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Drug Interactions between niacin / simvastatin and Ryzodeg 70/30

This report displays the potential drug interactions for the following 2 drugs:

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Major

niacin simvastatin

Applies to: niacin / simvastatin and niacin / simvastatin

ADJUST DOSE: Severe myopathy and rhabdomyolysis have been reported with concomitant use of HMG-CoA reductase inhibitors (i.e., statins) and niacin. The mechanism is unknown; however, the development of myopathy has been associated with both the administration of statins alone and lipid-modifying dosages of niacin (1 g/day or more) alone. Certain populations may be more susceptible to the interaction. In a double-blind, randomized cardiovascular outcomes trial for simvastatin, the incidence of myopathy was found to be higher in patients of Chinese descent (0.43%) compared to patients not of Chinese descent (0.03%) taking 40 mg simvastatin and lipid-modifying dosages of a niacin-containing product. The cause of the increased risk is unknown, and it is also unknown if the increased risk applies to other Asian populations or to other statins when given to Chinese patients.

MANAGEMENT: Concomitant use of statins with lipid-modifying dosages of niacin (1 g/day or more) should be approached cautiously and only if the benefit of further alterations in lipid levels is anticipated to outweigh the potential risks. Addition of niacin to statin therapy typically provides little additional reduction in LDL cholesterol, but further reductions of triglycerides and increases in HDL cholesterol may be attained. If the combination is prescribed, lower dosages of the statin should be considered. Coadministration of simvastatin with high doses of niacin (1 g/day or more) is not recommended in Chinese patients due to an increased risk of myopathy. Lovastatin labeling recommends that the dosage not exceed 20 mg daily when prescribed with lipid-modifying dosages of niacin. All patients should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.

References

  1. Mauro VF "Clinical pharmacokinetics and practical applications of simvastatin." Clin Pharmacokinet 24 (1993): 195-202
  2. Mauro VF, MacDonald JL "Simvastatin: a review of its pharmacology and clinical use." DICP 25 (1991): 257-64
  3. Reaven P, Witztum JL "Lovastatin, nicotinic acid, and rhabdomyolysis." Ann Intern Med 109 (1988): 597-8
  4. Norman DJ, Illingworth DR, Munson J, Hosenpud J "Myolysis and acute renal failure in a heart-transplant recipient receiving lovastatin." N Engl J Med 318 (1988): 46-7
  5. Malloy MJ, Kane JP, Kunitake ST, Tun P "Complementarity of colestipol, niacin, and lovastatin in treatment of severe familial hypercholesterolemia." Ann Intern Med 107 (1987): 616-23
  6. "Product Information. Mevacor (lovastatin)." Merck & Co., Inc PROD (2002):
  7. "Product Information. Zocor (simvastatin)." Merck & Co., Inc PROD (2001):
  8. "Product Information. Lipitor (atorvastatin)." Parke-Davis PROD (2001):
  9. "Product Information. Baycol (cerivastatin)." Bayer PROD (2001):
  10. "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc (2003):
  11. "Product Information. Vytorin (ezetimibe-simvastatin)." Merck & Co., Inc (2004):
  12. FDA. U.S. Food and Drug Administration "FDA drug safety communication: Ongoing safety review of high-dose Zocor (simvastatin) and increased risk of muscle injury. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm204882.htm" (2010):
View all 12 references

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Moderate

niacin insulin aspart

Applies to: niacin / simvastatin and Ryzodeg 70 / 30 (insulin aspart / insulin degludec)

MONITOR: The efficacy of insulin and other antidiabetic agents may be diminished by certain drugs, including atypical antipsychotics, corticosteroids, diuretics, estrogens, gonadotropin-releasing hormone agonists, human growth hormone, phenothiazines, progestins, protease inhibitors, sympathomimetic amines, thyroid hormones, L-asparaginase, alpelisib, copanlisib, danazol, diazoxide, isoniazid, megestrol, omacetaxine, phenytoin, sirolimus, tagraxofusp, temsirolimus, as well as pharmacologic dosages of nicotinic acid and adrenocorticotropic agents. These drugs may interfere with blood glucose control because they can cause hyperglycemia, glucose intolerance, new-onset diabetes mellitus, and/or exacerbation of preexisting diabetes.

