Genitourinary tract agents

Generic and Brand Names

• Benign prostatic hyperplasia and lower urinary tract symptoms

  • Alpha-1 blockers tamsulosin Flomax alfuzosin Uroxatral silodosin Rapaflo doxazosin Cardura terazosin Hytrin

  • 5 alpha reductase inhibitors finasteride Proscar dutasteride Avodart

  • Phosphodiesterase 5 inhibitor for LUTS tadalafil Cialis

  • Storage symptom add ons antimuscarinics oxybutynin Ditropan ER tolterodine Detrol ER solifenacin Vesicare darifenacin Enablex fesoterodine Toviaz trospium Sanctura

  • Beta 3 agonists mirabegron Myrbetriq vibegron Gemtesa

• Overactive bladder and urge incontinence

  • Antimuscarinics and beta 3 agonists as above

  • OnabotulinumtoxinA Botox intradetrusor

  • Desmopressin DDAVP Nocdurna for nocturia

• Urinary tract infection focused urologic agents

  • Nitrofurantoin Macrobid Macrodantin fosfomycin Monurol methenamine hippurate or mandelate Hiprex Mandelamine phenazopyridine Azo Pyridium

• Interstitial cystitis bladder pain syndrome

  • Pentosan polysulfate sodium Elmiron amitriptyline generic hydroxyzine Atarax cimetidine Tagamet intravesical agents dimethyl sulfoxide RIMSO 50 heparin lidocaine combinations

• Erectile dysfunction and related

  • PDE5 inhibitors sildenafil Viagra tadalafil Cialis vardenafil Levitra Staxyn avanafil Stendra

  • Alprostadil intraurethral MUSE intracavernosal Caverject Edex

• Urolithiasis prevention and medical expulsive therapy

  • Potassium citrate Urocit K sodium bicarbonate generic thiazide and thiazide like diuretics hydrochlorothiazide chlorthalidone indapamide allopurinol Zyloprim febuxostat Uloric tamsulosin Flomax for expulsive therapy selected distal ureteral stones

• Enuresis nocturia

  • Desmopressin DDAVP Nocdurna antimuscarinics in refractory cases

Class

• Symptom directed pharmacotherapy across benign prostatic hyperplasia overactive bladder urinary tract infection supportive agents interstitial cystitis erectile dysfunction nephrolithiasis prevention and nocturia

Mechanism of Action

• Alpha-1 blockers relax prostatic and bladder neck smooth muscle via alpha-1A antagonism tamsulosin silodosin selective alfuzosin functionally uroselective doxazosin terazosin nonselective

• 5 alpha reductase inhibitors inhibit type II finasteride and type I II dutasteride conversion of testosterone to dihydrotestosterone reduce prostate volume and PSA

• Antimuscarinics inhibit M3 mediated detrusor contractions reduce urgency frequency incontinence

• Beta 3 agonists stimulate detrusor beta 3 receptors increase bladder capacity reduce urgency with minimal anticholinergic effects

• Tadalafil enhances nitric oxide cGMP signaling improving LUTS via prostatic and bladder neck smooth muscle relaxation and pelvic perfusion

• OnabotulinumtoxinA blocks acetylcholine release at detrusor neuromuscular junction decreases overactivity

• Nitrofurantoin damages bacterial DNA in urine compartment

• Fosfomycin inhibits MurA peptidoglycan synthesis single dose cystitis

• Methenamine releases formaldehyde in acidic urine nonantibiotic prophylaxis

• Phenazopyridine local urinary analgesic for short term dysuria relief

• Pentosan polysulfate putative glycosaminoglycan layer replenishment analgesic effect in IC BPS

• PDE5 inhibitors facilitate penile smooth muscle relaxation penile blood inflow

• Alprostadil PGE1 direct smooth muscle relaxation intracavernosal intraurethral

• Potassium citrate alkalinizes urine increases citrate to inhibit calcium stone crystallization

• Thiazides reduce urinary calcium excretion

• Allopurinol reduces uric acid production for uric acid and hyperuricosuric calcium stones

• Desmopressin V2 agonist concentrates urine reduces nocturnal urine production

Indications

• BPH LUTS symptom relief alpha-blockers prostate size reduction and progression risk reduction 5ARI combination therapy when prostate enlarged storage symptom add on antimuscarinic or beta 3 agonist tadalafil for mixed LUTS and erectile dysfunction

