www.amh.net.au 13.1.1 Anticholinergics Special cases 13.1 Drugs for urinary tract disorders Urinary incontinence There are 3 main types of urinary incontinence, which may occur separately or in combination: – urge: involuntary loss of urine accompanied or preceded by a sudden urge to void (bladder overactivity) – stress: involuntary leakage on effort, exertion, sneezing or coughing – overflow: urinary retention and bladder distension caused by outlet obstruction (eg prostatic enlargement) or detrusor underactivity. Before starting drug treatment Ask the patient to keep a bladder diary for three 24hour periods; this may help to identify the type of incontinence and possible aetiology; tests (eg urinalysis, urodynamic assessment) may be necessary. Manage contributing factors, eg UTI, faecal loading, excessive fluid intake, unstable diabetes, obesity; reduce intake of caffeinated or alcoholic drinks. Also consider drugs as a cause of incontinence, eg selective alpha-blockers (eg prazosin), diuretics, anticholinesterases (eg donepezil), sedatives. Opioids and drugs with anticholinergic effects (see Table B–2 p 957) may cause urinary retention (p 519) and overflow incontinence. Drug-induced incontinence is particularly common in the elderly. Consider non-drug measures to help bladder control including pelvic floor exercises and bladder training (particularly useful for stress and urge incontinence respectively). Protective pads and scheduled voiding may be helpful in managing incontinence, especially in people with cognitive impairment or limited mobility. Rationale for drug use Incontinence resistant to non-drug measures. Relieve symptoms, reduce complications of incontinence and improve quality of life. Drug choice Anticholinergics (p 519) reduce bladder muscle contractility and increase bladder capacity, and are mainly used for urge incontinence. They may increase voiding dysfunction, causing hesitancy and retention in susceptible people. The benefit from anticholinergics varies between individuals; on average there is one fewer episode of incontinence per 48 hours compared with placebo, with no evidence of superior efficacy with newer agents (eg solifenacin, darifenacin) compared to oxybutynin. Stop if there is no benefit after 4 weeks of treatment. Propantheline is no longer recommended for treatment of urinary incontinence. Selective alpha-blockers block receptors in bladder neck and urethra, which may help to reduce outflow obstruction and overflow incontinence in males (see Urinary retention p 519) but may precipitate or worsen incontinence in women. AMH © 2013 Incontinence in neurological disease is a complex condition and is best managed by a specialist. Mainstays of treatment are intermittent selfcatheterisation, behavioural modification, and anticholinergics. Botulinum toxin (p 842) injected into the bladder wall, surgery and the use of urinary appliances may be useful. Practice points • intermittent catheterisation is preferred in most cases of overflow incontinence occurring postoperatively, postpartum or after neurological damage when improvement with time can be expected • evidence suggests vaginal oestrogen may be effective for incontinence in postmenopausal women with urogenital symptoms; systemic oestrogens may worsen incontinence • surgery is often successful if conservative measures fail • specialists sometimes use anticholinergics with selective alpha-blockers in men with coexisting urge incontinence and bladder outlet obstruction Urinary retention Urinary retention may be acute or chronic. Causes include outflow obstruction (see also Benign prostatic hyperplasia p 522), detrusor hypocontractility, infection or neurological impairment. Acute urinary retention is common postpartum and postoperatively. Drugs (eg anticholinergics, opioids, sympathomimetics) or constipation may contribute. Catheterisation is the preferred treatment and is necessary to preserve bladder and renal functions. Drug treatment should not be used without first ensuring that the bladder is emptying with catheterisation; use of parasympathomimetics, such as bethanechol, is not recommended. A selective alpha-blocker (eg alfuzosin) given daily for 2–3 days before catheter removal increases the rate of successful voiding in men >65 years with acute urinary retention due to BPH. Intermittent catheterisation may be preferred to an indwelling catheter in chronic retention. Practice points • following an episode of acute retention, check that bladder emptying continues to be satisfactory by measuring post-void residual volume 13.1.1 Anticholinergics For additional information see Anticholinergics p 684 See also Urinary incontinence p 519 For drug interactions see Anticholinergics p 856 Darifenacin p 520 Oxybutynin p 520 Propantheline p 520 Solifenacin p 521 Tolterodine p 521 Indications Urinary urge incontinence 519 13 13.1.1 Anticholinergics Precautions Treatment with drugs with anticholinergic effects (Table B-2 p 957)—additive anticholinergic effect increases therapeutic and adverse effects; avoid combination. Dementia—anticholinergics are best avoided; they may worsen symptoms and antagonise therapeutic effects of anticholinesterases. Urinary retention Avoid use in urinary retention or significant bladder outlet obstruction. Urinary symptoms may worsen in men with bladder outlet obstruction (prostatic enlargement increases the risk of urinary retention). Measure post-void residual volume in men before starting treatment; monitor for urinary retention especially during initial treatment when risk appears highest. Elderly Elderly people may be more sensitive to anticholinergic adverse effects such as urinary retention, blurred vision, dry mouth, constipation and confusion. Adverse effects are usually dose related; start with low dosage and increase cautiously to the lowest effective dose. Comparative information 13 There is no evidence that any anticholinergic is the most effective. Oral oxybutynin has the highest incidence of dry mouth. Limited evidence suggests CNS effects may be less likely to occur with the more selective agents (eg solifenacin, darifenacin) than with oxybutynin. Small studies indicate solifenacin has a higher incidence of constipation than oxybutynin or tolterodine. Solifenacin may increase the QT interval, especially at high doses. All are available as tablets; oxybutynin is also available as a patch. Counselling This medicine may cause drowsiness, dizziness or blurred vision; if affected, do not drive or operate machinery. Darifenacin For additional information see Anticholinergics p 519 For drug interactions see Anticholinergics p 856, Darifenacin p 856 Indications Urinary urge incontinence Precautions Hepatic Manufacturer recommends reducing dose in moderate impairment and avoiding use in severe impairment (no data). Pregnancy No human data; Australian category B3. www.amh.net.au Do not exceed 7.5 mg daily in people with moderate hepatic impairment or taking potent CYP3A4 inhibitors (eg itraconazole, ketoconazole, ritonavir). Counselling Swallow tablet whole; do not crush or chew. tab, 7.5 mg (controlled