AHFS Class:

• Miotics 52:40.20

Generic Name(s):

• Pilocarpine

• Pilocarpine Hydrochloride

• Pilocarpine Nitrate

Pilocarpine, a direct-acting parasympathomimetic agent, is a miotic.

Pilocarpine shares the uses of the miotics.

Because of its increased duration of effect and less frequent administration, pilocarpine hydrochloride gel may provide some advantages over ophthalmic solutions of the drug in some patients with open-angle glaucoma, particularly those in whom compliance with frequent-dosing regimens with ophthalmic solutions is a problem. Pilocarpine hydrochloride gel is used mainly for the chronic treatment of open-angle (chronic simple, noncongestive) glaucoma. Ophthalmic solutions of the drug are preferred when an acute reduction in IOP and/or an intense miotic effect are necessary such as in the emergency treatment of acute angle-closure glaucoma prior to surgery, for the reduction of IOP and the protection of the lens prior to goniotomy or iridectomy, or to counteract the mydriatic effects of sympathomimetic agents following ophthalmologic examinations. It is not known whether unresponsiveness develops more or less frequently to the gel than to pilocarpine ophthalmic solutions.

Administration

Pilocarpine hydrochloride is applied topically to the conjunctival sac as an ophthalmic solution. If pilocarpine hydrochloride gel is used concomitantly with ophthalmic solutions, the solutions should be instilled first and the gel should be applied at least 5 minutes later.

Following topical instillation of miotic ophthalmic solutions, finger pressure should be applied on the lacrimal sac for 1-2 minutes to minimize drainage into the nose and throat and reduce the risk of absorption and systemic reactions. Excess solution around the eye should be removed with a tissue and any medication on the hands should be rinsed off immediately.

Dosage

Dosage and concentrations of pilocarpine hydrochloride are expressed in terms of the salt.

Ophthalmic Solutions

For the treatment of glaucoma, the concentration and frequency of instillation of pilocarpine hydrochloride ophthalmic solutions must be adjusted to the requirements and responses of individual patients as determined by tonometric readings before and during therapy. The usual dosage is 1-2 drops of a 1-4% solution every 4-12 hours. Concentrations greater than 4% are only occasionally more effective than lower concentrations of the drug. The manufacturers state that pilocarpine hydrochloride ophthalmic solutions may be used concomitantly with other miotics, sympathomimetic agents, β-adrenergic blocking agents, carbonic anhydrase inhibitors, or hyperosmotic agents.

For emergency treatment of acute angle-closure glaucoma, the usual dose is 1 drop of a 2% solution in the affected eye every 5-10 minutes for 3-6 doses, followed by 1 drop every 1-3 hours until the pressure is controlled. To prevent a bilateral attack, some clinicians recommend instillation of 1 drop of a 1-2% solution in the unaffected eye every 6-8 hours.

To counteract the mydriatic effects of sympathomimetic agents, the usual dose is 1 drop of a 1% solution of pilocarpine hydrochloride in the affected eye. Dosages of 1 drop of a 2% solution of pilocarpine hydrochloride 4 times immediately prior to iridectomy and 1 drop of a 2% solution of pilocarpine hydrochloride every 6 hours prior to surgery for congenital glaucoma (goniotomy) have been used. Pilocarpine hydrochloride 2% solution may be used to fill the gonioscopic lens prior to goniotomy, or 1 drop of a 2% solution of pilocarpine hydrochloride may be administered every 6 hours plus 3 times in the 30 minutes immediately preceding goniotomy, with or without concomitant administration of acetazolamide.

Ophthalmic Gel

Dosage of pilocarpine hydrochloride ophthalmic gel should be based on periodic tonometric readings. The usual dosage of the drug as the 4% gel is a 1.3-cm (0.5-inch) ribbon applied into the lower conjunctival sac once daily at bedtime. To ensure adequate control of IOP throughout the 24-hour dosing interval, IOP should be measured just prior to the next dose at least once following initiation of therapy with the gel. The manufacturer states that the gel may be used concomitantly with other miotics, sympathomimetic agents, β-adrenergic blocking agents, carbonic anhydrase inhibitors, or hyperosmotic agents.

Pilocarpine shares the toxic potentials of the direct-acting miotics, and the usual precautions of miotic therapy should be observed.

