Vibegron for Overactive Bladder in Men With Benign Prostatic Hyperplasia

Overview:

Vibegron is a selective agonist of the beta-3 adrenergic receptor. Vibegron is generally given to patients who have symptoms of increased urgency to urinate, overactive bladder, or urinary incontinence (bladder control loss). On 30th December 2020, Vibegron received its approval for use in treating overactive bladder by the United States Food and Drug Administration (USFDA). On May 13, 2024, Vibegron received its approval to treat overactive bladder in men who are pharmacologically treated for benign prostatic hyperplasia. So, Vibegron becomes the first and only selective beta agonist drug that is used in managing overactive bladder secondary to benign prostatic hypertrophy (increased prostate gland size).

Dosage and Route of Administration:

The dosage of Vibegron to treat an overactive bladder is 75 milligrams (mg). This dosage remains the same even for males taking medicines for benign prostatic hyperplasia. The tablet containing 75 mg of Vibegron should be taken once daily.

For Patients:

What Is an Overactive Bladder?

Overactive bladder is an ailment in which the affected individuals may feel a greater urgency to urinate or experience an abnormally high frequency of urination, resulting in urinary incontinence. The smooth muscles surrounding the urinary bladder undergo involuntary contraction even before the bladder becomes full. This reflexive action can cause the person to urinate immediately, thus causing an overactive bladder.

What Are the Causes of Overactive Bladder?

• Any mishaps in the signaling process between the bladder and the brain can cause the bladder’s smooth muscles to contract frequently without will. This occurs due to neurological conditions affecting the brain like Parkinson’s disease (nervous system disorder), multiple sclerosis (damaged nerve sheaths due to aberrant immune action in the body), spinal cord injuries due to trauma, or stroke (damaged brain parenchyma due to reduced blood supply).

• The smooth muscles in the bladder area may weaken and lose their ability to control the urination process due to physiological processes like aging.

• When the bladder has a structural and functional deformity, it can become overactive. Such conditions may include calculi within the bladder or urinary tract, tumors in the urinary bladder, or a hypertrophied prostate gland.

• Irritation of the bladder's smooth muscles due to infections in the urinary system can cause an overactive bladder.

• Medicines taken by the patients, like diuretics, can cause an overactive bladder and increase urinary frequency.

• Hormonal changes secondary to menopause can cause overactive bladder in females.

• Bladder function can also be altered due to pelvic surgeries performed previously in the affected patients.

What Is the Relationship Between Overactive Bladder and Benign Prostatic Hyperplasia?

In older men, the incidence of benign prostate hyperplasia is high, and it occurs due to non-malignant enlargement of the prostate gland in such males. This distension of the prostate gland can pressurize the structures of the urinary bladder, including the smooth muscles. There can be a urinary obstruction in benign prostatic hyperplasia, which forces the urinary bladder to push out the urine. Thus, the bladder becomes overactive due to benign prostatic hyperplasia. So, such affected males will require treatment for both the enlarged prostate and overactive bladder for smooth functioning.

Why Is Vibegron Given for an Overactive Bladder?

The urinary bladder contains a smooth muscle called the detrusor that helps in the proper functioning of the bladder and controls the process of urination by contraction and relaxation. It contains several receptors like alpha-adrenergic receptors, muscarinic receptors (M2 and M3), beta-adrenergic receptors (B3), and purinergic receptors (P2X1). Of all these receptors, beta-adrenergic receptors in the detrusor muscle are responsible for relaxing the bladder.

For an overactive bladder, the main motto is to reduce the contractile activity of the detrusor smooth muscle so that the muscle is not activated involuntarily. To achieve this, Vibegron is prescribed. By acting as an agonist on the beta-3 adrenergic receptors of the detrusor, Vibegron relaxes the bladder and reduces the urge to urinate and urinary incontinence.

Unlike other medications used for such overactive bladder, which work by blocking the effects of acetylcholine on the bladder muscles (antimuscarinics), Vibegron specifically targets the beta-3 receptors in the bladder. Activation of these receptors helps to inhibit the contraction of the detrusor muscle during the bladder’s storage phase of the filling cycle, thus allowing for greater bladder capacity and reducing the sensation of urgency. Vibegron is also given for males who are pharmacologically under treatment for benign prostatic hyperplasia to treat overactive bladder as there is no aggravation of symptoms pertaining to benign prostatic hyperplasia.

