58 DRUG TOPICS APRIL 19 2004 www.drugtopics.com

The Food & Drug Administra-tion wants to alert healthcare

providers to formulation changesthat have occurred with Kaopec-tate and the potential for con-sumers to confuse the multipleavailable formulations and dosinginstructions under this productname. The current Kaopectatemarketed is not the formulationyou remember with Kaolin andPectin. In the late 1980sor early ’90s, the manu-facturer reformulatedthe product to containattapulgite. Then in2003, the sponsor refor-mulated the productagain, this time to in-clude bismuth subsali-cylate as the activeingredient. Followingthis 2003 reformulation,the FDA received six medicationerror reports involving confusionover the “new and improved”Kaopectate.

Two reports involved errors inproduct purchase. In one case, anemergency physician prescribedKaopectate for a very young child.In talking with the mother of thechild, the pharmacist found thatthe child also had a fever. Thepharmacist called the physician toadvise him of the change in for-mulation, and the physiciandirected the pharmacist not to fillthe prescription for the child. Areport of the second case describesseveral consumers who returnedthe new Kaopectate because, uponreading the label, they realizedthat it was not appropriate forthem. Neither of the reports notedany patient harm, as the errorswere intercepted before reachingthe patient.

The remaining four medicationerror reports for Kaopectate

describe the potential for medica-tion errors due to its reformulationas a salicylate, concerns over thelack of promotion and education onthe new formulation, inadequatelabeling, and packaging of thenewly formulated Kaopectate.According to the reporters, thesponsor did not adequately informhealthcare providers and patients ofthis important reformulation.

Lastly, the currently marketed“new and improved” formulationwith bismuth subsalicylate notonly contains a salicylate, it alsohas dosing instructions for chil-dren under 12 years of age. Salicy-lates are not generally recom-mended for children because ofrisks of Reye’s syndrome, salicy-late allergy, and salicylate over-dosage. To further confuse mat-ters, according to the final FDArule on antidiarrheal monograph,effective April 17, 2004, bismuthsubsalicylate will no longer belabeled with pediatric dosinginstructions. Until existing sup-plies of the attapulgite and subsal-icylate product labeled with pedi-

atric dosing instructions aredepleted, all three formulationsmay be stored near each other inthe pharmacy and possibly be con-fused.

Why the formulation change?In 2003, the active ingredient inKaopectate was reformulated tocontain bismuth subsalicylate,replacing attapulgite as the ac-

tive ingredient. The FDAfound attapulgite efficacydata to be inadequate and,thus, attapulgite was notincluded as a monographingredient in the April 17,2003, final rule. Only bis-muth subsalicylate andkaolin are generally recog-nized as safe and effectiveas OTC antidiarrhealdrugs in the final rule.

Moreover, in the changes of theApril 17, 2003, final rule, bismuthsubsalicylate may only be labeledfor adults and children 12 years andover because data are needed tosupport use in children under 12years of age.

What are the safety concerns?In light of the formulation changesthat have already occurred and thefuture labeling changes with Kao-pectate, there are several importantfactors to be considered by healthcarepractitioners to appropriately alertand educate unwary consumers.

•Fomulation change confusionThe sponsor, Pharmacia ConsumerHealthcare, notes that the older for-mulation of Kaopectate with atta-pulgite will remain in stores untilsold. Thus, stores will likely haveboth formulations of Kaopectate ontheir shelves. A consumer not real-izing the formulation change mayunknowingly grab the new bottle,

To report a problem with an FDA-regulated product, please call 1-800-FDA-1088.

Safety Page

ByLinda Y. Kim-Jung, R.Ph.;

Carol Holquist, R.Ph.; and Jerry Phillips, R.Ph.

Kaopectate reformulation and upcoming labeling changes

Original Dose: Take first dose atKaopectate first sign of diarrhea and(Attapulgite) after each subsequent bowel750 mg/15mL movement. Maximum six

times in 24 hours

3 to 6 years 1/2 tablespoonful (7.5 mL)

6 to 12 years 1 tablespoonful (15 mL)

12 years and over 2 tablespoonfuls (30 mL)

and ingest a salicylate-containingproduct. Although the new formu-lation contains a salicylate warningstatement on the label, it is notprominent and could be easilyoverlooked. This could lead to seri-ous medical consequences such asReye’s syndrome, salicylate allergy,and salicylate overdosage. Likeaspirin, bismuth subsalicylate prod-ucts could potentially have manydrug-to-drug and drug-to-diseaseinteractions.

