Skip to main content
Log in

Oral Pilocarpine: A Review of its Pharmacological Properties and Clinical Potential in Xerostomia

  • Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript



Pilocarpine is a cholinergic agonist which stimulates salivary secretion both in individuals with normal salivary gland function and in those with impaired salivary flow (xerostomia or oral dryness). A rapid increase in salivary flow rate is observed following oral pilocarpine administration and peak levels are maintained for at least 1 to 2 hours. Mean salivary flow rates after administration of pilocarpine are 2- to 10-fold higher than after placebo, and no evidence of tolerance to the pharmacological effects of the drug has been observed during prolonged administration for up to 5 months.

The clinical efficacy of oral pilocarpine in relieving symptoms of xerostomia (resulting from radiation therapy to the head and neck region or salivary gland dysfunction), including oral dryness and difficulty in chewing, swallowing and speaking, has been demonstrated in double-blind placebo-controlled clinical trials. In these studies, pilocarpine 5 to 10mg 3 times daily increased salivary flow and improved symptoms of xerostomia in a significantly higher percentage of patients than did placebo (54 versus 25% in one study).

Preliminary findings indicate that administration of pilocarpine during radiation therapy may reduce the severity of xerostomia; however, this requires further investigation.

The majority of patients receiving oral pilocarpine therapy for xerostomia experience adverse events (most commonly sweating); however, these are generally mild and tolerable in nature.

Thus, pilocarpine is an effective agent for the treatment of xerostomia, increasing salivary flow and reducing symptom severity to a significantly greater extent than placebo. Further clinical trials should evaluate the potential beneficial effects of pilocarpine on the incidence of dental caries and oral candidiasis during prolonged therapy, its prophylactic efficacy during radiation therapy and its efficacy relative to that of other salivary stimulants.


Xerostomia (oral dryness) is caused by changes in salivary gland function. This may result from radiation therapy to the head and neck region, the use of drugs with anticholinergic/antiadrenergic properties, or systemic disease such as the autoimmune disease Sjögren’s syndrome, which causes structural damage to the glands. The symptoms of xerostomia, which include increased dental caries, difficulty in chewing, swallowing and speaking, and an increased incidence of oral candidiasis, can have a significant effect on quality of life. Treatment options (including salivary stimulants and saliva substitutes) are largely palliative and generally offer only short term relief of symptoms.

Pharmacological Properties

Pilocarpine is a muscarinic cholinergic agonist. Its ability to stimulate salivary secretion in both healthy volunteers and patients with xerostomia has been known to Western medicine for more than a century, with recent studies demonstrating its superior efficacy relative to that of placebo. Salivary flow can be stimulated within 15 minutes of oral pilocarpine administration and peak flow rates maintained for at least 1 to 2 hours in patients with xerostomia. In one study, the mean salivary flow rate was 2- to 10-fold higher after pilocarpine treatment than after placebo, and the drug appeared to increase salivary flow to a greater extent than citrate. No evidence of tolerance to the salivary stimulating properties of pilocarpine was observed during prolonged therapy for 5 months.

While studies in partially desalivated animals have indicated that prolonged administration of pilocarpine may reduce the incidence of caries and oral infection, this remains to be shown in humans.

The pharmacokinetic properties of oral pilocarpine in patients with xerostomia require further study. Peak plasma drug concentrations following 2 days’ oral administration of pilocarpine 5 or 10mg 3 times daily to 30 healthy male volunteers were 15 and 41 μg/L, respectively, and were reached in 1.25 and 0.85 hours, respectively. The rate of absorption was decreased when the drug was taken with food. Pilocarpine was eliminated predominantly in the urine with an elimination half-life of 0.76 and 1.35 hours following administration of a 5 or 10mg dose 3 times daily, respectively.

Clinical Potential

The clinical efficacy of pilocarpine as a salivary stimulant has been investigated in patients with salivary gland dysfunction (predominantly Sjögren’s syndrome) or radiation-induced xerostomia in double-blind placebo-controlled studies. Pilocarpine 5 to 10mg 3 times daily was effective in stimulating salivary secretion and improving symptoms of xerostomia, including dry mouth, difficulty in swallowing, chewing and speaking, in a significantly higher percentage of patients than placebo.

