Glucose Monitoring Test Strips that utilize Glucose Dehydrogenase

AL10-01

October 1, 2009

Item: Glucose Monitoring Test Strips that utilize Glucose

Dehydrogenase Pyrroloquinoline Quinone (GDH-PQQ)

methodology may give falsely elevated glucose results

General Information: On August 13, 2009, FDA issued a Public Health Notification:

Potentially Fatal Errors with GDH-PQQ Glucose Monitoring

Technology (Attachment 1).

In certain patients who are receiving therapeutic products containing

certain non-glucose sugars such as maltose, xylose and galactose

(Table 1), results may be falsely elevated if GDH-PQQ methodology

is utilized by the test strips and their associated devices

(Attachment

1). These non-glucose sugars may mask significant hypoglycemia or

prompt excessive insulin administration, leading to serious patient

injury or death.

Actions: 1. By Close of Business (COB) October 16, 2009, the Facility

Director (or designee) will:

a. Determine the brand of glucometers used in the VAMC clinics,

inpatient and outpatient areas and determine if the identified

glucometers are using GDH-PQQ methodology. (List of GDH-

PQQ glucometers are found on pages 8 and 9 of this Alert).

NOTE: Facilities may switch to non GDH-PQQ methodology

POC testing devices in their patient care areas.

b. Assure that if glucometers with GDH-PQQ methodology are

used, complete remaining actions on this Alert.

NOTE: If non GDH-PQQ methodology glucometers are used,

no further action is required. Defer to action 3.

c. Assure that a comprehensive list of Veterans receiving

peritoneal dialysis (PD), including those VA patients on

contracted services, is developed and a letter is sent to each

identified Veteran requesting contact with the medical center to

confirm the type of PD solution the Veteran is using

(Attachment 2). In lieu of a letter, the medical center may

contact the Veterans directly.

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d. Assure that all Veterans currently (and future) receiving the

peritoneal dialysis solution, Extraneal, are confirmed to have:

i. Received a Baxter safety kit including a safety alert

bracelet and are encouraged to wear it. See Link

below.

http://www.glucosesafety.com/us/index.html

ii. If an outpatient receiving Extraneal requires a home

glucose monitoring device the appropriate blood

glucose meter (i.e., using non-GDH-PQQ methodology)

has been dispensed.

http://www.glucosesafety.com/us/pdf/countryspecific_glu

cose_list.pdf

e. Assure that a comprehensive list of all at-risk outpatients,

including those VA patients on contracted services, is compiled

(in addition to the PD patients) to include individuals on the

other interfering therapies (i.e. Abatacept, Immune Globulin,

etc.). The Chief of Pharmacy (or designee) shall ensure

identified outpatients and future at-risk patients have blood

glucose monitors that do not use the GDH-PQQ methodology.

f. Assure that, for facilities that use POC blood glucose monitors

with GDH-PQQ methodology) in their patient care areas:

i. That a comprehensive list of all at-risk patient care

areas is compiled for the facility and CBOCs. Such

areas should include, at minimum, dialysis units,

rheumatology and infusion clinics but may also include

other areas of vulnerability. Additional areas include

departments where such interfering agents are

administered or where patients are unable to

participate in their care due to confusion or

unresponsiveness (e.g., ED, ICU, post-operative

suites, etc.).

ii. That all clinical staff, particularly those in at-risk patient

care areas, are educated on the risks of falsely

elevated glucose readings when using POC blood

glucose monitors using GDH-PQQ methodology.

iii. All at-risk patient care area clinical staff are advised to

use the facility’s clinical laboratory for glucose testing in

lieu of point-of-care (POC) blood glucose testing.

2. By COB October 16, 2009, the Pharmacy ADPAC (or designee)

will ensure that:

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a. The following medications/solutions are available for selection

as non-VA medications in CPRS, to facilitate drug interaction

checks when providers select these medications.

• Extraneal (Icodextrin)

• Gammimune (Immune Globulin Intravenous)

• HepaGam B (Hepatitis B Immune Globulin Intravenous)

• Orencia (Abatacept)

• Bexxar (tositumomab and Iodine 131tositumomab)

b. Interfering medications (Table 1) used at the facility shall not

be selectable via the in-patient or outpatient alphabetical

medication lists in CPRS. These medications shall only be

available via consult and/or quick order highlighting the drug-

device interaction risks.

