Drug General Information (ID: DDIC912BDS)
  Drug Name Levothyroxine Drug Info Glyburide Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antithyroid Agents Antidiabetic Agents
  Structure

 Mechanism of Levothyroxine-Glyburide Interaction (Severity Level: Moderate)
     Antagonize the effect of antidiabetic agents Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Levothyroxine Glyburide
      Mechanism 1 Hyperglycemia Antidiabetic agent
      Key Mechanism Factor 1
Factor Name Antidiabetic agents
Factor Description The hypoglycemic effect of antidiabetes may be reduced, leading to higher blood glucose, increased blood glucose fluctuations, and the possibility of hyperglycemic complications
      Mechanism Description
  • Antagonize the effect of Glyburide when combined with Levothyroxine 
      Mechanism 2 Hyperglycemic effects Antidiabetic agent
      Key Mechanism Factor 2
Factor Name Antidiabetic agents
Factor Description The hypoglycemic effect of antidiabetes may be reduced, leading to higher blood glucose, increased blood glucose fluctuations, and the possibility of hyperglycemic complications
      Mechanism Description
  • Antagonize the effect of Glyburide when combined with Levothyroxine 

Recommended Action
      Management Close clinical monitoring of glycemic control is recommended following initiation or discontinuation of these drugs, and the dosages of concomitant antidiabetic agents adjusted as necessary. Patients should be advised to notify their physician if their blood glucose is consistently high or if they experience symptoms of severe hyperglycemia such as excessive thirst and increases in the volume or frequency of urination.

References
1 Al-Rubeaan K, Ryan EA "Phenytoin-induced insulin insensitivity." Diabet Med 8 (1991): 968-70. [PMID: 1838051]
2 Andersen OO, Persson I "Carbohydrate metabolism during treatment with chlorthalidone and ethacrynic acid." Br Med J 2 (1968): 798-801. [PMID: 5656298]
3 Bell DS "Insulin resistance. An often unrecognized problem accompanying chronic medical disorders." Postgrad Med 93 (1993): 99-103,. [PMID: 8098525]
4 Berlin I "Prazosin, diuretics, and glucose intolerance." Ann Intern Med 119 (1993): 860. [PMID: 8257545]
5 Black DM, Filak AT "Hyperglycemia with non-insulin-dependent diabetes following intraarticular steroid injection." J Fam Pract 28 (1989): 462-3. [PMID: 2703816]
6 Blayac JP, Ribes G, Buys D, Puech R, Loubatieres-Mariani MM "Effects of a new benzothiadiazine derivative, LN 5330, on insulin secretion." Arch Int Pharmacodyn Ther 253 (1981): 154-63. [PMID: 6119962]
7 Carter BL, Small RE, Mandel MD, Starkman MT "Phenytoin-induced hyperglycemia." Am J Hosp Pharm 38 (1981): 1508-12. [PMID: 7294047]
8 Charan VD, Desai N, Singh AP, Choudhry VP "Diabetes mellitus and pancreatitis as a complication of L- asparaginase therapy." Indian Pediatr 30 (1993): 809-10. [PMID: 8132268]
9 Chaudhuri ML, Catania J "A comparison of the effects of bumetanide (Burinex) and frusemide on carbohydrate metabolism in the elderly." Br J Clin Pract 42 (1988): 427-9. [PMID: 3255422]
10 Chowdhury FR, Bleicher SJ "Chlorthalidone--induced hypokalemia and abnormal carbohydrate metabolism." Horm Metab Res 2 (1970): 13-6. [PMID: 5520746]
