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Drug Interactions between glimepiride and hydrochlorothiazide / timolol

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

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Interactions between your drugs

Moderate

timolol hydroCHLOROthiazide

Applies to: hydrochlorothiazide / timolol and hydrochlorothiazide / timolol

MONITOR: Although they are often combined in clinical practice, diuretics and beta-blockers may increase the risk of hyperglycemia and hypertriglyceridemia in some patients, especially in patients with diabetes or latent diabetes. In addition, the risk of QT interval prolongation and arrhythmias (e.g. torsades de pointes) due to sotalol may be increased by potassium-depleting diuretics.

MANAGEMENT: Monitoring of serum potassium levels, blood pressure, and blood glucose is recommended during coadministration. Patients should be advised to seek medical assistance if they experience dizziness, weakness, fainting, fast or irregular heartbeats, or loss of blood glucose control.

References

  1. Dornhorst A, Powell SH, Pensky J (1985) "Aggravation by propranolol of hyperglycaemic effect of hydrochlorothiazide in type II diabetics without alteration of insulin secretion." Lancet, 1, p. 123-6
  2. Roux A, Le Liboux A, Delhotal B, Gaillot J, Flouvat B (1983) "Pharmacokinetics in man of acebutolol and hydrochlorothiazide as single agents and in combination." Eur J Clin Pharmacol, 24, p. 801-6
  3. Dean S, Kendall MJ, Potter S, Thompson MH, Jackson DA (1985) "Nadolol in combination with indapamide and xipamide in resistant hypertensives." Eur J Clin Pharmacol, 28, p. 29-33
  4. (2002) "Product Information. Lozol (indapamide)." Rhone Poulenc Rorer
  5. Marcy TR, Ripley TL (2006) "Aldosterone antagonists in the treatment of heart failure." Am J Health Syst Pharm, 63, p. 49-58
View all 5 references

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Moderate

timolol glimepiride

Applies to: hydrochlorothiazide / timolol and glimepiride

MONITOR: Beta-blockers may inhibit some of the normal physiologic response to hypoglycemia. Symptoms of hypoglycemia such as tremor and tachycardia may be absent, making it more difficult for patients to recognize an oncoming episode. In addition, multiple effects on glucose metabolism have been reported, usually with the noncardioselective beta-blockers (e.g., propranolol, pindolol, timolol) but occasionally also with relatively beta-1 selective agents (e.g., atenolol, metoprolol, nebivolol). Specifically, inhibition of catecholamine-mediated glycogenolysis and glucose mobilization in association with beta-blockade can potentiate insulin-induced hypoglycemia in diabetics and delay the recovery of normal blood glucose levels. Prolonged and severe hypoglycemia may occur, although these events have rarely been reported. Significant increases in blood pressure and bradycardia can also occur during hypoglycemia in diabetics treated with insulin and beta-blockers due to antagonism of epinephrine's effect on beta-2 adrenergic receptors, which leads to unopposed alpha-adrenergic effects including vasoconstriction. Other effects reported with various beta-blockers include decreased glucose tolerance and decreased glucose-induced insulin secretion.

MANAGEMENT: In general, cardioselective beta-blockers are considered safer than noncardioselective agents in the treatment of diabetic patients. Nevertheless, caution is advised if they are prescribed to patients treated with insulin or oral antidiabetic agents that can cause hypoglycemia (e.g., insulin secretagogues), as cardioselectivity is not absolute and larger doses of beta-1 selective agents may pose some of the same risks as nonselective agents. Patients should be advised of the need for regular blood glucose monitoring and be aware that certain symptoms of hypoglycemia such as tremor and tachycardia may be masked. However, other symptoms such as headache, dizziness, drowsiness, confusion, nausea, hunger, weakness, and perspiration may be unaffected. The same precautions are applicable in diabetic patients treated with ophthalmic beta-blockers.

