Why is pilocarpine no longer used as a first-line treatment?

October 8, 2025 •

3 min read

For many decades, pilocarpine was a standard treatment for glaucoma, but its use has significantly declined in favor of newer medications. This shift was driven by pilocarpine’s poor patient tolerability, inconvenient dosing schedule, and the emergence of more effective and better-tolerated pharmacological alternatives.

Quick Summary

Pilocarpine is less commonly used due to its severe side effects, frequent dosing requirements, and the availability of superior alternative medications. Modern treatments offer better tolerability, more convenient dosing, and fewer complications for conditions like glaucoma and dry mouth.

Key Points

Poor Tolerability: Severe side effects like blurred vision, eye irritation, and systemic issues such as excessive sweating led to poor patient acceptance.
Inconvenient Dosing: For conditions like glaucoma, pilocarpine’s short half-life required frequent, multiple-times-daily applications, negatively impacting patient compliance.
Superior Alternatives Exist: The development of newer medications like prostaglandin analogues for glaucoma and other cholinergic agonists for dry mouth offered better efficacy and fewer side effects.
Modern Niche Applications: Though no longer first-line, pilocarpine remains relevant for specific uses, including new formulations for presbyopia (Vuity) and tablets for severe dry mouth.
Vehicle Issues: Older ophthalmic formulations of pilocarpine were highly acidic, causing significant burning and stinging upon instillation.

Pilocarpine, a cholinergic agonist, was once a cornerstone of treatment for several conditions, most notably glaucoma and dry mouth (xerostomia). By stimulating muscarinic receptors, it increases aqueous outflow from the eye to lower intraocular pressure (IOP) and boosts saliva and tear production from exocrine glands. While its mechanisms of action were effective, a combination of significant drawbacks led to its widespread replacement in first-line therapy.

The primary reasons for pilocarpine's decline

Several key issues contributed to pilocarpine falling out of favor among both patients and clinicians. These problems centered on its demanding regimen, unpleasant side effects, and the introduction of advanced alternatives that offered a better overall patient experience.

Poor patient tolerability and side effects

One of the most significant factors driving patients away from pilocarpine was its range of bothersome and sometimes severe side effects. For ophthalmic use in glaucoma, the medication's miotic effect (constricting the pupil) and other irritants caused considerable discomfort and functional vision issues. Common ocular side effects included blurred or dim vision, eye irritation, headaches, brow ache, and prolonged pupillary constriction. Rare but serious complications like retinal detachment were also possible. For systemic use (oral tablets for dry mouth), pilocarpine caused widespread cholinergic side effects such as excessive sweating, nausea, gastrointestinal distress, urinary frequency, rhinitis, and flushing.

Inconvenient and complex dosing

For glaucoma, pilocarpine's short half-life necessitated a frequent dosing schedule, typically requiring administration four times per day. This regimen placed a substantial burden on patients, making it difficult to maintain compliance and often leading to missed doses.

Advent of superior alternatives

The 1990s saw the introduction of new drug classes for glaucoma, such as prostaglandin analogues (PGAs), offering advantages over pilocarpine. PGAs like latanoprost are highly effective at lowering IOP, require only a single daily dose, and have a more favorable side effect profile. Other glaucoma treatments, including beta-blockers, alpha-adrenergic agonists, and rho kinase inhibitors, also provide effective IOP reduction with less burdensome dosing and better tolerability. For xerostomia, other cholinergic agonists like cevimeline and various saliva substitutes are available.

Comparison Table: Pilocarpine vs. Modern Glaucoma Treatments


Feature	Pilocarpine (Ophthalmic)	Modern Alternatives (e.g., PGAs)
Dosing Frequency	3–4 times daily	Once daily (most PGAs)
Ocular Side Effects	Significant, including blurred vision, brow ache, and eye irritation	Generally mild, with some potential for redness and pigmentation changes
Systemic Side Effects	Risk of systemic effects like sweating and nausea	Minimal systemic absorption and side effects
Patient Compliance	Low due to frequent dosing and poor tolerability	High due to once-daily dosing and better tolerability
Cost	Less expensive in generic form	Variable, newer formulations may be more costly

Modern resurgence and specific indications

Despite its decline as a first-line treatment, pilocarpine is not completely obsolete. New applications include an optimized formulation (Vuity) approved in 2021 for treating presbyopia, designed to improve near vision with fewer side effects. Pilocarpine also continues to be used in specific clinical scenarios such as acute angle-closure glaucoma to lower sudden, high IOP, as oral tablets for severe dry mouth in Sjögren’s syndrome and radiation-induced xerostomia, and sometimes during eye examinations for diagnostic purposes.

Conclusion

The reasons why is pilocarpine no longer used as a first-line medication for widespread conditions like glaucoma are clear and compelling. The demanding dosing regimen, poor patient tolerability, and significant side effects made it an inferior choice compared to the safer, more convenient, and equally or more effective alternatives that emerged over time. While its role has diminished, pilocarpine is not extinct and has been revitalized in new formulations for niche applications like presbyopia and remains a relevant treatment for specific instances of dry mouth. For more information on the efficacy of pilocarpine tablets for dry mouth and eye symptoms in Sjögren's Syndrome, consult this study from the Archives of Internal Medicine.

Frequently Asked Questions

Yes, pilocarpine is still used today but primarily for specific, niche applications rather than as a first-line therapy. New formulations, like Vuity for presbyopia, have emerged, and oral tablets are still prescribed for severe dry mouth associated with conditions like Sjögren's syndrome.

Prostaglandin analogues, such as latanoprost, have largely replaced pilocarpine as the first-line treatment for glaucoma. These medications are more effective and better tolerated, with a more convenient once-daily dosing schedule.

For ophthalmic use, common side effects include blurred vision, poor night vision, eye irritation, headaches, and brow ache. For oral use, common side effects are excessive sweating, nausea, diarrhea, and increased urinary frequency.

In its ophthalmic form, pilocarpine causes the pupil to constrict (miosis). This constriction restricts the amount of light entering the eye, leading to blurred or dim vision, especially in low-light environments, and difficulty with night vision.

While oral pilocarpine (Salagen) is still used for dry mouth caused by conditions like Sjögren's syndrome, another cholinergic agonist, cevimeline (Evoxac), is also available and may cause less sweating in some patients. In addition, many over-the-counter saliva substitutes and gels are available.

A new, optimized formulation of pilocarpine eye drops, branded as Vuity, was approved to treat presbyopia. This medication uses a lower concentration and an improved vehicle to temporarily improve near vision with fewer side effects than older pilocarpine formulations.

The requirement for frequent daily dosing, up to four times for glaucoma, created a significant compliance challenge. This inconvenience, combined with its bothersome side effects, led many patients to prefer newer medications with more manageable schedules.