How Is Vibegron Taken?

Vibegron is available as a 75 milligrams tablet that should be consumed once a day. Vibegron can also be crushed and taken along with applesauce or water. It is recommended that Vibegron be swallowed completely with one glass of water.

Drug Storage:

Vibegron is recommended to be stored under controlled room temperature (approximately 20 to 25 degrees Celsius (77 degrees Fahrenheit).

Missed Dose:

If a dose of Vibegron is missed, patients can skip that particular dose and continue with the next dosage of Vibegron.

Overdose:

Overdosing Vibegron does not cause any significant adverse effects on the body. If the patient experiences any side effects after taking Vibegron, a treatment focusing on symptomatic relief would suffice.

What Are the Side Effects of Taking Vibegron?

• The most common side effect reported by people taking Vibegron is urinary retention. After taking Vibegron, there can be obstruction of the urinary tract, which can obstruct the urinary flow. This results in urinary retention within the bladder. This is especially common among people who take antimuscarinics (drugs targeting the M2 and M3 receptors in the detrusor muscle) for treating overactive bladder.

Other Side Effects Noted Are:

• Headache.

• Nausea.

• Vomiting.

• Inflammation in the nasal and pharyngeal areas.

• Diarrhea (loose and watery stool).

• Frequent infection in the upper respiratory tract.

• Dry mouth.

• Inflammation of the bronchus.

• Urinary tract infection.

• Skin rashes.

• Itching.

• Drug eruptions.

• Severe dizziness.

• Back pain.

• Troubled breathing.

• Cough.

• Swelling.

• Increased blood pressure.

• Palpitations.

• Nasal congestion.

• Runny nose.

• Sore throat.

Less than two percent of the people also reported constipation and hot flushing following the intake of Vibegron.

What Are the Precautions to Take Before Taking Vibegron?

• Patients who have allergies to the contents of the Vibegron drug should inform the doctor as there is an increased incidence of allergic reactions (like itching, eczema, and eruptions) following Vibegron intake.

• Patients with liver or kidney impairment should be wary about Vibegron intake as the drug affects the liver and kidney during the process of absorption and metabolism.

• People taking Vibegron should inform the doctor about their drug intake before any dental or surgical procedure that requires aestheticization. This is because Vibegron can influence the choice of the anesthesia that should be used for the surgical procedure.

• People taking Vibegron should also take copious amounts of water and stay hydrated.

For Doctors:

Clinical Pharmacology:

Vibegron selectively activates beta-3 adrenergic receptors located predominantly in the detrusor muscle of the bladder. This activation leads to the relaxation of the detrusor muscle during the bladder-filling phase, thereby increasing bladder capacity and reducing involuntary contractions associated with an overactive bladder. Unlike antimuscarinic agents, which have been conventionally used for the treatment of overactive bladder, Vibegron's mechanism of action is more specific and does not exert anticholinergic effects.

Indications:

Vibegron is indicated for patients who have increased urge, increased urinary frequency, and urge urinary incontinence, which forms a part of the overactive bladder syndrome. As a result, Vibegron helps in treating overactive bladder.

Contraindications:

• Patients allergic to Vibegron ingredients are contraindicated.

• Patients with uncontrolled hypertension (high blood pressure) are not indicated for treatment with Vibegron as there are chances for exacerbation.

• People with severely impaired liver and kidney function.

Drug Ingredients:

Active Ingredient: Vibegron

Inactive Ingredients:

• Hydroxypropyl cellulose.

• Croscarmellose sodium.

• Mannitol.

• Magnesium stearate.

• Cellulose.

• Triacetin.

• Lactose monohydrate.

• Titanium dioxide.

Half-Life:

The half-life of Vibegron is approximately 30.8 hours.

Pharmacokinetics:

Absorption:

Within one to three hours of taking Vibegron, the maximum plasma concentration is reached. The absorption process of Vibegron is not affected by the presence of food. Hence, Vibegron can be taken orally with or without food intake. There was no change in the absorption of Vibegron even when crushed and consumed with applesauce.

