Key points
- We recommend to consult your poison centre with the use of this antidote.
- This antidote is only available through the Special Access Program. Accessibility may vary according to the hospital and the province.
- The use of physostigmine is contra-indicated in mixed drug poisoning or poisoning of unknown etiology, particularly when accompanied by QRS widening or any other intraventricular conduction problem.
- Close monitoring and careful titration is necessary to avoid cholinergic toxicity from too rapid physostigmine administration (either from repeat dosing frequency or infusions).
- Onset of action occurs between 5 and 10 minutes after IV administration and the duration varies between 30 min and 5 hours depending on the severity of the anticholinergic poisoning to be reversed.
+ Synonyms and other terms
- Anticholium®
- Antilirium®
- Physostigmine salicylate
+ Indications
- Anticholinergic symptoms: pure, moderate, or severe.
- Anticholinergic delirium.
+ Dosage
+ Pediatric Dose
- 0.01-0.02 mg/kg IV injection (max. 0.5 mg per dose).
- Doses may be repeated every 20-30 minutes until desired clinical effect is achieved (maximum 2 mg in the first hour).
- Physostigmine infusions have been successfully used in doses of up to 0.03 mg/kg/h (max 2 mg/h) for a period of 16.5 hrs to reverse anticholinergic symptoms.
+ Adult Dose
- 0.5 mg IV injection.
- Doses may be repeated every 20-30 minutes until desired clinical effect is achieved (maximum 2 mg in the first hour).
- Physostigmine infusions have been successfully used at doses of up to 2 mg/h for a period of 8 hrs to reverse anticholinergic symptoms.
+ Renal Impairment
- No data suggests that the dose should be modified for short-term use.
+ Hepatic Impairment
- No data suggests that the dose should be modified for short-term use.
+ Hemodialysis Patient
- No data suggests that the dose should be modified for short-term use.
+ Pregnancy
- Do not hesitate to use physostigmine during pregnancy if the anticipated toxic effects pose a significant risk of morbidity or mortality.
- No data suggests that the dose should be modified for short-term use.
+ Obese or Overweight Patient
- No data suggests that the dose should be modified for short-term use.
+ Adverse effects
- Muscarinic cholinergic effects such as bradycardia, atrioventricular block, asystole, nausea, vomiting, miosis, salivation, bronchorrhea, bronchospasm.
- Generalized convulsions, muscle weakness and fasciculation if there is significant stimulation of nicotinic cholinergic receptors.
+ Monitoring
- Cardiac monitoring and a neurological examination are recommended regularly, once an hour minimum, during physostigmine infusions in order to detect cholinergic signs (bronchorrhea, miosis), that would indicate a need to reduce the dose.
+ End of treatment
- Sustained resolution of anticholinergic symptoms.
+ Special Notes on Administration
Intravenous Route (IV)
- Direct IV:
- Administer 0.4 mg/ml undiluted solution by direct IV at a maximum rate of 1 mg/min in adults and 0.5 mg/min in children.
- May be diluted in NS to facilitate administration of smaller doses.
- Continuous IV infusion:
- Suggested Preparation:
- 6 mg (15 ml) in 235 ml D5W.
- Final volume = 250 ml.
- Final concentration = 0.024 mg/ml.
- Suggested Preparation:
Subcutaneous Route (SC)
- Possible alternative to IV route.
Intramuscular Route (IM)
- Possible alternative to IV route (peak absorption may not occur before 20-30 minutes).
Intraosseous Route (IO)
- No available data.
Enteral Route (OG or NG Tube)
- Not recommended as first-pass effect is too great for rapid systemic efficiency.
Compatibility
Partial list only. Consult the pharmacist on duty at your health care facility.
- Compatible solutes: NS, D5W.
- Y-site compatibility: No data available.
- Y-site Incompatibilities: No data available.
Stability
- Keep the ampoules at room temperature between 15°C and 25°C.
- No data stability for the diluted solution in NS or D5W, use fresh solution only.
