias, and testicular malignancies, among others – are surviving longer,” Dr Williams said. “As a result, cancer treatments now focus not only on survival but on quality of life, and fertility and fertility potential is a large component of quality of life after cancer treatment.” Continued efforts should be made to educate healthcare professionals about sperm cryopreservation, with an emphasis on improving the comprehensive cancer care and posttreatment quality of life in these patients, he added. ❖

Novellus Healthcare Communications

13


NEWS FROM THE UROLOGY NURSE

Anejaculation Common After Radiotherapy for Prostate Cancer BY JESSICA A. SMITH

Most men who undergo radiation therapy (RT) for prostate cancer will develop anejaculation over time, according to Doron Stember, MD, a urology fellow at Memorial Sloan-Kettering Cancer Center in New York City, who presented at the American Urological Association 2010 annual meeting the results of a study that examined the ejaculation profiles of 364 men who underwent localized RT for prostate cancer. “It is widely known that anejaculation occurs after a radical prostatectomy and may be a significant cause of bother and sexual dissatisfaction,” Dr Stember said. “In contrast, patients and physicians do not commonly associate radiation therapy

with anejaculation. We undertook this study because our clinical experience has suggested that many men do, in fact, lose antegrade ejaculatory function after RT.” The overwhelming majority of prior analyses of patients with pelvic RT-associated sexual dysfunction have focused on erectile dysfunction, often without mention of changes in ejaculatory dysfunction. Anejaculation is thought to result from a progressive scarring mechanism in the prostate tissue (including the ejaculatory ducts) that leads to obstruction of the ejaculate. Overall, 16% of the men in this study complained of anejaculation at 1 year, 69% at 3 years, and 89% at 5 years. “There was

a clear trend toward an increasing proportion of patients experiencing anejaculation…after RT,” he said. The risk factors for failure to ejaculate at 3 years included: • High RT doses • Older age • A history of androgen deprivation therapy • Smaller prostates at the time of RT. Orgasm domain scores on the widely validated International Index of Erectile Function questionnaire decreased markedly throughout follow-up. “We recommend that the high likelihood of inability to ejaculate should be discussed with men prior to RT,” Dr Stember advised. ❖

