Myrbetriq

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Myrbetriq

Classes

Beta-3 Adrenergic Agonists

Administration
Oral Administration

If a dose is missed, administer it as soon as possible unless more than 12 hours have passed. If 12 hours have passed, skip the missed dose and take the next dose at the usual time.
Mirabegron extended-release tablets and extended-release oral suspension are not substitutable on a mg-per-mg basis. Do not combine extended-release tablets and extended-release oral suspension to achieve the total dose.

Oral Solid Formulations

Extended-release tablets
Adult patients: administer with or without food.
Pediatric patients: administer with food.
Swallow whole with water. Do not crush, chew, or divide.

Oral Liquid Formulations

Extended-release oral suspension (8 mg/mL after reconstitution)
Discard the pouch and desiccant; tap the closed bottle several times to loosen the granules.
Add 100 mL of water to the bottle and shake vigorously for 1 minute. Let stand for 10 to 30 minutes and then shake vigorously again for 1 minute. If granules have not dispersed, shake again for 1 minute.
Take with food.
Storage: Store reconstituted suspension at 20 to 25 degrees C (68 to 77 degrees F) for up to 28 days; discard unused portion after 28 days.

Adverse Reactions
Severe

vasculitis / Delayed / 0-1.0
stroke / Early / 0.4-0.4
atrial fibrillation / Early / 0.2-0.2
ocular hypertension / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known

Moderate

hypertension / Early / 7.5-24.0
constipation / Delayed / 1.6-4.7
cystitis / Delayed / 2.1-2.1
sinus tachycardia / Rapid / 1.2-1.6
palpitations / Early / 0-1.0
gastritis / Delayed / 0-1.0
nephrolithiasis / Delayed / 0-1.0
vaginitis / Delayed / 0-1.0
elevated hepatic enzymes / Delayed / Incidence not known
urinary retention / Early / Incidence not known
confusion / Early / Incidence not known
hallucinations / Early / Incidence not known
blurred vision / Early / Incidence not known

Mild

infection / Delayed / 0-24.4
pharyngitis / Delayed / 3.5-5.8
headache / Early / 2.1-4.1
xerostomia / Early / 2.8-2.8
back pain / Delayed / 2.8-2.8
dizziness / Early / 2.7-2.7
sinusitis / Delayed / 0-2.7
influenza / Delayed / 2.6-2.6
nausea / Early / 0.4-2.3
cough / Delayed / 2.3-2.3
rhinitis / Early / 0-2.3
arthralgia / Delayed / 1.3-2.1
diarrhea / Early / 1.2-1.5
abdominal pain / Early / 0.6-1.4
fatigue / Early / 1.2-1.4
dyspepsia / Early / 0-1.0
bladder discomfort / Early / 0-1.0
vaginal irritation / Early / 0-1.0
urticaria / Rapid / 0-1.0
rash / Early / 0-1.0
pruritus / Rapid / 0-1.0
purpura / Delayed / 0-1.0
insomnia / Early / Incidence not known
anxiety / Delayed / Incidence not known
xerophthalmia / Early / Incidence not known

Common Brand Names

Myrbetriq

Dea Class

Rx

Description

Oral beta-3 adrenoreceptor agonist
Used for overactive bladder (OAB) in adults as monotherapy or in combination with bladder-specific antimuscarinics and for neurogenic detrusor overactivity (NDO) in pediatric patients 3 years and older
May increase blood pressure; do not use in patients with severe uncontrolled hypertension

Dosage And Indications
For the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urinary urgency, and urinary frequency. Oral dosage (extended-release tablets) Adults

25 mg PO once daily, initially. May increase the dose to 50 mg PO once daily after 4 to 8 weeks if needed.

For the treatment of neurogenic detrusor overactivity (neurogenic bladder). Oral dosage (extended-release oral suspension) Children and Adolescents 3 to 17 years weighing 35 kg or more

48 mg PO once daily. May increase dose to 80 mg PO once daily after 4 to 8 weeks if needed.

Children and Adolescents 3 to 17 years weighing 22 to 34 kg

32 mg PO once daily initially. May increase dose to 64 mg PO once daily after 4 to 8 weeks if needed. Evaluate patients periodically for potential dosage adjustments based on weight.

