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Innohep (tinzaparin) Disease Interactions

There are 5 disease interactions with Innohep (tinzaparin):

Major

Anticoagulants (Includes Innohep) ↔ Peptic Ulcer Disease

Severe Potential Hazard, Moderate plausibility

Applies to: Bleeding

Anticoagulants are contraindicated in patients with active major bleeding or those patients at risk for hemorrhage. Hemorrhage due to heparin derivatives may be treated with protamine sulfate 1%. However, protamine sulfate may not completely neutralize the anti- Factor Xa activity.

References

  1. "Product Information. Heparin Sodium (heparin)." Lilly, Eli and Company, Indianapolis, IN.
  2. "Product Information. Fragmin (dalteparin)." Pharmacia and Upjohn, Kalamazoo, MI.
  3. Breddin HK "Low molecular weight heparins and bleeding." Semin Thromb Hemost 15 (1989): 401-4
  4. "Product Information. Lovenox (enoxaparin)." Rhone-Poulenc Rorer, Collegeville, PA.
  5. "Product Information. Orgaran (danaparoid)." Organon, West Orange, NJ.
  6. Hirsh J, Fuster V "Guide to anticoagulant therapy. 1. Heparin." Circulation 89 (1994): 1449-68
  7. Walker AM, Jick H "Predictors of bleeding during heparin therapy." JAMA 244 (1980): 1209-12
  8. Nieuwenhuis HK, Albada J, Banga JD, Sixma JJ "Identification of risk factors for bleeding during treatment of acute venous thromboembolism with heparin or low molecular weight heparin." Blood 78 (1991): 2337-43
  9. Nieuwenhuis HK, Albada J, Banga JD, Sixma JJ "Identification of risk factors for bleeding during treatment of acute venous thromboembolism with heparin or low molecular weight heparin." Blood 78 (1991): 2337-43
  10. Sugiyama T, Itoh M, Ohtawa M, Natsuga T "Study on neutralization of low molecular weight heparin (LHG) by protamine sulfate and its neutralization characteristics." Thromb Res 68 (1992): 119-29
  11. Oates JA, Wood AJJ "Heparin." N Engl J Med 324 (1991): 1565-74
View all 11 references
Major

Heparin (Includes Innohep) ↔ Active Bleeding

Severe Potential Hazard, High plausibility

Applies to: Abnormal Uterine Bleeding, Diverticulitis, Hypertension, Bleeding, Peptic Ulcer, Colonic Ulceration, Ulcerative Colitis, Myeloproliferative Disorder, Liver Disease, Coagulation Defect, Infectious Endocarditis

The use of heparin is contraindicated in patients with uncontrollable active bleeding, except when the bleeding is due to disseminated intravascular coagulation. Hemorrhage can occur at virtually any site in patients receiving heparin. An unexplained drop in hematocrit or blood pressure, or any other unexplained symptom, should lead to serious consideration of a hemorrhagic event. Therapy with heparin should be used with extreme caution in patients with known bleeding disorders or disease states that may predispose to hemorrhage during heparin administration, including hemophilia, thrombocytopenia, certain vascular purpuras, ulcerative gastrointestinal lesions, diverticulitis, ulcerative colitis, severe liver disease, subacute bacterial endocarditis, severe hypertension, myeloproliferative disorders, and threatened abortion. Blood coagulation tests (e.g., whole blood clotting time, activated partial thromboplastin time) should be performed at appropriate intervals during full-dose heparin administration. In addition, periodic platelet counts, hematocrits, and tests for occult blood in stool are recommended during the entire course of heparin therapy. There is usually no need to monitor coagulation parameters in patients receiving low-dose heparin, except in patients undergoing major surgery. For low molecular weight heparin (LMWH), coagulation tests such as prothrombin time (PT) and aPTT are relatively insensitive measures of LMWH activity and not suitable for routine monitoring. Anti-Factor Xa may be used to monitor the anticoagulant effect of LMWH in patients with significant renal impairment, abnormal coagulation parameters, or bleeding during therapy.

