openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 2 matching rows.
warnings and cautions
5 WARNINGS AND PRECAUTIONS Seizure Risk: The risk is dose dependent. Discontinue if seizure occurs ( 4 , 5.3 , 7.3 ). Neuropsychiatric Adverse Events During Smoking Cessation: Postmarketing reports of serious or clinically significant neuropsychiatric adverse events 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. Observe patients attempting to quit smoking with FORFIVO XL for the occurrence of such symptoms and instruct them to discontinue FORFIVO XL and contact a healthcare provider if they experience such adverse events ( 5.2 ). Hypertension: FORFIVO XL can increase blood pressure. Monitor blood pressure before initiating treatment and periodically during treatment ( 5.4 ). Activation of Mania/Hypomania: Screen patients for bipolar disorder and monitor for these symptoms ( 5.5 ). Psychosis and Other Neuropsychiatric Reactions: Discontinue if such reactions occur ( 5.6 ). Angle-closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants ( 5.7 ). 5.1 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 (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 studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to 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 4400 patients. 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 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients 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 1000 patients treated) are provided in Table 1 . Table 1. Risk Differences in the Number of Suicidality Cases by Age Group in the Pooled Placebo-controlled Trials of Antidepressants in Pediatric and Adult Patients Age Range (Years) Drug-Placebo Difference in Number of Cases of Suicidality per 1000 Patients Treated Increases Compared to Placebo < 18 14 additional cases 18-24 5 additional cases Decreases Compared to 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, ie, 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 and Use in Specific Populations ( 8.4 ) ]. 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 MDD 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 [see Patient Counseling Information ( 17 ) ]. Prescriptions for FORFIVO XL 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 FORFIVO XL is not approved for smoking cessation treatment, but bupropion hydrochloride sustained-release is approved for this use. 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 FORFIVO XL 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. 5.3 Seizure Bupropion can cause seizure. The risk of seizure is dose related. FORFIVO XL should be discontinued and not restarted in patients who experience a seizure while on treatment. 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 FORFIVO XL. FORFIVO XL is contraindicated in patients with a seizure disorder or conditions that increase the risk of seizure (eg, severe head injury, arteriovenous malformation, central nervous system [CNS] tumor or CNS infection, severe stroke, anorexia nervosa or bulimia, or abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs) [see Contraindications ( 4 ) ]. The following conditions can also increase the risk of seizure: concomitant use of other medications that lower the seizure threshold (eg, other bupropion products, antipsychotics, tricyclic antidepressants, theophylline, and systemic corticosteroids), metabolic disorders (eg, hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxia), or use of illicit drugs (eg, 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, excessive use of alcohol, use of benzodiazepines, sedatives/hypnotics, or opiates. Incidence of Seizure with Bupropion Use The incidence of seizure with bupropion extended-release has not been formally evaluated in clinical trials. In studies using bupropion hydrochloride sustained-release up to 300 mg/day, the incidence of seizure was approximately 0.1% (1/1000 patients). In a large prospective, follow-up study, the seizure incidence was approximately 0.4% (13/3200 patients) with bupropion hydrochloride immediate-release in the range of 300 to 450 mg/day. Additional data accumulated for bupropion immediate-release suggests that the estimated seizure incidence increases almost tenfold between 450 and 600 mg/day. The 600-mg dose is twice the usual adult dose and one and one-third the maximum recommended daily dose (450 mg) of FORFIVO XL. This disproportionate increase in seizure incidence with dose incrementation calls for caution in dosing. 5.4 Hypertension Treatment with FORFIVO XL can result in elevated blood pressure and hypertension. Assess blood pressure before initiating treatment with FORFIVO XL, and monitor periodically during treatment. The risk of hypertension is increased if FORFIVO XL 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 hydrochloride, nicotine transdermal system (NTS), the combination of sustained-release bupropion hydrochloride 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 hydrochloride and NTS. In this trial, 6.1% of subjects treated with the combination of sustained-release bupropion and NTS had treatment-emergent hypertension compared to 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 patients, leading to discontinuation of bupropion treatment. There are no controlled studies assessing the safety of bupropion in patients with a recent history of myocardial infarction or unstable cardiac disease. 5.5 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 FORFIVO XL, screen patients for a history of bipolar disorder and the presence of risk factors for bipolar disorder (eg, family history of bipolar disorder, suicide, or depression). FORFIVO XL is not approved for the treatment of bipolar depression. 5.6 Psychosis and Other Neuropsychiatric Reactions Depressed patients treated with bupropion 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. Discontinue FORFIVO XL if these reactions occur. 5.7 Angle-closure Glaucoma Angle-closure Glaucoma: The pupillary dilation that occurs following use of many antidepressant drugs including FORFIVO XL may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. 5.8 Hypersensitivity Reactions Anaphylactoid/anaphylactic reactions have occurred during clinical trials with bupropion. Reactions have been characterized by symptoms such as 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 FORFIVO XL and consult a healthcare provider if they develop an allergic or anaphylactoid/anaphylactic reaction (eg, skin rash, pruritus, hives, chest pain, edema, and shortness of breath) during treatment. There are reports of arthralgia, myalgia, fever with rash, and other symptoms of serum sickness suggestive of delayed hypersensitivity.