Pilocarpine (Ophthalmic)


VA CLASSIFICATION
Primary: OP118

Commonly used brand name(s): Adsorbocarpine; Akarpine; Isopto Carpine; Minims Pilocarpine; Miocarpine; Ocu-Carpine; Ocusert Pilo-20; Ocusert Pilo-40; P.V. Carpine Liquifilm; Pilagan; Pilocar; Pilopine HS; Piloptic-1; Piloptic-1/2; Piloptic-2; Piloptic-3; Piloptic-4; Piloptic-6; Pilostat; Spersacarpine.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antiglaucoma agent (ophthalmic)—

miotic—

Indications

Accepted

Glaucoma, open-angle (treatment)—Pilocarpine is indicated primarily for the treatment of open-angle (chronic simple) glaucoma. It may be used in conjunction with a carbonic anhydrase inhibitor, epinephrine, timolol, fluorescein, or anesthetic, antibiotic, or anti-inflammatory steroid ophthalmic solutions. {08} {33} {38}

Glaucoma, angle-closure {01} (treatment)—Pilocarpine (hydrochloride or nitrate) ophthalmic solution is indicated for use alone or in combination with carbonic anhydrase inhibitors or hyperosmotic agents to lower intraocular pressure in the emergency treatment of acute angle-closure glaucoma prior to surgery or laser iridotomy. In addition, pilocarpine may be indicated for the treatment of chronic angle-closure glaucoma.

Glaucoma, angle-closure, during or after iridectomy (treatment)— Pilocarpine (hydrochloride or nitrate) ophthalmic solution may be indicated for the treatment of angle-closure glaucoma during or after iridectomy. {01}

Glaucoma, secondary {01} (treatment)—Pilocarpine may be indicated for the treatment of nonuveitic secondary glaucoma.

Miosis induction, postoperative or
Miosis induction, following ophthalmoscopy—Pilocarpine (hydrochloride or nitrate) ophthalmic solution is indicated to produce miosis in order to counteract the effects of cycloplegics and mydriatics following surgery or ophthalmoscopic examination. {08} {38}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Pilocarpine: 208.26
    Pilocarpine hydrochloride: 244.72
    Pilocarpine nitrate: 271.27

Mechanism of action/Effect:

Pilocarpine is a parasympathomimetic that directly stimulates cholinergic receptors. It produces contraction of the iris sphincter muscle, resulting in pupillary constriction (miosis); constriction of the ciliary muscle, resulting in increased accommodation; and reduction in intraocular pressure associated with an increase in the outflow and a decrease in the inflow of aqueous humor. {24} {33}

In chronic open-angle glaucoma, the exact mechanism by which miotics lower intraocular pressure is not precisely known; however, contraction of the ciliary muscle apparently opens the intertrabecular spaces and facilitates aqueous humor outflow. {24} {33} There is also a decrease in the rate of inflow of aqueous humor. {24}

In angle-closure glaucoma, constriction of the pupil apparently pulls the iris away from the trabeculum, thereby relieving blockage of the trabecular meshwork.

Onset of action:

Miosis—Solution (1%): Within 10 to 30 minutes.

Time to peak effect:


Reduction in intraocular pressure:

Ocular system: 1.5 to 2 hours.

Solution: Within 75 minutes, depending on strength used.


Duration of action:


Miosis:

Solution: About 4 to 8 hours.



Reduction in intraocular pressure:

Ocular system: 7 days.

Solution: 4 to 14 hours, depending on strength used.



Precautions to Consider

Carcinogenicity

No long-term studies have been done. {30} {33}

Pregnancy/Reproduction

Pregnancy—
Studies have not been done in humans; {30} {33} however, ophthalmic pilocarpine may be systemically absorbed.

Studies have not been done in animals. {30} {33}

FDA Pregnancy Category C. {30} {33} {38}

Breast-feeding

It is not known whether pilocarpine is distributed into breast milk {30} {33} and problems in humans have not been documented. However, ophthalmic pilocarpine may be systemically absorbed. {07}

Pediatrics

Appropriate studies on the relationship of age to the effects of pilocarpine have not been performed in the pediatric population. However, no pediatrics-specific problems have been documented to date.


