Instructions Buprinol modified-release tablets 150 mg container #30
Composition
active ingredient: bupropion hydrochloride;
1 modified-release tablet contains bupropion hydrochloride 150 mg;
excipients: hydroxypropylcellulose (Klucel EXF); silicified microcrystalline cellulose (ProSolv® SMCC 90); stearic acid 50; magnesium stearate;
extended-release coating: Opadry white, 29A18501 (ethylcellulose, hydroxypropylcellulose, titanium dioxide (E 171), triethyl citrate);
Modified release coating: methacrylate acid - ethyl acrylate copolymer (1:1) (Eudragit L-100-55); triethyl citrate; talc.
Dosage form
Modified-release tablets.
Main physicochemical properties: round biconvex tablets, film-coated, creamy white to pale yellow in color and with a diameter of 8.13 ± 0.4 mm.
Pharmacotherapeutic group
Other antidepressants. ATX code N06A X12.
Pharmacological properties
Pharmacodynamics.
Bupropion is a selective inhibitor of neuronal reuptake of catecholamines (norepinephrine and dopamine) with minimal effect on indoleamine (serotonin) reuptake and lack of monoamine oxidase (MAO) inhibition. It is believed that the antidepressant action of bupropion is mediated by noradrenergic and/or dopaminergic mechanisms.
Pharmacokinetics.
Absorption
Following oral administration of 300 mg of bupropion hydrochloride once daily as modified-release tablets to healthy volunteers, the maximum plasma concentration (Cmax) was approximately 160 ng/mL and was observed at approximately 5 hours. At steady state, the Cmax and area under the pharmacokinetic concentration-time curve (AUC) of hydroxybupropion are approximately 3- and 14-fold higher than those of bupropion, respectively. The Cmax of threohydrobupropion at steady state is similar to that of bupropion and the AUC is approximately 5-fold higher, while plasma concentrations of erythrohydrobupropion are comparable to those of bupropion. Peak plasma levels of hydroxybupropion are reached at 7 hours, while those of threohydrobupropion and erythrohydrobupropion are reached at 8 hours. The AUC and Cmax values of bupropion and its active metabolites hydroxybupropion and threohydrobupropion are proportional to the increase in dose in the dose range of 50-200 mg after a single dose and in the dose range of 300-450 mg/day after continuous administration.
The absolute bioavailability of bupropion is unknown, but urinary excretion data indicate that at least 87% of a bupropion dose is absorbed.
Taking bupropion modified-release tablets with food does not significantly affect the absorption of the drug.
Distribution
Bupropion is widely distributed – its volume of distribution is approximately 2000 liters.
Bupropion, hydroxybupropion, and threohydrobupropion are moderately bound to plasma proteins (84%, 77%, and 42%, respectively).
Bupropion and its metabolites are excreted in human breast milk. Animal studies indicate that bupropion and its active metabolites cross the blood-brain barrier and placenta. Positron emission tomography studies in healthy volunteers indicate that bupropion penetrates the central nervous system (CNS) and binds to the striatal dopamine reuptake transporter (approximately 25% at 150 mg twice daily).
Metabolism
Bupropion is extensively metabolized in humans. Three pharmacologically active metabolites have been identified in plasma: hydroxybupropion and amino alcohol isomers, threohydrobupropion, and erythrohydrobupropion. These may be of clinical significance because their plasma concentrations are as high or higher than those of bupropion. The active metabolites are further metabolized to inactive metabolites (some of which have not been fully characterized but may include conjugates) and are excreted in the urine.
In vitro studies indicate that bupropion is metabolized to its major active metabolite hydroxybupropion primarily by CYP2B6, with CYP1A2, 2A6, 2C9, 3A4, and 2E1 being involved to a lesser extent. In contrast, the formation of threohydrobupropion involves carbonyl reduction but does not involve cytochrome P450 isoenzymes (see section 4.5).
The inhibitory potential of threohydrobupropion and erythrohydrobupropion for cytochrome P450 has not been studied.
Bupropion and hydroxybupropion are inhibitors of the CYP2D6 isoenzyme with Ki values of 21 and 13.3 μM, respectively (see section “Interaction with other medicinal products and other types of interactions”).
Studies have shown that bupropion induces its own metabolism in animals after subchronic administration. In humans, there is no evidence of enzyme induction of bupropion or hydroxybupropion in healthy volunteers or patients receiving recommended doses of bupropion hydrochloride for 10-45 days.
