we've already discussed generic and brand drug names but are there differences beyond the words that's the topic of this week's healthcare triage let's start with a story when a drug first comes to market in the United States its parent company can sell it exclusively under a brand name for a certain number of years this length of time depends how many years are left on the drugs patent and the type of exclusivity granted at the time of approval by the FDA when the patent or exclusivity runs out other manufacturers can begin making a generic the generic product is sometimes cheaper than the brand-name version this is probably why some generic products get a bad rap there's this pervasive misperception that generic things are generally not as good as the brand because they're cheaper while this may be true about those weird store brand Froot Loops with no bird on the box the same logic can't really be applied to generic drugs here's why before a company can manufacture and market a generic drug in the United States it must submit an abbreviated new drug application or a NDA to the FDA this application includes data providing the generic product is both pharmaceutical e-equivalent and bio equivalent to the branded product pharmaceutical equivalents means that the generic drug contains the same drug compound as the innovator drug as well as having the same strength same route of administration and same dosage form to achieve bioequivalence the generic product must have the same effect as the brand drug meaning that the compound has the same action in the body in the same amount of time but make no mistake just because the brand and generic have identical drug molecules and are bio equivalent and pharmaceutically equivalent does not mean that they are the same in every way that's because of excipient s-- excipient SAR the inactive ingredients in a drug product or the stuff that's not the active drug molecule let's say it took a 10 milligram tablet of a popular allergy medication if you weigh the tablet on a scale it will definitely be heavier than 10 milligrams that's because 10 milligrams is really tiny it would be nearly impossible to make a drug tablet so small let alone expect someone to take it for example a quarter teaspoon of table salt weighs like 1500 milligrams 10 milligrams is like less than 10 grains of kosher salt some drugs use less than a milligram of ingredient even therefore drug manufacturers will use approved compounds like lactose starch and micro crystalline cellulose as dilute ins to bulk up tablets other excipient smite help tablets disintegrate in the digestive tract or provide flavoring and coloring the list goes on and get a little overwhelming when you start including dosage forms like inhalers patches creams and ointments generic and brand drugs will always have the same active ingredients but there excipient may vary one or the other may have slightly more or fewer types of inactive ingredients depending on their manufacturing processes coloring agents usually also differ so products can distinguish themselves but remember even though the entire ingredient list may not be exactly the same between brand and generic the generic manufacturer must still prove to the FDA that their product is entirely bio equivalent if not then an adjustment to the excipient may be warranted in the late 1960s an outbreak of intoxication occurred in Australia among patients taking the anticonvulsant drug phenytoin in an 87% of patients experiencing toxicity drug levels measured in the blood were well beyond the therapeutic range putting them at risk of side effects many patients have changes in gait and some even experience vomiting double vision and other abnormalities and mental function the good news is that the majority of people return to normal once their dose was lowered but why were patients that had been stable under any convulsant medication all of a sudden experiencing toxicity you guessed it excipient after evaluating the phenytoin capsule investigators discovered that in 1967 one manufacturer had changed its diluted or bulking agent from calcium disulfide dehydrate to lactose the lactose formulation allowed the phenytoin to dissolve more readily from the capsule leading to higher concentrations in the blood thus some patients began to experience toxic side effects while others that were previously getting little benefit from the phenytoin had their seizures under control for the first time this incident shows that excipient aren't inert and justifies why it's so critical that brand and generic drugs be both pharmaceutically and bio equivalent today the FDA and other regulatory bodies around the globe are really strict about all this approving generic forms of drugs willy-nilly in addition to being pharmaceutically equivalent and bioequivalent generic drugs must have the same strength identity purity and quality as the branded product so the FDA regulates things no surprises there but why should we take their word for it to the research a 2008 meta-analysis published in JAMA compared the clinical effectiveness of generic and brand name cardiovascular drugs the study included 38 randomized controlled trials of nine different subclasses of these medications bioequivalence was seen in all studies of beta blockers antiplatelet agents statins ACE inhibitors alpha blockers any rhythmic agents and warfarin it was seen in ten of eleven randomized controlled trials of diuretics and 71% of calcium channel blockers so not perfect but these differences were minor and did not impact clinical outcomes overall the aggregate effect of the meta-analysis indicated that there were no significant differences between brand and generic drugs the same study also examined editorials and commentaries discussing the interchangeability of branded generic cardiovascular drugs of 43 editorials more than half expressed a negative view of generic drugs let's look deeper some drugs have what's known as a narrow therapeutic index meaning that the drug is only effective within a very small dosage range too little and the drug will have no effect too much and the drug can cause harm one such drug is the blood thinner coumadin also known by its generic name warfarin not everyone responds to warfarin in the same way so those taking it have their blood monitored regularly so that our appropriate dose adjustments can be made because of this physicians and pharmacists are hesitant to interchange the brand than generic versions of coumadin and drugs like it but what did the data say a review article published in 2011 in the Journal of pharmacotherapy examined five randomized controlled trials and six observational studies comparing outcomes when switching patients from cumin into generic warfarin the observational study suggested that those switching between branded generics should be monitored more closely so perhaps there's a reason to be more cautious about switching between Brandon warfarin in the randomized controlled trials though there were no significant differences reported at all no studies showed that the branded drugs were more effective than the generic similar results were seen in systematic reviews of anti epileptic drugs even though national regulatory bodies require a mountain of data proving bioequivalence and independent studies have shown that generics are just as effective as innovator drugs there's still this lingering perception among some practitioners that generic drugs aren't as good a survey of 506 physicians the United States revealed that as many as 23% had negative opinions on the efficacy of generic drugs and those over the age of 55 were more than three times as likely to believe that another survey looked at both physicians and pharmacists while eleven point eight percent of doctors believed that generic drugs were less effective than the brand product only 2.3 percent of pharmacists shared this opinion why here's what Rachel thought pharmacist spent a lot of time in school learning about the chemical nature of drugs and how excipient work and drug products perhaps resulting in a higher degree of confidence and a well formulated generic conversely physicians may be more likely to hear first-hand accounts of patients being unhappy with a generic making them less likely to prescribe it in the future ignoring this has consequences a 2014 study compared adherence to statin therapies and patients that were started on either the brand or generic drug a significantly higher number of patients started on generics were compliant with their medication regimen and those taking generics had an eight percent reduction in hospitalization for acute coronary syndrome or stroke why could generics cost less and people are more likely to stick to stuff that's not as expensive for them this matters a chemical compound is a chemical compound and as long as bioequivalence is assured brand and generic drugs should give the same results there may be good reason to be cautious when switching back and forth between different formulations of certain narrow therapeutic index drugs but for the vast majority of small molecular drugs there's no difference don't get hung up on the labels healthcare triage is supported in part by viewers like you through patreon comm a service that allows you to support the show through a monthly donation your support helps make this bigger and better we'd especially like to thank a research associate Cameron Alexander and our first ever surgeon Admiral Sam thanks Cameron thanks Sam more information can be found at patreon.com slash healthcare triage