+ Available products
- Anticholium 1x5ml, German PZN 02398165, Special Access Program = yes.
- Anticholium 5x5ml, German PZN 02398142, Special Access Program = yes.
- Anticholium contains; Physostigmine salicylate 2mg/5ml
- Ordering procedure:
- Request an authorization to the Special Access Program of Health Canada
- Submit an order and the letter of authorization of the Special Access Program to vertrieb@koehler-chemie.de
- Ordering procedure:
+ Amount required to treat a person weighting 70kg during 24 hours
- At least 20 mg.
+ References
“2012 Annual Meeting of the North American Congress of Clinical Toxicology (NACCT) October 1–6, 2012 Las Vegas, NV, USA.” 2012. Clinical Toxicology 50 (7). Taylor & Francis:574–720.
Arens, Ann M., Krishna Shah, Suad Al-Abri, Kent R. Olson, and Tom Kearney. 2017a. “Safety and Effectiveness of Physostigmine: A 10-Year Retrospective Review.” Clinical Toxicology, July. Taylor & Francis, 1–7.
Boroughf, William J. 2016. “Physostigmine.” In Critical Care Toxicology, edited by Jeffrey Brent, Keith Burkhart, Paul Dargan, Benjamin Hatten, Bruno Megarbane, and Robert Palmer, 25:1–14. Cham: Springer International Publishing.
Burns, M. J., C. H. Linden, A. Graudins, R. M. Brown, and K. E. Fletcher. 2000. “A Comparison of Physostigmine and Benzodiazepines for the Treatment of Anticholinergic Poisoning.” Annals of Emergency Medicine 35 (4):374–81.
Dawson, Andrew H., and Nicholas A. Buckley. 2016a. “Pharmacological Management of Anticholinergic Delirium - Theory, Evidence and Practice.” British Journal of Clinical Pharmacology 81 (3):516–24.
Hail, Stacey Lynn, Adebisi Obafemi, and Kurt C. Kleinschmidt. 2013. “Successful Management of Olanzapine-Induced Anticholinergic Agitation and Delirium with a Continuous Intravenous Infusion of Physostigmine in a Pediatric Patient.” Clinical Toxicology 51 (3):162–66.
Hartvig, P., L. Wiklund, and B. Lindström. 1986. “Pharmacokinetics of Physostigmine after Intravenous, Intramuscular and Subcutaneous Administration in Surgical Patients.” Acta Anaesthesiologica Scandinavica 30 (2):177–82.
Kulka, Peter J., Hakki Toker, Jörg Heim, Alexander Joist, and Jens Jakschik. 2004. “Suspected Central Anticholinergic Syndrome in a 6-Week-Old Infant.” Anesthesia and Analgesia 99 (5):1376–78; table of contents.
Phillips, Michelle A., Nicole M. Acquisto, Rachel M. Gorodetsky, and Timothy J. Wiegand. 2014. “Use of a Physostigmine Continuous Infusion for the Treatment of Severe and Recurrent Antimuscarinic Toxicity in a Mixed Drug Overdose.” Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology 10 (2):205–9.
Pileggi, Dominic J., and Aaron M. Cook. 2016. “Neuroleptic Malignant Syndrome.” The Annals of Pharmacotherapy 50 (11):973–81.
Schulz, M., and A. Schmoldt. 1994. “Successful Physostigmine Treatment of Acute Dothiepin Intoxication.” Die Pharmazie 49 (8):614.
Suchard, Jeffrey R. 2003. “Assessing Physostigmine’s Contraindication in Cyclic Antidepressant Ingestions.” The Journal of Emergency Medicine 25 (2):185–91.
Watkins, Joseph W., Evan S. Schwarz, Anna M. Arroyo-Plasencia, Michael E. Mullins, and Toxicology Investigators Consortium investigators. 2015a. “The Use of Physostigmine by Toxicologists in Anticholinergic Toxicity.” Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology 11 (2):179–84.