Geriatrics


Appropriate studies on the relationship of age to the effects of pilocarpine have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Belladonna alkaloids, ophthalmic or
Cyclopentolate    (concurrent use may interfere with the antiglaucoma action of pilocarpine; also, concurrent use with pilocarpine counteracts the mydriatic effects of these medications; this anti-mydriatic effect may be used to therapeutic advantage)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Asthma, bronchial
Infectious conjunctivitis or keratitis, acute—for ocular system dosage form only
» Iritis, acute, or other conditions in which pupillary constriction is undesirable
Retinal detachment, history of or predisposition to{29}
Sensitivity to pilocarpine

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Intraocular pressure determinations    (recommended at periodic intervals during therapy)




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Symptoms of systemic absorption
    
Increased sweating{29}
    
muscle tremors
    
nausea, vomiting, or diarrhea{29}
    
troubled breathing or wheezing
    
watering of mouth{29}

Incidence less frequent or rare
    
Eye pain{25}{29}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Blurred vision or change in near or far vision{02}{29}
    
decrease in night vision{25}

Incidence less frequent
    
Eye irritation{02}{29}
    
headache or browache





Overdose
For specific information on the agents used in the management of ophthalmic pilocarpine overdose, see:
   • Atropine in Anticholinergics/Antispasmodics (Systemic) monograph.
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Treatment of overdose
If accidental overdosage occurs in the eye, flushing the eye with water or normal saline. {29}

If medication is accidentally ingested, inducing emesis or performing gastric lavage. {29} Patients should be observed for signs of pilocarpine toxicity (i.e., unusual watering of mouth, unusual sweating, nausea, vomiting, and diarrhea); if these occur, therapy with anticholinergics, such as atropine, may be necessary.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Pilocarpine (Ophthalmic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to pilocarpine
Other medical problems, especially acute iritis or other conditions in which pupillary constriction is undesirable

Proper use of this medication
Proper administration technique

Washing hands immediately after application to remove any medication that may be on them

» Importance of not using more medication than the amount prescribed

» Proper dosing
Missed dose:

• For solution dosage form—Using as soon as possible; not using if almost time for next dose; using next dose at regularly scheduled time


• For gel dosage form—Using as soon as possible; not using if not remembered until next day; using next dose at regularly scheduled time


• For eye system dosage form—Replacing as soon as possible; inserting next eye system at regularly scheduled time


» Proper storage

For gel or solution dosage forms
Preventing contamination: Not touching applicator tip to any surface; keeping container tightly closed

For ocular system dosage form
Reading patient instructions carefully before using

Not using if damaged

Removing and replacing with new unit if too much medicine is being released

Precautions while using this medication
Regular visits to physician to check eye pressure during therapy

» Caution if blurred vision or change in near or far vision occurs, especially at night


Side/adverse effects
Signs of potential side effects, especially symptoms of systemic absorption or eye pain


General Dosing Information
Tolerance to pilocarpine may develop with prolonged use. Effectiveness may be restored by changing to another miotic for a short time and then resuming the original medication.

For the ocular system dosage form
The system should be placed in the eye at bedtime so that the pilocarpine-induced myopia may reach a stable level by morning. {30}

Damaged or deformed systems should not be placed or retained in the eye. If a system is believed to be associated with an unexpected increase in action of the medication, it should be removed and replaced with a new system.

For the solution dosage forms
Although some manufacturers recommend a dose of 2 drops of an ophthalmic solution at appropriate intervals, the conjunctival sac will usually hold only 1 drop.

To avoid excessive systemic absorption, patient should press finger to the lacrimal sac during and for 1 or 2 minutes following instillation of the solution.

Although some manufacturers recommend that patients not wear soft contact lenses during treatment with pilocarpine ophthalmic solution, USP medical experts do not believe this precaution is necessary unless the patient has corneal epithelial problems and the medication is to be used more often than once every 1 to 2 hours. No significant problems have been documented with opththalmic solutions containing 0.03% or less of benzalkonium chloride as a preservative that are used in patients with no significant corneal surface problems.