MANAGEMENT: Caution is advised when drugs that can interfere with glucose metabolism are prescribed to patients with diabetes. 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. Likewise, patients should be observed for hypoglycemia when these drugs are withdrawn from their therapeutic regimen.

References

  1. Greenstone MA, Shaw AB "Alternate day corticosteroid causes alternate day hyperglycaemia." Postgrad Med J 63 (1987): 761-4
  2. 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
  3. Carter BL, Small RE, Mandel MD, Starkman MT "Phenytoin-induced hyperglycemia." Am J Hosp Pharm 38 (1981): 1508-12
  4. Al-Rubeaan K, Ryan EA "Phenytoin-induced insulin insensitivity." Diabet Med 8 (1991): 968-70
  5. 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
  6. 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
  7. Miller NR, Moses H "Transient oculomotor nerve palsy. Association with thiazide-induced glucose intolerance." JAMA 240 (1978): 1887-8
  8. Kansal PC, Buse J, Buse MG "Thiazide diuretics and control of diabetes mellitus." South Med J 62 (1969): 1372-9
  9. Andersen OO, Persson I "Carbohydrate metabolism during treatment with chlorthalidone and ethacrynic acid." Br Med J 2 (1968): 798-801
  10. Curtis J, Horrigan F, Ahearn D, Varney R, Sandler SG "Chlorthalidone-induced hyperosmolar hyperglycemic nonketotic coma." JAMA 220 (1972): 1592-3
  11. Chowdhury FR, Bleicher SJ "Chlorthalidone--induced hypokalemia and abnormal carbohydrate metabolism." Horm Metab Res 2 (1970): 13-6
  12. Diamond MT "Hyperglycemic hyperosmolar coma associated with hydrochlorothiazide and pancreatitis." N Y State J Med 72 (1972): 1741-2
  13. Jones IG, Pickens PT "Diabetes mellitus following oral diuretics." Practitioner 199 (1967): 209-10
  14. Black DM, Filak AT "Hyperglycemia with non-insulin-dependent diabetes following intraarticular steroid injection." J Fam Pract 28 (1989): 462-3
  15. 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
  16. 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
  17. Seltzer HS, Allen EW "Hyperglycemia and inhibition of insulin secretion during administration of diazoxide and trichlormethiazide in man." Diabetes 18 (1969): 19-28
  18. Jori A, Carrara MC "On the mechanism of the hyperglycaemic effect of chlorpromazine." J Pharm Pharmacol 18 (1966): 623-4
  19. 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
  20. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham PROD (2002):
  21. "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  22. "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  23. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  24. "Product Information. Synthroid (levothyroxine)." Abbott Pharmaceutical PROD (2002):
  25. "Product Information. Carafate (sucralfate)." Hoechst Marion Roussel PROD (2001):
  26. Stambaugh JE, Tucker DC "Effect of diphenylhydantoin on glucose tolerance in patients with hypoglycemia." Diabetes 23 (1974): 679-83
  27. 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
  28. Javier Z, Gershberg H, Hulse M "Ovulatory suppressants, estrogens, and carbohydrate metabolism." Metabolism 17 (1968): 443-56
  29. Sotaniemi E, Kontturi M, Larmi T "Effect of diethylstilbestrol on blood glucose of prostatic cancer patients." Invest Urol 10 (1973): 438-41
  30. Bell DS "Insulin resistance. An often unrecognized problem accompanying chronic medical disorders." Postgrad Med 93 (1993): 99-103,
  31. Berlin I "Prazosin, diuretics, and glucose intolerance." Ann Intern Med 119 (1993): 860
  32. Rowe P, Mather H "Hyperosmolar non-ketotic diabetes mellitus associated with metolazone." Br Med J 291 (1985): 25-6
  33. 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
  34. 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
  35. 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
  36. Goldman JA, Ovadia JL "The effect of estrogen on intravenous glucose tolerance in woman." Am J Obstet Gynecol 103 (1969): 172-8
  37. Hannaford PC, Kay CR "Oral contraceptives and diabetes mellitus." BMJ 299 (1989): 1315-6
