Fesoterodinefumarate

Description

Fesoterodine fumarate is a new drug for the treatment of overactive bladder syndrome developed by Pfizer, which was approved by the US FDA in October 2008. Fesoterodine fumarate is a prodrug, which is rapidly hydrolyzed in blood after oral administration to 5-hydroxymethyl tolterodine (5-HMT), which is also the active metabolite of tolterodine.

Biological activity

Fesoterodine Fumarate (SPM 907) is a prodrug of the muscarinic receptor antagonist 5-hydroxymethyl tolterodine, used to treat overactive bladder.

Side effects

The most common side effects was dry mouth, which was observed in the placebo group, the product 4 in the Phase II and Phase III clinical trials (a total of 2 859 patients, 2 288 taking this product for 8 to 12 weeks). The incidences of dry mouth at mg/d and 8 mg/d were 7%, 19%, and 35%, respectively, and the incidences of drug discontinuation due to dry mouth were 0.4%, 0.4%, and 0.8%, respectively. The second most common adverse reaction was constipation. The incidence of constipation in the placebo group and the 4 mg/d and 8 mg/d groups of this product was 2%, 4% and 6%, respectively. Other reported adverse events included loss of appetite, nausea, epigastric pain, urinary tract infection, upper respiratory tract infection, dry eyes, dysuria, urinary retention, cough, peripheral edema, back pain, insomnia, abnormal liver function, and rash.

Chemical Properties

White Solid

Uses

Fesoterodine fumarate (Toviaz) is an antimuscarinic agent and is rapidly de-esterified to its active metabolite 5-hydroxymethyl tolterodine that is a muscarinic receptor antagonist. Fesoterodine fumarate (Toviaz) is used to treat the symptoms of overactiv

Uses

(R)-Fesoterodine Fumarate is a muscarinic receptor antagonist for the treatment of Lower Urininary Tract Symptoms (LUTS). It is very similar to Tolterodine (T535800).

Clinical Use

Antimuscarinic:
Symptomatic treatment of urinary incontinence, frequency or urgency

Drug interactions

Potentially hazardous interactions with other drugs
 Anti-arrhythmics: increased risk of antimuscarinic side effects with disopyramide.
 Antifungals: dose reduction advised with itraconazole and ketoconazole.
 Antivirals: dose reduction advised with atazanavir, indinavir, ritonavir and saquinavir.
 Induction of CYP3A4 may lead to subtherapeutic plasma levels. Concomitant use with CYP3A4 inducers (e.g. carbamazepine, rifampicin, phenobarbital, phenytoin, St John's Wort) is not recommended.
 Co-administration of a potent CYP2D6 inhibitor may result in increased exposure and adverse events. A dose reduction to 4 mg may be needed' 

Metabolism

Rapidly and extensively hydrolysed to its active metabolite. The active metabolite is further metabolised in the liver to its carboxy, carboxy-N-desisopropyl, and N-desisopropyl metabolites via two major pathways involving CYP2D6 and CYP3A4. None of these metabolites contribute significantly to the antimuscarinic activity of fesoterodine. Approximately 70% of an oral dose of fesoterodine is recovered in the urine as metabolites, and a smaller amount in the faeces.