In a large multicentre study (n = 191), the overall severity of xerostomia was reduced in a significantly higher percentage of patients following 12 weeks’ treatment with pilocarpine 5mg 3 times daily (54%) than in those receiving placebo (25%). Pilocarpine treatment was associated with an increased ability to speak without requiring liquids, and a reduced need for oral comfort agents. The percentage of patients with an increase in whole and unstimulated parotid salivary flow rates was also higher in pilocarpine recipients versus placebo.

Unstimulated major salivary gland output was significantly increased in 26 of 39 patients after initial exposure to pilocarpine 5mg, and 27 of 31 patients showed symptom improvement after 1 months’ treatment with pilocarpine 5mg 3 times daily. A global assessment after 6 months of treatment showed 27 of 31 patients to have some symptom improvement (pronounced in 6 patients and moderate in 14) in this study.

Preliminary results of a small double-blind placebo-controlled study indicate that pilocarpine administration during radiation therapy may reduce the severity of xerostomia. Patients treated with pilocarpine 5mg 3 times daily starting the day before radiation therapy had smaller losses in salivary gland function following irradiation than those receiving placebo and reported fewer symptoms of xerostomia.

Tolerability Profile

Pilocarpine has been generally well tolerated in clinical trials. While adverse events were reported by most patients and were usually mild in severity, their incidence and severity were dose-related. Sweating was the most common effect, and occurred in 37 to 65% of patients treated with pilocarpine 5mg 3 times daily and in 80% of patients treated with the 10mg 3 times daily dosage in a large multicentre study. 5.5 and 29% of patients, respectively, withdrew from therapy during the 3-month treatment period because of excessive sweating.

Other events, which were probably related to the cholinergic activity of pilocarpine, included chills, nausea, dizziness, rhinitis, flushing, asthenia, urinary frequency, increased lacrimation, palpitations and gastrointestinal tract disturbance.

No significant effects have been observed on heart rate, blood pressure, or cardiac conductivity during pilocarpine therapy in patients with xerostomia to date; however, this requires further examination, especially in patients with possible complicating medical conditions.

Dosage and Administration

Oral pilocarpine 5mg 3 times daily is recommended for the initial treatment of xerostomia. This may be titrated up to 10mg 3 times daily in patients showing a poor response who tolerate the lower dosage. The lowest dosage that is effective and tolerable should be used for maintenance therapy.

Pilocarpine is contraindicated in patients with uncontrolled asthma, and in patients with acute iritis or narrow-angle glaucoma (unless required before surgery). Caution is advised when administering the drug to patients with controlled asthma, chronic bronchitis, chronic obstructive pulmonary disease or cardiovascular disease, or when coadministering the drug with β-adrenergic antagonists or drugs with parasympathomimetic or anticholinergic effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others


  1. Navazesh M, Ship II. Xerostomia: diagnosis and treatment. Am J Otolaryngol 1983; 4: 283–92

    Article  PubMed  CAS  Google Scholar 

  2. Sreebny LM, Valdini A. Xerostomia: a neglected symptom. Arch Intern Med 1987; 147: 1333–7

    Article  PubMed  CAS  Google Scholar 

  3. Toth BB, Martin JW, Fleming TJ. Oral complications associated with cancer therapy. J Clin Periodontol 1990; 17: 508–15

    Article  PubMed  CAS  Google Scholar 

  4. Ferguson MM. Pilocarpine and other cholinergic drugs in the management of salivary gland dysfunction. Oral Surg Oral Med Oral Pathol 1993; 75: 186–91

    Article  PubMed  CAS  Google Scholar 

  5. Frank RM, Herdly J, Philippe E. Acquired dental defects and salivary gland lesions after irradiation for carcinoma. J Am Dent Assoc 1953; 70: 868–83

    Google Scholar 

  6. Karmiol M, Walsh RF. Dental caries after radiotherapy of the oral regions. J Am Dent Assoc 1975; 91: 838–45

    PubMed  CAS  Google Scholar 

  7. Dreizen S, Brown LR, Handler S, et al. Radiation-induced xerostomia in cancer patients: effect on salivary and serum electrolytes. Cancer 1976; 38: 273–8

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  9. Vissink A, Panders AK, s-Gravenmade EJ, et al. The causes and consequences of hyposalivation. Ear Nose Throat J. 1988; 67: 166–76

