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Special Alerts
Medications for ADHD: AHA Clarification of Cardiovascular Screening Recommendation - May 2008
In an effort to reduce the rate of sudden cardiac death especially in pediatric patients receiving stimulant medications for the treatment of attention-deficit/hyperactivity disorder (ADHD), the American Heart Association (AHA) has issued a statement in April 2008 recommending that all children diagnosed with ADHD who may be candidates for stimulant medications have a thorough cardiovascular assessment prior to initiation of drug therapy. The AHA scientific statement was issued by the Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing. On May 16, 2008, the AHA issued a clarification of the recommendations due to the language regarding ECG recommendations and subsequent interpretations.
These recommendations are based on the Food and Drug Administration (FDA) reports of serious cardiovascular adverse events (including sudden death) in patients (both children and adults) taking usual doses of stimulant medications. Most of these patients were found to have underlying structural heart disease (eg, hypertrophic obstructive cardiomyopathy). In 2006, these reports prompted the FDA to recommend labeling changes of these medications to include warnings about cardiovascular events and to develop patient medication guides to be distributed with each prescription.
Stimulant medications theoretically increase cardiovascular risk due to potential effects on blood pressure elevation and increased heart rate. These effects have generally been considered clinically insignificant in most children, however, may be detrimental in certain patients with underlying cardiovascular disease. None of the medications have been shown to cause heart conditions or proven to have caused sudden cardiac death.
The committee suggests that patients needing the following ADHD medications receive a thorough cardiovascular assessment: Methylphenidate, amphetamine, dextroamphetamine, atomoxetine, clonidine, guanfacine, desipramine, imipramine, bupropion, and modafinil.
According to the clarified AHA recommendations, this assessment should include a combination of thorough medical history, family history, and physical examination with the intent to identify risk factors for sudden death. Although not mandatory, physicians should consider obtaining an ECG.
Patients already maintained on ADHD medications should not stop taking their medication. Instead, patients or their caregivers should contact their healthcare provider. It is reasonable that these patients undergo a similar cardiovascular assessment without interruption of therapy.
Press releases and clarified recommendations from the AHA note that the intent of this statement is not to reduce appropriate use of these medications, but to provide physicians with useful tools to identify heart conditions in children with ADHD in order to make more informed prescribing decisions. ECG testing is recommended as one option to be used as part of a combination screening process. They do suggest that a lack of ECG testing should not necessarily mean that treatment not be initiated.
The clarified statement has been endorsed by the American Academy of Child and Adolescent Psychiatry, the American College of Cardiology, Children and Adults with Attention-Deficit/Hyperactivity Disorder, and the National Initiative for Children's Healthcare Quality.
For more information, refer to:
http://americanheart.mediaroom.com/index.php?s=43&item=422
http://circ.ahajournals.org/cgi/content/full/CIRCULATIONAHA.107.189473/DC1
http://americanheart.mediaroom.com/index.php?s=43&item=398
http://www.fda.gov/medwatch/safety/2007/safety07.htm
http://www.fda.gov/bbs/topics/NEWS/2007/NEW01568.html
Nissen SE, “ADHD Drugs and Cardiovascular Risk,” N Engl J Med, 2006, 354(14):1445-48.
“Practice Parameter for the Assessment and Treatment of Children and Adolescents With Attention-Deficit/Hyperactivity Disorder,” J Am Acad Child Adolesc Psychiatry, 2007, 46(7):894-921.
Vetter VL, Elia J, Erickson CH, et al, “Cardiovascular Monitoring of Children and Adolescents With Heart Disease Receiving Stimulant Drugs. A Scientific Statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing,” Circulation, 2008, 117:2407-23.
Wilens TE, Prince JB, Spencer TJ, et al, “Stimulants and Sudden Death: What is a Physician to do?” Pediatrics, 2006, 118(3):1215-19.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section and/or refer to product labeling for additional detail.
