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Drug Interactions between Dura-Dumone and Humulin R U-500 KwikPen

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

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Moderate

estradiol insulin regular

Applies to: Dura-Dumone (estradiol / testosterone) and Humulin R U-500 KwikPen (insulin regular)

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 Likewise, patients should be observed for hypoglycemia when these drugs are withdrawn from their therapeutic regimen.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

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  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
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  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

testosterone insulin regular

Applies to: Dura-Dumone (estradiol / testosterone) and Humulin R U-500 KwikPen (insulin regular)

MONITOR: The hypoglycemic effect of insulin may be potentiated by certain drugs, including ACE inhibitors, angiotensin receptor blockers (ARBs), 4-aminoquinolines, amylin analogs, anabolic steroids, fibrates, monoamine oxidase inhibitors (MAOIs, including linezolid), salicylates, selective serotonin reuptake inhibitors (SSRIs), sulfonamides, disopyramide, propoxyphene, quinidine, quinine, and ginseng. These drugs may increase the risk of hypoglycemia by enhancing insulin sensitivity (ACE inhibitors, ARBs, fibrates, ginseng); stimulating insulin secretion (salicylates, disopyramide, pentoxifylline, propoxyphene, quinidine, quinine, MAOIs, ginseng); decreasing insulin clearance and resistance (4-aminoquinolines); increasing peripheral glucose utilization (SSRIs, insulin-like growth factor); inhibiting gluconeogenesis (SSRIs, MAOIs, insulin-like growth factor); slowing the rate of gastric emptying (amylin analogs); and/or suppressing postprandial glucagon secretion (amylin analogs). Clinical hypoglycemia has been reported during use of some of these agents alone or with insulin and/or insulin secretagogues. Use of SSRIs has also been associated with loss of awareness of hypoglycemia in isolated cases.

MANAGEMENT: Close monitoring for the development of hypoglycemia is recommended if these drugs are coadministered with insulin, particularly in patients with advanced age and/or renal impairment. The insulin dosage may require adjustment if an interaction is suspected. Patients should be apprised of the signs and symptoms of hypoglycemia (e.g., headache, dizziness, drowsiness, nausea, hunger, tremor, weakness, sweating, palpitations), how to treat it, and to contact their physician if it occurs. Patients should be observed for loss of glycemic control when these drugs are withdrawn.

