Problem Found With Generic Blood Pressure Medication

Consumers prescribed Toprol XL, a beta-1-selective adrenoreceptor blocker, approved for the treatment of high blood pressure, other cardiovascular disorders such as angina pectoris, and to reduce the occurrence of migraine headache, have been experiencing problems when switching to its generic, metoprolol succinate.

Toprol XL and its generic are expected to provide a controlled and predictable release of metoprolol administered once daily. However, shortly after the generics became available in November of 2006, consumers who switched from Toprol XL began experiencing serious side effects, such as a dramatic increase in blood pressure, an increase in heart rate and ectopic beats, nausea, dizziness, hives, and headache. These problems generally stopped when the consumer switched back to Toprol XL.

There are known side effects of Toprol XL, which include tiredness, dizziness, depression, diarrhea, itching or rash, shortness of breath, and bradycardia or slow heart rate. But the effects reported by patients who switched to the generic differ. In particular, increased blood pressure and heart rate is in direct contradiction to the known side effect of Toprol XL.

After a large number of patients voiced complaints, ConsumerLab tested Toprol XL and its generics, hoping to get to the root of the problem. According to ConsumerLab, the reported increase in blood pressure and heart rate suggests that some generics are not as effective as the original, possibly not providing high enough drug levels throughout the day.

Generics that are identical to the original drug are known as “authorized generics.” Among the products on the market, only products from Par Pharmaceutical are identical to original Toprol XL. Par has a supply arrangement with AstraZeneca, the maker of Toprol XL. Two other companies selling metoprolol succinate extended-release generics, identified in several of the complaints, Eon/Sandoz and Ethex, use tablets that differ from Toprol XL in their size and inactive ingredients.

These differences in pill design and inactive ingredients may not only affect how the drug is released from a tablet and the rate of that release, but may cause reactions in people who have chemical sensitivities. Information from the FDA and the manufacturers suggest that this may be the case with both Eon/Sandoz and Ethex products.

Unfortunately, the safety and efficacy of generic drugs are not clinically tested, unlike their original counterparts. The FDA instead relies on bioequivalence results; information from the manufacturers showing that, when administered, blood levels of their drugs are approximately the same as those for the original drug.

However, ConsumerLab.com notes that their research into generic forms of Wellbutrin XL, an anti-depressant, suggests that the bioequivalence results for a generic can vary in notable ways from that of the original drug and still be acceptable to the FDA. Also, the FDA does not make bioequivalence data for generic drugs available to the public.

ConsumerLab also uncovered a misbranding issue when examining the inserts from Eon/Sandoz and Ethex. All of these generics are named “Metoprolol Succinate Extended-release Tablets USP.” The term “USP” generally implies that it meets all specifications established by the United States Pharmacopeia. However, the Ethex product, according to its own published materials, does not meet the USP dissolution standard and the dissolution test described for the Sandoz generic in its FDA approval letter is not the USP method.

By including USP in their names, but not meeting the USP standard, both products appear to be misbranded. ConsumerLab fears that “such misbranding could lead pharmacists, physicians, or others to believe that these drugs behave just like the original Toprol XL, when that may not be the case.”

If you are having a problem with a generic version of Toprol XL, ConsumerLab suggests these options:

1. You can have your doctor prescribe the brand-name version and indicate “Dispense as Written” or “Do Not Substitute.”2. If your insurance will not cover the brand-name, ask your doctor to make a special request to your insurance company. However, if your insurance still won’t cover the original, you might consider:

• Trying a different generic, preferably made by the same company that makes the original drug (an “authorized generic”)
• Get the original at a reduced cost. Possibly due to competition, the price for original Toprol XL is not much greater than the generic. You may also save money by purchasing from a discount pharmacy.

3. Consider a different version of the drug. For example, if a once-a-day generic is not working, consider a twice-a-day or three-times-a-day version that will yield the same total daily dose.