PEP Topic 

Pilocarpine is a cholinergic agonist. It works by increasing the amount of saliva in the mouth. It is used to treat dry mouth and mucositis caused by radiotherapy in people with head and neck cancer. Pilocarpine comes as a tablet to take by mouth.

Effectiveness Not Established

Research Evidence Summaries

Awidi, A., Homsi, U., Kakail, R.I., Mubarak, A., Hassan, A., Kelta, M., … El-Aloosy, A.S. (2001). Double-blind, placebo-controlled cross-over study of oral pilocarpine for the prevention of chemotherapy-induced oral mucositis in adult patients with cancer. European Journal of Cancer, 37, 2010–2014.

doi: 10.1016/S0959-8049(01)00189-7

Intervention Characteristics/Basic Study Process:

Patients were given oral pilocarpine (OP) or placebo, 5 mg tablet blister pack, 1 hour before chemotherapy administration and 1 tablet every eight hours for seven days. After two weeks, the alternate arm was given with the same chemotherapy. Normal saline mouthwash only was permitted. No granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), or dose modifications were allowed. Empty blister packs were returned and remaining tablets were counted.

Sample Characteristics:

  • The study reported on 38 patients with various diagnoses and chemotherapy regimens.
  • Median age was 45.8 years, and the age range was 23–62 years.


The study was conducted from February to December of 2000.

Study Design:

This study had a randomized, double-blind, placebo-controlled, cross-over design.

Measurement Instruments/Methods:

Patients were seen daily on days 7–11 post-chemotherapy. Patients were checked for signs and symptoms of mucositis.

Mucositis was scored using three measures.

A. Method developed by J.P. Donnelly and colleagues, 1992

B. The World Health Organization (WHO) mucositis score

C. Report of mild, moderate, or severe

Peak A, B, and C scores and presence of mucositis were recorded.


Results for 32 patients receiving 82 courses of chemotherapy were included; six patients were excluded from the results because of protocol violations.

OP was effective in preventing and reducing the severity of mucositis (p < 0.005 and < 0.001).

Placebo versus OP scores were as follows.

A. 52 versus 11 (p < 0.001)

B.  25 versus 6 (p < 0.001)

C.  23 versus 6 (p < 0.001)

No course with mucositis: 20 versus 6 (p < 0.005)

Side effects included tachycardia and palpitations in one patient.


The study showed that oral pilocarpine was associated with lower rates and severity of oral mucositis.


The sample size was small.

Lockhart, P.B., Brennan, M.T., Kent, M.L., Packman, C.H., Norton, H.J., Fox, P.C., & Frenette, G. (2005). Randomized controlled trial of pilocarpine hydrochloride for the moderation of oral mucositis during autologous blood stem cell transplantation. Bone Marrow Transplantation, 35, 713–720.

doi: 10.1038/sj.bmt.1704820

Intervention Characteristics/Basic Study Process:

Patients were given a 5-mg pilocarpine tablet or placebo starting the day before the conditioning regimen, every 4 hours, for a total of 4 tablets per day. Patients continued taking tablets until absolute neutrophil count (ANC) was greater than 500 for 48 hours, discharge from hospital, or mucosal recovery.

Sample Characteristics:

  • The study reported on 36 patients with 20 receiving pilocarpine and 16 receiving placebo.
  • Patients were undergoing autologous stem cell transplant (SCT) with multiple (not all hemotologic) malignancies.

Study Design:

This was a prospective, double-blind, randomized, placebo-controlled trial. Patients were stratified by diagnosis and randomized by a computer-generated numbering scheme.

Measurement Instruments/Methods:

  • The World Health Organization (WHO) mucositis scale and CMC outcome measures toxicity criteria were used.
  • Numerous outcomes were measured.


  • No statistically significant differences were found in the incidence, severity, or duration of mucositis.
  • Pain at rest and with swallowing and the use of systemic narcotics were not significantly different.


Despite prior small trials that showed a benefit, this study clearly did not.  The intervention was not effective.

Nursing Implications:

A standardized scoring system is needed.

Systematic Review/Meta-Analysis

Jensen, S.B., Jarvis, V., Zadik, Y., Barasch, A., Ariyawardana, A., Hovan, A., . . . Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). (2013). Systematic review of miscellaneous agents for the management of oral mucositis in cancer patients. Supportive Care in Cancer, 21(11), 3223–3232.

doi: 10.1007/s00520-013-1884-6


To analyze the available literature and define clinical practice guidelines for the use of the following agents for the prevention and treatment of oral mucositis (OM): allopurinol, midline mucosa-sparing radiation blocks, payayor, pentoxifylline, timing of radiation therapy (morning versus afternoon), pilocarpine, bethanechol, chewing gum, propantheline, and tetrachlorodecaoxide

Search Strategy:

  • KEYWORDS: Oral mucositis, cancer therapy, supportive, palliative, prevention, treatment, and saliva
  • Inclusion and exclusion criteria were not listed in this report, but, rather, were referenced from the criteria listed in another referenced study.

Literature Evaluated:

A total of 99 references were retrieved. Of these, 18 were excluded based on the inclusion/exclusion criteria (which was not stated in the article). Of the remaining 81 papers, 49 pertained to agents of natural origin and the results on those agents were reported separately. This manuscript reported the results of the review of the remaining 32 papers that tested interventions that did not fit in any of the other categories and were classified as miscellaneous agents.

Studies were evaluated based on the list of major and minor flaws published by Hadorn. Level of evidence was assigned for each intervention based on the Somerfield criteria. A well-designed study was defined as a study with no major flaws per the Hadorn criteria. Findings from the reviewed studies were integrated into guidelines based on the overall level of evidence for each intervention.

Sample Characteristics:

  • A final sample of 32 papers addressing 10 interventions were included in the report.
  • The numbers of patients and sample ranges across all studies were not reported.
  • Patient populations included patients receiving high-dose chemotherapy before stem cell transplantation, patients receiving radiation therapy (RT) for head and neck cancer, and patients receiving bone marrow transplantation.

Phase of Care and Clinical Applications:

PHASE OF CARE: Active treatment


Suggestions were made against the use of systemic pilocarpine administered orally for prevention of OM during RT in patients with head and neck cancer and in patients receiving high-dose chemotherapy with or without total body irradiation, prior to hematopoietic stem cell transplantation as well as against the use of systemic pentoxifylline administered orally for the prevention of OM in patients undergoing bone marrow transplantation. No guideline was possible for any other agent reviewed because of inadequate or conflicting evidence.


None of the agents reviewed was determined to be effective for the prevention or treatment of OM. This review was inadequate and difficult for the reader to understand. The methods section was missing needed information to assess the interventions and the associated recommendations.


  • The scope of the analysis was too large, as 32 studies were included from which the review panel attempted to make recommendations about 10 different interventions.
  • The level of evidence was not explained to the reader, making it difficult to assess the results obtained and impossible to know if the study selection was biased.
  • The authors stated that the criteria for a well-designed study was no major flaws per the Hadorn criteria but did not tell the reader what the criteria were.
  • The authors were not clear if only well-designed studies were used exclusively.

Nursing Implications:

Many products on the market claim to prevent or treat OM. Nurses need to be well informed before recommending any products or interventions to patients. Further research is needed.