Wellbutrin SR
Name: Wellbutrin SR
- Wellbutrin SR side effects
- Wellbutrin SR drug
- Wellbutrin SR effects of
- Wellbutrin SR the effects of
- Wellbutrin SR wellbutrin sr side effects
- Wellbutrin SR weight loss
- Wellbutrin SR used to treat
- Wellbutrin SR is used to treat
- Wellbutrin SR missed dose
- Wellbutrin SR wellbutrin sr dosage
- Wellbutrin SR 200 mg
- Wellbutrin SR tablet
- Wellbutrin SR injection
- Wellbutrin SR dosage
- Wellbutrin SR 400 mg
- Wellbutrin SR 150 mg
- Wellbutrin SR oral dose
- Wellbutrin SR adverse effects
- Wellbutrin SR side effects of wellbutrin sr
- Wellbutrin SR effects of wellbutrin sr
Before Using Wellbutrin SR
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:
Allergies
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Pediatric
Appropriate studies have not been performed on the relationship of age to the effects of bupropion in the pediatric population. However, children are more sensitive to the effects of this medicine than adults when used for treating depression. Use of bupropion to treat depression in children is not recommended. Safety and efficacy of bupropion to help stop smoking have not been established in children.
Geriatric
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of bupropion in the elderly. However, elderly patients may be more sensitive to the effects of this medicine and are more likely to have age-related kidney or liver problems, which may require caution and an adjustment in the dose for patients receiving bupropion.
Pregnancy
| Pregnancy Category | Explanation | |
|---|---|---|
| All Trimesters | C | Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women. |
Breast Feeding
There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.
Interactions with Medicines
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
- Bromopride
- Furazolidone
- Iproniazid
- Isocarboxazid
- Linezolid
- Methylene Blue
- Metoclopramide
- Moclobemide
- Nialamide
- Phenelzine
- Procarbazine
- Rasagiline
- Selegiline
- Tranylcypromine
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Acetophenazine
- Aclidinium
- Acrivastine
- Alcaftadine
- Amantadine
- Ambenonium
- Amdinocillin
- Amdinocillin Pivoxil
- Amiloride
- Amineptine
- Aminophylline
- Amitriptyline
- Amitriptylinoxide
- Amoxapine
- Amphetamine
- Ampicillin
- Anisotropine
- Antazoline
- Aripiprazole
- Astemizole
- Atomoxetine
- Atropine
- Azatadine
- Azelastine
- Azlocillin
- Bacampicillin
- Belladonna Alkaloids
- Benperidol
- Benzphetamine
- Bepotastine
- Betamethasone
- Brexpiprazole
- Bromodiphenhydramine
- Bromperidol
- Brompheniramine
- Buclizine
- Budesonide
- Bupivacaine
- Butriptyline
- Butylscopolamine
- Carbamazepine
- Carbenicillin
- Carbimazole
- Carbinoxamine
- Carvedilol
- Chlorambucil
- Chlorotrianisene
- Chlorpheniramine
- Chlorphenoxamine
- Cimetidine
- Cimetropium
- Cinnarizine
- Citalopram
- Clemastine
- Clemizole
- Clidinium
- Clobetasone
- Clomipramine
- Clopidogrel
- Cloxacillin
- Clozapine
- Codeine
- Conjugated Estrogens
- Corticotropin
- Cortisone
- Cosyntropin
- Cyclacillin
- Cyclizine
- Cyclosporine
- Cyproheptadine
- Danazol
- Darifenacin
- Deflazacort
- Delavirdine
- Demecarium
- Desipramine
- Desonide
- Desvenlafaxine
- Deutetrabenazine
- Dexamethasone
- Dexbrompheniramine
- Dexchlorpheniramine
- Dextroamphetamine
- Dextromethorphan
- Dibenzepin
- Dicloxacillin