3. By COB November 16, 2009, the Patient Safety Manager will

document on the VHA Hazard Alerts and Recalls website that

facility leadership has reviewed and implemented these actions.

Sources: FDA and ISMP.

Additional Information: Sites in need of additional support for IT related processes are

advised to log a Remedy ticket or contact the VA Service Desk at

1-888-596-4357 for assistance.

For other vulnerabilities associated with the use of portable blood

glucose monitors, their associated test strips, and accessories. See

the link below.

http://www.patientsafety.gov/SafetyTopics/BloodGlucoseMonitors.pdf

Attachments: 1. FDA Public Health Notification: Potentially Fatal Errors with GDH-

PQQ* Glucose Monitoring Technology

2. Example letter to Veterans receiving peritoneal dialysis (PD)

Contact: Mr. Bryanne Patail or Mr. Keith Trettin at the VA National Center for

Patient Safety (NCPS) at (734) 930-5890,

Mr. Vincent Calabrese at the Pharmacy Benefits Management (PBM)

at (708) 786-7862.

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Table 1. Products that may cause a drug-device interaction with certain

glucose meters and test strips. (Courtesy of ISMP, Roche and Abbott).

Drug Indication

EXTRANEAL (icodextran) Peritoneal dialysis

GAMIMUNE N 5% and Immunodeficiency

OCTAGAM (immune globulin intravenous, human)

ORENCIA (abatacept) Rheumatoid arthritis

WINRHO SDF LIQUID [Rho (D) immune globulin Idiopathic

intravenous (human)] Thrombocytopenia Purpura

(ITP) and Rh transfusion

reaction

D-XYLOSE (d-xylose absorption test, blood and urine) Test for malabsorption

HEPAGAM B [hepatitis B immune globulin (human)] Acute exposure to HBsAG

or HBV

ADEPT ADHESION REDUCTION SOLUTION Reduce post surgical

(icodextran) laparoscopic

adhesions in gynecologic

surgery

BEXXAR (tositumomab and Iodine 131tositumomab) non-Hodgkin’s lymphoma

Vaccinia Immune Globulin (human) Treatment of adverse

reactions to smallpox

vaccine

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AL10-01

ATTACHMENT 1

FDA Public Health Notification: Potentially Fatal Errors with GDH-PQQ* Glucose

Monitoring Technology

* glucose dehydrogenase pyrroloquinoline quinone

Date: August 13, 2009

Dear Healthcare Practitioner:

This is to alert you to the possibility of falsely elevated blood glucose results when using GDH-

PQQ glucose test strips on patients who are receiving therapeutic products containing certain

non-glucose sugars. These sugars can falsely elevate glucose results, which may mask

significant hypoglycemia or prompt excessive insulin administration, leading to serious injury or

death. The following provides background information on this problem, a summary of fatality

reports FDA has received, and recommendations to reduce the risk. This problem can occur

wherever these products are used including in-patient and out-patient healthcare facilities, and

at home.

Nature of the problem

GDH-PQQ glucose monitoring measures a patient’s blood glucose value using methodology

that cannot distinguish between glucose and other sugars. Certain non-glucose sugars,

including maltose, xylose, and galactose, are found in certain drug and biologic formulations, or

can result from the metabolism of a drug or therapeutic product.

When these non-glucose sugars are present in the patient’s blood, using a GDH-PQQ glucose

test strip will produce an elevated glucose result which may suggest the need for clinical action.

This can lead to inappropriate dosing and administration of insulin, potentially resulting in

hypoglycemia, coma, or death.

In addition, cases of actual hypoglycemia may go unrecognized if the patient and healthcare

practitioner rely solely on the test result obtained with the GDH-PQQ glucose test strips.

Other glucose test strip methodologies are not affected by the presence of non-glucose

sugars. The unaffected methods are glucose oxidase, glucose dehydrogenase nicotine adenine

dinucleotide (GDH-NAD), or glucose dehydrogenase flavin adenine dinucleotide (GDH-FAD).

Laboratory-based blood glucose assays do not use GDH-PQQ methodology and are not subject

to falsely elevated results from non-glucose sugars.

Recommendations

• Avoid using GDH-PQQ glucose test strips in healthcare facilities.