  38. 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
  39. 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
  40. Domenet JG "Diabetogenic effect of oral diuretics." Br Med J 3 (1968): 188
  41. Coni NK, Gordon PW, Mukherjee AP, Read PR "The effect of frusemide and ethacrynic acid on carbohydrate metabolism." Age Ageing 3 (1974): 85-90
  42. 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
  43. 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
  44. 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
  45. 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
  46. 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
  47. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb PROD (2001):
  48. 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
  49. "Product Information. Precose (acarbose)." Bayer PROD (2001):
  50. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):
  51. "Product Information. Amaryl (glimepiride)." Hoechst Marion Roussel PROD (2001):
  52. 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
  53. Seifer DB, Freedman LN, Cavender JR, Baker RA "Insulin-dependent diabetes mellitus associated with danazol." Am J Obstet Gynecol 162 (1990): 474-5
  54. "Product Information. Crixivan (indinavir)." Merck & Co., Inc PROD (2001):
  55. 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
  56. "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc PROD (2001):
  57. Dube MP, Johnson DL, Currier JS, Leedom JM "Protease inhibitor-associated hyperglycaemia." Lancet 350 (1997): 713-4
  58. "Product Information. Oncaspar (pegaspargase)." Rhone Poulenc Rorer PROD (2001):
  59. "Product Information. Prandin (repaglinide)." Novo Nordisk Pharmaceuticals Inc PROD (2001):
  60. "Product Information. Elspar (asparaginase)." Merck & Co., Inc PROD (2001):
  61. "Product Information. Hyperstat (diazoxide)." Apothecon Inc (2022):
  62. "Product Information. Megace (megestrol)." Bristol-Myers Squibb PROD (2001):
  63. Walli R, Demant T "Impaired glucose tolerance and protease inhibitors." Ann Intern Med 129 (1998): 837-8
  64. "Product Information. Agenerase (amprenavir)." Glaxo Wellcome PROD (2001):
  65. 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
  66. Kaufman MB, Simionatto C "A review of protease inhibitor-induced hyperglycemia." Pharmacotherapy 19 (1999): 114-7
  67. "Product Information. Tolinase (tolazamide)." Pharmacia and Upjohn PROD (2001):
  68. "Product Information. Orinase (tolbutamide)." Pharmacia and Upjohn PROD (2001):
  69. "Product Information. Dymelor (acetohexamide)." Lilly, Eli and Company PROD (2001):
  70. Wehring H, Alexander B, Perry PJ "Diabetes mellitus associated with clozapine therapy." Pharmacotherapy 20 (2000): 844-7
  71. 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
  72. "Product Information. Fortovase (saquinavir)." Roche Laboratories PROD (2001):
  73. "Product Information. Starlix (nateglinide)." Novartis Pharmaceuticals PROD (2001):
  74. Hardy H, Esch LD, Morse GD "Glucose disorders associated with HIV and its drug therapy." Ann Pharmacother 35 (2001): 343-51
  75. Leary WP, Reyes AJ "Drug interactions with diuretics." S Afr Med J 65 (1984): 455-61
  76. "Product Information. NovoLOG Mix 70/30 (insulin aspart-insulin aspart protamine)." Novo Nordisk Pharmaceuticals Inc (2022):
  77. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb (2003):
  78. "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline (2003):
  79. "Product Information. Apidra (insulin glulisine)." Aventis Pharmaceuticals (2004):
  80. "Product Information. Prezista (darunavir)." Ortho Biotech Inc (2006):
  81. "Product Information. Zolinza (vorinostat)." Merck & Co., Inc (2006):
  82. "Product Information. Torisel (temsirolimus)." Wyeth-Ayerst Laboratories (2007):
  83. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
  84. "Product Information. Elzonris (tagraxofusp)." Stemline Therapeutics (2019):
  85. "Product Information. Piqray (alpelisib)." Novartis Pharmaceuticals (2019):
View all 85 references