- Dicyclomine
- Dienestrol
- Diethylstilbestrol
- Dimenhydrinate
- Diphenhydramine
- Diphenylpyraline
- Distigmine
- Donepezil
- Dopamine
- Dothiepin
- Doxepin
- Doxorubicin
- Doxorubicin Hydrochloride Liposome
- Doxylamine
- Droperidol
- Duloxetine
- Ebastine
- Echothiophate
- Edrophonium
- Efavirenz
- Eliglustat
- Emedastine
- Enflurane
- Epinastine
- Escitalopram
- Esterified Estrogens
- Estradiol
- Estramustine
- Estriol
- Estrone
- Estropipate
- Ethinyl Estradiol
- Famotidine
- Fesoterodine
- Flavoxate
- Flecainide
- Floxacillin
- Fludrocortisone
- Flunarizine
- Flunisolide
- Fluoxetine
- Fluticasone
- Fluvoxamine
- Fosphenytoin
- Galantamine
- Glycopyrrolate
- Guanidine
- Haloperidol
- Hetacillin
- Homatropine
- Hydrocortisone
- Hydroxyzine
- Hyoscyamine
- Imipramine
- Indalpine
- Iobenguane I 123
- Isoflurophate
- Isoniazid
- Isopropamide
- Ketamine
- Ketotifen
- Levocabastine
- Levodopa
- Levomilnacipran
- Lidocaine
- Lindane
- Lisdexamfetamine
- Lofepramine
- Lopinavir
- Loxapine
- Mebeverine
- Mebhydrolin
- Meclizine
- Memantine
- Mepenzolate
- Mestranol
- Metformin
- Methamphetamine
- Methantheline
- Methdilazine
- Methenolone
- Methicillin
- Methimazole
- Methixene
- Methylphenidate
- Methylprednisolone
- Methyltestosterone
- Metronidazole
- Mexiletine
- Mezlocillin
- Milnacipran
- Mizolastine
- Nafcillin
- Nalidixic Acid
- Nandrolone
- Nebivolol
- Nefazodone
- Neostigmine
- Niaprazine
- Nortriptyline
- Olopatadine
- Ondansetron
- Opipramol
- Ospemifene
- Oxacillin
- Oxaliplatin
- Oxandrolone
- Oxatomide
- Oxybutynin
- Oxymetholone
- Paramethasone
- Paroxetine
- Penicillin G
- Penicillin V
- Phenindamine
- Pheniramine
- Phenobarbital
- Phenyltoloxamine
- Phenytoin
- Physostigmine
- Pimozide
- Pinaverium
- Pindolol
- Piperacillin
- Pirenzepine
- Pivampicillin
- Pizotyline
- Polyestradiol Phosphate
- Prasugrel
- Prednisolone
- Prednisone
- Procainamide
- Procaine
- Promestriene
- Promethazine
- Propafenone
- Propantheline
- Propicillin
- Propiverine
- Propizepine
- Propranolol
- Protriptyline
- Pyrilamine
- Quinestrol
- Ranitidine
- Regorafenib
- Rimexolone
- Risperidone
- Ritonavir
- Rivastigmine
- Scopolamine
- Sertraline
- Sibutramine
- Solifenacin
- Sorafenib
- Stanozolol
- Sultamicillin
- Tacrine
- Terfenadine
- Testosterone
- Theophylline
- Thioridazine
- Thiotepa
- Thonzylamine
- Tibolone
- Ticarcillin
- Ticlopidine
- Timiperone
- Tiotropium
- Tolterodine
- Tramadol
- Trimeprazine
- Trimipramine
- Tripelennamine
- Triprolidine
- Tropicamide
- Trospium
- Umeclidinium
- Valbenazine
- Valethamate
- Varenicline
- Venlafaxine
- Vortioxetine
Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Aripiprazole Lauroxil
- Digoxin
- Isavuconazonium Sulfate
- St John's Wort
- Tipranavir
- Zolpidem
Interactions with Food/Tobacco/Alcohol
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.
- Ethanol
Other Medical Problems
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:
- Alcohol use, if stopped suddenly, or
- Eating disorders (eg, anorexia, bulimia), history of or
- Seizures, history of or
- Seizure medicine use, if stopped suddenly (eg, carbamazepine (Tegretol®), phenobarbital, phenytoin (Dilantin®)), or
- Sleeping or anxiety medicine use, if stopped suddenly (eg, alprazolam (Xanax®), lorazepam (Ativan®), temazepam (Restoril®), triazolam (Halcion®))—Should not be used in patients with these conditions.
