forfivo xl

Use one tablet (450 mg) once daily without regard to food ( 2.1 ). • Swallow the tablet whole. Do not chew, divide, or crush ( 2.1 ). • Do not initiate treatment with FORFIVO XL. Use another bupropion formulation for initial dose titration ( 2.2 ). • 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 ( 2.2 ). • Patients who are currently being treated with other bupropion products at 450 mg/day can be switched to equivalent dose of FORFIVO XL once daily ( 2.2 ). 2.1 General Instructions for Use One tablet (450 mg) of FORFIVO XL should be taken once daily without regard to meals. FORFIVO XL should be swallowed whole and not crushed, divided, or chewed. 2.2 Initial Treatment with FORFIVO XL 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. 2.3 Maintenance Treatment with FORFIVO XL It is generally agreed…

The following adverse reactions are discussed in greater detail in other sections of the labeling: • Suicidal thoughts and behaviors in children, adolescents, and young adults [see Warnings and Precautions ( 5.1 )] • Neuropsychiatric adverse events and suicide risk in smoking cessation treatment [see Warnings and Precautions ( 5.2 )] • Seizure [see Warnings and Precautions ( 5.3 )] • Hypertension [see Warnings and Precautions ( 5.4 )] • Activation of mania or hypomania [see Warnings and Precautions ( 5.5 )] • Psychosis and other neuropsychiatric events [see Warnings and Precautions ( 5.6 )] • Angle-closure Glaucoma [see Warnings and Precautions ( 5.7 )] • Hypersensitivity reactions [see Warnings and Precautions ( 5.8 )] Most common adverse reactions are (incidence ≥ 5%; ≥ 2 times placebo rate): dry mouth, nausea, insomnia, dizziness, pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitation, sweating, tinnitus, myalgia, anorexia, urinary frequency, rash ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact TWi Pharmaceuticals, Inc. at 1-844-518-2989 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the…

FORFIVO XL is contraindicated in patients with a seizure disorder [see Warnings and Precautions ( 5.3 )] . • FORFIVO XL is contraindicated in patients treated currently with other bupropion products because the incidence of seizure is dose dependent [see Warnings and Precautions ( 5.3 )] . • FORFIVO XL is contraindicated in 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 [see Warnings and Precautions ( 5.3 )] . • FORFIVO XL is contraindicated in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see Warnings and Precautions ( 5.3 ) and Drug Interactions ( 7.3 )] . • 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 [see Dosage and Administration ( 2.8 ), Warnings and Precautions ( 5.4 ), and Drug Interactions ( 7.6 )] . • FORFIVO XL is contraindicated in patients with known hypersensitivity to bupropion or the other ingredients of FORFIVO XL tablets. Anaphylactoid/anaphylactic reactions and Stevens-Johnson syndrome have been reported [see Warnings and Precautions ( 5.8 )] . •Seizure disorder ( 4 , 5.3 ) •Current use of other bupropion products ( 4 , 5.3 ) •Current or prior diagnosis of bulimia or anorexia nervosa ( 4 , 5.3 ) •Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs ( 4 , 5.3 ) • Monoamine Oxidase Inhibitors (MAOIs): Do not use MAOIs intended to treat psychiatric disorders with FORFIVO XL or within 14 days of stopping treatment with FORFIVO XL. Do not use FORFIVO XL within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start FORFIVO XL in a patient who is being treated with linezolid or intravenous methylene blue ( 4 , 7.6 ). •Known hypersensitivity to bupropion or other ingredients of FORFIVO XL ( 4 , 5.8 )

10.1 Human Overdose Experience Overdoses of up to 30 g or more of bupropion have been reported. Seizure was reported in approximately one third of all cases. Other serious reactions reported with overdoses of bupropion alone included hallucinations, loss of consciousness, mental status changes, sinus tachycardia, ECG changes such as conduction disturbances or arrhythmias, clonus, myoclonus, and hyperreflexia. Fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been reported mainly when bupropion was part of multiple drug overdoses. Although most patients recovered without sequelae, deaths associated with overdoses of bupropion alone have been reported in patients ingesting large doses of the drug. Multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest prior to death were reported in these patients. 10.2 Overdosage Management Consult a Certified Poison Control Center for up-to-date guidance and advice. Call 1-800-222-1222 or refer to www.poison.org. There are no known antidotes for bupropion. In case of an overdose, provide supportive care, including close medical supervision and monitoring. Consider the possibility of multiple drug overdose.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