• Overactive bladder urgency frequency urge incontinence antimuscarinic or beta 3 agonist step up to onabotulinumtoxinA refractory

• Uncomplicated cystitis nitrofurantoin or fosfomycin as first line per local guidance prophylaxis methenamine in recurrent UTI phenazopyridine short 2 to 3 days adjunct

• Interstitial cystitis BPS multimodal therapy pentosan polysulfate oral agents intravesical therapies

• Erectile dysfunction first line PDE5 inhibitors second line alprostadil or vacuum device combinations

• Urolithiasis prevention hypocitraturia calcium oxalate or uric acid stones potassium citrate hypercalciuria thiazide uric acid stones alkalinization and allopurinol medical expulsive therapy tamsulosin for selected distal ureteral stones

• Nocturia nocturnal polyuria desmopressin in carefully selected adults with sodium monitoring

Dosage and Administration

• Tamsulosin 0.4 mg daily after same meal may increase to 0.8 mg silodosin 8 mg daily with food alfuzosin ER 10 mg daily doxazosin 1 to 8 mg daily terazosin 1 to 10 mg nightly with BP titration

• Finasteride 5 mg daily dutasteride 0.5 mg daily fixed combinations available with alpha-blockers

• Oxybutynin ER 5 to 30 mg daily transdermal patch gel options tolterodine ER 2 to 4 mg daily solifenacin 5 to 10 mg daily darifenacin 7.5 to 15 mg daily fesoterodine 4 to 8 mg daily trospium 20 mg twice daily or ER 60 mg daily

• Mirabegron 25 to 50 mg daily vibegron 75 mg daily

• Tadalafil 5 mg once daily for LUTS with or without erectile dysfunction

• OnabotulinumtoxinA 100 units intradetrusor for OAB nonneurogenic 200 units for neurogenic OAB require intermittent catheterization readiness

• Nitrofurantoin monohydrate macrocrystals 100 mg twice daily 5 days uncomplicated cystitis

• Fosfomycin tromethamine 3 g oral single dose

• Methenamine hippurate 1 g twice daily with urinary acidification

• Phenazopyridine 200 mg three times daily after meals maximum 2 to 3 days

• Pentosan polysulfate 100 mg three times daily taken before meals

• Sildenafil 25 to 100 mg as needed tadalafil 5 to 20 mg as needed or 2.5 to 5 mg daily vardenafil 5 to 20 mg as needed avanafil 50 to 200 mg as needed

• Alprostadil intracavernosal 2.5 to 20 mcg titrated intraurethral 125 to 1000 mcg

• Potassium citrate 10 to 30 mEq two or three times daily titrate to urine pH 6.0 to 7.0 for uric acid stones 6.5 to 7.0 for cystine stones

• Thiazides HCTZ 12.5 to 25 mg daily chlorthalidone 12.5 to 25 mg daily indapamide 1.25 to 2.5 mg daily

• Allopurinol 100 to 300 mg daily adjust to uric acid and renal function

• Desmopressin nocturia men SL 55 mcg women SL 27.7 mcg or oral 0.1 to 0.2 mg at bedtime follow product label and sodium monitoring plan

Monitoring

• BPH LUTS symptom scores IPSS blood pressure orthostatic signs ejaculatory effects PSA and prostate size on 5ARI

• OAB post void residual if antimuscarinic or Botox renal function with mirabegron blood pressure with mirabegron

• UTI symptom resolution urine culture adherence adverse events hepatic function if long term nitrofurantoin

• IC BPS pain and urgency scores ophthalmic exam for pentosan polysulfate maculopathy if long term

• ED blood pressure adverse events vision or hearing symptoms when on PDE5 inhibitors

• Stone prevention 24 hour urine chemistries serum electrolytes bicarbonate uric acid periodic imaging

• Desmopressin serum sodium baseline within 7 days at one month then periodically higher frequency in elderly or high risk

Contraindications

• Alpha-blockers with strong CYP3A4 inhibitors tamsulosin silodosin hypotension history orthostatic intolerance

