Dealing with complex overactive bladder syndrome patient profiles with focus on fesoterodine: in or out of the EAU guidelines?

Figures & data

Table 1 Pharmacological and pharmacokinetic properties of antimuscarinic agents

Molecules	Oxybutynin	Tolterodine	Trospium	Propiverine	Darifenacin	Solifenacin	Fesoterodine/5-HMT
Molecular weight	393.9	475.6	427.97	403.95	507.5	480.55	527.66
Lipophilicity	>3.3	1.83	–1.22	Lipophilic	2.7	1.69	0.74
Pgp substrate	No	No	Yes	No	Yes	No	Yes

Notes: Data from Chancellor and Boone,³¹ Cetinel and Onal,³³ Kerdraon et al,³⁸ Malhotra et al.⁴² Copyright © 2011. MHRA. Adapted from Medicines and Healthcare Products Regulatory Agency. Public assessment report – mutual recognition procedure: Mictonorm XL 45 mg modified release capsules (propiverine hydrochloride). 2011. Available from: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con143796.pdf.⁴⁰

Abbreviation: HMT, hydroxymethyl tolterodine.

Figure 1 Actions of acetylcholine on M₂ and M₃ receptors.

Notes: Stimulation of M₃ receptors activates PLC and phosphoinositide hydrolysis, leading to inositol triphosphate (IP₃) and diacylglycerol (DAG) formation, inducing calcium release and detrusor contraction. M₂ receptors inhibit AC, and may aid bladder contraction by reversing cAMP-induced relaxation. Data from Abrams and Andersson,⁵⁴ Sellers and Chess-Williams,⁵⁵ and Chapple.⁵⁶
Abbreviations: ACh, acetylcholine; cAMP, cyclic adenosine monophosphate; NA, noradrenaline; β₃, beta-3 adrenergic receptor; M₂, M₃, muscarinic receptors.

Table 2 Rating of OAB medical drugs on the LUTS-FORTA classification

Drug class	Agent	FORTA class
Antimuscarinics
	Darifenacin	C
	Fesoterodine	B
	Oxybutynin standard dose/immediate release	D
	Oxybutynin low dose/extended release	C
	Propiverine	D (C)*
	Solifenacin	C
	Tolterodine	C
	Trospium	C (B)*
β3-agonist
	Mirabegron	C

Note:

* FORTA class attributed in the first round. Class A (absolutely), indispensable drug, clear-cut benefit in terms of efficacy:safety ratio proven for a given indication in older people; class B (beneficial), drugs with proven or obvious efficacy in older people, but limited extent of effect or safety concerns; class C (careful), drugs with questionable efficacy/safety profiles in older people, to be avoided, or omitted in the presence of too many other drugs, lack of benefits, or emerging side effects – review/find alternatives; class D (do not), avoid in older people, omit first, review/find alternatives.

Abbreviations: FORTA, Fit for the Aged; LUTS, lower-urinary-tract symptoms; OAB, overactive bladder syndrome.

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