For example, bismuth subsalicy-late could have interactions withanticoagulants, hypoglycemicagents, and nonsteroidal anti-inflammatory drugs (NSAIDs)and other anti-inflammatory med-ications. Medical condi-tions such as gout, stom-ach ulcer, kidney dis-ease, and bleeding prob-lems could become moreproblematic with the useof a salicylate-containingproduct. A medical sce-nario was published inthe ISMP MedicationSafety Alert (March 20,2003). “Bismuth Subsali-cylate also can lead to darkened orblack-colored stools. A patientreporting this finding might be mis-diagnosed with sustained gastroin-testinal bleeding if the practitioneris unaware of the change in formu-lation.”

•Confusion with pediatric dosingFollowing the final rule’s effectivedate of April 19, 2004, bismuth sub-salicylate may only be labeled foradults and children 12 years andover. However, products that arealready in the store (i.e., with labelingfor children under 12 years old) cancontinue to be sold, as there will notbe a recall. As a result, there will betwo versions of the newly formulatedKaopectate with different pediatricdosing requirements, which may fur-ther confuse healthcare practitionersand consumers.

Here are two examples of possi-

ble pediatric dosing errors whichmay occur due to the formulationchange and the labeling changewith Kaopectate.

A consumer not realizing theformulation change from atta-pulgite to bismuth subsalicylatemay unknowingly grab the newbottle, and give a child a largerdose than required, thinking thatthe product is still the old Kaopec-tate with attapulgite. For example,a six-year-old child’s dose is onetablespoonful (15 mL) for the Kao-pectate with attapulgite, whereasthe dose is two teaspoonfuls (10mL) for Kaopectate with bismuthsubsalicylate. See tables (page 58and below) for the different

dosage recommendations betweenthe original and new Kaopectate.

Secondly, consumers will likelyget mixed dosing informationbecause one version of Kaopectatewith subsalicylate states that it isappropriate for children under 12years of age and yet another ver-sion of Kaopectate with bismuthsubsalicylate is not labeled forchildren under 12 years of age.Based on the old product withattapulgite and the bismuth sub-salicylate with pediatric dosinglabels, consumers may still givethe product to children under 12or at an inappropriately high dose,which may result in harm.

In order to avoid confusion withthe new formulation and the pro-duct’s labeling changes, here aresome measures pharmacists can take: •Be aware of the new active ingre-dient and its potential adverse

effects. The current label containsinformation to convey the changein active ingredient but this infor-mation is subtle and can easily beoverlooked. •Be aware that, potentially, theremay be three versions of Kaopectateon the pharmacy shelf: One versionof Kaopectate with attapulgite, a sec-ond version of Kaopectate with bis-muth subsalicylate (with pediatricdosing instructions), and a third ver-sion of Kaopectate with bismuth sub-salicylate without pediatric dosing. •Provide shelf talkers or someother visual aid to alert consumersabout the change in ingredient. Forexample, the shelf talker might say,“This product has been reformulat-

ed and now contains aSalicylate, a new activeingredient. If you havequestions, talk to thePharmacist.” In addition,physically separate thedifferent formulations tominimize potential con-fusion for consumers. •Advise patients not toremove the back panelpeel-up label, which

contains all the Drug Facts. Thepeel-up label could easily tear orbe removed and discarded. This isproblematic as the peel-up labelcontains the drug warnings,dosage directions, detailed salicy-late warnings, lot number, andexpiration date.

If you become aware of medica-tion errors involving Kaopectateor other products, please reportthem to the FDA MedWatch pro-gram at www.fda.gov/medwatch.In addition, medication errors canbe reported to the USP MedicationErrors Reporting Program in coop-eration with the Institute for SafeMedication Practices at 1-800-23-ERROR or at www.usp.org.

Linda Y. Kim-Jung is a Safety Evaluator; CarolHolquist is the Deputy Director of the Division ofMedication Errors and Technical Support; and JerryPhillips is the Associate Director for Medication ErrorPrevention, Office of Drug Safety, at the Food & DrugAdministration.

Safety Page

New & improved Dose: Repeat dose everyKaopectate 1/2 hour-1 hour as needed,(Bismuth subsalicylate) to a maximum of eight doses262 mg/15 mL in a 24-hour period.

Three to five years 1 teaspoonful (5 mL)

Six to eight years 2 teaspoonfuls (10 mL)

9 to 11 years 1 tablespoonful (15 mL)

12 years and over 2 tablespoonfuls (30 mL)

60 DRUG TOPICS APRIL 19 2004 www.drugtopics.com