- Arteriovenous malformation (circulation problem) or
- Brain tumor or infection or
- Diabetes or
- Drug or alcohol abuse or
- Head injury, severe or
- Hypoglycemia (low blood sugar) or
- Hyponatremia (low sodium in the blood) or
- Hypoxia (low oxygen in the blood) or
- Liver disease, severe
- Stroke, history of—May increase the risk of seizures.
- Bipolar disorder (type of depression), or risk of or
- Glaucoma, angle closure or
- Hypertension (high blood pressure) or
- Mania or hypomania (type of mental disease), history of or
- Psychosis (type of mental disease) or
- Schizophrenia (type of mental disease)—Use with caution. May make these conditions worse.
- Kidney disease or
- Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
Precautions While Using Wellbutrin SR
It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly and to check for unwanted effects.
Do not take bupropion with a monoamine oxidase (MAO) inhibitor (eg, isocarboxazid [Marplan®], linezolid [Zyvox®], phenelzine [Nardil®], selegiline [Eldepryl®], tranylcypromine [Parnate®]). Do not start taking bupropion during the 2 weeks after you stop a MAO inhibitor. Wait for 2 weeks after stopping bupropion before you start taking a MAO inhibitor. If you take them together or do not wait 2 weeks, you may have confusion, agitation, restlessness, stomach or bowel symptoms, a sudden high body temperature, an extremely high blood pressure, or severe convulsions.
Check with your doctor before using this medicine with alcohol or other medicines that affect the central nervous system (CNS). The use of alcohol or other medicines that affect the CNS with bupropion may worsen the side effects of this medicine, such as dizziness, poor concentration, drowsiness, unusual dreams, and trouble with sleeping. Some examples of medicines that affect the CNS are antihistamines or medicine for allergies or colds, sedatives, tranquilizers, or sleeping medicines, medicine for depression, medicine for anxiety, prescription pain medicine or narcotics, medicine for attention deficit and hyperactivity disorder, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics.
Bupropion may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies, or to become more depressed. Make sure the doctor knows if you have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. Also tell your doctor if you have sudden or strong feelings, such as feeling nervous, angry, restless, violent, or scared. If you or your caregiver notice any of these side effects, tell your doctor right away.
Your blood pressure might get too high while you are using this medicine. This may cause headaches, dizziness, or blurred vision. You might need to measure your blood pressure at home. If you think your blood pressure is too high, call your doctor right away.
This medicine may cause a serious type of allergic reaction called anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, swelling of the face, tongue, or throat, trouble breathing, or chest pain.
Serious skin reactions can occur with this medicine. Check with your doctor right away if you have blistering, peeling, or loosening of the skin, red skin lesions, severe acne or a skin rash, sores or ulcers on the skin, or fever or chills with this medicine.
Drinking alcoholic beverages should be limited or avoided, if possible, with bupropion. This will help prevent seizures.
This medicine may cause some people to have a false sense of wellbeing, or to become drowsy, dizzy, or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are drowsy, dizzy, or less alert.
Do not stop taking this medicine without checking first with your doctor. Your doctor may want you to gradually reduce the amount you are taking before stopping it completely. This is to decrease the chance of having certain side effects when you stop the medicine, such as agitation, anxiety, dizziness, a feeling of constant movement of self or surroundings, headaches, increased sweating, nausea, trembling or shaking, trouble with sleeping or walking, or unusual tiredness.
Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, unusual tiredness or weakness, or yellow eyes or skin. These could be symptoms of a serious liver problem.
This medicine may cause a change in your appetite or weight. Your doctor may need to check your weight on a regular basis.
Before you have any medical tests, tell the medical doctor in charge that you are taking this medicine. The results of some tests may be affected by this medicine.
Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.
