Glycopyrronium Other names: Glycopyrronium bromide

In patients with severe renal impairment (estimated glomerular filtration rate below 30 ml/min/1.73 m²), including those with end-stage renal disease requiring dialysis, glycopyrronium bromide should be used only if the expected benefit outweighs the potential risk. These patients should be monitored closely for potential adverse reactions.

In a clinical study in healthy volunteers, cimetidine, an inhibitor of organic cation transport which is thought to contribute to the renal excretion of glycopyrronium bromide, increased total exposure (AUC) to glycopyrronium by 22% and decreased renal clearance by 23%. Based on the magnitude of these changes, no clinically relevant drug interaction is expected when glycopyrronium bromide is co-administered with cimetidine or other inhibitors of organic cation transport.

Glycopyrronium bromide should be used with caution in patients with narrow-angle glaucoma or urinary retention.

Patients should be informed about the signs and symptoms of acute narrow-angle glaucoma and should be informed to stop using glycopyrronium and to contact their doctor immediately should any of these signs or symptoms develop.

Patients with unstable ischaemic heart disease, left ventricular failure, history of myocardial infarction, arrhythmia (excluding chronic stable atrial fibrillation), a history of long QT syndrome or whose QTc (Fridericia method) was prolonged (>450 ms for males or >470 ms for females) were excluded from the clinical trials, and therefore the experience in these patient groups is limited. Glycopyrronium should be used with caution in these patient groups.

There are no data from the use of glycopyrronium bromide in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Glycopyrronium should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the foetus.

It is unknown whether glycopyrronium bromide is excreted in human milk. However, glycopyrronium bromide (including its metabolites) was excreted in the milk of lactating rats. The use of glycopyrronium by breast-feeding women should only be considered if the expected benefit to the woman is greater than any possible risk to the infant.

Fertility

Reproduction studies and other data in animals do not indicate a concern regarding fertility in either males or females.

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

Summary of the safety profile

The most common anticholinergic adverse reaction was dry mouth (2.4%). The majority of the reports of dry mouth were suspected to be related to the medicinal product and were mild, with none being severe.

The safety profile is further characterised by other symptoms related to the anticholinergic effects, including signs of urinary retention, which were uncommon. Gastrointestinal effects including gastroenteritis and dyspepsia were also observed. Adverse reactions related to local tolerability included throat irritation, nasopharyngitis, rhinitis and sinusitis.

Summary of adverse reactions

Adverse reactions reported during the first six months of two pooled pivotal Phase III trials of 6 and 12 months duration are listed by MedDRA system organ class. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse reaction is based on the following convention: 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); not known (cannot be estimated from the available data).

Infections and infestations

Common: Nasopharyngitis¹

Uncommon: Rhinitis, Cystitis

Immune system disorders

Uncommon: Hypersensitivity, Angioedema²

Metabolism and nutrition disorders

Uncommon: Hyperglycaemia

Psychiatric disorders

Common: Insomnia

Nervous system disorders

Common: Headache³

Uncommon: Hypoaesthesia

Cardiac disorders

Atrial fibrillation Palpitations

Respiratory, thoracic and mediastinal disorders

Uncommon: Sinus congestion, Productive cough, Throat irritation, Epistaxis, Dysphonia²

Not known: Paradoxical bronchospasm²

Gastrointestinal disorders

Common: Dry mouth, Gastroenteritis

Uncommon: Nausea², Vomiting^1,2, Dyspepsia, Dental caries

Skin and subcutaneous tissue disorders

Uncommon: Rash, Pruritus²

Musculoskeletal and connective tissue disorders

Common: Musculoskeletal pain^1,2

Uncommon: Pain in extremity, Musculoskeletal chest pain

Renal and urinary disorders

Common: Urinary tract infection³

Uncommon: Dysuria, Urinary retention

General disorders and administration site conditions

Uncommon: Fatigue, Asthenia

¹ More frequent for glycopyrronium bromide than placebo in the 12 months database only.
² Reports have been received from post-approval marketing experience in association with the use of glycopyrronium bromide. These were reported voluntarily from a population of uncertain size, and it is therefore not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure. Therefore the frequency was calculated from clinical trial experience.
³ Seen more frequently for glycopyrronium bromide than placebo in elderly >75 years only.

Description of selected adverse reactions

In the pooled 6-month database the frequency of dry mouth was 2.2% versus 1.1%, of insomnia 1.0% versus 0.8%, and of gastroenteritis 1.4% versus 0.9%, for glycopyrronium bromide and placebo respectively.

Dry mouth was reported mainly during the first 4 weeks of treatment with a median duration of four weeks in the majority of patients. However in 40% of cases symptoms continued for the entire 6-month period. No new cases of dry mouth were reported in months 7-12.