Indicated for the treatment of major depressive disorder (MDD), as defined by the Diagnostic and Statistical Manual (DSM).

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials. In patients of all ages who are started on antidepressant therapy, monitor closely for worsening and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber.

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.

Do not initiate treatment with FORFIVO XL because the 450 mg tablet is the only available dose formulation. Use another bupropion formulation for initial dose titration (referring to prescribing information of other bupropion products).

FORFIVO XL can be used in patients who are receiving 300 mg/day of another bupropion formulation for at least 2 weeks, and require a dosage of 450 mg/day. Patients who are currently being treated with other bupropion products at 450 mg/day can be switched to an equivalent dose of FORFIVO XL once daily.

Because there is no lower dose strength for FORFIVO XL, FORFIVO XL is not recommended in patients with hepatic impairment.

Because there is no lower dose strength for FORFIVO XL, FORFIVO XL is not recommended in patients with renal  impairment.

It is generally agreed that acute episodes of depression require several months or longer of sustained antidepressant treatment beyond the response in the acute episode. It is unknown whether the 450 mg dose needed for maintenance treatment is identical to the dose that provided an initial response.

FORFIVO XL is contraindicated in:

• patients with a seizure disorder
• patients treated currently with other bupropion products because the incidence of seizure is dose dependent
• patients with a current or prior diagnosis of bulimia or anorexia nervosa because a higher incidence of seizures was observed in such patients treated with bupropion
• patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs
• the use of MAOIs (intended to treat psychiatric disorders) concomitantly with FORFIVO XL or within 14 days of discontinuing treatment with FORFIVO XL is contraindicated. There is an increased risk of hypertensive reactions when FORFIVO XL is used concomitantly with MAOIs. The use of FORFIVO XL within 14 days of discontinuing treatment with an MAOI is also contraindicated. Starting FORFIVO XL in a patient treated with reversible MAOIs such as linezolid or intravenous methylene blue is contraindicated

The consumption of alcohol during treatment with FORFIVO XL should be avoided.

Anaphylactoid/anaphylactic reactions and Stevens-Johnson syndrome have been reported.

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.

Treatment with FORFIVO XL can result in elevated blood pressure and hypertension.The risk of hypertension is increased if FORFIVO XL is used concomitantly with MAOIs or other drugs that increase dopaminergic or noradrenergic activity.

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.

Depressed patients treated with bupropion have had a variety of neuropsychiatric signs and symptoms, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion.

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.

There are reports of arthralgia, myalgia, fever with rash, and other symptoms of serum sickness suggestive of delayed hypersensitivity.

Concomitant treatment with Ticlopidine and Clopidogrel can increase bupropion exposures but decrease hydroxybupropion exposure. Co-administration of FORFIVO XL with ticlopidine or clopidogrel is not recommended.

Concomitant treatment with Ritonavir, Lopinavir, and Efavirenz can decrease bupropion and hydroxybupropion exposure. Patients receiving any of these drugs with bupropion may need increased doses of bupropion, but the maximum recommended dose of bupropion should not be exceeded.

Although not systematically studied Carbamazepine, Phenobarbital, and Phenytoin may induce metabolism of bupropion and may decrease bupropion exposure.

If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion but the maximum recommended dose should not be exceeded.  Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, and hydroxybupropion) are CYP2D6 inhibitors. Therefore, co-administration of bupropion with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (eg, venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (eg, haloperidol, risperidone, and thioridazine), beta-blockers (eg, metoprolol), and Type 1C antiarrhythmics (eg, propafenone, and flecainide). When used concomitantly with bupropion, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.

Drugs that require metabolic activation by CYP2D6 to be effective (eg, tamoxifen) theoretically could have reduced efficacy when administered concomitantly with inhibitors of CYP2D6 such as bupropion. Patients treated concomitantly with FORFIVO XL and such drugs may require increased doses of the drug.

Because there is no lower strength for FORFIVO XL, concurrent administration of FORFIVO XL tablets and agents that lower the seizure threshold (eg, other bupropion products, antipsychotics, antidepressants, theophylline, or systemic corticosteroids) should be undertaken only with extreme caution.

Bupropion, levodopa, and amantadine have dopamine agonist effects. CNS toxicity has been reported when bupropion was co-administered with levodopa or amantadine.

False-positive urine immunoassay screening tests for amphetamines have been reported in patients taking bupropion. This is due to lack of specificity of some screening tests. False-positive test results may result even following discontinuation of bupropion therapy.

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 possible association. The United Healthcare database lacked sufficient power to evaluate this association; the NBDPS found increased risk for LVOTO.

Bupropion and its metabolites are present in human milk.

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• Use in patients under the age of 18. GoToSource

• Smoking cessation. GoToSource

• Seasonal affective disorder. GoToSource

• Weight loss, dysthymic disorder, social phobia, ADHD, anxiety and methamphetamine and cocaine cravings. GoToSource

• Neuropathic pain. GoToSource

• Restless legs syndrome. GoToSource

• Post-traumatic stress disorder. GoToSource

• Restlessness after a traumatic brain injury. GoToSource

• Atopic dermatitis and psoriasis. GoToSource

• Schizophrenia. GoToSource

• Panic disorder. GoToSource

• Bipolar disorder. GoToSource

Suicidal thoughts and behaviors. GoToSource

Seizures. GoToSource

Activation of mania or hypomania. GoToSource

Psychosis. GoToSource

Insomnia, constipation, dizziness, dry mouth, hypertension and anaphylactic reactions. GoToSource

Pruritus (severe itching of the skin), urticaria (hives), serum sickness like reaction (allergic reaction) and stevens-johnson syndrome (severe skin disorder). GoToSource

Eosinophilia (higher than normal level of a type of white blood cell). GoToSource

Stuttering. GoToSource

Serotonin syndrome (potentially life-threatening drug reaction). GoToSource

Acute dystonia (movement disorder). GoToSource

Hyponatremia (low sodium level in the blood). GoToSource

Thrombotic thrombocytopenic purpura (blood disorder causing blood clots to form in small blood vessels). GoToSource

Hepatitis (inflammation of the liver). GoToSource

Urinary incontinence. GoToSource

No major injury lawsuits reported.