References

  1. Shepherd AM, Lin M-S, Keeton TK (1981) "Hypoglycemia-induced hypertension in a diabetic patient on metoprolol." Ann Intern Med, 94, p. 357-8
  2. Micossi P, Pollavini G, Raggi U, et al. (1984) "Effects of metoprolol and propranolol on glucose tolerance and insulin secretion in diabetes mellitus." Horm Metab Res, 16, p. 59-63
  3. Popp DA, Tse TF, Shah SD, et al. (1984) "Oral propranolol and metoprolol both impair glucose recovery from insulin-induced hypoglycemia in insulin-dependent diabetes mellitus." Diabetes Care, 7, p. 243-7
  4. Mann SJ, Krakoff LR (1984) "Hypertensive crisis caused by hypoglycemia and propranolol." Arch Intern Med, 144, p. 2427-8
  5. Groop L, Totterman KJ, Harno K, Gordin A (1982) "Influence of beta-blocking drugs on glucose metabolism in patients with non-insulin dependent diabetes mellitus." Acta Med Scand, 211, p. 7-12
  6. Viberti GC, Keen H, Bloom SR (1980) "Beta blockade and diabetes mellitus: effect of oxprenolol and metoprolol on the metabolic, cardiovascular, and hormonal response to insulin-induced hypoglycemia in insulin-dependent diabetics." Metabolism, 29, p. 873-9
  7. Viberti GC, Keen H, Bloom SR (1980) "Beta blockade and diabetes mellitus: effect of oxprenolol and metoprolol on the metabolic, cardiovascular, and hormonal response to insulin-induced hypoglycemia in normal subjects." Metabolism, 29, p. 866-72
  8. Newman RJ (1976) "Comparison of propranolol, metoprolol, and acebutolol on insulin-induced hypoglycaemia." Br Med J, 2, p. 447-9
  9. Smith U (1978) "Beta blockade in diabetes." N Engl J Med, 299, p. 1467
  10. Zaman R, Kendall MJ, Biggs PI (1982) "The effect of acebutolol and propranolol on the hypoglycaemic action of glibenclamide." Br J Clin Pharmacol, 13, p. 507-12
  11. Munroe WP, Rindone JP, Kershner RM (1985) "Systemic side effects associated with the ophthalmic administratiion of timolol." Drug Intell Clin Pharm, 19, p. 85-9
  12. Ostman J (1983) "B-adrenergic blockade and diabetes mellitus." Acta Med Scand, 672, p. 69-77
  13. Deacon SP, Karunanayake A, Barnett D (1977) "Acebutolol, atenolol, and propranolol and metabolic responses to acute hypoglycaemia in diabetes." Br Med J, 12, p. 1255-7
  14. Pollare T, Lithell H, Selinus I, Berne C (1989) "Sensitivity to insulin during treatment with atenolol and metoprolol: a randomised, double blind study of effects on carbohydrate and lipoprotein metabolism in hypertensive patients." BMJ, 298, p. 1152-7
  15. Sinclair AJ, Davies IB, Warrington SJ (1990) "Betaxolol and glucose-insulin relationships: studies in normal subjects taking glibenclamide or metformin." Br J Clin Pharmacol, 30, p. 699-702
  16. (1975) "New Zealand Committee on Adverse Drug Reactions. Ninth Annual Report." N Z Dent J, 71, p. 28-32
View all 16 references

