SOAP note AHA Week 7
Maleficient
BPHtreatment.consultpharm.15.pdf
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IN PRACTICE
Introduction Benign prostatic hyperplasia (BPH), also known as benign prostatic hypertrophy, is a nonmalignant adenomatous overgrowth of the periurethral prostate gland that is commonly seen in aging men. The enlarged prostate has been thought to contribute to the impairment of the bladder’s ability to completely empty, which in turn contributes to the overall lower urinary tract symptoms (LUTS). According to the American Urological Association’s (AUA) Guidelines for the Management of
BPH, this is thought to occur as a result of direct bladder outlet obstruction (BOO) and increased smooth muscle tone and resistance from the enlarged prostate.1 Chronic BOO secondary to BPH may lead to urinary retention, renal insufficiency, recurrent urinary tract infections, hematuria, and bladder calculi. In addition, symptoms attributed to BPH can potentially have a huge impact on quality of life (QOL) and sleep patterns.1 The prevalence of histopathologic BPH is age dependent, with initial development usually occurring after age 40.1 In men 60
Todd J. Woodard, Kendra R. Manigault, Niesha N. McBurrows, Tiffany L. Wray, Laresa M. Woodard
Management of Benign Prostatic Hyperplasia in Older Adults Benign prostatic hyperplasia (BPH), also known as benign prostatic hypertrophy, is a nonmalignant adenomatous overgrowth of the periurethral prostate gland commonly seen in aging men. Historically, it has been assumed that the pathophysiology of lower urinary tract symptoms in men is the result of bladder outlet obstruction associated with prostate enlargement. Symptoms such as urinary hesitancy, incomplete bladder emptying, dribbling or prolonged urination, nocturia, urinary urgency, and/or urge incontinence are common. Understanding the differential diagnosis and ordering appropriate laboratory tests are essential in accurately identifying a BPH diagnosis. Management can be broken down into medical or pharmacological and surgical therapies. This article aims to provide an overview of BPH and its management in older adults.
KEY WORDS: Benign prostatic hyperplasia, BPH, Incontinence, Men’s health, Older adults, Urinary, Urology.
ABBREVIATIONS: AUA = American Urological Association, AUA-SI = American Urological Association Symptom Index, BOO = Bladder outlet obstruction, BPH = Benign prostatic hyperplasia, CAM = Complementary and alternative medicine, DRE = Digital rectal examination, IFIS = Intraoperative floppy iris syndrome, IPSS = International Prostate Symptom Score, LUTS = Lower urinary tract symptoms, MIT = Minimally invasive therapy, PDE-5 = Phosphodiesterase type 5, PSA = Prostate- specific antigen, QOL = Quality of life, TUIP = Transurethral incision of the prostate, TUMT = Transurethral microwave thermotherapy, TUNA = Transurethral needle ablation, TURP = Transurethral resection of the prostate, TUVP = Transurethral electrovaporization.
nocturia, urinary urgency, and urge incontinence.6,7 Unfortunately, these symptoms are not specific to BPH, and the presence of these symptoms is not sufficient to make a diagnosis of BPH.8
Diagnosis and Evaluation The diagnosis of BPH begins with obtaining a complete medical history, including a description of any specific urinary symptoms the patient may be experiencing.9 Providers should assess for the severity, annoyance, and impact of LUTS on QOL. As previously mentioned, problems with urine storage, voiding, and post-micturition symptoms (i.e., dribbling) comprise types of LUTS, though presenting symptoms may depend on the underlying pathophysiology causing them.10 It is also important to screen for hematuria, dysuria, and pain. During the evaluation of patients with LUTS, other potential causes of LUTS must be excluded (Table 2).11-13 Other diagnostic components of the relevant medical history include a record of voiding habits, and results of the American Urological Association Symptom Index (AUA-SI) and the International Prostate Symptom Score (IPSS), which are questionnaires that address LUTS symptoms and impact on QOL. The AUA-SI is commonly used to assess a patient’s obstructive and irritative voiding symptoms. Patients rate seven symptoms from 0 to 5 (0 corresponds to no problems, 5 corresponds to severe symptoms) based on their perceived severity. Scores less than 8 are categorized as mild, scores between 8 and 19 are
years of age and older, 50% have been diagnosed with BPH, and 75% of men older than 70 years of age have one or more symptoms attributable to BPH. By 85 years of age, 90% of men have symptoms of BPH. 2 The treatment of BPH poses a substantial burden to the health care system, with annual expenditures attributable to the treatment of BPH and its associated symptoms estimated at $4 billion.3 Because the prevalence and costs associated with BPH are substantial, the last decade has brought significant advancements in our understanding of BPH and increased interest in its management.