References

  1. Sugiyama T, Itoh M, Ohtawa M, Natsuga T "Study on neutralization of low molecular weight heparin (LHG) by protamine sulfate and its neutralization characteristics." Thromb Res 68 (1992): 119-29
  2. Nieuwenhuis HK, Albada J, Banga JD, Sixma JJ "Identification of risk factors for bleeding during treatment of acute venous thromboembolism with heparin or low molecular weight heparin." Blood 78 (1991): 2337-43
  3. Breddin HK "Low molecular weight heparins and bleeding." Semin Thromb Hemost 15 (1989): 401-4
  4. Nicholson CD, Meuleman DG, Magnani HN, Egberts JF, Leibowitz DA, Spinler SA, Cziraky MJ "Danaparoid is not a low-molecular-weight heparin." Am J Hosp Pharm 51 (1994): 2049-50
  5. Chong BH, Magnani HN "Orgaran in heparin-induced thrombocytopenia." Haemostasis 22 (1992): 85-91
  6. Bergqvist D, Burmark US, Frisell J, Hallbook T, Lindblad B, Risberg B, Torngren S, Wallin G "Prospective double-blind comparison between Fragmin and conventional low-dose heparin: thromboprophylactic effect and bleeding complications." Haemostasis 16 Suppl 2 (1986): 11-8
  7. Magnani HN "Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with orgaran (Org 10172) [published erratum appears in Thromb Haemost 1993 Dec 20;70(6):1072]." Thromb Haemost 70 (1993): 554-61
  8. "Product Information. Orgaran (danaparoid)." Organon, West Orange, NJ.
  9. "Product Information. Lovenox (enoxaparin)." Rhone-Poulenc Rorer, Collegeville, PA.
  10. "Product Information. Fragmin (dalteparin)." Pharmacia and Upjohn, Kalamazoo, MI.
  11. de Valk HW, Banga JD, Wester JW, Brouwer CB, van Hessen MW, Meuwissen OJ, Hart HC, Sixma JJ, Nieuwenhuis HK "Comparing subcutaneous danaparoid with intravenous unfractionated heparin for the treatment of venous thromboembolism. A randomized controlled trial." Ann Intern Med 123 (1995): 1-9
  12. "Product Information. Heparin Sodium (heparin)." Lilly, Eli and Company, Indianapolis, IN.
View all 12 references
Major

Heparin (Includes Innohep) ↔ Renal Dysfunction

Severe Potential Hazard, High plausibility

Applies to: Renal Dysfunction

Systemic exposure and the risk of bleeding may be increased when heparin is used in the presence of severe renal impairment. Therapy with heparin should be administered cautiously in patients with significantly impaired renal function. A reduction in dosage may be necessary.

Major

Heparin (Includes Innohep) ↔ Thrombocytopenia

Severe Potential Hazard, High plausibility

Applies to: Thrombocytopenia, Heparin-Induced Thrombocytopenia

The use of heparin is contraindicated in patients with severe thrombocytopenia. Acute thrombocytopenia can occur in patients receiving heparin, with a reported incidence of up to 30%. Platelet counts should be obtained before and periodically during heparin administration, including regular and repeated use of heparin flush solutions if given for longer than 5 days. Mild thrombocytopenia with counts above 100,000/mm3 may remain stable or reverse despite continued heparin administration. However, thrombocytopenia of any degree should be closely monitored. Therapy should be discontinued if the count falls below 100,000/mm3 or if recurrent thrombosis develops, and an alternative, nonheparin anticoagulant (e.g., argatroban, bivalirudin, lepirudin) administered if necessary. Heparin-induced thrombocytopenia (HIT) is a serious antibody-mediated reaction resulting from irreversible aggregation of platelets. HIT may progress to the development of venous and arterial thromboses, a condition referred to as heparin-induced thrombocytopenia and thrombosis (HITT). Thrombotic events may also be the initial presentation for HITT, and may include deep vein thrombosis, pulmonary embolism, cerebral vein thrombosis, limb ischemia, stroke, myocardial infarction, mesenteric thrombosis, renal artery thrombosis, skin necrosis, gangrene of the extremities that may lead to amputation, and possibly death. Both HIT and HITT can occur up to several weeks after the discontinuation of heparin therapy. Patients presenting with thrombocytopenia or thrombosis after discontinuation of heparin should be evaluated for HIT and HITT. Following an episode, any future use of heparin should be avoided, and use of low-molecular weight heparin should consider the potential for cross-reactivity with the HIT antibody and approached with extreme caution, if not otherwise contraindicated.