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Moderate

hydroCHLOROthiazide glimepiride

Applies to: hydrochlorothiazide / timolol and glimepiride

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 (1987) "Alternate day corticosteroid causes alternate day hyperglycaemia." Postgrad Med J, 63, p. 761-4
  2. Pollare T, Lithell H, Berne C (1989) "A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension." N Engl J Med, 321, p. 868-73
  3. Carter BL, Small RE, Mandel MD, Starkman MT (1981) "Phenytoin-induced hyperglycemia." Am J Hosp Pharm, 38, p. 1508-12
  4. Al-Rubeaan K, Ryan EA (1991) "Phenytoin-induced insulin insensitivity." Diabet Med, 8, p. 968-70
  5. Chaudhuri ML, Catania J (1988) "A comparison of the effects of bumetanide (Burinex) and frusemide on carbohydrate metabolism in the elderly." Br J Clin Pract, 42, p. 427-9
  6. Goldman JA, Neri A, Ovadia J, Eckerling B, Vries A, de (1969) "Effect of chlorothiazide on intravenous glucose tolerance in pregnancy." Am J Obstet Gynecol, 105, p. 556-60
  7. Miller NR, Moses H (1978) "Transient oculomotor nerve palsy. Association with thiazide-induced glucose intolerance." JAMA, 240, p. 1887-8
  8. Kansal PC, Buse J, Buse MG (1969) "Thiazide diuretics and control of diabetes mellitus." South Med J, 62, p. 1372-9
  9. Andersen OO, Persson I (1968) "Carbohydrate metabolism during treatment with chlorthalidone and ethacrynic acid." Br Med J, 2, p. 798-801
  10. Curtis J, Horrigan F, Ahearn D, Varney R, Sandler SG (1972) "Chlorthalidone-induced hyperosmolar hyperglycemic nonketotic coma." JAMA, 220, p. 1592-3
  11. Chowdhury FR, Bleicher SJ (1970) "Chlorthalidone--induced hypokalemia and abnormal carbohydrate metabolism." Horm Metab Res, 2, p. 13-6
  12. Diamond MT (1972) "Hyperglycemic hyperosmolar coma associated with hydrochlorothiazide and pancreatitis." N Y State J Med, 72, p. 1741-2
  13. Jones IG, Pickens PT (1967) "Diabetes mellitus following oral diuretics." Practitioner, 199, p. 209-10
  14. Black DM, Filak AT (1989) "Hyperglycemia with non-insulin-dependent diabetes following intraarticular steroid injection." J Fam Pract, 28, p. 462-3
  15. Gunnarsson R, Lundgren G, Magnusson G, Ost L, Groth CG (1980) "Steroid diabetes--a sign of overtreatment with steroids in the renal graft recipient?" Scand J Urol Nephrol Suppl, 54, p. 135-8
  16. Murphy MB, Kohner E, Lewis PJ, Schumer B, Dollery CT (1982) "Glucose intolerance in hypertensive patients treated with diuretics: a fourteen-year follow-up." Lancet, 2, p. 1293-5
  17. Seltzer HS, Allen EW (1969) "Hyperglycemia and inhibition of insulin secretion during administration of diazoxide and trichlormethiazide in man." Diabetes, 18, p. 19-28
  18. Jori A, Carrara MC (1966) "On the mechanism of the hyperglycaemic effect of chlorpromazine." J Pharm Pharmacol, 18, p. 623-4
  19. Erle G, Basso M, Federspil G, Sicolo N, Scandellari C (1977) "Effect of chlorpromazine on blood glucose and plasma insulin in man." Eur J Clin Pharmacol, 11, p. 15-8
  20. (2002) "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham
  21. (2002) "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals
  22. (2002) "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals
  23. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  24. (2002) "Product Information. Synthroid (levothyroxine)." Abbott Pharmaceutical
  25. (2001) "Product Information. Carafate (sucralfate)." Hoechst Marion Roussel
  26. Stambaugh JE, Tucker DC (1974) "Effect of diphenylhydantoin on glucose tolerance in patients with hypoglycemia." Diabetes, 23, p. 679-83
  27. Malherbe C, Burrill KC, Levin SR, Karam JH, Forsham PH (1972) "Effect of diphenylhydantoin on insulin secretion in man." N Engl J Med, 286, p. 339-42
  28. Javier Z, Gershberg H, Hulse M (1968) "Ovulatory suppressants, estrogens, and carbohydrate metabolism." Metabolism, 17, p. 443-56
  29. Sotaniemi E, Kontturi M, Larmi T (1973) "Effect of diethylstilbestrol on blood glucose of prostatic cancer patients." Invest Urol, 10, p. 438-41