Ophthalmic Dosage Forms

PILOCARPINE OCULAR SYSTEM USP

Usual adult and adolescent dose
Antiglaucoma agent (ophthalmic)
Topical, to the conjunctiva, 1 ocular system delivering 20 or 40 mcg (0.02 or 0.04 mg) per hour, once every seven days. {02} {30}


Usual pediatric dose
Antiglaucoma agent (ophthalmic)
Infants: Safety and efficacy have not been established. {27}

Children: See Usual adult and adolescent dose. {27}


Usual geriatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


20 mcg (0.02 mg) per hour for seven days (Rx) [Ocusert Pilo-20{30}]


40 mcg (0.04 mg) per hour for seven days (Rx) [Ocusert Pilo-40{31}]

Canada—


20 mcg (0.02 mg) per hour for seven days (Rx) [Ocusert Pilo-20]


40 mcg (0.04 mg) per hour for seven days (Rx) [Ocusert Pilo-40]

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F). {30}

Auxiliary labeling:
   • For the eye.
   • Refrigerate. {02} {30}

Note: Include patient instructions when dispensing.



PILOCARPINE HYDROCHLORIDE OPHTHALMIC GEL

Usual adult and adolescent dose
Antiglaucoma agent (ophthalmic)
Topical, to the conjunctiva, approximately 1.5 cm (1/2-inch strip) of a 4% gel once a day at bedtime. {03} {36}


Usual pediatric dose
Antiglaucoma agent (ophthalmic)
Safety and efficacy have not been established. {27} {36}


Usual geriatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


4% (Rx) [Pilopine HS{23}{28}{36}]

Canada—


4% (Rx) [Pilopine HS{45}]

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F), in a tight container, unless otherwise specified by manufacturer. Protect from freezing. {03}

Stability:
The 5-gram size requires refrigeration; the 3.5-gram size can be stored at room temperature. {03} {23}

Auxiliary labeling:
   • For the eye.
   • Keep container tightly closed.


PILOCARPINE HYDROCHLORIDE OPHTHALMIC SOLUTION USP

Usual adult and adolescent dose
Antiglaucoma agent (ophthalmic)


Chronic glaucoma:
Topical, to the conjunctiva, 1 drop of a 0.5 to 4% solution up to four times a day. {07} {33}



Acute angle-closure glaucoma:
Topical, to the conjunctiva, 1 drop of a 1 or 2% solution every five to ten minutes for three to six doses, then 1 drop every one to three hours until intraocular pressure is reduced.

Note: To possibly avoid a bilateral attack of angle-closure glaucoma, 1 drop of a 1 or 2% solution may be instilled in the unaffected eye every six to eight hours. However, more intensive treatment may precipitate an attack in the unaffected eye and should be avoided.



Miotic


To counteract mydriatic effects of sympathomimetics:
Topical, to the conjunctiva, 1 drop of a 1% solution.



Prior to surgery for congenital glaucoma (goniotomy):
Topical, to the conjunctiva, 1 drop of a 2% solution every four to six hours (usually for one or two doses) before surgery.



Prior to iridectomy:
Topical, to the conjunctiva, 1 drop of a 2% solution for four doses immediately before surgery.



Usual pediatric dose
See Usual adult and adolescent dose. {27}

Note: For infants, the administration of solutions with strengths greater than 1% is not recommended. {27}


Usual geriatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


0.25% (Rx) [Isopto Carpine{33}][Generic]


0.5% (Rx) [Isopto Carpine] [Ocu-Carpine] [Pilocar] [Piloptic-1/2] [Pilostat][Generic]{33}{34}{35}{37}{40}


1% (Rx) [Adsorbocarpine] [Akarpine] [Isopto Carpine] [Ocu-Carpine] [Pilocar] [Piloptic-1] [Pilostat][Generic]{32}{33}{34}{35}{37}{39}{40}


