A primer on brand name drugs and generics

That there are some serious misunderstandings out there about the difference between name-brand drugs and generics, as well as some bizarre assumptions about the merits of newer drugs.  So here’s a quick primer on how you (and everyone else) are sometimes not getting accurate information about your pharmaceuticals.

As a society, we’re addicted to drugs.  Almost all of them are legal, and we’re not abusing them per se, but we want them desperately.  The problem is that so many of the new prescription drugs we take are no better than old drugs that are less expensive.  Since new drugs are almost always more expensive, we’re wasting money.  In some cases, the older drugs are actually better – meaning that we’re spending more for less benefit.  Even more concerning, sometimes new drugs aren’t actually “new” at all, making their production and marketing suspect at best.

I want to state clearly the following caveats: I don’t hate drug companies.  I don’t hate people who work for drug companies. I don’t even hate drugs.  In fact, I, as a practicing physician, have seen drugs save lives, improve health, and make daily life incredibly better.  But that doesn’t mean the pharmaceutical industry gets a free pass.

Often, completely new drugs come to market along with a huge advertising campaign and the promise of research showing their effectiveness.  The problem is that to get FDA approval, drug companies only need to show that their drug is more effective than a placebo.  That’s right – effective doesn’t mean better than what is already available, it means better than nothing.  And often, unless a drug company pays for a head-to-head comparison, this type of research just won’t happen.

Once in a blue moon, however, these studies do happen.  One of the biggest and best of them was the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).  Drugs for high blood pressure are intended to reduce the risk of complications or death due to coronary artery disease or other cardiovascular disease.  There were so many drugs to choose from for this trial (at different costs) that the National Heart, Lung, and Blood Institute (NHLBI) primarily organized and supported a randomized, controlled trial to examine which was best.  This study was enormous; it took place in 623 centers in the United States, Canada, Puerto Rico, and the U.S. Virgin Islands between 1994 and 1998, and included over 33,000 participants.  Patients received one of four drugs:

  • Amlodipine, a calcium channel blocker
  • Doxazosin, an alpha-adrenergic blocker
  • Lisinopril, an angiotensin-converting enzyme inhibitor
  • Chlorthalidone, a diuretic

The last of these, the diuretic, was the oldest of the drugs, and by far the cheapest.  However, at the end of the study, the results were clear.  This old, cheap diuretic was significantly better at preventing at least one of the major types of cardiovascular disease when compared to the other, newer drugs. Since the diuretic was also significantly less expensive, it should be the drug of choice in initial treatment of high blood pressure.  However, it usually is not.

The other drugs in the ALLHAT study were good faith efforts to create new molecules to treat a chronic disease.  However, in many other instances, new drugs are just sleight of hand “changes” to old drugs that have no expectation of being better.  When creating drugs through organic synthesis, mirror image molecules are created.

So, if drug D is created, in the last step you wind up with half D and half D’ (the mirror image of D).  The mirror image is usually inert and has no effect on the drug or the individual taking the drug, but it is left in because there is an expense to remove it.  Years ago, the drug companies hit upon a brilliant idea.  If they removed that non-working, mirror image part of the pill, they could claim they devised a new drug!

A primer on brand name drugs and generics

Think this is rare?  Ever heard of Nexium (“the purple pill”)?  Nexium is just Prilosec, with the mirror image part removed.  And Prilosec is an effective, and now generic, drug for heartburn.  Prilosec is P + P’; Nexium is just P.  There is no reason to believe that equivalent amounts of the two drugs are not the same – and research supports this.  Four head-to-head studies compared 20 milligrams of Prilosec to 20 or 40 milligrams of Nexium.  But you have to remember – half of Prilosec is P’(filler)!  So these studies really compared 10 milligrams of P to 20 or 40 milligrams of P.  Shouldn’t more be better? One would think so, but it was barely so, and only in half the studies.  And, of course, none of the advertising stated that you could get the same improvement just by taking more Prilosec.

