Optacarpine

Approved Indications:

• Primary open-angle glaucoma:
  Lowers intraocular pressure (IOP) by increasing aqueous humor outflow.
• Acute angle-closure glaucoma with pupillary block:
  Used to induce miosis prior to iridectomy or laser surgery.
• Ocular hypertension:
  Reduces IOP in patients who are intolerant or unresponsive to other agents.
• Xerostomia (dry mouth):
• Caused by radiation therapy for head and neck cancers.
• Associated with Sjögren’s syndrome (autoimmune origin).

Clinically Accepted Off-label Uses:

• Adie’s tonic pupil:
  Improves near response and pupil reactivity in parasympathetic denervation.
• Pilocarpine diagnostic testing:
  Used in dilute concentrations to confirm cholinergic supersensitivity.
• Visual enhancement in presbyopia:
  Investigated as low-dose ophthalmic solution for temporary near vision improvement.

Routes of Administration:

• Ophthalmic (eye drops)
• Oral (tablets)

Ophthalmic Dosage (for Glaucoma and Ocular Hypertension):

Adults:

• Instill 1–2 drops of pilocarpine 1%–4% solution into the affected eye(s) up to 4 times daily.

Acute angle-closure glaucoma:

• Instill 1 drop of 2% solution every 5–10 minutes for up to 6 doses, then reduce frequency based on clinical need.

Children (≥2 years):

• Use 1% solution cautiously; dosing based on physician discretion.

Oral Dosage (for Xerostomia):

Adults:

• 5 mg orally three times daily, increase to 10 mg TID if tolerated.

Maximum Dose: 30 mg/day
Duration: Long-term use may be needed; periodic reassessment recommended.

Renal Impairment:

• Use with caution; initiate at lowest dose.

Hepatic Impairment:

• Caution advised; monitor closely.

Elderly:

• Begin at lower doses due to increased sensitivity to cholinergic effects.

Administration Notes:

• Oral tablets should be taken with water.
• Ophthalmic drops should be used at regular intervals and not during night driving due to miosis-induced poor night vision.

Pilocarpine Hydrochloride is a direct-acting muscarinic cholinergic receptor agonist, primarily targeting M3 receptors. In the eye, it causes contraction of the ciliary muscle and sphincter pupillae, leading to miosis and increased trabecular meshwork outflow, which reduces intraocular pressure. In the salivary glands, it stimulates muscarinic receptors to increase saliva production. Systemically, it may also stimulate sweat and other exocrine glands due to its parasympathomimetic activity. These effects collectively alleviate symptoms of glaucoma and xerostomia.

Ophthalmic Use:

• Absorption: Minimal systemic absorption; primarily local effect
• Onset: 10–30 minutes
• Duration: 4–8 hours (depends on formulation strength)

Oral Use:

• Absorption: Rapid after ingestion
• Bioavailability: Approximately 40–70%
• Tmax: 0.5–1 hour
• Half-life: ~0.75 to 1 hour
• Metabolism: Hepatic (mainly)
• Elimination: Primarily via renal excretion as metabolites

• Pregnancy:
• Category C (oral use): Animal studies show adverse fetal effects. No adequate human data. Use only if benefits outweigh risks.
• Ophthalmic form: Low systemic absorption; considered safer under physician supervision.
• Lactation:
• Unknown whether excreted in breast milk.
• Use with caution; monitor for cholinergic side effects in the infant.
• Clinical Guidance:
• Avoid high-dose oral therapy in pregnancy and lactation.
• Ophthalmic use generally considered safe when medically necessary.

• Primary Class: Cholinergic agonist
• Subclass: Direct muscarinic receptor stimulant (Parasympathomimetic agent)

• Hypersensitivity to pilocarpine or any component of the formulation
• Acute iritis or anterior uveitis
• Uncontrolled asthma (oral formulation)
• Gastrointestinal or urinary tract obstruction
• Cardiovascular instability (e.g., bradycardia, hypotension with oral use)
• Children under 2 years (safety not established)

• Asthma/COPD: Risk of bronchospasm; avoid oral use in uncontrolled cases
• Cardiovascular disease: May exacerbate bradycardia and hypotension
• Peptic ulcer or GI spasm: Cholinergic stimulation may worsen symptoms
• Ocular inflammation: Avoid in iritis or uveitis
• Night vision impairment: Miosis may reduce low-light vision—advise caution when driving at night
• Systemic exposure (oral): Monitor for sweating, salivation, diarrhea, or dizziness in susceptible individuals

Ophthalmic Use:

• Common:
• Eye irritation
• Blurred or dim vision
• Brow ache
• Lacrimation
• Less Common:
• Conjunctival hyperemia
• Retinal detachment (rare but serious)
• Reduced night vision

Oral Use:

• Common:
• Sweating
• Salivation
• Nausea
• Flushing
• Chills
• Rare/Serious:
• Bronchospasm
• Bradycardia
• Syncope
• Gastrointestinal cramps

Note: Most adverse effects are dose-related and resolve after dose reduction or discontinuation.

• Anticholinergics (e.g., atropine): May antagonize pilocarpine's effects
• Beta-blockers: Additive bradycardic or hypotensive effects
• Cholinesterase inhibitors (e.g., donepezil): Increased risk of cholinergic toxicity
• Alcohol: May potentiate hypotension and dizziness
• CYP2A6 metabolism (oral form): Limited evidence of interaction; monitor when used with strong CYP inducers/inhibitors

• Pilocarpine 1.25% ophthalmic solution recently approved (e.g., Vuity®) for treatment of presbyopia in adults.
• Xerostomia management guidelines continue to recommend pilocarpine as first-line pharmacologic therapy for radiation-induced dry mouth and Sjögren’s syndrome.
• No major guideline changes in glaucoma protocols involving pilocarpine, though its use has declined due to newer agents.

Ophthalmic Solution:

• Store at 15°C to 25°C (59°F to 77°F)
• Protect from light and moisture
• Do not freeze
• Keep container tightly closed

Oral Tablets:

• Store at 20°C to 25°C (68°F to 77°F)
• Protect from humidity
• Store in original packaging

General Handling:

• Shake ophthalmic solution well before use (if directed)
• Keep all forms out of reach of children
• Discard any unused portion after expiry