    PubMed  CAS  Google Scholar 

  10. Valdez IH, Atkinson JC, Ship JA, et al. Major salivary gland function in patients with radiation-induced xerostomia: flow rates and sialoehemistry. Radiation Oncology Biol Phys 1993; 25: 41–7

    Article  CAS  Google Scholar 

  11. Eneroth CM, Henrikson CO, Jackobsson PÅ. Effects of fractionated radiotherapy on salivary gland function. Cancer 1972; 30: 1147–53

    Article  PubMed  CAS  Google Scholar 

  12. Diagnosis of Sjögren’s syndrome. Lancet 1992; 340: 150

  13. Bjerrum K, Prause JU. Primary Sjögren’s syndrome: a subjective description of the disease. Clin Exp Rheumatol 1990; 8: 283–8

    PubMed  CAS  Google Scholar 

  14. Pilocarpine used to stimulate normal saliva production. J Am Dent Assoc 1985; 111: 310

  15. Butt GM. Drug-induced xerostomia. J Can Dent Assoc 1991; 57: 391–3

    PubMed  CAS  Google Scholar 

  16. Sreebny LM, Schwartz SS. Reference guide to drugs and dry mouth. Gerontology 1986; 5: 75–99

    CAS  Google Scholar 

  17. Kreienbaum MA, Page DP. Stability of pilocarpine hydrochloride and pilocarpine nitrate ophthalmic solutions submitted by US hospitals. Am J Hosp Pharm 1986; 43: 109–17

    PubMed  CAS  Google Scholar 

  18. Gibbs IS, Tuckerman MM. Formulation of a stable pilocarpine hydrochloride solution. J Pharm Sci 1974; 63: 276–9

    Article  PubMed  CAS  Google Scholar 

  19. Neville GA, Hasan FB, Smith ICP. Quantitative analysis of degradation products in pilocarpine hydrochloride opthalmic formulations. J Pharm Sci 1976; 65: 638–42

    Google Scholar 

  20. MGI Pharma. Salagen (pilocarpine hydrochloride): treatment for radiation-induced xerostomia in head and neck cancer patients. Minneapolis, USA.

  21. Oral pilocarpine for xerostomia. Med Lett Drugs Ther 1994 August; 36: 76

  22. Iwabuchi Y, Masuhara T. Subtypes of the muscarine receptors that are involved in pilocarpine-induced secretion of saliva from rat sublingual glands. Asia Pac J Pharmacol 1992 Dec; 7: 271–6

    CAS  Google Scholar 

  23. Mandel ID, Katz R, Zengo A, et al. The effect of pharmacologic agents on salivary secretion and composition in man. I. Pilocarpine, atropine and anticholinesterases. J Oral Ther Pharmacol 1967; 4: 192–9

    PubMed  CAS  Google Scholar 

  24. Mandel ID, Katz RL. Effect of pilocarpine and a beta adrenergic blocking agent on human saliva. Pharmacol Ther Dent 1971; 1: 71–82

    CAS  Google Scholar 

  25. Prutting J. Pilocarpine nitrate and psychostimulants. JAMA 1965; 193: 236–7

    Article  PubMed  CAS  Google Scholar 

  26. Rhodus NL, Schuh MJ. Effects of pilocarpine on salivary flow in patients with Sjogren’s syndrome. Oral Surg Oral Med Oral Pathol 1991; 72: 545–9

    Article  PubMed  CAS  Google Scholar 

  27. Greenspan D, Daniels TE. Effectiveness of pilocarpine in postradiation xerostomia. Cancer 1987; 59: 1123–5

    Article  PubMed  CAS  Google Scholar 

  28. Fox PC, van der Ven PF, Baum BJ, et al. Pilocarpine for the treatment of xerostomia associated with salivary gland dysfunction. Oral Surg Oral Med Oral Pathol 1986; 61: 243–8

    Article  PubMed  CAS  Google Scholar 

  29. Fox PC, Atkinson JC, Macynski AA, et al. Pilocarpine treatment of salivary gland hypofunction and dry mouth (xerostomia). Arch Intern Med 1991; 151: 1149–52

    Article  PubMed  CAS  Google Scholar 

  30. Schuller DE, Stevens P, Clausen KP, et al. Treatment of radiation side effects with oral pilocarpine. J Surg Oncol 1989; 42: 272–6

