Wellbutrin SR - Warnings & Precautions

Hepatic Impairment

WELLBUTRIN SR should be used with extreme caution in patients with severe hepatic cirrhosis. In these patients a reduced frequency and/ or dose is required, as peak bupropion, as well as AUC, levels are substantially increased and accumulation is likely to occur in such patients to a greater extent than usual. The dose should not exceed 100 mg every day or 150 mg every other day in these patients (see CLINICAL PHARMACOLOGY, PRECAUTIONS, and DOSAGE AND ADMINISTRATION).

Potential for Hepatotoxicity

In rats receiving large doses of bupropion chronically, there was an increase in incidence of hepatic hyperplastic nodules and hepatocellular hypertrophy. In dogs receiving large doses of bupropion chronically, various histologic changes were seen in the liver, and laboratory tests suggesting mild hepatocellular injury were noted.

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PRECAUTIONS

General

Agitation and Insomnia

Patients in placebo-controlled trials with WELLBUTRIN SR Tablets experienced agitation, anxiety, and insomnia as shown in Table 1.

Table 1. Incidence of Agitation, Anxiety, and Insomnia in Placebo-Controlled Trials

Adverse Event Term

WELLBUTRIN SR 300 mg/ day

(n = 376)

WELLBUTRIN SR 400 mg/ day

(n = 114) Placebo (n = 385) Agitation 3% 9% 2%

Anxiety 5% 6% 3% Insomnia 11% 16% 6%

In clinical studies, these symptoms were sometimes of sufficient magnitude to require treatment with sedative/ hypnotic drugs. Symptoms were sufficiently severe to require discontinuation of treatment in 1% and 2.6% of patients treated with 300 and 400 mg/ day, respectively, of WELLBUTRIN SR Tablets and 0.8% of patients treated with placebo.

Psychosis, Confusion, and Other Neuropsychiatric Phenomena: Depressed patients treated with an immediate-release formulation of bupropion or with WELLBUTRIN SR Tablets have been reported to show a variety of neuropsychiatric signs and symptoms, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion. In some cases, these symptoms abated upon dose reduction and/ or withdrawal of treatment. Activation of Psychosis and/ or Mania: Antidepressants can precipitate manic episodes in bipolar disorder patients during the depressed phase of their illness and may activate latent psychosis in other susceptible patients. WELLBUTRIN SR is expected to pose similar risks. Altered Appetite and Weight: In placebo-controlled studies, patients experienced weight gain or weight loss as shown in Table 2.