Isosorbide Dinitrate + Hydralazine Hydrochloride interactions

Food & lifestyle

• alcohol

  Moderate

  Synergy

  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.

  What to do: 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.

  8 sources

  1. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595

• alcohol

  Moderate

  Synergy

  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.

  What to do: 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.

  8 sources

  1. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595

Conditions

Conditions in which Isosorbide Dinitrate + Hydralazine Hydrochloride needs care, as documented in this source.

• Anemia

  Major

  Some manufacturers and medical references consider the use of nitrates and nitrites to be contraindicated in patients with severe anemia. Nitrates and nitrites can cause methemoglobinemia, primarily in high-dose intravenous therapy or acute poisoning and in patients with NADH reductase deficiency. However, elevations of methemoglobin may also occur with commonly used dosages. While probably not of routine clinical significance, the increases may be important in certain patient populations such as those with coronary insufficiency or anemia.

  14 sources

  1. Fibuch EE, Cecil WT, Reed WA "Methemoglobinemia associated with organic nitrate therapy." Anesth Analg 58 (1979): 521-3
  2. Arsura E, Lichstein E, Guadagnino V, Nicchi V, Sanders M, Hollander G, Greengart A "Methemoglobin levels produced by organic nitrates in patients with coronary artery disease." J Clin Pharmacol 24 (1984): 160-4
  3. Curry SC, Arnold-Capell P "Toxic effects of drugs used in the ICU. Nitroprusside, nitroglycerin, and angiotensin-converting enzyme inhibitors." Crit Care Clin 7 (1991): 555-81
  4. Kaplan K, Davison R "Nitroglycerin and methemoglobinemia." Am J Cardiol 57 (1986): 1004
  5. Saxon SA, Silverman ME "Effects of continuous infusion of intravenous nitroglycerin on methemoglobin levels." Am J Cardiol 56 (1985): 461-4
  6. Gibson GR, Hunter JB, Raabe DS, Jr Manjoney DL, Ittleman FP "Methemoglobinemia produced by high-dose intravenous nitroglycerin." Ann Intern Med 96 (1982): 615-6
  7. Robicsek F "Acute methemoglobinemia during cardiopulmonary bypass caused by intravenous nitroglycerin infusion." J Thorac Cardiovasc Surg 90 (1985): 931-4
  8. "Product Information. Nitrostat (nitroglycerin)." Parke-Davis (2002):

  Show all 14 sourcesShow fewer sources

  9. Forsyth RJ, Moulden A "Methaemoglobinaemia after ingestion of amyl nitrite." Arch Dis Child 66 (1991): 152
  10. Pierce JM, Nielsen MS "Acute acquired methaemoglobinaemia after amyl nitrite poisoning." BMJ 298 (1989): 1566
  11. Sutton M, Jeffrey B "Acquired methemoglobinemia from amyl nitrate inhalation." J Emerg Nurs 18 (1992): 8-9
  12. Sobey RJ, Campbell CM "A 37-year-old with amyl nitrite-induced methemoglobinemia." J Emerg Nurs 18 (1992): 11-3
  13. Edwards RJ, Ujma J "Extreme methaemoglobinaemia secondary to recreational use of amyl nitrite." J Accid Emerg Med 12 (1995): 138-42
  14. Machabert R, Testud F, Descotes J "Methaemoglobinaemia due to amyl nitrite inhalation: a case report." Hum Exp Toxicol 13 (1994): 313-4

• Bone Marrow Failure Disorders

  Major

  Hydralazine may rarely cause blood dyscrasias at recommended dosages. Reduction in hemoglobin, red cell count, agranulocytosis, leukopenia, and purpura have been reported. Therapy with hydralazine should be administered cautiously in patients with these preexisting conditions and if such abnormalities develop during the course of therapy, treatment should be discontinued. Monitoring blood counts should be considered for those patients at higher risk.

