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Pilocarpine Hydrochloride

Class: Parasympathomimetic (Cholinergic) Agents
Chemical Name: (3S,4R)-3-ethyl-4-[(3-methylimidazol-4-yl)methyl]oxolan-2-one;hydrochloride
Molecular Formula: C11H16N2O2•HCl
CAS Number: 54-71-7
Brands: Salagen

Medically reviewed on Aug 1, 2018

Introduction

Pilocarpine hydrochloride is a parasympathomimetic (cholinergic) agent.

Uses for Pilocarpine Hydrochloride

Pilocarpine hydrochloride has the following uses:

Pilocarpine hydrochloride tablets are indicated for 1) the treatment of symptoms of dry mouth from salivary gland hypofunction caused by radiotherapy for cancer of the head and neck; and 2) the treatment of symptoms of dry mouth in patients with Sjogren’s Syndrome.1

Pilocarpine Hydrochloride Dosage and Administration

General

Pilocarpine hydrochloride is available in the following dosage form(s) and strength(s):

Tablets: 5 mg. Each tablet contains 5 mg pilocarpine hydrochloride.1

Tablets: 7.5 mg. Each tablet contains 7.5 mg pilocarpine hydrochloride.1

Dosage

Adults

Head and Neck Cancer Patients: The recommended initial dose of pilocarpine hydrochloride tablets is 5 mg taken three times a day. Dosage should be titrated according to therapeutic response and tolerance. The usual dosage range is up to 15–30 mg per day (not to exceed 10 mg per dose). Although early improvement may be realized, at least 12 weeks of uninterrupted therapy with pilocarpine hydrochloride tablets may be necessary to assess whether a beneficial response will be achieved. The incidence of the most common adverse events increases with dose. The lowest dose that is tolerated and effective should be used for maintenance.1

Sjogren’s Syndrome Patients: The recommended dose of pilocarpine hydrochloride tablets is 5 mg taken four times a day. Efficacy was established by 6 weeks of use.1

Special Populations

Hepatic Impairment: Regardless of the indication, the starting dose in patients with moderate hepatic impairment should be 5 mg twice daily, followed by adjustment based on therapeutic response and tolerability. Patients with mild hepatic insufficiency do not require dosage reductions. The use of pilocarpine in patients with severe hepatic insufficiency is not recommended.1

Cautions for Pilocarpine Hydrochloride

Contraindications

Pilocarpine hydrochloride tablets are contraindicated in patients with uncontrolled asthma, known hypersensitivity to pilocarpine, and when miosis is undesirable, e.g., in acute iritis and in narrow-angle (angle closure) glaucoma.1

Warnings/Precautions

Warnings

Cardiovascular Disease

Patients with significant cardiovascular disease may be unable to compensate for transient changes in hemodynamics or rhythm induced by pilocarpine. Pulmonary edema has been reported as a complication of pilocarpine toxicity from high ocular doses given for acute angle-closure glaucoma. Pilocarpine should be administered with caution in and under close medical supervision of patients with significant cardiovascular disease.1

Ocular Effects

Ocular formulations of pilocarpine have been reported to cause visual blurring which may result in decreased visual acuity, especially at night and in patients with central lens changes, and to cause impairment of depth perception. Caution should be advised while driving at night or performing hazardous activities in reduced lighting.1

Pulmonary Disease

Pilocarpine has been reported to increase airway resistance, bronchial smooth muscle tone, and bronchial secretions. Pilocarpine hydrochloride should be administered with caution to and under close medical supervision in patients with controlled asthma, chronic bronchitis, or chronic obstructive pulmonary disease requiring pharmacotherapy.1

General Precautions

Pilocarpine toxicity is characterized by an exaggeration of its parasympathomimetic effects. These may include: headache, visual disturbance, lacrimation, sweating, respiratory distress, gastrointestinal spasm, nausea, vomiting, diarrhea, atrioventricular block, tachycardia, bradycardia, hypotension, hypertension, shock, mental confusion, cardiac arrhythmia, and tremors.1

The dose-related cardiovascular pharmacologic effects of pilocarpine include hypotension, hypertension, bradycardia, and tachycardia.1

Pilocarpine should be administered with caution to patients with known or suspected cholelithiasis or biliary tract disease. Contractions of the gallbladder or biliary smooth muscle could precipitate complications including cholecystitis, cholangitis, and biliary obstruction.1

Pilocarpine may increase ureteral smooth muscle tone and could theoretically precipitate renal colic (or “ureteral reflux”), particularly in patients with nephrolithiasis.1

Cholinergic agonists may have dose-related central nervous system effects. This should be considered when treating patients with underlying cognitive or psychiatric disturbances.1

Hepatic Insufficiency: Based on decreased plasma clearance observed in patients with moderate hepatic impairment, the starting dose in these patients should be 5 mg twice daily, followed by adjustment based on therapeutic response and tolerability. Patients with mild hepatic insufficiency (Child-Pugh score of 5–6) do not require dosage reductions. To date, pharmacokinetic studies in subjects with severe hepatic impairment (Child-Pugh score of 10–15) have not been carried out. The use of pilocarpine in these patients is not recommended.1

