Generic substitution: issues for problematic drugs

• Published in: Southern medical journal (Birmingham, Ala.) Vol. 94; no. 1; pp. 16 - 21
• Main Authors: Henderson, J D, Esham, R H
• Format: Journal Article
• Language: English
• Published: United States 01.01.2001
• Subjects: Albuterol - pharmacokinetics; Albuterol - standards; Albuterol - supply & distribution; Anticoagulants - pharmacokinetics; Anticoagulants - standards; Anticoagulants - supply & distribution; Bronchodilator Agents - pharmacokinetics; Bronchodilator Agents - standards; Bronchodilator Agents - supply & distribution; Cardiotonic Agents - pharmacokinetics; Cardiotonic Agents - standards; Cardiotonic Agents - supply & distribution; Digoxin - pharmacokinetics; Digoxin - standards; Digoxin - supply & distribution; Drug Approval - methods; Drugs, Generic - pharmacokinetics; Drugs, Generic - standards; Drugs, Generic - supply & distribution; Humans; Reproducibility of Results; Therapeutic Equivalency; Thyroxine - pharmacokinetics; Thyroxine - standards; Thyroxine - supply & distribution; United States; United States Food and Drug Administration; Warfarin - pharmacokinetics; Warfarin - standards; Warfarin - supply & distribution; United States
• ISSN: 0038-4348
• DOI: 10.1097/00007611-200101000-00003

The methodology and criteria for bioequivalence testing have been firmly established by the Food and Drug Administration (FDA). For certain drugs with a narrow therapeutic index (e.g., digoxin, levothyroxine, warfarin), generic substitution may not be advisable or even allowable, depending on the substitution laws of individual states. Digoxin and levothyroxine tablets are examples of drugs for which no New Drug Applications (NDAs) currently exist. However, commercially available generic products for both of these drugs have not been determined by the FDA to be therapeutically equivalent to the innovator products. Generic versions of warfarin have been approved by the FDA as being therapeutically equivalent to the innovator products, as have generic versions of the rescue inhaler albuterol. Yet, misinformation and myths persist regarding the adequacy and proven reliability of the FDA's determination of bioequivalence for these products.