Children and Adolescents 3 to 17 years weighing 11 to 21 kg

24 mg PO once daily. May increase dose to 48 mg PO once daily after 4 to 8 weeks if needed. Evaluate patients periodically for potential dosage adjustments based on weight.

Oral dosage (extended-release tablets) Children and Adolescents 3 to 17 years weighing 35 kg or more

25 mg PO once daily. May increase dose to 50 mg PO once daily after 4 to 8 weeks if needed.

Dosing Considerations
Hepatic Impairment

Extended-release tablet
Mild hepatic impairment (Child Pugh Class A): No dosage adjustment needed.
Moderate hepatic impairment (Child Pugh Class B): Do not exceed 25 mg once daily.
Severe hepatic impairment (Child Pugh Class C): Not recommended.
 
Extended-release oral suspension
Mild hepatic impairment (Child Pugh Class A): No dosage adjustment needed.
Moderate hepatic impairment (Child Pugh Class B):
Patients weighing 11 to 21 kg: Do not exceed 24 mg once daily.
Patients weighing 22 to 34 kg: Do not exceed 32 mg once daily.
Patients weighing 35 kg or more: Do not exceed 48 mg once daily.
Severe hepatic impairment (Child Pugh Class C): Not recommended.

Renal Impairment

Extended-release tablet
eGFR 30 mL/minute/1.73 m2 or more: No dosage adjustment needed.
eGFR 15 to 29 mL/minute/1.73 m2: Do not exceed 25 mg once daily.
eGFR less than 15 mL/minute/1.73 m2: Not recommended.
 
Extended-release oral suspension
eGFR 30 mL/minute/1.73 m2 or more: No dosage adjustment needed.
eGFR 15 to 29 mL/minute/1.73 m2:
Patients weighing 11 to 21 kg: Do not exceed 24 mg once daily.
Patients weighing 22 to 34 kg: Do not exceed 32 mg once daily.
Patients weighing 35 kg or more: Do not exceed 48 mg once daily.
eGFR less than 15 mL/minute/1.73 m2: Not recommended.
 
Intermittent hemodialysis
Not recommended in patients with end-stage renal disease (ESRD) or patients on dialysis.