release), 28, Enablex (NV) tab, 15 mg (controlled release), 28, Enablex (NV) Oxybutynin For additional information see Anticholinergics p 519 For drug interactions see Anticholinergics p 856 Indications Urinary urge incontinence Precautions Pregnancy Little experience; Australian category B1. Breastfeeding Unlikely to be of concern. Adverse effects Common facial flushing (more common in children) Patch, application site reactions (eg rash, itch, erythema, vesicles) Dosage Adult Oral Usual range, 2.5–5 mg 2 or 3 times daily; maximum 20 mg daily. Elderly, start with 2.5 mg at night and increase slowly if necessary. Patch 1 patch applied twice a week (every 3–4 days). Child >5 years Oral, initially 2.5 mg twice daily; if necessary, increase to 5 mg 2 or 3 times daily. Counselling Patch Apply to dry, unbroken skin on your abdomen, hip or buttock. Remove and safely dispose of patch after 3–4 days and put a new patch on a different area (do not apply to the same place within 7 days). Practice points Patch • dry mouth may be less common than with oral oxybutynin; however, application site reactions are common (>10%) and may be intolerable tab, 5 mg (scored), 100, Ditropan (AV), Oxybutynin (SZ), PBS-R1 patch, 3.9 mg/24 hours, 8, Oxytrol (HS), PBS-R2 1 2 detrusor overactivity detrusor overactivity in patients unable to take tablets Propantheline Breastfeeding For additional information see Anticholinergics p 519 For drug interactions see Anticholinergics p 856 No human data. Indications Dosage Adult, initially 7.5 mg once daily; if necessary, increase dose after at least 2 weeks to 15 mg once daily. 520 Urinary urge incontinence Precautions Pregnancy Little experience; Australian category B2. AMH © 2013 www.amh.net.au 13.1.2 Drugs for nocturnal enuresis Breastfeeding Dosage Unlikely to be of concern. Adult, 2 mg twice daily; reduce to 1 mg twice daily if necessary to minimise adverse effects. Dosage Adult 15–30 mg 2 or 3 times daily. Elderly, start with 15 mg twice daily. Practice points • propantheline is now rarely used for urinary incontinence tab, 15 mg, 100, Pro-Banthine (AS), PBS-R1 1 detrusor overactivity Solifenacin For additional information see Anticholinergics p 519 For drug interactions see Anticholinergics p 856, Solifenacin p 856 Indications Urinary urge incontinence Precautions Risk factors for prolonged QT interval (p 272)—solifenacin may increase the QT interval especially at doses higher than recommended (eg if concentration increased by a drug interaction or reduced clearance). CrCl <30 mL/minute or hepatic impairment 1 mg twice daily. tab, 1 mg, 56, Detrusitol (PF) tab, 2 mg, 56, Detrusitol (PF) 13.1.2 Drugs for nocturnal enuresis Nocturnal enuresis in children Involuntary loss of urine (usually nocturnal) is normal in young children, but can cause concern if it persists after 5 years of age when micturition control is normally achieved. Bed-wetting generally relates to a maturational delay and usually resolves spontaneously. Most cases of primary nocturnal enuresis are due to nocturnal polyuria, sleep arousal difficulties or bladder dysfunction including low bladder capacity. Psychological factors may be important in secondary nocturnal enuresis. Before starting treatment No human data. Wait until the child is at least 5 years old before starting any treatment (7 years is usual). Exclude structural abnormalities and other organic causes, such as UTI, constipation, or diabetes, and ensure a normal daily fluid intake and toileting pattern. Assess whether social or emotional problems may be a contributing factor. There is a significant relapse rate with all treatments; alarms are associated with a lower relapse rate than drug treatment but are slower to take effect. Dosage Non-drug treatment Adult, initially 5 mg once daily; if necessary, increase dose to 10 mg once daily. Do not exceed 5 mg daily in people with moderate hepatic impairment, CrCl <30 mL/minute or taking potent CYP3A4 inhibitors (eg itraconazole, ketoconazole, ritonavir). Non-drug treatment is preferred initially; rewards for agreed behaviour and enuresis alarms are often successful. Although usually used in older children, alarms may be considered in children 5–7 years old depending on level of understanding and motivation. Counselling When to start drug treatment Swallow tablet whole; do not crush or chew. tab, 5 mg, 30, Vesicare (CS) tab, 10 mg, 30, Vesicare (CS) After non-drug measures have failed or are inappropriate. Special circumstances when more control is desirable, eg sleeping away from home. Tolterodine Drug choice Renal Do not exceed initial dose if CrCl <30 mL/minute. Hepatic Do not exceed initial dose in moderate impairment; avoid use in severe impairment. Pregnancy No human data; Australian category B3. Breastfeeding For additional information see Anticholinergics p 519 For drug interactions see Anticholinergics p 856, Tolterodine p 856 Indications Urinary urge incontinence Precautions Renal Reduce dose if CrCl <30 mL/minute. Hepatic Reduce dose in hepatic impairment. Pregnancy No human data; avoid use; Australian category B3. Breastfeeding Desmopressin (p 522): first-line drug treatment; an antidiuretic hormone analogue that is often effective with fewer adverse effects than TCAs. Use with caution if fluid overload is undesirable, eg renal disease, cardiovascular disease, cystic fibrosis. Imipramine (p 759) is often effective but adverse effects and risks in overdose limit its use to secondline treatment on specialist advice. Recommended maximum treatment course is 3 months; withdraw gradually. Practice points • refer to a specialist if bedwetting is unresponsive to an alarm and desmopressin No human data. AMH © 2013 521 13 13.2 Drugs for benign prostatic hyperplasia and prostatitis Desmopressin For additional information see Desmopressin p 442 See also Nocturnal enuresis in children p 521 tab, 200 mcg (scored), 30, Minirin (FP), PBS-A1 wafer, 120 mcg (sublingual), 30, Minirin Melt (FP), PBS-A1 wafer, 240 mcg (sublingual), 30, Minirin Melt (FP), PBS-A1 nasal spray, 10 mcg/dose, 6 mL, 60 doses, Minirin (FP), PBS-A1 1 Indications www.amh.net.au primary nocturnal enuresis in patients >6 years when an enuresis alarm is contraindicated or ineffective Nocturnal enuresis in children Precautions Intranasal use—hyponatraemia has been reported more often with intranasal use (mainly associated with excess fluid intake and inappropriate use); use only if oral or sublingual route is inappropriate. Inability to comply with fluid restrictions—avoid use in children unable or unwilling to restrict fluid intake for 9 hours; hyponatraemia and seizures can occur with excess fluid intake. Adverse effects Common headache Intranasal: nosebleed, rhinitis, nausea, abdominal pain Infrequent hyponatraemia, water intoxication, seizures, syncope, allergy, emotional disturbances Dosage Child 6 years or older Oral tablet, initially 200 micrograms at bedtime; increase to 400 micrograms at bedtime if needed. Sublingual wafer, initially 120 micrograms at bedtime; increase to 240 micrograms at bedtime if needed. Intranasal, initially 20 micrograms at bedtime. Maintenance 10–40 micrograms at bedtime. Dose equivalence 120 micrograms sublingual wafer is approximately equivalent to 200 micrograms oral tablet. Counselling 13 Be careful that the child takes the correct dose and only sips of fluid (eg no more than a total of one glass) from 1 hour before the dose to 8 hours after it. Do not give the dose if the child is vomiting or has diarrhoea. Wafer: place the wafer under your tongue and allow it to dissolve; do not swallow. Practice points • desmopressin should be used only to treat nocturnal enuresis when an enuresis alarm has failed or is inappropriate • treat for 1–3 months, then withdraw to assess for relapse • response may improve if dose is given 1–2 hours before bedtime, but the child must be able to comply with fluid restriction from 1 hour before the dose • if fluid intake is unrestricted water retention with possible hyponatraemia may occur • there is no dose equivalence between oral and intranasal dosage forms • desmopressin is used overseas to treat adults with nocturia associated with nocturnal polyuria or MS 522 13.2 Drugs for benign prostatic hyperplasia and prostatitis Benign prostatic hyperplasia Incidence of BPH increases with age. Symptoms may include voiding symptoms (eg hesitancy, straining, weak or intermittent urine flow, sensation of incomplete emptying) and/or bladder storage symptoms (eg urgency, frequency, nocturia). The severity of symptoms is not related to prostate size. Complications such as acute urinary retention (p 519) or renal impairment may also occur. Rationale for drug use Improve symptoms by decreasing urinary outflow resistance. Reduce long-term complications. Before starting treatment Assess symptom severity using a scoring system such as the International Prostate Symptom Score. It can also be used to monitor progress and response to treatment. Assess prostate size. Look for aggravating factors such as constipation, diuretics, or drugs with anticholinergic or sedating effects. Advise on measures such as reducing caffeine and alcohol intake, bladder training and reducing fluid intake at times when urinary frequency is inconvenient (eg at night). Patients with uncomplicated BPH not bothered by symptoms may be managed with watchful waiting (education, reassurance, lifestyle measures and periodic monitoring). When to start treatment Consider drug treatment when symptoms are troublesome, it is preferred by the patient, and surgery is not indicated. Drug choice Prostate size is the most important factor influencing drug choice. Symptomatic relief requires continuous treatment. Selective alpha-blockers Can improve symptoms within 48 hours (full effect in 4–6 weeks) and also improve urinary flow rates. They appear to be effective regardless of prostate size. 5-alpha-reductase inhibitors Are an option when prostate >30–40 cm3. In addition to improving symptoms and urinary flow rate, they also reduce prostate size and rates of acute urinary retention and surgery. However, it may take 6 months of treatment before symptoms improve (full effect after 12–18 months). AMH © 2013 www.amh.net.au 13.2 Drugs for benign prostatic hyperplasia and prostatitis Combination treatment As a selective alpha-blocker relieves symptoms more rapidly than a 5-alpha-reductase inhibitor, consider combination treatment when prostate >30–40 cm3 and rapid relief of troublesome symptoms is required. Optimal duration of combination treatment is uncertain. There is some evidence that the selective alpha-blocker can be stopped after 6–12 months of combination treatment in most patients without worsening urinary symptoms. However, some patients, especially those with severe baseline symptoms, may benefit from continuing the combination. Other treatment Surgery (such as transurethral resection of the prostate) is more effective than drug treatment and is an appropriate option when symptoms are more severe, when drug treatment is ineffective or not tolerated and when there are complications such as urinary retention. Practice points • men with a prostate >30–40 cm3 who are not bothered by their symptoms may be offered a 5-alpha-reductase inhibitor to reduce the risk of disease progression • specialists sometimes add an anticholinergic to a selective alpha-blocker in men who have continuing storage symptoms (bladder overactivity) • saw palmetto (Serenoa repens) is no more effective than placebo in improving lower urinary tract symptoms of BPH (Cochrane systematic review) Prostatitis There are 3 main types: Acute bacterial prostatitis is associated with an acute UTI (may follow trauma or bladder outflow obstruction) with similar pathogens, eg E. coli, Klebsiella, Enterococci spp. It is a serious, severe illness; cure is likely, but it may progress to chronic prostatitis. Chronic bacterial prostatitis is associated with chronic or relapsing UTI (same pathogen in urinary and prostatic fluid); may be asymptomatic between UTI, but usually there is pain and discomfort. It has a more favourable prognosis than chronic pelvic pain syndrome. Chronic prostatitis/chronic pelvic pain syndrome is not associated with UTI but has similar symptoms (eg pelvic pain, lower urinary tract symptoms) to chronic bacterial prostatitis, and is much more common. Rationale for drug use Provide symptom relief, cure any infection and reduce likelihood of complications. Before starting treatment Obtain urine (and blood, where appropriate) for culture (avoid prostatic massage in acute prostatitis). AMH © 2013 In chronic prostatitis, exclude other causes such as UTI, prostatic abscess, epididymitis, urethritis, and cancer. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) at www.upointmd. com/NIHCPSIEnglish.pdf may be useful in assessing symptom severity and response to treatment. Treatment Acute bacterial prostatitis Severe infections require IV antibacterials (eg ampicillin plus gentamicin) and fluid replacement. For mild-to-moderate infections, begin empirical treatment with an oral antibacterial that is effective against most urinary pathogens, eg ciprofloxacin (p 129) or trimethoprim (p 152) for 4 weeks (minimum 14 days). Change the antibacterial according to urine culture results if necessary. Most antibacterials will penetrate the inflamed prostate well. Ensure adequate hydration, rest and analgesia (paracetamol or an NSAID); consider bowel function (constipation may increase pain). Repeat urine culture after the course is finished to check whether the infection has cleared; then investigate for any contributing structural abnormalities. Chronic bacterial prostatitis General measures as for acute bacterial prostatitis; however, as inflammation is not intense, penetration of antibacterials into prostate tissue may be poor. Treat for 4–6 weeks with an antibacterial that penetrates the prostate well, eg trimethoprim, norfloxacin or ciprofloxacin. Doxycycline may be used if intracellular bacteria, eg Chlamydia, are suspected or cultured. Chronic prostatitis/chronic pelvic pain syndrome Although symptoms usually improve over time, chronic prostatitis frequently relapses and is difficult