Medication Safety Issues
Sound-alike/look-alike issues:
BuPROPion may be confused with busPIRone
Wellbutrin SR® may be confused with Wellbutrin XL™
Wellbutrin XL™ may be confused with Wellbutrin SR®
Zyban® may be confused with Zagam®, Diovan®
Pronunciation
(byoo PROE pee on)
U.S. Brand Names
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of major depressive disorder, including seasonal affective disorder (SAD); adjunct in smoking cessation
Use: Unlabeled/Investigational
Attention-deficit/hyperactivity disorder (ADHD); depression associated with bipolar disorder
Restrictions
An FDA-approved medication guide concerning the use of antidepressants in children, adolescents, and young adults must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm. Dispense to parents or guardians of children and adolescents receiving this medication.
Pregnancy Risk Factor
C
Pregnancy Considerations
Due to adverse events observed in some animal studies, bupropion is classified as pregnancy category C. A significant increase in major teratogenic effects has not been observed following exposure to bupropion during pregnancy; however, the risk of spontaneous abortions may be increased (additional studies are needed to confirm). The long-term effects on development and behavior have not been studied.Pregnancy itself does not provide protection against depression. The ACOG recommends that therapy with antidepressants during pregnancy be individualized and should incorporate the clinical expertise of the mental health clinician, obstetrician, primary care provider, and pediatrician. If treatment is needed, consider gradually stopping antidepressants 10-14 days before the expected date of delivery to prevent potential withdrawal symptoms in the infant. If this is done and the woman is considered to be at risk of relapse from her major depressive disorder, the medication can be restarted following delivery, although the dose should be readjusted to that required before pregnancy. Bupropion has also been evaluated for smoking cessation during pregnancy; current recommendations suggest that pharmacologic treatments be considered only after other therapies have failed. A registry has been established for women exposed to bupropion during pregnancy (800-336-2176).
Lactation
Enters breast milk/not recommended (AAP rates “of concern”)
Breast-Feeding Considerations
Bupropion and its metabolites are excreted into breast milk, although neither bupropion nor its metabolites have been detected in the plasma of breast-fed infants. Adverse events have not been reported in older breast-fed infants; however, a seizure was noted in one 6-month old infant (a causal effect could not be confirmed). Breast-feeding is not recommended by the manufacturer. The AAP considers bupropion to be a “drug for which the effect on the nursing infant is unknown, but may be of concern.”
Contraindications
Hypersensitivity to bupropion or any component of the formulation; seizure disorder; anorexia/bulimia; use of MAO inhibitors within 14 days; patients undergoing abrupt discontinuation of ethanol or sedatives (including benzodiazepines); patients receiving other dosage forms of bupropion
Warnings/Precautions
Boxed warnings:
• Suicidal thinking/behavior: See “Major psychiatric warnings” below.
Major psychiatric warnings:
• [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ?65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1-2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Bupropion is not FDA approved for use in children.
• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Patients treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.
• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.
• May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Bupropion is not FDA approved for bipolar depression.
Concerns related to adverse effects:
• CNS stimulation: May cause CNS stimulation (restlessness, anxiety, insomnia) or anorexia.
• Cognitive impairment: May cause motor or cognitive impairment in some patients, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Delayed hypersensitivity reactions: Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity resembling serum sickness have been reported.
• Seizures: The risk of seizures is dose-dependent and increased in patients with a history of seizures, anorexia/bulimia, head trauma, CNS tumor, severe hepatic cirrhosis, abrupt discontinuation of sedative-hypnotics or ethanol, medications which lower seizure threshold (antipsychotics, antidepressants, theophyllines, systemic steroids), stimulants, or hypoglycemic agents. Discontinue and do not restart in patients experiencing a seizure.
• Sexual dysfunction: The incidence of sexual dysfunction with bupropion is generally lower than with SSRIs.
• Weight loss: May cause weight loss; use caution in patients where weight loss is not desirable.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with cardiovascular disease, history of hypertension, or coronary artery disease; treatment-emergent hypertension (including some severe cases) has been reported, both with bupropion alone and in combination with nicotine transdermal systems.
• Hepatic impairment: Use with caution in patients with hepatic impairment; reduced dose recommended.
• Renal impairment: Use with caution in patients with renal impairment; reduced dose recommended.
