The beta-3 adrenergic agonist mirabegron (Myrbetriq) gained an indication for neurogenic detrusor overactivity (NDO), a form of bladder dysfunction, in children 3 and older, the Thursday. The drug will be available as extended-release tablets and granules for oral suspension.
"Mirabegron, the active ingredient in Myrbetriq and Myrbetriq Granules, works by a different mechanism of action from the currently approved treatments, providing a new treatment option for these young patients," said Christine Nguyen, MD, director of FDA's Division of Urology, Obstetrics and Gynecology, Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, in a statement. "We remain committed to facilitating the development and approval of safe and effective therapies for pediatric NDO patients."
NDO is caused by disease (such as spina bifida) or damage (such as spinal cord injury) in the nervous system. Overactivity of the detrusor, a muscle in the bladder wall, leads to sporadic contractions, increasing pressure in the bladder and decreasing the volume of urine it can hold. If NDO is not treated, increased pressure potentially can harm the upper urinary tract and lead to possible permanent kidney damage. Spontaneous bladder muscle contractions can also lead to urine leakage, with symptoms of urinary urgency, frequency, and incontinence.
Mirabegron's efficacy in pediatric NDO was established in a of 86 patients ages 3 to 17. After 24 weeks of treatment, improvements occurred in patients' maximum bladder capacity, number of detrusor contractions, volume of urine held until first contraction, and number of daily urine leakage episodes.
Urinary tract infection, nasopharyngitis, constipation, and headache were the most common side effects. Mirabegron may increase blood pressure or may make blood pressure worse in patients with a history of hypertension, the FDA warned. The drug also may cause angioedema; patients should stop taking it immediately and seek medical attention if they experience angioedema associated with upper airway swelling, which could be life-threatening.
Mirabegron was approved for adults with overactive bladder in 2012. Though there were concerns about increases in blood pressure and heart rate before the drug was approved, a real-world study showed that adults taking mirabegron for overactive bladder did not have an increased risk of cardiovascular events compared with those taking other drugs for the condition.
"Myrbetriq and Myrbetriq Granules are two different products and they are not substitutable on a milligram-per-milligram basis," the FDA noted. A recommended dosage for the granule formulation has not been determined for adults.