AstraZeneca, the maker of Nexium and Prilosec, isn’t the only drug company to do this.  Lexapro is “half” of Celexa (Forest Pharmaceuticals).  Nuvigil is “half” of Provigil (Cephalon).  Xyzal (Sanofi-Aventis) is “half” of Zyrtec (Pfizer).  Lunesta is “half” of Imovane (Sepracor).  Levaquin is “half” of Floxin (Ortho-McNeil Pharmaceutical).  Focalin is “half” of Ritalin (Novartis Pharmaceuticals).  And so on and so forth. In fact, since 1990, the proportion of these “half” drugs, among approved new drugs worldwide, has become greater than half of those new approvals.

These aren’t even the worst offenders.  In the worst cases, all that the drug companies change is the color of the pill.

A primer on brand name drugs and generics

Sarafem, marketed by Lilly for premenstrual dysmorphic disorder, is exactly the same molecule as that found in Prozac.  The only difference, besides the cost, is that Prozac has a green coating, and Sarafem’s is pink.  That’s it.  There is no reason you couldn’t just buy cheaper generic Prozac (Fluoxetine) and color it pink for the exact same experience and effect.

Are you on a high blood pressure medication that is not a diuretic?  Did your doctor explain why he thought the more expensive drug was necessary?  Do you think the cost is worth the difference?

Are you on Nexium?  Did your doctor explain to you the real difference between that and generic Prilosec?  Do you think the cost is worth the difference?

Are you on Sarafem?  Did your doctor explain to you that generic Prozac is the exact same molecule?  Do you think the cost is worth the difference?

Should insurance have to cover many of these?  Should the government?  Should you?

Aaron E. Carroll is an associate professor of Pediatrics at Indiana University School of Medicine who blogs at The Incidental Economist.

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  • http://www.drmintz.com Matthew Mintz

    Overall, a very informative piece. A few comments:
    1. You are correct about the isomer or “mirror image” drugs, except that sometimes by removing the mirror image of the older drug, you can achieve equal efficacy with fewer side effects or superior efficacy at the same milligram dose. So, yes, you are correct that it may not be fair to compare equivalent doses of Prilosec and Nexium because half of Prilosec is filler; however, 40mg is the max dose for both drugs, such that 40mg of Nexium is likely going to do better then 40mg of Prilosex. In other words, if 40mg of Prilosec isn’t working, Nexium may do the trick. In realtiy, 9/10 generic omeprazole will do just fine, but there are times where Nexium is the only thing that can help patients.
    2. Your choice of ALLHAT is an interesting one. It certainly shows the need for comparative effectiveness. However, at the time of the study, only chlorthalidone was generic, and now they all are. In addition, amlodipine and lisinopril may actually be better choices in many patients. A parallel study was done in Europe (different population) called the ASCOT study which found different results (diuretic was not as good as others). The US guidelines did not include ASCOT in their analysis, but the European’s did (their NICE comparative effective group is what the US would like to accomplish) and actually recommend greater use of lisinopril and amlodipine.
    3. Cost is complicated. This is especially true when drugs like Prilosec and Zyrtec (and now Allegra) go over the counter. The insurance companies often want the patients to use these drugs instead so they don’t have to pay for them. Many have actually increased the co-pay for the generic omeprazole, to encourage patients to buy it out of pocket over- the-counter. The branded drugs (which are at least better in theory), often will offer coupons to offset a high co-pay. In other words, with a coupon card the expensive branded medication (Nexium, Dexilant) may be cheaper for the patient (though possibly not better) then paying for the generic prescription or over the counter version.

    These comments aside, the overall message of this post is important. The approval system for drugs in the US have given drug companies incentives to produce medications that may be only marginal improvements than previous versions. One solution to the problem is that the FDA ought to require that drugs within the same class be approved not just to be more effective then placebo, but either better than the older drug in that class or safer. Secondly, industry should somehow be made to contribute to (but not control) true comparative effectiveness research which is desparately needed. Finally, the clock should start ticking on patent expirations not when the molecue is discovered, but rather when the product is approved. This will incentive companies to come out with the best products first and not focus on marginal improvements on existing products to extend patent life.

