Pilocarpine Hydrochloride

Pronunciation: PYE-loe-KAR-peen HYE-droe-KLOR-ide
Class: Cholinergic agent, Ophthalmic agent, miotic and antiglaucoma

Trade Names

Isopto-Carpine
- Solution, ophthalmic 1%
- Solution, ophthalmic 2%
- Solution, ophthalmic 4%

Piloptic-1/2
- Solution, ophthalmic 0.5%

Piloptic-1
- Solution, ophthalmic 1%

Piloptic-2
- Solution, ophthalmic 2%

Piloptic-3
- Solution, ophthalmic 3%

Piloptic-4
- Solution, ophthalmic 4%

Piloptic-6
- Solution, ophthalmic 6%

Pilopine HS
- Gel, ophthalmic 4%

Salagen
- Tablets 5 mg
- Tablets 7.5 mg

Minims-Pilocarpine (Canada)

Pharmacology

Ophthalmic

Decreases IOP by constricting pupil and stimulating ciliary muscles to open trabecular meshwork spaces and facilitate outflow of aqueous humor.

PO

Stimulates exocrine glands including mucous cells of respiratory tract and salivary glands in oral cavity.

Pharmacokinetics

Absorption

T _max is 0.85 to 1.25 h. C _max is 15 to 41 ng/mL. AUC is 33 to 108 h•ng/mL. High-fat meals decreased the rate of absorption.

Metabolism

Limited information available; however, its thought to occur at neuronal synapses and probably in the plasma.

Elimination

Urine (as unchanged pilocarpine, minimal active/inactive degradation products). Half-life is 0.76 to 1.35 h.

Onset

20 min.

Peak

1 h.

Duration

3 to 5 h.

Special Populations

Renal Function Impairment

No effect on pilocarpine pharmacokinetics.

Hepatic Function Impairment

In patients with mild to moderate hepatic function impairment, pilocarpine Cl is decreased, resulting in an increase in the pilocarpine C _max and half-life.

Gender

Elderly women had C _max and AUC approximately twice that of elderly and younger men.

Indications and Usage

Ophthalmic gel

To control IOP.

Ophthalmic solution

Management of glaucoma, especially open-angle glaucoma; management of acute (closed-angle) glaucoma alone and in combination with other cholinergic agent or carbonic anhydrase inhibitors.

PO

Treatment of xerostomia (dry mouth) in patients with malfunctioning salivary glands because of radiotherapy for cancer of head and neck; relief of dry mouth in patients with Sjögren syndrome.

Unlabeled Uses

Relief of dry mouth in patients with graft-vs-host disease (PO); keratoconjunctivitis sicca (dry eye syndrome).

Contraindications

Ophthalmic, PO

When miosis is undesirable (eg, acute iritis, narrow-angle glaucoma); hypersensitivity to any component of the product.

PO

Uncontrolled asthma.

Dosage and Administration

Adults

PO Titrate dosage based on therapeutic response and tolerance. To reduce the incidence and severity of adverse reactions, use the lowest effective dose. Do not exceed a maximum of 10 mg/dose or 30 mg daily.

Radiation-Induced Xerostomia
Adults

PO 5 mg 3 times daily. If no response, increase dosage to 10 mg 3 times daily. Continue uninterrupted for at least 12 wk before assessing for full therapeutic benefit (max, 30 mg/day).

Sjögren Syndrome
Adults

PO 5 mg 4 times daily. Continue uninterrupted for at least 6 wk before assessing for full therapeutic benefit.

Glaucoma
Adults

Ophthalmic solution Instill 1 to 2 drops in affected eye(s) up to 4 times daily. More concentrated solutions are sometimes used.

Adults

Ophthalmic gel Apply one-half inch ribbon in lower conjunctival sac of affected eye(s) once daily at bedtime.

Hepatic Function Impairment
Adults

PO Moderate hepatic function impairment: Start with 5 mg twice daily, adjusting the dose based on therapeutic response and tolerability. Avoid use in patients with severe hepatic function impairment.

General Advice

PO

• Administration with a high-fat meal reduces pilocarpine absorption.
• Give medication with food if GI distress occurs.

Ophthalmic

• To avoid contamination, do not touch tip of container to any surface. Replace cap after administration.
• During acute phase, the mitotic agent must be instilled into the unaffected eye to prevent an attack of angle-closure glaucoma.

Storage/Stability

Ophthalmic solution/PO

Store at controlled room temperature (59° to 86°F).

Ophthalmic gel

Store at 36° to 80°F. Avoid excessive heat. Do not freeze.

Drug Interactions

Anticholinergics

May antagonize action of pilocarpine (PO, ophthalmic).

Beta-blockers

Potential for cardiac conduction disturbances with oral pilocarpine.

Food (high-fat meal)

Decreases the rate of pilocarpine absorption.

Parasympathomimetics

Additive pharmacologic effects and increased toxicity possible.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (3%); palpitations, tachycardia (1% to 2%).

CNS

Asthenia, dizziness (12%); headache (11%); somnolence, tremor (1% to 2%). Ophthalmic: Periorbital or temporal headache.

Dermatologic

Sweating (68%); flushing (13%); pruritus, rash (1% to 2%).

EENT

Rhinitis (14%); amblyopia (4%); abnormal vision, blurred vision, conjunctivitis, epistaxis, tinnitus, voice alteration (1% to 2%).

Ophthalmic

Burning or discomfort; ciliary spasm; conjunctival vascular congestion; induced myopia; lacrimation; lens opacity; reduced visual acuity; retinal detachment; superficial keratitis.

GI

Nausea (15%); diarrhea, dyspepsia (7%); vomiting (4%); increased salivation (3%); constipation, dysphagia, flatulence, glossitis, stomatitis, taste perversion (1% to 2%).

Genitourinary

Urinary frequency (12%); urinary incontinence, urinary tract infection, vaginitis (1% to 2%).

Hypersensitivity

Allergic reaction (1% to 2%).

Lab Tests

Abnormalities including chemistry, hematology, and urinalysis (1% to 2%).

Musculoskeletal

Back pain, myalgias (1% to 2%).

Respiratory

Increased cough, sinusitis (1% to 2%); bronchial spasm, pulmonary edema.

Miscellaneous

Chills (15%); edema (5%); pain (4%); accidental injury, face edema, fever (1% to 2%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Elderly patients also may be at increased risk for certain adverse reactions during therapy, including diarrhea, urinary frequency, and dizziness.

Hepatic Function

Dose reduction may be needed in patients with hepatic function impairment.

Special Risk Patients

Use with caution in patients with known or suspected cholelithiasis or biliary tract disease, nephrolithiasis, or underlying cognitive or psychiatric disturbances.

Cardiovascular

Dose-related CV effects include bradycardia, hypertension, hypotension, and tachycardia.

Miosis

May cause difficulty in dark adaptation; therefore, caution is needed in night driving and in other hazardous situations in poor illumination.

Pulmonary disease

Pilocarpine can increase airway resistance, bronchial smooth muscle tone, and bronchial secretions. Use with caution in patients with controlled asthma, chronic bronchitis, or COPD requiring treatment.

Visual blurring

Ophthalmic preparations can cause visual blurring, which may result in decreased visual acuity, especially at night and in patients with central lens changes. Advise patients to use caution while driving at night or when performing hazardous activities in reduced lighting.

Overdosage

Symptoms

Bronchial constriction in asthmatic patients, death, exaggerated parasympathomimetic effects including AV block, bradycardia, cardiac arrhythmias, diarrhea, GI spasm, headache, hypertension, hypotension, lacrimation, mental confusion, nausea, respiratory distress, salivation, shock, sweating, tachycardia, tremors, visual disturbances, and vomiting.

Patient Information

• Ophthalmic
• For treatment of glaucoma, emphasize need to adhere to medical regimen to prevent blindness.
• Advise patients that their vision may be impaired, affecting their ability to drive safely.
• Explain that long-term therapy may be required.
• Instruct patient to wash hands thoroughly before and after using ophthalmic preparation.
• Review proper procedure for administration of ophthalmic preparations.
• Explain that ophthalmic preparations may sting upon instillation, especially with first few doses.
• Tell patient to discard solution after expiration date.
• Explain that medication may cause headache or brow ache and that because of blurring and altered distance vision and night vision, to use caution while night driving or performing hazardous tasks in poor lighting.
• Explain that during acute phases, a miotic (agent that causes pupil to constrict) also must be instilled into unaffected eye to prevent occurrence of angle-closure glaucoma.

• PO
• Advise patients to drink additional water or noncaffeinated fluids during therapy.
• Tell patients to report the following symptoms to health care provider: chills, diarrhea, dizziness, fluid retention, flushing, frequent urination, headache, indigestion, nasal congestion, nausea, sweating, tearing, weakness.

Copyright © 2009 Wolters Kluwer Health.