Bupropion: Contraindications/Precautions
Absolute contraindications are in italics.
- abrupt discontinuation
- anorexia nervosa
- breast-feeding
- bulimia nervosa
- seizure disorder
- seizures
- acute myocardial infarction
- alcoholism
- biliary cirrhosis
- bipolar disorder
- cardiac disease
- children
- diabetes mellitus
- driving or operating machinery
- elderly
- ethanol intoxication
- head trauma
- heart failure
- hepatic disease
- hypertension
- intracranial mass
- mania
- myocardial infarction
- neonates
- obesity treatment
- pregnancy
- psychosis
- renal failure
- renal impairment
- substance abuse
- suicidal ideation
- tics
- tobacco smoking
- Tourette’s syndrome
Bupropion Contraindications/Precautions
NOTE: Given that there are multiple dosage forms of bupropion available, it is important to be familiar with each product name and dosing schedule to avoid dosing errors.
Bupropion is contraindicated in patients with a history of a previous hypersensitivity or severe adverse reaction (e.g., seizures) due to bupropion. Delayed hypersensitivity reactions, consisting of arthralgia, myalgia, fever and rash have been reported in association with bupropion and may resemble serum sickness.
Avoid abrupt discontinuation of bupropion in most circumstances. Bupropion is contraindicated in patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines) because such discontinuation may lower the seizure threshold. Bupropion should not be used by patients with a preexisting seizure disorder. The incidence of seizures occuring with bupropion is dose-dependent, and seizures estimated to occur in 1-2 of every 1000 patients treated. According to the manufacturer, the incidence of seizures in patients taking Wellbutrin® XL as a single dose of 450 mg is 0.4%. At dosages of 600 mg/day (immediate-release) the risk of seizures increases 10-fold compared to the seizure risk at 450 mg/day. Do not exceed maximum recommended single or total daily dosages. Patients who are taking bupropion for smoking cessation (e.g., Zyban ®) should not also take bupropion for depressive disorders (e.g., Wellbutrin®), and vice-versa. Healthcare professionals should be aware that bupropion is available under several brand names for various treatment indications in order to avoid these adverse reactions. Patients who have a history of seizures are most at risk, but patients with eating disorders have been shown to have an increased incidence of seizures; therefore, bupropion is also contraindicated in patients with a current or previous history of anorexia nervosa or bulimia nervosa. Other predisposing factors that may increase the risk of seizures include alcoholism, head trauma, intracranial mass or CNS tumor, severe hepatic or biliary cirrhosis, substance abuse [such as sedative (including benzodiazepine) or opioid abuse], and use of concomitant medications (e.g., antipsychotics, antidepressants, theophylline, tramadol, systemic corticosteroids) that lower seizure threshold. Other medications associated with an increased seizure risk include opiates, amphetamines, cocaine, over-the-counter or prescription stimulants or anorectics (obesity treatment) and oral hypoglycemics or insulin for the treatment of diabetes mellitus.
All effective antidepressants can transform depression into mania or hypomania in predisposed individuals (i.e., patients with bipolar disorder or latent psychosis). If a patient develops manic symptoms, bupropion should be held and appropriate therapy initiated to treat the manic symptoms.
Bupropion is not FDA-approved for the treatment depression in pediatric patients. The possibility of a suicide attempt is inherent in patients with depressive symptoms, whether these occur in primary depression or in association with another primary disorder such as OCD. Patients with suicidal ideation, including both adult and pediatric patients, should be closely supervised, whether or not they are taking an antidepressant. In addition, all antidepressants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. In October, 2004, the FDA directed manufacturers of all antidepressants to include a Black Box warning detailing the risk of suicide in pediatric patients. A causal role for antidepressants in inducing suicidality has been established in pediatric patients. The risk of suicidality for these drugs was identified in a pooled analysis of 24 placebo-controlled trials (n=4400) lasting up to 16 weeks in pediatric patients with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants (SSRIs and others). The average risk of such events on drug was 4% and 2% for placebo; however, no suicides occurred in these trials. Based on these data, FDA has determined that the following points are appropriate for inclusion in the boxed warning: antidepressants increase the risk of suicidal thinking and behavior (suicidality) in pediatric patients with MDD and other psychiatric disorders (OCD, social anxiety disorder); anyone considering the use of an antidepressant in a pediatric patient for any clinical use must balance the risk of increased suicidality with the clinical need; patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior, particularly within the first few months of starting therapy or at the time of dose increases or decreases; such observation would generally include at least weekly face-to-face contact with patients, family members or caregivers during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks; additional contact by telephone may be appropriate between face-to-face visits; adults with MDD or co-morbid depression in the setting of other psychiatric illness being treated with antidepressants should be observed similarly for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes; families and caregivers should be advised to closely observe the patient (adult or child) on a daily basis for the emergence of agitation, irritability, unusual changes in behavior, emergence of suicidality, and to communicate immediately with the prescriber. It is unknown if the suicidality risk in pediatric patients extends to longer-term therapy (i.e., beyond several months) or to adult patients. In patients who exhibit changes in symptoms (see Adverse Events), worsening of depression or emergent suicidality, a decision should be made to change or discontinue treatment. If discontinuing, medication should be tapered as rapidly as possible, but with recognition that abrupt discontinuation can also cause adverse symptoms. A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described represent such a conversion is unknown. Patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder prior to initiating treatment. Such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that bupropion is not approved for use in treating bipolar depression.
The concurrent administration of an MAO inhibitor and bupropion (for the treatment of depression or for smoking cessation) is contraindicated. At least 14 days should elapse between the discontinuation of the MAO inhibitor and initiation of bupropion treatment (see Drug Interactions).