NOV0310 14

November 2010


BRIEF SUMMARY For full Prescribing Information, see package insert. INDICATIONS AND USAGE RAPAFLO, a selective alpha-1 adrenergic receptor antagonist, is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). RAPAFLO is not indicated for the treatment of hypertension. CONTRAINDICATIONS t Severe renal impairment (CCr < 30 mL/min) t Severe hepatic impairment (Child-Pugh score ≥ 10) t Concomitant administration with strong Cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, clarithromycin, itraconazole, ritonavir) [see Drug Interactions] WARNINGS AND PRECAUTIONS Orthostatic Effects Postural hypotension, with or without symptoms (e.g., dizziness) may develop when beginning RAPAFLO treatment. As with other alpha-blockers, there is potential for syncope. Patients should be cautioned about driving, operating machinery, or performing hazardous tasks when initiating therapy [see Adverse Reactions and Use in Specific Populations]. Renal Impairment In a clinical pharmacology study, plasma concentrations (AUC and Cmax) of silodosin were approximately three times higher in subjects with moderate renal impairment compared with subjects with normal renal function, while half-lives of silodosin doubled in duration. The dose of RAPAFLO should be reduced to 4 mg in patients with moderate renal impairment. Exercise caution and monitor such patients for adverse events [see Use in Specific Populations]. RAPAFLO is contraindicated in patients with severe renal impairment [see Contraindications]. Hepatic Impairment RAPAFLO has not been tested in patients with severe hepatic impairment, and therefore, should not be prescribed to such patients [see Contraindications and Use in Specific Populations]. Pharmacokinetic Drug-Drug Interactions In a drug interaction study, co-administration of a single 8 mg dose of RAPAFLO with 400 mg ketoconazole, a strong CYP3A4 inhibitor, caused a 3.8-fold increase in maximum plasma silodosin concentrations and 3.2-fold increase in silodosin exposure (i.e., AUC). Concomitant use of ketoconazole or other strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ritonavir) is therefore contraindicated [see Drug Interactions]. Pharmacodynamic Drug-Drug Interactions The pharmacodynamic interactions between silodosin and other alpha-blockers have not been determined. However, interactions may be expected, and RAPAFLO should not be used in combination with other alpha-blockers [see Drug Interactions]. A specific pharmacodynamic interaction study between silodosin and antihypertensive agents has not been performed. However, patients in the Phase 3 clinical studies taking concomitant antihypertensive medications with RAPAFLO did not experience a significant increase in the incidence of syncope, dizziness, or orthostasis. Nevertheless, exercise caution during concomitant use with antihypertensives and monitor patients for possible adverse events [see Adverse Reactions and Drug Interactions]. Caution is also advised when alpha-adrenergic blocking agents including RAPAFLO are co-administered with PDE5 inhibitors. Alpha-adrenergic blockers and PDE5 inhibitors are both vasodilators that can lower blood pressure. Concomitant use of these two drug classes can potentially cause symptomatic hypotension [see Drug Interactions]. Carcinoma of the Prostate Carcinoma of the prostate and BPH cause many of the same symptoms. These two diseases frequently co-exist. Therefore, patients thought to have BPH should be examined prior to starting therapy with RAPAFLO to rule out the presence of carcinoma of the prostate. Intraoperative Floppy Iris Syndrome Intraoperative Floppy Iris Syndrome has been observed during cataract surgery in some patients on alpha-1 blockers or previously treated with alpha-1 blockers. This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents; progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs; and potential prolapse of the iris toward the phacoemulsification incisions. Patients planning cataract surgery should be told to inform their ophthalmologist that they are taking RAPAFLO [see Adverse Reactions]. Laboratory Test Interactions No laboratory test interactions were observed during clinical evaluations. Treatment with RAPAFLO for up to 52 weeks had no significant effect on prostate-specific antigen (PSA). ADVERSE REACTIONS Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In U.S. clinical trials, 897 patients with BPH were exposed to 8 mg RAPAFLO daily. This includes 486 patients exposed for 6 months and 168 patients exposed for 1 year. The population was 44 to 87 years of age, and predominantly Caucasian. Of these patients, 42.8% were 65 years of age or older and 10.7% were 75 years of age or older. In double-blind, placebo controlled, 12-week clinical trials, 466 patients were administered RAPAFLO and 457 patients were administered placebo. At least one treatment-emergent adverse reaction was reported by 55.2% of RAPAFLO treated patients (36.8% for placebo treated). The majority (72.1%) of adverse reactions for the RAPAFLO treated patients (59.8% for placebo treated) were qualified by the investigator as mild. A total of 6.4% of RAPAFLO treated patients (2.2% for placebo treated) discontinued therapy due to an adverse reaction (treatment-emergent), the most common reaction being retrograde ejaculation (2.8%) for RAPAFLO treated patients. Retrograde ejaculation is reversible upon discontinuation of treatment. Adverse Reactions observed in at least 2% of patients: The incidence of treatment-emergent adverse reactions listed in the following table were derived from two 12-week, multicenter, double-blind, placebo-controlled clinical studies of RAPAFLO 8 mg daily in BPH patients. Adverse reactions that occurred in at least 2% of patients treated with RAPAFLO and more frequently than with placebo are shown in Table 1. Table 1 Adverse Reactions Occurring in ≥ 2% of Patients in 12-week, Placebo-Controlled Clinical Trials Adverse Reactions Retrograde Ejaculation Dizziness Diarrhea Orthostatic Hypotension Headache Nasopharyngitis Nasal Congestion

RAPAFLO N = 466 n (%) 131 (28.1) 15 (3.2) 12 (2.6) 12 (2.6) 11 (2.4) 11 (2.4) 10 (2.1)

Placebo N = 457 n (%) 4 (0.9) 5 (1.1) 6 (1.3) 7 (1.5) 4 (0.9) 10 (2.2) 1 (0.2)

In the two 12-week, placebo-controlled clinical trials, the following adverse events were reported by between 1% and 2% of patients receiving RAPAFLO and occurred more frequently than with placebo: insomnia, PSA increased, sinusitis, abdominal pain, asthenia, and rhinorrhea. One case of syncope in a patient taking prazosin concomitantly and one case of priapism were reported in the RAPAFLO treatment group. In a 9-month open-label safety study of RAPAFLO, one case of Intraoperative Floppy Iris Syndrome (IFIS) was reported. Postmarketing Experience The following adverse reactions have been identified during post approval use of silodosin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Skin and subcutaneous tissue disorders: toxic skin eruption, purpura Hepatobiliary disorders: jaundice, impaired hepatic function associated with increased transaminase values