Pathophysiology and Clinical Manifestations Located anterior to the rectum, the prostate is a heart- shaped, walnut-sized gland that is located below the urinary bladder. The prostate surrounds the proximal urethra, and its major function is to secrete fluids that make up a portion of the ejaculate volume. The weight of a normal prostate in an adult male is between 7 grams and 16 grams. Physical examination of the prostate must be done by digital rectal examination (DRE), and it is manually palpated by placing a finger into the rectum. 4
BOO in men with BPH is said to be attributed to both static and dynamic factors. Static factors relate to an anatomic enlargement of the prostate gland, which encroaches on the prostatic urethra and bladder outlet, thereby obstructing urinary flow. The dynamic obstruction is related to the tension of the prostate’s smooth muscle.5 Symptoms of BPH can be a result of these static and/or dynamic manifestations, and this should be taken into account when drug therapy is considered. Historically, it has been assumed that the pathophysiology of LUTS in men is the result of BOO associated with prostate enlargement. LUTS are not classified as a disease, but as a group of disorders affecting the prostate and bladder that share a common clinical manifestation. LUTS can be categorized into voiding and storage symptoms (Table 1). Voiding symptoms may include urinary hesitancy, the sensation of incomplete bladder emptying, weak urinary stream, terminal or postmicturition dribbling, or prolonged urination. Storage symptoms can include increased urinary frequency,
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Table 1. Lower Urinary Tract Symptoms
Source: Reference 6, 7.
Voiding Storage
Urinary hesitancy Urinary frequency Poor urinary flow Nocturia Sensation of complete bladder emptying Urinary urgency Weak urinary stream Urge incontinence Post-micturition dribbling Prolonged urination
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considered moderate, and scores greater than or equal to 20 are categorized as severe.14
Physical examination aids in reaching the correct diagnosis, and begins with inspection of the male genitalia, careful DRE to estimate prostate size, and assessment for tenderness to palpation of prostate and for structures like the bladder. If the prostate is enlarged it may feel soft and symmetric without any nodules or indurations during DRE. Performing a related neurological exam helps to rule out other causes of urinary symptoms and assist with determining the differential diagnosis. Laboratory and procedural tests of diagnostic use encompass urinalysis followed by urine culture if abnormal, serum prostate-specific antigen (PSA) level, ultrasound of the prostate and upper and lower urinary tract, post-void residual volume
measurement, cystoscopy, and uroflowmetry.15 Measuring the PSA may be beneficial if the DRE is deferred. The PSA is a marker that may correlate with prostate size or enlargement. A prostate is considered enlarged when the volume is greater than 40 mL (Table 3). A detailed approach guides appropriate diagnosis and management recommendations.
Management
Nonpharmacological Therapy Watchful waiting or active surveillance is commonly utilized in BPH patients who are asymptomatic or have mild symptoms (AUA-SI < 8); however, patients with moderate or severe symptoms (AUA-SI ≥ 8) who have not developed complications or are not bothered by their symptoms may also elect to use this monitoring strategy (Table 4).1,16 During watchful waiting, patients return to clinic at regular intervals (12 months) for evaluation of symptoms but do not receive treatment.1 Symptom improvement with watchful waiting may be negligible, but a slight improvement has been seen in up to one third of men.1,17
MANAGEMENT OF BPH
Table 2. Common Differential Diagnoses for BPH
Abbreviation: BPH = Benign prostatic hyperplasia. Source: References 7, 11-13.
Neurogenic Bladder Prostatitis Bladder Cancer Prostate Cancer Urinary Tract Infection Diabetes Erectile Dysfunction Cardiovascular Disease Neurologic Disease Sexually Transmitted Diseases
Table 3. PSA Level Correlation to Prostate Volume of 40 mL
Abbreviation: PSA = Prostate-specific antigen. Source: References 7, 13.
Age PSA Level
≥ 50 1.6 mcg/L ≥ 60 2.0 mcg/L ≥ 70 2.4 mcg/L
Table 4. American Urologic Association Symptom Index
Source: References1, 7, 13, 15.