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Moderate

niacin insulin degludec

Applies to: niacin / simvastatin and Ryzodeg 70 / 30 (insulin aspart / insulin degludec)

MONITOR: The efficacy of insulin and other antidiabetic agents may be diminished by certain drugs, including atypical antipsychotics, corticosteroids, diuretics, estrogens, gonadotropin-releasing hormone agonists, human growth hormone, phenothiazines, progestins, protease inhibitors, sympathomimetic amines, thyroid hormones, L-asparaginase, alpelisib, copanlisib, danazol, diazoxide, isoniazid, megestrol, omacetaxine, phenytoin, sirolimus, tagraxofusp, temsirolimus, as well as pharmacologic dosages of nicotinic acid and adrenocorticotropic agents. These drugs may interfere with blood glucose control because they can cause hyperglycemia, glucose intolerance, new-onset diabetes mellitus, and/or exacerbation of preexisting diabetes.

MANAGEMENT: Caution is advised when drugs that can interfere with glucose metabolism are prescribed to patients with diabetes. 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. Likewise, patients should be observed for hypoglycemia when these drugs are withdrawn from their therapeutic regimen.

References

  1. Greenstone MA, Shaw AB "Alternate day corticosteroid causes alternate day hyperglycaemia." Postgrad Med J 63 (1987): 761-4
  2. 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
  3. Carter BL, Small RE, Mandel MD, Starkman MT "Phenytoin-induced hyperglycemia." Am J Hosp Pharm 38 (1981): 1508-12
  4. Al-Rubeaan K, Ryan EA "Phenytoin-induced insulin insensitivity." Diabet Med 8 (1991): 968-70
  5. 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
  6. 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
  7. Miller NR, Moses H "Transient oculomotor nerve palsy. Association with thiazide-induced glucose intolerance." JAMA 240 (1978): 1887-8
  8. Kansal PC, Buse J, Buse MG "Thiazide diuretics and control of diabetes mellitus." South Med J 62 (1969): 1372-9
  9. Andersen OO, Persson I "Carbohydrate metabolism during treatment with chlorthalidone and ethacrynic acid." Br Med J 2 (1968): 798-801
  10. Curtis J, Horrigan F, Ahearn D, Varney R, Sandler SG "Chlorthalidone-induced hyperosmolar hyperglycemic nonketotic coma." JAMA 220 (1972): 1592-3
  11. Chowdhury FR, Bleicher SJ "Chlorthalidone--induced hypokalemia and abnormal carbohydrate metabolism." Horm Metab Res 2 (1970): 13-6
  12. Diamond MT "Hyperglycemic hyperosmolar coma associated with hydrochlorothiazide and pancreatitis." N Y State J Med 72 (1972): 1741-2
  13. Jones IG, Pickens PT "Diabetes mellitus following oral diuretics." Practitioner 199 (1967): 209-10
  14. Black DM, Filak AT "Hyperglycemia with non-insulin-dependent diabetes following intraarticular steroid injection." J Fam Pract 28 (1989): 462-3
  15. 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
  16. 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
  17. Seltzer HS, Allen EW "Hyperglycemia and inhibition of insulin secretion during administration of diazoxide and trichlormethiazide in man." Diabetes 18 (1969): 19-28
  18. Jori A, Carrara MC "On the mechanism of the hyperglycaemic effect of chlorpromazine." J Pharm Pharmacol 18 (1966): 623-4
  19. 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
  20. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham PROD (2002):
  21. "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  22. "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  23. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  24. "Product Information. Synthroid (levothyroxine)." Abbott Pharmaceutical PROD (2002):
  25. "Product Information. Carafate (sucralfate)." Hoechst Marion Roussel PROD (2001):
  26. Stambaugh JE, Tucker DC "Effect of diphenylhydantoin on glucose tolerance in patients with hypoglycemia." Diabetes 23 (1974): 679-83
  27. 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
  28. Javier Z, Gershberg H, Hulse M "Ovulatory suppressants, estrogens, and carbohydrate metabolism." Metabolism 17 (1968): 443-56
  29. Sotaniemi E, Kontturi M, Larmi T "Effect of diethylstilbestrol on blood glucose of prostatic cancer patients." Invest Urol 10 (1973): 438-41
  30. Bell DS "Insulin resistance. An often unrecognized problem accompanying chronic medical disorders." Postgrad Med 93 (1993): 99-103,
  31. Berlin I "Prazosin, diuretics, and glucose intolerance." Ann Intern Med 119 (1993): 860