Special populations:
• Elderly: Use with caution in the elderly; may be at greater risk of accumulation during chronic dosing. Reduced dose recommended.
Dosage form specific issues:
• Extended release tablet: Insoluble tablet shell may remain intact and be visible in the stool.
Other warnings/precautions:
• Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.
Adverse Reactions
Frequencies, when reported, reflect highest incidence reported with sustained release product.
>10%:
Cardiovascular: Tachycardia (11%)
Central nervous system: Headache (25% to 34%), insomnia (11% to 20%), dizziness (6% to 11%)
Gastrointestinal: Xerostomia (17% to 26%), weight loss (14% to 23%), nausea (1% to 18%)
Respiratory: Pharyngitis (3% to 13%)
1% to 10%:
Cardiovascular: Palpitation (2% to 6%), arrhythmias (5%), chest pain (3% to 4%), hypertension (2% to 4%, may be severe), flushing (1% to 4%), hypotension (3%)
Central nervous system: Agitation (2% to 9%), confusion (8%), anxiety (5% to 7%), hostility (6%), nervousness (3% to 5%), sleep disturbance (4%), sensory disturbance (4%), migraine (1% to 4%), abnormal dreams (3%), irritability (2% to 3%), somnolence (2% to 3%), pain (2% to 3%), memory decreased (up to 3%), fever (1% to 2%), CNS stimulation (1% to 2%), depression
Dermatologic: Rash (1% to 5%), pruritus (2% to 4%), urticaria (1% to 2%)
Endocrine & metabolic: Menstrual complaints (2% to 5%), hot flashes (1% to 3%), libido decreased (3%)
Gastrointestinal: Constipation (5% to 10%), abdominal pain (2% to 9%), diarrhea (5% to 7%), flatulence (6%), anorexia (3% to 5%), appetite increased (4%), taste perversion (2% to 4%), vomiting (2% to 4%), dyspepsia (3%), dysphagia (up to 2%)
Genitourinary: Urinary frequency (2% to 5%), urinary urgency (up to 2%), vaginal hemorrhage (up to 2%), UTI (up to 1%)
Neuromuscular & skeletal: Tremor (3% to 6%), myalgia (2% to 6%), weakness (2% to 4%), arthralgia (1% to 4%), arthritis (2%), akathisia (2%), paresthesia (1% to 2%), twitching (1% to 2%), neck pain
Ocular: Amblyopia (2%), blurred vision (2% to 3%)
Otic: Tinnitus (3% to 6%), auditory disturbance (5%)
Respiratory: Upper respiratory infection (9%), cough increased (1% to 4%), sinusitis (1% to 5%)
Miscellaneous: Infection (8% to 9%), diaphoresis increased (5% to 6%), allergic reaction (including anaphylaxis, pruritus, urticaria)
Postmarketing and/or case reports: Accommodation abnormality, aggression, akinesia, alopecia, amnesia, anemia, angioedema, aphasia, ataxia, atrioventricular block, bronchospasm, bruxism, chills, colitis, coma, coordination abnormal, cystitis, deafness, delirium, delusions, depersonalization, derealization, diplopia, dry eye, dysarthria, dyskinesia, dyspareunia, dysphoria, dystonia, ecchymosis, EEG abnormality, ejaculation abnormality, emotional lability, esophagitis, euphoria, exfoliative dermatitis, extrapyramidal syndrome, extrasystoles, facial edema, fever with rash (and other symptoms suggestive of delayed hypersensitivity resembling serum sickness), gastric reflux, gastrointestinal hemorrhage, gingivitis, glossitis, glycosuria, gum hemorrhage, gynecomastia, hallucinations, hepatic damage, hepatitis, hirsutism, hostility, hyper-/hypoglycemia, hyper-/hypokinesia, hypertonia, hypoesthesia, hypomania, impotence, intestinal perforation, intraocular pressure increased, jaundice, leg cramps, leukocytosis, leukopenia, libido increased, liver function abnormal, lymphadenopathy, maculopapular rash, malaise, manic reaction, menopause, MI, mouth ulcers, muscle rigidity, muscle weakness, musculoskeletal chest pain, mydriasis, myoclonus, neuralgia, neuropathy, painful erection, pancreatitis, pancytopenia, paranoia, paranoid reaction, phlebitis, pneumonia, photosensitivity, postural hypotension, prostate disorder, pulmonary embolism, restlessness, rhabdomyolysis, salivation increased, salpingitis, sciatica, seizure, SIADH, stomach ulcer, stomatitis, stroke, suicidal ideation, syncope, tardive dyskinesia, thirst, thrombocytopenia, tongue edema, urinary incontinence, urinary retention, vaginitis, vasodilation, vertigo
Metabolism/Transport Effects