  • soloFP

    Patients are more likely to take drugs that they can afford. Generic drugs are affordable and usually very safe. It often is the latest brand name drugs that are being recalled, such as the inhaled insuline fiasco. Unless a patient requests brand name and wants to pay a Tier 3 copay, I usually use generic meds. It saves a lot of time not having to prior auth brand name meds that do not do any better than most generics. If a patient cannot afford a drug, that patient often tries self dosing the meds every other day to save money. This is really common with brand name statins and brand name BP meds.

  • http://www.drmintz.com Matthew Mintz

    @soloFP. Most of the drugs being recalled are drugs that have been around forever, but not faced current FDA scrutiny. Inhaled insulin was not recalled. Pfizer stopped making it because no one was using it. Most drugs (about 80%) prescribed are generic. However, not only are brand names sometimes needed, these days with rebates from the manufacture, sometimes they are actually cheaper for patients than generics. You mention statins. Liptor will go generic at the end of this year. Pfizer is offering Lipitor for $4 a month until this happens. In other words, you would be better off giving your patient Lipitor, a much more potent and effective statin, then generic simvastatin, and you will likely save your patient some money.

  • mc

    How about the Invega/risperidone issue-Invega is hundreds more. Xopenex and albuterol? Practically causes fights-some swear levalbuterol lasts longer and has less cardiac side effects-others say that is horribly wrong, there is no difference, that albuterol is a fraction of the cost and should always be substiuted.

  • http://www.drmintz.com Matthew Mintz

    @mc This is why this issue is so tricky. Invega is clearly a patent extender for risperidone, not proven to have any benefits in efficacy or safety, and thus not worth the extra money. Xopenex is different than albuterol, with a modest difference in side effects. Many patients tolerate albuterol just fine, but some that are sensitive to the side effects do much better with Xopenex. Thus, we have a slightly better product that might be worth the extra cost for some people. To complicate the matter more, the cost difference is only in the nebulized form. There are no generic albuterol inhalers (see this post http://drmintz.blogspot.com/2008/05/asthma-inhalers.html)
    Depending on your insurance, all the asthma inhalers (ProAir, Proventil, Ventolin, Xopenex) might cost the exact same thing (co-pay). In this instance, you have a slighty better product at the same cost, that may be significantly better in some patients.
    The bottom line is that the system needs to be changed that rewards pharma for coming out with better (safer and/or more effective) products, but discourages “me too” products like Invega that have no real benefit and are simply patent extenders.

  • James G, MD, PharmD

    @Matthew Mintz: I believe you’re incorrect on 2 points:
    1) While coupons given out by brand drug manufacturers may lower the cost for the patient now, they actually lead higher prescription drug insurance costs in the long term. Example: Let’s say Brand Drug A costs $100/month (acutally cheap for a brand name drug) and insurance cover this at $45 copay. Generic Drug B costs $10 per month and is a $5 copay. If the brand manufacturer offers a coupon to lower the patient’s copay to $5 to match the generic, the cost the patient is the same, but the insurance company pays a total of $55 for that brand drug and $5 for the generic. That added costs to the insurance company will eventually end up costing the patient more in the form of higher premiums. So coupons are great for the drug manufacturer (they make $60 even after the coupon), but bad for consumers on the long term. I’m not defending prescription drug insurance companies, but coupons are not a good reason choose brand name drugs over a cheaper generic.
    2) The “recalls” on generic drugs are only attempts by brand drug manufacturers to fleece comsumers. I say “recalls” because there is ZERO evidence that any of these older drugs are unsafe. The problem is that these “recalled” drugs were never studied for safety in true clinical studies. They’re safety was just assumed because they had been used safely for decades. So the brand drug manufacturers actually preformed studies on drugs that have been used forever and then used a loophole in FDA regulations to force generic manufacturers out of the market. With this new found exclusivity, brand name manufacturers could charge $100+ for drugs that used to cost $4/month. I recognize that it’s important to study safety of medications, but 40+ years worth experience is worth more than a 10 week safety study. If you can prove that any of these cheap, old generic drugs were any less safe that their expensive, new brand name counterparts, let me know, but I seriously doubt that you’ll be able to find that evidence.

