Page 16 - CUA guideline on adult overactive bladder

Guideline: Adult overactive bladder

Table 3. Specific age-related changes in pharmacokinetics, alteration in drug absorption, distribution, metabolism, and
clearance, and their potential effect on urinary incontinence (UI) drugs
Parameter Age-associated changes UI drugs potentially affected
Minimal quantitative change despite ↓ gastric motility, yet Extended-release preparations
Absorption little known regarding effect on slow-release agents
↓ Skin thickness Transdermal preparations
Decrease in lean body mass leads to ↓ Vd/ ↓ T½ for Lipophilic agents, tricyclic antidepressants
hydrophilic drugs and Vd/T½ for lipophilic agents
Distribution
Decreased protein binding in frail patients with low albumin, Tolterodine
leading to higher concentration of free drug
↓ Phase I reactions (oxidation/reduction) Tricyclic antidepressants
No change in phase II reactions (glycosylation)
↓ Hepatic blood flow and ↓ hepatic mass, leading to reduced
Hepatic clearance for agents with first-pass metabolism Oxybutynin, tolterodine, solifenacin, darifenacin
metabolism
Stereoselective selectivity in metabolism (hypothetical) Enantiomers
Oxybutynin, tolterodine, solifenacin, darifenacin,
Cytochrome P450
mirabegron, 5-hydroxymethyl tolterodine (clearance only)
Clearance Decrease in renal clearance Tolterodine fesoterodine (5-hydroxymethyl tolterodine)
T½: half-life; Vd: volume of distribution.

Availability of low-dose agents ADE

One.effect.of.the.underrepresentation.(if.not.exclusion).of. ADEs.are.extremely.common.in.older.persons, .with.rates.
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frail.older.persons.in.UI.drug.studies.is.a.lack.of.knowledge. up.to.35%.among.community-dwelling.persons.aged.>65.in.
regarding.minimal.effective.drug.doses.for.this.population.. the.US..Factors.associated.with.higher.ADEs.in.older.persons.
The.age-related.changes.in.pharmacology.suggest.that.some. are.higher.drug.doses,.age-related.pharmacological.changes,.
UI.drugs.may.be.effective.at.lower.than.standard.doses.in. polypharmacy,.comorbid.conditions.and.the.interactions.
frail.older.persons.with.concomitant.decreased.adverse. between.them,.and.female.sex. 240,241 .Older.people.are.at.high-
effects. .There.are.some.data.supporting.the.effective.use. er.risk.of.ADEs.from.AMs.because.of.age,.and.comorbidity-
234
of.low-dose.oxybutynin.in.older.persons.(Level of evidence related.changes.in.muscarinic.receptor.number.and.distribu-
242
2b, Grade C). 235,236 .A.single.study.has.assessed.low.standard. tion,.blood-brain.barrier.transport,.and.drug.metabolism. .
doses.of.trospium.chloride.and.solifenacin.in.combination.in. Whereas.AM.ADEs.in.younger.persons.are.bothersome,.in.
older.persons.(not.frail).of.average.age.69.years.in.compari- the.frail.elderly.they.can.result.in.serious.morbidity,.such.as.
son.to.higher.doses,.showing.higher.efficacy.of.combination. sedation,.heat.intolerance,.delirium,.and.falls..Xerostomia.is.
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lower-dose.therapy.(Level of evidence 2b, Grade B). 237 common.in.older.people. .In.general,.older.people,.women,.
and.those.taking.multiple.medications.are.more.likely.to.report.
Polypharmacy the.symptom..A.subcut.analysis.of.a.Canadian.randomized.
controlled.trial.of.solifenacin.5.mg/day.vs..oxybutynin.5.mg.
Approximately.60%.of.people.over.age.65.take.at.least.one. three.times.daily,.examined.the.tolerability.of.both.drugs.in.
prescribed.medication.and.about.one-third.take.more.than. subjects.under.and.over.the.age.of.65.years..The.study.found.
five.prescribed.drugs..In.addition,.many.older.persons.take. that.dry.mouth.was.no.more.common.amongst.those.over.
over-the-counter,.naturopathic,.or.herbal.agents.and.dietary. the.age.of.65,.but.was.more.common.and.more.severe.with.
supplements,.with.the.rate.of.use.varying.across.countries. oxybutynin.(Level of evidence 1b, Grade B). .In.those.over.
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and.cultures..In.2010‒2011,.approximately.15.1%.of.older. 75.years.of.age.treated.with.8.mg.vs..4.mg.of.fesoterodine.from.
adults.were.at.risk.for.a.potential.major.drug-drug.inter- a.pooled.analysis.of.data.from.registration.trials,.dry.mouth.
action.compared.with.an.estimated.8.4%.in.2005‒2006. was.more.common.in.the.older.sample;.this.finding.was.dupli-
(p<0 .001). .The.likelihood.of.adverse.drug.reactions.(ADEs). cated.in.a.prospective.trial.of.fesoterodine.in.older.patients.
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and.drug.interactions.rises.exponentially.as.the.number.of. (Level of evidence 1b, Grade B). 245,246 .Another.AM.ADE.to.
medications.increases..Changes.to.existing.drug.regimens. which.the.frail.elderly.may.be.predisposed.is.decreased.vis-
should.be.considered.in.the.management.of.UI.in.all.frail. ual.accommodation,.yet.this.has.been.specifically.evaluated.
older.people.(Level of evidence 3, Grade B).. only.in.young,.healthy.volunteers .and.a.single.prospective.
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248
cohort.including.patients.up.to.the.age.of.60.years. .Drug.
trials.typically.report.only.“blurred.vision,”.without.further.
characterization.

CUAJ • May 2017 • Volume 11, Issue 5 E157