Medicines Q&As Q&A 173.4 Can patients with renal impairment take glucosamine? Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp Date prepared: July 2013 Background Glucosamine, a naturally occurring sugar, serves as a building block for proteoglycans and glycosaminoglycans, which are important constituents of articular (joint) cartilage. Glucosamine is important for maintaining the elasticity, strength and resilience of cartilage in joints, which helps to reduce joint damage (1). The mechanism of action of glucosamine in humans is not understood and there is limited evidence to show that it is effective (2). Glucosamine is commonly used for the relief of pain and symptoms associated with osteoarthritis and other joint disorders. It is available in the form of tablets, capsules and powders as glucosamine sulphate and glucosamine hydrochloride. Glucosamine supplements are either produced synthetically or derived from the shells of shellfish (3). Glucosamine and its salts are widely available as licensed products or so-called “health supplements” for the symptomatic relief of osteoarthritis (4-7). They may be combined with other agents supposed to be of benefit including chondroitin, vitamins and various herbs (7). Answer Glucosamine is available in a variety of over-the-counter dietary supplements and as licensed prescription only medicines, therefore quality and content varies between products (3). Little information is available about herbs and dietary supplements in patients with renal impairment. There have been no studies of glucosamine use in patients with renal impairment and the manufacturers of the licensed products have no recommendations on dose modification in such patients (4-6). Acute interstitial nephritis has been reported as a possible adverse effect of glucosamine. A 75 year old man with a history of difficulty in passing urine, urgency and nocturia, was hospitalised and diagnosed with tubulointerstitial nephritis. The only medicine he had been exposed to was glucosamine (dose unknown) which he had been taking for two to three months to treat osteoarthritis. There were no other obvious precipitating causes and his symptoms significantly improved following discontinuation of the glucosamine (8,9). There have been anecdotal reports of non-specific renal impairment associated with glucosamine. This includes a report describing four episodes of proteinuria (10) and one report of renal dysfunction characterised by an elevated creatinine level. Routine blood analysis of a 79 year old woman following five months treatment with glucosamine (1 tablet daily) for osteoarthritis, revealed elevated urea and creatinine levels without proteinuria. Concomitant therapy included ciclosporin for myasthenia gravis. Following discontinuation of the glucosamine, the urea and creatinine levels gradually returned to normal (11). Although there have been anecdotal reports of renal toxicity associated with glucosamine, causality has not been established and long-term studies have not shown changes in renal function (12,13). Limited information is available on the pharmacokinetics of glucosamine. Glucosamine is a relatively small water soluble molecule (molecular mass 179) (4). Following oral administration, bioavailability is low due to first-pass hepatic metabolism. A notable proportion of glucosamine is metabolised into smaller molecules and ultimately into carbon dioxide, water and urea. Glucosamine is not protein bound but rather incorporated into plasma proteins and free glucosamine is not detectable in plasma. The elimination half-life of glucosamine incorporated into plasma proteins is 68 hours after single Available through NICE Evidence Search at www.evidence.nhs.uk 1 Medicines Q&As dose oral administration. Approximately 10% of an oral dose is excreted in the urine as unchanged substance (14). One source suggests that due to the characteristics of the drug, it is advisable to administer usual doses in mild renal impairment, to reduce the dose in moderate renal impairment, and to avoid in severe renal impairment and dialysis patients. However it should be noted that this is an old text (15). Glucosamine should be used with caution in patients with renal impairment, with monitoring of side effects and renal function (16). It is advisable to avoid use in patients with severe renal impairment and those on dialysis (15). Summary Glucosamine is used for the relief of pain