Drug Interactions

Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as diphenhydramine may be increased when co-administered with mirabegron. Diphenhydramine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with mirabegron may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Mirabegron is a moderate inhibitor of CYP2D6.
Acetaminophen; Chlorpheniramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary. (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary. (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary. (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6.
Acetaminophen; Dextromethorphan: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Dextromethorphan; Phenylephrine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Diphenhydramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as diphenhydramine may be increased when co-administered with mirabegron. Diphenhydramine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with mirabegron may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of mirabegron could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If mirabegron is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Mirabegron is a moderate inhibitor of CYP2D6.
Amitriptyline: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Amoxapine: (Major) Concomitant use of amoxapine with drugs that can inhibit cytochrome P450 2D6, such as mirabegron, may require lower doses than usually prescribed for either amoxapine or mirabegron. Furthermore, whenever mirabegron is withdrawn from co-therapy, an increased dose of the amoxapine may be required. It is desirable to monitor amoxapine plasma levels whenever amoxapine is going to be co-administered with another drug known to be an inhibitor of P450 2D6.
Aripiprazole: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of mirabegron. Patients receiving both a CYP3A inhibitor plus mirabegron may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; mirabegron is a moderate CYP2D6 inhibitor.
Asenapine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as asenapine may be increased when co-administered with mirabegron. Asenapine has been shown to be a CYP2D6 substrate in vitro. Appropriate monitoring and dose adjustment may be necessary.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6.
Atazanavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with mirabegron as there is a potential for elevated cobicistat concentrations. Mirabegron is a moderate CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6 and CYP3A4.
Atomoxetine: (Moderate) Because atomoxetine is primarily metabolized by CYP2D6, concurrent use of CYP2D6 inhibitors such as mirabegron may theoretically increase the risk of atomoxetine-induced adverse effects. Monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, QT prolongation).
Brimonidine; Timolol: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as timolol may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Brompheniramine; Dextromethorphan; Phenylephrine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6.
Carvedilol: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as carvedilol may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Celecoxib; Tramadol: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as tramadol may be increased when co-administered with mirabegron. Tramadol is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlordiazepoxide; Amitriptyline: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlorpheniramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6. (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlorpheniramine; Dextromethorphan: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary. (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary. (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary. (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with mirabegron may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Mirabegron is a moderate inhibitor of CYP2D6. (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with mirabegron may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of mirabegron could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If mirabegron is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Mirabegron is a moderate inhibitor of CYP2D6. (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlorpheniramine; Phenylephrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlorpheniramine; Pseudoephedrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlorpromazine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpromazine may be increased when co-administered with mirabegron. Chlorpromazine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Clomipramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Clozapine: (Moderate) Patients receiving clozapine in combination with a CYP2D6 inhibitor such as mirabegron should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. If the inhibitor is discontinued after dose adjustments are made, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary. Mirabegron is a moderate inhibitor of CYP2D6, and clozapine is a CYP2D6 substrate. Elevated plasma concentrations of clozapine may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects.
Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with mirabegron as there is a potential for elevated cobicistat concentrations. Mirabegron is a moderate CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6 and CYP3A4.
Codeine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6. (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as promethazine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6. (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as promethazine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Darifenacin: (Moderate) Mirabegron should be administered with caution in patients taking antimuscarinic medications for the treatment of overactive bladder, such as darifenacin, because of the risk of urinary retention. In addition, mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as darifenacin may be increased when administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with mirabegron as there is a potential for elevated cobicistat concentrations. Mirabegron is a moderate CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6 and CYP3A4.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is warranted when cobicistat is administered with mirabegron as there is a potential for elevated cobicistat concentrations. Mirabegron is a moderate CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6 and CYP3A4.
Delavirdine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as delavirdine may be increased when administered with mirabegron. Delavirdine has been shown to be a CYP2D6 substrate invitro. Appropriate monitoring and dose adjustment may be necessary.
Desipramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Bupropion: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as diphenhydramine may be increased when co-administered with mirabegron. Diphenhydramine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary. (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Guaifenesin: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Quinidine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Digoxin: (Major) Mirabegron increases digoxin exposure approximately 30% with concomitant use. Measure serum digoxin concentrations prior to initiating mirabegron. Reduce the digoxin dose by approximately 15% to 30% or modify the dosing frequency when given together. Monitor digoxin concentrations and titrate the dose to obtain the desired clinical effect.
Diphenhydramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as diphenhydramine may be increased when co-administered with mirabegron. Diphenhydramine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Diphenhydramine; Ibuprofen: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as diphenhydramine may be increased when co-administered with mirabegron. Diphenhydramine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Diphenhydramine; Naproxen: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as diphenhydramine may be increased when co-administered with mirabegron. Diphenhydramine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Diphenhydramine; Phenylephrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as diphenhydramine may be increased when co-administered with mirabegron. Diphenhydramine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Dolasetron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as dolasetron may be increased when co-administered with mirabegron. Dolasetron is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Donepezil: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as donepezil may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Donepezil; Memantine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as donepezil may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Dorzolamide; Timolol: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as timolol may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Doxepin: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Doxorubicin Liposomal: (Major) Mirabegron is a moderate CYP2D6 inhibitor; doxorubicin is a substrate of both CYP2D6 and CYP3A4. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of mirabegron and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Doxorubicin: (Major) Mirabegron is a moderate CYP2D6 inhibitor; doxorubicin is a substrate of both CYP2D6 and CYP3A4. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of mirabegron and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Duloxetine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as duloxetine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Dutasteride; Tamsulosin: (Moderate) The effect of mirabegron on tamsulosin pharmacokinetics was determined in drug interaction studies, there was a lack of pharmacokinetic interaction. However, it is recommended that mirabegron be administered with caution in patients taking other medications in the setting of risks for urinary obstruction because of the risk of urinary retention. This includes caution when used with tamsulosin. In addition, mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as tamsulosin may be increased when co-administered with mirabegron.
Eliglustat: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of mirabegron and eliglustat is not recommended. In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both mirabegron and a moderate or strong CYP3A inhibitor is contraindicated in all patients. Mirabegron is a moderate CYP2D6 inhibitor; eliglustat is a CYP2D6 and CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as mirabegron, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with mirabegron as there is a potential for elevated cobicistat concentrations. Mirabegron is a moderate CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6 and CYP3A4.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with mirabegron as there is a potential for elevated cobicistat concentrations. Mirabegron is a moderate CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6 and CYP3A4.
Fesoterodine: (Moderate) Mirabegron should be administered with caution in patients taking antimuscarinic medications for the treatment of overactive bladder, such as fesoterodine, because of the risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these medicines together.
Flecainide: (Major) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as flecainide may be increased when administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Fluoxetine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as fluoxetine may be increased when co-administered with mirabegron. Fluoxetine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Fluphenazine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as fluphenazine may be increased when co-administered with mirabegron. Fluphenazine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Fluticasone; Umeclidinium; Vilanterol: (Minor) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as umeclidinium may be increased when co-administered with mirabegron. Umeclidinium is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary. Monitor for dry mouth, constipation, blurred vision or urinary retention.
Fluvoxamine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as fluvoxamine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Fosamprenavir: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as fosamprenavir may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with mirabegron is necessary; the risk is increased in CYP2D6 poor metabolizers. Based on in vitro data, gefitinib is metabolized to O-desmethyl gefitinib by CYP2D6 and mirabegron is a CYP2D6 inhibitor. In healthy CYP2D6 poor metabolizers, the concentration of O-desmethyl gefitinib was not measurable and mean exposure to gefitinib was 2-fold higher compared to extensive metabolizers. The impact of CYP2D6 inhibitors on gefitinib pharmacokinetics has not been evaluated; however, the manufacturer recommends precautions based on exposure in patients with poor CYP2D6 metabolism.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with mirabegron may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of mirabegron could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If mirabegron is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Mirabegron is a moderate inhibitor of CYP2D6.
Haloperidol: (Moderate) Mirabegron is a substrate and a moderate inhibitor of CYP2D6. Exposure of drugs metabolized by CYP2D6 such as haloperidol may be increased when co-administered with mirabegron. Haloperidol is primarily metabolized by CYP2D6. In addition, in vitro data suggest that haloperidol has CYP2D6 inhibitory effects and has the potential to decrease the metabolism of CYP2D6 substrates such as mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with mirabegron may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of mirabegron could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If mirabegron is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Mirabegron is a moderate inhibitor of CYP2D6.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with mirabegron may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of mirabegron could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If mirabegron is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Mirabegron is a moderate inhibitor of CYP2D6.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with mirabegron may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of mirabegron could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If mirabegron is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Mirabegron is a moderate inhibitor of CYP2D6.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with mirabegron may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of mirabegron could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If mirabegron is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Mirabegron is a moderate inhibitor of CYP2D6.