  7 sources

  1. Koch-Weser J "Hydralazine." N Engl J Med 295 (1976): 320-3
  2. Orenstein AA, Yakulis V, Eipe J, Costea N "Immune hemolysis due to hydralazine." Ann Intern Med 86 (1977): 450-1
  3. Widerlov E, Karlman I, Storsater J "Hydralazine-induced neonatal thrombocytopenia." N Engl J Med 303 (1980): 1235
  4. Freestone S, Ramsay LE "Transient monoclonal gammopathy in hydralazine-induced lupus erythematosus." Br Med J 285 (1982): 1536-7
  5. Macleod WN "Anaemia in the hydrallazine-induced lupus syndrome." Scott Med J 28 (1983): 181-2
  6. Harrison BD, Laidlaw ST, Reilly JT "Fatal aplastic anaemia associated with lisinopril." Lancet 346 (1995): 247-8
  7. "Product Information. Apresoline (hydralazine)." Ciba-Geigy Pharmaceuticals (2001):

• Coronary Artery Disease

  Major

  The use of hydralazine is contraindicated in patients with coronary artery disease. Reflex tachycardia may commonly occur. Palpitations and chest pain have also been reported. Myocardial infarction has been associated with the use of hydralazine.

  3 sources

  1. Koch-Weser J "Hydralazine." N Engl J Med 295 (1976): 320-3
  2. Laslett LJ, DeMaria AN, Amsterdam EA, Mason DT "Hydralazine-induced tachycardia and sodium retention in heart failure: hemodynamic and symptomatic correlation by prazosin therapy." Arch Intern Med 138 (1978): 819-20
  3. Packer M, Meller J, Medina N, et al. "Provocation of myocardial ischemic events during initiation of vasodilator therapy for severe chronic heart failure." Am J Cardiol 48 (1981): 939-46

• Diseases requiring hemodialysis

  Major

  The combined effect of organic nitrates or nitrites with hemodialysis, which often lowers blood pressure, can cause life-threatening hypotension. Therapy with these agents should be administered cautiously in patients requiring hemodialysis. The medication should be withheld before undergoing dialysis, and hemodynamic stability should be established prior to resumption of medication following dialysis. Nitroglycerin and isosorbide dinitrate are moderately dialyzed.

  2 sources

  1. Imamura T, Tamura K, Taguchi T, Minoda M, Seita M "Reduction of nitroglycerin and isosorbide dinitrate by hemodialysis in refractory angina pectoris after acute myocardial infarction." Am J Cardiol 61 (1988): 954-5
  2. Dunetz PS "Dialysis patients and nitrates." Nursing 22 (1992): 4

• Heart Valve Diseases

  Major

  The use of hydralazine is contraindicated in patients with mitral valvular rheumatic heart disease.

  1 source

  1. "Product Information. Apresoline (hydralazine)." Ciba-Geigy Pharmaceuticals (2001):

• Hypotension

  Major

  Organic nitrates and nitrites may cause severe hypotension, syncope and shock, even with small doses. Hypotension induced by these agents may be accompanied by paradoxical bradycardia and increased angina pectoris. Therapy with nitrates and nitrites should be administered cautiously in patients who are volume-depleted or hypotensive (e.g., systolic blood pressure <90 mm Hg) or who, because of inadequate circulation to the brain or to other vital organs, would be unusually compromised by undue hypotension. Patients should be in a sitting or recumbent position during and immediately after drug administration, and monitored for symptoms of severe hypotension such as nausea, vomiting, weakness, pallor, perspiration, and syncope. Nitrate or nitrite therapy is considered contraindicated in patients with acute circulatory failure or shock.