List of GDH-PQQ Glucose Test Strips

• If your facility currently uses GDH-PQQ glucose test strips, NEVER use them on patients:

o who are receiving interfering products**, or

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ATTACHMENT 1 (continued)

o from whom or about whom you cannot obtain information regarding concomitant

medication use, e.g., patients who are unresponsive or cannot adequately

communicate.

**Interfering products containing non-glucose sugars include:

 Extraneal (icodextrin) peritoneal dialysis solution

 Some Immunoglobulins: Octagam 5%, Gamimune N 5%***, WinRho SDF

Liquid, Vaccinia Immune Globulin Intravenous(Human), and HepaGamB

 Orencia (abatacept)

 Adept adhesion reduction solution (4% icodextrin)

 BEXXAR radioimmunotherapy agent

 Any product containing, or metabolized into maltose, galactose or xylose.

Use ONLY laboratory-based glucose assays on these patients.

• Determine whether patients are receiving interfering products on admission and

periodically during their stay at your facility.

• Educate staff and patients about the potential for falsely elevated glucose results in the

presence of certain non-glucose sugars when using GDH-PQQ glucose test strips.

• Consider using drug interaction alerts in computer order entry systems, patient profiles

and charts to alert staff to the potential for falsely elevated glucose results.

• Periodically verify glucose meter results with laboratory-based glucose assays if you are

using GDH-PQQ test strips in patients who are not receiving interfering products.

*** Within the U.S., Gamimune N 5% has not been manufactured since December 2005, and no

lots are in distribution in the U.S.

In addition, an Advice for Patients can be found on the FDA Consumer website.

Reports received by FDA

From 1997-2009, FDA received 13 reports of death associated with GDH-PQQ glucose test

strips in which there was documented interference from maltose or other non-glucose sugars.

Six of the 13 deaths have occurred since 2008 despite FDA’s efforts to communicate the risk.

The deaths occurred in healthcare facilities. Ten of the 13 patients were receiving Extraneal

(icodextrin) peritoneal dialysis solution for renal failure. Three of the 13 patients were receiving

maltose-containing substances; one was receiving Potacor R, one was receiving Octagam

(IVIG), and another was receiving an infusion that contained maltose. Patients were treated with

insulin doses or insulin drips that were guided by falsely elevated results.

Eight reports specified that test result values generated on GDH-PQQ test strips were 3 to 15

times higher than corresponding laboratory results. For example, in one patient the GDH-PQQ

system generated a result of 200 mg/dL while the laboratory result was 19 mg/dL. In another

case, a patient undergoing peritoneal dialysis with Extraneal was tested with a GDH-PQQ test

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ATTACHMENT 1 (continued)

strip which gave a result of 193 mg/dL, while the result obtained using a laboratory instrument

was 8 mg/dL.

Some reports indicated that serious patient injury, such as hypoglycemia, confusion, neurologic

deterioration, severe hypoxia, brain damage, and coma occurred prior to death.

FDA is working with manufacturers to address patient safety problems with GDH-PQQ glucose

test strips and will continue to monitor adverse events associated with these products.

Reporting adverse events

FDA requires hospitals and other user facilities to report deaths and serious injuries associated

with the use of medical devices. If you suspect a reportable adverse event associated with a

glucose meter or glucose test strip, you should follow the reporting procedure established by

your facility. Prompt reporting of adverse events can improve FDA’s understanding of and ability

to communicate the risks associated with devices and assist in the identification of potential

future problems associated with medical devices. If you suspect a falsely elevated blood

glucose value associated with a non-glucose sugar interference, include information about the

associated drug or biologic product in your adverse event report.

We also encourage you to report any medical device adverse events related to glucose meters

or glucose test strips that do not meet the requirements for mandatory reporting. You can report

these directly to the device manufacturer or to MedWatch, the FDA’s voluntary reporting

program. This can be done online at https://www.accessdata.fda.gov /scripts/medwatch

/medwatch-online.htm, by phone at 1-800-FDA-1088, by FAX at 1-800-FDA-0178; or by mailing

FDA form 3500 (download from http://www.fda.gov/ Safety/MedWatch/

HowToReport/DownloadForms) to MedWatch, 5600 Fishers Lane, Rockville, MD 20857-9787.

Getting more information

If you have questions about this Notification, please contact FDA’s Office of Surveillance and

Biometrics by e-mail at [email protected]

or by phone at 301-796-6640.