Iloperidone: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as iloperidone may be increased whenadministered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Imipramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Indacaterol: (Minor) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as indacaterol may be increased when administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Indacaterol; Glycopyrrolate: (Minor) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as indacaterol may be increased when administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Isocarboxazid: (Moderate) It is unclear if it is safe to use of mirabegron with MAOI therapy. It may be best to use caution and avoid use together if possible. Use of mirabegron (a selective beta-3 adrenergic agonist) with non-selective MAOIs may theoretically result in an increased risk for high blood pressure. Mirabegron has increased blood pressure at clinically used doses (e.g., 50 mg/day). In these studies, at the maximum recommended dose of 50 mg/day, the mean maximum increase in systolic/diastolic blood pressure was approximately 3.5/1.5 mmHg greater than placebo. Beta-3 selectivity is usually lost at doses above those used clinically for overactive bladder (e.g, 200 mg/day PO). Sympathomimetic adrenergic agonists are typically contraindicated in patients receiving MAOIs. When administering a MAOI in close proximity to such a drug, at least 2 weeks should usually elapse between discontinuation of 1 agent and initiation of therapy with the other; consult the specific product literature for precise recommendations.
Ivermectin: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as ivermectin may be increased when co-administered with mirabegron. Ivermectin has been shown to be a CYP2D6 substrate in vitro. Appropriate monitoring and dose adjustment may be necessary.
Lopinavir; Ritonavir: (Moderate) Concurrent administration of mirabegron with ritonavir may result in elevated plasma concentrations of ritonavir. Mirabegron is a moderate inhibitor of CYP2D6. Ritonavir is a CYP2D6 substrate. Caution and close monitoring are advised if these drugs are administered together.
Maprotiline: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as maprotiline may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Meclizine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as meclizine may be increased when co-administered with mirabegron. Meclizine has been shown to be a CYP2D6 substrate in vitro. Appropriate monitoring and dose adjustment may be necessary.
Methadone: (Moderate) Concurrent use of methadone with mirabegron may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Monitor closely until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Methadone is a substrate for CYP3A4 and CYP2D6. Mirabegron is a moderate inhibitor of CYP2D6. Discontinuation of mirabegron in a patient taking methadone chronically may decrease methadone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If mirabegron is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate.
Metoprolol: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure. Metoprolol is a CYP2D6 substrate; mirabegron is a moderate CYP2D6 inhibitor. In drug interaction studies, mirabegron increased the Cmax and AUC of metoprolol by 90% and 229%, respectively, after multiple doses of 160 mg mirabegron IR tablets once daily for 5 days and a single dose of 100 mg metoprolol tablet administered before and concomitantly with mirabegron.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure. Metoprolol is a CYP2D6 substrate; mirabegron is a moderate CYP2D6 inhibitor. In drug interaction studies, mirabegron increased the Cmax and AUC of metoprolol by 90% and 229%, respectively, after multiple doses of 160 mg mirabegron IR tablets once daily for 5 days and a single dose of 100 mg metoprolol tablet administered before and concomitantly with mirabegron.
Mexiletine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as mexiletine may be increased when co-administered with mirabegron. Mexiletine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Mirtazapine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs partially metabolized by CYP2D6 such as mirtazapine may be increased when co-administered with mirabegron. Mirtazapine as a substrate for several CYP450 isoenzymes including 2D6, 1A2, and 3A4 in vitro. Appropriate monitoring and dose adjustment may be necessary.
Monoamine oxidase inhibitors: (Moderate) It is unclear if it is safe to use of mirabegron with MAOI therapy. It may be best to use caution and avoid use together if possible. Use of mirabegron (a selective beta-3 adrenergic agonist) with non-selective MAOIs may theoretically result in an increased risk for high blood pressure. Mirabegron has increased blood pressure at clinically used doses (e.g., 50 mg/day). In these studies, at the maximum recommended dose of 50 mg/day, the mean maximum increase in systolic/diastolic blood pressure was approximately 3.5/1.5 mmHg greater than placebo. Beta-3 selectivity is usually lost at doses above those used clinically for overactive bladder (e.g, 200 mg/day PO). Sympathomimetic adrenergic agonists are typically contraindicated in patients receiving MAOIs. When administering a MAOI in close proximity to such a drug, at least 2 weeks should usually elapse between discontinuation of 1 agent and initiation of therapy with the other; consult the specific product literature for precise recommendations.
Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with mirabegron. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as mirabegron, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible. Dose adjustment may be necessary.
Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with mirabegron. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as mirabegron, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible. Dose adjustment may be necessary.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as palonosetron may be increased when co-administered with mirabegron. Palonosetron is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Nirmatrelvir; Ritonavir: (Moderate) Concurrent administration of mirabegron with ritonavir may result in elevated plasma concentrations of ritonavir. Mirabegron is a moderate inhibitor of CYP2D6. Ritonavir is a CYP2D6 substrate. Caution and close monitoring are advised if these drugs are administered together.
Nortriptyline: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Olanzapine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as olanzapine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Olanzapine; Fluoxetine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as fluoxetine may be increased when co-administered with mirabegron. Fluoxetine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary. (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as olanzapine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Olanzapine; Samidorphan: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as olanzapine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of olice