DRUG INTERACTIONS Moderate and Strong CYP3A4 Inhibitors In a clinical metabolic inhibition study, a 3.8-fold increase in silodosin maximum plasma concentrations and 3.2-fold increase in silodosin exposure were observed with concurrent administration of a strong CYP3A4 inhibitor, 400 mg ketoconazole. Use of strong CYP3A4 inhibitors such as itraconazole or ritonavir may cause plasma concentrations of silodosin to increase. Concomitant administration of strong CYP3A4 inhibitors and RAPAFLO is contraindicated [see Contraindications and Warnings and Precautions]. The effect of moderate CYP3A4 inhibitors on the pharmacokinetics of silodosin has not been evaluated. Concomitant administration with moderate CYP3A4 inhibitors (e.g., diltiazem, erythromycin, verapamil) may increase concentration of RAPAFLO. Exercise caution and monitor patients for adverse events when co-administering RAPAFLO with moderate CYP3A4 inhibitors. Strong P-glycoprotein (P-gp) Inhibitors In vitro studies indicated that silodosin is a P-gp substrate. Ketoconazole, a CYP3A4 inhibitor that also inhibits P-gp, caused significant increase in exposure to silodosin. Inhibition of P-gp may lead to increased silodosin concentration. RAPAFLO is therefore not recommended in patients taking strong P-gp inhibitors such as cyclosporine. Alpha-Blockers The pharmacodynamic interactions between silodosin and other alpha-blockers have not been determined. However, interactions may be expected, and RAPAFLO should not be used in combination with other alpha-blockers [see Warnings and Precautions]. Digoxin The effect of co-administration of RAPAFLO and digoxin 0.25 mg/day for 7 days was evaluated in a clinical trial in 16 healthy males, aged 18 to 45 years. Concomitant administration of RAPAFLO and digoxin did not significantly alter the steady state pharmacokinetics of digoxin. No dose adjustment is required. PDE5 Inhibitors Co-administration of RAPAFLO with a single dose of 100 mg sildenafil or 20 mg tadalafil was evaluated in a placebocontrolled clinical study that included 24 healthy male subjects, 45 to 78 years of age. Orthostatic vital signs were monitored in the 12-hour period following concomitant dosing. During this period, the total number of positive orthostatic test results was greater in the group receiving RAPAFLO plus a PDE5 inhibitor compared with RAPAFLO alone. No events of symptomatic orthostasis or dizziness were reported in subjects receiving RAPAFLO with a PDE5 inhibitor. Other Concomitant Drug Therapy Antihypertensives The pharmacodynamic interactions between silodosin and antihypertensives have not been rigorously investigated in a clinical study. However, approximately one-third of the patients in clinical studies used concomitant antihypertensive medications with RAPAFLO. The incidence of dizziness and orthostatic hypotension in these patients was higher than in the general silodosin population (4.6% versus 3.8% and 3.4% versus 3.2%, respectively). Exercise caution during concomitant use with antihypertensives and monitor patients for possible adverse events [see Warnings and Precautions]. Metabolic Interactions In vitro data indicate that silodosin does not have the potential to inhibit or induce cytochrome P450 enzyme systems. Food Interactions The effect of a moderate fat, moderate calorie meal on silodosin pharmacokinetics was variable and decreased silodosin maximum plasma concentration (Cmax) by approximately 18 - 43% and exposure (AUC) by 4 - 49% across three different studies. Safety and efficacy clinical trials for RAPAFLO were always conducted in the presence of food intake. Patients should be instructed to take silodosin with a meal to reduce risk of adverse events. USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category B. RAPAFLO is not indicated for use in women. An embryo/fetal study in rabbits showed decreased maternal body weight at 200 mg/kg/day (approximately 13-25 times the maximum recommended human exposure or MRHE of silodosin via AUC). No statistically significant teratogenicity was observed at this dose. Silodosin was not teratogenic when administered to pregnant rats during organogenesis at 1000 mg/kg/day (estimated to be approximately 20 times the MRHE). No maternal or fetal effects were observed at this dose. Rats and rabbits do not produce glucuronidated silodosin, which is present in human serum at approximately 4 times the level of circulating silodosin and which has similar pharmacological activity to silodosin. No effects on physical or behavioral development of offspring were observed when rats were treated during pregnancy and lactation at up to 300 mg/kg/day. Pediatric Use RAPAFLO is not indicated for use in pediatric patients. Safety and effectiveness in pediatric patients have not been established. Geriatric Use In double-blind, placebo-controlled, 12-week clinical studies of RAPAFLO, 259 (55.6%) were under 65 years of age, 207 (44.4%) patients were 65 years of age and over, while 60 (12.9%) patients were 75 years of age and over. Orthostatic hypotension was reported in 2.3% of RAPAFLO patients < 65 years of age (1.2% for placebo), 2.9% of RAPAFLO patients ≥ 65 years of age (1.9% for placebo), and 5.0% of patients ≥ 75 years of age (0% for placebo). There were otherwise no significant differences in safety or effectiveness between older and younger patients. Renal Impairment The effect of renal impairment on silodosin pharmacokinetics was evaluated in a single dose study of six male patients with moderate renal impairment and seven male subjects with normal renal function. Plasma concentrations of silodosin were approximately three times higher in subjects with moderate renal impairment compared with subjects with normal renal function. RAPAFLO should be reduced to 4 mg per day in patients with moderate renal impairment. Exercise caution and monitor patients for adverse events. RAPAFLO has not been studied in patients with severe renal impairment. RAPAFLO is contraindicated in patients with severe renal impairment [see Contraindications and Warnings and Precautions]. Hepatic Impairment In a study comparing nine male patients with moderate hepatic impairment (Child-Pugh scores 7 to 9), to nine healthy male subjects, the single dose pharmacokinetics of silodosin were not significantly altered in patients with hepatic impairment. No dosing adjustment is required in patients with mild or moderate hepatic impairment. RAPAFLO has not been studied in patients with severe hepatic impairment. RAPAFLO is contraindicated in patients with severe hepatic impairment [see Contraindications and Warnings and Precautions]. OVERDOSAGE RAPAFLO was evaluated at doses of up to 48 mg/day in healthy male subjects. The dose-limiting adverse event was postural hypotension. Should overdose of RAPAFLO lead to hypotension, support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by maintaining the patient in the supine position. If this measure is inadequate, administration of intravenous fluid should be considered. If necessary, vasopressors could be used, and renal function should be monitored and supported as needed. Dialysis is unlikely to be of significant benefit since silodosin is highly (97%) protein bound.

