New Perspective on Anticholinergic Toxicity: Rivastigmine Emerges as a Practical Alternative During Physostigmine Shortages

Published: May 2025
Source: Mehrpour O, Marini M, Nakhaee S. Regul Toxicol Pharmacol. 2025;105857. DOI:10.1016/j.yrtph.2025.105857

Background

Physostigmine has long been the cornerstone antidote for managing severe anticholinergic toxicity. However, the recent halt in its U.S. manufacturing and international supply constraints have left emergency providers needing viable alternatives.

In a timely and comprehensive study, Dr. Omid Mehrpour and colleagues evaluate rivastigmine—an acetylcholinesterase inhibitor traditionally used for dementia—as a credible substitute, offering both the mechanistic rationale and a clinical workflow for toxicologic emergencies.

Key Findings and Dosing Strategy for Rivastigmine

Rivastigmine, unlike physostigmine, is an irreversible cholinesterase inhibitor with a longer duration of action and multiple delivery options (oral and transdermal). It offers central muscarinic reversal but with slower CNS penetration.

The authors provide a clear, weight-based dosing algorithm:

Oral Administration of Rivastigmine

• Initial dose: 6 mg once

• Then: 3 mg every hour as needed

• Maximum: 12 mg in 24 hours

Transdermal Patch Dosing

• ≤100 kg: 9.5 mg/24 h patch

• >100 kg: 13.3 mg/24 h patch

• Pediatrics (<35 kg): 4.6 mg/24 h patch

Apply between the scapulae to reduce tampering; do not cut the patch.

Additionally, emerging intranasal microemulsion delivery systems may offer rapid CNS onset and improved usability.

Safety Considerations and Contraindications

While rivastigmine appears safe in observational reports, caution is advised in the following situations:

• TCA overdose with QRS >100 ms

• Bradycardia, AV block, hypotension

• Known allergy or contact dermatitis to rivastigmine

Common adverse effects to monitor:

• Nausea, diarrhea, bronchospasm, bradycardia

• Cholinergic crisis, especially in polypharmacy overdose

Clinical Implications

With global drug shortages now a recurrent challenge, rivastigmine stands out as a cost-effective, accessible, and evidence-supported alternative. Already stocked in most hospitals for dementia care, rivastigmine could be repurposed for toxicology with minimal logistical barriers.

Dr. Mehrpour’s team offers a concise, printable dosing algorithm for bedside use, supporting toxicologists and emergency clinicians facing physostigmine scarcity.

Access the Full Study:

Rivastigmine as an Alternative in Physostigmine Shortage for Anticholinergic Toxicity Treatment
Regulatory Toxicology and Pharmacology, 2025