1

Helping to achieve safe 

medication use

BEVACIZUMAB (AVASTIN®): COUNTERFEIT VIALS (400MG/16ML) IN U.S. 

DISTRIBUTION

ISSUE 2 VOLUME 2 FEBRUARY 2012

 BEVACIZUMAB (AVASTIN®): 

COUNTERFEIT VIALS

(400MG/16ML) IN U.S. 

DISTRIBUTION ............ 1

 MEDICATION SAFETY NEWS 

FROM THE VA NATIONAL

PHARMACY BENEFITS 

MANAGEMENT SERVICES 

[PBM] AND THE FOOD AND

DRUG ADMINISTRATION

[FDA]........................ 1-2

 DIAZEPAM AND DILTIAZEM 

POTENTIAL LOOK-ALIKE

(LA) / SOUND-ALIKE (SA) 

CONFUSION ............... 3Medication

A M ONT H L Y P U B LI C AT IO N FRO M V A M E D S AF E: 

V A ’S CO M P R EH E N SI V E P H A R M ACO V IG IL A NC E C E NT E R

Bevacizumab (Avastin®), a monoclonal antibody that blocks angiogenesis by inhibiting vascular endothelial growth factor A (VEGF-A), 

received initial FDA approval in 2004. This agent is indicated for the 

treatment of metastatic cancers (colorectal, breast, lung [nonsquamous non-small cell], and renal) as well as glioblastoma.1

 Offlabel use for macular degeneration and other vascular eye conditions 

has become a common practice as these conditions involve proliferation of blood vessels in the retina. 

FDA warns of counterfeit vials of bevacizumab (Avastin®) 

400mg/16mL distributed in the United States. The counterfeit versions have labeling that displays the product as Avastin, manufactured by Roche, but does not contain the medicine’s active ingredient 

(bevacizumab), as confirmed by laboratory tests conducted by Roche. 

This could result in patients not receiving adequate chemotherapy and 

optimum benefit. 

The counterfeit packages and vials have labels that display:

Roche as the manufacturer;

Batch numbers that start with B6010, B6011, or B86017;

French language.

FDA identified Quality Specialty Products (QSP), also known as 

Montana Health Care Solutions, as the supplier of the counterfeit 

bevacizumab (Avastin®). A company called Volunteer Distribution 

in Ganiesboro, Tennessee, distributes QSP’s products.

While Roche manufactures bevacizumab (Avastin®) for marketing 

outside of the United States, Genentech (a subsidiary of Roche) markets the only FDA-approved version of bevacizumab (Avastin®) for 

use in the United States. The FDA-approved product does not show a 

Roche logo on the packaging or vials. According to the FDA, no 

shortage of bevacizumab (Avastin®) exists, and current supplies adequately meet demand. 2 VA has not been affected by this counterfeit 

supply.

REFERENCES 

1. Avastin® (bevacizumab) [package insert]. South San Francisco, CA: Genentech, Inc.; 

September 2011. 

2. FDA Drug Safety and Availability: Counterfeit Version of Avastin in U.S. Distribution. 

http://www.fda.gov/Drugs/DrugSafety/ucm291960.htm (Accessed 02/16/12).

safety in seconds

EDITOR-IN-CHIEF | Marie Sales, Pharm.D.

VA Pharmacy Benefits Management Services [PBM] & Center for Medication Safety [VA MedSAFE]

1st Avenue—1 Block North of Cermak Road | Building 37; Room 139 | Hines, Illinois | 60141

www.pbm.va.gov

NEWS YOU CAN USE

FROM THE VA NATIONAL PBM: BULLETINS, COMMUNICATIONS, & RECALLS 

Aliskiren: Adverse Drug Events When Concomitantly Used with ACE Inhibitors or ARBs in Patients with Type II DM - National PBM 

Communication – 01/13/2012

Dronedarone and Cardiovascular Events in Permanent Atrial Fibrillation - National PBM Communication – 01/10/2012
2

NEWS YOU CAN USE

FROM THE FOOD AND DRUG ADMINISTRATION (FDA)

Tysabri - New risk factor for Progressive Multifocal Leukoencephalopathy (PML) associated with Tysabri (natalizumab)

01/20/2012 

As of January 2012, PML has developed in 201 out of approximately 96,582 patients treated with Tysabri worldwide. The risks and benefits of 

Tysabri treatment should be carefully considered in patients with risk factors for PML, which now include: 

The presence of anti-JCV antibodies. (NEW)

An analytically and clinically validated anti-JCV antibody detection test ordered by a healthcare professional (i.e., the Stratify JCV 

Antibody ELISA test) can determine a patient's anti-JCV antibody status.