to manage. No treatment has proven benefit; a trial of: – an antibacterial (as for chronic bacterial prostatitis) may be worthwhile, especially in recently diagnosed patients, as there may be undiagnosed bacterial infection – adequate analgesia (eg NSAID) and relief of constipation may help – one of the selective alpha-blockers (p 524) may ease pain and improve urinary symptoms – quercetin 500 mg twice daily, or pollen extract (Cernilton®, Prostat/Poltit®), may relieve symptoms, particularly pain (based on small placebo-controlled studies). Practice points • refer men with unexplained haematuria or longstanding chronic prostatitis to a specialist • avoid using nitrofurantoin as it penetrates prostatic tissue poorly • quercetin should not be used during quinolone treatment as it may decrease antibacterial efficacy 523 13 13.2.1 Selective alpha-blockers 13.2.1 Selective alpha-blockers For additional information see Selective alphablockers p 265 See also Benign prostatic hyperplasia p 522 For drug interactions see Alpha-blockers (selective) p 854 Alfuzosin p 524 Prazosin p 525 Tamsulosin p 525 Terazosin p 525 Mode of action Block alpha1 receptors, relaxing smooth muscle in the bladder neck and prostate, and decreasing resistance to urinary flow. Tamsulosin is more selective for the alpha1-receptor subtypes found in the bladder and prostate. Prazosin and terazosin are also arterial and venodilators due to blockade of postsynaptic alpha1 receptors and therefore inhibition of catecholamine-mediated vasoconstriction. Unlike nonselective alpha-blockers (eg phenoxybenzamine), they have little effect on presynaptic alpha2 receptors and are therefore less likely to cause reflex tachycardia. Indications Symptom relief in BPH Hypertension (see Selective alpha-blockers p 265) Precautions Volume depletion—risk of exacerbation of orthostatic hypotension. Treatment with antihypertensives—close supervision required because of possible additive hypotensive effects; combination with diuretics, beta-blockers, calcium channel blockers increases risk of first dose hypotension. 13 Cataract surgery Selective alpha-blockers (particularly tamsulosin) are associated with a risk of intra-operative floppy iris syndrome during cataract surgery. Interrupting treatment does not appear to reduce this risk; it may be necessary to modify surgical technique. Increased rates of postoperative ocular complications have been associated with tamsulosin use. Consider use of these agents, especially tamsulosin, carefully if cataract surgery is contemplated, as these complications have occurred even after these drugs were ceased. Renal Begin treatment cautiously in impairment as there may be a profound first dose effect (excessive hypotension). Hepatic Use with caution in impairment; alfuzosin is contraindicated. Elderly Use with caution (avoid prazosin); the elderly are more susceptible to orthostatic hypotension. Adverse effects Common first dose hypotension, orthostatic hypotension, dizziness (all less frequent with alfuzosin and tamsulosin); nasal congestion, urinary urgency, headache, weakness, fatigue, drowsiness 524 www.amh.net.au Infrequent tachycardia, palpitations, oedema, syncope, blurred vision, urinary incontinence, nausea, vomiting, dry mouth, increased sweating Rare rash, itch, depression, mood changes, dyspnoea, paraesthesia Comparative information Alfuzosin and tamsulosin are only indicated for BPH; prazosin and terazosin are also indicated for hypertension. All selective alpha-blockers appear to be similarly effective for BPH. Tamsulosin and alfuzosin have less effect on BP than prazosin or terazosin and may be a better choice for BPH; dosage titration is required with prazosin and terazosin to minimise hypotensive effects. Prazosin has a short duration of action and needs to be taken twice daily; alfuzosin, tamsulosin and terazosin can be taken once daily. Prazosin and terazosin are equally effective for treating hypertension but are only used third line. Counselling Dizziness on standing may occur especially when starting treatment or when the dose is increased. Get up gradually from sitting or lying to minimise this effect; sit or lie down if you become dizzy. Take the first dose at bedtime, but be careful if you get up during the night as you may feel dizzy. This medicine may cause drowsiness or dizziness; do not drive or operate machinery if affected. Tell your ophthalmologist you are taking, or have taken, this medicine if you are going to have cataract surgery. Practice points • add antihypertensives cautiously (particularly if taking prazosin or terazosin) as BP may fall sharply • first dose hypotension is more common with prazosin and terazosin; it is most serious in the elderly and in patients with fluid depletion or who are taking diuretics; for management, see First dose hypotension p 266 • if treatment with prazosin or terazosin is interrupted for several days, restart and titrate dosage as if starting for the first time • monitor BP (lying and standing) and for symptoms of hypotension, particularly during dose titration of prazosin or terazosin • stop if there is no improvement in symptoms of BPH after 4–6 weeks of maximal treatment • although not a marketed indication, selective alpha-blockers, usually tamsulosin, have been used in selected patients with small lower ureteral stones as they may help stone passage Alfuzosin For additional information see Selective alphablockers p 524 For drug interactions see Alpha-blockers (selective) p 854, Alfuzosin p 854 Indications Symptom relief in BPH Precautions Hepatic Contraindicated in hepatic impairment. AMH © 2013 www.amh.net.au 13.2.2 5-Alpha-reductase inhibitors Dosage Dosage 10 mg once daily. Initially, 1 mg daily for 7 days, then 2 mg daily for 7 days; then increase dose according to clinical response up to 5–10 mg each morning. Counselling Swallow whole. Take immediately after a meal for best absorption. tab, 10 mg (controlled release), 30, 60, Xatral SR (AV), RPBS-A[30]1 tab, 2 mg, 28, Hytrin (AB), RPBS-A1 tab, 5 mg, 28, Hytrin (AB), RPBS-A1 tab, 10 mg, 28, Hytrin (AB), RPBS-A1 1 Combination packs BPH, see PBS Prazosin For additional information see Selective alphablockers p 524 For drug interactions see Alpha-blockers (selective) p 854 Indications Symptom relief in BPH Hypertension (see Prazosin p 266) Adverse effects Rare priapism, hallucinations, confusion, nightmares, pancreatitis Dosage 0.5 mg twice daily for 3–7 days, then increase according to clinical response up to 2 mg twice daily. tab, 1 mg (scored), 100, Minipress (PF), Prazosin (CH, TW, TX), PBS tab, 2 mg (scored), 100, Minipress (PF), Prazosin (CH, TW, TX), PBS Tamsulosin For additional information see Selective alphablockers p 524 For drug interactions see Alpha-blockers (selective) p 854 Indications Symptom relief in BPH Combination with dutasteride Symptomatic BPH with prostate >30–40 cm3, see Dutasteride p 526 Adverse effects Common abnormal ejaculation Rare hypersensitivity reactions, angioedema, urticaria Dosage 400 micrograms once daily. Counselling Swallow whole, do not crush or chew. tab, 400 