Mirabegron

Tell your doctor about all prescription, non-prescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking, especially:

• Anticoagulants (blood thinners) such as Coumadin (warfarin)
• Norpramin (desipramine)
• Lanoxin (digoxin)
• Tambocor (flecainide)
• Other medications for overactive bladder, such as Enablex (darifenacin), Toviaz (fesoterodine), Anturol, Ditropan, Glenique, or Oxytrol (oxybutynin), VESIcare (solifenacin), Detrol (tolterodine), or Sanctura (trospium)
• Rythmol (propafenone)
• Toprol (metoprolol)
• Thioridazine

Myrbetriq and Other Interactions

Myrbetriq may make you dizzy.

Don't drive or perform activities that require alertness until you know how the medicine affects you.

Myrbetriq and Alcohol

Alcohol may worsen certain side effects of Myrbetriq.

Talk to your doctor about how much alcohol is safe to drink while taking this medicine.

Mirabegron is part of the drug class:

• Drugs for urinary frequency and incontinence

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Mirabegron may affect the way other medicines work, and other medicines may affect how mirabegron works.

Tell your doctor if you take:

• thioridazine (Mellaril or Mellaril-S)
• flecainide (Tambocor)
• propafenone (Rythmol)
• digoxin (Lanoxin)

This is not a complete list of mirabegron drug interactions. Ask your doctor or pharmacist for more information.

Do not take Mirabegron if you are allergic to it. 

Mirabegron can increase blood pressure. Your doctor should check your blood pressure often while you are taking mirabegron, particularly if you have a history of high blood pressure. 

This medication has caused urinary retention in patients with bladder outlet obstruction (BOO) and in patients taking antimuscarinic medicines for overactive bladder. Talk to your doctor if you are unsure if this applies to you. 

The recommended starting dose of mirabegron is 25 mg once daily with or without food. Mirabegron 25 mg is effective within 8 weeks. The dose may be increased to 50 mg once daily, if needed.

The daily dose of mirabegron should not be more than 25 mg once daily in people with severe kidney disease or moderate liver disease.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• digoxin;

• flecainide;

• propafenone; or

• thioridazine.

This list is not complete. Other drugs may interact with mirabegron, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Contraindications

• Manufacturer states none known.1

Warnings/Precautions

Cardiovascular Effects

Increased BP reported.1 Worsening of preexisting hypertension reported infrequently.1 Increases in SBP and DBP appeared to be dose related and reversible upon discontinuance of therapy.1

Measure BP periodically, especially in patients with preexisting hypertension.1 Avoid use in patients with severe uncontrolled hypertension (i.e., SBP ≥180 mm Hg, DBP ≥110 mm Hg).1

Causes only minimal QTc interval prolongation and slight increases in HR in healthy individuals.1

Genitourinary Effects

Urinary retention reported in patients with bladder outflow obstruction and in those receiving antimuscarinic agents for treatment of overactive bladder during postmarketing surveillance.1 Use with caution in such patients.1

Interactions with Drugs Metabolized by Hepatic Microsomal Enzymes

Possible increase in systemic exposure to substrates of CYP2D6 when used concomitantly with mirabegron.1 (See Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes under Interactions.) Appropriate monitoring recommended; dosage adjustment may be necessary, especially in patients receiving CYP2D6 substrates with a narrow therapeutic index.1 (See Specific Drugs under Interactions.)

Specific Populations

Category C.1

Distributed into milk in rats and detected in nursing pups; not known whether distributed into human milk.1 Discontinue nursing or the drug.1

Safety and efficacy not established.1

Pharmacokinetics not substantially affected by patient age.1 No substantial differences in safety and efficacy relative to younger adults; dosage adjustment not necessary.1

Increased plasma concentrations of mirabegron reported in patients with moderate hepatic impairment (Child-Pugh class B).1 (See Hepatic Impairment under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Not evaluated in patients with severe hepatic impairment (Child-Pugh class C); use not recommended in such patients.1

Increased plasma concentrations of mirabegron reported in patients with severe renal impairment (ClCr 15–29 mL/minute).1 (See Renal Impairment under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Not evaluated in patients with ESRD (ClCr <15 mL/minute or when hemodialysis required); use not recommended in such patients.1

Common Adverse Effects

Hypertension, nasopharyngitis, urinary tract infection, headache.1

Absorption

Bioavailability

Absolute bioavailability is 29 or 35% following mirabegron dosages of 25 or 50 mg, respectively.1

Peak plasma concentrations achieved at approximately 3.5 hours after oral administration.1 7

Steady-state concentrations achieved within 7 days of once-daily dosing.1 7

Steady-state concentrations following once-daily administration approximately twice as high as that observed following a single dose.1 7

Onset

Symptomatic improvement observed within 4 or 8 weeks with once-daily dosages of mirabegron 50 or 25 mg, respectively.1

Food

Peak plasma concentrations and AUC decreased by 45 and 17%, respectively, following administration of mirabegron 50 mg with a high-fat meal and by 75 and 51%, respectively, following a low-fat meal.1 However, safety and efficacy established when administered without regard to food.1 (See Administration under Dosage and Administration.)

