emsam

EMSAM should be applied to dry, intact skin on the upper torso (below the neck and above the waist), upper thigh or the outer surface of the upper arm once every 24 hours ( 2.1 ). • Initial Treatment: The recommended starting dose and target dose for EMSAM is 6 mg per 24 hours ( 2.1 ). Based on clinical judgment, dose increases should occur in increments of 3 mg per 24 hours (up to a maximum dose of 12 mg per 24 hours) at intervals of no less than 2 weeks ( 2.1 ). • Geriatric Use: The recommended dose for elderly patients (65 years and older) is EMSAM 6 mg per 24 hours daily ( 8.5 ). • Dietary Modifications with EMSAM 9 mg per 24 hours and 12 mg per 24 hours: Tyramine-rich foods and beverages should be avoided beginning on the first day of EMSAM 9 mg per 24 hours or 12 mg per 24 hours treatment, and should continue to be avoided for 2 weeks after a dose reduction to EMSAM 6 mg per 24 hours or following the discontinuation of EMSAM 9 mg per 24 hours or 12 mg per 24 hours ( 2.3 ). 2.1 Initial Treatment EMSAM should be applied to dry, intact skin on the upper torso (below the neck and above the waist), upper thigh or the outer surface of the upper arm once every 24 hours. The recommended starting dose and target dose for EMSAM is 6 mg per 24 hours. EMSAM has been systematically evaluated and shown to be effective in a dose range of 6 mg per 24 hours to 12 mg per 24 hours.…

The following adverse reactions are discussed in greater detail in other sections of the label. • Suicidal Thoughts and Behaviors [see Warnings and Precautions (5.1) ] . • Serotonin Syndrome [see Contraindications (4) and Warnings and Precautions (5.2) ] . • Blood Pressure Elevation [see Warnings and Precautions (5.3) ] . • Activation of Mania/Hypomania [see Warnings and Precautions (5.4) ] . • External Heat [see Warnings and Precautions (5.5) ] . • Adverse Reactions occurring at an incidence of 2% or More Among EMSAM-Treated Patients and greater than placebo: Application site reaction, headache, insomnia, diarrhea, dry mouth, dyspepsia, rash, pharyngitis, sinusitis ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-4-INFO-RX (1-877-446-3679) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial 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 rates observed in clinical practice. Patient Exposure The premarketing development program for EMSAM included selegiline exposures in patients and/or normal subjects from two different groups of studies: 702 healthy subjects in clinical pharmacology/pharmacokinetics studies and 2,036 exposures from patients…

EMSAM (selegiline transdermal system) is contraindicated with selective serotonin reuptake inhibitors (SSRIs, e.g., fluoxetine, sertraline, and paroxetine); serotonin and norepinephrine reuptake inhibitors (SNRIs, e.g., venlafaxine and duloxetine); the tricyclic antidepressants clomipramine and imipramine, the opiate analgesics meperidine, tramadol, methadone, pentazocine, and propoxyphene; and the antitussive agent dextromethorphan because of a risk of serotonin syndrome when EMSAM is used with these agents [see Warnings and Precautions (5.2) and Drug Interactions (7.1) ] . • Carbamazepine is contraindicated with EMSAM because of a possible increased risk of hypertensive crisis [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3) ] . • After stopping treatment with drugs contraindicated with EMSAM, a time period equal to 4 to 5 half-lives (approximately one week) of the drug or any active metabolite should elapse before starting therapy with EMSAM. Because of the long half-life of fluoxetine and its active metabolite, at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of treatment with EMSAM. • At least 2 weeks should elapse after stopping EMSAM before starting therapy with any drug that is contraindicated with EMSAM. • EMSAM is contraindicated in patients less than 12 years of age because of the potential for a hypertensive crisis [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3) ] . • EMSAM is contraindicated in patients with pheochromocytoma because MAOIs may precipitate a hypertensive crisis in such patients. • Serotonergic drugs: selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), clomipramine and imipramine, meperidine, tramadol, methadone, pentazocine, and propoxyphene; and the antitussive agent dextromethorphan should not be used with EMSAM because of a risk of serotonin syndrome ( 4 , 5.2 ). • Carbamazepine should not be used with EMSAM ( 4 , 5.3 ). • After stopping treatment with contraindicated medication, a time period equal to 4 to 5 half-lives (approximately one week) of the drug or any active metabolite should elapse before starting therapy with EMSAM. Because of the long half-life of fluoxetine and its active metabolite, at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of treatment with EMSAM ( 4 ). • At least 2 weeks should elapse after stopping EMSAM before starting therapy with a drug that is contraindicated with EMSAM ( 4 ). • EMSAM is contraindicated in patients less than 12 years of age ( 4 , 8.4 ). • Pheochromocytoma ( 4 ).

10.1 Signs and Symptoms EMSAM overdosage may resemble overdosage with other nonselective, oral MAOI antidepressants and present with any of the following: drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, trismus, opisthotonos, convulsions, coma, rapid and irregular pulse, hypertension, hypotension and vascular collapse, precordial pain, respiratory depression and failure, hyperpyrexia, diaphoresis, and cool, clammy skin. 10.2 Management of Overdose There are no specific antidotes for EMSAM. If symptoms of overdosage occur, immediately remove the EMSAM system and institute appropriate supportive therapy. For contemporary information on the management of poisoning or overdosage, contact the National Poison Control Center at 1-800-222-1222. Delays of up to 12 hours between ingestion of drug and the appearance of signs may occur, and peak effects may not be observed for 24 to 48 hours. Since death has been reported following overdosage with MAOI agents, hospitalization with close monitoring during this period is strongly recommended. In order to avoid the occurrence of hypertensive crisis (“cheese reaction”), dietary tyramine should be restricted for several weeks beyond recovery to permit regeneration of the peripheral MAO-A isoenzyme.