  32. Rowe P, Mather H "Hyperosmolar non-ketotic diabetes mellitus associated with metolazone." Br Med J 291 (1985): 25-6
  33. 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
  34. 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
  35. 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
  36. Goldman JA, Ovadia JL "The effect of estrogen on intravenous glucose tolerance in woman." Am J Obstet Gynecol 103 (1969): 172-8
  37. Hannaford PC, Kay CR "Oral contraceptives and diabetes mellitus." BMJ 299 (1989): 1315-6
  38. 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
  39. 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
  40. Domenet JG "Diabetogenic effect of oral diuretics." Br Med J 3 (1968): 188
  41. Coni NK, Gordon PW, Mukherjee AP, Read PR "The effect of frusemide and ethacrynic acid on carbohydrate metabolism." Age Ageing 3 (1974): 85-90
  42. 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
  43. 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
  44. 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
  45. 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
  46. 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
  47. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb PROD (2001):
  48. 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
  49. "Product Information. Precose (acarbose)." Bayer PROD (2001):
  50. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):
  51. "Product Information. Amaryl (glimepiride)." Hoechst Marion Roussel PROD (2001):
  52. 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
  53. Seifer DB, Freedman LN, Cavender JR, Baker RA "Insulin-dependent diabetes mellitus associated with danazol." Am J Obstet Gynecol 162 (1990): 474-5
  54. "Product Information. Crixivan (indinavir)." Merck & Co., Inc PROD (2001):
  55. 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
  56. "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc PROD (2001):
  57. Dube MP, Johnson DL, Currier JS, Leedom JM "Protease inhibitor-associated hyperglycaemia." Lancet 350 (1997): 713-4
  58. "Product Information. Oncaspar (pegaspargase)." Rhone Poulenc Rorer PROD (2001):
  59. "Product Information. Prandin (repaglinide)." Novo Nordisk Pharmaceuticals Inc PROD (2001):
  60. "Product Information. Elspar (asparaginase)." Merck & Co., Inc PROD (2001):
  61. "Product Information. Hyperstat (diazoxide)." Apothecon Inc (2022):
  62. "Product Information. Megace (megestrol)." Bristol-Myers Squibb PROD (2001):
  63. Walli R, Demant T "Impaired glucose tolerance and protease inhibitors." Ann Intern Med 129 (1998): 837-8
  64. "Product Information. Agenerase (amprenavir)." Glaxo Wellcome PROD (2001):
  65. 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
  66. Kaufman MB, Simionatto C "A review of protease inhibitor-induced hyperglycemia." Pharmacotherapy 19 (1999): 114-7
  67. "Product Information. Tolinase (tolazamide)." Pharmacia and Upjohn PROD (2001):
  68. "Product Information. Orinase (tolbutamide)." Pharmacia and Upjohn PROD (2001):
  69. "Product Information. Dymelor (acetohexamide)." Lilly, Eli and Company PROD (2001):
  70. Wehring H, Alexander B, Perry PJ "Diabetes mellitus associated with clozapine therapy." Pharmacotherapy 20 (2000): 844-7
  71. 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
  72. "Product Information. Fortovase (saquinavir)." Roche Laboratories PROD (2001):
  73. "Product Information. Starlix (nateglinide)." Novartis Pharmaceuticals PROD (2001):
  74. Hardy H, Esch LD, Morse GD "Glucose disorders associated with HIV and its drug therapy." Ann Pharmacother 35 (2001): 343-51
  75. Leary WP, Reyes AJ "Drug interactions with diuretics." S Afr Med J 65 (1984): 455-61
  76. "Product Information. NovoLOG Mix 70/30 (insulin aspart-insulin aspart protamine)." Novo Nordisk Pharmaceuticals Inc (2022):
  77. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb (2003):
  78. "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline (2003):
  79. "Product Information. Apidra (insulin glulisine)." Aventis Pharmaceuticals (2004):
  80. "Product Information. Prezista (darunavir)." Ortho Biotech Inc (2006):
  81. "Product Information. Zolinza (vorinostat)." Merck & Co., Inc (2006):
  82. "Product Information. Torisel (temsirolimus)." Wyeth-Ayerst Laboratories (2007):
  83. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
  84. "Product Information. Elzonris (tagraxofusp)." Stemline Therapeutics (2019):
  85. "Product Information. Piqray (alpelisib)." Novartis Pharmaceuticals (2019):
View all 85 references

