What is pilocarpine used for?

What is Pilocarpine Used For?

Pilocarpine is a cholinergic agonist used primarily for treating dry mouth (xerostomia) in patients with Sjögren's syndrome or following head and neck radiation, for managing presbyopia, and historically for lowering intraocular pressure in glaucoma, though it is now rarely used as first-line glaucoma therapy. 1

FDA-Approved Indications

Pilocarpine hydrochloride tablets are FDA-approved for two specific conditions 1:

• Treatment of dry mouth from salivary gland hypofunction caused by radiotherapy for head and neck cancer 1
• Treatment of dry mouth symptoms in patients with Sjögren's syndrome 1

Primary Clinical Uses

Sjögren's Syndrome and Xerostomia

Pilocarpine is highly effective for managing dry mouth and dry eye symptoms in Sjögren's syndrome, with the standard dosage of 20 mg/day (5 mg four times daily) showing greater improvement in dry mouth than dry eye symptoms. 2

• Pilocarpine works by binding to muscarinic receptors, stimulating secretion from salivary and sweat glands while improving tear production 2
• Salivary flow increases 2- to 3-fold compared to placebo, with effects maintained throughout 12 weeks of treatment 2, 3
• In clinical trials, 54% of patients receiving pilocarpine showed improvement versus 25% on placebo 4
• Peak salivary flow levels are maintained for at least 1-2 hours after administration 4

Treatment algorithm for Sjögren's syndrome 2:

• Mild glandular dysfunction: Start with non-pharmacological stimulation (sugar-free acidic candies, lozenges, or chewing gum) 2
• Moderate dysfunction or failed non-pharmacological approaches: Initiate pilocarpine 5 mg four times daily 2
• Severe dry eye with no salivary output: Add saliva substitution to pilocarpine therapy 2

Radiation-Induced Xerostomia

Pilocarpine significantly reduces radiation-induced xerostomia when used both during and after head and neck radiotherapy 5:

• When started concurrently with radiation and continued for 3 months post-treatment, pilocarpine produces mean subjective xerostomia scores of 40.3 mm versus 57 mm with placebo (P = 0.02) 5
• Objective xerostomia grades are also significantly better: 2.2 with pilocarpine versus 2.6 with placebo (P = 0.01) 5

Presbyopia Management

In 2021,1.25% pilocarpine ophthalmic solution (Vuity) was FDA-approved for daily use to treat presbyopia, representing a novel non-surgical management option. 6

• Critical safety warning: Retinal detachment and retinal tears have been reported with miotics, including 1.25% topical pilocarpine 6
• Mandatory screening: Dilated fundus examination is required in all patients prior to initiation to identify pre-existing retinal holes, tears, or breaks 6
• Individuals with pre-existing retinal disease are at increased risk for complications 6

Glaucoma (Historical Use)

Pilocarpine is now rarely used as first-line medication for glaucoma, though it remains useful as perioperative medication to prevent IOP spikes after laser trabeculoplasty. 6

• Evidence from systematic reviews indicates that initial pilocarpine medication is associated with more glaucoma progression than surgery in severe open-angle glaucoma 6
• Contemporary first-line medications (prostaglandin analogues, alpha2-agonists, topical carbonic anhydrase inhibitors) have replaced pilocarpine for primary glaucoma treatment 6
• Perioperative pilocarpine is effective and well-tolerated for preventing IOP spikes during the first 24 hours after laser trabeculoplasty 6
• Topical pilocarpine 2% solution four times daily or continuous delivery systems (Ocusert P-40) can reduce IOP in open-angle glaucoma 7

Adverse Effects and Monitoring

The most common side effect is excessive sweating, occurring in over 40% of patients with Sjögren's syndrome, though only approximately 2% discontinue treatment due to adverse effects. 2

• Most adverse events are mild and tolerable in nature 4
• Sweating is the primary reason for treatment discontinuation when it occurs 2
• Cevimeline, an alternative muscarinic agonist, may have fewer systemic side effects but is not as widely available globally 2
• No evidence of tolerance to pilocarpine's pharmacological effects has been observed during prolonged administration up to 5 months 4

Important Clinical Caveats

• Drug-induced ocular mucous membrane pemphigoid: Pilocarpine (along with timolol) can produce OMMP-like disease ranging from self-limited to progressive disease indistinguishable from true OMMP 6
• Retinal complications with ophthalmic formulation: The risk of retinal detachment and tears necessitates pre-treatment dilated fundus examination 6
• Pressure-lowering for myopia: Timolol (not pilocarpine specifically) failed to show retardation of myopia progression, and IOP-lowering approaches are not recommended for myopia control 6