Score Recommendation
< 8 (Mild symptoms) Watchful waiting
8-19 (Moderate symptoms) Pharmacotherapy (if bothersome) OR Surgery (if BPH complications)
20-35 (Severe symptoms) Pharmacotherapy (if bothersome) OR Surgery (if BPH complications)
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Behavior modification may also minimize LUTS and is often recommended in addition to watchful waiting.1,14 Recommendations include limiting fluid intake in the evening to decrease risk of nocturia, avoiding excessive alcohol and caffeine, consuming a healthy diet, smoking cessation, and exercise. Physical activity was associated with a decreased risk of BPH, surgery for BPH, and symptomatic BPH when compared with inactivity, emphasizing the benefit of increased activity in BPH patients.15,18
In addition, avoiding drugs that can exacerbate urinary symptoms is an important facet of behavior modification.1,16 Several drug classes should be used with caution or avoided in patients with BPH (Table 5). In general, medications with significant anticholinergic effects (e.g., antihistamines, tricyclic antidepressants) should be avoided because of risk of acute urinary retention; alpha-adrenergic agonist (e.g., pseudoephedrine, phenylephrine) may cause muscle contractions and problems with bladder emptying. Beta-adrenergic agonist (e.g., terbutaline) may prevent voiding resulting from relaxation of the bladder detrusor muscle.14 Testosterone supplementation should be avoided or used with caution in patients with BPH because of testosterone’s role in prostate enlargement.14 Large doses of diuretics can cause polyuria and increase the frequency of voiding in patients with BPH. Symptom distress may be decreased by avoiding triggers and medication management.1
Pharmacological Therapy
Alpha 1 Receptor-Antagonists
There are three alpha1 adrenoceptor subtypes: α1A, α1B,
and α1D. The α1B subtype regulates blood pressure via vascular smooth muscle contraction, and α1D subtype is thought to be associated with bladder muscle contraction and sacral spinal cord innervation.19 The α1a adrenoceptors in the human prostate, bladder base, bladder neck, prostatic capsule, and prostate urethra mediate contraction of the smooth muscle in these tissues.20 In response to alpha-adrenergic receptor stimulation, smooth muscles in the prostate gland contract, causing
constriction of the prostatic urethra.13 Alpha1 receptor antagonists, commonly referred to as alpha1-blocker, work by relaxing smooth muscle tone in the prostate and the bladder neck.21 Terazosin, doxazosin, tamsulosin, alfuzosin, and silodosin are the alpha1-blockers that are approved by the Food and Drug Administration (FDA) for BPH. (Table 5 compares drug-specific features.) Terazosin, doxazosin, and alfuzosin are nonselective in that they block all three α1 adrenergic receptor subtypes, in comparison with tamsulosin, which blocks α1A and α1D adrenergic receptors with 10-fold greater affinity than α1B. Silodosin blocks α1A with 162-fold greater affinity than α1B adrenergic receptors.22 In addition to being FDA-approved for BPH, terazosin and doxazosin are also FDA-approved for hypertension. Prazosin is another alpha-blocker FDA-approved for hypertension but used off-label for BPH. Though terazosin, doxazosin, and prazosin are commonly used for hypertension, in particular comorbid hypertension, these medications are not recommended as first-line agents in the treatment of hypertension because they are less effective than thiazide diuretics and angiotensin-converting enzyme inhibitors in preventing cardiovascular outcomes.23 Terazosin and doxazosin also require dose titration, usually over several weeks, to minimize orthostatic hypotension and dizziness after initial administration, which could be problematic for the older adult and increase the risk of falls. Risk of orthostatic hypotension is increased when terazosin
Table 5. Medication Classes Associated with Lower Urinary Tract Symptoms
Source: References: 1, 7.
• Antihistamines (e.g., Diphenhydramine, Chlorpheniramine)
• Decongestants (e.g., Pseudoephedrine, Phenylephrine)
• Diuretics (e.g., Furosemide, Bumetanide)
• Opiates (e.g., Morphine, Oxycodone)
• Tricyclic Antidepressants (e.g., Amitriptyline, Imipramine)
• Testosterone Replacement (e.g., Depo-Testosterone, Androderm)
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MANAGEMENT OF BPH
and doxazosin are combined with phosphodiesterase inhibitors used to treat erectile dysfunction, a common combination of medications found in older men. Tamsulosin, alfuzosin, and silodosin have a lower potential to cause hypotension and syncope than either terazosin or doxazosin.24 For tamsulosin and silodosin, the less effect on blood pressure is thought to result from its higher selectivity for the α1 receptors.19,20 Alfuzosin is not specific for the a subtypes, but its lower rate of orthostatic effects, relative to terazosin and doxazosin, is possibly a result of its extended-release formulation. This lower risk of hypotension may be an attractive option for older men at risk for falls. Symptomatic improvement may be seen as early as two to four weeks of therapy.13 All alpha-blockers can potentially lead to fall, fractures, and head trauma secondary to hypotension. Therapies for erectile dysfunction such as sildenafil, vardenafil, and tadalafil are selective inhibitors of cyclic guanosine monophosphate-specific phosphodiesterase type 5 (PDE-5). There are currently precautions in the prescribing information of these agents, as they can lower blood pressure significantly when used concomitantly with α1 receptor-antagonist.25-27 Patients should be on a stable alpha-blocker dose before starting PDE-5 inhibitors, sildenafil, vardenafil, and tadalafil. In patients who