Wellbutrin SR Side Effects
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
More common- Anxiety
- dry mouth
- hyperventilation
- irregular heartbeats
- irritability
- restlessness
- shaking
- trouble sleeping
- Buzzing or ringing in the ears
- headache (severe)
- skin rash, hives, or itching
- Confusion
- fainting
- false beliefs that cannot be changed by facts
- having extreme distrust of people
- seeing, hearing, or feeling things that are not there
- seizures
- trouble concentrating
- Actions that are out of control
- anger
- assaulting or attacking others
- being aggressive or impulsive
- chest pain or discomfort
- fast or pounding heartbeat
- force
- inability to sit still
- need to keep moving
- sweating
- talking, feeling, or acting with excitement
Get emergency help immediately if any of the following symptoms of overdose occur:
Symptoms of overdose- Lightheadedness, dizziness, or fainting
- loss of consciousness
- slow or irregular heartbeat
- unusual tiredness
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common- Constipation
- decrease in appetite
- dizziness
- increased sweating
- stomach pain
- trembling
- unusual weight loss
- Blurred vision
- change in sense of taste
- drowsiness
- frequent need to urinate
- sore throat
- unusual feeling of well-being
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
Uses of Wellbutrin SR
- It is used to treat low mood (depression).
- It may be given to you for other reasons. Talk with the doctor.
How is this medicine (Wellbutrin SR) best taken?
Use Wellbutrin SR as ordered by your doctor. Read all information given to you. Follow all instructions closely.
- Do not take this medicine more often than you are told. This may raise the risk of seizures. Be sure you know how far apart to take your doses.
- Take in the morning if taking once a day.
- Take with or without food.
- If you are not able to sleep, do not take Wellbutrin SR too close to bedtime. Talk with your doctor.
- Swallow whole. Do not chew, break, or crush.
- To gain the most benefit, do not miss doses.
- Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
- If you have trouble swallowing, talk with your doctor.
What do I do if I miss a dose?
- Skip the missed dose and go back to your normal time.
- Do not take 2 doses at the same time or extra doses.
Wellbutrin SR Dosage and Administration
General Instructions for Use
To minimize the risk of seizure, increase the dose gradually [see Warnings and Precautions (5.3)]. WELLBUTRIN SR tablets should be swallowed whole and not crushed, divided, or chewed. Wellbutrin SR may be taken with or without food.
The usual adult target dose for WELLBUTRIN SR is 300 mg per day, given as 150 mg twice daily. Initiate dosing with 150 mg per day given as a single daily dose in the morning. After 3 days of dosing, the dose may be increased to the 300-mg-per-day target dose, given as 150 mg twice daily. There should be an interval of at least 8 hours between successive doses. A maximum of 400 mg per day, given as 200 mg twice daily, may be considered for patients in whom no clinical improvement is noted after several weeks of treatment at 300 mg per day. To avoid high peak concentrations of bupropion and/or its metabolites, do not exceed 200 mg in any single dose.
It is generally agreed that acute episodes of depression require several months or longer of antidepressant drug treatment beyond the response in the acute episode. It is unknown whether the dose of WELLBUTRIN SR needed for maintenance treatment is identical to the dose that provided an initial response. Periodically reassess the need for maintenance treatment and the appropriate dose for such treatment.
Dose Adjustment in Patients with Hepatic Impairment
In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose of Wellbutrin SR is 100 mg per day or 150 mg every other day. In patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].
Dose Adjustment in Patients with Renal Impairment
Consider reducing the dose and/or frequency of Wellbutrin SR in patients with renal impairment (Glomerular Filtration Rate less than 90 mL per min) [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Antidepressant
At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of therapy with Wellbutrin SR. Conversely, at least 14 days should be allowed after stopping Wellbutrin SR before starting an MAOI antidepressant [see Contraindications (4), Drug Interactions (7.6)].
Use of Wellbutrin SR with Reversible MAOIs Such as Linezolid or Methylene Blue
Do not start Wellbutrin SR in a patient who is being treated with a reversible MAOI such as linezolid or intravenous methylene blue. Drug interactions can increase the risk of hypertensive reactions. In a patient who requires more urgent treatment of a psychiatric condition, non-pharmacological interventions, including hospitalization, should be considered [see Contraindications (4), Drug Interactions (7.6)].
In some cases, a patient already receiving therapy with Wellbutrin SR may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of hypertensive reactions in a particular patient, Wellbutrin SR should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with Wellbutrin SR may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue.
The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg per kg with Wellbutrin SR is unclear. The clinician should, nevertheless, be aware of the possibility of a drug interaction with such use [see Contraindications (4), Drug Interactions (7.6)].
