Pharmacy & Therapeutics - January 2009 - (Page 26) Pharmaceutical Approval Update Mar vin M. Goldenberg, PhD, RPh, MS Fesoterodine Fumarate Extended-Release Tablets (Toviaz) Manufacturer: Schwarz Pharma, Zwickau, Germany (distributed by Pfizer) Indication: Fesoterodine fumarate is indicated for the treatment of overactive bladder (OAB) in patients with urge urinar y incontinence, urgency, and frequency. Drug Class: This agent is designated as isobutyric acid 2-((R)-3-diisopropylammonium-1-phenylpropyl)-4-(hydroxymethyl) phenyl ester hydrogen fumarate. Uniqueness of Drug: Fesoterodine is rapidly de-esterified to its active metabolite, (R)-2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethyl-phenol, or 5-hydroxymethyl tolterodine, a muscarinic receptor antagonist. The active metabolite is further metabolized in the liver to its carboxy, carboxy-Ndesisopropyl, and N-desisopropyl metabolites via two major pathways involving cytochrome P450 2D6 and CYP 3A4. None of these metabolites contribute significantly to the anti muscarinic activity of fesoterodine. The extended-release tablet contains either 4 mg or 8 mg of fesoterodine fumarate. Precautions: Bladder outlet obstruction. Fesoterodine fumarate should be administered with caution to patients with bladder outlet obstruction because of the risk of urinary retention. Decreased gastrointestinal motility. As with other antimuscarinic drugs, fesoterodine fumarate should be used with caution in patients with decreased gastrointestinal (GI) tract motility (e.g., as in severe constipation). Controlled narrow-angle glaucoma. Caution should be exercised for patients with narrow-angle glaucoma, and this drug should be prescribed only when the potential benefits outweigh the risks. Reduced hepatic function. No dosing adjustments are necessary for patients with mild or moderate hepatic impairment. Fesoterodine fumarate has not been studied in patients with severe hepatic impairment and is thus not recommended for this population. Myasthenia gravis. Caution should be used for patients with myasthenia gravis, which is characterized by decreased cholinergic activity at the neuromuscular junction. Reduced renal function. There are no dosing adjustments for patients with mild or moderate renal insufficiency. Doses greater than 4 mg are not recommended in patients with severe renal insufficiency. Administration with CYP 3A4 inhibitors. Doses higher than 4 mg are not recommended if patients are taking a potent CYP 3A4 inhibitor, such as ketoconazole (Nizoral, PriCara), itraconazole (Sporanox, PriCiara), or clarithromycin (Biaxin, Abbott). If patients are taking weak or moderate CYP 3A4 The author is President of Pharmaceutical and Scientific Services at Marvin M. Goldenberg, LLC, in Westfield, N.J. His e-mail address is marvinmgoldenberg@verizon.net. inhibitors (e.g., erythromycin), careful assessment of tolerability at the 4 mg daily dose is advised before the daily dose is increased to 8 mg. Although the potential for this specific interaction was not examined in a clinical study, some pharmacokinetic interaction is expected, albeit less than that observed with potent CYP 3A4 inhibitors. Dosage and Administration: The recommended starting dose is 4 mg once daily. Depending on the patient’s response and tolerability, the dose may be increased to 8 mg once daily. The daily dose should not exceed 4 mg in patients with severe renal insufficiency (a creatinine clearance [CrCl] below 30 mL/minute) or in those taking potent CYP 3A4 inhibitors. The tablet is taken with liquid and swallowed whole. It can be taken with or without food and should not be chewed, divided, or crushed. The extended-release tablet contains either 4 mg or 8 mg of fesoterodine fumarate. Inactive ingredients are glyceryl behenate, hypromellose, indigo carmine aluminum lake, lactose monohydrate, soya lecithin, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide, and xylitol. Contraindications: Fesoterodine fumarate is not recommended for patients with severe hepatic impairment. Commentary: OAB is a bothersome medical condition that affects an estimated one in six Americans, yet it remains highly undertreated. Fesoterodine fumarate can help regulate involuntary bladder contractions, which cause frequent, sudden urges to urinate. The drug is structurally related to Pfizer’s tolterodine tartrate extended-release capsules (Detrol LA). Two efficacious and well-tolerated doses, 4 mg and 8 mg, allow dosing flexibility to optimize treatment. Symptoms of OAB can have a significant impact on workplace productivity, social and sexual activity, and sleep. OAB may also result in falls and fractures, urinary tract infections, skin disorders, and depression. Despite the impact of OAB on patients’ lives, the embarrassment and stigma associated with incontinence can cause patients to try to hide the condition from families, friends, and even their doctors. As a result, many patients with incontinence suffer without seeking help. People with OAB symptoms should be encouraged to speak to their physicians about their problem in order to improve their quality of life. Source: www.pfizer.com Rufinamide (Banzel) Manufacturer: Eisai, Woodcliff Lake, N.J. Indication: Rufinamide is indicated for the adjunctive treatment of seizures associated with Lennox–Gastaut syndrome in adults and in children four years of age and older. Drug Class: The chemical name is 1-[(2,6-difluorophenyl) methyl]-1H-1,2,3-triazole-4 carboxamide. Rufinamide, a triazole derivative, is structurally unrelated to currently marketed antiepileptic drugs. 26 P&T® • January 2009 • Vol. 34 No. 1 http://www.pfizer.com
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