References

  1. Kelton JG, Sheridan D, Santos A, et al "Heparin-induced thrombocytopenia: laboratory studies." Blood 72 (1988): 925-30
  2. Warkentin TE, Hirsh J, Kelton JG "Heparin-induced thrombocytopenia." N Engl J Med 333 (1995): 1007
  3. Magnani HN "Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with orgaran (Org 10172) [published erratum appears in Thromb Haemost 1993 Dec 20;70(6):1072]." Thromb Haemost 70 (1993): 554-61
  4. Berkowitz N, Beckman J "Heparin-induced thrombocytopenia." N Engl J Med 333 (1995): 1006
  5. Force RW "Heparin-induced thrombocytopenia." Am J Health Syst Pharm 52 (1995): 2528
  6. Sandler RM, Seifer DB, Morgan K, Pockros PJ, Wypych J, Weiss LM, Schiffman S "Heparin-induced thrombocytopenia and thrombosis: detection and specificity of a platelet-aggregating IgG." Am J Clin Pathol 83 (1985): 760-4
  7. Kleinschmidt S, Seyfert UT "Heparin-associated thrombocytopenia (HAT) - still a diagnostic and therapeutical problem in clinical practice." Angiology 46 (1995): 37-44
  8. Rissieri DA, Wong WM, Gockerman JP "Thrombocytosis associated with low-molecular-weight heparin." Ann Intern Med 125 (1996): 157
  9. Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, Kelton JG "Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin." N Engl J Med 332 (1995): 1330-5
  10. Rizzieri DA, Wong WM, Gockerman JP "Thrombocytosis associated with low-molecular-weight heparin." Ann Intern Med 125 (1996): 157
  11. Ramakrishna R, Manoharan A, Kwan YL, Kyle PW "Heparin-induced thrombocytopenia: cross-reactivity between standard heparin, low molecular weight heparin, dalteparin (fragmin) and heparinoid, danaparoid (orgaran)." Br J Haematol 91 (1995): 736-8
  12. Platell CF, Tan EG "Hypersensitivity reactions to heparin: delayed onset thrombocytopenia and necrotizing skin lesions." Aust N Z J Surg 56 (1986): 621-3
  13. Kikta MJ, Keller MP, Humphrey PW, Silver D, Towne JB, Tsapogas M "Can low molecular weight heparins and heparinoids be safely given to patients with heparin-induced thrombocytopenia syndrome?" Surgery 114 (1993): 705-10
  14. Hougardy N, Machiels JP, Ravoet C "Heparin-induced thrombocytopenia." N Engl J Med 333 (1995): 1007
  15. "Product Information. Orgaran (danaparoid)." Organon, West Orange, NJ.
  16. Bell WR, Royall RM "Heparin-associated thrombocytopenia: a comparison of three heparin preparations." N Engl J Med 303 (1980): 902-7
  17. Lecompte T, Luo SK, Stieltjes N, Lecrubier C, et al "Thrombocytopenia associated with low-molecular-weight heparin." Lancet 338 (1991): 1217
  18. Cines DB, Kaywin P, Bina M, et al "Heparin-associated thrombocytopenia." N Engl J Med 303 (1980): 788-95
  19. Tezcan AZ, Tezcan H, Gastineau DA, Armitage JO, Haire WD "Heparin-induced thrombocytopenia after bone marrow transplantation: report of two cases." Bone Marrow Transplant 14 (1994): 487-90
  20. Bergqvist D, Burmark US, Frisell J, Hallbook T, Lindblad B, Risberg B, Torngren S, Wallin G "Prospective double-blind comparison between Fragmin and conventional low-dose heparin: thromboprophylactic effect and bleeding complications." Haemostasis 16 Suppl 2 (1986): 11-8
  21. Eichinger S, Kyrle PA, Brenner B, Wagner B, Kapiotis S, Lechner K, Korninger HC "Thrombocytopenia associated with low-molecular-weight heparin" Lancet 337 (1991): 1425-6
  22. Balestra B, Quadri P, Biasiutti FD, Furlan M, Lammle B "Low molecular weight heparin-induced thrombocytopenia and skin necrosis distant from injection sites." Eur J Haematol 53 (1994): 61-3
  23. Bleasel JF, Rasko JE, Rickard KA, Richards G "Acute adrenal insufficiency secondary to heparin-induced thrombocytopenia-thrombosis syndrome." Med J Aust 157 (1992): 192-3
  24. Peters FPJ, Doevendans PAFM, Erdkamp FLG, Vanderent FWC, Deheer F "Low molecular weight heparin-induced thrombocytopenia and thrombosis." Eur J Haematol 56 (1996): 329-30
  25. Yamamoto S, Koide M, Matsuo M, Suzuki S, Ohtaka M, Saika S, Matsuo T "Heparin-induced thrombocytopenia in hemodialysis patients." Am J Kidney Dis 28 (1996): 82-5
  26. Chong BH "Heparin-induced thrombocytopenia." Aust N Z J Med 22 (1992): 145-52
  27. Rice P, Dace S, Mcmullin MF, Clements WDB "Heparin induced thrombocytopenia causing life-threatening postoperative haemorrhage." Br J Clin Pract 50 (1996): 404-5
  28. Slocum MM, Adams JG, Teel R, Spadone DP, Silver D "Use of enoxaparin in patients with heparin-induced thrombocytopenia syndrome." J Vasc Surg 23 (1996): 839-43
  29. Warkentin TE, Hayward CP, Smith CA, et al "Determinants of donor platelet variability when testing for heparin-induced thrombocytopenia." J Lab Clin Med 120 (1992): 371-9
  30. "Product Information. Lovenox (enoxaparin)." Rhone-Poulenc Rorer, Collegeville, PA.
  31. Munver R, Schulman IC, Wolf DJ, Rosengart TK "Heparin-induced thrombocytopenia and thrombosis: presentation after cardiopulmonary bypass." Ann Thorac Surg 58 (1994): 1764-6
  32. Luzzatto G, Cordiano I, Patrassi G, Fabris F "Heparin-induced thrombocytopenia: discrepancy between the presence of IgG cross-reacting in vitro with fraxiparine and its successful clinical use." Thromb Haemost 75 (1996): 211-2
  33. "Product Information. Heparin Sodium (heparin)." Lilly, Eli and Company, Indianapolis, IN.
  34. Chong BH, Magnani HN "Orgaran in heparin-induced thrombocytopenia." Haemostasis 22 (1992): 85-91
  35. Schiele F, Vuillemenot A, Kramarz P, Kieffer Y, Anguenot T, Bernard Y, Bassand JP "Use of recombinant hirudin as antithrombotic treatment in patients with heparin-induced thrombocytopenia." Am J Hematol 50 (1995): 20-5
  36. Monreal M, Lafoz E, Salvador R, Roncales J, Navarro A "Adverse effects of three different forms of heparin therapy: thrombocytopenia, increased transaminases, and hyperkalaemia." Eur J Clin Pharmacol 37 (1989): 415-8
  37. Gruel Y, Lang M, Darnige L, Pacouret G, Dreyfus X, Leroy J, Charbonnier B "Fatal effect of re-exposure to heparin after previous heparin- associated thrombocytopenia and thrombosis ." Lancet 336 (1990): 1077-8
  38. Shumate MJ "Heparin-induced thrombocytopenia." N Engl J Med 333 (1995): 1006-7
  39. Monreal M, Lafoz E, Salvador R, Roncales J, Navarro A "Adverse effects of three different forms of heparin therapy: thrombocytopenia, increased transaminases, and hyperkalaemia." Eur J Clin Pharmacol 37 (1989): 415-8
View all 39 references
Major