11 Coni NK, Gordon PW, Mukherjee AP, Read PR "The effect of frusemide and ethacrynic acid on carbohydrate metabolism." Age Ageing 3 (1974): 85-90. [PMID: 4854754]
12 Curtis J, Horrigan F, Ahearn D, Varney R, Sandler SG "Chlorthalidone-induced hyperosmolar hyperglycemic nonketotic coma." JAMA 220 (1972): 1592-3. [PMID: 4624522]
13 Diamond MT "Hyperglycemic hyperosmolar coma associated with hydrochlorothiazide and pancreatitis." N Y State J Med 72 (1972): 1741-2. [PMID: 4504065]
14 Dimitriadis G, Tegos C, Golfinopoulou L, Roboti C, Raptis S "Furosemide-induced hyperglycaemia - the implication of glycolytic kinases." Horm Metab Res 25 (1993): 557-9. [PMID: 8288156]
15 Domenet JG "Diabetogenic effect of oral diuretics." Br Med J 3 (1968): 188. [PMID: 5662559]
16 Dube MP, Johnson DL, Currier JS, Leedom JM "Protease inhibitor-associated hyperglycaemia." Lancet 350 (1997): 713-4. [PMID: 9291911]
17 Elmfeldt D, Berglund G, Wedel H, Wilhelmsen L "Incidence and importance of metabolic side-effects during antihypertensive therapy." Acta Med Scand Suppl 672 (1983): 79-83. [PMID: 6138939]
18 Erle G, Basso M, Federspil G, Sicolo N, Scandellari C "Effect of chlorpromazine on blood glucose and plasma insulin in man." Eur J Clin Pharmacol 11 (1977): 15-8. [PMID: 832653]
19 Goldman JA, Neri A, Ovadia J, Eckerling B, Vries A, de "Effect of chlorothiazide on intravenous glucose tolerance in pregnancy." Am J Obstet Gynecol 105 (1969): 556-60. [PMID: 4898816]
20 Goldman JA, Ovadia JL "The effect of estrogen on intravenous glucose tolerance in woman." Am J Obstet Gynecol 103 (1969): 172-8. [PMID: 4303772]
21 Greenstone MA, Shaw AB "Alternate day corticosteroid causes alternate day hyperglycaemia." Postgrad Med J 63 (1987): 761-4. [PMID: 3444801]
22 Gunnarsson R, Lundgren G, Magnusson G, Ost L, Groth CG "Steroid diabetes--a sign of overtreatment with steroids in the renal graft recipient?" Scand J Urol Nephrol Suppl 54 (1980): 135-8. [PMID: 7013032]
23 Haiba NA, el-Habashy MA, Said SA, Darwish EA, Abdel-Sayed WS, Nayel SE "Clinical evaluation of two monthly injectable contraceptives and their effects on some metabolic parameters." Contraception 39 (1989): 619-32. [PMID: 2666019]
24 Hannaford PC, Kay CR "Oral contraceptives and diabetes mellitus." BMJ 299 (1989): 1315-6. [PMID: 2513935]
25 Hardy H, Esch LD, Morse GD "Glucose disorders associated with HIV and its drug therapy." Ann Pharmacother 35 (2001): 343-51. [PMID: 11261533]
26 Harper R, Ennis CN, Heaney AP, Sheridan B, Gormley M, Atkinson AB, Johnston GD, Bell PM "A comparison of the effects of low- and conventional-dose thiazide diuretic on insulin action in hypertensive patients with NIDDM." Diabetologia 38 (1995): 853-9. [PMID: 7556989]
27 Javier Z, Gershberg H, Hulse M "Ovulatory suppressants, estrogens, and carbohydrate metabolism." Metabolism 17 (1968): 443-56. [PMID: 4171881]
28 Jones IG, Pickens PT "Diabetes mellitus following oral diuretics." Practitioner 199 (1967): 209-10. [PMID: 6058641]
29 Jori A, Carrara MC "On the mechanism of the hyperglycaemic effect of chlorpromazine." J Pharm Pharmacol 18 (1966): 623-4. [PMID: 4381950]
30 Kansal PC, Buse J, Buse MG "Thiazide diuretics and control of diabetes mellitus." South Med J 62 (1969): 1372-9. [PMID: 5366432]