mcg (controlled release), 30, Flomaxtra (CS), RPBS-A1 1 BPH where surgery is inappropriate or other drug treatment has failed or is contraindicated Terazosin For additional information see Selective alphablockers p 524 For drug interactions see Alpha-blockers (selective) p 854 Indications Symptom relief in BPH Hypertension (see Terazosin p 266) AMH © 2013 tab, 1 mg, 7; tab, 2 mg, 7, Hytrin Starter Pack (AB), RPBS-A1 1 BPH where surgery is inappropriate or other drug treatment has failed or is contraindicated 13.2.2 5-Alpha-reductase inhibitors See also Benign prostatic hyperplasia p 522 Dutasteride p 526 Finasteride p 526 Mode of action Inhibit 5-alpha-reductase, which converts testosterone to dihydrotestosterone (a potent cellular androgen that stimulates prostate growth). They reduce prostate size and improve symptoms and urinary flow rate. Indications BPH Adverse effects Common impotence, decreased libido, ejaculation disorder (including decreased ejaculate volume) Infrequent breast tenderness or enlargement Rare allergic reaction Comparative information Dutasteride has a long half-life (3–5 weeks) compared with finasteride (6 hours) and can still be detected 4–6 months after stopping treatment. Finasteride inhibits the type 2 isoenzyme of 5alpha-reductase and dutasteride inhibits both the type 1 and type 2 isoenzymes. Although dutasteride reduces serum dihydrotestosterone by about 90% compared with 70% with finasteride, limited evidence from short-term studies suggests there are no major differences between them in terms of reduction of prostate size, symptom improvement, urinary flow rate or adverse effects. Practice points • women who are or may become pregnant should not handle capsules or broken or crushed tablets without gloves (Australian category X) • efficacy depends on prostate size; men with a smaller prostate (<30 cm3) are unlikely to benefit • it may take >6 months of treatment before symptoms improve • long-term use of 5-alpha-reductase inhibitors reduces the risk of acute urinary retention and the need for surgery; finasteride also reduces the risk of recurrence of haematuria • after 6 months of dutasteride or 1 year of finasteride (5 mg daily) prostate specific antigen (PSA) concentration is reduced by an average of 50% (further reductions may occur with longer therapy, particularly with dutasteride); take into consideration when measuring PSA 525 13 13.3 Drugs for erectile dysfunction • if PSA concentration begins to rise at all during treatment, assess for prostate cancer (it is unclear whether there is an increased risk of high-grade tumours in men taking 5-alpha-reductase inhibitors) • 6 months after stopping treatment, PSA concentrations have generally returned to baseline Dutasteride For additional information see 5-Alpha-reductase inhibitors p 525 Indications Symptomatic BPH with prostate >30–40 cm3 (includes combination with tamsulosin) Precautions Combination with tamsulosin—the incidence of orthostatic hypotension may be higher when taking the combination capsule compared to taking dutasteride and tamsulosin separately due to differences in formulation. Dosage 500 micrograms once daily. Combination with tamsulosin For additional information see Tamsulosin p 525 1 capsule once daily. Counselling Swallow whole; do not open or chew the capsules as the contents may irritate your mouth and throat. Combination with tamsulosin Swallow whole. Take this medicine about 30 minutes after a meal. Do not take it on an empty stomach as this may increase the risk of side effects, eg dizziness on standing. cap, 500 mcg, 30, Avodart (GK), PBS-A1 Combination products 13 cap, dutasteride 500 mcg, tamsulosin (controlled release) 400 mcg, 30, Duodart (GK), PBS-A1 1 urinary tract symptoms due to BPH, see PBS Finasteride For additional information see 5-Alpha-reductase inhibitors p 525 Indications Symptomatic BPH with prostate >30–40 cm3 Androgenetic alopecia in men (see Finasteride p 382) Dosage 5 mg once daily. Practice points • breast cancer has been reported in men taking finasteride; the association between finasteride and increased risk of breast cancer is unclear; monitor for any changes in breast tissue tab, 5 mg, 28, Finpro (RZ), RPBS-A1 tab, 5 mg, 30, Finasta (SZ), Proscar (MK), RPBS-A1 tab, 5 mg, 30, Finnacar (AS), Finasteride (CR, RA, TX) 1 BPH, see PBS 526 www.amh.net.au 13.3 Drugs for erectile dysfunction Erectile dysfunction Rationale for drug use Achievement of penile erection adequate for sexual intercourse. Before starting treatment Determine and treat underlying cause if possible. It is often associated with conditions such as cardiovascular disease, diabetes and hypertension, and may be an indicator for unrecognised disease. Assess cardiovascular status in relation to the stress induced by sexual activity; for most people this will be roughly equivalent to mild-tomoderate exercise, an exercise test may be useful. Erectile dysfunction is often due to a combination of organic and psychogenic problems: – organic causes include neurological, vascular, endocrine, structural, drug-induced (eg betablockers, alcohol misuse) – psychogenic: may respond to counselling or behaviour therapy; attention to psychological factors is important in all cases. If irreversible organic causes are implicated, the 3 main treatments are drug treatment, vacuum pump (which induces erection by negative pressure) and prostheses. Drug choice Phosphodiesterase 5 inhibitors are taken orally; other drug treatments require penile injection. Phosphodiesterase 5 inhibitors (sildenafil, tadalafil, vardenafil) are the drugs of choice due to their effectiveness and ease of use; onset of effect is about 30 minutes to 1 hour and they are generally well tolerated. Most clinical experience has been gained with sildenafil. They should be used alone as safety and efficacy are not well established for combination treatments, although some studies suggest that combining alprostadil with sildenafil may be helpful. They are contraindicated in men taking nitrates. Alprostadil is effective alone or with other agents; of the injectable products, it is least likely to cause penile fibrosis or priapism. Papaverine may be used alone or in combination; consider only if intracavernosal alprostadil is inappropriate. Phentolamine (p 448) must be used with papaverine and/or alprostadil injection to be effective. Practice points • ideal dose should produce an erection that lasts no more than 1 hour • a smaller dose is required to maintain adequate erection at home than in the clinic • regular medical review during treatment course is necessary • discourage ‘social’ use by men who do not have potency problems, since they have a greater risk of priapism • consider surgery if there is continued failure of drug treatment AMH © 2013 www.amh.net.au 13.3.1 Phosphodiesterase 5 inhibitors Priapism Eyes • explain treatment of priapism to patient • if erection lasts >2 hours taking two 60 mg pseudoephedrine (p 393) tablets may help • emergency medical treatment is necessary if erection lasts more than 4 hours; continued erection requires aspiration of 20–50 mL of blood from the corpus cavernosum via a 19 or 21 gauge butterfly needle; this may be repeated on the other side if necessary • if still unsuccessful, urgent urological review is necessary Contraindicated with a history of non-arteritic anterior ischaemic optic neuropathy (NAION). Avoid use if there is significant vision loss in one eye due to the risk of serious ocular adverse effects in other eye (see NAION below). The effect of PDE5 inhibitors on retinal phosphodiesterase in patients with hereditary degenerative retinal disorders (eg retinitis pigmentosa) is unknown; avoid use in these patients. 