are stable on alpha1 receptor-antagonist, PDE-5 inhibitors should be initiated at lowest recommended dose.25-27 It is suggested that men separate the doses of alpha1 antagonist and PDE-5 inhibitors by at least four hours.24 In general it is recommended that tamsulosin, alfuzosin, and silodosin be used in men who are also using PDE-5 inhibitors.24 Ejaculatory dysfunction is a side effect associated with alpha1 blockers, particularly tamsulosin and silodosin. These particular side effects are important because erectile dysfunction commonly affects men with BPH. In a systemic review and meta-analysis, it was found that ejaculatory dysfunction was significantly more prevalent with alpha1 antagonist than placebo (P < 0.0001), in particular, considering tamsulosin (P = 0.006) or silodosin (P < 0.0001), with tamsulosin associated with significant lower risk of ejaculatory dysfunction than silodosin (P < 0.00001). Doxazosin and terazosin were associated with risk similar to placebo.28 Ejaculatory dysfunction
was significantly more common with combination therapy, compared with alpha1 antagonist alone (P < 0.0001) or with 5-alpha reductase inhibitors alone (P = 0.02), and was significantly more common with the 5-alpha reductase inhibitors, compared with placebo (P < 0.0001). Both finasteride (P < 0.0001) and dutasteride (P = 0.0002) were associated with significantly higher risk of ejaculatory dysfunction than placebo.28 Alpha1-blockers have also been associated with intraoperative floppy iris syndrome (IFIS). IFIS is observed during cataract surgery in patients taking alpha1-blockers. This condition is characterized by a flaccid and billowing iris, iris prolapse, and intraoperative pupil constrictions.29,30 It is important that patients who are undergoing cataract surgery be counseled to inform the ophthalmologist that they are on or have been on alpha1 receptor-antagonist. Prior to cataract surgery a thorough medication history should be obtained. Surgeons who are undertaking cataract surgery need to identify patients who have received in the past or are currently are receiving a1 receptor-antagonist so that intraoperative strategies can be employed to circumvent IFIS adverse events.31 Discontinuing a1 receptor-antagonist has not shown to prevent or decrease the severity of IFIS, thus the recommendation to stop alpha1 antagonist prior to surgery is no longer valid.32 Tamsulosin is most commonly associated with IFIS, but it can also be seen with terazosin, doxazosin, and alfuzosin.33
5-Alpha Reductase Inhibitors Finasteride and dutasteride are approved by FDA for BPH (see Table 6 for a comparison). They act by inhibiting the conversion of testosterone to dihydrotestosterone, suppressing prostate growth.34 Unlike alpha1 receptor- antagonists, which have been shown to relieve symptoms and work by relaxing smooth muscle tissue, 5-alpha reductase inhibitors actually reduce prostate volume by inducing epithelial atrophy.35 They do not provide immediate symptomatic relief and can take approximately six months before beneficial effects are seen.36 These agents are more effective in patients with a prostate size greater than 40 mL.37 In a meta-analysis comparing finasteride and dutasteride, there was no statistically
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Table 6. Pharmacological Agents for BPH
Drug Name
Alfuzosin (Uroxatral)
Doxazosin (Cardura, Cardura XL)
Terazosin (Hytrin)
Silodosin (Rapaflo)
Tamsulosin (Flomax)
Dosage
10 mg daily
Immediate release: 1 mg daily; titrate every 1-2 weeks max of 8 mg daily
Extended release: 4 mg once daily; titrate every 3-4 weeks to max of 8 mg daily
1 mg at bedtime; titrate over several weeks; if no response after 4-6 weeks of 10 mg/day, may increase to 20 mg/day
8 mg daily
0.4-0.8 mg daily
Adverse Reactions
Dizziness, orthostatic hypotension, syncope, fatigue, headache, floppy iris syndrome
Dizziness, malaise, orthostatic hypotension, fatigue, headache, syncope, floppy iris syndrome
Dizziness, muscle weakness, orthostatic hypotension, syncope, floppy iris syndrome
Retrograde ejaculation, orthostatic hypotension, dizziness, floppy iris syndrome
Orthostatic hypotension, dizziness, headache, ejaculation failure, floppy iris syndrome
Renal
Use caution in severe renal impairment < 30 mL/min
No dosage adjustment recommendations provided in manufacturer’s labeling
No dosage adjustment necessary
Clcr > 50 mL/ minute: no dosage adjustment necessary
Clcr 30-50 mL/ minute: 4 mg once daily
Clcr < 30 mL/ minute: Use is contraindicated
Clcr ≥10: no dose adjustment necessary; Clcr < 10 mL/minute: has not been studied
Hepatic
Child Pugh B or C use is contraindicated
Mild to moderate hepatic dysfunction: use caution
Severe hepatic impairment: not recommended
No dosage adjustment provided in manufacturer’s labeling
Child Pugh A or B: no dosage adjustment necessary
Child Pugh C: contraindicated
Mild to moderate hepatic impairment: no adjustment necessary; severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling
Clinical Pearls
When using concurrently with PDE-5 inhibitors initiate PDE-5 inhibitor at lowest possible dose
Highest incidence of abnormal ejaculation. Low incidence of dizziness and hypotension
Low incidence of dizziness and hypotension
Non-selective Alpha 1 -Blockers
Selective Alpha1a-Blockers
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Table 6. Pharmacological Agents for BPH (continued)
Drug Name
Finasteride (Proscar)
Dutasteride (Avodart)
Dutasteride/ Tamsulosin (Jalyn)
Tadalafil (Cialis)
Dosage
5 mg daily
0.5 mg daily
0.5/0.4 mg daily
5 mg daily
Source: Lexi-Comp, Inc. (Lexi-Drugs®). Lexi-Comp, Inc.; January 21, 2016. Abbreviations: BPH = Benign prostatic hyperplasia, Clcr = Creatinine clearance, PDE-5 = Phosphodiesterase type 5.
