Pharmacology Page 5
Cardiovascular Disease: There is no clinical experience establishing the safety of bupropion in patients with a recent history of myocardial infarction or unstable heart disease. In a study of depressed inpatients with
stable congestive heart failure, bupropion was associated with a rise in supine blood pressure, resulting in discontinuation of 2 patients for exacerbation of baseline hypertension.
Hepatic or Renal Disease: Because bupropion and its metabolites are almost completely excreted through the kidney and metabolites are likely to undergo conjugation in the liver prior to urinary excretion, treatment of patients with renal or hepatic
impairment should be initiated at the lowest recommended dose (see Dosage) as bupropion and its metabolites may accumulate in such patients to a greater extent than usual (See Pharmacology, Pharmacokinetics).
Occupational Hazards: Any psychoactive drug may impair judgment, thinking or motor skills. Therefore patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably
certain that the drug treatment does not affect their performance adversely.
Children: The safety and effectiveness of bupropion in individuals under 18 years old have not been established.
Geriatrics: There is limited experience with bupropion in the elderly. In general, older patients are known to metabolize drugs more slowly and to be more sensitive to the anticholinergic, sedative, and cardiovascular side
effects of antidepressant drugs.
Drug Interactions: Cytochrome P450 2B6: In vitro studies indicate that bupropion is primarily metabolized to hydroxybupropion by the CYP2B6 isoenzyme (see Pharmacology, Pharmacokinetics). Therefore, the potential exists for
a drug interaction between bupropion and drugs that affect the CYP2B6 isoenzyme metabolism (e.g., orphenadrine and cyclophosphamide). The threohydrobupropion metabolite of bupropion does not appear to be produced by the cytochrome P450 isoenzymes.
No systematic data have been collected on the metabolism of bupropion following concomitant administration with other drugs or alternatively, the effect of concomitant administration of bupropion on the metabolism of other drugs.
Following chronic administration of bupropion, 100 mg t.i.d. to 8 healthy male volunteers for 14 days, there was no evidence of induction of its own metabolism.
Because bupropion is extensively metabolized, the coadministration of other drugs may affect its clinical activity. In particular, certain drugs may induce the metabolism of bupropion (e.g., carbamazepine, phenobarbital, phenytoin).
MAO Inhibitors: Studies in animals demonstrate that the acute toxicity of bupropion is enhanced by the MAO inhibitor, phenelzine (see Contraindications).
Adverse Events Occurring at an Incidence of 1% or More Among Patients Treated with Bupropion in Placebo Controlled Trials: Table I enumerates treatment-emergent adverse events that occurred at an incidence of 1% or more and
were more frequent than in the placebo group in patients participating in placebo-controlled clinical trials. Reported adverse events were classified using a COSTART-based Dictionary.
Drug Abuse and Dependence: Bupropion is likely to have a low abuse potential. There have been few reported cases of drug dependence and withdrawal symptoms associated with the immediate-release formulation of bupropion. In human
studies of abuse liability, individuals experienced with drugs of abuse reported that bupropion produced a feeling of euphoria and desirability. In these a single dose of 400 mg (1.33 times the recommended daily dose) of the immediate-release
formulation of bupropion produced mild amphetamine-like effects compared to placebo on the Morphine-Benzedrine Subscale of the Addiction Research Center Inventories (ARCI), which is indicative of euphorigenic properties and a score intermediate
between placebo and amphetamine on the Liking Scale of the ARCI. Higher doses could not be tested because of the risk of seizure.
Dosage And Administration: The usual recommended dose is 100 to 150 mg/day given once daily. As with all antidepressants, the full antidepressant effect may not be evident until several weeks of treatment. In patients who are
not responding to a dose of 150 mg/day the dose may be increased up to a maximum of 300 mg/day. Dose increases should occur at intervals of at least 1 week. In order to minimize the risk of seizures (see Warnings), single doses of bupropion
should not exceed 150 mg. Doses greater than 150 mg/day should be administered b.i.d, preferably with at least 8 hours between successive doses.
Geriatrics, Debilitated, Hepatic, and Renal Impairment: In subjects with hepatic impairment limited pharmacokinetic data demonstrates a prolonged half-life of hydroxybupropion (see Pharmacology). No pharmacokinetic or therapeutic
trials have been conducted to systematically investigate dose requirements in patients who are elderly, debilitated or renally impaired (see Precautions). As such patients may have reduced clearance of bupropion and its metabolites, and/or increased
sensitivity to the side effects of CNS active drugs, treatment with bupropion should be initiated at the lowest recommended dose (100 mg/day).
Patients should be advised to swallow bupropion sustained release tablets whole with fluids, and not to chew, divide, crush or otherwise tamper with the tablets in any way that might affect the release rate of bupropion.
Availability And Storage: 100 mg: Each blue, round, biconvex, film-coated, sustained-release tablet, printed WELLBUTRIN SR 100", contains: bupropion HCl 100 mg. Nonmedicinal ingredients: carnauba wax, cysteine hydrochloride,
edible black ink, FD&C Blue No. 1 Lake, hydroxypropylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80 and titanium dioxide. Bottles of 60.
Store between 15 and 25°C away from direct sunlight. |
