noted
to have a small arachnoid cyst on MRI and a history of six alcoholic drinks per
day after he experienced a seizure on the 66th day of
treatment. In addition, three patients
experienced seizures as sequelae following overdoses with bupropion sustained-release:
patient 036-004 had ingested her last bupropion sustained-release prior to a
period of three days of intermittent cocaine abuse that culminated in an
overdose with over 500 chlordiazepoxide and phencyclidine; after “hoarding
tablets” for some time, patient 081-011 took an overdose of a “handful” of 150
mg tablets of bupropion sustained-release; and patient 90-022 ingested 600 mg
of bupropion sustained-release over a 24-hour period to “catch up” on
previously missed doses. Two patients
experienced seizures that were considered unrelated to bupropion
sustained-release intake: patient 08-004 experienced a seizure on the first day
of the study before taking her first dose of medication and patient 022-032
experienced a seizure 39 days after discontinuing the study after one dose of
bupropion sustained-release. No other
seizures were reported.
Six
patients died during the protocol: three patients committed suicide; two
patients died of cardiac disease, and one patient was murdered. None of the deaths were considered to be
attributable to bupropion sustained-release.
A total of 2572 patients (83% of 3100) were assessed as having either no
side effects or side effects which did not significantly interfere with their
functioning.
8.5.6
Withdrawal Phenomena/Abuse Potential
The
sponsor reports no instances of bupropion sustained-release abuse or
dependence. Withdrawal phenomena were
not formally assessed after patients discontinue bupropion sustained-release. In the development of bupropion immediate-release,
the sponsor noted that a dose of 400 mg produced a modest elevation over
placebo responses on the morphine benzedrine group subscale of the Addition
Research Center Index, and a score intermediate between amphetamine and placebo
on the Liking Scale of the Addiction Research Center Index.
8.5.7
Human Reproduction Data
Human reproduction data is lacking from both the clinical use of bupropion immediate-release and bupropion sustained-release. The sponsor does not report any pregnancies during bupropion sustained-release clinical trials.
8.5.8
Overdose Experience
There
is very limited experience with overdoses of bupropion sustained-release. There were no overdoses of active medication
in the controlled clinical trials.
There were three overdoses with bupropion sustained-release in protocol
208. Patient 004-019, a 37-year-old
male, ingested three grams of medication and two beers. He vomited quickly afterwards and reported
lightheadedness and blurred vision. He
was released after evaluation. Patient
081-011, a 34-year-old female, ingested a “handful” of bupropion
sustained-release 150 mg tablets. She
vomited quickly afterwards, and then appeared lethargic and confused. In the emergency room she experienced a
generalized convulsive seizure. After
gastric lavage and treatment with charcoal and magnesium sulfate, the patient
was released. Patient 09-022, a
35-year-old male, took an extra 300 mg over the course of 24 hours in order to
“catch up” on missed doses. He
experienced a generalized seizure approximately six hours after the last dose
of medication.
The
manufacturer reports that bupropion immediate-release overdoses of up to 17.5
grams have been reported. Seizure was
reported in approximately one-third of all cases. Other serious reactions reported with overdoses of the compound
included hallucinations, loss of consciousness, and tachycardia. Fever, muscle rigidity, rhabdomyolysis,
hypotension, stupor, coma, and respiratory failure have been reported when the
drug was part of a multiple drug overdose.
Bupropion
Sustained-Release Clinical Review 40
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