  30. Bell DS (1993) "Insulin resistance. An often unrecognized problem accompanying chronic medical disorders." Postgrad Med, 93, 99-103,
  31. Berlin I (1993) "Prazosin, diuretics, and glucose intolerance." Ann Intern Med, 119, p. 860
  32. Rowe P, Mather H (1985) "Hyperosmolar non-ketotic diabetes mellitus associated with metolazone." Br Med J, 291, p. 25-6
  33. Haiba NA, el-Habashy MA, Said SA, Darwish EA, Abdel-Sayed WS, Nayel SE (1989) "Clinical evaluation of two monthly injectable contraceptives and their effects on some metabolic parameters." Contraception, 39, p. 619-32
  34. Virutamasen P, Wongsrichanalai C, Tangkeo P, Nitichai Y, Rienprayoon D (1986) "Metabolic effects of depot-medroxyprogesterone acetate in long-term users: a cross-sectional study." Int J Gynaecol Obstet, 24, p. 291-6
  35. Dimitriadis G, Tegos C, Golfinopoulou L, Roboti C, Raptis S (1993) "Furosemide-induced hyperglycaemia - the implication of glycolytic kinases." Horm Metab Res, 25, p. 557-9
  36. Goldman JA, Ovadia JL (1969) "The effect of estrogen on intravenous glucose tolerance in woman." Am J Obstet Gynecol, 103, p. 172-8
  37. Hannaford PC, Kay CR (1989) "Oral contraceptives and diabetes mellitus." BMJ, 299, p. 1315-6
  38. Spellacy WN, Ellingson AB, Tsibris JC (1989) "The effects of two triphasic oral contraceptives on carbohydrate metabolism in women during 1 year of use." Fertil Steril, 51, p. 71-4
  39. Ludvik B, Clodi M, Kautzky-Willer A, Capek M, Hartter E, Pacini G, Prager R (1993) "Effect of dexamethasone on insulin sensitivity, islet amyloid polypeptide and insulin secretion in humans." Diabetologia, 36, p. 84-7
  40. Domenet JG (1968) "Diabetogenic effect of oral diuretics." Br Med J, 3, p. 188
  41. Coni NK, Gordon PW, Mukherjee AP, Read PR (1974) "The effect of frusemide and ethacrynic acid on carbohydrate metabolism." Age Ageing, 3, p. 85-90
  42. Schmitz O, Hermansen K, Nielsen OH, Christensen CK, Arnfred J, Hansen HE, Mogensen CE, Orskov H, Beck-Nielsen H (1986) "Insulin action in insulin-dependent diabetics after short-term thiazide therapy." Diabetes Care, 9, p. 631-6
  43. Blayac JP, Ribes G, Buys D, Puech R, Loubatieres-Mariani MM (1981) "Effects of a new benzothiadiazine derivative, LN 5330, on insulin secretion." Arch Int Pharmacodyn Ther, 253, p. 154-63
  44. Elmfeldt D, Berglund G, Wedel H, Wilhelmsen L (1983) "Incidence and importance of metabolic side-effects during antihypertensive therapy." Acta Med Scand Suppl, 672, p. 79-83
  45. Winchester JF, Kellett RJ, Boddy K, Boyle P, Dargie HJ, Mahaffey ME, Ward DM, Kennedy AC (1980) "Metolazone and bendroflumethiazide in hypertension: physiologic and metabolic observations." Clin Pharmacol Ther, 28, p. 611-8
  46. Petri M, Cumber P, Grimes L, Treby D, Bryant R, Rawlins D, Ising H (1986) "The metabolic effects of thiazide therapy in the elderly: a population study." Age Ageing, 15, p. 151-5
  47. (2001) "Product Information. Glucophage (metformin)." Bristol-Myers Squibb
  48. Harper R, Ennis CN, Heaney AP, Sheridan B, Gormley M, Atkinson AB, Johnston GD, Bell PM (1995) "A comparison of the effects of low- and conventional-dose thiazide diuretic on insulin action in hypertensive patients with NIDDM." Diabetologia, 38, p. 853-9
  49. (2001) "Product Information. Precose (acarbose)." Bayer
  50. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
  51. (2001) "Product Information. Amaryl (glimepiride)." Hoechst Marion Roussel
  52. Charan VD, Desai N, Singh AP, Choudhry VP (1993) "Diabetes mellitus and pancreatitis as a complication of L- asparaginase therapy." Indian Pediatr, 30, p. 809-10
  53. Seifer DB, Freedman LN, Cavender JR, Baker RA (1990) "Insulin-dependent diabetes mellitus associated with danazol." Am J Obstet Gynecol, 162, p. 474-5
  54. (2001) "Product Information. Crixivan (indinavir)." Merck & Co., Inc
  55. Pickkers P, Schachter M, Hughes AD, Feher MD, Sever PS (1996) "Thiazide-induced hyperglycaemia: a role for calcium-activated potassium channels?" Diabetologia, 39, p. 861-4