Adverse Reactions
Orthostatic hypotension, dizziness, decreased libido, impotence
Decreased libido, impotence
Decreased libido, impotence, abnormal ejaculation, decrease in sperm count, floppy iris syndrome
Flushing, headache, dyspepsia, hypotension
Renal
No adjustment necessary
No adjustment necessary
Clcr >10: no adjustment
Clcr ≥ 51 mL/ minute: No dosage adjustment necessary.
Clcr 30-50 mL/ minute: Initial: 2.5 mg once daily; maximum: 5 mg once daily.
Clcr < 30 mL/minute: not recommended.
Hemodialysis: Use not recommended
Hepatic
Use with caution
There are no dosage adjustments provided in the manufacturer’s labeling
Not defined
Child Pugh A or B: use with caution; Child Pugh C: not recommended
Clinical Pearls
May take up to 6 months before effects are seen; Should not be touched or handled by women who are pregnant or are of childbearing age
Do not use with alpha blockers for BPH; CYP3A4 inhibitors (strong): max dose 2.5 mg
5-Alpha Reductase Inhibitors
PDE-5 inhibitors
significant differences in the treatment of symptomatic BPH. The treatment effects of dutasteride compared with finasteride were not significant in peak urinary flow (weighted mean difference [WMD] = 0.76, 95% confidence interval [CI] -0.67-2.00) and total prostate volume (WMD = -7.6, 95% CI -21-6.6). There was, however, a significant reduction in IPSS in the dutasteride
group compared with the finasteride group (WMD = -1.8, 95% CI -2.90 to -0.11).38 These agents may actually affect the clinical course of BPH, unlike alpha-blockers.13
Major adverse effects associated with 5-alpha reductase inhibitors include decreased libido and ejaculatory or erectile dysfunction.13 AUA recommends that patients have a baseline PSA measured before initiating therapy
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with finasteride and dutasteride as they may shrink the prostate and lower PSA levels by an average of 50%.7 It is also important to note that these agents are a category X; therefore, women who are pregnant or of childbearing age should not handle these drugs.7
PDE-5 Inhibitors Over the years PDE-5 inhibitors have been studied and showed some promise in treating LUTS associated with BPH, in particular vardenafil and tadalafil. The effect of PDE-5 on cyclic guanosine monophosphate concentration is also observed in the prostate, the bladder, and their vascular supply. The mechanism for reducing BPH symptoms has not been well established.27 Symptom improvement with these agents is usually seen within one to two weeks of initiation of treatment. Since combinations of nonselective alpha-blocking agents have an increased risk of hypotension when used in conjunction with PDE-5 inhibitors, their combined use should be avoided. However, selective alpha-blocking agents in combination with PDE-5 inhibitors may be an option. PDE-5 inhibitors have become a reasonable option for men with BPH and concomitant erectile dysfunction. Although both have been studied, tadalafil is the only one in its class to gain FDA approval for the treatment of BPH.7 It is prescribed at a dose of 5 mg daily. When initiated with finasteride it is recommended for up to 26 weeks because the incremental benefit of tadalafil decreases from 4 weeks to 26 weeks and the incremental benefit of tadalafil beyond 26 weeks is unknown.39 Drug interaction consideration should be taken into account when using tadalafil because use with nitrates is contraindicated. Also, cytochrome P450 3A4 inhibitors may increase tadalafil’s concentration, thus increasing risk of side effects such as headache, indigestion, nasal congestion, and myalgia.7 Table 5 has commonly used FDA-approved treatment options for BPH.