ridine and mirabegron is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and mirabegron may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If mirabegron is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and mirabegron is a moderate CYP2D6 inhibitor.
Ondansetron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs partially metabolized by CYP2D6, such as ondansetron may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Oxybutynin: (Moderate) Mirabegron should be administered with caution in patients taking antimuscarinic medications for the treatment of overactive bladder, such as oxybutynin, because of the risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Palonosetron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as palonosetron may be increased when co-administered with mirabegron. Palonosetron is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Paroxetine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with mirabegron is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and mirabegron is a moderate CYP2D6 inhibitor.
Pentamidine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as systemic pentamidine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Perphenazine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as perphenazine may be increased when co-administered with mirabegron. Perphenazine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Perphenazine; Amitriptyline: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as perphenazine may be increased when co-administered with mirabegron. Perphenazine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary. (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Phenelzine: (Moderate) It is unclear if it is safe to use of mirabegron with MAOI therapy. It may be best to use caution and avoid use together if possible. Use of mirabegron (a selective beta-3 adrenergic agonist) with non-selective MAOIs may theoretically result in an increased risk for high blood pressure. Mirabegron has increased blood pressure at clinically used doses (e.g., 50 mg/day). In these studies, at the maximum recommended dose of 50 mg/day, the mean maximum increase in systolic/diastolic blood pressure was approximately 3.5/1.5 mmHg greater than placebo. Beta-3 selectivity is usually lost at doses above those used clinically for overactive bladder (e.g, 200 mg/day PO). Sympathomimetic adrenergic agonists are typically contraindicated in patients receiving MAOIs. When administering a MAOI in close proximity to such a drug, at least 2 weeks should usually elapse between discontinuation of 1 agent and initiation of therapy with the other; consult the specific product literature for precise recommendations.
Pimozide: (Moderate) Caution is advisable during concurrent use of pimozide and moderate CYP2D6 inhibitors such as mirabegron. Pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. While the manufacturer has provided no guidance regarding pimozide use with mild or moderate CYP2D6 inhibitors, concurrent use of the drug with more potent inhibitors of CYP2D6 is contraindicated. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Pirfenidone: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as pirfenidone may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Promethazine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as promethazine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Promethazine; Dextromethorphan: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as promethazine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary. (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Promethazine; Phenylephrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as promethazine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Propafenone: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as propafenone may be increased when administered with mirabegron. This is especially true for patients who are also CYP2D6 poor metabolizers (PMs). Therefore, appropriate monitoring and dose adjustment may be necessary.
Propranolol: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as propranolol may be increased when co-administered with mirabegron. Propranolol is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as propranolol may be increased when co-administered with mirabegron. Propranolol is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Protriptyline: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Quinine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as quinine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Ranolazine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as ranolazine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Ritonavir: (Moderate) Concurrent administration of mirabegron with ritonavir may result in elevated plasma concentrations of ritonavir. Mirabegron is a moderate inhibitor of CYP2D6. Ritonavir is a CYP2D6 substrate. Caution and close monitoring are advised if these drugs are administered together.
Sertraline: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as sertraline may be increased when co-administered with mirabegron. Sertraline has been shown to be a CYP2D6 substrate and a mild to moderate inhibitor of CYP2D6 in vitro. Mirabegron exposure may also increase. Appropriate monitoring and dose adjustment may be necessary.
Solifenacin: (Moderate) Limit the solifenacin dose to 5 mg/day when used in combination mirabegron, and monitor for signs and symptoms of urinary retention.
Tamsulosin: (Moderate) The effect of mirabegron on tamsulosin pharmacokinetics was determined in drug interaction studies, there was a lack of pharmacokinetic interaction. However, it is recommended that mirabegron be administered with caution in patients taking other medications in the setting of risks for urinary obstruction because of the risk of urinary retention. This includes caution when used with tamsulosin. In addition, mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as tamsulosin may be increased when co-administered with mirabegron.
Tetrabenazine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as tetrabenazine may be increased when administered with mirabegron. Two of the primary metabolites of tetrabenazine, alpha-dihydrotetrabenzaine (alpha-HTBZ) and beta-dihydrotetrabenazine (beta-HTBZ), are substrates for CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Thioridazine: (Contraindicated) Mirabegron is a moderate inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, due to elevated serum concentrations of thioridazine.
Timolol: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as timolol may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Tolterodine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as tolterodine may be increased when administered with mirabegron. Tolterodine is primarily metabolized by CYP2D6. Mirabegron should also be used with caution in patients taking antimuscarinic medications for the treatment of overactive bladder because of the risk of urinary retention. Appropriate monitoring and dose adjustment may be necessary. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Tramadol: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as tramadol may be increased when co-administered with mirabegron. Tramadol is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Tramadol; Acetaminophen: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as tramadol may be increased when co-administered with mirabegron. Tramadol is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Tranylcypromine: (Moderate) It is unclear if it is safe to use of mirabegron with MAOI therapy. It may be best to use caution and avoid use together if possible. Use of mirabegron (a selective beta-3 adrenergic agonist) with non-selective MAOIs may theoretically result in an increased risk for high blood pressure. Mirabegron has increased blood pressure at clinically used doses (e.g., 50 mg/day). In these studies, at the maximum recommended dose of 50 mg/day, the mean maximum increase in systolic/diastolic blood pressure was approximately 3.5/1.5 mmHg greater than placebo. Beta-3 selectivity is usually lost at doses above those used clinically for overactive bladder (e.g, 200 mg/day PO). Sympathomimetic adrenergic agonists are typically contraindicated in patients receiving MAOIs. When administering a MAOI in close proximity to such a drug, at least 2 weeks should usually elapse between discontinuation of 1 agent and initiation of therapy with the other; consult the specific product literature for precise recommendations.
Tricyclic antidepressants: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Trimipramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Trospium: (Moderate) Mirabegron should be administered with caution in patients taking antimuscarinic medications for the treatment of overactive bladder, such as oxybutynin, because of the risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Umeclidinium: (Minor) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as umeclidinium may be increased when co-administered with mirabegron. Umeclidinium is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary. Monitor for dry mouth, constipation, blurred vision or urinary retention.
Umeclidinium; Vilanterol: (Minor) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as umeclidinium may be increased when co-administered with mirabegron. Umeclidinium is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary. Monitor for dry mouth, constipation, blurred vision or urinary retention.
Venlafaxine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as venlafaxine may be increased when co-administered with mirabegron. Venlafaxine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Vilazodone: (Minor) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as vilazodone may be increased when co-administered with mirabegron. However, CYP2D6 is a minor metabolic pathway for vilazodone. Appropriate monitoring may be necessary.
Warfarin: (Moderate) When given in combination, mirabegron increased the mean warfarin (S- and R-warfarin) Cmax by approximately 4% and the AUC by approximately 9% when administered as a single dose of 25 mg warfarin after multiple doses of 100 mg mirabegron. Following a single dose administration of 25 mg warfarin, mirabegron had no effect on INR and prothrombin time. However, the effect of mirabegron on multiple doses of warfarin and on warfarin pharmacodynamic end points such as INR and prothrombin time has not been fully investigated. Therefore, careful monitoring and dose adjustment may be necessary.

