Hospital Pharmacy - October 2017 - 593

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HPXXXX10.1177/0018578717727176Hospital Pharmacy

Current FDA-Related Drug Information

Summaries of Safety Labeling Changes
Approved By FDA- Boxed Warnings
Highlights April-June 20171
The FDA's MedWatch program safety labeling changes for
boxed warnings are compiled quarterly for drugs and therapeutic biologics where important changes have been made
to the safety information. These and other label changes are
searchable in the Drug Safety Labeling Changes (SLC)
database2, where data are available to the public in downloadable and searchable formats. Boxed warnings are ordinarily used to highlight either: adverse reactions so serious

Hospital Pharmacy
2017, Vol. 52(9) 593-595
© The Author(s) 2017
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https://doi.org/10.1177/0018578717727176
DOI: 10.1177/0018578717727176
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in proportion to the potential benefit from the drug that it is
essential that it be considered in assessing the risks and
benefits of using the drug; OR serious adverse reactions
that can be prevented/reduced in frequency or severity by
appropriate use of the drug; OR FDA approved the drug
with restrictions to ensure safe use because FDA concluded
that the drug can be safely used only if distribution or use is
restricted.

AVANDAMET (NDA-021410) (METFORMIN HYDROCHLORIDE; ROSIGLITAZONE MALEATE)
Edited Boxed Warning (additions are underlined)
WARNING: CONGESTIVE HEART FAILURE and LACTIC ACIDOSIS
Rosiglitazone maleate: CONGESTIVE HEART FAILURE
** Thiazolidinediones, including rosiglitazone, cause or exacerbate congestive heart failure in some patients. After initiation of
AVANDAMET, and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid
weight gain, dyspnea, and/or edema). If these signs and symptoms develop, the heart failure should be managed according to current
standards of care. Furthermore, discontinuation or dose reduction of AVANDAMET must be considered.
** AVANDAMET is not recommended in patients with symptomatic heart failure. Initiation of AVANDAMET in patients with
established NYHA Class III or IV heart failure is contraindicated.
Metformin hydrochloride: LACTIC ACIDOSIS
** Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant
bradyarrhythmias. The onset of metformin- associated lactic acidosis often subtle, accompanied only by nonspecific symptoms such
as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin- associated lactic acidosis was characterized
by elevated blood lactate levels (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and increased lactate/
pyruvate ratio; and metformin plasma levels generally >5 mcg/mL.
** Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic
anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other
procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment. Steps to reduce the
risk of and manage metformin-associated lactic acidosis in these high-risk groups are provided in the Full Prescribing Information.
** If metformin-associated lactic acidosis is suspected, immediately discontinue AVANDAMET and institute general supportive measures
in a hospital setting. Prompt hemodialysis is recommended.

GLUMETZA (NDA-021748) (METFORMIN HYDROCHLORIDE)
Edited Boxed Warning (additions are underlined)
Lactic Acidosis
Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant
bradyarrhythmias. The onset of metformin- associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such
as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin- associated lactic acidosis was characterized by
elevated blood lactate levels (> 5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/
pyruvate ratio, and metformin plasma levels generally >5 mcg/mL.
Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase
inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures,
hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full prescribing
information.
If metformin-associated lactic acidosis is suspected, immediately discontinue GLUMETZA and institute general supportive measures in a
hospital setting. Prompt hemodialysis is recommended.
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