31 Kaufman MB, Simionatto C "A review of protease inhibitor-induced hyperglycemia." Pharmacotherapy 19 (1999): 114-7. [PMID: 9917085]
32 Leary WP, Reyes AJ "Drug interactions with diuretics." S Afr Med J 65 (1984): 455-61. [PMID: 6701709]
33 Ludvik B, Clodi M, Kautzky-Willer A, Capek M, Hartter E, Pacini G, Prager R "Effect of dexamethasone on insulin sensitivity, islet amyloid polypeptide and insulin secretion in humans." Diabetologia 36 (1993): 84-7. [PMID: 8436259]
34 Malherbe C, Burrill KC, Levin SR, Karam JH, Forsham PH "Effect of diphenylhydantoin on insulin secretion in man." N Engl J Med 286 (1972): 339-42. [PMID: 5008555]
35 Mauss S, Wolf E, Jaeger H "Impaired glucose tolerance in HIV-positive patients receiving and those not receiving protease inhibitors." Ann Intern Med 130 (1999): 162-3. [PMID: 10068370]
36 Miller NR, Moses H "Transient oculomotor nerve palsy. Association with thiazide-induced glucose intolerance." JAMA 240 (1978): 1887-8. [PMID: 691201]
37 Murphy MB, Kohner E, Lewis PJ, Schumer B, Dollery CT "Glucose intolerance in hypertensive patients treated with diuretics: a fourteen-year follow-up." Lancet 2 (1982): 1293-5. [PMID: 6128594]
38 Petri M, Cumber P, Grimes L, Treby D, Bryant R, Rawlins D, Ising H "The metabolic effects of thiazide therapy in the elderly: a population study." Age Ageing 15 (1986): 151-5. [PMID: 3739851]
39 Pickkers P, Schachter M, Hughes AD, Feher MD, Sever PS "Thiazide-induced hyperglycaemia: a role for calcium-activated potassium channels?" Diabetologia 39 (1996): 861-4. [PMID: 8817113]
40 Pollare T, Lithell H, Berne C "A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension." N Engl J Med 321 (1989): 868-73. [PMID: 2671740]
41 Product Information. Agenerase (amprenavir). Glaxo Wellcome, Research Triangle Pk, NC.
42 Product Information. Amaryl (glimepiride). Hoechst Marion-Roussel Inc, Kansas City, MO.
43 Product Information. Apidra (insulin glulisine). Aventis Pharmaceuticals, Bridgewater, NJ.
44 Product Information. Carafate (sucralfate). Hoechst Marion-Roussel Inc, Kansas City, MO.
45 Product Information. Crixivan (indinavir). Merck & Co, Inc, West Point, PA.
46 Product Information. Diabeta (glyburide). Hoechst Marion-Roussel Inc, Kansas City, MO.
47 Product Information. Diabinese (chlorpropamide). Pfizer US Pharmaceuticals, New York, NY.
48 Product Information. Dymelor (acetohexamide) Lilly, Eli and Company, Indianapolis, IN.
49 Product Information. Elspar (asparaginase). Merck & Co, Inc, West Point, PA.
50 Product Information. Elzonris (tagraxofusp). Stemline Therapeutics, New York, NY.
51 Product Information. Fortovase (saquinavir) Roche Laboratories, Nutley, NJ.
52 Product Information. Glucophage (metformin). Bristol-Myers Squibb, Princeton, NJ.
53 Product Information. Glucotrol (glipizide). Pfizer US Pharmaceuticals, New York, NY.
54 Product Information. Hyperstat I.V. (diazoxide). Schering Corp, Kenilworth, NJ.
55 Product Information. Lexiva (fosamprenavir). GlaxoSmithKline, Research Triangle Park, NC.
56 Product Information. Megace (megestrol). Bristol-Myers Squibb, Princeton, NJ.
57 Product Information. Norvir (ritonavir). Abbott Pharmaceutical, Abbott Park, IL.
58 Product Information. NovoLog Mix 70/30 (insulin aspart-insulin aspart protamine). Novo Nordisk Pharmaceuticals Inc, Princeton, NJ.
