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Answer

Hello and thank you for submitting your question! I am more than happy to help you decipher this somewhat confusing situation.

You are correct that both of the products you mention in your question are diltiazem 360 mg extended-release capsules.

However, they are each generic versions for different brand name drugs.

'Diltiazem 360 mg extended-release capsules (NDC 47335-0679-81)' is the generic for the brand name drug Cardizem CD while the other diltiazem 360 mg extended-release capsule product (NDC 47335-0673-81) is the generic for Tiazac.

This is somewhat of an unusual situation since both of these brand name drugs (Cardizem CD and Tiazac) contain the same active ingredient (diltiazem), but they are nonetheless different drug products, each with unique properties.

I'll discuss what all this means in more detail below but as a general point, your pharmacy shouldn't be switching between them since they technically are not considered therapeutically equivalent by the FDA. In other words, they are not interchangeable.


Therapeutic Equivalence

Most states have 'generic substitution laws' that require pharmacies to dispense a 'therapeutically equivalent' generic product for a brand name one. There are exceptions to this, but in general, if your doctor writes you a prescription for a brand name product, it will be filled generically (if one is available).

This concept of 'therapeutic equivalence' can be a little confusing, but basically, it is a system that exists that links drugs (namely brand and generic products) based on their 'bioequivalence' to each other (bioequivalence in this sense is defined as two drugs having the same rate and extent of absorption). Drugs that have the same rate and extent of absorption should, in theory, exhibit the same clinical effect.

When your pharmacy substitutes a generic drug for a brand name that your doctor has written for, the generic drug must be classified as 'therapeutically equivalent'.

The FDA defines 'therapeutic equivalence' as the following:

"Approved drug products are considered to be therapeutic equivalents only if they are pharmaceutical equivalents for which bioequivalence has been demonstrated, and they can be expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labeling."

For example, if your are prescribed Lipitor and you are dispensed the generic (atorvastatin), you can feel confident taking it since it has been tested to show bioequivalence and is classified as 'therapeutically equivalent' to the brand.

The same goes for all generics substituted for a brand name product.

The reference guide for 'therapeutic equivalence' is known as the 'Orange Book'. In this reference, anyone can look up drugs and their approved generic equivalents.

I won't get into the entire Orange Book rating system, but if a brand and generic drug share the code 'AB', that signifies clinical studies show them to be bioequivalent, and therefore, substitutable.

Going back to the Lipitor example, if you are dispensed the generic atorvastatin, that atorvastatin will be rated 'AB' to Lipitor.

Things unfortunately get a little confusing when there are multiple brand name products that contain the same active ingredient. This is the case for diltiazem containing products.

When there is more than one brand name product (also referred to as a 'reference' product), they are associated a three-character codes instead of the standard two-character code. So, instead of AB, they would be assigned AB1, AB2, AB3 etc...for each product (e.g. brand name product 'one' would have AB1, brand name product 'two' would have AB2 and so on).

As mentioned in the first section of this answer, you wrote in about two different diltiazem products and I said that they are generics for two different brand names. These two brand names are:

  • Cardizem CD
  • Tiazac

Cardizem CD is assigned an Orange Book code of AB3.

Cardizem CD AB3 Code

Tiazac is assigned an Orange Book code of AB4.

Tiazac AB4 Code1

A very important point here is that you can only legally substitute a generic drug for a brand name if it has the same character code. So, for example, you can substitute an AB2 for an AB2, but not an AB1 for an AB2.

The FDA resource page discussing Orange Book codes states this specifically:

"Drugs coded as AB under a heading are considered therapeutically equivalent only to other drugs coded as AB under that heading. Drugs coded with a three-character code under a heading are considered therapeutically equivalent only to other drugs coded with the same three-character code under that heading."

Let's revisit the two different diltiazem 360 mg extended-release capsule NDCs you asked about:

  • NDC 47335-0679-81 (a blue/white capsule)
  • NDC 47335-0673-81 (a green capsule)

The diltiazem product with the NDC 47335-0679-81 is the generic for Cardizem CD. Both products are assigned the Orange Book code of AB3.

The diltiazem product with the NDC 47335-0673-81 is the generic for Tiazac. Both products are assigned the Orange Book code of AB4.

As stated before, you can only legally substitute products if they are the same Orange Book code. Therefore, you should not substitute Cardizem CD generics for Tiazac generics. They are different products with different properties (even though they are both extended-release diltiazem).

I discuss the differences between Cardizem CD and Tiazac in the next section.


Tiazac Vs. Cardizem CD

Even though both Tiazac (first approved in 1995) and Cardizem CD (first approved in 1991) are extended-release diltiazem capsules, there are two significant differences between them.

First, Tiazac capsules are smaller than Cardizem CD capsules. The diltiazem contained in Tiazac capsules (and approved generics) are more highly concentrated than other extended-release versions of diltiazem and are packed in smaller capsules.

Second, the specific release-mechanism is different for the two products.

Tiazac utilizes a single 'microbead' technology, which slowly release diltiazem over a 24-hours period. All of the beads release at the same rate.

Cardizem CD on the other hand, utilizes a 'dual microbead' system. One type of microbead has a thin polymer coating while the other microbeads have a thicker polymer coating. The thin coated microbeads release about 40% of the drug over the first 12 hours after dosing and the thicker coated microbeads release the remaining diltiazem during the second 12 hours. In other words, the beads have two different release rates (unlike Tiazac, which has one).

It is worth reiterating that Tiazac and Cardizem CD (and approved generics for each product) are not substitutable with one other. They are unique drug products that are not 'therapeutically equivalent'. They differ not only in their release-mechanism, but also in their pharmacokinetic properties (i.e. as they relate to drug absorption, distribution in the body, metabolism and elimination).


Final Words

You stated in your question that you were unsure why there was such a price difference between the two diltiazem products.

I hope this answer shed some light on this...that they are generics for different brand name products so they aren't directly comparable when it comes to price. The generic for Cardizem CD is much more expensive than the generic for Tiazac.

Thank you again for using us and let us know if you have any follow-up questions!


Summary

  • There are multiple diltiazem extended-release capsule formulations available, including Cardizem CD and Tiazac. They are not all considered equivalent to one another.
  • A generic drug is approved based on bioequivalence studies for a particular brand name drug (i.e. reference drug) and is assigned a corresponding Orange Book code (e.g. AB1, AB2).
  • A generic diltiazem extended-release capsule product is only legally substitutable with its reference drug (e.g. Cardizem CD or Tiazac etc...), which will have the same Orange Book Code (e.g. AB1 for AB1).
  • Generic diltiazem extended-release capsules, even if they are the same strength, cannot be substituted for one another if they have different Orange Book codes. Therefore, generics for Cardizem CD cannot legally be substituted with generics for Tiazac since they have different Orange Book codes.

  • References
    1. Drugs@FDA: Tiazac. FDA
    2. Drugs@FDA: Cardizem CD. FDA
    3. Cardizem CD Prescribing Information. AccessFDA
    4. Tiazac Prescribing Information. AccessFDA
    5. Comparisons of the effects of different long-acting delivery systems on the pharmacokinetics and pharmacodynamics of diltiazem. Oxford Academic
    6. Orange Book Preface. FDA