Contraindications
Warnings and Precautions
Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults
Patients with MDD, both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment.
Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (selective serotonin reuptake inhibitors [SSRIs] and others) show that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with MDD and other psychiatric disorders. Short-term clinical trials did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults beyond age 24; there was a reduction with antidepressants compared with placebo in adults aged 65 and older.
The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short‑term trials of 9 antidepressant drugs in over 4,400 subjects. The pooled analyses of placebo‑controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short‑term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 subjects. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger subjects for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1,000 subjects treated) are provided in Table 1.
| Age Range | Drug-Placebo Difference in Number of Cases of Suicidality per 1,000 Subjects Treated |
| Increases Compared with Placebo | |
| <18 | 14 additional cases |
| 18-24 | 5 additional cases |
| Decreases Compared with Placebo | |
| 25-64 | 1 fewer case |
| ≥65 | 6 fewer cases |
No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.
It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.
All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, 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 [see Boxed Warning].
The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.
Families and caregivers of patients being treated with antidepressants for MDD or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for WELLBUTRIN SR should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
5.2 Neuropsychiatric Adverse Events and Suicide Risk in Smoking Cessation Treatment
Wellbutrin SR is not approved for smoking cessation treatment; however, it contains the same active ingredient as the smoking cessation medication ZYBAN. Serious neuropsychiatric adverse events have been reported in patients taking bupropion for smoking cessation. These postmarketing reports have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide [see Adverse Reactions (6.2)]. Some patients who stopped smoking may have been experiencing symptoms of nicotine withdrawal, including depressed mood. Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication. However, some of these adverse events occurred in patients taking bupropion who continued to smoke.
Neuropsychiatric adverse events occurred in patients without and with pre-existing psychiatric disease; some patients experienced worsening of their psychiatric illnesses. Observe patients for the occurrence of neuropsychiatric adverse events. Advise patients and caregivers that the patient should stop taking WELLBUTRIN and contact a healthcare provider immediately if agitation, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior. In many postmarketing cases, resolution of symptoms after discontinuation of bupropion was reported. However, the symptoms persisted in some cases; therefore, ongoing monitoring and supportive care should be provided until symptoms resolve.
Seizure
Wellbutrin SR can cause seizure. The risk of seizure is dose-related. The dose should not exceed 400 mg per day. Increase the dose gradually. Discontinue Wellbutrin SR and do not restart treatment if the patient experiences a seizure.
The risk of seizures is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Consider these risks before initiating treatment with Wellbutrin SR. Wellbutrin SR is contraindicated in patients with a seizure disorder, current or prior diagnosis of anorexia nervosa or bulimia, or undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see Contraindications (4), Drug Interactions (7.3)]. The following conditions can also increase the risk of seizure: severe head injury; arteriovenous malformation; CNS tumor or CNS infection; severe stroke; concomitant use of other medications that lower the seizure threshold (e.g., other bupropion products, antipsychotics, tricyclic antidepressants, theophylline, and systemic corticosteroids); metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxia); use of illicit drugs (e.g., cocaine); or abuse or misuse of prescription drugs such as CNS stimulants. Additional predisposing conditions include diabetes mellitus treated with oral hypoglycemic drugs or insulin; use of anorectic drugs; and excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates.
Incidence of Seizure with Bupropion Use
When WELLBUTRIN SR is dosed up to 300 mg per day, the incidence of seizure is approximately 0.1% (1/1,000) and increases to approximately 0.4% (4/1,000) at the maximum recommended dose of 400 mg per day.
The risk of seizure can be reduced if the dose of Wellbutrin SR does not exceed 400 mg per day, given as 200 mg twice daily, and the titration rate is gradual.
Hypertension
Treatment with Wellbutrin SR can result in elevated blood pressure and hypertension. Assess blood pressure before initiating treatment with Wellbutrin SR, and monitor periodically during treatment. The risk of hypertension is increased if Wellbutrin SR is used concomitantly with MAOIs or other drugs that increase dopaminergic or noradrenergic activity [see Contraindications (4)].