Distribution:

Following absorption, Vibegron is distributed throughout the body. Vibegron demonstrates a moderate level of binding to plasma proteins (roughly around 50 percent), which helps in maintaining a balanced distribution between the blood and tissues. The volume of distribution of Vibegron indicates that it is well-distributed in body tissues, including the bladder (the region where the therapeutic effect of the drug is necessary). This distribution profile ensures that sufficient concentrations of Vibegron reach the target beta-3 adrenergic receptors in the detrusor muscle of the bladder.

Metabolism:

Vibegron undergoes metabolism primarily in the hepatic system (liver). The metabolizing enzyme of Vibegron is CYP3A4. This enzymatic pathway transforms Vibegron into various metabolites, which are then processed for elimination.

Elimination:

Vibegron is primarily eliminated from the body through fecal excretion. After undergoing metabolism in the liver, the metabolites of Vibegron are excreted into the bile and eventually passed out of the body in the feces (approximately 59 percent). A smaller portion of Vibegron and its metabolites (20 percent) are eliminated by renal excretion in the urine.

Pharmacodynamics:

The pharmacodynamics of Vibegron involve the targeted activation of beta-3 adrenergic receptors predominantly found in the detrusor muscle of the bladder. When these receptors are stimulated, they induce relaxation of the detrusor muscle during the bladder's filling phase. This relaxation increases the bladder's capacity to hold urine back and inhibits the frequency of involuntary contraction. Unlike antimuscarinic drugs that block acetylcholine receptors in the detrusor muscle and can cause side effects like dry mouth and constipation, Vibegron offers a more specific mechanism of action with a lower side effect profile. The selective action of Vibegron on beta-3 receptors leads to improved bladder storage without significantly affecting the receptors involved in bladder contraction, thus maintaining normal voiding function. This targeted therapeutic approach makes Vibegron an effective and well-tolerated option for managing overactive bladder. This can be a great option for patients with benign prostate hyperplasia and secondary overactive bladder.

Clinical Toxicity:

There are no severe toxic effects following the intake of Vibegron. Some adverse effects noted after Vibegron intake are:

• Excessive relaxation of the detrusor muscle caused by Vibegron intake can lead to incomplete bladder emptying or urinary retention as Vibegron increases the capacity of the bladder. This occurs particularly in patients with benign prostatic hyperplasia or bladder obstruction disorders. Further, retention of urine in the bladder can act as a nidus for infection to develop in the bladder and the urinary system.

• Sometimes, patients may experience a sudden elevation in the levels of blood pressure after taking Vibegron. If there are any symptoms aggravated due to increased blood pressure, they should be relieved symptomatically.

• There can also be an exacerbation of liver dysfunctions in people with existing hepatic disorders.

Drug Interactions:

• The most important drug interaction observed is with Digoxin. When Vibegron and digoxin are taken together, there is a potential for Vibegron to increase the plasma concentration of digoxin. This interaction occurs because Vibegron can inhibit plasma glycoprotein, a transport protein that is highly essential in the renal and hepatic excretion of digoxin. By inhibiting the necessary plasma glycoprotein, Vibegron can decrease the clearance of digoxin from the body, leading to higher digoxin levels in the blood. Thus, elevated levels of digoxin can increase the risk of digoxin toxicity in the affected patient.

• Using Vibegron along with anticholinergics (against M2 and M3 receptors in the detrusor) for overactive bladder certainly increases the susceptibility to develop urinary retention in such patients.

• Vibegron was not reported to interact with any other CYP3A4 inducers or inhibitors.

Guidelines for Specific Population:

Pregnant and Nursing Mothers

There is no sufficient data regarding the influence of Vibegron on developing fetuses in a pregnant lady. Also, there is no information about the excretion of Vibegron in breast milk. So, Vibegron is generally not given to pregnant or lactating mothers.

Pediatric Population

Clinical studies have not been performed on pediatric individuals to know the safety of their population. So, Vibegron is not prescribed for the pediatric population.

Geriatric Individuals

Most of the clinical studies regarding the efficacy of Vibegron were done among individuals who are more than 75 years of age and the results were normal. This means that there is no need for dose modification in the geriatric population, and Vibegron can be used safely for geriatric people with overactive bladder.