Adverse Reactions to Anticoagulants and to Antiplatelet Drugs Recorded by the German Spontaneous Reporting System

ABSTRACT

According to their code of professional conduct, German physicians are obliged to report suspected cases of adverse drug reactions (ADRs) to the Drug Commission of the German Medical Association (AkdÄ). On the basis of an agreement between the German Medical Association and the Federal Institute for Drugs and Medical Devices (BfArM) a common pharmacovigilance database within the German spontaneous reporting system was created.

A user-friendly application program developed in-house enables the user to conduct searches about reported ADRs covering a wide variety of questions within a short period of time.

ADRs caused by anticoagulants and by antiplatelet drugs still belong to the most reported adverse events. The most frequently reported suspected drugs are heparins, followed by ticlopidine, phenprocoumon, acetylsalicylic acid, and clopidogrel. Bleeding complications are the most often described ADR symptoms of any anticoagulation therapy, especially of phenprocoumon and acetylsalicylic acid. Another serious ADR is heparin-induced thrombocytopenia or changes in blood counts (CBC) due to ticlopidine and clopidogrel. During the past few years a reduction in severe reactions, such as cerebral hemorrhage, especially with fatal outcome was detectable because of better clinical management of oral anticoagulant therapy and of adverse events concerning heparin.

Drug Commission of the German Medical Association - adverse drug reactions - pharmacovigilance - spontaneous reporting system - antiplatelet drugs

REFERENCES

• 1 Hasford J, Lamprecht T. Company observational post-marketing studies: drug risk assessment and drug research in special populations-a study-based analysis.  Eur J Clin Pharmacol. 1998;  53 369-371
• 2 Breckenridge A. For the good of the patient: risks and benefits of medicine.  Pharmacoepidemiol Drug Saf. 2003;  12 145-150
• 3 Evans S JW. Pharmacovogilance: a science or fielding emergencies?.  Stat Med. 2000;  19 3199-3209
• 4 Edwards I R. Who cares about pharmacovigilance?.  Eur J Clin Pharmacol. 1997;  53 83-88
• 5 Hasford J, Goettler M, Munter K H, Müller-Oerlinghausen B. Physicians' knowledge and attitudes regarding the spontaneous reporting system for adverse drug reactions.  J Clin Epidemiol. 2002;  55 945-950
• 6 Schnurrer J U, Frölich J C. Zur Häufigkeit und Vermeidbarkeit von tödlichen unerwünschten Arzneimittelwirkungen.  Internist (Berl). 2003;  44 889-895
• 7 Alvarez-Requejo A, Carvajal A, Bégaud B, Moride  Y, Vega T, Arias L H. Under-reporting of adverse drug reactions. Estimate based on a spontaneous reporting scheme and a sentinel system.  Eur J Clin Pharmacol. 1998;  54 483-488
• 8 Arnaiz J A, Carné X, Riba N, Codina C, Ribas  J, Trilla A. The use of evidence in pharmacovigilance. Case reports as the reference source for drug withdrawals.  Eur J Clin Pharmacol. 2001;  57 89-91
• 9 Waller P C, Evans S JW. A model for the future conduct of pharmacovigilance.  Pharmacoepidemiol Drug Saf. 2003;  12 17-29
• 10 Sackett D L. The fall of “clinical research” and the rise of “clinical-practice research.”  Clin Invest Med. 2000;  23 379-381
• 11 Sackett D L, Haynes R B. The architecture of diagnostic research.  BMJ. 2002;  324 539-541
• 12 Meister W. Die Anwendungsbeobachtung-eine Beobachtung der Anwendung.  Dtsch Med Wochenschr. 2003;  128 859-862
• 13 Briguori C, Manganelli F, Picardi M, Villari  B, Ricciardelli B. Thrombocytopenia and purpura-like lesions associated with clopidogrel.  Ital Heart J. 2001;  2 935-937
• 14 Reichenberger F, Wirtz H, Paschke R. Clopidogrel and side effects.  Cardiology. 2001;  96 51-52
• 15 Dillon W C, Eckert G J, Dillon J C, Ritchie M E. Incidence of thrombocytopenia following coronary stent placement using abciximab plus clopidogrel or ticlopidine.  Catheter Cardiovasc Interv. 2000;  50 426-430
• 16 Schwabe U, Paffrath D Arzneiverordnungs-Report 1998-2003. Berlin/Heidelberg, Germany; Springer-Verlag 1999-2004
• 17 Mörsdorf S, Leipnitz G, Pindur G et al.. Improved therapeutic safety of oral anticoagulant therapy in Germany: the Saarland Model.  Semin Thromb Hemost. 1999;  25 49-55
• 18 Wenzel E, Keller-Stanislawski B, Tiaden J D et al.. Antithrombotische, blutstillende und antianämische Mittel. In: Müller-Oerlinghausen B Handbuch der unerwünschten Arzneimittelwirkungen München/Jena, Germany; Urban und Fischer 1999
• 19 Munter K H, Schenk J F, Thrun F, Tiaden J D, Wenzel E, Muller-Oerlinghausen B. The “Phoenix” ADR database of the Drug Commission of the German Medical Profession-a clinically useful approach to optimize evidence-based medicine in Germany.  Semin Thromb Hemost. 1999;  25 57-64
• 20 Schenk J F, Mörsdorf S, Pindur G. Analysis and occurrence of adverse events with oral anticoagulant therapy.  Semin Thromb Hemost. 1999;  25 65-71
• 21 Taborski U, Müller-Berghaus G. State-of-the-art patient self-management for control of oral anticoagulation.  Semin Thromb Hemost. 1999;  25 43-47
• 22 Mörsdorf S, Erdlenbruch W, Taborski U et al.. Training of patients for self-management of oral anticoagulant therapy: standards, patient suitability, and clinical aspects.  Semin Thromb Hemost. 1999;  25 109-115
• 23 Blandfort R. Expertengespräch und “Konsensus-Konferenz” im Auftrag der AkdÄ und der Landesärztekammer des Saarlandes am 12.5.1995. White-Clot-Syndrom [Expert discussion group and consensus conference on behalf of the Drug Committee of German Medical Community and Saarland Federal Medical Group 12 May 1995. Agreement on practical procedures for rapid, safe diagnosis and therapy of “white clot” syndrome].  Chirurg. 1995;  66 262-264