2% (Rx) [Adsorbocarpine] [Akarpine] [Isopto Carpine] [Ocu-Carpine] [Pilocar] [Piloptic-2] [Pilostat][Generic]{32}{33}{34}{35}{37}{39}{40}


3% (Rx) [Isopto Carpine] [Ocu-Carpine] [Pilocar] [Piloptic-3] [Pilostat][Generic]{33}{34}{35}{37}{40}


4% (Rx) [Adsorbocarpine] [Akarpine] [Isopto Carpine] [Ocu-Carpine] [Pilocar] [Piloptic-4] [Pilostat][Generic]{32}{33}{34}{35}{39}{40}


5% (Rx) [Isopto Carpine] [Ocu-Carpine][Generic]{33}{34}


6% (Rx) [Isopto Carpine] [Ocu-Carpine] [Pilocar] [Piloptic-6] [Pilostat][Generic]{33}{34}{35}{37}{40}


8% (Rx) [Isopto Carpine][Generic]{33}{41}


10% (Rx) [Isopto Carpine{33}]

Canada—


0.5% (Rx) [Isopto Carpine{42}]


1% (Rx) [Isopto Carpine] [Miocarpine] [Pilostat] [Spersacarpine]{42}{44}{46}


2% (Rx) [Isopto Carpine] [Miocarpine] [Pilostat] [Spersacarpine]{42}{44}{46}


4% (Rx) [Isopto Carpine] [Miocarpine] [Pilostat] [Spersacarpine]{42}{44}{46}


6% (Rx) [Isopto Carpine] [Miocarpine]{42}{44}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from freezing.

Auxiliary labeling:
   • For the eye.
   • Keep container tightly closed.


PILOCARPINE NITRATE OPHTHALMIC SOLUTION USP

Usual adult and adolescent dose
Antiglaucoma agent (ophthalmic)


Chronic glaucoma:
Topical, to the conjunctiva, 1 drop of a 1 to 4% solution two to four times a day. {08} {38}



Acute angle-closure glaucoma:
Topical, to the conjunctiva, 1 drop of a 1 or 2% solution every five to ten minutes for three to six doses, then 1 drop every one to three hours until intraocular pressure is reduced.

Note: To possibly avoid a bilateral attack of angle-closure glaucoma, 1 drop of a 1 or 2% solution may be instilled in the unaffected eye every six to eight hours. However, more intensive treatment may precipitate an attack in the unaffected eye and should be avoided.



Miotic


To counteract mydriatic effects of sympathomimetics:
Topical, to the conjunctiva, 1 drop of a 1% solution.



Prior to surgery for congenital glaucoma (goniotomy):
Topical, to the conjunctiva, 1 drop of a 2% solution every four to six hours (usually for one or two doses) before surgery.



Prior to iridectomy:
Topical, to the conjunctiva, 1 drop of a 2% solution for four doses immediately before surgery.



Usual pediatric dose
See Usual adult and adolescent dose. {27}

Note: For infants, the administration of solutions with strengths greater than 1% is not recommended. {27}


Usual geriatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


1% (Rx) [Pilagan{38}]


2% (Rx) [Pilagan{38}]


4% (Rx) [Pilagan{38}]

Canada—


1% (Rx) [P.V. Carpine Liquifilm{22}]


2% (Rx) [Minims Pilocarpine{43}] [P.V. Carpine Liquifilm{22}]


4% (Rx) [Minims Pilocarpine{43}] [P.V. Carpine Liquifilm{22}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing. {08}

Auxiliary labeling:
   • For the eye.
   • Keep container tightly closed.
   • Shake well. {08}



Revised: 06/21/1995



References
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  1. Pilocar 0.5, 1, 2, 3, 4, 6% (IOLAB). In: PDR Physicians' desk reference for ophthalmology. 23rd ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 284.
  1. Pilopine HS gel 4% (IOLAB) In: PDR Physicians' desk reference for ophthalmology. 23rd ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 232.
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  1. Pilopine HS 4% (Alcon). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 1024.
  1. Spersacarpine 1, 2, 4% (CIBA Vision). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 1229.
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