Patients negative for anti-JCV antibodies can still develop PML due to the potential for a false negative test result or a new JCV infection.

Extended duration of Tysabri treatment (i.e., beyond 2 years).

Prior immunosuppressive drug therapy (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, or mycophenolate mofetil).

Patients with all three known risk factors have an estimated risk of PML of 11/1,000. Updates to the Tysabri label will include new information 

on the estimated PML incidence stratified by risk factor.

Notes: Based on postmarketing PML data and Tysabri use data as of September 1, 2011.

†Data beyond 4 years of treatment are limited.

* Risk in anti-JCV antibody positive patients was estimated based on the assumptions that 18% of Tysabri-treated MS patients have a history of prior immunosuppressant treatment and that 55% 

of Tysabri-treated MS patients are anti-JCV antibody positive.

*

The anti-JCV antibody status was determined using an anti-JCV antibody test (ELISA) that has been analytically and clinically validated and is configured with detection and inhibition steps to 

confirm the presence of JCV-specific antibodies with a false negative rate of 3%.

Adcetris - New Boxed Warning and Contraindication for Adcetris (brentuximab vedotin)

01/13/2012 

Progressive multifocal leukoencephalopathy (PML) - New boxed warning on product label highlights risk as additional cases surface.

To date, three patients developed PML while receiving treatment with Adcetris (two recent as per above and one documented 

in the Warnings and Precautions section of the label at the time of approval in August 2011).

A 48 year old man with Hodgkin’s lymphoma (HL) [whose past medical history included treatment with multiple 

chemotherapeutic agents and targeted radiation therapy] presented with left-sided weakness and slurred speech after 

the third dose of Adcetris. Cerebrospinal fluid was positive for John Cunningham (JC) virus. The patient died within 

four weeks of onset of symptoms.

A 50 year old man with HL (whose past medical history included prior treatment with multiple chemotherapeutic 

agents, targeted radiation therapy, and autologous stem cell transplant) presented to the local emergency room with 

complaints of changes in speech, difficulty writing with his right hand, right lower extremity weakness, poor coordination, poor balance, and left-sided sensory deficits after receiving eight cycles of Adcetris treatment. An immunostain of a spinal cord lesion biopsy was positive for JC virus. The patient continued to deteriorate, with recent loss 

of lower extremity motor function and deep tendon reflexes. He also experienced hand tremors and hypoactive arm 

reflexes.

A 38 year old female patient with a history of Stage IV cutaneous anaplastic large cell lymphoma (ALCL) [whose 

past medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy] 

complained of inability to read, inability to find words to express herself, memory lapses, and slight loss of balance 

after the second dose of Adcetris. A brain MRI revealed demyelination and JC virus appeared on brain biopsy. 

Treatment with Adcetris was discontinued.

Pulmonary toxicity - New contraindication on product label prohibits Adcetris use with bleomycin due to risk of pulmonary toxicity. 

A clinical trial comparing the combination of Adcetris plus Adriamycin (doxorubicin), bleomycin, vinblastine, and dacarbazine (ABVD) to the combination of Adcetris plus Adriamycin (doxorubicin), vinblastine, and dacarbazine (AVD) as frontline therapy for HL showed that an excessive number of patients in the Adcetris plus ABVD treatment group experienced non

-infectious pulmonary toxicity (approximately 40%, compared to a frequency of 10-25% reported in the literature with bleomycin-based regimens that do not contain Adcetris). 

No pulmonary toxicity has occurred thus far in the Adcetris plus AVD treatment group. 