Data from a comparative trial of the sustained-release formulation of bupropion HCl, nicotine transdermal system (NTS), the combination of sustained-release bupropion plus NTS, and placebo as an aid to smoking cessation suggest a higher incidence of treatment-emergent hypertension in patients treated with the combination of sustained-release bupropion and NTS. In this trial, 6.1% of subjects treated with the combination of sustained-release bupropion and NTS had treatment‑emergent hypertension compared with 2.5%, 1.6%, and 3.1% of subjects treated with sustained-release bupropion, NTS, and placebo, respectively. The majority of these subjects had evidence of pre-existing hypertension. Three subjects (1.2%) treated with the combination of sustained-release bupropion and NTS and 1 subject (0.4%) treated with NTS had study medication discontinued due to hypertension compared with none of the subjects treated with sustained-release bupropion or placebo. Monitoring of blood pressure is recommended in patients who receive the combination of bupropion and nicotine replacement.
In a clinical trial of bupropion immediate-release in MDD subjects with stable congestive heart failure (N = 36), bupropion was associated with an exacerbation of pre-existing hypertension in 2 subjects, leading to discontinuation of bupropion treatment. There are no controlled trials assessing the safety of bupropion in patients with a recent history of myocardial infarction or unstable cardiac disease.
Activation of Mania/Hypomania
Antidepressant treatment can precipitate a manic, mixed, or hypomanic manic episode. The risk appears to be increased in patients with bipolar disorder or who have risk factors for bipolar disorder. Prior to initiating Wellbutrin SR, screen patients for a history of bipolar disorder and the presence of risk factors for bipolar disorder (e.g., family history of bipolar disorder, suicide, or depression). Wellbutrin SR is not approved for use in treating bipolar depression.
Psychosis and Other Neuropsychiatric Reactions
Depressed patients treated with Wellbutrin SR have had a variety of neuropsychiatric signs and symptoms, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion. Some of these patients had a diagnosis of bipolar disorder. In some cases, these symptoms abated upon dose reduction and/or withdrawal of treatment. Instruct patients to contact a healthcare professional if such reactions occur.
Angle-Closure Glaucoma
The pupillary dilation that occurs following use of many antidepressant drugs including Wellbutrin SR may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.
Hypersensitivity Reactions
Anaphylactoid/anaphylactic reactions have occurred during clinical trials with bupropion. Reactions have been characterized by pruritus, urticaria, angioedema, and dyspnea requiring medical treatment. In addition, there have been rare, spontaneous postmarketing reports of erythema multiforme, Stevens‑Johnson syndrome, and anaphylactic shock associated with bupropion. Instruct patients to discontinue WELLBUTRIN SR and consult a healthcare provider if they develop an allergic or anaphylactoid/anaphylactic reaction (e.g., skin rash, pruritus, hives, chest pain, edema, and shortness of breath) during treatment.
There are reports of arthralgia, myalgia, fever with rash and other serum sickness-like symptoms suggestive of delayed hypersensitivity.
Use in specific populations
Pregnancy
Pregnancy Category C
Risk Summary
Data from epidemiological studies of pregnant women exposed to bupropion in the first trimester indicate no increased risk of congenital malformations overall. All pregnancies, regardless of drug exposure, have a background rate of 2% to 4% for major malformations, and 15% to 20% for pregnancy loss. No clear evidence of teratogenic activity was found in reproductive developmental studies conducted in rats and rabbits; however, in rabbits, slightly increased incidences of fetal malformations and skeletal variations were observed at doses approximately equal to the maximum recommended human dose (MRHD) and greater and decreased fetal weights were seen at doses twice the MRHD and greater. Wellbutrin SR should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Clinical Considerations
Consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum.
Human Data
Data from the international bupropion Pregnancy Registry (675 first trimester exposures) and a retrospective cohort study using the United Healthcare database (1,213 first trimester exposures) did not show an increased risk for malformations overall.