  12 sources

  1. Purvin VA, Dunn DW "Nitrate-induced transient ischemic attacks." South Med J 74 (1981): 1130-1
  2. Buckley R, Roberts R "Symptomatic bradycardia following the administration of sublingual nitroglycerin." Am J Emerg Med 11 (1993): 253-5
  3. von Arnim T, Autenrieth G, Bolte HD "Acute myocardial infarction during continuous electrocardiographic ST segment recording. Possible role of bradycardia and hypotension induced by glyceryl trinitrate." Br Heart J 51 (1984): 575-7
  4. Lancaster L, Fenster PE "Complete heart block after sublingual nitroglycerin." Chest 84 (1983): 111-2
  5. Ong EA, Bass S "Nitroglycerin-induced bradycardia and hypotension in acute myocardial infarction." Chest 77 (1980): 244
  6. Cunningham J "Hypotension following administration of sublingual nitroglycerin ." Heart Lung 8 (1979): 364
  7. Nemerovski M, Shah PK "Syndrome of severe bradycardia and hypotension following sublingual nitroglycerin administration." Cardiology 67 (1981): 180-9
  8. Brandes W, Santiago T, Limacher M "Nitroglycerin-induced hypotension, bradycardia, and asystole: report of a case and review of the literature." Clin Cardiol 13 (1990): 741-4

  Show all 12 sourcesShow fewer sources

  9. "Product Information. Isordil (isosorbide dinitrate)." Wyeth-Ayerst Laboratories (2002):
  10. "Product Information. ISMO (isosorbide mononitrate)." Wyeth-Ayerst Laboratories (2002):
  11. "Product Information. Tridil (nitroglycerin)." DuPont Pharmaceuticals (2002):
  12. "Product Information. Nitrostat (nitroglycerin)." Parke-Davis (2002):

• Intracranial Hypertension

  Major

  Organic nitrates and nitrites can increase cerebrospinal fluid pressure. Therapy with these agents should be administered cautiously, if at all, in patients with or at risk for intracranial hypertension, including those with cerebral hemorrhage, intracranial lesions, or recent head trauma.

  6 sources

  1. Ahmad S "Nitroglycerin and intracranial hypertension ." Am Heart J 121 (1991): 1850-1
  2. Gagnon RL, Marsh ML, Smith RW, Shapiro HM "Intracranial hypertension caused by nitroglycerin." Anesthesiology 51 (1979): 86-7
  3. Boggild M "Intracerebral haemorrhage after dermal nitrate application." BMJ 305 (1992): 1000
  4. Hannerz J, Greitz D "Cerebrospinal fluid pressure and venous pressure in "dynamite headache" and cluster headache attacks." Headache 32 (1992): 436-8
  5. "Product Information. Tridil (nitroglycerin)." DuPont Pharmaceuticals (2002):
  6. "Product Information. Nitrostat (nitroglycerin)." Parke-Davis (2002):

• Lupus Erythematosus, Systemic

  Major

  The use of hydralazine has been associated with the development of lupus erythematosus and lupus-like syndromes, as well as exacerbation of the disease. Hydralazine therapy should be withdrawn in patients experiencing worsening of preexisting lupus. Monitoring complete blood counts, and antinuclear antibody titers before and during prolonged therapy is recommended.

  21 sources

  1. Hahn BH, Sharp GC, Irvin WS, et al. "Immune responses to hydralazine and nuclear antigens in hydralazine-induced lupus erythematosus." Ann Intern Med 76 (1972): 365-74
  2. Carey RM, Coleman M, Feder A "Pericardial tamponade: a major presenting manifestation of hydralazine-induced lupus syndrome." Am J Med 54 (1973): 84-7
  3. Perry HM "Late toxicity to hydralazine resembling systemic lupus erythematosus or rheumatoid arthritis." Am J Med 54 (1973): 58-72
  4. Blumenkrantz N, Christiansen AH, Ullman S, Asboe-Hansen G "Hydralazine-induced lupoid syndrome." Acta Med Scand 195 (1974): 443-9
  5. Weinstein J "Hypocomplementemia in hydralazine-associated systemic lupus erythematosus." Am J Med 65 (1978): 553-6
  6. Freestone S, Ramsay LE "Transient monoclonal gammopathy in hydralazine-induced lupus erythematosus." Br Med J 285 (1982): 1536-7
  7. Macleod WN "Anaemia in the hydrallazine-induced lupus syndrome." Scott Med J 28 (1983): 181-2
  8. Ihle BU, Whitworth JA, Dowling JP, Kincaid-Smith P "Hydralazine and lupus nephritis." Clin Nephrol 22 (1984): 230-8