How Supplied

Mirabegron Oral Gran F/Recon: 1mL, 8mg
Myrbetriq Oral Tab ER: 25mg, 50mg

Maximum Dosage
Adults

50 mg/day PO for the extended-release tablets; safety and efficacy have not been established for the extended-release oral suspension.

Geriatric

50 mg/day PO for the extended-release tablets; safety and efficacy have not been established for the extended-release oral suspension.

Adolescents

weighing 35 kg or more: 80 mg/day PO for the extended-release oral suspension; 50 mg/day PO for the extended-release tablets.
weighing 22 to 34 kg: 64 mg/day PO for the extended-release oral suspension; safety and efficacy have not been established for the extended-release tablets.
weighing 11 to 21 kg: 48 mg/day PO for the extended-release oral suspension; safety and efficacy have not been established for the extended-release tablets.

Children

3 to 12 years weighing 35 kg or more: 80 mg/day PO for the extended-release oral suspension; 50 mg/day PO for the extended-release tablets.
3 to 12 years weighing 22 to 34 kg: 64 mg/day PO for the extended-release oral suspension; safety and efficacy have not been established for the extended-release tablets.
3 to 12 years weighing 11 to 21 kg: 48 mg/day PO for the extended-release oral suspension; safety and efficacy have not been established for the extended-release tablets.
1 to 2 years: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism Of Action

Mirabegron is a human beta-3 adrenergic receptor (AR) agonist. Mirabegron relaxes the detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle by activation of beta-3 AR which increases bladder capacity. Although mirabegron showed very low intrinsic activity for cloned human beta-1 AR and beta-2 AR, results in humans indicate that beta-1 AR stimulation occurred at a mirabegron dose of 200 mg.

