Cardizem CD Versus LA – What’s The Difference?

Let’s tackle a question I recently received. What’s the difference between Cardizem CD Versus LA? We will look closely at these two Cardizem formulations, as it seems many of us have questioned their clinical differences.

Both Cardizem CD and Cardizem LA formulations are designed to provide for an extended duration of medication delivery. The primary difference is in the drug delivery.  Cardizem CD  is designed with a dual microbead system enclosed within each capsule and results in two peaks on the concentration-time curve. The two unique microbeads contained within the capsule have a different thickness copolymer around them that controls the release of the diltiazem. The thin-coated beads release 40% of the total amount of diltiazem in the capsule in the first 12 hours, and those with thicker coating release the rest of the diltiazem in the next 12 hours. Cardizem LA  is a white film-coated tablet that is a graded extended-release system resulting in a single peak on the concentration-time curve.

Kinetics – Cardizem CD Versus LA

With the active ingredient being the same in each formulation, much of the PK information found on drug databases will not differentiate for each formulation of Cardizem (at least from our research), and the package inserts even utilize the same language in the Clinical Pharmacology section – which makes it even more difficult to key in on the subtle differences. In comparing the pharmacokinetic properties of Cardizem CD and LA, and generic ER formulations, we can see that they behave similarly:

Cardizem CD oral capsule:

  • bioavailability of 40%
  • detectable levels @ 2 hours
  • peak level @ 10-14 hours
  • t1/2 5-8hrs
  • Cannot open for administration 

Cardizem LA oral tablet:

  • bioavailability of 40%
  • detectable levels @ 3-4 hours
  • peak level @ 11-18 hours
  • t1/2 6-9hrs
  • Cannot be crushed for administration 

What If We Make An Error?

I remember an error with these formulations during my dispensing career. Is switching one for the other going to cause a clinical issue? An abnormal reaction due to one of the excipients is always a possibility but that is extremely rare. If the same dose is given, the likelihood that there will be a detectable clinical difference is very low in my opinion.

Have you seen issues and confusion with these formulations in your practice?

Looking for more on diltiazem – check out this podcast episode.

This article was written by Amy Van Loon, PharmD Candidate in collaboration with Eric Christianson, PharmD, BCPS, BCGP

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References

David H.G. Smith, Joel M. Neutel, Michael A. Weber, Comparisons of the effects of different long-acting delivery systems on the pharmacokinetics and pharmacodynamics of diltiazem, American Journal of Hypertension, Volume 12, Issue 10, October 1999, Pages 1030–1037, https://doi.org/10.1016/S0895-7061(99)00097-7

U.S. FDA Orange Book, Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm 

DailyMed: DILTIAZEM HYDROCHLORIDE capsule, extended release. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=355f560a-8ebb-4661-ad74-2a22f707d7f8

DailyMed: DILTIAZEM HYDROCHLORIDE- diltiazem hydrochloride capsule, extended release, PuraCap Laboratories LLC dba Blu Pharmaceuticals. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=35ba00e6-35c3-4407-9f25-f0a293387671&type=display

DailyMed: CARDIZEM CD- diltiazem hydrochloride capsule, coated, extended release. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1042fa13-e6af-46b9-8008-6c941f0978b1 

DailyMed: CARDIZEM LA- diltiazem hydrochloride tablet, extended release. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3e180dc7-c871-4efc-8755-cae882976c8d 

PDR by ConnectiveRx: Cardizem. https://www.pdr.net/drug-summary/?drugLabelId=Cardizem-diltiazem-hydrochloride-2077

Stephen P. Glasser MD. Diltiazem Hydrochloride: New Technologies and Evolution of Diltiazem: Clin. Cardiol. Vol. 26 (Suppl. IV), IV-16-IV-24 (2003). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6654580/pdf/CLC-26-16.pdf

Package Insert: BIOVAIL LABORATORIES INC. CARDIZEM LA (Diltiazem Hydrochloride) Extended Release Tablets Once-a-day dosage. https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021392lbl.pdf

UpToDate: Diltiazem: Drug Information. https://www.uptodate.com/ 

Micromedex: Diltiazem Hydrochloride. https://www-micromedexsolutions-com