CYP2B6 Inhibitors: Ticlopidine or clopidogrel may increase bupropion exposure. Coadministration of FORFIVO XL with ticlopidine or clopidogrel is not recommended ( 7.1 ). • CYP2B6 Inducers: Dose increase may be necessary if coadministered with CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin) based on clinical exposure, but should not exceed the maximum recommended dose ( 7.1 ). • Drugs Metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of: antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide). Consider dose reduction when using with bupropion ( 7.2 ). • Drugs That Lower Seizure Threshold: Dose FORFIVO XL with extreme caution ( 5.3 , 7.3 ). • Dopaminergic Drugs (levodopa and amantadine): CNS toxicity can occur when used concomitantly with FORFIVO XL ( 7.4 ). • MAOIs: Increased risk of hypertensive reactions can occur when used concomitantly with FORFIVO XL ( 7.6 ). • Drug-Laboratory Test Interactions: FORFIVO XL can cause false-positive urine test results for amphetamines ( 7.7 ). 7.1 Potential for Other Drugs to Affect FORFIVO XL Bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between FORFIVO XL and drugs that are inhibitors or inducers of CYP2B6. Inhibitors of CYP2B6 Ticlopidine and Clopidogrel: Concomitant treatment with these drugs can increase bupropion exposures but decrease hydroxybupropion exposure. Coadministration of FORFIVO XL with ticlopidine or clopidogrel is not recommended [see Clinical Pharmacology ( 12.3 )] . Inducers of CYP2B6 Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs 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 [see Clinical Pharmacology ( 12.3 )] . Carbamazepine, Phenobarbital, and Phenytoin: Although not systematically studied, these drugs may induce metabolism of bupropion and may decrease bupropion exposure [see Clinical Pharmacology ( 12.3 )] . 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. 7.2 Potential for FORFIVO XL to Affect Other Drugs Drugs Metabolized by CYP2D6 Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, and hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of bupropion with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g., haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., 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 (e.g., 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 [see Clinical Pharmacology ( 12.3 )] . 7.3 Drugs that Lower Seizure Threshold Because there is no lower strength for FORFIVO XL, concurrent administration of FORFIVO XL tablets and agents that lower the seizure threshold (e.g., other bupropion products, antipsychotics, antidepressants, theophylline, or systemic corticosteroids) should be undertaken only with extreme caution [see Warnings and Precautions ( 5.3 )] . 7.4 Dopaminergic Drugs (Levodopa and Amantadine) Bupropion, levodopa, and amantadine have dopamine agonist effects. CNS toxicity has been reported when bupropion was coadministered with levodopa or amantadine. Adverse reactions have included restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. It is presumed that the toxicity results from cumulative dopamine agonist effects. Because there is no lower strength for FORFIVO XL, administration of FORFIVO XL tablets to patients receiving either levodopa or amantadine concurrently should be undertaken with caution. 7.5 Use with Alcohol In postmarketing experience, there have been rare reports of adverse neuropsychiatric events or reduced alcohol tolerance in patients who were drinking alcohol during treatment with bupropion. Alcohol increased the release rate of FORFIVO XL in vitro . The consumption of alcohol during treatment with FORFIVO XL should be avoided. 7.6 Monoamine Oxidase Inhibitors (MAOIs) Bupropion inhibits the reuptake of dopamine and norepinephrine. Concomitant use of MAOIs and bupropion is contraindicated because there is an increased risk of hypertensive reactions if bupropion is used concomitantly with MAOIs. Studies in animals demonstrate that the acute toxicity of bupropion is enhanced by the MAOI phenelzine. At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of treatment with FORFIVO XL. Conversely, at least 14 days should be allowed after stopping FORFIVO XL before starting an MAOI antidepressant [see Dosage and Administration ( 2.7 , 2.8 ) and Contraindications ( 4 )] . 7.7 Drug-Laboratory Test Interactions 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. Confirmatory tests such as gas chromatography/mass spectrometry, will distinguish bupropion from amphetamines.