Anticholinergic (Antimuscarinic) Agents Traditionally, antimuscarinic agents have been thought to increase the risk of urinary retention. These agents have been studied in men with BPH who have symptoms of overactive bladder, and several studies have shown some
improvement of LUTS in men with BPH.7 Uroselective anticholinergic agents (i.e., solifenacin, fesoterodine, etc.) may be used in select BPH patients with bothersome voiding symptoms who have a postvoid residual volume < 250 mL.14 If an antimuscarinic is to be used, studies have suggested that patients be stable on an alpha-blocker dose prior to initiation. Their effects as add-on therapy may take anywhere from 8 to 12 weeks.7 Currently there are not any FDA-approved antimuscarinic agents for the treatment of BPH; however the AUA recognizes their potential role in the management of BPH.7
Combination Therapy Combination therapy is most commonly started when BPH symptoms are refractory to monotherapy.40 The multicenter randomized controlled trial, Medical Therapy of Prostatic Symptoms study, compared the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of BPH. This double-blind trial, with a mean follow-up of 4.5 years, enrolled 3,047 eligible patients with a median age of 62 years. The risk of overall progression was defined as increase above baseline of at least 4 points in the American Urological Association symptoms score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infections. The trial showed that risk of overall progression was significantly reduced by doxazosin (39% risk reduction; P < 0.001), and finasteride (34% risk reduction; P = 0.002), compared with placebo. The combination of these agents yielded a significant reduction in progression of disease (66%, compared with placebo; P < 0.001) compared with doxazosin (P < 0.001) or finasteride (P < 0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P < 0.001) and finasteride (P < 0.001), but not by doxazosin. Significant improvement in symptoms scores with doxazosin (P < 0.001), finasteride (P = 0.001), and combination therapy (P < 0.001) was noted with combination therapy being superior to both doxazosin (P = 0.006) and finasteride (P < 0.001) alone.35 In June 2010 a combination product of dutasteride and tamsulosin was approved by FDA for BPH under the trade name
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Jalyn®. Small studies have demonstrated that combining PDE-5 inhibitors with selective alpha-blockers might prove beneficial in providing further reductions in IPSS without notable increases in side effects.7
Alternative Therapy Complementary and alternative medicines (CAM) have been used to treat BPH for decades.1,41 Most CAM therapies consist of phytotherapy (the use of plant medications); however, acupuncture, homeopathy, and other treatment options are also included under the CAM umbrella.1,42 Because of a lack of evidence, the AUA recommends against the use of phytotherapy, combination phyotherapeutic agents, or other nonconventional therapies (e.g., acupuncture) for the treatment of LUTS caused by BPH.1 Despite this recommendation, patients may obtain herbal supplements over-the-counter (OTC). Use of phytotherapy presents a challenge since some patients do not inform their primary care providers they are using these drugs.1,43 Additionally, the effectiveness, safety, and purity of OTC medications is not routinely monitored; therefore, the quality of phytotherapy can vary vastly from manufacturer to manufacturer.
Many phytotherapies have been evaluated for BPH treatment. Some of the more popular agents include saw palmetto (Serenoa repens), stinging nettle root (Urtica dioica), African plum tree (Pygeum africanum), pumpkin seed (Cucurbita pepo), and rye pollen (Secale cereale).1,41,44 Saw palmetto is the most commonly used herbal supplement for BPH symptoms.1 The mechanism of action of saw palmetto is unclear; however, it is thought to have antiandrogenic, antiproliferative, and anti- inflammatory properties.15,44 Historically, saw palmetto was thought to be effective for BPH treatment; however, a 2011 study found a mean reduction in AUA-SI score of 2.20 points with saw palmetto and 2.99 with placebo at 72 weeks (P = 0.91).15,45 Study participants were, on average, 61 years of age, well-educated non-Hispanic white men, with a AUA-SI of 14.6. No subgroups (e.g., race, age, AUA-SI score, etc.) displayed clinically significant differences to saw palmetto versus placebo.45 Additionally, a systematic review showed inconsistent, but largely insignificant, improvement in BPH patients
treated with saw palmetto when compared with placebo.15,46 As a result, the use of saw palmetto has fallen out of favor and is not recommended.