  Show all 21 sourcesShow fewer sources

  9. Cameron HA, Ramsay LE "The lupus syndrome induced by hydralazine: a common complication with low dose treatment." Br Med J 289 (1984): 410-12
  10. Naparstek Y, Kopolovic J, Tur-Kaspa R, Rubinger D "Focal glumerulonephritis in the course of hydralazine-induced lupus syndrome." Arthritis Rheum 27 (1984): 822-5
  11. Shapiro KS, Pinn VW, Harrington JT, Levey AS "Immune complex glomerulonephritis in hydralazine-induced SLE." Am J Kidney Dis 3 (1984): 270-4
  12. Cush JJ, Goldings EA "Southwestern internal medicine conference: drug-induced lupus: clinical spectrum and pathogenesis." Am J Med Sci 290 (1985): 36-45
  13. Innes A, Rennie JA, Cato GR "Drug-induced lupus caused by very-low-dose hydralazine." Br J Rheumatol 25 (1986): 225-31
  14. Darwaza A, Lamey P-J, Connell JM "Hydrallazine-induced Sjogren's syndrome." Int J Oral Maxillofac Surg 17 (1988): 92-3
  15. Sturman SG, Kumararatne D, Beevers DG "Fatal hydralazine-induced systemic lupus erythematosus." Lancet 12/03/88 (1988): 1304
  16. Fleming MG, Bergfeld WF, Tomecki KJ, et al. "Bullous systemic lupus erythematosus." Int J Dermatol 28 (1989): 321-6
  17. Ramsey-Goldman R, Franz T, Solano FX, Medsger TA "Hydralazine induced lupus and sweet's syndrome: report and review of the literature." J Rheumatol 17 (1990): 682-4
  18. Lunde PK, Frislid K, Hansteen V "Disease and acetylation polymorphism." Clin Pharmacokinet 2 (1977): 182-97
  19. Timbrell JA, Facchini V, Harland SJ, Mansilla-Tinoco R "Hydralazine-induced lupus: is there a toxic metabolic pathway?" Eur J Clin Pharmacol 27 (1984): 555-9
  20. "Product Information. Apresoline (hydralazine)." Ciba-Geigy Pharmaceuticals (2001):
  21. Pirmohamed M "Hydralazine-induced lupus: yet another autoantibody! triplex-DNA stabilization by hydralazine and the presence of anti-(triplex DNA) antibodies in patients treated with hydralazine - comment." Hum Exp Toxicol 15 (1996): 361-2

• Myocardial Infarction

  Major

  The benefits of organic nitrates and nitrites in patients with acute myocardial infarction (AMI) or congestive heart failure have not been established and its use is not recommended in these settings. If used, it should be accompanied by careful clinical and hemodynamic monitoring to avoid the hazards of systemic hypotension and tachycardia, which in AMI can exacerbate myocardial ischemia. In general, oral or long-acting formulations of these drugs should not be used in the early management of AMI because of the difficulty in precisely controlling and rapidly terminating their hemodynamic effects should adverse reactions occur. Sublingual and other immediate- onset nitrates or nitrites should typically be avoided in suspected AMI with marked bradycardia or tachycardia, and should be used with extreme caution, if at all, in patients with right ventricular or inferior wall infarction. Rarely, sublingual nitroglycerin has produced hypotension accompanied by paradoxical bradycardia in patients with AMI and especially right ventricular infarction. The latter group of patients are also particularly dependent on adequate right ventricular preload to maintain cardiac output and can experience profound hypotension with nitrate or nitrite administration due to reduction of right ventricular preload.