FDA Medical Device Public Health Notifications are available on the Internet at

http://www.fda.gov/ MedicalDevices/Safety/ AlertsandNotices/ PublicHealthNotifications

. You

can also be notified through email each time a new Public Health Notification is added to our

web page. To subscribe, visit: http://service.govdelivery.com/

service/subscribe.html?code=USFDA_39.

Sincerely yours,

Daniel G. Schultz, MD

Director

Center for Devices and Radiological Health

Food and Drug Administration

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AL10-01

ATTACHMENT 1 (continued)

Related Links

• FDA Patient Safety News October 2008. Potentially Fatal Glucose Monitoring Errors with

Icodextrin

• FDA Drug Safety Newsletter Summer 2008. Volume1, Number 4. Icodextrin (marketed as

EXTRANEAL) and Point-of-Care Glucose Monitoring.

• Institute for Safe Medication Practices (ISMP) Medication Safety Alert! June 19, 2008.

FDA Advise-ERR: Prevent dangerous drug-device interaction causing falsely elevated

glucose levels.

• FDA Center for Biologics Evaluation and Research April 17, 2008. Fatal Iatrogenic

Hypoglycemia: Falsely Elevated Blood Glucose Readings with a Point-of-Care Meter Due

to a Maltose-Containing Intravenous Immune Globulin Product.

• FDA Patient Safety News February 2006 and September 2006. Avoiding Glucose

Monitoring Errors in Patients Receiving Other Sugars.

• FDA MedWatch Safety Alert 2005. Parenteral Maltose/Parenteral Galactose/Oral Xylose-

Containing Products.

List of GDH-PQQ Glucose Test Strips

The following test strips (with associated meters) use GDH-PQQ methodology as of August

2009:

Roche Diagnostics:

1. ACCU-CHEK Comfort Curve test strips, for use with:

o ACCU-CHEK Inform meters [model 2001201]

o ACCU-CHEK Complete meters [models 200 and 250]

o ACCU-CHEK Advantage meters [models 888, 831, 850, and 768]

o ACCU-CHEK Voicemate meters [model 0009221]

2. ACCU-CHEK Aviva test strips, for use with:

o ACCU-CHEK Aviva meters [models 525, 535, and 555]

3. ACCU-CHEK Compact test strips, for use with:

o ACCU-CHEK Compact meters [model GF]

o ACCU-CHEK Compact Plus meters [models GP and GT]

4. ACCU-CHEK Go test strips

o ACCU-CHEK Go meters [model GJ]

5. ACCU-CHEK Active test strips

o ACCU-CHEK Active meters [models GG and GN]



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ATTACHMENT 1 (continued)

Abbott Diabetes Care:

1. Freestyle test strips, for use with:

o FreeStyle meters

o FreeStyle Flash meters

o FreeStyle Freedom meters

2. Freestyle Lite test strips, for use with:

o FreeStyle Lite meters

o FreeStyle Freedom Lite meters

Home Diagnostics:

1. TRUEtest test strips

o TRUEresult meters

o TRUE2go meters

Smiths Medical:

1. Abbott Diabetes Care Freestyle test strips, for use with:

o CoZmonitor blood glucose module (for use with the Deltec Cozmo Insulin Pump)

Insulet:

1. Abbott Diabetes Care Freestyle test strips, for use with:

o OmniPod Insulin Management System

Note: Test strips currently on the market may be distributed under multiple trade names. In

addition, manufacturers of GDH-PQQ test strips currently on the market may subsequently

change to non-GDH-PQQ methodology. Therefore, healthcare providers (and patients) should

refer to device labeling or consult with test strip manufacturers to confirm the type of

methodology used.

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ATTACHMENT 2

Example letter to Veterans receiving peritoneal dialysis (PD)

Department of Veterans Affairs

VeteransHealthAdministration

Dear Veteran,

You have been identified as an individual receiving Peritoneal Dialysis. Since some of our dialysis

patients may receive treatment or management by a non-VA nephrologist, we would like to take the

opportunity to speak with you via phone to confirm that our records are complete and up-to-date with the

current type of peritoneal dialysis solution you are using. Please take the opportunity to contact us via

our 800 number <INSERT YOUR SPECIFIC NUMBER> to speak with a member of our

nursing/pharmacy staff by October 15

2009. This call should take only 5 minutes of your time.

Thank you for the opportunity to continue to serve you and your health care needs. Your participation

will help ensure the accuracy of your medical record.

Sincerely,