New low-dose liquid pilocarpine formulation for treating dry mouth in Sj\xf6gren\u2019s syndrome: clinical efficacy, symptom relief, and improvement in quality of life

Machiko Watanabe,Hiroyuki Hosono,Yoshinori Komagata,Fumio Itagaki,Hirotoshi Kikuchi,Chisato Yamada

doi:10.1186/s40780-018-0099-x

Machiko Watanabe, Hiroyuki Hosono + Show 4 more

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https://doi.org/10.1186/s40780-018-0099-x

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Abstract

BackgroundPatients with Sjögren’s syndrome (SS) typically present clinically with xerostomia (dry mouth) because of progressive damage to the exocrine glands. We developed a new, low-dose pilocarpine/sodium alginate (LPA) solution with pilocarpine hydrochloride to inhibit systemic adverse effects by administering via the oral mucosa. The purpose of this study was to assess its stability, safety, and efficacy.MethodsThe pilocarpine concentration in an LPA liquid formulation was measured 3, 7, 14, and 28 days after preparation to assess its stability. A prospective clinical trial was undertaken to assess the efficacy and safety of the LPA solution as a symptomatic treatment for dry mouth in SS. Patients (n = 24) with clinically significant xerostomia were enrolled after providing written informed consent. Whole-mouth salivary flow rate was measured twice; immediately before and 60 min after LPA application. Symptoms were assessed by questionnaire with visual analog scales or checkboxes before the first application (baseline), and then once daily for 7 days.ResultsThe pilocarpine content 3, 7, 14, and 28 days after preparation showed no marked change, confirming its stability. Salivary flow was significantly increased from 0.076 ± 0.092 g/30 s to 0.122 ± 0.140 g/30 s 60 min after LPA administration (P < 0.001). Dry mouth and thirstiness showed significant improvement compared with that of baseline (P ≤ 0.01). The only adverse effect was sweating, and no serious drug-related adverse events were reported.ConclusionsThis new, low-dose pilocarpine formulation was well-tolerated and resulted in significant improvements in symptoms of dry mouth and other xerostomic conditions in patients with SS.Trial registrationThe study approval number in the institution; 08–068-2. Registered January 19, 2009. UMIN000029307. Registered 27 September 2017 (retrospectively registered).

Highlights

Patients with Sjögren’s syndrome (SS) typically present clinically with xerostomia because of progressive damage to the exocrine glands
Pilocarpine hydrochloride tablets are currently indicated for the treatment of xerostomia in SS, their toxicity is frequently reported [4, 5]
Low-dose pilocarpine formulation of a pilocarpine/sodium alginate (LPA) solution

Summary

Introduction

Patients with Sjögren’s syndrome (SS) typically present clinically with xerostomia (dry mouth) because of progressive damage to the exocrine glands. Sjögren’s syndrome (SS), a chronic autoimmune disease with slow progression, is characterized by lymphocytic infiltration into the exocrine glands, resulting in xerostomia. As a result of exocrine dysfunction, most patients with SS have symptoms related to diminished activity of the salivary glands, which can cause difficulty chewing and swallowing food and speaking without frequent water intake [1]. Pilocarpine is a parasympathomimetic agent that functions primarily as a muscarinic agonist with mild βadrenergic activity. This alkaloid causes pharmacologic stimulation of exocrine glands in humans, resulting in diaphoresis, salivation, lacrimation, and gastric and pancreatic secretion. Pilocarpine hydrochloride tablets are currently indicated for the treatment of xerostomia in SS, their toxicity is frequently reported [4, 5]

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