13.3.1 Phosphodiesterase 5 inhibitors See also Erectile dysfunction p 526 For drug interactions see Phosphodiesterase 5 inhibitors p 924 Sildenafil p 528 Tadalafil p 528 Vardenafil p 529 Mode of action Sexual stimulation increases cyclic guanosine monophosphate (cGMP) levels, resulting in smooth muscle relaxation, inflow of blood to the corpus cavernosum and penile erection. These agents inhibit the breakdown of cGMP by phosphodiesterase type 5 (PDE5), increasing blood flow to the penis during sexual stimulation. Indications Erectile dysfunction Pulmonary arterial hypertension, see Phosphodiesterase 5 inhibitors p 295 Precautions Migraine—there are reports of these agents inducing migraine. Anatomical deformation of penis, sickle cell anaemia, myeloma, leukaemia—increases risk of priapism. Bleeding disorders, active peptic ulcer—platelets contain PDE5; no safety data. Other drugs Contraindicated with nitric oxide donors, organic nitrates or nitrites (including glyceryl trinitrate in any form, isosorbide mononitrate, isosorbide dinitrate, sodium nitroprusside, amyl nitrite, nicorandil) due to risk of profound hypotension or MI. If a nitrate is required, allow at least 24 hours (48 hours with tadalafil) after a dose of PDE5 inhibitor before giving a nitrate. A longer period may be required if elimination of the PDE5 inhibitor is delayed (eg due to drug interaction, renal or hepatic impairment, in the elderly). Monitor response carefully. Treatment with drugs that can cause hypotension, particularly selective alpha-blockers, may add to hypotension caused by PDE5 inhibitors. Consider starting with a low dose of PDE5 inhibitor. Patient should be stabilised on alpha-blocker therapy before starting a PDE5 inhibitor; if using prazosin or terazosin, separate doses by at least 4 hours (6 hours with vardenafil). AMH © 2013 Cardiovascular Contraindicated in men for whom sexual intercourse is inadvisable due to cardiovascular risk factors, eg unstable angina. Consider cardiovascular status in relation to stress risk arising from sexual activities, particularly as nitrates cannot be used readily; for most people this will be roughly equivalent to mild-to-moderate exercise; an exercise test may be useful. There are few or no safety data for men with hypotension (BP <90/50 mm Hg), uncontrolled hypertension, stroke or MI within the last 3–6 months, other severe cardiovascular disease (eg heart failure, uncontrolled arrhythmias). MI, TIA and stroke, including intracerebral bleeding, have occurred; association with PDE5 inhibitors is difficult to assess. Consider undiagnosed cardiovascular disorders before prescribing these agents. Adverse effects Frequency of adverse effects appears to be dose related. Common headache (>10%), dizziness, flushing, dyspepsia, nasal congestion/rhinitis Rare priapism (infrequent with vardenafil), vision loss due to NAION (below), migraine, seizures, sudden hearing loss (may be associated with tinnitus, vertigo or dizziness), transient amnesia, hypersensitivity NAION Vision loss due to NAION has been reported; cases include patients treated for pulmonary hypertension, some of whom were female. However, causality is unclear. Risk factors for NAION are similar to those for erectile dysfunction and incidence is similar to that in general population of men >50 years. Comparative information Efficacy: limited data suggest that sildenafil, tadalafil and vardenafil have similar efficacy. All are effective in erectile dysfunction due to diabetes, nerve-sparing prostatectomy or spinal cord injury, although efficacy rates are lower in diabetes or prostatectomy. Onset and duration of action: onset is about 30 minutes to 1 hour; sildenafil and vardenafil are short-acting and tadalafil is long-acting. Food delays the onset of action of sildenafil and vardenafil. Adverse effects: although headache is common for these drugs, that caused by tadalafil lasts for 3–8 hours. Sildenafil is most likely to cause visual changes. Vardenafil has prolonged the QT interval in healthy volunteers. 527 13 13.3.1 Phosphodiesterase 5 inhibitors Counselling Do not take this medication if you already take nitrates as the combination may cause a serious drop in your blood pressure. This can happen even if you take them on different days. Tell your health professional (even in a medical emergency) that you take this medicine before taking any new medicines. This medication may cause visual disturbances and dizziness. If you are affected do not drive or operate machinery. Tell your doctor immediately if you have any sudden loss of hearing or vision. Taking this medication may worsen any dizziness or faintness if you are already taking medication to lower your blood pressure. If also taking prazosin or terazosin, separate doses by at least 4 hours (6 hours if taking vardenafil). Practice points • safety and efficacy with other treatments for erectile dysfunction are not well studied, although some data suggest that combining sildenafil with alprostadil may be helpful in men refractory to monotherapy • as PDE5 inhibitors can overcome erectile dysfunction due to organic and psychogenic causes there is concern that such symptomatic treatment may lead to curable or serious diseases not being investigated • they are ineffective in the absence of sexual stimulation Sildenafil For additional information see Phosphodiesterase 5 inhibitors p 527 For drug interactions see Phosphodiesterase 5 inhibitors p 924, Sildenafil p 925 Indications 13 Erectile dysfunction Pulmonary arterial hypertension (see Sildenafil p 295) Precautions Renal Consider starting with a low dose if CrCl <30 mL/ minute. Hepatic www.amh.net.au Dosage Take about 1 hour before sexual activity; no more than 1 dose daily. Start with 50 mg; decrease dose to 25 mg or increase to a maximum of 100 mg depending on response and tolerability. Elderly, CrCl <30 mL/minute or mild-to-moderate hepatic impairment, consider starting with 25 mg, increasing to 50–100 mg as required and if tolerated. With erythromycin, ketoconazole, itraconazole or saquinavir, consider starting with 25 mg. With ritonavir, limit dose to 25 mg every 48 hours. Counselling If you take sildenafil with food it may take longer to work. tab, 25 mg, 4, Viagra (PF), RPBS-A1 tab, 50 mg, 4, Viagra (PF), RPBS-A1 tab, 100 mg, 4, 12, Viagra (PF), RPBS-A[4]1 1 erectile dysfunction, see PBS Tadalafil For additional information see Phosphodiesterase 5 inhibitors p 527 For drug interactions see Phosphodiesterase 5 inhibitors p 