Breeding
The mean apparent clearance after oral administration of bupropion hydrochloride is approximately 200 L/h, and the mean elimination half-life (T½) of bupropion is approximately 20 hours.
The T½ of hydroxybupropion is approximately 20 hours. The T½ of threohydrobupropion and erythrohydrobupropion is longer (37 and 33 hours, respectively), and the steady-state AUC values are 8 and 1.6 times higher than those of bupropion, respectively. Steady-state is reached for bupropion and its metabolites within 8 days.
The insoluble coating of the modified-release tablet may remain intact during passage through the gastrointestinal tract (GI) and be excreted in the feces.
Special patient groups
Elderly patients
Pharmacokinetic studies in the elderly have shown mixed results. A single-dose study showed that the pharmacokinetics of bupropion and its metabolites in the elderly did not differ from those in younger subjects. Another single- and multiple-dose pharmacokinetic study showed that accumulation of bupropion and its metabolites may occur to a greater extent in the elderly. Clinical experience has not revealed differences in tolerability between elderly and younger patients, but greater sensitivity in elderly patients cannot be excluded (see section 4.4).
Patients with renal insufficiency
The elimination of bupropion and its active major metabolites may be reduced in patients with renal impairment. Limited data in patients with end-stage renal disease or moderate to severe renal impairment suggest that the exposure to bupropion and/or its metabolites was increased (see section 4.4).
Patients with hepatic insufficiency
The pharmacokinetics of bupropion and its active metabolites were not statistically significantly different in patients with mild to moderate cirrhosis compared to healthy volunteers, although there was a large inter-patient variability (see section 4.4). In patients with severe cirrhosis, bupropion Cmax and AUC were significantly higher (mean difference of approximately 70% and 3-fold, respectively) and more variable than in healthy volunteers; the mean T½ was also longer (approximately 40%). For hydroxybupropion, the mean Cmax was lower (approximately 70%), the AUC was generally higher (approximately 30%), the median Tmax was later (approximately 20 hours), and the mean T½ was longer (approximately 4-fold) than in healthy volunteers. For threohydrobupropion and erythrohydrobupropion, mean Cmax was generally lower (approximately 30%), AUC was generally higher (approximately 50%), median Tmax was later (approximately 20 hours), and median T½ was longer (approximately 2-fold) than in healthy volunteers (see section 4.3).
In vitro release of bupropion with alcohol
In vitro studies have shown that at high alcohol concentrations (up to 40%) bupropion is released more rapidly from the modified-release formulation (up to 20% dissolved after 2 hours) (see section 4.5).
Indication
Buprinol is indicated for the treatment of depressive episodes (major depressive disorder).
Contraindication
The drug is contraindicated:
Patients with hypersensitivity to bupropion or any component of the drug;
patients receiving any other medicinal product containing bupropion, as the incidence of seizures is dose-dependent and to avoid overdose;
patients with existing seizure disorders or a history of seizures;
patients with known CNS tumors;
patients who, at any time during treatment, have suddenly stopped taking alcohol or any medicinal product known to be associated with a risk of seizures upon withdrawal (including benzodiazepines and benzodiazepine-like drugs);
patients with severe liver cirrhosis;
patients with current or history of bulimia nervosa or anorexia;
Simultaneously with MAO inhibitors. At least 14 days should elapse between the withdrawal of irreversible MAO inhibitors and the start of treatment with Buprinol. For reversible MAO inhibitors, a period of 24 hours is sufficient.
Interaction with other medicinal products and other types of interactions
Since MAO inhibitors A and B also activate catecholaminergic pathways, by a mechanism different from that of bupropion, the concomitant use of Buprinol and MAO inhibitors is contraindicated (see section "Contraindications"), as there is an increased likelihood of adverse reactions due to their concomitant use. At least 14 days should elapse between the withdrawal of irreversible MAO inhibitors and the initiation of treatment with Buprinol. For reversible MAO inhibitors, a period of 24 hours is sufficient.
Effects of bupropion on other drugs
Concomitant therapy with narrow therapeutic index drugs that are primarily metabolized by CYP2D6 should be initiated at the lower end of the dose range of the concomitant drug. Such drugs include: some antidepressants (e.g., desipramine, imipramine), antipsychotics (e.g., risperidone, thioridazine), beta-blockers (e.g., metoprolol), selective serotonin reuptake inhibitors (SSRIs), and type 1C antiarrhythmics (e.g., propafenone, flecainide). If Buprinol is added to the regimen of a patient already taking such a drug, a reduction in the dose of that drug should be considered. In these cases, the expected benefits of treatment with Buprinol should be carefully weighed against the potential risks.