  11 sources

  1. Scardi S, Zingone B, Pandullo C "Myocardial infarction following sublingual administration of isosorbide dinitrate." Int J Cardiol 26 (1990): 378-9
  2. Berisso MZ, Cavallini A, Iannetti M "Sudden death during continuous Holter monitoring out of hospital after nitroglycerin consumption." Am J Cardiol 54 (1984): 677-9
  3. Buckley R, Roberts R "Symptomatic bradycardia following the administration of sublingual nitroglycerin." Am J Emerg Med 11 (1993): 253-5
  4. Ong EA, Canlas C, Smith W "Nitroglycerin-induced asystole ." Arch Intern Med 145 (1985): 954
  5. von Arnim T, Autenrieth G, Bolte HD "Acute myocardial infarction during continuous electrocardiographic ST segment recording. Possible role of bradycardia and hypotension induced by glyceryl trinitrate." Br Heart J 51 (1984): 575-7
  6. Lancaster L, Fenster PE "Complete heart block after sublingual nitroglycerin." Chest 84 (1983): 111-2
  7. Brandes W, Santiago T, Limacher M "Nitroglycerin-induced hypotension, bradycardia, and asystole: report of a case and review of the literature." Clin Cardiol 13 (1990): 741-4
  8. "Product Information. Isordil (isosorbide dinitrate)." Wyeth-Ayerst Laboratories (2002):

  Show all 11 sourcesShow fewer sources

  9. "Product Information. ISMO (isosorbide mononitrate)." Wyeth-Ayerst Laboratories (2002):
  10. "Product Information. Tridil (nitroglycerin)." DuPont Pharmaceuticals (2002):
  11. "Product Information. Nitrostat (nitroglycerin)." Parke-Davis (2002):

• Cardiomyopathy, Hypertrophic

  Moderate

  Organic nitrates and nitrites may aggravate the angina associated with hypertrophic cardiomyopathy and should be administered cautiously in patients with this condition.

  4 sources

  1. "Product Information. Isordil (isosorbide dinitrate)." Wyeth-Ayerst Laboratories (2002):
  2. "Product Information. ISMO (isosorbide mononitrate)." Wyeth-Ayerst Laboratories (2002):
  3. "Product Information. Tridil (nitroglycerin)." DuPont Pharmaceuticals (2002):
  4. "Product Information. Nitrostat (nitroglycerin)." Parke-Davis (2002):

• Cardiovascular Diseases

  Moderate

  The vasodilatory effects of hydralazine may aggravate cerebral vasculopathy. Therapy with hydralazine should be administered cautiously in patients with cerebral vasculopathy.

  2 sources

  1. Koch-Weser J "Hydralazine." N Engl J Med 295 (1976): 320-3
  2. "Product Information. Apresoline (hydralazine)." Ciba-Geigy Pharmaceuticals (2001):

• Kidney Diseases

  Moderate

  The use of hydralazine has been associated with the development of glomerulonephritis. Hydralazine should be used with caution in patients with advanced renal damage and these patients may require a lower dose. Renal function should be monitored and supported as required.

  1 source

  1. "Product Information. Apresoline (hydralazine)." Ciba-Geigy Pharmaceuticals (2001):

• Glaucoma

  Minor

  Some medical references state that organic nitrates and nitrites may increase intraocular pressure and should be used with caution in patients with glaucoma. However, the effect on intraocular pressure is variable and brief, and there is no evidence that these drugs precipitate narrow-angle glaucoma. Amyl nitrate typically may cause a slight rise of 3+ mm for several seconds followed by a fall in intraocular pressure for 10 to 20 minutes, the latter secondary to a fall in blood pressure. Nitroglycerin rarely produces ocular side effects, and oral nitroglycerin appears to have few to no significant ocular side effects.

  1 source

  1. Fraunfelder FT, Fraunfelder FW; Randall JA "Drug-Induced Ocular Side Effects" Boston, MA: Butterworth-Heinemann (2001):