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Pilocarpine Hydrochloride

Class: Parasympathomimetic (Cholinergic) Agents
VA Class: AU900
Chemical Name: (3S-cis)-2(3H)-furanone, 3-ethyl-dihydro-4-[(1-methyl-1H-imidazol-5-yl)methyl] mono-hydrochloride
Molecular Formula: C11H16N2O 2
CAS Number: 54-71-7
Brands: Salagen

Medically reviewed by Drugs.com. Last updated on Aug 1, 2018.

Introduction

Cholinergic agonist; binds to muscarinic receptors.1 5

Uses for Pilocarpine Hydrochloride

Radiation-induced Dry Mouth

Symptomatic treatment of radiation-induced dry mouth (xerostomia) in patients with head and neck cancer.1 8 13

Dry Mouth Secondary to Sjögren Syndrome

Symptomatic treatment of dry mouth in patients with Sjögren syndrome.1 6 7 9 14

There are few comparative studies of pilocarpine and cevimeline (a similar muscarinic agonist).4 5 Although both drugs can increase salivary flow and improve symptoms of dry mouth, adverse effects may differ based on differences in selectivity and affinity for muscarinic receptors.4 5 (See Actions.)

Pilocarpine Hydrochloride Dosage and Administration

Administration

Oral Administration

Administer orally 3–4 times daily.1 2

Dosage

Available as pilocarpine hydrochloride; dosage expressed in terms of the salt.1 2

Adults

Radiation-induced Dry Mouth
Oral

Initially, 5 mg 3 times daily; titrate dosage based on therapeutic response and tolerance.1

Usual dosage range is 15–30 mg daily given in divided doses (not to exceed 10 mg per dose).1

Adverse effects are dose related; use lowest effective and tolerated dosage for maintenance therapy.1

At least 12 weeks of continuous therapy may be necessary to achieve therapeutic benefit.1

Dry Mouth Secondary to Sjögren Syndrome
Oral

Recommended dosage is 5 mg 4 times daily.1 To minimize incidence of sweating, some clinicians recommend initiating therapy at a low dosage (e.g., 2 mg once or twice daily), then gradually increasing up to 5 mg 3 or 4 times daily.6

In clinical studies, a therapeutic effect was observed by 6 weeks of treatment.1

Prescribing Limits

Adults

Radiation-induced Dry Mouth
Oral

Do not exceed 10 mg per dose.1

Special Populations

Hepatic Impairment

Mild hepatic impairment: No dosage adjustment required.1

Moderate hepatic impairment: Reduce initial dosage to 5 mg twice daily regardless of indication; adjust subsequent dosage based on response and tolerability.1 (See Hepatic Impairment under Cautions.)

Severe hepatic impairment: Use not recommended.1

Renal Impairment

Manufacturer makes no specific dosage recommendations.1

Geriatric Patients

Manufacturer makes no specific dosage recommendations.1

Cautions for Pilocarpine Hydrochloride

Contraindications

  • Known hypersensitivity to pilocarpine.1 2

  • Uncontrolled asthma.1 2

  • Patients in whom miosis is undesirable (e.g., those with acute iritis, angle-closure glaucoma).1 2

Warnings/Precautions

Warnings

Cardiovascular Effects

Risk of altered cardiac conduction and/or heart rate.1 Patients with clinically important cardiovascular disease may be unable to compensate for transient changes in hemodynamics or heart rhythm induced by pilocarpine.1

Use with caution and under close medical supervision in patients with a history of cardiovascular disease (e.g., angina pectoris, MI).1

Ocular Effects

Blurred vision reported with ophthalmic formulations.1 May result in impaired depth perception and decreased visual acuity, especially at night and in patients with central lens changes; may impair ability to drive at night or perform hazardous activities in reduced lighting.1 (See Advice to Patients.)

Pulmonary Effects

May increase airway resistance, bronchial smooth muscle tone, and bronchial secretions.1 Use with caution and under close medical supervision in patients with controlled asthma, chronic bronchitis, or COPD.1

General Precautions

Parasympathomimetic Effects

Possible exaggeration of parasympathomimetic effects (e.g., headache, visual disturbance, lacrimation, sweating, respiratory distress, GI spasm, nausea, vomiting, diarrhea, AV block, tachycardia, bradycardia, hypotension, hypertension, shock, mental confusion, cardiac arrhythmia, tremors).1

Sweating is the most common adverse effect.1 6 8 13 14 Excessive sweating may cause dehydration.1 (See Advice to Patients.)