CardioGen-82 - Update: Preliminary findings from ongoing investigations of CardioGen-82

01/12/2012 (***UPDATE FROM 07/26/2011***)

FDA states that substandard manufacturing procedures for CardioGen-82 did not result in the excessive radiation exposure detected in some 

patients as previously thought. None of the recalled CardioGen-82 generators that had undergone testing for structural or functional inadequacies showed signs of strontium breakthrough. Preliminary data from a manufacturer study reveals that out of 375 patients surveyed at 43 clinical 

sites, 54 patients (from 2 clinical sites [recognized as having poor documentation of compliance for recommended strontium breakthrough testing] ) reported abnormal screening test results. FDA continues to work with the manufacturer to assess possible causes for excessive radiation 

exposure in patients at certain clinical sites.

Anti-JCV Antibody Positive* Anti-JCV Antibody Positive*

Tysabri Exposure† No Prior Immunosuppressant Use Prior Immunosuppressant Use

1-24 months <1/1,000 2/1,000

25-48 months 4/1,000 11/1,000
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Getting the most from our 

safety surveillance

DIAZEPAM AND DILTIAZEM | POTENTIAL LOOK-ALIKE (LA)/SOUNDALIKE (SA) CONFUSION

Two VA medical centers reported an LA/SA 

error between diltiazem and diazepam secondary to nursing staff withdrawing the wrong 

medication from the automated dispensing 

system in the emergency department (ED). In 

one instance, typing “DI” into the automated 

dispensing system listed “DIAZEPAM” first, 

which staff inadvertently pulled from the 

machine and injected into the patient instead 

of the intended diltiazem. The nurse realized 

the administration of the incorrect diazepam 

and notified the physician, who subsequently 

ordered and administered flumazenil to 

counter its effects. The patient remained in 

the ED for monitoring with no adverse 

events reported. A root-cause analysis is 

pending. In the other case, the facility took 

corrective action by requiring verification by 

a witness whenever retrieving diazepam from 

the automated dispensing system. 

Diazepam and diltiazem is not a medication 

name pair recognized by the Institute for 

Safe Medication Practices (ISMP) as having 

the potential for look-alike/sound-alike (LA/

SA) confusion. Diazepam is a benzodiazepine used in the treatment of anxiety, 

muscle spasms, seizures, and symptoms of 

alcohol withdrawal. Diltiazem is a calciumchannel blocker used in the treatment of cardiovascular issues, such as hypertension and/

or elevated heart rate. Incorrectly receiving 

diazepam instead of diltiazem in the ED 

would subject the patient to suboptimal blood 

pressure and/or heart rate control in a critical 

setting, while introducing the risks of possible exposure to patients with contraindications to diazepam (i.e., patients with myasthenia gravis, severe respiratory insufficiency, severe hepatic insufficiency, sleep 

apnea syndrome, and acute narrow angle 

glaucoma) or other risk factors that may preclude its use (concomitant use of agents that 

may potentiate the action of diazepam, such 

as phenothiazines, narcotics, barbiturates, 

MAO inhibitors and other antidepressants; 

history of drug abuse and dependence). The 

risk of a benzodiazepine overdose (i.e., respiratory depression) also increases due to the 

difference in product strengths and dosing. 

On the other hand, patients inadvertently 

administered diltiazem instead of diazepam 

may experience hypotension and/or a possible decrease in heart rate without receiving 

urgently needed anxiolytic, muscle relaxant, 

sedative, or anticonvulsant effects.

REFERENCES

1. Field Information Report.

2. ISMP’s List of Confused Drug Names. June 2011. Horsham, PA: Institute of Safe Medication Practices. Available 

at: http://ismp.org/tools/confuseddrugnames.pdf . (Accessed 

02/01/2012).

PROVIDER

RECOMMENDATIONS: 

Consider informing health care 

staff of the potential for LA/SA 

confusion between diazepam 

and diltiazem when withdrawing 

these medications via the automated dispensing system, especially if selection of either medication occurs via an alphabetic 

medication list.

Consider carefully checking the 

name, dosage, and indication 

when either diazepam or diltiazem is ordered, especially if 

selection of either medication 

occurs via an alphabetic medication list in the automated dispensing system.

Consider ensuring that a method 

is in place to help differentiate 

the products when using an 

automated dispensing system to 

avoid future LA/SA confusion.

Continue to report any closecalls and/or actual errors involving LA/SA name pair confusion 

to Muriel.Burk@va.gov .