warfarin and Urinary-Bladder--Overactive

Mirabeg ron is a selective β3-adrenoceptor agonist approved for the treatment of overactive bladder (OAB). Four phase 1 studies were conducted in healthy subjects to evaluate the potential for pharmacokinetic interactions between mirabegron and metformin, warfarin, digoxin, or a combination oral contraceptive (COC).. Thirty-two male subjects received metformin (500 mg twice daily) or mirabegron (160 mg once daily) alone, in combination or with placebo. Twenty-four male and female subjects received single doses of warfarin (25 mg) alone and in combination with mirabegron (100 mg once daily). Twenty-five male and female subjects were administered digoxin (0.25 mg) alone and in combination with mirabegron (100 mg once daily). Thirty female subjects received low-dose COC containing ethinylestradiol (EE)/levonorgestrel (LNG) (30/150 µg once daily) in combination with mirabegron (100 mg once daily) or placebo. Pharmacokinetic parameters were determined by non-compartmental methods. Absence of a Pharmacokinetic interaction was concluded if the 90 % confidence intervals (CI) of geometric least-squares means ratio of area under the curve (AUC) and maximum concentration (C. Mirabegron increased digoxin AUC and C. No dose adjustment of either drug is required when mirabegron is administered concomitantly with metformin, warfarin or COC. Patients receiving mirabegron with digoxin may require additional monitoring of digoxin concentrations with dose adjustments where necessary, due to its narrow therapeutic index.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Area Under Curve; Contraceptives, Oral, Combined; Digoxin; Double-Blind Method; Drug Interactions; Female; Healthy Volunteers; Humans; Male; Metformin; Thiazoles; Urinary Bladder, Overactive; Warfarin

The symptoms of overactive bladder (OAB) can be treated with oral medications using a variety of antimuscarinic medications and, more recently, mirabegron, a beta-3 agonist. However, the use of these medications may be limited for patients because of adverse drug reactions, contraindications, and those who are refractory to oral medications. Recently, intravesical injections of onabotulinumtoxinA (onaBoNTA) have been proven to be safe and effective as an alternative to oral OAB medications. Although this procedure is typically thought to be outside the realm of a consultant pharmacist, there are incidences in which a pharmacist can make a substantial impact on patient care. The patient, a 71-year old female, presents to her urologist for evaluation to assess appropriateness of intravesical onaBoNTA injections. She has failed multiple oral medications for the treatment of her OAB with urge incontinence. The procedure is further complicated by the patient's past medical history of atrial fibrillation (A fib), deep vein thrombosis (DVT), and pulmonary embolism (PE) that require anticoagulation with warfarin therapy. This case demonstrates the use of onaBoNTA for OAB in a patient concomitantly receiving warfarin for A fib, PE, and DVT. Specifically, it demonstrates discontinuation, bridge therapy, and reinitiation of warfarin on a patient undergoing intravesical injections of onaBoNTA for OAB, and a collaborative approach to care between a pharmacist and a urologist.

Topics: Acetylcholine Release Inhibitors; Aged; Anticoagulants; Botulinum Toxins, Type A; Female; Humans; Treatment Outcome; Urinary Bladder, Overactive; Warfarin