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.

7.1 Serotonergic Drugs Serious, sometimes fatal, central nervous system (CNS) toxicity referred to as the “serotonin syndrome” has been reported with the combination of nonselective MAOIs and serotonergic drugs. Use of EMSAM with these drugs is contraindicated [see Contraindications (4) and Warnings and Precautions (5.2) ] . 7.2 Tyramine EMSAM has the capacity to inhibit intestinal MAO, which is responsible for the catabolism of tyramine in food and beverages. As a result of this inhibition, large amounts of tyramine may enter the systemic circulation and precipitate a sudden, large rise in blood pressure or hypertensive crisis [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.2) ] . A diet low in tyramine content may be necessary to avoid this interaction. Studies to evaluate the potential for EMSAM to inhibit tyramine metabolism have been conducted and, overall, the data for EMSAM 6 mg per 24 hours support a recommendation that a modified diet is not required at this dose. Due to the more limited data available for EMSAM 9 mg per 24 hours and the results from the Phase I tyramine challenge study in fed volunteers administered EMSAM 12 mg per 24 hours, patients receiving these doses should follow Dietary Modifications Required for Patients Taking EMSAM 9 mg per 24 hours and 12 mg per 24 hours below [see Clinical Pharmacology (12.2) ] . Dietary Modifications Required for Patients Taking EMSAM 9 mg per 24 hours and 12 mg per 24 hours The foods and beverages listed in Table 5 should be avoided beginning on the first day of EMSAM 9 mg per 24 hours or 12 mg per 24 hours treatment, and should continue to be avoided for 2 weeks after a dose reduction to EMSAM 6 mg per 24 hours or following the discontinuation of EMSAM 9 mg per 24 hours or 12 mg per 24 hours. Table 5. Food and Beverages to Avoid and Those which are Acceptable [see References (15) ] Class of Food and Beverage Tyramine-Rich Foods and Beverages to Avoid Acceptable Foods and Drinks, Containing No or Little Tyramine Meat, Poultry, and Fish Air dried, aged and fermented meats, sausages and salamis (including cacciatore, hard salami and mortadella); pickled herring; and any spoiled or improperly stored meat, poultry, and fish (e.g., foods that have undergone changes in coloration, odor, or become moldy); spoiled or improperly stored animal livers Fresh meat, poultry, and fish, including fresh processed meats (e.g., lunch meats, hot dogs, breakfast sausage, and cooked sliced ham) Vegetables Broad bean pods (fava bean pods) All other vegetables Dairy Aged cheeses Processed cheeses, mozzarella, ricotta cheese, cottage cheese, and yogurt Beverages All varieties of tap beer and beers that have not been pasteurized so as to allow for ongoing fermentation Concomitant use of alcohol with EMSAM is not recommended. (Bottled and canned beers and wines contain little or no tyramine.) Miscellaneous Concentrated yeast extract (e.g., Marmite), sauerkraut, most soybean products (including soy sauce and tofu), OTC supplements containing tyramine Brewer’s yeast, baker’s yeast, soy milk, commercial chain restaurant pizzas prepared with cheeses low in tyramine 7.3 Sympathomimetic Amines and Buspirone The use of EMSAM with sympathomimetic amines or buspirone may produce substantial elevations in blood pressure. Therefore, monitor blood pressure if EMSAM is used with any of the following drugs: buspirone, amphetamines, and cold products or weight-reducing preparations that contain sympathomimetic amines (e.g., pseudoephedrine, phenylephrine, phenylpropanolamine, and ephedrine). 7.4 Effect of Other Drugs on EMSAM Carbamazepine is contraindicated with MAOIs, including selegiline [see Contraindications (4) , Warnings and Precautions (5.3) and Clinical Pharmacology (12.3) ] . No dose adjustment for EMSAM is needed when EMSAM is used concomitantly with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and CYP3A4 inhibitors (e.g., ketoconazole). No clinically meaningful change in selegiline exposure was seen when EMSAM was co-administered with alcohol, alprazolam, ibuprofen, olanzapine, risperidone, levothyroxine, and ketoconazole [see Clinical Pharmacology (12.3) ] . 7.5 Effect of EMSAM on Other Drugs Use of alcohol while taking EMSAM is not recommended, even though EMSAM has not been shown to increase the impairment of mental and motor skills caused by alcohol (0.75 mg per kg) [see Clinical Pharmacology (12.3) ] . Monitor blood pressure if sympathomimetic agents (e.g., phenylpropanolamine (PPA) or pseudoephedrine) are used with EMSAM, even though selegiline does not appear to affect the pharmacokinetics of PPA or pseudoephedrine [see Clinical Pharmacology (12.3) ] . No dose adjustment of alprazolam, ibuprofen, levothyroxine, olanzapine, risperidone, warfarin, or strong CYP3A4 inhibitors (e.g., ketoconazole) is necessary when these drugs are used in combination with EMSAM. EMSAM had no clinically relevant effect on pharmacokinetics of these drugs.