  • http://www.drmintz.com Matthew Mintz, MD

    @James G, MD Pharm D
    We are not in disagreement.
    1. I am not suggesting that doctors prescribe branded drugs with a coupon in favor of generics, especially since the coupons eventually run out (though some are lasting up to a year). My point was the math is often not that simple. In your scenario the branded drug with coupon and the generic were both $5; however, this is not often the case. Most patients with commercial insurance do not pay $5 for generics anymore and the $4 Walmart/Target list is limited. Let’s say you have a patient with diabetes who needs a 40% reduction in their LDL. The 2 statins at Walmart are not potent enough to achieve this goal. 40mg to 80mg of generic simvastatin might do the trick, but this will be at minimum a $10 co-pay for the patient (and since they are diabetic, the patient is likely on at least 3 more drugs). Lipitor is a more potent statin, so 10 or 20mg should get the patient to goal (probably with fewer side effects). Pfizer now has coupons that bring the copayment for Lipitor down to $4 until it goes generic at the end of the year. In this scenario, what is the ethical thing to do? Do I write a prescription for an inferior drug that will cost my patient more money to save the insurance a few bucks in the hopes of lowering premiums or do I write for the superior drug that will cost my patient less money, knowing that this will cost the insurance company more and possibly contribute to higher premiums?
    2. You are absolutely correct about the generic recalls. The worst example is colchicine. A very effective and safe drug that has been used for many years by millions of patients is no longer available, and patients with gout are now forced to take a branded and more expensive formulation due to the FDA loophole. My point was to respond to SoloFP’s comment that “It often is the latest brand name drugs that are being recalled.” It is true that there is some risk to a drug recently introduced to the market because rare side effects not seen in clinical trials may not have been uncovered. However, the safety review process for newer drugs is much more rigorous and after a million or so patients have taken a drug, it is unlikely that new and unexplained safety issues will arise. Track record is certainly very important, and we should always be alert for the next Vioxx; but it is a much bigger leap to say generics are much safer than branded drugs. There are many generic products available now that would never be approved by today’s FDA.

  • PharmaVet

    Interesting conversation that has ensued from Dr. Carroll’s original post. I read it this morning and was disappointed at some of the misinformaiton and misleading from one person’s perspective. He and I are in the same geographic location, Indianapolis, and are influenced heavily by the corporate HQ for Eli Lilly. Hence, his reference to Sarafem.

    Disclaimer: I do not and have not ever worked for Eil Lilly.

    That being said, Sarafem has been off the market for several years. It was a marketing flop. It was fluoxetine HCl, the active ingredient in Prozac, but it was launched way before Prozac went generic. It had a different indication (for Women’s Health). I thought it was a horrible decision, but mentioning it in the article is a little deceiving because it has been off the docket for almost 10 years once Prozac went generic.

    Let’s point blame in all directions, if we’re going to be fair. Blame the pharmaceutical companies for developing isomeric products, but also blame the insurance companies for covering them, the FDA for approving them (and, the FDA is requiring companies to do active comparator studies for approval), the pharmacies for filling them, and the practitioners for prescribing them.

    However, are you really looking out for the patient’s best interest if you’re not offering the patient the opportunity to choose? GIve the patient the choice explaining that it MAY be a higher copay.

    Dr. Mintz is correct – often the cost of OTC Claritin is considerably higher to me, the patient, than the cost of other medications. I choose the prescription because I don’t tolerate Claritin well anymore. However, be fair regarding the cost of medications with the vouchers/coupons available – when offered, it is the manufacturer, the pharamceutical company, that incurs the cost of reducing the cost of the medication in conjunction with the contracted rate through the insurance company.

    When going through chemo 3 years ago, the only anti-emetic that gave me relief was Emend. It was expensive. I didn’t care. The insurance company had already spend tens of thousands of dollars on chemo, PET/CT scans, bone marrow biopsies – I was OK paying $80 out of my own pocket. I appreciated having the choice.

    In summary – stop prescribing based upon your own agenda and start prescribing what’s in the patient’s best interest (collaborate with them as a partner in their healthcare).