59 Product Information. Oncaspar (pegaspargase). Rhone-Poulenc Rorer, Collegeville, PA.
60 Product Information. Orinase (tolbutamide) Pharmacia and Upjohn, Kalamazoo, MI.
61 Product Information. Piqray (alpelisib). Novartis Pharmaceuticals, East Hanover, NJ.
62 Product Information. Prandin (repaglinide). Novo Nordisk Pharmaceuticals Inc, Princeton, NJ.
63 Product Information. Precose (acarbose). Bayer, West Haven, CT.
64 Product Information. Prezista (darunavir). Ortho Biotech Inc, Bridgewater, NJ.
65 Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc, Rockville, MD.
66 Product Information. Reyataz (atazanavir). Bristol-Myers Squibb, Princeton, NJ.
67 Product Information. Starlix (nateglinide) Novartis Pharmaceuticals, East Hanover, NJ.
68 Product Information. Synthroid (levothyroxine). Abbott Pharmaceutical, Abbott Park, IL.
69 Product Information. Thorazine (chlorpromazine). SmithKline Beecham, Philadelphia, PA.
70 Product Information. Tolinase (tolazamide) Pharmacia and Upjohn, Kalamazoo, MI.
71 Product Information. Torisel (temsirolimus). Wyeth-Ayerst Laboratories, Philadelphia, PA.
72 Product Information. Viracept (nelfinavir). Agouron Pharma Inc, La Jolla, CA.
73 Product Information. Zolinza (vorinostat). Merck & Company Inc, West Point, PA.
74 Rowe P, Mather H "Hyperosmolar non-ketotic diabetes mellitus associated with metolazone." Br Med J 291 (1985): 25-6. [PMID: 3926049]
75 Schmitz O, Hermansen K, Nielsen OH, Christensen CK, Arnfred J, Hansen HE, Mogensen CE, Orskov H, Beck-Nielsen H "Insulin action in insulin-dependent diabetics after short-term thiazide therapy." Diabetes Care 9 (1986): 631-6. [PMID: 3542455]
76 Seifer DB, Freedman LN, Cavender JR, Baker RA "Insulin-dependent diabetes mellitus associated with danazol." Am J Obstet Gynecol 162 (1990): 474-5. [PMID: 2309833]
77 Seltzer HS, Allen EW "Hyperglycemia and inhibition of insulin secretion during administration of diazoxide and trichlormethiazide in man." Diabetes 18 (1969): 19-28. [PMID: 5761863]
78 Sotaniemi E, Kontturi M, Larmi T "Effect of diethylstilbestrol on blood glucose of prostatic cancer patients." Invest Urol 10 (1973): 438-41. [PMID: 4704169]
79 Spellacy WN, Ellingson AB, Tsibris JC "The effects of two triphasic oral contraceptives on carbohydrate metabolism in women during 1 year of use." Fertil Steril 51 (1989): 71-4. [PMID: 2642814]
80 Stambaugh JE, Tucker DC "Effect of diphenylhydantoin on glucose tolerance in patients with hypoglycemia." Diabetes 23 (1974): 679-83. [PMID: 4851631]
81 Tsiodras S, Mantzoros C, Hammer S, Samore M "Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and lipodystrophy - A 5-year cohort study." Arch Intern Med 160 (2000): 2050-6. [PMID: 10888979]
82 Virutamasen P, Wongsrichanalai C, Tangkeo P, Nitichai Y, Rienprayoon D "Metabolic effects of depot-medroxyprogesterone acetate in long-term users: a cross-sectional study." Int J Gynaecol Obstet 24 (1986): 291-6. [PMID: 2878838]
83 Walli R, Demant T "Impaired glucose tolerance and protease inhibitors." Ann Intern Med 129 (1998): 837-8. [PMID: 9841594]
84 Wehring H, Alexander B, Perry PJ "Diabetes mellitus associated with clozapine therapy." Pharmacotherapy 20 (2000): 844-7. [PMID: 10907975]
85 Winchester JF, Kellett RJ, Boddy K, Boyle P, Dargie HJ, Mahaffey ME, Ward DM, Kennedy AC "Metolazone and bendroflumethiazide in hypertension: physiologic and metabolic observations." Clin Pharmacol Ther 28 (1980): 611-8. [PMID: 7438679]