Peak plasma concentrations and AUC were similar following multiple oral doses in geriatric individuals (≥65 years of age) compared with younger adults (18–45 years of age).1 7

Mean peak plasma concentrations and AUC increased by 16 and 17%, respectively, in poor CYP2D6 metabolizers compared with extensive CYP2D6 metabolizers.1

Peak plasma concentrations and AUC increased by approximately 40–50% in females compared with males.1 Systemic exposure about 20–30% higher in females compared with males after adjusting for differences in body weight.1

Pharmacokinetics of mirabegron similar in white and black individuals.1 Increased exposure observed in Japanese individuals compared with North American individuals; extent of differences decreased when peak plasma concentrations and AUC normalized for dose and body weight.1

Mild hepatic impairment (Child-Pugh class A): Mean peak plasma concentrations and AUC increased by 9 and 19%, respectively, compared with those observed in individuals with normal hepatic function.1

Moderate hepatic impairment (Child-Pugh class B): Mean peak plasma concentrations and AUC increased by 175 and 65%, respectively, compared with those observed in individuals with normal hepatic function.1 (See Hepatic Impairment under Dosage and Administration.)

Severe hepatic impairment (Child-Pugh class C): Effect on pharmacokinetics not studied.1 (See Hepatic Impairment under Dosage and Administration.)

Mild renal impairment (estimated GFR 60–89 mL/minute per 1.73 m2): Mean peak plasma concentrations and AUC increased by 6 and 31%, respectively, compared with those observed in individuals with normal renal function.1

Moderate renal impairment (estimated GFR 30–59 mL/minute per 1.73 m2): Mean peak plasma concentrations and AUC increased by 23 and 66%, respectively, compared with those observed in individuals with normal renal function.1 (See Renal Impairment under Dosage and Administration.)

Severe renal impairment (estimated GFR 15–29 mL/minute per 1.73 m2): Mean peak plasma concentrations and AUC increased by 92 and 118%, respectively, compared with those observed in individuals with normal renal function.1 Not studied in patients with ESRD (ClCr <15 mL/minute) or in those requiring hemodialysis.1 (See Renal Impairment under Dosage and Administration.)

Distribution

Extent

Extensively distributed.1

Distributed into erythrocytes; erythrocyte concentrations about twofold higher than plasma concentrations in vitro.1

Distributed into milk in rats and detected in nursing pups.1 Not known whether distributed into human milk.1

Plasma Protein Binding

Approximately 71% (moderate affinity for albumin and α1-acid glycoprotein).1

Elimination

Metabolism

Undergoes hepatic metabolism via multiple pathways involving dealkylation, oxidation, direct glucuronidation, and amide hydrolysis.1 6 CYP isoenzymes 2D6 and 3A4 may be involved in the oxidative metabolism of mirabegron but have limited role in overall drug elimination.1 Butyrylcholinesterase, UGT, and possibly alcohol dehydrogenase also appear to be involved in mirabegron metabolism.1

Two major glucuronide metabolites represent 16 and 11% of total drug exposure, respectively; these metabolites pharmacologically inactive at the β3-adrenergic receptor.1 7

Elimination Route

Eliminated principally by renal clearance via active tubular secretion along with glomerular filtration.1

Approximately 55 and 34% of total radioactivity was recovered in urine and feces, respectively; approximately 25% of the radioactive dose was recovered as unchanged drug excreted in urine and 0% in feces.1

Half-life

Approximately 50 hours.1

• Selective β3-adrenergic agonist.1 3 4 5 8

• Stimulates human β1-adrenergic receptors at higher than recommended dosages (200 mg).1

• Relaxes the detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle resulting in increased bladder capacity via activation of β3-adrenergic receptors.1 5

• Increased intraocular pressure not observed in healthy individuals following once-daily administration.1

Take mirabegron only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance for side effects.

mirabegron comes with a patient information leaflet. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Swallow the extended-release tablet whole and with water. Do not crush, break, or chew it. You may take mirabegron with or without food.