• 5ARI pregnancy women of childbearing potential handling precautions children

• Antimuscarinics urinary retention gastric retention uncontrolled narrow angle glaucoma

• Mirabegron severe uncontrolled hypertension

• Botox urinary retention untreated UTI

• Nitrofurantoin creatinine clearance less than 30 mL min late third trimester pregnancy neonatal risk

• Fosfomycin limited for pyelonephritis bacteremia

• Methenamine severe hepatic insufficiency or severe dehydration urine pH not acidic

• Phenazopyridine severe renal or hepatic impairment

• Pentosan polysulfate hypersensitivity history of pigmentary maculopathy

• PDE5 inhibitors concomitant nitrates or guanylate cyclase stimulators riociguat severe hypotension recent stroke MI

• Alprostadil sickle cell disease predisposition to priapism bleeding disorders

• Potassium citrate hyperkalemia chronic kidney disease with low GFR active UTI struvite stones

• Thiazides sulfonamide allergy severe hyponatremia

• Allopurinol hypersensitivity HLA B 58 01 risk populations

• Desmopressin hyponatremia polydipsia heart failure uncontrolled hypertension loop diuretics or glucocorticoids

Precautions

• Intraoperative floppy iris syndrome with tamsulosin inform ophthalmology before cataract surgery

• 5ARI reduce PSA by about fifty percent adjust interpretation assess high grade cancer risk counseling

• Antimuscarinics cognitive adverse effects in older adults prefer trospium or darifenacin if cognitive risk

• Mirabegron modest blood pressure and heart rate rise consider ECG if arrhythmia history

• Nitrofurantoin long term pulmonary hepatic neuropathy risks monitor if prophylaxis

• Pentosan polysulfate cumulative dose dependent maculopathy baseline and periodic ophthalmic exams

• PDE5 inhibitors counsel on priapism NAION rare risk drug and alcohol interactions

• Desmopressin strict fluid restriction evening through overnight stop during intercurrent illness

Adverse Effects

• Alpha-blockers dizziness orthostatic hypotension ejaculatory disorders nasal congestion fatigue

• 5ARI decreased libido erectile dysfunction gynecomastia depression

• Antimuscarinics dry mouth constipation blurred vision cognitive impairment urinary retention

• Beta 3 agonists hypertension nasopharyngitis headache tachycardia rare urinary retention

• Botox urinary retention UTI hematuria localized pain

• Nitrofurantoin nausea headache rare pulmonary hepatitis neuropathy hemolysis in G6PD deficiency

• Fosfomycin diarrhea nausea headache

• Methenamine dysuria rash crystalluria with alkaline urine

• Phenazopyridine orange discoloration of urine GI upset methemoglobinemia with overdose

• Pentosan polysulfate nausea diarrhea hair loss elevated liver enzymes maculopathy

• PDE5 inhibitors headache flushing dyspepsia nasal congestion back pain vision color tinge rare hearing loss

• Alprostadil penile pain priapism fibrosis urethral burning

• Potassium citrate GI upset hyperkalemia alkalosis

• Thiazides hypokalemia hyponatremia hyperuricemia photosensitivity

• Allopurinol rash rare DRESS syndrome hepatotoxicity

• Desmopressin hyponatremia headache nausea seizures with severe sodium drop

Drug Interactions

• Alpha-blockers additive hypotension with PDE5 inhibitors space dosing

• 5ARI minimal CYP interactions dutasteride via CYP3A4 caution with strong inhibitors

• Antimuscarinics additive anticholinergic burden CYP3A4 interactions for solifenacin darifenacin tolterodine

• Mirabegron moderate CYP2D6 inhibitor elevates metoprolol desipramine dose adjust

• Nitrofurantoin antagonized by magnesium trisilicate antacids

• Fosfomycin minimal interactions

• Methenamine reduced effect with urinary alkalinizers sulfonamides crystalluria risk

• PDE5 inhibitors nitrates contraindicated caution with alpha-blockers and strong CYP3A4 inhibitors

• Allopurinol interacts with azathioprine 6 mercaptopurine reduce thiopurine dose markedly

• Thiazides increase lithium levels caution

• Desmopressin increased hyponatremia risk with SSRIs TCAs NSAIDs carbamazepine thiazides

