Pilocarpine hydrochloride relieves xerostomia in chronic graft-versus-host disease: a sialometrical study

Abstract

Summary:Bone marrow transplantation is considered to be the treatment of choice for various hematological and solid malignancies, as well as for bone marrow failure syndromes and some genetic diseases. Unfortunately, a great number of patients who receive allogeneic BMT suffer from graft-versus-host disease (GVHD) following the procedure. Xerostomia is considered to be one of the most annoying complications of chronic GVHD (cGVHD), and the rapidly growing number of BMT patients with prolonged survival renders GVHD-related xerostomia a major clinical problem. As pilocarpine hydrochloride has been shown to relieve xerostomia in other disease categories, we administered pilocarpine hydrochloride 30 mg/day to six cGVHD patients and measured their whole saliva, parotid and submandibular-sublingual flow rates in both resting and stimulated conditions. Mean values of flow rates of whole saliva in resting conditions at 2 weeks, 2 months and 6 months following administration of pilocarpine hydrochloride 30 mg/day were 0.71 ؎ 0.12 ml/min, 0.59 ؎ 0.07 ml/min and 0.56 ؎ 0.11 ml/min, respectively. In stimulated conditions, mean values were 1.7 ؎ 0.3 ml/min, 1.0 ؎ 0.17 ml/min and 0.94 ؎ 0.21 ml/min, respectively. The mean values of whole saliva flow rates under both conditions represented an increase of 224-284% and 134-247%, respectively (P Ͻ 0.01). The pattern and magnitude of parotid and submandibular-sublingual flow rate increases following pilocarpine hydrochloride administration were similar. Patients were followed for 6 months and demonstrated increased levels of secretion, with some reduction after the initial peak values. The medication was discontinued at 2 months and reinstated after 2 weeks in three patients. This resulted in rapid flow rate reduction followed by another profound increase. Contrary to the sialometrical analysis, the subjective scoring showed no fluctuations during the study period. We discuss these results in the context of the clinical experience of xerostomic patients in whom even a minute increase in secretion may be significant. Our results demonstrate that objective and subjective relief from xerostomia in cGVHD patients can be achieved with the routine oral administration of pilocarpine hydrochloride.

Effect of pilocarpine hydrochloride on unstimulated whole saliva flow rate and composition in patients with chronic graft-versus-host disease (cGVHD)

“…It seems that pilocarpine may increase the output of saliva composition. Consistent with others 3,4,19,26 our study may indicate that pilocarpine normalizes salivary flow and composition alteration in cGVHD patients.…”

“…Any increase in salivation, no matter how small, which is accompanied by an increase in the production of beneficial constituents, may be a benefit to patients with xerostomia. 3,4 …”

“…1 Unfortunately, a number of patients who receive allogeneic BMT suffer from chronic graft-versus-host disease (cGVHD) following the procedure. [2][3][4][5][6] Oral symptoms in extensive form are present in approximately 80% of patients. 5 Usually, atrophy of mucous membranes promotes the development of severe periodontitis and caries.…”

Oral complications of cancer and cancer therapy

“…Pilocarpine hydrochloride, a nonspecific muscarinic and weak b-adrenergic agonist, 99 was the first drug approved in the United States to be shown to increase salivary flow rates under both resting and stimulated conditions compared with baseline (standard dosing of 5 mg 3 times a day). 103 However, there have been mixed results reported for the administration of pilocarpine during RT as a preventive agent. 79,104,105 Cevimeline is a selective M3 muscarinic receptor acetylcholine analog that when administered orally at a dose of 30 mg given 3 times daily has been shown to increase nonstimulated salivary flow.…”

Effect of pilocarpine mouthwash on salivary flow

“…The results showed that pilocarpine is superior to placebo to relieve xerostomia complaints. At the present time it has been well established that oral pilocarpine is able to improve sicca symptoms, in particular those related to eyes and mouth in patients with systemic disorders such as Sjögrens syndrome (22)(23)(24) or other autoimmune conditions (25) and secondary to radiation therapy (26). After oral administration, the most common side effect is sweating, but urinary and gastrointestinal disturbances are also frequently reported (3,6,22).…”