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Drug and food interactions

Major

simvastatin food

Applies to: niacin / simvastatin

GENERALLY AVOID: Coadministration with grapefruit juice may significantly increase the plasma concentrations of lovastatin and simvastatin and their active acid metabolites. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. When a single 60 mg dose of simvastatin was coadministered with 200 mL of double-strength grapefruit juice three times a day, simvastatin systemic exposure (AUC) increased by 16-fold and simvastatin acid AUC increased by 7-fold. Administration of a single 20 mg dose of simvastatin with 8 ounces of single-strength grapefruit juice increased the AUC of simvastatin and simvastatin acid by 1.9-fold and 1.3-fold, respectively. The interaction has also been reported with lovastatin, which has a similar metabolic profile to simvastatin. Clinically, high levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

ADJUST DOSING INTERVAL: Fibres such as oat bran and pectin may diminish the pharmacologic effects of HMG-CoA reductase inhibitors by interfering with their absorption from the gastrointestinal tract.

Coadministration with green tea may increase the plasma concentrations of simvastatin. The mechanism of interaction has not been established, but may involve inhibition of organic anion transporting polypeptide (OATP) 1B1- and/or 2B1-mediated hepatic uptake of simvastatin by catechins in green tea. The interaction was suspected in a 61-year-old man who experienced muscle intolerance during treatment with simvastatin while drinking an average of 3 cups of green tea daily. He also experienced similar muscle intolerance (leg cramps without creatine phosphokinase elevation) during treatments with atorvastatin and rosuvastatin while drinking green tea. Pharmacokinetic studies performed during his usual green tea intake demonstrated an approximately two-fold higher exposure to simvastatin lactone (the administered form of simvastatin) than that observed after stopping green tea intake for a month. He was also able to tolerate simvastatin after discontinuing green tea consumption. The authors of the report subsequently conducted two independent studies to assess the effect of different green tea preparations on simvastatin pharmacokinetics. One study was conducted in 12 Italian subjects and the other in 12 Japanese subjects. In the Italian study, administration of a single 20 mg dose of simvastatin following pretreatment with 200 mL of a hot green tea standardized infusion 3 times daily for 14 days (estimated daily intake of 335 mg total catechins and 173 mg epigallocatechin-3-gallate (EGCG), the most abundant and biologically active catechin in green tea) was found to have no significant effect on mean peak plasma concentration (Cmax) or systemic exposure (AUC) of simvastatin lactone and simvastatin acid relative to administration with water. However, green tea increased simvastatin lactone AUC (0-6h) by about two-fold in 3 of the study subjects. In the Japanese study, administration of a single 10 mg dose of simvastatin following pretreatment with 350 mL of a commercial green tea beverage twice daily for 14 days (estimated daily intake of 638 mg total catechins and 322 mg EGCG) did not affect mean simvastatin lactone Cmax or AUC to a statistically significant extent compared to administration with water, but increased mean simvastatin acid Cmax and AUC by 42% and 22%, respectively. Similar to the first study, green tea increased simvastatin lactone AUC (0-6h) by two- to three-fold in 4 of the study subjects. Although not studied, the interaction may also occur with lovastatin due to its similar metabolic profile to simvastatin.