Substrate of CYP1A2 (minor), 2A6 (minor), 2B6 (major), 2C9 (minor), 2D6 (minor), 2E1 (minor), 3A4 (minor); Inhibits CYP2D6 (weak)
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP2B6 Inducers (Strong): May increase the metabolism of CYP2B6 Substrates. Risk C: Monitor therapy
CYP2B6 Inhibitors (Moderate): May decrease the metabolism of CYP2B6 Substrates. Risk C: Monitor therapy
CYP2B6 Inhibitors (Strong): May decrease the metabolism of CYP2B6 Substrates. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the neurotoxic (central) effect of BuPROPion. Risk X: Avoid combination
Ritonavir: May decrease the serum concentration of BuPROPion. Risk C: Monitor therapy
Tricyclic Antidepressants: BuPROPion may decrease the metabolism of Tricyclic Antidepressants. Exceptions: Amoxapine; Protriptyline. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase CNS depression).
Herb/Nutraceutical: Avoid valerian, St John's wort, SAMe, gotu kola, kava kava (may increase CNS depression).
Storage
Store at controlled room temperature of 20°C to 25°C (68°F to 77°F).
Wellbutrin XL™: Store at 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Aminoketone antidepressant structurally different from all other marketed antidepressants; like other antidepressants the mechanism of bupropion's activity is not fully understood. Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine, and does not inhibit monoamine oxidase or the reuptake of serotonin. Metabolite inhibits the reuptake of norepinephrine. The primary mechanism of action is thought to be dopaminergic and/or noradrenergic.
Pharmacodynamics/Kinetics
Absorption: Rapid
Distribution: Vd: 19-21 L/kg
Protein binding: 82% to 88%
Metabolism: Extensively hepatic via CYP2B6 to hydroxybupropion; non-CYP-mediated metabolism to erythrohydrobupropion and threohydrobupropion. Metabolite activity ranges from 20% to 50% potency of bupropion.
Bioavailability: 5% to 20% in animals
Half-life:
Distribution: 3-4 hours
Elimination: 21 ± 9 hours; Metabolites: Hydroxybupropion: 20 ± 5 hours; Erythrohydrobupropion: 33 ± 10 hours; Threohydrobupropion: 37 ± 13 hours (metabolite accumulation has been noted in ESRD).
Time to peak, serum: Bupropion: ~3 hours; bupropion extended release: ~5 hours
Metabolites: Hydroxybupropion, erythrohydrobupropion, threohydrobupropion: 6 hours
Excretion: Urine (87%); feces (10%)
Dosage
Oral:
Children and Adolescents: ADHD (unlabeled use): 1.4-6 mg/kg/day
Adults:
Depression:
Immediate release: 100 mg 3 times/day; begin at 100 mg twice daily; may increase to a maximum dose of 450 mg/day
Sustained release: Initial: 150 mg/day in the morning; may increase to 150 mg twice daily by day 4 if tolerated; target dose: 300 mg/day given as 150 mg twice daily; maximum dose: 400 mg/day given as 200 mg twice daily
Extended release: Initial: 150 mg/day in the morning; may increase as early as day 4 of dosing to 300 mg/day; maximum dose: 450 mg/day
SAD (Wellbutrin XL™): Initial: 150 mg/day in the morning; if tolerated, may increase after 1 week to 300 mg/day
Note: Prophylactic treatment should be reserved for those patients with frequent depressive episodes and/or significant impairment. Initiate treatment in the Autumn prior to symptom onset, and discontinue in early Spring with dose tapering to 150 mg/day for 2 weeks
Smoking cessation (Zyban®): Initiate with 150 mg once daily for 3 days; increase to 150 mg twice daily; treatment should continue for 7-12 weeks
Elderly: Depression: 50-100 mg/day, increase by 50-100 mg every 3-4 days as tolerated; there is evidence that the elderly respond at 150 mg/day in divided doses, but some may require a higher dose. Note: Patients with Alzheimer's dementia-related depression may require a lower starting dosage of 37.5 mg once or twice daily (100 mg/day sustained release), increased as needed up to 300 mg/day in divided doses (300 mg/day for sustained release)
Dosing conversion between immediate, sustained, and extended release products: Convert using same total daily dose (up to the maximum recommended dose for a given dosage form), but adjust frequency as indicated for sustained (twice daily) or extended (once daily) release products.
