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
Thank you for your very professional explanation. It’s
amazing that a pharmaceutical company would produce
such similar medications.
Love this! I like learning a little bit of deeper knowledge than just what the PI can provide. Or at least your/your students’ interpretation of these hazy areas.
When Cardizem LA came out I vaguely remember that the proposed advantage was that the formulation was designed to have the drug level peak at the time of day when cardiac events were most likely to occur. So if taken in the am, drug level peaking in the overnight hours. Doesn’t really make sense once at steady state. The tablet is smaller and possibly easier to swallow than the CD XR caps so there’s that