The stinging nettle root is thought to inhibit the binding of the sex hormone binding globulin to its receptor and have an antiproliferative effect in vitro along with other potential effects.41,44 At this time there is insufficient evidence to recommend for or against its use in BPH symptom improvement. Several studies with stinging nettle root contain additional phytotherapy (e.g., saw palmetto, African plum tree), which makes it more challenging to determine the effectiveness of the stinging nettle root alone. The African plum tree inhibits androgen and progesterone receptors as well as the cell proliferation of human prostatic cells.41 Trials with the African plum tree have provided promising results; however, many trials are short in duration, evaluate a small number of patients, and use varying extracts.41 Pumpkin seed is a plant source of beta-sitosterol, which is believed to have antiproliferative effects on prostate tissue.44 Evidence is lacking on the effectiveness of pumpkin seed in BPH symptoms; however, beta-sitosterol appears to reduce BPH symptoms and may also lower cholesterol.44 Rye pollen extract contains beta- sterols, which are thought to relax urethral smooth muscle tone, increase bladder muscle contractility, and potentially decrease inflammation. Data pertaining to rye pollen are promising; however, formulations differ greatly, which affects recommendations.41
Conflicting evidence exists for phytotherapy used for the treatment of BPH symptoms.1,44 Additionally, drug formulations, purity, and formulations differ widely, which increases the challenges associated with providing recommendations for the use of phytotherapy. Additional high-quality studies are necessary to prove the effectiveness of CAM therapies. Based on the conflicting results and lack of oversight, health care providers should recommend against the use of phytotherapy for the management of BPH symptoms.
Surgical Management Surgical treatments in general are not intended as first- line therapy options. These interventions are usually reserved for severe symptoms: medical treatment
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failure, intolerance to medications, larger prostate sizes, refractory urinary retention, persistent hematuria, and/ or bladder stones.7,13,47 Surgical treatment options can be divided into two categories: invasive procedures and minimally invasive therapy (MIT).
Invasive Procedures Surgery that involves making an incision in the patient’s body and inserting instruments or medical devices into it is considered invasive. These instruments can either be needles, tubes, devices or scopes. These types of surgeries can potentially leave large wounds that can be painful and take a long time to heal. These surgeries also have a higher incidence of erectile dysfunction and retrograde ejaculation compared with MIT.
Open Prostatectomy Open prostatectomy, or the surgical removal of the prostate gland, previously was the gold standard of treatment prior to the development of transurethral resection of the prostate (TURP).48 This procedure is the most effective procedure for improving LUTS and the lowest risk for re-operation. With its great effectiveness comes the highest rate of complications, such as transfusions, erectile dysfunction, and retrograde ejaculation. This procedure is also reserved for those with larger prostates (> 80 mL).49
Transurethral Resection of the Prostate As the current gold standard surgical therapy, TURP uses electric current or laser light during this procedure.47,50 A scope inserted through the penis is then utilized to gain visualization and resection. TURP does not remove the entire prostate and there may be less of a need for further treatment for BPH after surgery. This procedure has great outcomes and is always used as a comparison to other surgical therapies. This procedure is recommended for men with prostate volumes of 30-80 mL in size and improves symptoms in 90% of cases.49,51
Transurethral Incision of the Prostate (TUIP) TUIP is a potential option for those patients with BPH who have a smaller prostate (less than 30 mL or < 25 g)
but major blockage.50,51 This may also be a good option for younger, sexually active men. This surgery involves making minute cuts in the neck of the bladder and in the prostate, thereby making the urethra wider. As a result, reduced pressure of the prostate on the urethra occurs, making it easier to urinate.50 This option may be less invasive than TURP. Follow-up treatment may be necessary for some men. Efficacy may be comparable to TURP but may have a higher risk of re-operation long-term.49,52
Minimally Invasive Therapies These types of surgeries limit incision sizes and operate with less injury to the body than invasive procedures. In general they are safer than open surgery and allow for faster recovery and heal with less pain and scarring. There are several types of MIT available that would be beyond the scope of this article to discuss. We will focus on four techniques that have become common. MITs are typically less invasive in that, instead of cutting directly into tissue, they involve heating the prostate gland by various means such as microwave, laser, or electrical methods. Most of these procedures are also recommended for smaller prostates.
