mice with equal doses of BSR and BIR. The sponsor states, “When administered to mice in equal doses, a sustained release formulation of bupropion produces significantly fewer convulsions than an immediate release aqueous formulation.” This is animal data that implies that BSR is less likely to cause seizures in humans and might therefore be safer to use than BIR with respect to seizures. The large body of human data is for the 300 mg/day dose level which is at the lowest end of the recommended dose range of 300-400 mg/day.
Absorption, Distribution, Pharmacokinetics, and Elimination Section: This section removes the information for BIR and inserts the data for BSR.
Indications and Usage Section: This section removes the specific seizure incidence information and refers the prescriber to the Warning section.
Contraindications Section: The contraindications remain for patients with a seizure disorder and patients with bulimia or anorexia nervosa.
Warning Section:
Seizures: A review of the extended treatment protocol (study 208) is presented and clearly states what the seizure incidence is for doses of 300 mg/day. The BIR seizure incidence data is presented after this.
Hepatotoxicity warnings remain unchanged.
Precautions Section: This section is amended to present the safety data of BSR with respect to agitation and insomnia. Precautions against psychosis, confusion and other neuropsychiatric phenomena have subsumed the terms delusions, paranoia, and psychotic episodes under the term psychosis. The section discussing altered appetite and weight was amended to reflect the sponsors experience with BSR and still reports data from comparison studies with BIR and TCAs.
Information to patients section: This section was changed to reflect the use of Wellbutrin SR in the place of Wellbutrin. Changes in the dosing schedule, and most importantly, the reference to seizure risks and precautions has been removed.
Drug Interactions, Carcinogenesis-Mutagenesis-Impairment-of-Fertility, Pregnancy, and Pediatric Use sections are essentially unchanged. Data on use of BSR in the elderly was added based on experience from the extended safety study (208).
Adverse Events section: This section reflects tabular results of adverse events encountered by the 987 patients who were involved in the controlled clinical trials groups. This is somewhat misleading in that only half of the patients (487) received BSR in the
Page 2 NDA 20,358
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