4.1. Therapeutic indications

Obgemsa is indicated in symptomatic treatment of adult patients with overactive bladder (OAB) syndrome.

4.2. Posology and method of administration

Posology

The recommended dose is 75 mg once daily.

Special populations

Renal impairment

No dose adjustment for vibegron is recommended for patients with mild, moderate, or severe renal impairment (15 mL/min < GFR < 90 mL/min and not requiring dialysis). Vibegron has not been studied in patients with end-stage renal disease (GFR < 15 mL/min with or without haemodialysis) and is therefore not recommended in these patients (see section 5.2).

Hepatic impairment

No dose adjustment for vibegron is recommended for patients with mild to moderate hepatic impairment (Child-Pugh A and B). Vibegron has not been studied in patients with severe hepatic impairment (Child-Pugh C) and is therefore not recommended in this patient population (see section 5.2).

Paediatric population

The safety and efficacy of vibegron in children below 18 years of age have not yet been established.

No data are available.

Method of administration

Oral administration, with or without food. Swallow with a glass of water.

Obgemsa 75 mg film-coated tablets may also be crushed, mixed with a tablespoon (approximately 15 mL) of soft food (e.g. applesauce) and taken immediately with a glass of water.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

Patients with bladder outlet obstruction and patients taking antimuscarinics medicinal products for OAB

Urinary retention has been reported in patients taking vibegron. The risk of urinary retention may be increased in patients with bladder outlet obstruction and also in patients taking muscarinic antagonist medicinal product concomitantly with vibegron treatment. Signs and symptoms of urinary retention should be monitored before and during the treatment with vibegron, particularly in patients with clinically significant bladder outlet obstruction, in patients with conditions predisposing for bladder outlet obstruction, and in patients taking muscarinic antagonist medicinal product concomitantly with vibegron.

Vibegron should be discontinued in patients who develop urinary retention.

Excipients

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'.

4.5. Interaction with other medicinal products and other forms of interaction

Vibegron is a substrate for cytochrome P450 (CYP) 3A4, multiple UGT enzymes and the efflux transporter P-glycoprotein (P-gp).

Medicinal products affecting the exposure of vibegron

CYP3A4/P-gp inhibitors

Vibegron exposure (AUC) was increased 2.1--and 1.6-fold in the presence of the strong and moderate inhibitor of CYP3A/P-gp ketoconazole and diltiazem, respectively, in healthy volunteers. No dose-adjustment is needed when vibegron is combined with strong and moderate inhibitors of CYP3A and/or P-gp.

CYP3A4/P-gp inducers

Vibegron AUC was not affected by repeat-dose administration of rifampicin, a strong inducer of CYP3A/P-gp, in healthy volunteers, while vibegron Cmax was 86% higher. No dose adjustment is needed for vibegron when administered with CYP3A or P-gp inducers.

Effect of vibegron on other medicinal products.

A single dose of 100 mg vibegron increased Cmax and AUC by 21% and 11%, respectively, of the P-gp substrate digoxin in healthy volunteers. Serum digoxin concentrations should be monitored and used for titration of the digoxin dose to obtain the desired clinical effect.

The potential for interaction with P-gp by vibegron should be considered when combined with sensitive P-gp substrates with narrow therapeutic index e.g. dabigatran etexilate, apixaban or rivaroxaban.

Vibegron is an inhibitor of OCT1 in vitro. This interaction has not been studied in vivo and the clinical relevance is currently unknown.

Pharmacodynamic interactions

Co-administration of vibegron with metoprolol, a representative beta-blocker, or amlodipine, a representative vasodilator, did not result in a clinically meaningful decrease or increase in systolic blood pressure (SBP) relative to metoprolol alone or amlodipine alone.

Paediatric population

Interaction studies have only been performed in adults.

4.6. Fertility, pregnancy and lactation

Women of childbearing potential

Vibegron is not recommended in women of childbearing potential not using contraception.

Pregnancy

There are no or limited amount of data from the use of vibegron in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3).

Vibegron is not recommended during pregnancy. When pregnancy is planned or diagnosed, treatment with vibegron should be stopped and, if appropriate, alternative therapy should be started.

Breast-feeding

It is unknown whether vibegron/metabolites are excreted in human milk.

Available non-clinical data in animals have shown excretion of vibegron/metabolites in milk (see section 5.3).

A risk to the newborns/infants cannot be excluded.

Vibegron should not be used during breast-feeding.

Fertility

The effect of vibegron on human fertility has not been established. Studies in animals have not shown effects on female or male rat fertility (see section 5.3).

4.7. Effects on ability to drive and use machines

Obgemsa has no or negligible influence on the ability to drive and use machines.

4.8. Undesirable effects

Summary of the safety profile

The most frequently reported adverse reactions include urinary tract infection (6.6%), headache (5.0%), diarrhoea (3.1%) and nausea (3.0%).

The frequency of adverse drug reactions that led to treatment discontinuation is 0.9%. The most common adverse reactions leading to treatment discontinuation are: headache (0.5%), constipation, diarrhoea, nausea and rash (0.2% each).

Tabulated list of adverse reactions

The table below reflects the adverse reactions observed with vibegron obtained from the phase 3 12-week study, phase 3 long-term extension study and post-marketing data.

The frequency of adverse reactions is defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000) and not known (cannot be established from the available data).

Table 1: Adverse reactions reported for vibegron 75 mg

System organ class

Adverse reaction

Frequency

Infections and infestations

Urinary tract infection

Common

Nervous system disorders

Headache

Common

Vascular disorders

Hot flush

Uncommon

Gastrointestinal disorders

Constipation, Diarrhoea, Nausea

Common

Skin and subcutaneous tissue disorders

Rasha

Uncommon

Renal and urinary disorders

Urinary retentionb

Uncommon

Investigations

Residual urine volume increased

Common

a includes rash pruritic and rash erythematous

b includes urinary straining

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: https://yellowcard.mhra.gov.uk/ or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

The cases of overdose have been reported in a dose range between 100 and 375 mg per day. All observed adverse events following the reported overdose were non-serious. The reported adverse events were gastrointestinal disorders, headache and dyspnoea.

In case of suspected overdose, treatment should be symptomatic and supportive.