There is evidence of the potentially life-threatening development of serotonin syndrome with the simultaneous use of Buprinol with serotonergic drugs such as SSRIs or serotonin-norepinephrine reuptake inhibitors (SNRIs) (see section "Special warnings and precautions for use").
Medicinal products that require metabolic activation by CYP2D6 (e.g. tamoxifen) may have reduced efficacy when co-administered with CYP2D6 inhibitors such as bupropion (see section 4.4).
Although citalopram (an SSRI) is not primarily metabolized by CYP2D6, in one study bupropion increased the Cmax and AUC of citalopram by 30% and 40%, respectively.
Concomitant use of digoxin with bupropion may result in decreased digoxin levels. In one clinical study, digoxin AUC0-24 was decreased and renal clearance was increased in healthy volunteers based on a cross-over comparison. The physician should be aware that digoxin levels may increase upon discontinuation of bupropion, and the patient should be closely monitored for signs of possible digoxin toxicity.
Effects of other drugs on bupropion
Bupropion is metabolized to its major active metabolite, hydroxybupropion, primarily by the cytochrome P450 CYP2B6 (see Pharmacokinetics). Concomitant use of medicinal products that may affect the metabolism of bupropion via the CYP2B6 isoenzyme (e.g. CYP2B6 substrates: cyclophosphamide, ifosfamide and CYP2B6 inhibitors: orphenadrine, ticlopidine, clopidogrel) may result in increased plasma levels of bupropion and decreased levels of the active metabolite hydroxybupropion. The clinical consequences of inhibition of bupropion metabolism via the CYP2B6 enzyme and, consequently, changes in the bupropion-hydroxybupropion ratio are currently unknown.
Since bupropion is extensively metabolized, caution is recommended when co-administering bupropion with drugs known to induce metabolism (e.g. carbamazepine, phenytoin, ritonavir, efavirenz) or inhibit metabolism (e.g. valproate) as this may affect its clinical efficacy and safety.
In a series of studies in healthy volunteers, ritonavir (100 mg twice daily or 600 mg twice daily) or ritonavir 100 mg co-administered with lopinavir 400 mg twice daily reduced the dose-dependent exposure of bupropion and its major metabolites by approximately 20-80% (see Pharmacokinetics). Similarly, efavirenz 600 mg once daily for 2 weeks reduced bupropion exposure by approximately 55% in healthy volunteers. The clinical implications of this reduction in exposure are unclear but may include reduced efficacy in the treatment of major depression. Patients taking either of these agents with bupropion may require an increase in the dose of bupropion, but the maximum recommended dose of bupropion should not be exceeded.
Other interaction information
Bupropion should be used with caution in patients receiving concomitant levodopa or amantadine therapy. Limited clinical data suggest a higher incidence of adverse reactions (e.g. nausea, vomiting and neuropsychiatric disorders - see section 4.8) in patients receiving bupropion concomitantly with levodopa or amantadine.
Although clinical data do not identify a pharmacokinetic interaction between bupropion and alcohol, there have been rare reports of adverse neuropsychiatric events or decreased alcohol tolerance in patients who consumed alcohol during bupropion treatment. Alcohol consumption should be minimized or avoided during bupropion treatment.
Pharmacokinetic studies of bupropion and benzodiazepines administered concomitantly have not been conducted.
Based on in vitro metabolic pathways, there is no evidence for such an interaction. After concomitant administration of bupropion with diazepam in healthy volunteers, sedation was less than with diazepam alone.
There has been no systematic evaluation of the combination of bupropion with antidepressants (except desipramine and citalopram), benzodiazepines (except diazepam), or neuroleptics. Clinical experience with the combination with St. John's wort is also limited.
Concomitant use of bupropion and nicotine transdermal system (NTS) may lead to an increase in blood pressure.
Application features
The recommended dose of bupropion should not be exceeded because bupropion is associated with a dose-dependent risk of seizures. The overall incidence of seizures with bupropion in clinical trials at doses up to 450 mg/day was approximately 0.1%.