    Article  PubMed  CAS  Google Scholar 

  31. Vivino FB, Hermann GA, Huang CH, et al. Preliminary study of pilocarpine tablets in Sjogren’s syndrome [abstract no. 296]. Arthritis Rheum 1994 September; 37 (9) Suppl.: S208

    Google Scholar 

  32. 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

    PubMed  CAS  Google Scholar 

  33. Valdez IH, Wolff A, Atkinson JC, et al. Use of pilocarpine during head and neck radiation therapy to reduce xerostomia and salivary dysfunction. Cancer 1993; 71: 1848–51

    Article  PubMed  CAS  Google Scholar 

  34. Greenspan D. Oral complications of cancer therapies. Management of salivary dysfunction. NCI Monograph 1990; 9: 159–61

    Google Scholar 

  35. Kohn WG, Ship JA, Atkinson JC, et al. Salivary gland99mTC-scintigraphy: a grading scale and correlation with major salivary gland flow rates. J Oral Pathol Med 1992; 21: 70–4

    Article  PubMed  CAS  Google Scholar 

  36. Fox PC. Systemic therapy of salivary gland hypofunction. J Dent Res 1987; 66 Spec: 689–92

    PubMed  Google Scholar 

  37. Leach SA, Connell R. Reversal of fissure caries in the albino rat by stimulating salivary flow with piloearpine. Caries Res 1990; 24: 127–9

    Article  PubMed  CAS  Google Scholar 

  38. O’Connell AC, Pearson SK, Bowen WH. Piloearpine alters caries development in partially desalivated rats. J Dent Res 1994; 73: 637–43

    PubMed  Google Scholar 

  39. Ortiz GC, Pearson SK, Bowen WH. Influence of piloearpine, propranolol, and atropine on susceptibility to infection [abstract 186]. J Dent Res 1992; 71: 129

    Google Scholar 

  40. Hunt.TL. A double-blind, placebo-controlled, multiple-dose, tolerance and pharmacokinetic study of oral piloearpine hydrochloride (HC1) in healthy male subjects. MGI Pharma (Minneapolis) data on file. MGI 647.83.CR91-03; Dec 24, 1991.

  41. Hunt TL. The effect of a high fat meal on the bioavailability of oral piloearpine hydrochloride (HC1) in healthy, male subjects. MGI Pharma (Minneapolis) data on file. MGI 647.83.CR91-02; Dec 27, 1991.

  42. Hunt TL. A single-dose, pharmacokinetic study of oral piloearpine hydrochloride (HC1) (5mg) in elderly subjects. MGI Pharma (Minneapolis) data on file. MGI 647.83.CR91-05; Jan 3, 1992.

  43. Carlson AV, Crittenden AL. The relationship of ptyalin concentration to the diet and to the rate of secretion of saliva. Am J Physiol 1910; 26: 169–77

    Google Scholar 

Download references

Author information

Authors and Affiliations


Additional information

Various sections of the manuscript reviewed by: W.H. Bowen, Department of Dental Research, University of Rochester, Rochester, New York, USA; J. Ekström, Department of Pharmacology, Göteborg University, Göteborg, Sweden; J.B. Epstein, Division of Dentistry, Cancer Control Agency of British Columbia, Vancouver, British Columbia, Canada; U.G. Friis, Department of Pharmacology, University of Odense, Odense, Denmark; T. Hara, Department of Child Neurology, Tottori University School of Medicine, Yonago City, Japan; H. Joensuu, Department of Oncology and Radiotherapy, University of Turku Central Hospital, Turku, Finland; J.T. Johnson, Division of Head and Neck Oncology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh Pennsylvania, USA; F.G. Leveque, Department of Otolaryngology, Harper Hospital, Detroit, Michigan, USA; T. Nederfors, Department of Hospital Dentistry, Central Hospital, Halmstad, Sweden; S. Shiozawa, Department of Medicine, Kobe University School of Medicine, Kobe, Japan; D. Zegarelli, Columbia Presbyterian Medical Center, New York, New York, USA.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wiseman, L.R., Faulds, D. Oral Pilocarpine: A Review of its Pharmacological Properties and Clinical Potential in Xerostomia. Drugs 49, 143–155 (1995).

Download citation

  • Published:

  • Issue Date:

  • DOI: