Dosage and administration
Wellbutrin tablets are swallowed whole, not chewed, not breaking or grinding, as this may lead to an increased risk of adverse reactions, including convulsive disorders.
Treatment of depression
The clinical effect appears 14 days after the start of therapy. As with all antidepressants, the antidepressant effect may occur after several weeks of treatment.
The maximum single dose of sustained release bupropion should be no more than 450 mg. The interval between doses of the drug should be at least 24 hours after the last dose. Increase the dose should not be more than 100 mg per day for three days.
- Start of treatment: Wellbutrin starting dose is 150 mg once a day, in the morning. If an adequate therapeutic response is not achieved, it is recommended to increase the dose to the usual target dose for adults, 300 mg per day, 1 time per day.
- Increasing the dose above 300 mg per day: increasing the dose to a maximum daily 450 mg 1 time per day is possible for patients who do not show clinical improvement after several weeks of therapy at a dose of 300 mg per day.
- Maintenance Therapy: acute episodes of depression require continuous treatment for a duration of 6 months after reaching the initial therapeutic response. The effectiveness of bupropion (300 mg per day) has been proven with long-term therapy (up to 1 year).
Kids and teens
The safety and effectiveness of bupropion in patients under the age of 18 years has not been established.
Treatment of depression in special patient groups
- Elderly patients: Elderly patients are more likely to develop a hypersensitivity reaction, therefore, the dose or frequency of Wellbutrin should be reduced.
- Patients with impaired renal function: the treatment of such patients should be started with a lower dose of the drug, since bupropion and its metabolites may accumulate in such patients to a greater extent than usual. The dose of the drug for these patients should not exceed 150 mg 1 time per day.
- Patients with impaired liver function. Due to the fact that the difference in pharmacokinetics increases in patients with impaired mild or moderate liver function, they may require an increase in the interval between doses of the drug.
- The dose of Wellbutrin in patients with severe liver cirrhosis should not exceed 150 mg 1 time in 2 days.
Special instructions when taking Wellbutrin
Do not exceed the recommended dose of bupropion, since the risk of seizures due to its reception is dose-dependent. In general, the incidence of seizures when taking Wellbutrin tablets at a dose of 450 mg per day in clinical studies was approximately 0.1%.
The occurrence of seizures resulting from the use of bupropion is associated with the presence of risk factors. Therefore, bupropion should be administered with extreme caution to patients who have one or more conditions that reduce the threshold of convulsive readiness, including:
- traumatic brain injuries in history;
- CNS tumors;
- convulsive disorders in history;
- concomitant therapy with other drugs that reduce the threshold of convulsive readiness.
In addition, caution must be exercised in clinical situations involving an increased risk of seizures, including the abuse of alcohol or sedatives, the use of hypoglycemic drugs or insulin, and the use of stimulants or drugs to reduce appetite (sibutramine). If convulsions occur during treatment, bupropion should be discontinued, and resumption of bupropion therapy is not recommended.
With the development of hypersensitivity reactions, Wellbutrin should be canceled immediately. The physician should be aware that the symptoms may persist after discontinuation of the drug, and appropriate medical intervention may be required.
Liver function disorders
Bupropion is extensively metabolized in the liver to form active metabolites, which are further metabolized. Wellbutrin should be used with caution in patients with impaired liver function, it is necessary to resolve the issue of increasing the intervals between taking in patients with mild and moderately impaired liver function.
The drug should be used with extreme caution in patients with severe cirrhosis of the liver. In such patients, a reduction in the frequency of administration is required, since the maximum concentrations of bupropion are significantly increased, and cases of cumulation in such patients are more frequent than usual. All patients with impaired liver function should be carefully monitored for the development of undesirable reactions (eg, insomnia, dry mouth, seizures), which may be a sign of high concentrations of bupropion or its metabolites.
Patients with impaired renal function and elderly patients
Bupropion undergoes intensive metabolism in the liver to form active metabolites, which are subsequently excreted by the kidneys. Therefore, treatment of patients with impaired renal function should be initiated with lower doses, since bupropion and its metabolites may accumulate in the body in such patients more often than usual. Such patients should be carefully monitored for the development of undesirable reactions (for example, insomnia, dry mouth, seizures), which may be signs of high concentrations of bupropion or its metabolites.
Clinical studies did not reveal differences in the tolerability of bupropion in elderly and younger patients. However, the possibility of hypersensitivity in some elderly patients cannot be ruled out; therefore, it may be necessary to reduce the dose or frequency of taking the drug.
Use in children and adolescents under the age of 18
Treatment with antidepressants is associated with an increased risk of suicidal thoughts and behavior in children and adolescents with major depressive disorder and other mental disorders.
Clinical deterioration and suicidal risk associated with mental disorders in adults
In patients with depression, exacerbation of the symptoms of the disease and / or the appearance of suicidal thoughts and suicidal behavior can be observed regardless of whether they receive antidepressants. Because improvement may not occur within the first few weeks of treatment or longer, patients should be carefully monitored for clinical deterioration (including the development of new symptoms) and suicidal behavior / thoughts, especially at the beginning of the course of treatment and during dose changes (increases or decreases in ). This risk persists until a pronounced remission is achieved. Clinical experience with all antidepressants shows that suicidal risk may increase in the early stages of recovery.
Patients with a history of suicidal behavior or suicidal thoughts, young patients, as well as patients with suicidal thoughts before treatment are most at risk of suicide. Such patients should be closely monitored during treatment. In addition, a meta-analysis of placebo-controlled clinical trials of antidepressant use in adult patients with major depression or other mental disorders showed an increased risk of suicidal thoughts and behavior associated with taking antidepressants compared with placebo in patients younger than 25 years of age.
Patients and caregivers should be warned about the need for close monitoring of the condition of patients (including the emergence of new symptoms), and in case of deterioration of their condition and / or the appearance of suicidal thoughts / behavior or auto-aggression, and if they occur, contact immediately for medical care.
These symptoms may be associated with both the underlying disease and the drug therapy being administered.
In the case of clinical deterioration (including the appearance of new symptoms) and / or the emergence of suicidal thoughts / behavior, especially if the symptoms are severe, have a sudden onset and have not manifested before treatment, it is necessary to make a decision to change the treatment regimen, including possible Wellbutrin.
Mental disorders, including mania and bipolar disorder
Psychotic disorders and mania were observed, mainly in patients with a history of mental illness. In addition, a major depressive episode may be the initial manifestation of bipolar disorder. It is generally accepted (although this has not been proven in controlled clinical studies) that treating such an episode with antidepressants alone can increase the likelihood of accelerated development of a mixed / manic episode in patients at risk for bipolar disorder.
Limited clinical data on the use of bupropion in combination with mood stabilizers in patients with bipolar disorder in history show a low frequency of transition to the manic phase. Before treatment, a thorough screening should be conducted to assess the risk of bipolar disorder (including data on suicides, bipolar disorder, and family history of depression).
There are limited clinical data on the use of bupropion for the treatment of depression in patients with cardiovascular diseases. Care must be taken when applying bupropion in such patients. However, bupropion was generally well tolerated in quit smoking studies in patients with coronary heart disease. In studies in non-depressed patients (including both smokers and non-smokers) with grade 1 untreated hypertension, bupropion did not have a statistically significant effect on blood pressure. However, in the course of routine observation, there have been cases of increased blood pressure (sometimes severe). Concomitant use of bupropion and the nicotinic transdermal system may cause an increase in blood pressure.
Before prescribing a combination of bupropion and the nicotinic transdermal system in order to treat nicotine addiction, information on the use of the corresponding transdermal system must be taken into account; BP monitoring should be provided.
Rare cases of neurological and mental disorders, as well as reduced tolerance to alcohol in patients receiving bupropion have been reported. During treatment with Wellbutrin, you must minimize or avoid alcohol.
Influence on ability to drive motor transport and control mechanisms
Like other drugs that affect the central nervous system, Wellbutrin can adversely affect the ability to perform tasks that require clarity of consciousness, as well as physical activity and cognitive skills. Patients should be careful when driving and / or other mechanisms.
- Bupropion undergoes metabolism with the formation of its main active metabolite hydroxybupropion, mainly with the participation of the P450 IIB6 isoenzyme (CYP2B6). Therefore, care should be taken with the simultaneous appointment of Wellbutrin with drugs that affect the activity of the CYP2B6 isoenzyme (for example, orphenadrine, cyclophosphamide, ifosfamide, ticlopidine, clopidogrel).
- In an in vitro study of the P450 enzyme system, bupropion and hydroxybupropion have been shown to be inhibitors of the metabolism of the CYP2D6 isoenzyme.
- Simultaneous use of bupropion with drugs that are predominantly metabolized by CYP2D6 isoenzyme (such as beta-blockers (for example, metoprolol), antiarrhythmic agents, selective serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics) should be started when reaching the bottom of the lower range; . If Wellbutrin therapy joins an already taken treatment regimen with a drug that is metabolized by CYP2D6 isoenzyme, it is necessary to consider reducing the dose of the concomitant drug, which is especially important for drugs with a narrow therapeutic index.
- Despite the fact that citalopram does not undergo preferential metabolism by means of the CYP2D6 isoenzyme, in one study it was found that with the use of bupropion, its Cmax and AUC were increased by 30% and 40%, respectively.
- Since bupropion undergoes active metabolism, the simultaneous administration of drugs, inducers (for example, carbamazepine, phenobarbital, phenytoin, ritonavir, efavirenz) or inhibitors of cytochrome P450 isoenzymes can affect the therapeutic effect of Wellbutrin.
- In studies involving healthy volunteers, taking ritonavir (in doses of 100 mg 2 times a day or 600 mg 2 times a day) or a combination of ritonavir (100 mg) and lopinavir (400 mg) 2 times a day reduced the exposure of bupropion and its metabolites, depending on from a dose of approximately 20-80%. Efavirenz (at a dose of 600 mg 1 time per day) for two weeks reduced the exposure to bupropion by approximately 55%. This effect is presumably mediated by the induction of the metabolism of bupropion. As a result, patients receiving these drugs may require a higher dose of bupropion, but the dose should not exceed the maximum.
- Limited clinical data revealed an increase in the incidence of neuropsychiatric adverse reactions in patients receiving bupropion simultaneously with levodopa or amantadine. Care must be taken with the concomitant administration of Wellbutrin to patients receiving Levodopa or Amantadine.
- Repeated doses of bupropion did not have a statistically significant effect on lamotrigine single-dose pharmacokinetics: in 12 patients, the AUC of glucoronide lamotrigine increased only slightly.
- The simultaneous use of Wellbutrin and the nicotinic transdermal system may cause an increase in blood pressure.
- Drugs that require metabolic activation through a CYP2D6 isoenzyme (for example, tamoxifen) may be less effective when taken orally with inhibitors of CYF2D6, such as bupropion.