Generic substitution: Issues for problematic drugs

The methodology and criteria for bioequivalence testing have been firmly es tablished by the Food and Drug Administration (FDA), For certain drugs with a narrow therapeutic index (eg, digoxin, levothyroxine, warfarin), generic substitution may not be advisable or even allowable, depending on the subs titution laws of individual states. Digoxin and levothyroxine tablets are e xamples of drugs for which no New Drug Applications (NDAs) currently exist. However, commercially available generic products for both of these drugs h ave 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 m yths persist regarding the adequacy and proven reliability of the FDA's det ermination of bioequivalence for these products.