In the presence of factors that lower the seizure threshold, there is an increased risk of seizures when using bupropion. Therefore, Buprinol should be used with caution in patients with one or more risk factors that lower the seizure threshold.
Before prescribing Buprinol, an assessment of the existing risk factors that lead to a lower seizure threshold for each patient should be conducted, which include:
Concomitant use of other drugs that lower the seizure threshold (e.g. antipsychotics, antidepressants, antimalarials, tramadol, theophylline, systemic steroids, quinolones and sedative antihistamines).
Alcohol abuse (see section "Contraindications").
History of traumatic brain injury.
Diabetes mellitus, which is treated with hypoglycemic drugs or insulin.
Use of stimulants or anorectics.
Buprinol should be discontinued and not used in patients who develop seizures during treatment.
Interactions (see section “Interaction with other medicinal products and other types of interactions”)
Due to pharmacokinetic interactions, the plasma levels of bupropion or its metabolites may change, which may increase the likelihood of adverse reactions (e.g., dry mouth, insomnia, seizures), so caution should be exercised when using bupropion concomitantly with drugs that may induce or inhibit the metabolism of bupropion.
Bupropion inhibits metabolism via the cytochrome P450 2D6 isoenzyme. Caution should be exercised when concomitantly administering drugs metabolized by this enzyme.
According to literature data, drugs that inhibit CYP2D6 may lead to a decrease in the concentration of endoxifen, which is the active metabolite of tamoxifen. Therefore, the use of bupropion, which is a CYP2D6 inhibitor, should be avoided if possible during tamoxifen treatment (see section "Interaction with other medicinal products and other forms of interaction").
Neuropsychiatry
Suicide/suicidal thoughts or clinical worsening
Depression is associated with an increased risk of suicidal thoughts and behavior and suicide (suicide-related events). This risk persists until significant remission occurs. Improvement may not occur during the first few weeks of treatment or even longer, and patients should be closely monitored for clinical worsening and suicidal tendencies until such improvement occurs. General clinical experience confirms an increased risk of suicide in the early stages of treatment.
Patients with a history of suicidal ideation or a significant level of suicidal ideation prior to initiation of treatment are known to be at increased risk of suicidal thoughts or suicide attempts and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials with antidepressants has shown an increased risk of suicidal behaviour in adult patients with psychiatric disorders treated with antidepressants compared to placebo in patients aged <25 years.
The use of Buprinol, especially in the early stages of treatment and after dose changes, should be accompanied by close monitoring of patients, especially those at high risk. Patients (and caregivers of patients) should be warned about the need to monitor for any worsening of symptoms, suicidal behavior or thoughts, and unusual changes in behavior. If such symptoms occur, they should seek medical attention immediately.
The appearance of some neuropsychiatric symptoms may be related to both the underlying disease and the treatment.
In patients who develop suicidal thoughts/behavior, consideration should be given to changing the treatment regimen, including the possibility of discontinuing treatment, especially if such symptoms are severe, develop suddenly, or if they were not part of the patient's presenting symptoms.
Neuropsychiatric symptoms have been reported (see section 4.8). Psychotic and manic states have been observed predominantly, especially in patients with a history of psychiatric illness. In addition, major depressive disorder may be the initial manifestation of bipolar disorder. It is generally believed (although not proven in controlled clinical trials) that treatment of such disorders with a single antidepressant may itself increase the likelihood of mixed/manic disorders in patients at risk of developing bipolar disorder. Limited clinical data on the use of bupropion in combination with mood stabilizers in patients with a history of bipolar disorder indicate a low likelihood of transition to mania. Before starting treatment with antidepressants, patients should be appropriately evaluated to determine whether they are at risk of developing bipolar disorder. Such evaluation should include detailed psychiatric history, including family history, suicide, bipolar disorder and depression.
Animal studies suggest the potential for bupropion to be addictive. However, human abuse potential studies and extensive clinical experience indicate that bupropion has a low abuse potential.
Clinical experience with bupropion in patients receiving electroconvulsive therapy (ECT) is limited. Therefore, bupropion should be used with caution in patients receiving ECT.