Transurethral Microwave Thermotherapy (TUMT) This procedure allows microwaves to raise the temperature in the prostate to destroy growing cells without affecting normal cells. This procedure does not require anesthesia. TUMT has been found safe and effective with improvements in urine flow rate and minimal impairment on sexual function. Men with various medical problems that do not make invasive surgery an ideal option may be good candidates for TUMT. Also men with weak hearts might be appropriate candidates because of a lack of blood loss during the procedure.52
Transurethral Electrovaporization (TUVP) TUVP is a method that combines similarities to TURP and TUIP, by engaging high electrical currents to vaporize and coagulate the obstructing prostate tissue. Though several patients have had irritative side effects to this
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MANAGEMENT OF BPH
procedure, long-term efficiency comparable to TURP has been recognized. Men with medium to large prostates may be good candidates who want to avoid more invasive surgeries.51,52
Transurethral Needle Ablation (TUNA) TUNA involves placing a scope in the penis through the urethra guiding tiny needles into the prostate tissue. Radio waves are passed through these needles to create heat, which kills the prostate tissue and shrinks the prostate size. This is considered a short-term treatment that may require future treatments. Serious complications are low and sexual side effects are minimal. Since there is no blood loss involved this procedure may be ideal for men with weaker hearts.52
Laser Prostatectomy Now becoming a widespread technique for MIT, laser ablation uses one of four types of lasers for treatment. This procedure provides significant improvement in urinary flow rates and symptoms. Also it has an advantage of minimal blood loss, which may be good for those with heart problems. It also provides reduced hospital stay, impotence rates, and bladder neck contractures, compared with TURP and other therapies.48
Conclusion and Pharmacist’s Role With expanding pharmacotherapeutic and surgical strategies for treating BPH, the role of the pharmacists continues to expand, making them essential to the interdisciplinary team of clinicians. Treatment expectations, medication safety, and patient compliance all become important when ensuring that the patient receives the expected therapeutic outcome from any of the provided interventions. Pharmacists are front-line practitioners—ensuring medication is safe and effective for each individual patient, and educating him or her on behavioral techniques.49 With these medication therapies come potential drug interactions, contraindications, and side effects that pharmacists, the medication experts, are best suited to help manage. In addition, surgical procedures can result in complications, and the pharmacist can help resolve any medication-related
complications that may result. Additionally, pharmacists can help set realistic treatment goals and expectations, taking into consideration other comorbidies in this population.
Todd J. Woodard, PharmD, BCPP, BCPS, CGP, is senior clinical pharmacist, Peach State Health Plan, Atlanta, Georgia, and adjunct clinical assistant professor, Philadelphia College of Osteopathic Medicine School of Pharmacy, Suwanee, Georgia. Kendra R. Manigault, PharmD, BCPS, BCACP, CDE, is clinical assistant professor, Mercer University College of Pharmacy, Atlanta. Niesha N. McBurrows, PharmD, is ambulatory care clinical pharmacist, Lakeland Community Based Outpatient Clinic, James A. Haley Veterans’ Affairs Hospital, Lakeland, Florida. Tiffany L. Wray, PharmD, BCPS, is ambulatory care clinical pharmacy specialist, Kaiser Permanente, Towne Park Comprehensive Medical Facility, Kennesaw, Georgia. Laresa M. Woodard, MMSc, PA-C, is physician assistant, Interventional Radiology, Emory University Hospital, Atlanta.
For correspondence: Todd J. Woodard, PharmD, BCPP, BCPS, CGP, Peach State Health Plan, 1100 Circle 75 Parkway, Suite 1100, Atlanta, GA 30339; Phone: 678-556-2293; Fax: 866-374-1579; E-mail: [email protected].
Disclosure: No funding was received for the development of this manuscript. The authors have no potential conflicts of interest.
Consult Pharm 2016;31:412-424.
© 2016 American Society of Consultant Pharmacists, Inc. All rights reserved.
Doi:10.4140/TCP.n.2016.412.
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ASCP A M
16
November 4-6, 2016 | Hilton Anatole | Dallas, Texas
Robert J. Miller Research & Education Poster Session
Saturday, November 5 10:15 am – 11:45 am
3:45 pm – 5:15 pm
Learn from your peers as colleagues share their research findings, clinical innovations, and practice management insights through poster presentations. The 2016 Poster Session is supported by the ASCP Foundation in honor of Robert J. Miller, former president and long-time member of ASCP. Bob Miller was known for his enthusiasm and desire to nuture others’ growth.
AM16-Posters.indd 1 7/20/16 2:06 PM
Publish Your Research in The Consultant Pharmacist
The Consultant Pharmacist welcomes reports of original, well-designed research and clinical reviews that are applicable to consultant pharmacy and senior care practice. The journal also encourages submission of literature reviews, case reports, and opinions on important clinical or professional issues.
Sharing research findings, clinical innovations, and practice management insights in the journal is an excellent way to expand the knowledge base of those working to improve the lives of seniors.
The Consultant Pharmacist seeks manuscripts on: • Medication therapy management • Consultant pharmacy services in the assisted
living setting • Innovative programs to improve medication
management during transitions of care • Health care needs of elderly in various
community based and long-term care settings • Medication-related problems in the elderly in a
wide range of settings
The journal also accepts letters to the editor, opinion pieces, and discussions of personal experiences in care of the elderly.
The journal, indexed by MEDLINE, the Cumulative Index of Nursing and Allied Health, EMBASE.com, Excerpta Medica, and International Pharmaceutical Abstracts, offers an efficient peer-review process. Approved manuscripts generally are published within nine months of acceptance.
For author and submission instructions, visit tcp.msubmit.net
For additional information, contact: H. Edward Davidson, PharmD, MPH
Editor-in-Chief The Consultant Pharmacist
[email protected] 757-625-6040