Dosing adjustment/comments in renal impairment: Per the manufacturer, the elimination of hydroxybupropion and threohydrobupropion are reduced in patients with end-stage renal failure. Other research has noted a reduction in bupropion clearance (Turpeinen, 2007). Consider a reduction in frequency and/or dosage in this patient population.
Dosing adjustment in hepatic impairment:
Note: The mean AUC increased by ~1.5-fold for hydroxybupropion and ~2.5-fold for erythro/threohydrobupropion; median Tmax was observed 19 hours later for hydroxybupropion, 31 hours later for erythro/threohydrobupropion; mean half-life for hydroxybupropion increased fivefold, and increased twofold for erythro/threohydrobupropion in patients with severe hepatic cirrhosis compared to healthy volunteers.
Mild-to-moderate hepatic impairment: Use with caution and/or reduced dose/frequency
Severe hepatic cirrhosis: Use with extreme caution; maximum dose:
Wellbutrin®: 75 mg/day
Wellbutrin SR®: 100 mg/day or 150 mg every other day
Wellbutrin XL™: 150 mg every other day
Zyban®: 150 mg every other day
Administration: Oral
May be taken without regard to meals. Zyban® and extended release tablets should be swallowed whole; do not crush, chew, or divide. The insoluble shell of the extended-release tablet may remain intact during GI transit and is eliminated in the feces. Data from the manufacturer states that dividing Wellbutrin® SR tablets resulted in an increased rate of release at 15 minutes: “However, the divided tablet retained its sustained-release characteristics with similar increases of released bupropion at each sampling point beyond 15 minutes when compared to the intact Wellbutrin® SR tablet...” Bupropion is hydroscopic and therefore should be stored in a dry place. Splitting of large quantities in advance of administration is not advised since loss of potency may result. If necessary, splitting should be done cleanly without crushing.
Monitoring Parameters
Body weight; mental status for depression, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks
When used for the treatment of ADHD, thoroughly evaluate for cardiovascular risk. Monitor heart rate, blood pressure, and consider obtaining ECG prior to initiation (Vetter, 2008).
Reference Range
Therapeutic levels (trough, 12 hours after last dose): 50-100 ng/mL
Patient Education
Be aware that bupropion is marketed under different names and should not be taken together; Zyban® is for smoking cessation and Wellbutrin® is for treatment of depression. Note: Excessive use or abrupt discontinuation of alcohol or sedatives may alter seizure threshold.
Depression: Take as directed, in equally divided doses; do not take in larger dose or more often than recommended. Do not discontinue this medicine without consulting prescriber. Do not use alcohol or OTC medications not approved by prescriber. May cause drowsiness, clouded sensorium, headache, restlessness, or agitation (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea, vomiting, or dry mouth (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); weight loss; constipation (increased exercise, fluids, fruit, or fiber may help); or impotence (reversible). Report persistent CNS effects (eg, agitation, confusion, anxiety, restlessness, insomnia, psychosis, hallucinations, seizures); suicidal ideation; muscle weakness or tremor; skin rash or irritation; chest pain or palpitations, abdominal pain or blood in stools; yellowing of skin or eyes; or respiratory difficulty, bronchitis, or unusual cough.
