PVmap™ of the Week
ProSanos has initiated a program to publicly provide a limited set of PVmaps™
generated from the FDA's Adverse Event database. A different map will be posted
each week focusing on a drug and adverse event combination that is a current topic
of discussion within the industry or in the published literature. For more
information about PVmaps
or the PVmap of the Week program, .
Amiodarone, Gatifloxacin, and Contradictory Effects (4/1/07)
The March 2007 issue of Drug Safety carries a comprehensive review of
drug-induced endocrine and metabolic disorders.30 The review contains
a discussion of drug-induced hyper- and hypothyroidism. A section of that
discussion is devoted specifically to the cardiovascular drug amiodarone,
which can cause both hyperthyroidism and hypothyroidism. Its effect on the
thyroid in an individual patient depends in part on whether or not the patient
is iodine-deficient, along with a set of other factors discussed in the
article.
The associations of both hyperthyroidism and hypothyroidism with amiodarone
are clearly seen in a Drug-focused PVmap for this compound.
The PVmap above uses the publicly-available data from the FDA via its
Adverse Event Reporting System (AERS) with data covering the period from 2001
through the first quarter of 2006. This is a Drug-focused PVmap that shows the
adverse events that are most strongly associated with Amiodarone in the upper
right hand corner of the graph. PVmaps' visual interface allows the user to
easily observe multiple associated MedDRA terms. In the Pvmap above, we see
these seemingly "contradictory" adverse events (hyperthyroidism and
hypothyroidism) that are discussed in the article.
There are many cases in which a single drug can be associated with both one
event and its physiological opposite. Last year, the New England Journal of
Medicine carried an article associating the antibiotic gatifloxacin with both
hyperglycemia and hypoglycemia in the elderly.31
The Drug-focused Pvmap above strikingly highlights these
"contradictory" adverse events two dots next to each other. Further
down the map, we also find blood glucose increased next to blood
glucose decreased.
PVmaps provides a way to visually investigate the most important components of
the drug's safety profile, including instances where a drug is associated with
adverse events with seemingly "contradictory" medical conditions.
While these conditions could not co-exist in the context of a single patient,
they make sense for a population, and often indicate an underlying failure of a
homeostatic mechanism associated with a drug.
About Drug-focused PVmaps
Above is a Drug-focused PVmap, allowing you to visualize which adverse events
are most highly associated with a particular drug of interest. In the map
directly above, the drug is gatifloxacin and the red dots represent
Adverse Events reported in the AERS database to be associated with gatifloxacin.
On the horizontal axis of this graph is the reporting ratio that
compares the number of cases of a particular adverse event with the number
expected due to chance alone. The vertical axis expresses the statistical
significance of the finding. Dots above the horizontal blue line and to the
right of the vertical blue line represent "significant signals".
The adverse events with the strongest association to gatifloxacin appear at the
top and to the right on the PVmap.
To learn more about PVMaps projects in your therapeutic area or indication,
please .
Disclaimers
- ProSanos is not affiliated with the authors of cited
references, and this article does not imply endorsement of their findings,
content, or offerings.
- Potential risks highlighted by drug safety analysis must be balanced against
the clinical benefit attained by the use of a pharmaceutical product in a given
clinical situation. Nothing in these analyses is intended to influence the
practice of medicine, nor to weigh the benefits of one product over another.
- Whether the reporting ratio of an adverse event is high enough to influence the
decision to use a given product or products can only be determined by a complete
analysis of the benefits, risks, and therapeutic alternatives.
- Use of the publicly available FDA AERS data does not imply endorsement or
agreement of the findings by the FDA Center for Drug Evaluation and Research.
- There are many factors that can influence how the adverse events are reported
in the AERS database and may impact the resulting safety signal. These include but
are not limited to: publicity and media attention, litigation, length of time drug
is on the market, whether the event in question has been previously attributed
to the drug, the source of the report, etc.
- AERS data must often be "cleaned" prior to analysis. This process may include
de-duplication, reconciliation of misspelled product names, mapping of adverse
events terms, and other manipulations which could introduce bias into the analysis.
- PVmaps has been evaluated as a safety signal investigation tool for over two years.
References
- Ma RCW, Kong APS, Chan N, et al.
Drug-Induced Endocrine and Metabolic Disorders. Drug Safety 2007;30(3):215-245.
- Park-Wyllie LY, Juurlink DN, Kopp A, et al. Outpatient Gatifloxacin Therapy
and Dysglycemia in Older Adults. N Engl J Med 2006;354:1352-1361.
