Glycopyrronium Bromide

(BAN, rINN)
Glycopyrronium Bromide Chemical formula
Synonyms: AHR-504; Bromuro de glicopirronio; Glikopironyum Bromür; Glycopyrrolate nium, bromure de; Glykopyrroniumbromid; Glykopyrroniumbromidi. 3-( ium bromide.
Cyrillic synonym: Гликопиррония Бромид.

💊 Chemical information

Chemical formula: C19H28BrNO3 = 398.3.
CAS — 596-51-0.
ATC — A03AB02.
ATC Vet — QA03AB02.

Pharmacopoeias.

In Chin. and US.

USP 31

(Glycopyrrolate). A white, odourless, crystalline powder. Soluble 1 in 4.2 of water, 1 in 30 of alcohol, 1 in 260 of chloroform, and 1 in 35 000 of ether. Store in airtight containers.

Incompatibility.

Glycopyrronium bromide is incompatible with alkalis.

Stability.

Investigation of the compatibility of glycopyrronium bromide with infusion solutions and additives showed that the stability of glycopyrronium bromide is questionable above a pH of 6, owing to ester hydrolysis. 1 1. Ingallinera TS, et al. Compatibility of glycopyrrolate injection with commonly used infusion solutions and additives. Am J Hosp Pharm 1979; 36: 508–10. Correction. ibid.; 745.

💊 Adverse Effects, Treatment, and Precautions

As for Atropine Sulfate.

Renal impairment.

A comparison1 of the pharmacokinetics of intravenous glycopyrronium in 11 uraemic and 7 control patients indicated that the renal elimination of glycopyrronium is considerably prolonged in patients with uraemia. The mean amount of a dose excreted in the urine within 3 hours of a dose was 0.7% in the uraemic patients and 50% in the control patients; 24-hour excretion was 7% and 65%, respectively. The authors concluded that repeated or large doses of glycopyrronium should be avoided or perhaps the drug should not be used in patients with uraemia.
1. Kirvelä M, et al. Pharmacokinetics of glycopyrronium in uraemic patients. Br J Anaesth 1993; 71: 437–9.

💊 Interactions

💊 Pharmacokinetics

Glycopyrronium bromide is poorly absorbed from the gastrointestinal tract; about 10 to 25% is absorbed after an oral dose. Glycopyrronium bromide penetrates the blood-brain barrier only poorly. Glycopyrronium is excreted in bile and urine.
1. Kaltiala E, et al. The fate of intravenous [ H]glycopyrrolate in man. J Pharm Pharmacol 1974; 26: 352–4
2. Ali-melkkilä TM, et al. Pharmacokinetics of IM glycopyrronium. Br J Anaesth 1990; 64: 667–9
3. Rautakorpi P, et al. Pharmacokinetics of glycopyrrolate in children. J Clin Anesth 1994; 6: 217–20.

💊 Uses and Administration

Glycopyrronium bromide is a quaternary ammonium antimuscarinic with peripheral effects similar to those of atropine. After intramuscular doses, onset of effects is within 15 to 30 minutes; vagal blocking effects last for 2 to 3 hours and antisialagogue effects persist for up to 7 hours. After intravenous doses, onset of actions occurs within 1 minute. Glycopyrronium bromide is used similarly to atropine in anaesthetic practice. It has also been used in the iontophoretic treatment of hyperhidrosis and as an adjunct in the treatment of peptic ulcer disease. It is also under investigation for the treatment of chronic moderate to severe drooling in children. See under headings below for details of dosage in specific indications.

Anaesthesia.

Glycopyrronium bromide is given as a premedicant before general anaesthesia to diminish the risk of vagal inhibition of the heart and to reduce salivary and bronchial secretions. It is given in doses of 200 to 400 micrograms intravenously or intramuscularly before the induction of anaesthesia; alternatively, it may be given in a dose of 4 to 5 micrograms/kg to a maximum of 400 micrograms. If necessary, similar or lower doses may be given intravenously during the operation and repeated if required. A suggested dosage for premedication in neonates is 5 micrograms/kg given intravenously or intramuscularly; doses in children aged 1 month and over are 4 to 8 micrograms/kg up to a maximum of 200 micrograms. Glycopyrronium bromide is given before or with anticholinesterases to counteract their muscarinic effects when they are used to reverse the effects of competitive muscle relaxants. The dose is glycopyrronium bromide 200 micrograms intravenously per 1 mg of neostigmine (or per 5 mg of pyridostigmine); alternatively, it may be given in a dose of 10 to 15 micrograms/kg intravenously with neostigmine 50 micrograms/kg. A suggested dosage for neonates and children is 10 micrograms/kg intravenously with neostigmine 50 micrograms/kg. Glycopyrronium bromide can be given mixed in the same syringe with the anticholinesterase, and it has been suggested that greater cardiovascular stability results from use in this way.

