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

Abstract

A double-blind, placebo-controlled study was conducted to evaluate the effect of orally administered pilocarpine on unstimulated whole-saliva flow and composition in 28 patients with chronic graft-versus-host disease (cGVHD). Thirteen patients were treated with pilocarpine of 20 mg/ day orally for 7 days, and 15 patients with placebo. Unstimulated whole saliva was collected in the morning on four occasions (30 min before pilocarpine or placebo intake, and 1 h, 1 day and 7 days after the first intake). Significantly, higher salivary flow rates, and sodium and total protein outputs were observed in the second samples of pilocarpine-treated patients compared with controls, whereas calcium and IgA outputs were not altered. Changes in these parameters were not significant in the third and fourth samples, although they were higher in the pilocarpine group. Patients who had received pilocarpine expressed satisfaction with their treatment. These data suggest that pilocarpine may improve salivary flow rate and the feeling of xerostomia in patients with cGVHD.

Immune Processes and Pathogenic Fibrosis in Ocular Chronic Graft-Versus-Host Disease and Clinical Manifestations after Allogeneic Hematopoietic Stem Cell Transplantation

“…70 Pilocarpine stimulation may be effective for ocular surface in some cases. 71 There is no specific therapy for ocular fibrosis at present. In this regard, topical tranilast may be useful for the treatment of early dry eye associated with cGVHD through inhibiting TGF-b signaling for ocular fibrosis, although further study is needed to confirm the efficacy.…”

How we treat oral chronic graft-versus-host disease

“…Of note, patients with cGVHD-associated xerophthalmia may also benefit from this therapy. 15,54,58 Systemic immunosuppressive therapy, however, tends to be relatively ineffective in improving symptoms of salivary gland cGVHD.…”

“…Both of these agents are US Food and Drug Administration-approved for the management of xerostomia in patients who have received head and neck radiation therapy, but not cGVHD specifically, and appear to have similar rates of efficacy and side effects. 15,55,[57][58][59] In the absence of adverse effects, patients should continue to take the medication for at least 8 weeks and the initial dose can be doubled (eg, increasing pilocarpine from 5-10 mg) before making a determination that they are nonresponders. 15 Sialogogue therapy is not immunosuppressive but is contraindicated in patients with pulmonary cGVHD (or other obstructive pulmonary disease) because of the potential for stimulation of pulmonary secretions resulting in wheezing and difficulty breathing.…”

“…15,[54][55][56][57][58] Approximately 50% of patients respond with improved salivary flow and decreased xerostomia symptoms; and although full response may take up to 8-12 weeks, improvement is typically noted within 1-2 weeks of beginning therapy. Primarily because of cost considerations, we prescribe pilocarpine (Salagen, 5 mg orally 3 times a day) as initial therapy, reserving cevimeline (Evoxac, 30 mg 3 times a day) for those who do not respond.…”

Technological development and evaluation on sialagogue activity of a spray-like liquid formulation of pilocarpine

“…Currently, systemic pilocarpine is indicated for the management of xerostomia secondary to irradiation damage, chronic Graft-Versus-Host disease and glandular autoimmune attack given by Sjögren's syndrome (Fávaro et al, 2006;Agha-Hosseini et al, 2007). Furthermore is the sole sialagogue agent approved by FDA for radiotherapy treatment (Kaluzny et al, 2014).…”