Biliary Effects

Use with caution in patients with known or suspected cholelithiasis or biliary tract disease.1

Contraction of gallbladder or biliary smooth muscle could precipitate complications (e.g., cholecystitis, cholangitis, biliary obstruction) in patients with cholelithiasis.1

Renal Effects

May increase ureteral smooth muscle tone, and theoretically cause renal colic or ureteral reflux in patients with nephrolithiasis.1

CNS Effects

Dose-related CNS effects reported; use caution in patients with underlying cognitive or psychiatric disturbances.1

Specific Populations

Pregnancy

No adequate and well-controlled studies in pregnant women; fetotoxicity and developmental abnormalities reported in animal studies.1

Use during pregnancy only if potential benefit justifies potential risk to the fetus.1

Lactation

Not known whether pilocarpine is distributed into human milk; discontinue nursing or the drug.1 2

Pediatric Use

Safety and efficacy not established in children.1 2

Geriatric Use

In patients ≥65 years of age with head and neck cancer, adverse effects generally similar to those observed in younger adults.1

In patients ≥65 years of age with Sjögren syndrome, increased incidence of urinary frequency, diarrhea, and dizziness reported compared with younger patients.1

Hepatic Impairment

Clearance decreased in patients with hepatic impairment.1 (See Special Populations under Pharmacokinetics.) Dosage reduction required in patients with moderate hepatic impairment.1 (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Pharmacokinetics not substantially altered in patients with renal impairment (mean Clcr 25.4 mL/minute; range 9.8–40.8 mL/minute).1

Common Adverse Effects

Radiation-induced dry mouth: Sweating, nausea, rhinitis, diarrhea, chills, flushing, urinary frequency, dizziness, asthenia, headache, dyspepsia, lacrimation, edema.1

Dry mouth secondary to Sjögren syndrome: Sweating, urinary frequency, nausea, flushing, rhinitis, diarrhea, headache, flu syndrome, dyspepsia, dizziness.1

Interactions for Pilocarpine Hydrochloride

Specific Drugs

Drug

Interaction

Comments

Antimuscarinic agents (e.g., atropine, ipratropium)1

Potential for antagonism of antimuscarinic effects1

β-Adrenergic blocking agents1

Possible cardiac conduction disturbances1

Caution is advised if used concomitantly1

Parasympathomimetic agents1

Possible additive effects1

Pilocarpine Hydrochloride Pharmacokinetics

Absorption

Bioavailability

In healthy individuals, peak plasma concentrations achieved in approximately 1 hour.1

Onset

In healthy individuals, onset of effect approximately 20 minutes.1

Duration

In healthy individuals, duration of effect approximately 3–5 hours.1

Food

Food decreases rate of absorption; time to peak concentration under fasting conditions and after a meal were 0.87 and 1.47 hours, respectively.1

Distribution

Extent

Not known whether pilocarpine is distributed into milk.1

Plasma Protein Binding

Does not bind to plasma proteins at concentrations of 5–25,000 ng/mL.1 Effect on plasma protein binding of other drugs not evaluated.1

Elimination

Metabolism

Limited information available; however, drug inactivation is thought to occur at neuronal synapses and possibly also in plasma.1

Elimination Route

Limited information available.1 Inactive or minimally active degradation products excreted in urine.1

Half-life

0.76–1.35 hours depending on dose.1

Special Populations

Mild to moderate hepatic impairment: Following administration of a single 5-mg dose, total plasma clearance decreased by 30%, systemic exposure increased by 100%, and peak plasma concentrations increased by about 30%; half-life was prolonged to 2.1 hours.1 2

Stability

Storage

Oral

Tablets

Up to 25°C (may be exposed to 15–30°C).1

Actions

  • Exerts a broad spectrum of pharmacologic effects with predominant muscarinic action.1 5

  • In sufficient dosages, can increase exocrine (e.g., salivary, sweat) gland secretion; also may increase bronchial smooth muscle tone and enhance tone and motility of GI, urinary tract, gallbladder, and biliary duct smooth muscle.1 5

  • Dose-related smooth muscle stimulation of the intestinal tract may cause increased tone, increased motility, spasm, and tenesmus.1