Bupropion is classified as FDA category B. In rats or rabbits, there are no data that suggests fetal harm or an adverse effect on fertility. There is insufficient data with human gestation, however, so bupropion should be used during pregnancy only when clearly needed. The manufacturer of Wellbutrin® and Zyban ®, Glaxo Wellcome Inc., maintains a bupropion Pregnancy Registry. Healthcare providers are encouraged to register patients who have received bupropion during pregnancy by calling (888) 825-5249, ext. 39441. Pregnant smokers should be encouraged to attempt educational and behavioral interventions before pharmacologic approaches are used. While not reported for bupropion, neonates exposed to selected antidepressants late in the third trimester have developed symptoms consistent with either a direct toxic effect of the antidepressants or a potential drug discontinuation syndrome. When treating a pregnant woman, the physician should carefully consider the potential risks and benefits of treatment. If clinically feasible, tapering of the medication prior to delivery may be considered.
Bupropion should not be used by nursing mothers because the drug is excreted into human breast milk, potentially causing adverse effects, like seizures, in breast-fed infants. Peak breast milk concentrations of bupropion and its metabolites are present within 2-4 hours after an oral dose. A decision should be made to either discontinue bupropion or discontinue breast-feeding, taking into account the importance of the medication to the mother.
Bupropion should be used with extreme caution in patients with hepatic disease (including mild to moderate hepatic cirrhosis), renal impairment, or renal failure because active metabolites could accumulate. Bupropion undergoes extensive hepatic metabolism and excretion in the urine as metabolites. Consider reduced dosages in these patient populations based on the degree of organ impairment and closely monitor for adverse reactions that could indicate high drug or metabolite levels. In patients with severe hepatic impairment (e.g., Child-Pugh Class C cirrhosis) dosage reduction is required (see Dosage).
Of roughly 6000 patients in bupropion studies for both smoking cessation and depression, 275 were 65 and over and 47 were 75 and over. Several hundred elderly patients 65 years of age and older have also been studied (in depression) with the immediate release formulation. Most pharmacokinetic data do not indicate differences among healthy elderly patients taking bupropion versus normal adults. However, both initial and maintenance doses should be reduced in elderly patients if hepatic or renal impairment or debilitating disease is present. Multiple dose pharmacokinetic studies have indicated the elderly may be at risk for bupropion and metabolite accumulation. The manufacturer warns that it may be useful to monitor renal function in the elderly. Bupropion may also cause weight loss which may be significant for elderly or otherwise debilitated patients.
Rarely, bupropion may cause a fast or irregular heart beat or increases in blood pressure in some patients. It should be used with caution in patients with a recent history of acute myocardial infarction or unstable cardiac disease, including heart failure. Pharmacokinetic studies suggest that left ventricular dysfunction results in lowered metabolism and excretion of bupropion and its metabolites. Because bupropion may increase blood pressure in some patients, patients with hypertension should have their blood pressure checked while on bupropion treatment. Bupropion may be used in combination with nicotine transdermal systems (NTS) as an aide to smoking cessation. In clinical trials, new onset treatment-induced hypertension or exacerbation of existing high blood pressure occurred more commonly in patients using the combination bupropion-NTS therapy. In some cases the exacerbation of hypertension required discontinuation of bupropion treatment. Patients should quit tobacco smoking prior to initiating the nicotine therapy in the bupropion-NTS combination regimen to reduce the risk of unwanted cardiac side effects. Close blood pressure monitoring is recommended. Patients who are taking bupropion should not self-treat with OTC nicotine products; the bupropion-NTS combination should only be used under the prescription and advice of a health-care prescriber. When used as monotherapy, patients should schedule to stop tobacco smoking during the second week of taking bupropion. When bupropion is used for smoking cessation, it should be noted that cessation of tobacco smoking may result in elevated serum concentrations of some drugs that are hepatically metabolized, such as theophylline and warfarin (see Drug Interactions) due to lowered induction of hepatic oxidative microsomal enzymes (tobacco smoke induces hepatic enzymes). Downward dosage adjustments of such drugs and more frequent monitoring may be required during smoking cessation.
At this time, the safety and efficacy of bupropion treatment for smoking cessation have not been established in children or adolescents under the age of 18 years. Children aged 6 years and older with depression or ADHD have been studied in clinical trials of bupropion, but data on pediatric safety is limited. Bupropion, like other medications for ADHD, may precipitate motor or phonetic tics in those with Tourette’s syndrome. In October, 2004, the FDA directed manufacturers of all antidepressants to include a Black Box warning detailing the risk of suicide in pediatric patients. A causal role for antidepressants in inducing suicidality has been established in pediatric patients (see Contraindications, suicidal ideation). Pediatric patients should be monitored closely for the risk of suicide with any antidepressant medication. Among the antidepressants, only fluoxetine is approved for use in treating depression in pediatric patients. Fluoxetine, sertraline, fluvoxamine, and clomipramine are approved for OCD in pediatric patients. None of the drugs is approved for other psychiatric indications in children. Pediatric patients being treated with antidepressants for any indication should be observed daily by caregivers for clinical worsening, as well as agitation, irritability, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. If concerns arise, contact with health care providers should be made immediately. Antidepressants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. A patient Medication Guide about using antidepressants in children and adolescents is available. Health care providers should instruct patients and caregivers to read the guide and discuss any questions with them.
Patients should be warned to use caution when driving or operating machinery or performing other tasks that require mental alertness until they know how bupropion will affect them. Some patients have reported lower alcohol tolerance during treatment with bupropion; advise patients that the consumption of alcohol should be minimized or avoided; avoid ethanol intoxication.
[ Last revised: 2/4/2005 1:44:00 PM ]
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