References

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  3. Verdy M, Charbonneau L, Verdy I, Belanger R, Bolte E, Chiasson JL "Fenfluramine in the treatment of non-insulin-dependent diabetics: hypoglycemic versus anorectic effect." Int J Obes 7 (1983): 289-97
  4. Baciewicz AM, Swafford WB Jr "Hypoglycemia induced by the interaction of chlorpropamide and co-trimoxazole." Drug Intell Clin Pharm 18 (1984): 309-10
  5. Richardson T, Foster J, Mawer GE "Enhancement by sodium salicylate of the blood glucose lowering effect of chlorpropamide-drug interaction or summation of similar effects." Br J Clin Pharmacol 22 (1986): 43-8
  6. Johnson J, Dobmeier M "Symptomatic hypoglycemia secondary to a glipizide-trimethoprim/sulfamethoxazole drug interaction." DICP 24 (1990): 250-1
  7. Goldberg IJ, Brown LK, Rayfield EJ "Disopyramide (norpace)-induced hypoglycemia." Am J Med 69 (1980): 463-6
  8. Quevedo SF, Krauss DS, Chazan JA, et al. "Fasting hypoglycemia secondary to disopyramide therapy." JAMA 245 (1981): 2424
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  10. Nappi JM, Dhanani S, Lovejoy JR, VanderArk C "Severe hypoglycemia associated with disopyramide." West J Med 138 (1983): 95-7
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  35. Johnson JA, Kappel JE, Sharif MN "Hypoglycemia secondary to trimethoprim/sulfamethoxazole administration in a renal transplant patient." Ann Pharmacother 27 (1993): 304-6
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  47. Aleyassine H, Lee SH "Inhibition of insulin release by substrates and inhibitors of monoamine oxidase." Am J Physiol 222 (1972): 565-9
  48. Cooper AJ, Ashcroft G "Potentiation of insulin hypoglycaemia by M.A.O.I. antidepressant drugs." Lancet 1 (1966): 407-9
  49. Herings RMC, Deboer A, Stricker BHC, Leufkens HGM, Porsius A "Hypoglycaemia associated with use of inhibitors of angiotensin converting enzyme." Lancet 345 (1995): 1195-8
  50. Ahmad S "Drug interaction induces hypoglycemia." J Fam Pract 40 (1995): 540-1
  51. Feher MD, Amiel S "ACE inhibitors and hypoglycaemia." Lancet 346 (1995): 125-6
  52. Paolisso G, Balbi V, Gambardella A, Varricchio G, Tortoriello R, Saccomanno F, Amato L, Varricchio M "Lisinopril administration improves insulin action in aged patients with hypertension." J Hum Hypertens 9 (1995): 541-6
  53. Darcy PF, Griffin JP "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev 14 (1995): 211-31
  54. Kubacka RT, Antla EJ, Juhl RP, Welshman IR "Effects of aspirin and ibuprofen on the pharmacokinetics and pharmacodynamics of glyburide in healthy subjects." Ann Pharmacother 30 (1996): 20-6
  55. Deeg MA, Lipkin EW "Hypoglycemia associated with the use of fluoxetine." West J Med 164 (1996): 262-3
  56. Hellman B "Potentiating effects of drugs on the binding of glibenclamide to pancreatic beta cells." Metabolism 23 (1974): 839-46
  57. Hekimsoy Z, Biberoglu S, Comlekci A, Tarhan O, Mermut C, Biberoglu K "Trimethoprim/sulfamethoxazole-induced hypoglycemia in a malnourished patient with severe infection." Eur J Endocrinol 136 (1997): 3046
  58. Iida H, Morita T, Suzuki E, Iwasawa K, Toyooka T, Nakajima T "Hypoglycemia induced by interaction between clarithromycin and disopyramide." Jpn Heart J 40 (1999): 91-6
  59. Morris AD, Newton RW, Boyle DI, et al. "ACE inhibitor use is associated with hospitalization for severe hypoglycemia in patients with diabetes." Diabetes Care 20 (1997): 1363-7
  60. Abad S, Moachon L, Blanche P, Bavoux F, Sicard D, Salmon-Ceron D "Possible interaction between glicazide, fluconazole and sulfamethoxazole resulting in severe hypoglycaemia." Br J Clin Pharmacol 52 (2001): 456-7
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  62. "Product Information. Humulin 70/30 (insulin isophane-insulin regular)." Lilly, Eli and Company (2002):
  63. Pollak PT, Mukherjee SD, Fraser AD "Sertraline-induced hypoglycemia." Ann Pharmacother 35 (2001): 1371-4
  64. Hundal RS, Petersen KF, Mayerson AB, et al. "Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes." J Clin Invest 109 (2002): 1321-6
  65. "Product Information. Apidra (insulin glulisine)." Aventis Pharmaceuticals (2004):
  66. Fogari R, Zoppi A, Corradi L, Pierangelo L, Mugellini A, Lusardi P "Comparative effects of lisinopril and losartan on insulin sensitivity in the treatment of non diabetic hypertension." Br J Clin Pharmacol 46 (1998): 467-71
  67. Vuorinen-Markkola H, Yki-Jarvinen H "Antihypertensive therapy with enalapril improves glucose storage and insulin sensitivity in hypertensive patients with non-insulin-dependent diabetes mellitus." Metabolism 44 (1995): 85-9
  68. "Product Information. Increlex (mecasermin)." Tercica Inc (2005):
  69. Vuksan V, Sievenpiper JL, Koo VY, et al. "American ginseng (Panax quinquefolius L) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus." Arch Intern Med 160 (2000): 1009-13
  70. Vuksan V, Stavro MP, Sievenpiper JL, et al. "Similar postprandial glycemic reductions with escalation of dose and administration time of American ginseng in type 2 diabetes." Diabetes Care 23 (2000): 1221-6
  71. Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V "Variable effects of American ginseng: a batch of American ginseng (Panax quinquefolius L.) with a depressed ginsenoside profile does not affect postprandial glycemia." Eur J Clin Nutr 57 (2003): 243-8
  72. Ben Salem C, Fathallah N, Hmouda H, Bouraoui K "Drug-induced hypoglycaemia: an update." Drug Saf 34 (2011): 21-45
  73. "Product Information. Afrezza (insulin inhalation, rapid acting)." MannKind Corporation (2014):
  74. "Product Information. Ryzodeg 70/30 FlexTouch (insulin aspart-insulin degludec)." Novo Nordisk Pharmaceuticals Inc (2015):
  75. "Product Information. Tresiba FlexTouch (insulin degludec)." Novo Nordisk Pharmaceuticals Inc (2015):
  76. World Health Organization "WHO Public Assessment Reports (WHOPARs) https://extranet.who.int/pqweb/medicines/prequalification-reports/whopars" (2020):
View all 76 references

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Drug and food interactions

Moderate

insulin regular food

Applies to: Humulin R U-500 KwikPen (insulin regular)

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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Minor

estradiol food

Applies to: Dura-Dumone (estradiol / testosterone)

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

References

  1. Weber A, Jager R, Borner A, et al. "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception 53 (1996): 41-7
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet 20 (1995): 219-24

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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.

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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.

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