924, Tadalafil p 925 Indications Erectile dysfunction Pulmonary arterial hypertension (see Tadalafil p 296) Precautions Renal Intermittent use: reduce dose when CrCl <30 mL/ minute. Daily use: not recommended when CrCl <30 mL/ minute. Hepatic Intermittent use: reduce dose in mild-to-moderate impairment (Child-Pugh class A or B). Limited data in severe impairment (Child-Pugh class C). Daily use has not been evaluated in hepatic impairment. Adverse effects More common with 20 mg dose; usually transient and decrease with continued use. Consider starting with a low dose in mild-tomoderate hepatic impairment; manufacturer contraindicates use in severe impairment (no data). Common Elderly Infrequent Half-life is increased; consider starting with a low dose. headache lasting 3–8 hours, back pain (unrelated to physical activity), muscle aches conjunctival hyperaemia, sensations of eye pain, swollen eyelids Adverse effects Common Rare rash, diarrhoea, UTIs, abnormal vision (below) Dosage Intermittent use Take 30 minutes – 12 hours before sexual activity (may be effective for up to 36 hours); no more than 1 dose daily. If required at least twice a week consider daily use (below). Start with 10 mg; decrease dose to 5 mg or increase to a maximum of 20 mg depending on response and tolerability. With ketoconazole or ritonavir, initially 5 mg; maximum 10 mg in 72 hours. Rare tachycardia, hypotension, syncope Abnormal vision Mild, transient retinal effects including blue-green colour tinge, light sensitivity, blurred vision. More common at doses of 100 mg and above. Long-term effects unknown. Serous macular detachment has very rarely been associated with sildenafil. 528 changes in colour vision AMH © 2013 www.amh.net.au Renal impairment CrCl <30 mL/minute, limit dose to 10 mg daily. Hepatic impairment Mild-to-moderate, limit dose to 10 mg daily. Daily use Consider when intermittent use is tolerated and taken at least twice a week. 2.5–5 mg once daily. With ketoconazole or ritonavir, maximum 2.5 mg once daily. Practice points • regularly reassess need for daily dosing as data on long-term effects of PDE5 inhibition in men with erectile dysfunction are limited tab, 5 mg, 28, Cialis (LY) tab, 10 mg, 4, Cialis (LY), RPBS-A1 tab, 20 mg, 4, 8, Cialis (LY), RPBS-A[4]1 1 erectile dysfunction, see PBS Vardenafil For additional information see Phosphodiesterase 5 inhibitors p 527 For drug interactions see Phosphodiesterase 5 inhibitors p 924, Vardenafil p 925 Indications Erectile dysfunction Precautions Prolonged QT interval or risk factors for prolonged QT interval (p 272)—vardenafil may prolong the QT interval and increase the risk of arrhythmia; avoid use if risk factors cannot be corrected. Treatment with HIV PIs or >200 mg daily of ketoconazole or itraconazole—contraindicated by the manufacturer. Hepatic Avoid in severe hepatic impairment (Child-Pugh class C); reduce dose in moderate impairment (Child-Pugh class B). Elderly May be unable to tolerate maximum dose of 20 mg (increased frequency of headaches and dizziness compared with younger patients). Adverse effects More common with 20 mg dose; usually transient, mild-to-moderate and decrease with continued use. Common nausea Infrequent abdominal pain, back pain, photosensitivity, abnormal vision, eye pain, facial oedema, hypertension, palpitation, tachycardia, arthralgia, myalgia, rash, itch Rare hypotension, peripheral oedema, anaphylaxis Dosage Take 30–60 minutes before sexual activity; no more than 1 dose daily. Start with 10 mg; decrease dose to 5 mg or increase to a maximum of 20 mg depending on response and tolerability. AMH © 2013 13.3.2 Other drugs for erectile dysfunction With itraconazole or ketoconazole 200 mg daily or erythromycin, limit dose to 5 mg daily. With itraconazole or ketoconazole 400 mg daily, HIV PIs (except ritonavir) or clarithromycin, limit dose to 2.5 mg daily. With ritonavir, limit dose to 2.5 mg in 72 hours. Hepatic impairment Moderate, start with 5 mg; increase to 10 mg, depending on response and tolerability. Counselling You can take vardenafil with or without food, but if you take it with a fatty meal, it takes longer to work. Practice points • the difference between a 10 mg and 20 mg dose is most likely to be evident in those who are more severely affected or have diabetes, nervesparing prostatectomy, or longer duration of erectile dysfunction tab, 5 mg, 4, Levitra (BN) tab, 10 mg, 4, Levitra (BN), RPBS-A1 tab, 20 mg, 4, 8, Levitra (BN), RPBS-A[4]1 1 erectile dysfunction, see PBS 13.3.2 Other drugs for erectile dysfunction Alprostadil p 529 Papaverine p 530 Alprostadil See also Erectile dysfunction p 526 Also known as prostaglandin E1. Mode of action Dilates cavernosal arteries. Relaxes smooth muscle of corpus cavernosum and spongiosum. Indications 13 Erectile dysfunction, treatment and diagnostic testing Maintenance of the patent ductus arteriosus in neonates with congenital heart defects, until surgery can be performed (Prostin VR®, seek specialist advice) Precautions Conditions predisposing to priapism (sickle cell anaemia, myeloma, leukaemia)—contraindicated. Men for whom sexual intercourse is inadvisable— contraindicated. HIV, hepatitis B or C—bleeding at injection site may increase risk of transmission of disease to partner. Genitourinary Contraindicated in patients with penile fibrosis or penile implant. Patients with anatomical deformation of the penis, eg Peyronie’s disease, require urological assessment; painful erections are more likely to occur and fibrosis may result from treatment. Adverse effects Common penile pain, erection lasting 4–6 hours, fibrotic change (may be more likely with increasing duration of use) 529 13.4 Urinary alkalinisers and acidifiers Infrequent Mode of action paroxysmal tachycardia) may occur. Manufacturer recommends obtaining ECG before starting treatment in elderly patients. Genitourinary Contraindicated in patients with penile fibrosis or penile implant. Patients with anatomical deformation of penis, eg Peyronie’s disease, may require urological assessment; painful erections are more likely to occur. Hepatic Avoid use in severe impairment. Adverse effects Systemic effects are rare. Loss of penile sensation and difficulty in obtaining an erection may occur. Common pain and bruising on injection, priapism, penile fibrosis (related to injection volume >1 mL and minimal if used with alprostadil) Infrequent penile pain Rare dizziness, tachycardia, hepatitis, allergy Dosage Intracavernosal injection, initially 5–15 mg; adjust up to 60 mg according to response. Use the lowest effective dose, which may be as low as 2.5 mg. Usual range 30–60 mg. Administration advice See material available from manufacturer. The first dose should be given by a medical practitioner and the procedure for self-administration explained. Counselling Be careful when getting up from sitting or lying as this injection may make you feel dizzy. Tell your doctor if you have increased or new pain in your penis, or if you notice lumps or bending of the penis. Practice points • check on dosage being used and possible development of fibrosis at