Smoking cessation: Use as directed; do not take extra doses. Do not combine nicotine patches with use of Zyban® unless approved by prescriber. May cause dry mouth and insomnia (these may resolve with continued use). Report any respiratory difficulty, unusual cough, dizziness, or muscle tremors.
Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.
Geriatric Considerations
Limited data available about the use of bupropion in the elderly; two studies have found it equally effective when compared to imipramine. Its side effect profile (minimal anticholinergic and blood pressure effects) may make it useful in persons who do not tolerate traditional cyclic antidepressants. A single and multiple dose pharmacokinetic study suggested that accumulation of bupropion and its metabolites may occur in the elderly.
Additional Information
Risk of seizures: When using immediate release tablets, seizure risk is increased at total daily dosage >450 mg, individual dosages >150 mg, or by sudden, large increments in dose. Data for the immediate-release formulation of bupropion revealed a seizure incidence of 0.4% in patients treated at doses in the 300-450 mg/day range. The estimated seizure incidence increases almost 10-fold between 450 mg and 600 mg per day. Data for the sustained release dosage form revealed a seizure incidence of 0.1% in patients treated at a dosage range of 100-300 mg/day, and increases to ~0.4% at the maximum recommended dose of 400 mg/day.
Anesthesia and Critical Care Concerns/Other Considerations
There are relatively few cardiovascular side effects compared to tricyclic antidepressants. However, several case reports include cardiovascular complications, including hypotension and MI. Use with caution in patients with recent MI or unstable angina. Recent information suggests that hypertension, in some cases severe and requiring acute treatment, has been reported in patients receiving bupropion alone, and especially when bupropion is used in conjunction with nicotine replacement therapy. Monitoring of blood pressure is recommended in patients receiving the combination of bupropion and nicotine replacement, particularly in those with hypertension and/or significant coronary artery disease.
Cardiovascular Considerations
There are relatively few cardiovascular side effects compared to tricyclic antidepressants. However, several case reports include cardiovascular complications, including hypotension, hypertension, and MI. Use with caution in patients with recent MI or unstable angina. Recent information suggests that hypertension, in some cases severe and requiring acute treatment, has been reported in patients receiving bupropion alone, and especially when bupropion is used in conjunction with nicotine replacement therapy. These events have been observed in both patients with and without evidence of pre-existing hypertension. Data from a comparative study of sustained-release bupropion, nicotine transdermal system (NTS), the combination of sustained-release bupropion and NTS, and placebo suggest a higher incidence of treatment-emergent hypertension (>6%) in patients treated with the combination of sustained-release bupropion and NTS. The majority of these patients had evidence of pre-existing hypertension. Monitoring of blood pressure is recommended in patients receiving the combination of bupropion and nicotine replacement, particularly in those with hypertension and/or significant coronary artery disease. Possible potential problems need to be balanced against the very substantial benefits of smoking cessation.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Abnormal taste, significant xerostomia (normal salivary flow resumes with discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Part of the mechanism of bupropion is to block reuptake of norepinephrine along with dopamine. Because of the potential for norepinephrine elevation within CNS synapses, it is suggested that vasoconstrictor be administered with caution and to monitor vital signs in dental patients taking antidepressants that affect norepinephrine in this way.
Mental Health: Child/Adolescent Considerations
Attention-deficit/hyperactivity disorder (ADHD): 1.4-5.7 mg/kg/day (mean: 3.3 mg/kg/day) was utilized in 15 ADHD subjects 7-17 years of age (Barrickman, 1995); 72 children with ADHD (6-12 years of age) received 3-6 mg/kg/day (Conners, 1996); adolescents with conduct disorder and substance use disorder were titrated to a maximum fixed daily dose of 300 mg (Riggs, 1998). The immediate-release dosage form was studied in clinical trials for indications other than depression in 104 pediatric patients. This limited exposure does not allow for assessment of the safety of bupropion in pediatric patients.
Barrickman LL, Petty PJ, Allen AJ, et al, “Bupropion Versus Methylphenidate in the Treatment of Attention-Deficit Hyperactivity Disorder,” J Am Acad Child Adolesc Psychiatry, 1995, 34(5):649-57.
