GUIDELINE GL 2018/38 Version No. 2.0 ADULT - Physostigmine for the management of Version No. 1.0 delirium associated with anticholinergic agent toxicity

PURPOSE

This guideline provides recommendations regarding best practice on the use of physostigmine for the management of delirium associated with anticholinergic agent toxicity in adults.

SCOPE

This guideline applies to all nursing, medical and pharmacist staff within the Metro South Hospital and Health Service. Prescribing physostigmine for this indication must be on the advice of or under the supervision of a Clinical Toxicologist.

DEFINITIONS

Anticholinergic agents: 1. Sedating antihistamines (e.g. promethazine, cyproheptadine, dexchlorpheniramine, cyclizine, diphenhydramine, doxylamine, pheniramine trimeprazine) 2. Anticholinergic drugs (e.g. Benztropine, biperiden, benzhexol [trihexyphenidyl] ) 3. Anticholinergic plants (e.g. Brugmansia species or Angel’s Trumpet) 4. Other medicines with anticholinergic properties. Certain antidepressants and antipsychotics may have the potential to cause anticholinergic delirium

INDICATION

• Confirmed or suspected anticholinergic toxicity.

CONTRAINDICATIONS

Enhanced cholinergic tone can predictably exacerbate many conditions. Physostigmine should only be used in critical care areas where cardiac monitoring is available. Physostigmine should be used with caution in patients with the following conditions: • Asthma/Chronic Obstructive Pulmonary Disease

• Cardiovascular Disease • Peripheral Vascular Disease

Page 1 of 4

• Gastrointestinal obstruction

• Urinary obstruction • Bradycardia • Concomitant depolarizing neuromuscular blocker (succinylcholine/suxamethonium) or choline esters (bethanechol) – risk of cholinergic crisis

PRECAUTIONS

• Sulfite sensitivity – some physostigmine product formulations contain sodium bisulfite, which may cause anaphylaxis and severe asthma in susceptible individuals.

PRESENTATION

• 2mg in 5mL ampoule • 1mg/mL in 2mL ampoule = 2mg/2mL ampoule

DILUTION / RECONSTITUTION

• 2mg in 5mL ampoule: Dilute 2mg up to 10mL with 0.9% sodium chloride to give a concentration of 0.2mg/mL

• 1mg/mL in 2mL ampoule: Dilute up to 10mL with 0.9% sodium chloride to give a concentration of 0.2mg/mL

DOSAGE & ADMINISTRATION

• 0.4mg (400mcg=2mL) IV as a bolus over 10 seconds. • Dose may be repeated every 10 minutes as required up to a maximum dose of 2mg. • A response should be seen after 0.4-1.2mg • Because of the short half-life of physostigmine, repeat dosing after 60 minutes may be necessary to treat recurrence of toxicity. • Total maximum dose in 24 hours is 4mg. If more than 4mg is required, contact a Clinical Toxicologist for advice.

RISKS (Adverse Effects)

• Hypersensitivity • Cholinergic toxicity. If excessive cholinergic effects occur, discontinue use. Signs of cholinergic excess include: o bradycardia o bronchorrhoea o bronchospasm o diarrhoea o seizures

Page 2 of 4

• Management of cholinergic toxicity includes supportive care and intravenous atropine. Atropine should be readily available in the area where physostigmine is administered.

SUPPLY

• Physostigmine is not licensed in Australia. A Special Access Scheme (SAS) Category A form must be completed for each patient before the product can be supplied.

REFERENCES

1. Micromedex. Physostigmine Drug Monograph [Accessed September 2017] 2. Andrew H. Dawson & Nicholas A. Buckley. Pharmacological management of anticholinergic delirium -theory, evidence and practice. Br J Clin Pharmacology 2015; 81: 516-524. 3. Burns MJ, Linden CH, Graudins A et al. A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Annals of Emergency Medicine 2000; 35:374-381. 4. Stilson M, Kelly K & Suchard J. Physostigmine as an Antidote. CJEM 2001; 4: 47-8 5. Arens et al. Safety and Effectiveness of Physostigmine: A 10-year retrospective review. Clin Tox 2017; 1-7.

GUIDELINE DETAILS

Guideline Number Portfolio Executive Director GL 2018/38 Dr Susan O’Dwyer Executive Director Medical Services Guideline Name Metro South Health Physostigmine for the management of delirium associated with anticholinergic agent toxicity Approving Officer Chair, Metro South Health Medicines Policy Reference Management Committee PL 2016/0048 Metro South Health Medicines Management Approving Date Committee 22 August 2018

Supersedes Effective From ADULT - Physostigmine for the management of 22 March 2018 delirium associated with anticholinergic agent toxicity v2.0 Date of Last Review

March 2018 Procedure Author

Pharmacist Advanced, Metro South Health Medicines Management Committee Date of Next Review March 2019

Page 3 of 4

Version Amendment 1.0 New 2.0 Change to volume of concentration for 1mg/mL in 2mL ampoule to ensure 0.2mg/mL

Page 4 of 4