Manufactured by: Watson Laboratories, Inc., Corona, CA 92880 USA Distributed by: Watson Pharma, Inc., Morristown, NJ 07962 USA Under license from: Kissei Pharmaceutical Co., Ltd., Nagano, Japan Address medical inquiries to: WATSON Medical Communications, P.O. Box 1953, Morristown, NJ 07962-1953 800-272-5525 For additional information see: www.rapaflo.com or call 1-866-RAPAFLO (727-2356) Rx Only Revised: November 2009 173761-2 S1109


IN THE TREATMENT OF SYMPTOMATIC BPH*

RAPID RELIEF THAT KEEPS HIM GOING

*Benign prostatic hyperplasia

RAPAFLO® is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). RAPAFLO® is not indicated for the treatment of hypertension. Important Safety Information RAPAFLO® is contraindicated in patients with severe renal impairment (CCr <30 mL/min), severe hepatic impairment (Child-Pugh score ≥10), and with use of strong CYP3A4 inhibitors. Postural hypotension with or without symptoms (eg, dizziness) may develop when beginning treatment with RAPAFLO®. As with all alpha-blockers, there is a potential for syncope. Patients should be warned of the possible occurrences of such events and should avoid situations where injury could result. RAPAFLO® should be used with caution in patients with moderate renal impairment. Patients should be assessed to rule out the presence of prostate cancer prior to starting treatment with RAPAFLO®. Patients planning cataract surgery should inform their ophthalmologist that they are taking RAPAFLO®. The most common side effects are retrograde ejaculation, dizziness, diarrhea, orthostatic hypotension, headache, nasopharyngitis, and nasal congestion. Please see brief summary of Full Prescribing Information on adjacent page. Models are for illustrative purposes only.

www.rapaflo.com

© 2010, Watson Pharma, Inc., Morristown, NJ 07960. All rights reserved.

06318 1/10

Reports from the Society of Urologic Nurses and Associates (SUNA) 2010  

The Urology Nurse - NP/PA November 2010, VOL 2, NO 6 • SUPPLEMENT

Read more
Read more
Similar to
Popular now
Just for you