Conners CK, Casat CD, Gualtieri CT, et al, “Bupropion Hydrochloride in Attention Deficit Disorder With Hyperactivity,” J Am Acad Child Adolesc Psychiatry, 1996, 35(10):1314-21.
Riggs PD, Leon SL, Mikulich SK, et al, “An Open Trial of Bupropion for ADHD in Adolescents With Substance Use Disorders and Conduct Disorder,” J Am Acad Child Adolesc Psychiatry, 1998, 37(12):1271-8.
Nursing: Physical Assessment/Monitoring
Assess other medications patient may be taking for effectiveness and interactions. Perform careful cardiovascular assessment prior to initiating therapy. Monitor blood pressure at beginning of therapy and periodically with long-term use. Monitor therapeutic effectiveness and adverse reactions at beginning of therapy and periodically with long-term use. Monitor for clinical worsening and suicidality, especially at the beginning of therapy or when dose changes occur. Taper dosage slowly when discontinuing. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as hydrochloride: 75 mg [generic for Wellbutrin®], 100 mg [generic for Wellbutrin®]
Wellbutrin®: 75 mg, 100 mg
Tablet, extended release, as hydrochloride: 100 mg [generic for Wellbutrin® SR], 150 mg [generic for Wellbutrin® SR], 150 mg [generic for Zyban®], 200 mg [generic for Wellbutrin® SR], 300 mg [generic for Wellbutrin XL™]
Budeprion™ SR: 100 mg [generic for Wellbutrin® SR; contains tartrazine], 150 mg [generic for Wellbutrin® SR]
Budeprion XL®: 150 mg [generic for Wellbutrin® XL], 300 mg [contains tartrazine; generic for Wellbutrin® XL]
Buproban™: 150 mg [generic for Zyban®]
Wellbutrin XL™: 150 mg, 300 mg
Tablet, sustained release, as hydrochloride: 100 mg [generic for Wellbutrin® SR], 150 mg [generic for Wellbutrin® SR], 150 mg [generic for Zyban®], 200 mg [generic for Wellbutrin® SR]
Wellbutrin® SR: 100 mg, 150 mg, 200 mg
Zyban®: 150 mg
Pricing: U.S. (www.drugstore.com)
Tablet, 12-hour (Budeprion SR)
100 mg (60): $69.99
150 mg (30): $34.99
Tablet, 12-hour (BuPROPion HCl)
150 mg (60): $69.98
200 mg (60): $124.99
Tablet, 12-hour (BuPROPion HCl (Smoking Deter))
150 mg (60): $69.98
Tablet, 12-hour (Wellbutrin SR)
100 mg (60): $196.83
150 mg (60): $194.45
200 mg (60): $368.47
Tablet, 12-hour (Zyban)
150 mg (60): $198.72
Tablet, 24-hour (Budeprion XL)
150 mg (30): $125.99
300 mg (30): $129.98
Tablet, 24-hour (BuPROPion HCl)
300 mg (30): $132.98
Tablet, 24-hour (Wellbutrin XL)
150 mg (30): $152.19
300 mg (30): $201.40
Tablets (BuPROPion HCl)
75 mg (90): $61.99
100 mg (90): $79.99
Tablets (Wellbutrin)
75 mg (90): $181.93
100 mg (90): $240.31
References
American Academy of Pediatrics Committee on Drugs, “The Transfer of Drugs and Other Chemicals Into Human Milk,” Pediatrics, 2001, 108(3):776-89.
“American Academy of Pediatrics Subcommittee on Attention-Deficit/Hyperactivity Disorder and Committee on Quality Improvement. Clinical Practice Guidelines: Treatment of the School-Aged Child With Attention-Deficit/Hyperactivity Disorder,” Pediatrics, 2001, 108(4):1033-44.
Barrickman LL, Petty PJ, Allen AJ, et al, “Bupropion Versus Methylphenidate in the Treatment of Attention-Deficit Hyperactivity Disorder,” J Am Acad Child Adolesc Psychiatry, 1995, 34(5):649-57.
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