    • Jackie

      Well said.

    • pao

      ” stop prescribing based upon your own agenda and start prescribing what’s in the patient’s best interest (collaborate with them as a partner in their healthcare).”
      Simple but true….may I add “do no harm ” as vital and valuable checks on abuses and greed!

  • gzuckier

    On a related note:

    From $10 to $1,500: How a cheap drug that prevents preterm birth got outrageously expensive
    By MIKE STOBBE
    01:37 am, 03/10/2011
    Associated Press Newswires
    (c) 2011. The Associated Press. All Rights Reserved.

    ATLANTA (AP) – The price of preventing preterm labor is about to go through the roof.

    A drug for high-risk pregnant women has cost about $10 to $20 per injection. Next week, the price shoots up to $1,500 a dose, meaning the total cost during a pregnancy could be as much as $30,000.

    That’s because the drug, a form of progesterone given as a weekly shot, has been made cheaply for years, mixed in special pharmacies that custom-compound treatments that are not federally approved.

    But recently, KV Pharmaceutical of suburban St.Louis won government approval to exclusively sell the drug, known as Makena (Mah-KEE’-Nah). The March of Dimes and many obstetricians supported that because it means quality will be more consistent and it will be easier to get.

    None of them anticipated the dramatic price hike, though — especially since most of the cost for development and research was shouldered by others in the past.

    Last month, KV sent cease-and-desist letters to compounding pharmacies, telling them they could face FDA enforcement actions if they kept making the drug.

  • gzuckier

    “The problem is that to get FDA approval, drug companies only need to show that their drug is more effective than a placebo. That’s right – effective doesn’t mean better than what is already available, it means better than nothing. And often, unless a drug company pays for a head-to-head comparison, this type of research just won’t happen.”

    in Europe there’s something of a drive to move towards “active comparator” studies for approval. But, to be fair, there’s a whole new can of worms associated with such trials. For instance, just the question of which comparator drug of typically many for any disease? Then, it has to be established that the comparator drug is properly handled, stored, and administered, so as to not artificially lower the threshold of superiority for the experimental drug. The difference in efficacy between the two drugs is presumably much lower than that between the experimental drug and placebo, therefore the trial has to be longer and/or involve more patients to get sufficient statistical power; this means exposing more patients to the experimental treatment, which means more risky. Meanwhile, the actual adverse event rate of the experimental drug is masked by the rate of adverse events in the comparator drug, which is typically higher than that which would be seen for a placebo. Just to name a few issues off the top of my head.

  • Jackie

    After Avastin had performed below expectation for treating late stage breast cancer, the FDA tightened its approval procedure and forced T-DM1 to undergo Phase III trials instead of getting the ‘fast-tract’.

    The breast cancer community that’s been awaiting T-DM1 now scrambles to travel all over the country in order to participate in the expanded access trials now available at 200 different locations.

    Several of our support group members who had participated in the earlier trials saw complete response. Their ‘cured’ status prompted other late stage survivors to fly out of state in order to get access. We all felt that the FDA should have fast-tracted T-DM1 instead of conducting more double-blind trials. The long-term surviovrs of our group know the chemo drugs so well the ‘double-blind’ procedure could not ‘blind’ them.

    They are in remission, and they know they’d received T-DM1. And many others are now ‘die waiting’…

  • Jackie

    fast-’track’.

  • http://www.ericsaysit.com ericsaysit

    Great stuff. I believe that Nexium is a perfect example of maketing winning over good professional judgement. Drug companies are running out of patentable compounds. This is painfully obvious given the recent approval of Colcrys which bullied it’s way to becoming the only approved colchicine product available on the U.S. market. Now we have a company which is performing minor studies on legend drugs in order to get a patent to raise the price from a few dollars to several hundred dollars. This is the most shameful tactic I’ve seen yet. I’m a strong proponent of generic drug use. My personal blog however, does focus on branded drug discount programs. I hate manufacturer incentives for overpriced drugs, but until the costs comes down, I recommend that everyone who needs these drugs take the discount. http:www.ericsaysit.com

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