  56. (2001) "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc
  57. Dube MP, Johnson DL, Currier JS, Leedom JM (1997) "Protease inhibitor-associated hyperglycaemia." Lancet, 350, p. 713-4
  58. (2001) "Product Information. Oncaspar (pegaspargase)." Rhone Poulenc Rorer
  59. (2001) "Product Information. Prandin (repaglinide)." Novo Nordisk Pharmaceuticals Inc
  60. (2001) "Product Information. Elspar (asparaginase)." Merck & Co., Inc
  61. (2022) "Product Information. Hyperstat (diazoxide)." Apothecon Inc
  62. (2001) "Product Information. Megace (megestrol)." Bristol-Myers Squibb
  63. Walli R, Demant T (1998) "Impaired glucose tolerance and protease inhibitors." Ann Intern Med, 129, p. 837-8
  64. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  65. Mauss S, Wolf E, Jaeger H (1999) "Impaired glucose tolerance in HIV-positive patients receiving and those not receiving protease inhibitors." Ann Intern Med, 130, p. 162-3
  66. Kaufman MB, Simionatto C (1999) "A review of protease inhibitor-induced hyperglycemia." Pharmacotherapy, 19, p. 114-7
  67. (2001) "Product Information. Tolinase (tolazamide)." Pharmacia and Upjohn
  68. (2001) "Product Information. Orinase (tolbutamide)." Pharmacia and Upjohn
  69. (2001) "Product Information. Dymelor (acetohexamide)." Lilly, Eli and Company
  70. Wehring H, Alexander B, Perry PJ (2000) "Diabetes mellitus associated with clozapine therapy." Pharmacotherapy, 20, p. 844-7
  71. Tsiodras S, Mantzoros C, Hammer S, Samore M (2000) "Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and lipodystrophy - A 5-year cohort study." Arch Intern Med, 160, p. 2050-6
  72. (2001) "Product Information. Fortovase (saquinavir)." Roche Laboratories
  73. (2001) "Product Information. Starlix (nateglinide)." Novartis Pharmaceuticals
  74. Hardy H, Esch LD, Morse GD (2001) "Glucose disorders associated with HIV and its drug therapy." Ann Pharmacother, 35, p. 343-51
  75. Leary WP, Reyes AJ (1984) "Drug interactions with diuretics." S Afr Med J, 65, p. 455-61
  76. (2022) "Product Information. NovoLOG Mix 70/30 (insulin aspart-insulin aspart protamine)." Novo Nordisk Pharmaceuticals Inc
  77. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb
  78. (2003) "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline
  79. (2004) "Product Information. Apidra (insulin glulisine)." Aventis Pharmaceuticals
  80. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc
  81. (2006) "Product Information. Zolinza (vorinostat)." Merck & Co., Inc
  82. (2007) "Product Information. Torisel (temsirolimus)." Wyeth-Ayerst Laboratories
  83. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
  84. (2019) "Product Information. Elzonris (tagraxofusp)." Stemline Therapeutics
  85. (2019) "Product Information. Piqray (alpelisib)." Novartis Pharmaceuticals
View all 85 references

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Drug and food interactions

Moderate

glimepiride food

Applies to: glimepiride

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

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Moderate

timolol food

Applies to: hydrochlorothiazide / timolol

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  8. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
View all 8 references

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Moderate

hydroCHLOROthiazide food

Applies to: hydrochlorothiazide / timolol

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  8. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
View all 8 references

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Moderate

timolol food

Applies to: hydrochlorothiazide / timolol

ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.

References

  1. Kirch W, Schafer-Korting M, Axthelm T, Kohler H, Mutschler E (1981) "Interaction of atenolol with furosemide and calcium and aluminum salts." Clin Pharmacol Ther, 30, p. 429-35

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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.