MANAGEMENT: Patients receiving therapy with lovastatin, simvastatin, or red yeast rice (which contains lovastatin) should be advised to avoid the consumption of grapefruit and grapefruit juice. Fluvastatin, pravastatin, pitavastatin, and rosuvastatin are metabolized by other enzymes and may be preferable alternatives in some individuals. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed. Also, patients should either refrain from the use of oat bran and pectin, or separate the administration times by at least 2 to 4 hours if concurrent use cannot be avoided. Caution may be advisable when coadministered with green tea or green tea extracts. Dosing reduction of the statin and/or limiting consumption of green tea and green tea products may be required if an interaction is suspected.

References

  1. Richter WO, Jacob BG, Schwandt P "Interaction between fibre and lovastatin." Lancet 338 (1991): 706
  2. "Product Information. Mevacor (lovastatin)." Merck & Co., Inc PROD (2002):
  3. "Product Information. Zocor (simvastatin)." Merck & Co., Inc PROD (2001):
  4. Kantola T, Kivisto KT, Neuvonen PJ "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther 63 (1998): 397-402
  5. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  6. Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther 64 (1998): 477-83
  7. Thompson PD, Clarkson P, Karas RH "Statin-associated myopathy." JAMA 289 (2003): 1681-90
  8. Neuvonen PJ, Backman JT, Niemi M "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet 47 (2008): 463-74
  9. Werba JP, Giroli M, Cavalca V, Nava MC, Tremoli E, Dal Bo L "The effect of green tea on simvastatin tolerability." Ann Intern Med 149 (2008): 286-7
  10. Werba JP, Misaka S, Giroli MG, et al. "Overview of Green Tea Interaction with Cardiovascular Drugs." Curr Pharm Des (2014):
  11. Roth M, Timmermann BN, Hagenbuch B "Interactions of green tea catechins with organic anion-transporting polypeptides." Drug Metab Dispos 39 (2011): 920-6
  12. Knop J, Misaka S, Singer K, et al. "Inhibitory effects of green tea and (-)-epigallocatechin gallate on transport by OATP1B1, OATP1B3, OCT1, OCT2, MATE1, MATE2-K and P-glycoprotein." PLoS One 10 (2015): e0139370
View all 12 references

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Moderate

insulin aspart food

Applies to: Ryzodeg 70/30 (insulin aspart/insulin degludec)

GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes. A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan. Alcohol should not be consumed on an empty stomach or following exercise.