Lmwh (Includes Innohep) ↔ Prematurity

Severe Potential Hazard, Moderate plausibility

Applies to: Prematurity/Underweight in Infancy

Some preparations (i.e., multiple-dose vials) of low molecular weight heparin (LMWH) contain benzyl alcohol as a preservative. Benzyl alcohol in bacteriostatic saline intravascular flush and endotracheal tube lavage solutions has been associated with fatalities and severe respiratory and metabolic complications in low-birthweight premature infants. Symptoms include a striking onset of gasping respiration, hypotension, bradycardia, and cardiovascular collapse. The manufacturers recommend that use of these products be avoided in all neonates whenever possible. Nevertheless, many experts feel that, in the absence of benzyl alcohol-free equivalents, the amount of the preservative present in these formulations should not necessarily preclude their use if they are clearly indicated. The American Academy of Pediatrics considers benzyl alcohol in low doses (such as when used as a preservative in some medications) to be safe for newborns. LMWHs are not approved for use in pediatric patients.

Innohep (tinzaparin) drug Interactions

There are 285 drug interactions with Innohep (tinzaparin)

Innohep (tinzaparin) alcohol/food Interactions

There is 1 alcohol/food interaction with Innohep (tinzaparin)

Drug Interaction Classification

The classifications below are a general guideline only. It is difficult to determine the relevance of a particular drug interaction to any individual given the large number of variables.
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 information available.

Do not stop taking any medications without consulting your healthcare provider.

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