Comparison Table 1 — BPH Therapy Options

Attribute	Alpha-1 blockers	5 alpha reductase inhibitors	Tadalafil daily	Add on antimuscarinic	Add on beta 3 agonist
Onset of symptom relief	Days to weeks	Months 3 to 6	Weeks	Weeks	Weeks
Effect on prostate size	None	Reduces 20 to 30 percent	None	None	None
Prevents retention surgery progression	No	Yes	No	No	No
Blood pressure impact	Orthostasis risk higher with nonselective	Minimal	Minimal	Minimal	May increase BP
Sexual side effects	Ejaculatory disorders	Decreased libido ED	Improves erectile function	Dry mouth constipation	Headache hypertension
Best candidates	Any prostate size rapid relief	Prostate enlarged PSA elevated	LUTS plus ED	Predominant storage symptoms with controlled PVR	Storage symptoms intolerance to antimuscarinic
Key cautions	IFIS cataract surgery	PSA interpretation cancer risk counseling	Avoid nitrates severe hypotension	Cognitive effects glaucoma retention	Hypertension tachycardia

Comparison Table 2 — Overactive Bladder Pharmacotherapy

Attribute	Antimuscarinics ER formulations	Beta 3 agonists mirabegron vibegron	OnabotulinumtoxinA intradetrusor
Efficacy urgency incontinence reduction	Moderate	Moderate similar to antimuscarinics	High in refractory cases
Tolerability	Dry mouth constipation cognitive effects in elderly	Better mouth and bowel tolerability mild BP HR rise	Risk of urinary retention intermittent catheterization need UTI
CNS penetration	Variable lower with trospium darifenacin	Minimal	Local bladder effect
Special notes	Try ER or transdermal oxybutynin to reduce side effects	Mirabegron is CYP2D6 inhibitor	Office based procedure effects last 6 to 9 months

Comparison Table 3 — UTI Focused GU Agents

Agent	Role	Typical Regimen	Key Strengths	Key Limits
Nitrofurantoin	First line uncomplicated cystitis	100 mg twice daily 5 days	Low collateral damage concentrates in urine	Not for pyelonephritis or CrCl less than 30
Fosfomycin	First line single dose cystitis	3 g once	Single dose activity vs ESBL	Lower cure rates in some settings avoid for pyelo
Methenamine	Prophylaxis recurrent UTI	1 g twice daily with urine acidification	Nonantibiotic avoids resistance	Needs acidic urine avoid with alkalinizers
Phenazopyridine	Analgesic adjunct	200 mg three times daily 2 to 3 days	Rapid dysuria relief	Symptomatic only discoloration methemoglobinemia risk

Comparison Table 4 — Erectile Dysfunction Therapies

Attribute	Sildenafil	Tadalafil	Vardenafil	Avanafil	Alprostadil intracavernosal intraurethral
Onset	30 to 60 min	30 to 60 min daily or on demand	30 to 60 min	15 to 30 min	Minutes after administration
Duration	4 to 6 h	Up to 36 h	4 to 6 h	6 h	Short requires titration
Food effect	High fat meal delays	Minimal	High fat meal delays	Minimal	None
Pros	Cost data CV outcomes with tadalafil for LUTS	Daily option for LUTS plus ED long window	Orally disintegrating form available	Fast onset	Works when PDE5 fail contraindicated with nitrates still
Cons	Headache flushing visual color tinge	Back pain myalgia	QT caution with some antiarrhythmics	Headache cost	Invasive priapism fibrosis training required

Comparison Table 5 — Stone Prevention

Stone type driver	First line agent	Target and notes	Alternatives adjuncts
Calcium oxalate hypocitraturia	Potassium citrate	Urine citrate above 320 mg day pH around 6.5	Thiazide for hypercalciuria dietary sodium restriction
Calcium stones hypercalciuria	Thiazide or thiazide like diuretic	Reduce urinary calcium	Potassium citrate if hypocitraturia present
Uric acid stones low urine pH	Potassium citrate	Urine pH 6.0 to 7.0 dissolve and prevent	Allopurinol if hyperuricosuria
Cystine stones	High dose potassium citrate	Urine pH 7.0 to 7.5 increase solubility	Thiol drugs specialist use sodium restriction high fluids