Gastrointestinal disorders.

Antimuscarinics, including glycopyrronium bromide, have a limited role as antispasmodics, and have been used as adjuncts in the treatment of peptic ulcer disease. As an adjunct in the treatment of peptic ulcer disease the usual initial dose of glycopyrronium bromide has been 3 to 6 mg daily by mouth in divided doses adjusted according to response to a maximum of 8 mg daily; a maintenance dose of 1 mg twice daily is often adequate. Doses of 100 to 200 micrograms have been given by intramuscular or intravenous injection.

Hyperhidrosis.

Adverse effects generally preclude oral use of antimuscarinics for the management of hyperhidrosis, but glycopyrronium, has been applied topically as an alternative to aluminium salts. In studies involving 22 patients with the Frey syndrome (localised flushing and sweating on eating) glycopyrronium bromide as 1 and 2% cream or roll-on solution gave good control of symptoms;1 patients tended to prefer the roll-on lotion as it was easier to apply. Topical hyoscine as 0.25, 1, or 3% solution or cream also gave control of sweating, but was associated with a much higher incidence of adverse effects. Patients with diabetic gustatory sweating have also noted a reduction in the frequency and severity of episodes after applying glycopyrronium 0.5% cream.2 Glycopyrronium bromide has also been used as a 0.05% solution in the iontophoretic treatment of hyperhidrosis.
1. Hays LL, et al. The Frey syndrome: a simple, effective treatment. Otolaryngol Head Neck Surg 1982; 90: 419–25
2. Shaw JE, et al. A randomised controlled trial of topical glycopyrrolate, the first specific treatment for diabetic gustatory sweating. Diabetologia 1997; 40: 299–301.

Palliative care.

Glycopyrronium bromide is used in palliative care as an alternative to hyoscine to reduce excessive respiratory secretions. A dose of 200 micrograms may be given subcutaneously or intramuscularly every 4 hours. Alternatively, a dose of 0.6 to 1.2 mg may be given by continuous subcutaneous infusion over 24 hours.

Respiratory-tract disorders.

Antimuscarinics have potent bronchodilatory activity and some, such as ipratropium, may be used in the management of reversible airways obstruction. Glycopyrronium has been studied, although it is not one of the preferred drugs.
1. Schroeckenstein DC, et al. Twelve-hour bronchodilation in asthma with a single aerosol dose of the anticholinergic compound glycopyrrolate. J Allergy Clin Immunol 1988; 82: 115–19
2. Gilman MJ, et al. Comparison of aerosolized glycopyrrolate and metaproterenol in acute asthma. Chest 1990; 98: 1095–8
3. Cydulka RK, Emerman CL. Effects of combined treatment with glycopyrrolate and albuterol in acute exacerbation of chronic obstructive pulmonary disease. Ann Emerg Med 1995; 25: 470–3.

💊 Preparations

USP 31: Glycopyrrolate Injection; Glycopyrrolate Tablets.

Proprietary Preparations

Arg.: Acpan; Austral.: Robinul; Austria: Robinul; Belg.: Robinul; Denm.: Robinul; Fin.: Robinul; Ger.: Robinul; Hong Kong: Robinul†; Norw.: Robinul; NZ: Robinul; S.Afr.: Robinul; Swed.: Robinul; UK: Robinul; USA: Robinul. Multi-ingredient: Fin.: Gastrodyn comp. Used as an adjunct in: Belg.: Robinul-Neostigmine; Denm.: Robinul-Neostigmin; Fin.: Glycostigmin; Robinul-Neostigmin; Norw.: Robinul-Neostigmin; Swed.: Robinul-Neostigmin; Switz.: Robinul-Neostigmine; UK: Robinul-Neostigmine.
Published May 08, 2019.