Specific Populations

Pregnancy

Pilocarpine was associated with a reduction in the mean fetal body weight and an increase in the incidence of skeletal variations when given to pregnant rats at a dosage of 90 mg/kg/day (approximately 26 times the maximum recommended dose for a 50 kg human when compared on the basis of body surface area [mg/m2] estimates). These effects may have been secondary to maternal toxicity. In another study, oral administration of pilocarpine to female rats during gestation and lactation at a dosage of 36 mg/kg/day (approximately 10 times the maximum recommended dose for a 50 kg human when compared on the basis of body surface area [mg/m2] estimates) resulted in an increased incidence of stillbirths; decreased neonatal survival and reduced mean body weight of pups were observed at dosages of 18 mg/kg/day (approximately 5 times the maximum recommended dose for a 50 kg human when compared on the basis of body surface area [mg/m2] estimates) and above. There are no adequate and well-controlled studies in pregnant women. Pilocarpine tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.1

Lactation

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from pilocarpine tablets, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the woman.1

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.1

Geriatric Use

Head and Neck Cancer Patients: In the placebo-controlled clinical trials, the mean age of patients was approximately 58 years (range 19 to 80). Of these patients, 97/369 (61/217 receiving pilocarpine) were over the age of 65 years. In the healthy volunteer studies, 15/150 subjects were over the age of 65 years. In both study populations, the adverse events reported by those over 65 years and those 65 years and younger were comparable. Of the 15 elderly volunteers (5 women, 10 men), the 5 women had higher Cmax’s and AUC’s than the men.1

Sjogren’s Syndrome Patients: In the placebo-controlled clinical trials, the mean age of patients was approximately 55 years (range 21 to 85). The adverse events reported by those over 65 years and those 65 years and younger were comparable except for notable trends for urinary frequency, diarrhea, and dizziness.1

Hepatic Impairment

Based on decreased plasma clearance observed in patients with moderate hepatic impairment, the starting dose in these patients should be 5 mg twice daily, followed by adjustment based on therapeutic response and tolerability. Patients with mild hepatic insufficiency (Child-Pugh score of 5–6) do not require dosage reductions. To date, pharmacokinetic studies in subjects with severe hepatic impairment (Child-Pugh score of 10–15) have not been carried out. The use of pilocarpine in these patients is not recommended.1

Common Adverse Effects

Head and Neck Cancer Patients: The most frequent adverse experiences associated with pilocarpine hydrochloride tablets were a consequence of the expected pharmacologic effects of pilocarpine.1

Sjogren’s Syndrome Patients: In the 2 placebo-controlled studies, the most common adverse events related to drug use were sweating, urinary frequency, chills, and vasodilatation (flushing). The most commonly reported reason for patient discontinuation of treatment was sweating.1

Drug Interactions

Specific Drugs

Pilocarpine should be administered with caution to patients taking beta-adrenergic antagonists because of the possibility of conduction disturbances.1

Drugs with parasympathomimetic effects administered concurrently with pilocarpine would be expected to result in additive pharmacologic effects.1

Pilocarpine might antagonize the anticholinergic effects of drugs used concomitantly. These effects should be considered when anticholinergic properties may be contributing to the therapeutic effect of concomitant medication (e.g., atropine, inhaled ipratropium).1

While no formal drug interaction studies have been performed, the following concomitant drugs were used in at least 10% of patients in either or both Sjogren’s efficacy studies: acetylsalicylic acid, artificial tears, calcium, conjugated estrogens, hydroxychloroquine sulfate, ibuprofen, levothyroxine sodium, medroxyprogesterone acetate, methotrexate, multivitamins, naproxen, omeprazole, paracetamol, and prednisone.1

Actions

Clinical Pharmacology

Pharmacodynamics: Pilocarpine is a cholinergic parasympathomimetic agent exerting a broad spectrum of pharmacologic effects with predominant muscarinic action. Pilocarpine, in appropriate dosage, can increase secretion by the exocrine glands. The sweat, salivary, lacrimal, gastric, pancreatic, and intestinal glands and the mucous cells of the respiratory tract may be stimulated. When applied topically to the eye as a single dose it causes miosis, spasm of accommodation, and may cause a transitory rise in intraocular pressure followed by a more persistent fall. Dose-related smooth muscle stimulation of the intestinal tract may cause increased tone, increased motility, spasm, and tenesmus. Bronchial smooth muscle tone may increase. The tone and motility of urinary tract, gallbladder, and biliary duct smooth muscle may be enhanced. Pilocarpine may have paradoxical effects on the cardiovascular system. The expected effect of a muscarinic agonist is vasodepression, but administration of pilocarpine may produce hypertension after a brief episode of hypotension. Bradycardia and tachycardia have both been reported with use of pilocarpine.1

Advice to Patients

  • Patients should be informed that pilocarpine may cause visual disturbances, especially at night, that could impair their ability to drive safely.1

  • If a patient sweats excessively while taking pilocarpine hydrochloride and cannot drink enough liquid, the patient should consult a physician. Dehydration may develop.1

Additional Information

AHFSfirstRelease. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Pilocarpine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablet, Film Coated

5 mg*

Salagen

Eisai Inc.

7.5 mg*

Salagen

Eisai Inc.

AHFS Drug Information. © Copyright 2018, Selected Revisions September 3, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Eisai Inc.. Salagen (pilocarpine hyrochloride) oral prescribing information. 2018 Jun. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fb4810ec-d26f-429d-b87c-5898a7870169

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