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STATIN DRUG CLASS: FDA-APPROVED LABELING UPDATES 

Helping to achieve safe 

medication use

ISSUE 3 VOLUME 2 MARCH 2012

 STATIN DRUG CLASS: FDAAPPROVED LABELING UPDATES ...................... 1,2,3

 MEDICATION SAFETY NEWS 

FROM THE VA NATIONAL

PHARMACY BENEFITS 

MANAGEMENT SERVICES 

[PBM] AND THE FOOD AND

DRUG ADMINISTRATION

[FDA]........................ 2

 PROCEDURAL ERROR

LEADS TO MEDICATION

ERROR...................... 3Medication

In February 2012, the FDA announced safety-labeling changes for 

the statin drug class. The labeling changes resulted from a comprehensive review of the statin class by the FDA and included 

updated information regarding routine monitoring of liver enzymes in patients on statins; newly recognized adverse drug 

events for the statin class; and new contraindications and dose 

limitations for lovastatin when combined with certain medications. A summary of the labeling changes is discussed below. 

Monitoring Liver Enzymes: Routine periodic monitoring of liver 

function tests is no longer recommended in patients receiving 

statin therapy. Based upon the evidence reviewed, the FDA concluded that liver toxicity with statins is rare and unpredictable and 

periodic monitoring does not appear to prevent or detect serious 

liver injury associated with statins. If signs and symptoms of liver 

injury manifest during statin therapy, the statin should be withheld 

and if another cause for the liver injury cannot be identified, the 

statin should not be restarted. New recommendations include 

testing of liver enzymes at baseline (prior to statin use) and as 

clinically indicated thereafter. Routine, periodic testing is no 

longer recommended.

Adverse Events Associated with Statin Therapy now Included 

in Statin Labels: Information regarding reported cases of nonserious, reversible cognitive impairment as well as impaired fasting glucose, incident diabetes and increases in hemoglobin A1C 

(HbA1c) associated with statin therapy has been added to statin 

labels. 

Cognitive adverse events-From their review, the FDA noted 

that post-marketing reports of cognitive impairment typically 

occurred in patients older than 50 years who experienced reduced memory or loss of memory that resolved when the 

statin was discontinued. From this information, along with 

observational studies and clinical trials, the FDA concluded 

that the onset of cognitive impairment was quite variable 

(days to years of exposure), was not associated with a specific 

statin, age of the patient, statin dose or use of other concurrent 

medications. Furthermore, the data reviewed do not support 

impaired cognition as a common event or one that leads to 

clinically important declines in cognition during treatment 

with statins.

Impaired fasting glucose, incident diabetes and increased 

HbA1c-Prompted in part by findings from two large clinical 

trials (Justification for the Use of Statins in Primary Prevent--

ion [JUPITER] and Pravastatin and Atorvastatin Evaluation 

and Infection Therapy-Thrombolysis in Myocardial Infarction 

(continued on page 2)

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

safety in seconds

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
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NEWS YOU CAN USE

FROM THE FOOD AND DRUG ADMINISTRATION (FDA)

Important safety label changes to cholesterol-lowering statin drugs

02/28/2012

Revisions to the drug labels for the statin drug class include:

A change in hepatic monitoring requirements; testing of liver enzymes before statin therapy and as clinically indicated thereafter will 

suffice instead of the previous routine/periodic monitoring.

New adverse event information; cognitive adverse events (memory loss and/or confusion) and increases in glycosylated hemoglobin 

(HbA1c) as well as fasting plasma glucose have been observed/reported with statin use.

Updates in lovastatin drug-drug interactions, contraindications, and dose limits; this will help to reduce the risk of potential adverse 

events (i.e., muscle injury) when combined with certain medications.

For more information, see “Statin Drug Class: FDA-Approved Labeling Updates” on page 1.

CardioGen-82 - Planned return of CardioGen-82 to market with new Boxed Warning

02/15/2012 (*** UPDATE FROM 01/12/2012 ***) 

CardioGen-82 will return to the U.S. market with revised FDA-approved labeling that includes a Boxed Warning regarding unintended 

radiation exposure when the levels of Sr-82 or Sr-85 in the rubidium Rb chloride injection exceed limits ; additional testing information 

for reducing the risk of exposure to unintended levels of strontium radiation; and instructions on how to identify expired generators and 

when to stop their use. For optimal results, providers should follow the directions in the new labeling.

Victrelis - Important drug interactions between Victrelis (boceprevir) and ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitor drugs

02/8/2012 

Co-administration of boceprevir (Victrelis, a hepatitis C virus [HCV] protease inhibitor) and ritonavir-boosted human immunodeficiency 

virus (HIV) protease inhibitors atazanavir, lopinavir, and darunavir results in a drug interation that can potentially reduce the effectiveness of each, making the use of their combinations not recommended. Boceprevir (Victrelis) is not indicated for use in patients with both 

HIV-1 and chronic HCV infections due to lack of safety and efficacy data in this coinfected population. In the case of previously initiated coadministration, providers should closely monitor for HCV treatment response and for HCV and HIV virologic rebound. 

