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A Guide to Medications Inducing Salivary Gland Dysfunction

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A Guide to Medications Inducing Salivary Gland Dysfunction Drugs R D DOI 10.1007/s40268-016-0153-9 SYSTEMATIC REVIEW A Guide to Medications Inducing Salivary Gland Dysfunction, Xerostomia, and Subjective Sialorrhea: A Systematic Review Sponsored by the World Workshop on Oral Medicine VI 1,2 3 4 5 Andy Wolff • Revan Kumar Joshi • Jo¨rgen Ekstro¨m • Doron Aframian • 6 7 8 Anne Marie Lynge Pedersen • Gordon Proctor • Nagamani Narayana • 9 10 11,12 13 Alessandro Villa • Ying Wai Sia • Ardita Aliko • Richard McGowan • 13 6,14 15 16 Alexander Ross Kerr • Siri Beier Jensen • Arjan Vissink • Colin Dawes Ó The Author(s) 2016. This article is published with open access at Springerlink.com Abstract chemical substances with a higher level of evidence and 50 Background Medication-induced salivary gland dysfunc- with a moderate level of evidence of causing the above- tion (MISGD), xerostomia (sensation of oral dryness), and mentioned disorders. At the first level of the Anatomical subjective sialorrhea cause significant morbidity and Therapeutic Chemical (ATC) classification system, 9 of 14 impair quality of life. However, no evidence-based lists of anatomical groups were represented, mainly the alimen- the medications that cause these disorders exist. tary, cardiovascular, genitourinary, nervous, and respira- Objective Our objective was to compile a list of medica- tory systems. Management strategies include substitution tions affecting salivary gland function and inducing or discontinuation of medications whenever possible, oral xerostomia or subjective sialorrhea. or systemic therapy with sialogogues, administration of Data Sources Electronic databases were searched for rel- saliva substitutes, and use of electro-stimulating devices. evant articles published until June 2013. Of 3867 screened Limitations While xerostomia was a commonly reported records, 269 had an acceptable degree of relevance, quality outcome, objectively measured salivary flow rate was of methodology, and strength of evidence. We found 56 rarely reported. Moreover, xerostomia was mostly assessed & Andy Wolff 10 McGill University, Faculty of Dentistry, Montreal, QC, [email protected] Canada 11 Faculty of Dental Medicine, University of Medicine, Tirana, 1 Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel Albania 2 Saliwell Ltd, 65 Hatamar St, 60917 Harutzim, Israel 12 Broegelmann Research Laboratory, Department of Clinical 3 Department of Oral Medicine and Radiology, DAPMRV Science, University of Bergen, Bergen, Norway Dental College, Bangalore, India 13 New York University, New York, NY, USA 4 Department of Pharmacology, Institute of Neuroscience and 14 Department of Dentistry and Oral Health, Aarhus University, Physiology, The Sahlgrenska Academy at the University of Aarhus, Denmark Gothenburg, Go¨teborg, Sweden 15 Department of Oral and Maxillofacial Surgery, University of 5 The Hebrew University, Jerusalem, Israel Groningen, University Medical Center Groningen, 6 Department of Odontology, Faculty of Health and Medical Groningen, The Netherlands Sciences, University of Copenhagen, Copenhagen, Denmark 16 Department of Oral Biology, University of Manitoba, 7 Mucosal and Salivary Biology Division, Dental Institute, Winnipeg, MB, Canada King’s College London, London, UK 8 Department of Oral Biology, University of Nebraska Medical Center (UNMC) College of Dentistry, Lincoln, NE, USA 9 Division of Oral Medicine and Dentistry, Department of Oral Medicine Infection and Immunity, Brigham and Women’s Hospital, Harvard School of Dental Medicine, Boston, MA, USA A. Wolff et al. as an adverse effect rather than the primary outcome of salivary gland dysfunction (MISGD). The possible adverse medication use. This study may not include some medi- effects associated with these disorders, especially SGH, cations that could cause xerostomia when administered in include dental caries, dysgeusia, oral mucosal soreness, and conjunction with others or for which xerostomia as an oral candidiasis. adverse reaction has not been reported in the literature or Current literature guiding clinicians in the prescribing of was not detected in our search. medications while considering the relevant adverse effects Conclusions We compiled a comprehensive list of medi- on salivary glands is very scarce. Most of the available cations with documented effects on salivary gland function literature attempting to list relevant drugs comprises a or symptoms that may assist practitioners in assessing compendium based on manufacturers’ drug profiles, nar- patients who complain of dry mouth while taking medi- rative reviews, and case reports, or original research papers cations. The list may also prove useful in helping practi- not containing a overall list of medications [1–10]. A tioners anticipate adverse effects and consider alternative systematic evidence-based list that identifies and lists medications. medications that could objectively be associated with MISGD, xerostomia, or subjective sialorrhea is lacking. Hence, the MISGD group of the World Workshop on Oral Medicine VI (WWOM VI) aimed to review the current Key Points knowledge on this subject and compile a list of medications and their objective effects on salivary gland function, based We compiled a comprehensive list of medications on a high level of evidence and relevance. with documented effects on salivary gland function or symptoms that may assist practitioners assessing patients who complain of dry mouth while taking 2 Materials and Methods medications. The list may also prove useful in helping The MISGD group comprised five reviewers (AA, RJ, NN, practitioners anticipate oral adverse effects and YS, and AlV), six consultants (senior experts in fields consider alternative medications. related to MISGD: DA, CD, JE, AMP, GP, and ArV), one research librarian (RM), one group head (AW), and two supervisors on behalf of the WWOM VI Steering Com- mittee (SBJ and ARK). This review addresses one of the 1 Introduction MISGD topics covered by the group, an updated classifi- cation of medications reported to cause objective SGD. The Increased life expectancy, aging populations, and the research method was based on the policies and standards association of these with polypharmacy have been set forth by a task force for WWOM IV [11] and by the intriguing topics over the last few decades. The World PRISMA (Preferred Reporting Items for Systematic Health Statistics of 2014 published on the World Health Reviews and Meta-Analyses) statement [12], which was Organization website reports a life expectancy of 55–87 adapted to the current review. years in its various constituent countries, with even the lower economy countries reporting rapid increases in life 2.1 Step 1: Scope Definition expectancy. However, with increased age comes a greater number of ailments, which in turn is indicative of a higher The current review covered seven research questions, as intake of medications. follows: Medications for the treatment of various diseases may Which medications have been reported to induce: also cause adverse effects, including those related to the 1. SGD in humans? oral cavity by their effects on the salivary glands. Apart 2. SGD in animals? from medications used to treat salivary gland disorders, 3. xerostomia but not SGD? other medications can also have the following adverse 4. drooling but not SGD? effects: salivary gland dysfunction (SGD), including sali- 5. xerostomia-related oral symptoms (but not SGD) other vary gland hypofunction (SGH) (an objectively measured than excessive dryness/wetness? decrease in salivation) or objective sialorrhea (an excessive 6. xerostomia but have not been tested yet for induction secretion of saliva), xerostomia (subjective feeling of dry of SGD? mouth), or subjective sialorrhea (feeling of having too 7. drooling but have not been tested yet for induction of much saliva). Medication-induced SGH and objective SGD? sialorrhea are collectively termed medication-induced Guide to Medications Inducing Salivary Gland Dysfunction, Xerostomia and Subjective Sialorrhea 2.2 Step 2: Search Term Selection their reviews. Papers were then divided among the reviewers, who analyzed publication titles, abstracts, and The following keywords and subject headings were selec- the materials and methods sections for key parameters. ted for each research question: 2.6 Medication General Inclusion and Exclusion Q1. Medication/drugs/humans AND salivary gland dys- Criteria function, xerostomia, dry mouth, reduced salivary flow rate, hyposalivation, sialorrhea, drooling. 1. Particular drugs for which MISGD has been reported Q2. Medication/drugs/animals AND salivary gland dys- were included. function, reduced salivary flow rate, hyposalivation, 2. A group of drugs or a combination of two or more drugs drooling. without specifying the individual MISGD of each drug Q3. Medication/drugs AND xerostomia, dry mouth, under the group or combination were excluded. hyposalivation AND NOT salivary dysfunction. 3. Drugs reported to induce SGD or used in therapeutic Q4. Medication/drugs AND drooling/sialorrhea/hyper- aspects of SGD were excluded. Thus, parasympath- salivation/ptyalism/increased salivary flow rate omimetics (e.g., pilocarpine and cevimeline) and the AND NOT salivary dysfunction. anti-cholinesterases (e.g., physostigmine and neostig- Q5. Medication/drugs AND salivary glands/saliva/xeros- mine), which are used for stimulation of salivary flow in tomia/dry mouth/hyposalivation AND NOT salivary patients experiencing a dry mouth, were not included. gland dysfunction, oral sensory complaints. 4. Research drugs that were not yet
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