No increased risk for cardiovascular malformations overall has been observed after bupropion exposure during the first trimester. The prospectively observed rate of cardiovascular malformations in pregnancies with exposure to bupropion in the first trimester from the international Pregnancy Registry was 1.3% (9 cardiovascular malformations/675 first-trimester maternal bupropion exposures), which is similar to the background rate of cardiovascular malformations (approximately 1%). Data from the United Healthcare database and a case-control study (6,853 infants with cardiovascular malformations and 5,763 with non-cardiovascular malformations) from the National Birth Defects Prevention Study (NBDPS) did not show an increased risk for cardiovascular malformations overall after bupropion exposure during the first trimester.
Study findings on bupropion exposure during the first trimester and risk for left ventricular outflow tract obstruction (LVOTO) are inconsistent and do not allow conclusions regarding a possible association. The United Healthcare database lacked sufficient power to evaluate this association; the NBDPS found increased risk for LVOTO (n = 10; adjusted OR = 2.6; 95% CI: 1.2, 5.7), and the Slone Epidemiology case control study did not find increased risk for LVOTO.
Study findings on bupropion exposure during the first trimester and risk for ventricular septal defect (VSD) are inconsistent and do not allow conclusions regarding a possible association. The Slone Epidemiology Study found an increased risk for VSD following first trimester maternal bupropion exposure (n = 17; adjusted OR = 2.5; 95% CI: 1.3, 5.0) but did not find increased risk for any other cardiovascular malformations studied (including LVOTO as above). The NBDPS and United Healthcare database study did not find an association between first trimester maternal bupropion exposure and VSD.
For the findings of LVOTO and VSD, the studies were limited by the small number of exposed cases, inconsistent findings among studies, and the potential for chance findings from multiple comparisons in case control studies.
Animal Data
In studies conducted in rats and rabbits, bupropion was administered orally during the period of organogenesis at doses of up to 450 and 150 mg per kg per day, respectively (approximately 11 and 7 times the MRHD, respectively, on a mg per m2 basis). No clear evidence of teratogenic activity was found in either species; however, in rabbits, slightly increased incidences of fetal malformations and skeletal variations were observed at the lowest dose tested (25 mg per kg per day, approximately equal to the MRHD on a mg per m2 basis) and greater. Decreased fetal weights were observed at 50 mg per kg and greater.
When rats were administered bupropion at oral doses of up to 300 mg per kg per day (approximately 7 times the MRHD on a mg per m2 basis) prior to mating and throughout pregnancy and lactation, there were no apparent adverse effects on offspring development.
Nursing Mothers
Bupropion and its metabolites are present in human milk. In a lactation study of 10 women, levels of orally dosed bupropion and its active metabolites were measured in expressed milk. The average daily infant exposure (assuming 150 mL per kg daily consumption) to bupropion and its active metabolites was 2% of the maternal weight-adjusted dose. Exercise caution when Wellbutrin SR is administered to a nursing woman.
Pediatric Use
Safety and effectiveness in the pediatric population have not been established [see Boxed Warning, Warnings and Precautions (5.1)].
Geriatric Use
Of the approximately 6,000 subjects who participated in clinical trials with bupropion sustained-release tablets (depression and smoking cessation trials), 275 were aged ≥65 years and 47 were aged ≥75 years. In addition, several hundred subjects aged ≥65 years participated in clinical trials using the immediate-release formulation of bupropion (depression trials). No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and excreted by the kidneys. The risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be necessary to consider this factor in dose selection; it may be useful to monitor renal function [see Dosage and Administration (2.3), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Renal Impairment
Consider a reduced dose and/or dosing frequency of Wellbutrin SR in patients with renal impairment (Glomerular Filtration Rate: less than 90 mL per min). Bupropion and its metabolites are cleared renally and may accumulate in such patients to a greater extent than usual. Monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures [see Dosage and Administration (2.3), Clinical Pharmacology (12.3)].
Hepatic Impairment
In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose of Wellbutrin SR is 100 mg per day or 150 mg every other day. In patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].
In Summary
Common side effects of Wellbutrin SR include: dizziness, insomnia, nausea, pharyngitis, weight loss, and xerostomia. Other side effects include: abdominal pain, agitation, anxiety, arthralgia, chest pain, migraine, myalgia, palpitations, skin rash, tinnitus, tremor, urinary frequency, hypertension, anorexia, diaphoresis, dysgeusia, and flushing. See below for a comprehensive list of adverse effects.