A patient presents to the pharmacy with a prescription for 'brand name' Zestril® (lisinopril by Astra Zeneca) from a local physician. You explain to them you only have the generic lisinopril and would have contact the provider regarding a change to the generic. The patient is insistent that they 'must have the brand name product because this is their blood pressure medicine.'

What do you tell the patient? How do you educate the patient and the provider regarding the use of AB-rated generic drugs?

Few things seem to elevate some patients' and providers' blood pressure like the subject of generic drugs. I'm going to try to dispel some myths about generic drugs, explain a little about FDA rating of generics, and hopefully, educate a little on why AB rated generics are good, inexpensive, and a smart way to do business.

Clarification - generic substitution is different from therapeutic substitution. Generics substitution is using a generic drug for a brand name drug (same drug, same strength, same dosage form). For example, dispensing generic metformin 500mg tablets for Glucophage® 500mg tablets. Therapeutic substitution (usually done in hospital via a P&T decision) is substituting one drug for another drug deemed therapeutically equivalent. For example, your P&T decides that Levaquin® 500mg tablets po QD is therapeutically equivalent to Cipro® 500mg po BID and all orders for Cipro 500mg po BID are changed to Levaquin 500mg po QD (unless some clinical reason dictates ONLY
Cipro like post exposure anthrax prophylaxis, Pseudomonas infection, etc).  The P&T committee defines these clinical reasons when the therapeutic equivalence is decided.  The reference to determine if a drug how a generic drug is rated to its brand name equivalent (or reference listed drug) is the FDA "Orange Book". The Orange Book is available on line at http://www.fda.gov/cder/ob/default.htm.  You can search by brand name or generic name.

I believe concerns raised when generic drugs first became available have pretty much been dispelled. The FDA now rates generic drugs either "A" or "B". "A" rated drugs are deemed bioequivalent, demonstrated through human study (AB rated) or considered inherently unlikely to have bioavailability problems (AA rated).  Other "A" rated non-oral drugs are considered bioequivalent by the FDA. "A" rated drugs are generically interchangeable with their brand name equivalents. AB rated generic drugs are tested in a cohort of healthy volunteers (usually 24-36). Blood levels are periodically measured and plotted. The area under the curve (AUCs) for the tested generic drugs must fall within 80-125% of the AUC for the brand name drug.  Historically, the AUCs of these AB rated generics fall within + 3% of the brand name drug.

In a 1998 "Dear Doctor" letter ("Therapeutic equivalence of generic drugs letter to practitioners,
http://www.fda.gov/cder/news/nightgenltr.htm ), the FDA states they 'regularly assess the quality of products in the marketplace and thoroughly researches and evaluates reports of alleged drug product inequivalence'.  In the same letter, the FDA states that in one instance the FDA tested over 400 samples for 24 marketed brand name and generic products and ALL were found to meet the established standards of purity and quality. The Medical Letter (2002:44:89-90) states, "Well documented therapeutic inequivalence between brand name and FDA-approved generic drugs has not been reported."

I think there's a perception amongst patients and some providers that generics drugs just aren't as good, generic drugs don't work, and/or generic drugs are another mechanism to save money at all costs. When looked at objectively, these differences haven't been elucidated scientifically. Patients may voice concerns or complaints or side effects when switched to generic drugs. The FDA hypothesizes that "because patients may pay closer attention to their symptoms when the substitution of one drug product for another occurs, an increase in symptoms may be reported at that time, and anecdotal reports of decreased efficacy or increased toxicity may result. When investigated by the FDA, no problems attributed to substitution of one approved drug product for another has occurred." Certainly, there MAY be patients who, for whatever reasons, respond better or have better disease control with the brand name drug. I think this is clearly the exception and
NOT the rule with approved generic drugs.

Certain drugs such as carbamazepine [Tegretol®] and phenytoin [Dilantin®] have inherent bioavailability problems. Losses of seizure control and drug toxicity have been reported with both brand name and generic versions of these drugs. Most DoD clinicians, when polled before a
recent DoD P&T meeting regarding generic carbamazepine, stated they didn't have a strong preference for brand name over the generic but strongly agreed the SAME product (brand or generic) be available and dispensed on a regular basis instead of switching back and forth between brand and generic or different AB rated generics. The DoD Pharmacoeconomic Center (PEC) along with the Defense Supply Center Philadelphia (DSCP) have written multiple single source generic contracts to avoid this situation. A list of joint DoD/VA single source generic contracts can be found at http://www.dmmonline.com/pharm/contractlist.asp    

Finally, generics are significantly less expensive than brand name drugs. Most civilian pharmacy benefit managers (PBMs) have a mandatorygeneric substitution policy. Generic drugs are offered at a lower co-pay. Brand name drugs are usually available but at a higher co-pay to the patient. For example, the very robust DoD pharmacy benefit charges a $3 co-pay for generic drugs and $9 for brand name drugs. Co-pays in other plans are generally much more substantial than the above stated $3 and $9. I don't have the exact final numbers but the DoD pharmacy benefit for FY02 should come in at ~ $2.5 BILLION (MTFs, Mail Order, Retail Network). With the ever-growing costs, increasing utilization, new drugs, and technology, the DoD medical system needs to use generic drugs, when possible. Remember, just because a drug goes generic doesn't mean it becomes ineffective - it just gets less expensive.