Pilocarpine hydrochloride gel is usually well tolerated. In one 30-day study in adults with increased IOP, the type and severity of adverse effects were similar with once-daily dosing of the gel or application of a solution 4 times daily. Lacrimation, burning or discomfort, temporal or periorbital headache, ciliary spasm, conjunctival vascular congestion, superficial keratitis, and myopia have occurred in patients receiving the gel. Ocular reactions usually occur during initiation of therapy with the gel but often resolve with continued therapy. Ocular irritation (burning or discomfort) frequently occurs and may occasionally require discontinuance of the gel. Blurring of vision also occurs frequently, usually persisting for several hours in the morning following bedtime application of the gel, but generally is minor and usually does not interfere with daily activity or reading vision; however, discontinuance of the gel may occasionally be necessary. Crusting of the gel on the eyelids may occur overnight and the eyelids may occasionally stick together in the morning; the crusting can be washed away with water. Mild to moderate, superficial, punctate keratitis over the lower portion of the cornea occurred in about 40% of patients during the first 2 weeks of therapy with the gel in one study, but this effect usually resolved with continued therapy. Subtle, diffuse, superficial corneal changes (e.g., small focal gray opacities [haze] in anterior stroma and Bowman's zone) occurred in about 20% of patients in this study during long-term therapy, usually after 9-12 months of therapy (after 4 months in one patient); many of these patients had punctate keratitis during initiation of therapy. Although these corneal changes were not associated with symptoms, therapy with the gel was discontinued after 1 year in all patients who developed corneal opacities in this study. Corneal opacities may persist for prolonged periods following discontinuance of the gel. The mechanism of these changes currently is not known.

Pharmacokinetics

Following topical application of a 1% solution of pilocarpine hydrochloride to the conjunctival sac, miosis occurs within 10-30 minutes, is maximal within 30 minutes, and usually persists 4-8 hours or rarely up to 20 hours. Reduction in intraocular pressure (IOP) is detectable within 60 minutes and is maximal within 75 minutes. Reduced IOP persists 4-14 hours, depending on the concentration of drug used. Spasms of accommodation begin in approximately 15 minutes and persist 2-3 hours.

Following topical application of pilocarpine hydrochloride 4% in a carbomer 940 gel base in adults with increased IOP, a bedtime dose of gel decreased IOP for about 18-24 hours after application. IOP in the morning was generally reduced to a slightly greater extent than in the afternoon. The carbomer 940 gel base provides a highly viscous preparation which results in prolonged retention of the drug in the precorneal area; compared with a topically applied solution of the drug, the gel results in increased corneal bioavailability secondary to decreased elimination of pilocarpine from precorneal areas and has an increased duration of ocular effects. In one study in adults with increased IOP who received single bedtime doses of pilocarpine hydrochloride 4% gel in one eye and a 4% solution 4 times daily in the other eye, IOP reduction and pupillary diameter were similar for both preparations for about 18 hours after application of the gel. In rabbits, pilocarpine hydrochloride 2% in a carbomer 940 gel was retained in the lower conjunctival sac for about 4-6 hours; miosis was maximal within 1 hour and persisted for an average of about 8.5 hours.

Chemistry and Stability

Chemistry

Pilocarpine, a direct-acting parasympathomimetic agent, is an alkaloid obtained from Pilocarpus microphyllus or jaborandi.

Ophthalmic pilocarpine preparations are commercially available as the hydrochloride salt. Pilocarpine hydrochloride occurs as hygroscopic, colorless, translucent, odorless crystals with a faintly bitter taste and has solubilities of approximately 3.33 g/mL in water and 333 mg/mL in alcohol at 25°C.

Commercially available ophthalmic solutions are sterile, buffered aqueous solutions of pilocarpine hydrochloride, which may contain suitable antimicrobial agents, stabilizers, and additives to increase viscosity. Pilocarpine hydrochloride solutions have a pH of 3.5-5.5.

Pilocarpine hydrochloride ophthalmic gel is sterile and contains the drug in an aqueous gel base. The gel base contains more than 90% water and also contains carbomer 940 (3.5% w/w), a polymer of acrylic acid cross-linked with a polyfunctional agent which provides a high viscosity for the gel. The gel also contains benzalkonium chloride as a preservative, edetate disodium, and hydrochloric acid and/or sodium hydroxide to adjust the pH to 4.7-4.9.

Stability

Commercially available pilocarpine preparations differ in stability, and the manufacturer's storage recommendations should be followed. Pilocarpine hydrochloride ophthalmic gel should be stored at 2-27°C; freezing and excessive heat should be avoided.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.