Is atropine (antimuscarinic) ophthalmic solution to be administered sublingually?

From the Guidelines

Atropine ophthalmic solution should not be administered sublingually, as it is specifically formulated for topical ocular administration only. The concentration, formulation, and sterility requirements for ophthalmic preparations differ significantly from those designed for sublingual administration 1. Using ophthalmic atropine sublingually could lead to improper dosing, as the concentration in eye drops (typically 0.5% to 1%) is designed for local effect on the eye, not systemic absorption through the oral mucosa. Additionally, ophthalmic preparations often contain preservatives and other ingredients that are not intended for oral use and could potentially cause irritation or adverse effects when placed under the tongue.

Key considerations for the administration of atropine include:

• The route of administration: atropine ophthalmic solution is intended for topical ocular administration only 1
• The concentration and formulation: ophthalmic preparations have specific requirements that differ from those designed for sublingual administration 1
• The potential risks and side effects: using ophthalmic atropine sublingually could lead to improper dosing, irritation, or adverse effects 1

If sublingual atropine is medically necessary, a proper formulation specifically designed for this route of administration should be used instead. Systemic atropine for medical emergencies is typically administered via injection 1. Using medications through unintended routes of administration is dangerous and should be avoided. The most recent and highest quality study, published in 2023, supports the use of atropine ophthalmic solution for topical ocular administration only 1.

From the FDA Drug Label

ATROPINE SULFATE OPHTHALMIC SOLUTION, 1%, for topical ophthalmic use In individuals from three (3) months of age or greater 1 drop topically to the cul-de-sac of the conjunctiva, forty minutes prior to the intended maximal dilation time (2.1)

The atropine (antimuscarinic) ophthalmic solution is to be administered topically to the eye, not sublingually. The recommended administration is 1 drop to the cul-de-sac of the conjunctiva. 2

From the Research

Administration of Atropine Ophthalmic Solution

• Atropine 1% ophthalmic solution can be administered sublingually, as evidenced by studies 3, 4, 5, 6.
• The sublingual administration of atropine has been explored for various purposes, including the management of terminal respiratory secretions 3, as a contingency medical countermeasure for nerve agent toxicity 4, and for the treatment of sialorrhoea in neurological disabled patients 5, 6.

Efficacy and Safety of Sublingual Atropine

• Studies have shown that sublingual atropine can be effective in reducing or resolving terminal respiratory secretions 3 and sialorrhoea 5, 6.
• The safety and tolerability of sublingual atropine have also been evaluated, with reports of minimal side effects, such as dry mouth and unpleasant taste 4, 6.
• However, cases of atropine-induced toxicity have been reported after off-label sublingual administration of eyedrop for sialorrhoea treatment in neurological disabled patients 5.

Pharmacokinetics of Sublingual Atropine

• The systemic bioavailability of sublingual atropine has been estimated to be around 60% compared to intravenous administration 4.
• The pharmacokinetics of sublingual atropine have been characterized by large interindividual differences in absorption and elimination phases 7.
• The terminal half-life of atropine in plasma has been reported to be unaffected by the route of drug administration 7.