Hypersensitivity
Patients who develop hypersensitivity reactions while taking Buprinol should discontinue use immediately. The physician should be aware that symptoms may worsen or return after stopping Buprinol and should provide symptomatic treatment for an appropriate period of time (at least one week). Typical symptoms include skin rash, itching, urticaria or chest pain, but serious adverse reactions may also occur, including angioedema (Quincke's edema), dyspnoea/bronchospasm, anaphylactic shock, erythema multiforme or Stevens-Johnson syndrome. In addition, arthralgia, myalgia and fever have been reported in association with rash and other symptoms suggestive of a delayed-type hypersensitivity reaction (see section 4.8). In most patients, symptoms decreased and gradually disappeared over time after stopping bupropion and starting treatment with antihistamines or corticosteroids.
Cardiovascular disorders
There are limited clinical data on the treatment of depression with bupropion in patients with cardiovascular disease. Caution should be exercised when treating this group of patients. However, in smoking cessation studies, bupropion was generally well tolerated in patients with ischemic cardiovascular disease.
Blood pressure
In studies of non-depressed patients with stage 1 hypertension who received bupropion, no significant increase in blood pressure was observed. However, in clinical practice, hypertension has been observed in patients receiving bupropion, which in some cases was severe (see section 4.8) and required emergency treatment. This has been observed in both patients with and without pre-existing hypertension.
Baseline blood pressure should be established at baseline and monitored regularly, especially in patients with hypertension. Consideration should be given to discontinuing Buprinol if a clinically significant increase in blood pressure is observed.
Concomitant use of bupropion with nicotine patches may lead to an increase in blood pressure.
Brugada syndrome
Bupropion may induce Brugada syndrome, a rare inherited sodium channel disease of the heart with characteristic ECG changes (right bundle branch block and ST segment elevation in the right precordial leads), which can lead to cardiac arrest or sudden death.
Special patient groups
Pediatric patients
Antidepressant treatment of children and adolescents with major depressive disorder and other psychiatric disorders is associated with an increased risk of suicidal thoughts and behavior.
Patients with liver dysfunction
Bupropion is metabolized in the liver to active metabolites with their further metabolism. No statistically significant differences were observed between the pharmacokinetics of bupropion in patients with mild to moderate liver cirrhosis and in healthy volunteers. The level of bupropion in the blood plasma varied more between individual patients, therefore the drug Buprinol should be used with caution in patients with mild to moderate liver dysfunction (see section "Method of administration and dosage").
All patients with hepatic impairment should be monitored regularly for possible adverse reactions (e.g. insomnia, dry mouth, seizures) that may indicate elevated levels of bupropion or its metabolites.
Bupropion is excreted primarily in the urine as metabolites. Therefore, bupropion and its active metabolites may accumulate to a greater extent than usual in patients with impaired renal function. All patients should be carefully monitored for possible adverse reactions (e.g. insomnia, dry mouth, seizures) that may indicate high levels of the active substance or its metabolites (see section 4.2).
Elderly patients
The efficacy of bupropion in elderly patients is controversial. In clinical trials, elderly patients followed the same treatment regimen as adult patients, but greater sensitivity in some elderly patients cannot be ruled out.
Effect on urinalysis
Because bupropion has a chemical structure similar to that of amphetamine, it interferes with the analytical method used in some rapid urine tests. This can lead to false-positive results, especially for amphetamines. A positive result should usually be confirmed by more accurate methods.
Incorrect route of administration
Buprinol is for oral use only. Inhalation of crushed tablets or injection of dissolved bupropion has been reported, which may result in faster release, faster absorption, and potential overdose. Seizures and/or fatalities have been reported with intranasal or parenteral administration of bupropion.
Serotonin syndrome
Cases of potentially life-threatening serotonin syndrome have been reported in the post-marketing setting with the concomitant use of bupropion and serotonergic medicinal products such as SSRIs or SSRIsN (see section 4.5). If concomitant treatment with other serotonergic agents is clinically warranted, close monitoring of the patient is recommended, particularly at the start of treatment and in the event of dose increases.
Serotonin syndrome may include changes in mental status (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, blood pressure fluctuations, hyperthermia), neuromuscular abnormalities (e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). If serotonin syndrome is suspected, dose reduction or discontinuation should be considered, depending on the severity of symptoms.
Use during pregnancy or breastfeeding
Pregnancy
Some epidemiological studies of pregnancy outcomes following exposure to bupropion during the first trimester of pregnancy have shown an association with an increased risk of certain congenital cardiovascular malformations, including ventricular septal defects and left ventricular outflow tract defects. However, these findings are inconsistent across studies. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Buprinol should not be used during pregnancy unless the clinical condition of the woman requires treatment with bupropion and there are no alternative treatments.