regular follow-up visits • stop treatment if fibrosis develops • tolerance may develop, requiring an increase in dosage Relaxation of all vascular components of the penile erectile system. inj, 12 mg/mL, 10 mL, 5, Papaverine (HS) inj, 30 mg/mL, 1 mL, 5, Papaverine (HS) fainting, painful erection, erection lasting >6 hours, testicular pain, bruising, injection site reactions, hypotension, dizziness Dosage Give by intracavernosal injection. Usual range, 10–20 micrograms; maximum dose 60 micrograms. Use no more than 1 injection in 24 hours; may be used up to 3 times a week. Erectile dysfunction of predominantly psychogenic or unknown aetiology Initially, 2.5 micrograms; increase in increments of 2.5 micrograms according to response. Erectile dysfunction of organic origin, including vasculopathy Initially, 5 micrograms; increase in increments of 5 micrograms according to response. Adjunct in diagnosis of impotence Initially, 2.5 micrograms; increase in increments of 2.5 micrograms. Administration advice See pack insert and material available from manufacturer. The first dose should be given by a medical practitioner and the procedure for selfadministration explained. Counselling Tell your doctor if you have increased or new pain in your penis, or if you notice lumps or bending of the penis. Store below 25C; once solution is made use it as soon as possible (but you can keep it in the fridge for up to 24 hours if necessary). Practice points • check on dosage being used and possible development of fibrosis at regular follow-up visits • stop treatment if fibrosis develops 13 www.amh.net.au inj, 10 mcg, 0.5 mL (syringe), 2, Caverject Impulse (PF), RPBS-A[6]1 inj, 20 mcg, 0.5 mL (syringe), 2, Caverject Impulse (PF), RPBS-A[6]1 inj, 500 mcg/mL, 1 mL, 5, Prostin VR (PF) 1 erectile dysfunction, see PBS Papaverine See also Erectile dysfunction p 526 Indications Erectile dysfunction Precautions Conditions predisposing to priapism (sickle cell anaemia, myeloma, leukaemia)—contraindicated. Men for whom sexual intercourse is inadvisable—contraindicated. HIV, hepatitis B or C—bleeding at injection site may increase risk of transmission of disease to partner. Cardiovascular Contraindicated in patients with complete atrioventricular block. Use with caution in cardiac conduction disorders or unstable cardiovascular disease as transient ectopic rhythms of ventricular origin (eg premature beats, 530 13.4 Urinary alkalinisers and acidifiers Alkalinisation May relieve the discomfort of UTIs, help treat certain types of renal stones, or be used in specialist settings to treat some metabolic and renal disorders. Alkalinisation is not possible if CrCl is <30 mL/ minute. Drug choice See Table 13–1 Urinary alkalinisers p 531 AMH © 2013 www.amh.net.au 13.6 Bladder instillations Table 13–1 Urinary alkalinisers Product Ingredients size, Electrolyte content Pack PBS status sodium bicarbonate, citric acid, tartaric acid, sodium saccharin 24.5 mmol (564 mg) 28 sodium bicarbonate, citric acid, tartaric acid (contains sucrose 720 mg/sachet) 17.3 mmol (397 mg) 28 28.3 mmol (650 mg) 28, RPBS-R2 28 mmol (644 mg) 28, RPBS-R2 Sodium-containing1 Citralite® sachet (AV) ® Citravescent sachet (AV) Uracol® sachet (GM) Ural® sachet (AS) Uricalm® sachet (CG) Sodibic® capsule (AS) sodium bicarbonate, sodium citrate, citric acid, tartaric acid, sodium saccharin 28.3 mmol (650 mg) 28 sodium bicarbonate 840 mg 10 mmol (230 mg) 100, PBS potassium citrate 1.08 g 10 mmol (390 mg) 100 Potassium-containing Urocit-K® tablet (OA) 1 2 use with caution or avoid in people who require sodium restriction for relief of urinary symptoms when antibacterial or other therapy alone is inappropriate Combination of citric acid, tartaric acid, sodium bicarbonate and sucrose/saccharin: use 1–2 sachets in a glass of water 3 or 4 times daily for symptomatic relief of UTI. Sodium bicarbonate capsules: use alone as an alkaliniser, eg in the treatment of renal tubular acidosis. Dose according to response (1–6 capsules daily). Potassium citrate: use 3–6 tablets daily in 2 or 3 doses, with or after food, to prevent calcium or uric acid kidney stones. Avoid in people with, or at risk of, hyperkalaemia. Acidification May rarely be used to increase the excretion of lipid-soluble basic drugs, treat certain types of renal stones, or in combination with hexamine hippurate. Products used include ammonium chloride and ascorbic acid. Evidence for efficacy is limited. Prevention Recurrence rate is high. Increasing fluid intake (to achieve a urine output of >2 L daily if possible) is important in prevention. Dietary measures may also help, eg a low-oxalate diet for those at risk of calcium stones. When fluid and dietary measures are ineffective, consider drug treatment to prevent formation of new stones or growth of existing stones; seek specialist advice. Allopurinol decreases urinary urate; used for uric acid or calcium oxalate stones in people with hyperuricosuria. Potassium citrate increases urine pH and citrate concentration and inhibits crystal formation; used for uric acid or calcium stones, especially in people with hypocitraturia. Thiazide diuretics reduce calcium excretion; used for calcium stones in people with hypercalciuria. 13 Effect of drugs on kidney stones 13.5 Drugs for kidney stones Kidney stones These are common and renal colic due to movement of a stone into the ureter is the most common symptom: 70–80% consist of calcium oxalate and/or calcium phosphate, with 5–10% containing uric acid. Treatment of acute renal colic Relieve pain (see Renal colic p 41). For nausea and vomiting use metoclopramide (p 491) or prochlorperazine (p 492). Normal fluid intake is recommended; increasing urine output through high fluid intake is likely to increase the risk of obstruction and worsen pain. Up to 80% of ureteral stones <5 mm will pass spontaneously, usually within 4 weeks. Selective alpha-blockers (usually tamsulosin) have been used to help passage of lower ureteral stones <10 mm in selected patients with controlled symptoms. AMH © 2013 Whether ascorbic acid increases the risk of calcium oxalate stone formation is unclear; doses >1 g daily should be avoided. The effect of calcium supplementation on risk of stone recurrence is unclear; use calcium and vitamin D supplements with caution, and take calcium with food to bind oxalate and decrease urinary oxalate excretion. Carbonic anhydrase inhibitors, eg acetazolamide, topiramate, can increase risk of calcium phosphate stones; probenecid can increase risk of uric acid stones. Renally excreted drugs with low solubility at urine pH, eg triamterene, may crystallise in the urinary tract forming stones, especially at high doses. 13.6 Bladder instillations Solutions of chemicals or drugs may be instilled into the bladder for a variety of indications, including postoperative irrigation (glycine), clot retention (sodium chloride 0.9%), treatment of infection (chlorhexidine), interstitial or haemorrhagic cystitis (dimethyl sulfoxide, oxychlorosene), and the treatment of local neoplastic conditions. 531
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