and symptoms associated with osteoarthritis. The majority of preparations are unlicensed and sold as dietary supplements; therefore quality and content varies between products. Little information is available about “natural products” in patients with renal impairment. There have been no studies of glucosamine use in patients with renal impairment. Acute interstitial nephritis has been reported as a possible adverse effect of glucosamine. There have been anecdotal reports of non-specific renal impairment associated with glucosamine. Although there have been anecdotal reports of renal toxicity associated with glucosamine, causality has not been established and longterm studies have not shown changes in renal function. Glucosamine is extensively metabolised in the liver but has some renal excretion. Glucosamine should be used with caution in patients with renal impairment, with monitoring of side effects and renal function. It is advisable to avoid use of glucosamine in patients with severe renal impairment and those on dialysis until more data is available. Limitations There is a lack of data on glucosamine and no studies of glucosamine use in patients with renal impairment. The National Institute of Health and Clinical Excellence (NICE) does not recommend glucosamine products for the treatment of osteoarthritis (17). References 1. Mason P, editor. Dietary Supplements 4th edition. London: Pharmaceutical Press; 2012, p 239-251. 2. Joint Formulary Committee. British national Formulary. Electronic edition. No. 65. London: BMJ Publishing Group Ltd and RPS Publishing, 2013. Accessed via http://www.bnf.org/ on 09/04/13. 3. Glucosamine for knee osteoarthritis – What’s new? Drug Ther Bull 2008; 46: 81-4. 4. Summary of Product Characteristics: Alateris, Laboratoires Expanscience. Date of revision of text 04/08/10. Accessed via www.mhra.gov.uk on 06/08/13. 5. Summary of Product Characteristics: Glusartel. Rottapharm Ltd. Date of revision of the text 22/10/2010. Accessed via www.mhra.gov.uk on 06/08/13. Available through NICE Evidence Search at www.evidence.nhs.uk 2 Medicines Q&As 6. Summary of Product Characteristics: Dolenio. Blue Bio Pharmaceutics Ltd. Date of revision of the text 29/06/2012. 7. Sweetman S, editor. Martindale: The complete drug reference. London: Pharmaceutical Press. Electronic version. Accessed via www.medicinescomplete.com on 09/04/13 8. Audimoolam VK, Bhandari S. Acute interstitial nephritis induced by glucosamine. Nephrol Dial Transplant 2006; 21: 2031 (letter). 9. Ahmed R. Acute tubulointerstitial nephritis induced by glucosamine: comment on the letter by Audimoolam VK, Bhandari S. Nephrol Dial Transplant 2007; 22: 282 (letter). 10. Danao-Camara T. Potential side effects of treatment with glucosamine and chondroitin. Arthritis Rheum 2000; 43: 2853 (letter). 11. Guillaume MP, Peretz A. Possible association between glucosamine treatment and renal toxicity. Arthritis Rheum 2001; 44: 2943-4 (letter). 12. Reginster JY, Deroisy R, Rovati LC et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 2001;357:251-6. 13. Pavelka K, Gatterova J, Olejarova M et al. Glucosamine sulfate use and delay of progression of knee osteoarthritis: A 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 2002;162:2113-23. 14. Setnikar, Palumbo R, Canali S et al. Pharmacokinetics of glucosamine in man. Arzneimittelforschung 1993; 43: 1109-13 15. Gunter Seyffart, editor. Drug dosage in renal insufficiency. Netherlands: Kluwer Academic Publishers; 1991, p 271-2 16. Henderson S. Glucosamine – what are the adverse effects? UKMi Medicines Q&A 143.3 August 2012. Accessed via https://www.evidence.nhs.uk/search?q=Glucosamine%20ADVERSE%20EFFECTS&om=%5 B%7B%22srn%22%3A%5B%22%20ukmi%20%22%5D%7D%5D on 06/08/13 17. NICE Clinical Guideline 59 Osteoarthritis www.nice.org.uk/CG059 Accessed 01/08/13 Quality Assurance Prepared by Alison Alvey, South West Medicines Information and Training, Bristol. Date this version prepared July 2013 Checked by Julia Kuczynska, South West Medicines Information and Training, Bristol. Date of check 6th August 2013 Search strategy Embase 1974 to date (Glucosamine and kidney-failure) Medline 1996 to date (Glucosamine and kidney-failure) In-house database/ resources (including the Natural Medicines Comprehensive Database and Drugdex). Personal communication with manufacturer (William Ransom & Son PLC, June 2008) Available through NICE Evidence Search at www.evidence.nhs.uk 3