Dosing

The dose of mirabegron will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of mirabegron. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (extended-release tablets):
  • To treat bladder problems:
    • Adults—At first, 25 milligrams (mg) once a day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 50 mg per day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of mirabegron, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• Myrbetriq

Hypersensitivity to mirabegron or any component of the formulation

Canadian labeling: Additional contraindications (not in U.S. labeling): Severe uncontrolled hypertension (systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg); pregnancy

Refer to adult dosing.

Applies to mirabegron: oral tablet extended release

Along with its needed effects, mirabegron may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking mirabegron:

• Bladder pain
• bloody or cloudy urine
• blurred vision
• difficult, burning, or painful urination
• dizziness
• frequent urge to urinate
• headache
• lower back or side pain
• nervousness
• pounding in the ears
• slow, fast, or irregular heartbeat

• Blindness
• decrease in vision
• eye pain
• lower abdominal or stomach pain
• nausea or vomiting
• pain in the groin or genitals
• tearing or eyes

• Blistering, peeling, or loosening of the skin
• chills
• cough
• decrease in the frequency of urination
• decrease in urine volume
• diarrhea
• difficulty in passing urine (dribbling)
• itching
• joint or muscle pain
• red skin lesions, often with a purple center
• red, irritated eyes
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• unusual tiredness or weakness

Some side effects of mirabegron may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abdominal or stomach pain
• back pain
• body aches or pain
• difficulty having a bowel movement (stool)
• difficulty with breathing
• difficulty with moving
• dry mouth
• ear congestion
• fever
• loss of voice
• muscle aches
• muscle stiffness
• sneezing
• stuffy or runny nose

• Acid or sour stomach
• belching
• burning feeling in the chest or stomach
• full or bloated feeling
• heartburn
• hives or welts
• indigestion
• itching
• itching or pain of the vagina or genital area
• pain or tenderness around the eyes and cheekbones
• pressure in the stomach
• redness of the skin
• shortness of breath or troubled breathing
• skin rash
• stomach discomfort or upset
• swelling of the lips
• tenderness in the stomach area
• thick, white vaginal discharge with mild or no odor

Applies to mirabegron: oral tablet extended release

Cardiovascular

Very common (10% or more): Hypertension (up to 11.3%)
Common (1% to 10%): Tachycardia
Uncommon (0.1% to 1%): Atrial fibrillation, palpitations[Ref]

Dermatologic

Uncommon (0.1% to 1%): Urticaria, rash, pruritus, lip edema, macular rash, papular rash
Rare (less than 0.1%): Leukocytoclastic vasculitis, purpura, angioedema[Ref]

Gastrointestinal

Common (1% to 10%): Nausea, constipation, diarrhea, abdominal pain
Uncommon (0.1% to 1%): Dyspepsia, gastritis, abdominal distension
Rare (less than 0.1%): Lip edema[Ref]

Genitourinary

Common (1% to 10%): Urinary tract infection
Uncommon (0.1% to 1%): Nephrolithiasis, bladder pain, cystitis, vaginal infection, vulvovaginal pruritus
Postmarketing reports: Urinary retention[Ref]

Musculoskeletal

Common (1% to 10%): Arthralgia
Uncommon (0.1% to 1%): Joint swelling[Ref]

Nervous system

Common (1% to 10%): Headache, fatigue, dizziness[Ref]

Ocular

Uncommon (0.1% to 1%): Glaucoma, blurred vision, dry eyes
Rare (less than 0.1%): Eyelid edema[Ref]

Oncologic

Rare (less than 0.1%): Prostate cancer[Ref]

Respiratory

Common (1% to 10%): Nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis[Ref]

Hepatic

Uncommon (0.1% to 1%): Increased ALT, AST, and GGT[Ref]

Some side effects of mirabegron may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Use is not recommended in women of childbearing potential not using contraception unless the potential benefit to the patient outweighs the risk to the fetus. AU TGA pregnancy category: B3 US FDA pregnancy category: C Comments: -Women who become pregnant during treatment with this drug are encouraged to contact their physician.

In animals, embryofetal toxicities, including heart malformations (dilated aorta cardiomegaly), pulmonary malformations, postimplantation loss, wavy ribs, delayed ossification, and decreased number of ossified sternebrae, metacarpi or metatarsi, have been reported at doses associated with maternal toxicity and significantly higher than would be expected in humans. There are no controlled data in human pregnancy. AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.