8.8
Summary of Drug Interactions
8.8.1
Drug-Demographic Interactions
Effect
of gender, age, and race on the incidence of the common, drug-related events
(see section 8.5.1) of agitation, dry mouth, pharyngitis, rash, sinusitis, sweating,
tinnitus, and tremor were explored in the following manner. Combing data from the two placebo-controlled
trials (203 and 205), relative risks for males and females were calculated for
each of the adverse events considered:
RRm =Bupropion sustained-release rate in
males + Placebo rate in males
RRf = Bupropion sustained-release rate in
females + Placebo rate in females
The
ratio of these relative risks was then calculated RRf ÷ RRm. To determine confidence intervals for the
relative risk ratios, odds ratios for males and females were determined along
with a common odds ratio (Mantel-Haenszel method). Homogeneity of the odds ratios so obtained was then assessed with
the Breslow-Day test. Similar methods
were applied for age (<60 years old vs. ≥ 60 years old and for race
(white vs. non-white).
With
these methods, dry mouth (p=0.04) and tinnitus (p=0.025) were both identified
as more frequently apparent drug-related adverse events in females than in
males. Because these demographic
findings arose out of multiple comparisons, however, their value should be
interpreted cautiously. No other
adverse events were
significantly
linked to other demographic factors.
8.8.2
Drug-Disease Interactions
The
sponsor has not studied interactions of bupropion sustained-release with other
diseases beyond depression in humans. A
detailed study of bupropion immediate-release in patients with heart disease
has been published, however (Roose et al, Am J Psychiatry (1991)
148:512-516). In patients with
depression and preexisting left ventricular dysfunction, ventricular
arrythmias, and/or conduction disease who were taking a mean of 442 mg/day
bupropion immediate-release, over three weeks the medicine caused a slight rise
in supine blood pressure, but did not exacerbate ventricular arrythmias or
affect pulse rate. It caused a low rate
of orthostatic hypotension and was discontinued in 14% of the patients because
of adverse effects, including exacerbation of baseline hypertension.
8.8.3
Drug-Drug Interactions
The
sponsor has not studied interactions of bupropion sustained-release with other
drugs in humans. One report in the
medical literature notes that bupropion immediate-release causes an increased
risk of increased agitation, confusion, hallucinations, and nausea and vomiting
when administered with levodopa.
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