Proton Pump Inhibitors - Clostridum difficile–associated diarrhea can be associated with stomach acid drugs known as proton pump inhibitors (PPIs)

02/08/2012 

Evidence from case reports submitted to FDA’s Adverse Drug Event Reporting System (AERS) as well as in the medical literature suggests a positive association between the use of PPIs and Clostridium difficile (C. difficile) infection and disease, including C. difficileassociated diarrhea (CDAD) [1.4 to 2.75 times higher risk in PPI-exposed patients compared to non-PPI-exposed patients]. Aside from 

PPI use, additional factors that may influence the risk of CDAD could include elderly age, chronic and/or concomitant underlying medical conditions, or broad spectrum antibiotic use. Limited data impedes further evaluation of the relationship between the risk of C. difficile infection or CDAD and prior PPI use, PPI dose and duration of use, and use of over-the-counter PPIs . Consider a diagnosis of 

CDAD in PPI users with diarrhea that does not improve, or abdominal pain and fever.

NEWS YOU CAN USE

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

Lo/Ovral-28 and Norgestrel/Ethinyl Estradiol Tablets - Recall for Inexact Tablet Counts or Out of Sequence Tablets - National PBM 

Communication – 02-03-2012

(continued from page 1)

22 [PROVE-IT TIMI 22]) of a higher incidence of new diabetes or worsened glycemic control in the statin or high-dose 

statin group in each trial, the FDA reviewed the published 

literature and identified several meta-analyses and epidemiological data that supported an effect of statins on incident diabetes (1/1000 patient years [1 case of DM for every 255 patients treated for 4 years] in one meta-analysis involving over 

90,000 patients) and increases in HbA1c and/or fasting 

plasma glucose. 

Despite this new information, the FDA indicates that they 

“...continue to believe that the cardiovascular benefits of statins 

outweigh these small risks.”

Lovastatin Drug Interactions: Prompted by the updated simvastatin safety labeling in June 2011 (originating primarily from the 

SEARCH trial), the lovastatin label has been modified as well due 

to similar physiochemical and pharmacokinetic properties between lovastatin and simvastatin. The updated lovastatin label also 

includes new contraindications for lovastatin and more aggressive 

dose limits for lovastatin when combined with certain medications 

(See Table 1 on page 3). 

Helping to achieve safe medication use

STATIN DRUG CLASS: FDA-APPROVED LABELING CHANGES
3

Getting the most from our 

safety surveillance

PROCEDURAL ERROR LEADS TO MEDICATION ERROR

Two VA medical centers have reported a procedural error that 

led to a potential for patient harm. In both cases, the error occurred due to staff bypassing standard operating procedures resulting in no final check of a technician’s work by a pharmacist. 

According to one site report, a technician made a mistake repackaging medications and did not obtain a final check from a 

pharmacist, resulting in the improper labeling and packaging of 

two medications: thiamine (a B-complex vitamin) as carbamazapime (an anti-epileptic medication used in managing seizures 

and other psychiatric disorders), and vice versa. The two medications, available in tablet form, appear similar. Out of twentyone inpatients possibly affected by this error, five patients may 

have received thiamine instead of carbamazepine while sixteen 

patients may have received carbamazepine instead of thiamine. 

Pharmacy Service implemented immediate corrective actions 

including checking all unit dose inventory to confirm correct 

medications; removing all pharmacy technicians from unit dose 

packaging duties until they have completed re-training in this 

procedure; and requiring closer oversight by a pharmacist for 

unit dose packaging. Both facilities documented no patient 

harm. 

To prevent ongoing issues of this nature, pharmacy staff should 

take the opportunity to review their procedures and to conduct 

spot checks in order to ensure understanding and completion of 

all steps. 

REFERENCES

1. FIELD Information Report.

VA MedSAFE recommends that facilities continue to report adverse events related to statins or other medications to the VA Adverse Drug Event Reporting System (VA ADERS) as well as to 

the FDA’s Adverse Event Reporting System (AERS-MedWatch). 

Use of these adverse event-reporting systems helps the VA and 

FDA observe for trends in adverse events and may help detect 

safety signals after a drug is marketed.

REFERENCES

FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering 

statin drugs. http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm . (Accessed 

02/28/2012).

Contributed by: Cathy Kelley, Pharm.D.

(continued from page 2)

TABLE 1. LOVASTATIN : FDA-APPROVED LABELING CHANGES FOR CONTRAINDICATIONS, DOSE LIMITS, 

AND OTHER SPECIAL INSTRUCTIONS

Helping to achieve safe medication use

STATIN DRUG CLASS: FDA-APPROVED LABELING CHANGES