Pharmacokinetics

Mirabegron is administered orally. It is extensively distributed throughout the body. Approximately 71% is bound to human plasma proteins with a moderate affinity for albumin and alpha-1 acid glycoprotein. In vitro, it distributes to erythrocytes with concentrations about 2-fold higher than in plasma. Mirabegron is metabolized via multiple pathways involving dealkylation, oxidation, (direct) glucuronidation, and amide hydrolysis. Mirabegron is the major circulating component. Two non-active metabolites were observed in human plasma and are phase 2 glucuronides representing 16% and 11% of total exposure, respectively. Although in vitro studies suggest a role for CYP2D6 and CYP3A4 in the oxidative metabolism of mirabegron, in vivo results indicate that these isozymes play a limited role in the overall elimination of the drug. Renal elimination of mirabegron is primarily through active tubular secretion along with glomerular filtration. Urinary elimination of unchanged mirabegron is dose-dependent and ranges from approximately 6% after a daily dose of 25 mg to 12.2% after a daily dose of 100 mg. In studies, 55% of radiolabeled mirabegron was recovered in the urine and 34% in the feces; approximately 25% of unchanged mirabegron was recovered in urine and 0% in feces. The terminal elimination half-life is approximately 50 hours.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP2D6, P-gp
Mirabegron is a moderate CYP2D6 inhibitor and may reduce the elimination of other drugs dependent on this isozyme for metabolism. Because of the limited role of CYP3A4 and CYP2D6 in the overall elimination of mirabegron in vivo, drug-drug interactions with inducers or inhibitors of these 2 enzymes do not have a significant effect on mirabegron disposition and no dosage adjustments of mirabegron are needed. Involvement of butylcholinesterase, uridine diphospho-glucuronosyltransferases (UGT) and possibly alcohol dehydrogenase metabolism has been demonstrated for mirabegron. Mirabegron is also a substrate for butyrylcholinesterase, UGT, the efflux transporter P-glycoprotein (P-gp), and the influx organic cation transporters (OCT) OCT1, OCT2, and OCT3; however, clinically significant drug-drug interactions related to these drug transporters are unclear. A small effect of mirabegron on digoxin, a P-gp substrate with a narrow therapeutic index, has been noted and requires caution with concurrent use.

Oral Route

After oral administration in adult patients, mirabegron Cmax is attained at approximately 3.5 hours. Absolute bioavailability is dose-proportional, increasing from 29% to 35% as dose increases from 25 to 50 mg; mean Cmax and AUC increase more than dose-proportionally, especially for doses greater than 50 mg. In the overall population of males and females, a 2-fold increase in dose from 50 to 100 mg increased Cmax and AUC by approximately 2.9- and 2.6-fold, respectively, whereas a 4-fold increase in dose from 50 to 200 mg increased Cmax and AUC by approximately 8.4- and 6.5-fold. There are no clinically significant differences in mirabegron pharmacokinetics when administered with or without food in adult patients. Steady state concentrations are achieved within 7 days. Plasma exposure of mirabegron at steady state is approximately double that seen after a single dose.

Pregnancy And Lactation
Pregnancy

There are no adequate and well-controlled studies of the use of mirabegron during human pregnancy to inform drug-associated risk for birth defects or miscarriage. Mirabegron administration to pregnant animals during organogenesis resulted in reversible skeletal variations (in rats) at 22-fold (via AUC) the maximum recommended human dose (MRHD) of 50 mg/day and decreased fetal body weights (in rabbits) at 14-fold the MRHD. At maternally toxic exposures in rats (96-fold), decreased fetal weight and increased fetal mortality were observed and, in rabbits (36-fold), cardiac findings (fetal cardiomegaly and fetal dilated aortae) were observed. Women who become pregnant during mirabegron treatment are encouraged to contact their physician.

Use mirabegron with caution during breast-feeding. There is no information regarding the presence of mirabegron in human milk, the effects on the breast-fed child, or the effects on milk production. Mirabegron-related material was present in rat milk and in the stomach of nursing pups following administrations of a single 10 mg/kg oral dose of radiolabeled mirabegron to lactating rats. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.