  • May have paradoxical effects on the cardiovascular system (e.g., hypotension and hypertension, bradycardia and tachycardia).1

  • Pharmacologically similar to cevimeline.5 Both drugs are effective in increasing salivary flow, but exhibit differences in selectivity and affinity for specific muscarinic receptors.1 5 12 15 Cevimeline exhibits higher affinity for M3 muscarinic receptors in lacrimal and salivary glands than for M2 receptors in cardiac tissue.5 15

Advice to Patients

  • Risk of visual disturbances, especially at night; advise patients to use caution when driving at night or performing hazardous activities in reduced lighting.1

  • Risk of dehydration if excessive sweating occurs; advise patients to consult their clinician if they experience excessive sweating but cannot drink enough liquids.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

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

Tablets

5 mg*

Pilocarpine Hydrochloride Tablets

Salagen

Eisai

7.5 mg*

Pilocarpine Hydrochloride Tablets

Salagen

Eisai

AHFS DI Essentials™. © Copyright 2019, Selected Revisions January 7, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Eisai. Salagen (pilocarpine hydrochloride) film-coated tablets prescribing information. Woodcliff Lake, NJ; 2018 Jun.

2. Impax Generics. Pilocarpine hydrochloride film-coated tablets prescribing information. Hayward, CA; 2016 Mar.

3. Moutsopoulos HM and Tzioufas AG. Sjögren’s syndrome. In: Kasper DL, Fauci AS, Hauser SL et al, eds. Harrison’s principles of internal medicine. 19th ed. New York: McGraw-Hill Education; 2015:2166-9

4. Noaiseh G, Baker JF, Vivino FB, et al. Clin Exp Rheumatol. Comparison of the discontinuation rates and side-effect profiles of pilocarpine and cevimeline for xerostomia in primary Sjögren's syndrome. 2014 Jul-Aug;32(4):575-7.

5. Braga MA, Tarzia O, Bergamaschi CC, et al. Comparison of the effects of pilocarpine and cevimeline on salivary flow. Int J Dent Hyg. 2009 May;7(2):126-30.

6. Mariette X, Criswell LA. Primary Sjögren's Syndrome. N Engl J Med. 2018; 378:931-939. http://www.ncbi.nlm.nih.gov/pubmed/29514034?dopt=AbstractPlus

7. Ramos-Casals M, Tzioufas AG, Stone JH et al. Treatment of primary Sjögren syndrome: a systematic review. JAMA. 2010; 304:452-60. http://www.ncbi.nlm.nih.gov/pubmed/20664046?dopt=AbstractPlus

8. Johnson JT, Ferretti GA, Nethery WJ et al. Oral pilocarpine for post-irradiation xerostomia in patients with head and neck cancer. N Engl J Med. 1993; 329:390-5. http://www.ncbi.nlm.nih.gov/pubmed/8326972?dopt=AbstractPlus

9. Vivino FB, Carsons SE, Foulks G et al. New Treatment Guidelines for Sjögren's Disease. Rheum Dis Clin North Am. 2016; 42:531-51. http://www.ncbi.nlm.nih.gov/pubmed/27431353?dopt=AbstractPlus

12. Anon. Cevimeline (Evoxac) for dry mouth. Med Lett Drugs Ther. 2000; 42:70. http://www.ncbi.nlm.nih.gov/pubmed/10932302?dopt=AbstractPlus

13. LeVeque FG, Montgomery M, Potter D et al. A multicenter, randomized, double-blind, placebo-controlled, dose-titration study of oral pilocarpine for treatment of radiation-induced xerostomia in head and neck cancer patients. J Clin Oncol. 1993; 11:1124-31. http://www.ncbi.nlm.nih.gov/pubmed/8501499?dopt=AbstractPlus

14. Vivino FB, Al-Hashimi I, Khan Z et al. Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjögren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group. Arch Intern Med. 1999; 159:174-81. http://www.ncbi.nlm.nih.gov/pubmed/9927101?dopt=AbstractPlus

15. Fife RS, Chase WF, Dore RK et al. Cevimeline for the treatment of xerostomia in patients with Sjögren syndrome: a randomized trial. Arch Intern Med. 2002; 162:1293-300. http://www.ncbi.nlm.nih.gov/pubmed/12038948?dopt=AbstractPlus

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