Breastfeeding period
Bupropion and its metabolites are excreted in human milk. A decision must be made whether to discontinue breast-feeding or to discontinue bupropion therapy taking into account the benefit of breast-feeding for the newborn/infant and the benefit of bupropion therapy for the mother.
Fertility
There are no data on the effects of bupropion on human fertility. Reproductive toxicity studies conducted in rats did not confirm a negative effect on fertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
As with other drugs that affect the central nervous system, bupropion may affect the ability to perform tasks requiring increased attention and coordination of movements. Therefore, patients should be careful when driving or operating machinery until they are sure that Buprinol does not affect their attention and coordination of movements.
Method of administration and doses
Dosage
Adults
The recommended initial dose is 150 mg once daily. The optimal dose has not been established in clinical studies. If no improvement is observed after 4 weeks of treatment with 150 mg of Buprinol, the dose can be increased to 300 mg, given once daily. There should be an interval of at least 24 hours between consecutive doses.
The onset of action of bupropion was noted 14 days after the start of therapy. As with all other antidepressants, the full antidepressant effect of Buprinol is not apparent until several weeks of treatment.
Patients with depression should receive treatment for a sufficient period of time, at least 6 months, to ensure that their symptoms are no longer present.
Transition of patients taking bupropion extended-release tablets for the treatment of depression
When switching patients from taking bupropion extended-release tablets twice daily to Buprinol, the same total daily dose should be administered whenever possible.
Pediatric patients
Buprinol is not indicated for use in children or adolescents under 18 years of age (see section 4.4). The safety and efficacy of Buprinol in patients under 18 years of age have not been established.
Elderly patients
The drug has shown mixed efficacy in elderly patients. In a clinical study, elderly patients followed the same dosing regimen as adult patients. Greater sensitivity in some elderly patients cannot be ruled out.
Patients with liver dysfunction
Patients with impaired liver function should use Buprinol with caution (see section "Special warnings and precautions for use").
Due to increased pharmacokinetic variability in patients with mild to moderate hepatic impairment, the recommended dose for these patients is 150 mg once daily.
Patients with renal impairment
The recommended dose for patients with renal impairment is 150 mg once daily, as bupropion and its active metabolites may accumulate to a greater extent in such patients than usual (see section 4.4).
Method of application
The tablets should be swallowed whole. The tablets should not be cut, crushed or chewed as this may lead to an increased risk of adverse reactions, including seizures.
Buprinol can be taken regardless of food intake.
Discontinuation of treatment
Although withdrawal symptoms, which were reported spontaneously and not systematically, were not observed in clinical trials with bupropion, the possibility of gradual withdrawal may be considered. Bupropion selectively inhibits neuronal reuptake of catecholamines. Therefore, withdrawal symptoms cannot be ruled out.
Children.
Bupropion is not indicated for use in children or adolescents under 18 years of age (see section 4.4). The safety and efficacy of bupropion in patients under 18 years of age have not been established.
Overdose
Doses as high as 10 times the maximum therapeutic dose have been reported. In addition to those reported as adverse reactions, overdose has resulted in symptoms such as drowsiness, loss of consciousness and/or electrocardiogram (ECG) changes such as conduction disturbances (including QRS prolongation), arrhythmia and tachycardia. QT prolongation has also been reported, but usually in association with QRS prolongation and increased heart rate.
Although most patients recovered without complications, there have been rare reports of fatal outcomes associated with bupropion, which have occurred in patients taking high doses of the drug.
Treatment: In case of overdose, hospitalization is recommended. ECG and vital signs should also be monitored. Adequate airway patency, oxygenation, and ventilation should be ensured. Activated charcoal is recommended. There is no specific antidote for bupropion. Further patient care should be provided as clinically indicated.
Adverse reactions
The following adverse reactions have been identified in clinical experience and are classified according to frequency and system organ class. Adverse reactions are classified according to frequency and convention: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000); frequency unknown (cannot be estimated from the available data).
Blood and lymphatic system disorders:
Frequency unknown: Anemia, leukopenia and thrombocytopenia.
Immune system disorders*:
Common: Hypersensitivity reactions such as urticaria;
Very rare: More severe hypersensitivity reactions including angioedema, dyspnoea/bronchospasm and anaphylactic shock. Arthralgia, myalgia and