References

  1. Jerntorp P, Almer LO "Chlorpropamide-alcohol flushing in relation to macroangiopathy and peripheral neuropathy in non-insulin dependent diabetes." Acta Med Scand 656 (1981): 33-6
  2. Jerntorp P, Almer LO, Holin H, et al. "Plasma chlorpropamide: a critical factor in chlorpropamide-alcohol flush." Eur J Clin Pharmacol 24 (1983): 237-42
  3. Barnett AH, Spiliopoulos AJ, Pyke DA, et al. "Metabolic studies in chlorpropamide-alcohol flush positive and negative type 2 (non-insulin dependent) diabetic patients with and without retinopathy." Diabetologia 24 (1983): 213-5
  4. Hartling SG, Faber OK, Wegmann ML, Wahlin-Boll E, Melander A "Interaction of ethanol and glipizide in humans." Diabetes Care 10 (1987): 683-6
  5. "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  6. "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  7. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  8. Skillman TG, Feldman JM "The pharmacology of sulfonylureas." Am J Med 70 (1981): 361-72
  9. "Position Statement: evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes related complications. American Diabetes Association." Diabetes Care 25(Suppl 1) (2002): S50-S60
  10. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
View all 10 references

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Moderate

insulin degludec food

Applies to: Ryzodeg 70/30 (insulin aspart/insulin degludec)

GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes. A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan. Alcohol should not be consumed on an empty stomach or following exercise.

References

  1. Jerntorp P, Almer LO "Chlorpropamide-alcohol flushing in relation to macroangiopathy and peripheral neuropathy in non-insulin dependent diabetes." Acta Med Scand 656 (1981): 33-6
  2. Jerntorp P, Almer LO, Holin H, et al. "Plasma chlorpropamide: a critical factor in chlorpropamide-alcohol flush." Eur J Clin Pharmacol 24 (1983): 237-42
  3. Barnett AH, Spiliopoulos AJ, Pyke DA, et al. "Metabolic studies in chlorpropamide-alcohol flush positive and negative type 2 (non-insulin dependent) diabetic patients with and without retinopathy." Diabetologia 24 (1983): 213-5
  4. Hartling SG, Faber OK, Wegmann ML, Wahlin-Boll E, Melander A "Interaction of ethanol and glipizide in humans." Diabetes Care 10 (1987): 683-6
  5. "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  6. "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  7. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  8. Skillman TG, Feldman JM "The pharmacology of sulfonylureas." Am J Med 70 (1981): 361-72
  9. "Position Statement: evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes related complications. American Diabetes Association." Diabetes Care 25(Suppl 1) (2002): S50-S60
  10. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
View all 10 references

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Moderate

niacin food

Applies to: niacin / simvastatin

GENERALLY AVOID: Ethanol can exacerbate the cutaneous flushing that is a common side effect of niacin. At least one case of delirium and lactic acidosis has been reported with coadministration of these drugs, although data are limited.

MANAGEMENT: Coadministration should probably be discouraged, particularly since chronic consumption of large amounts of alcohol is associated with hyperlipidemia.

References

  1. Schwab RA, Bachhuber BH "Delirium and lactic acidosis caused by ethanol and niacin coingestion." Am J Emerg Med 9 (1991): 363-5

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Moderate

simvastatin food

Applies to: niacin / simvastatin

MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.

MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.

References

  1. "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb PROD (2001):
  2. "Product Information. Zocor (simvastatin)." Merck & Co., Inc PROD (2001):
  3. "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals PROD (2001):
  4. "Product Information. Lipitor (atorvastatin)." Parke-Davis PROD (2001):
  5. "Product Information. Altocor (lovastatin)." Andrx Pharmaceuticals (2002):
  6. "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc (2003):
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  8. Cerner Multum, Inc. "Australian Product Information." O 0
  9. "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic) (2010):
View all 9 references

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Minor

niacin food

Applies to: niacin / simvastatin

A single case has been reported in which cutaneous flushing and tremors were noted in a woman who was taking niacin while wearing a nicotine patch. The mechanism is suspected to be synergistic cutaneous vasodilatory effects. The clinical significance of this possible interaction is not known.

References

  1. Rockwell KA Jr "Potential interaction between niacin and transdermal nicotine." Ann Pharmacother 27 (1993): 1283-8

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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