Selegiline is classified as a selective, monoamine oxidase (MAO) type-B inhibitor. Selegiline is available orally for the treatment of Parkinson's disease as an adjunct to levodopa/carbidopa, and transdermally as a skin patch for the treatment of major depressive disorder in adults. Although adverse effects such as hypertensive crisis occur from inhibition of MAO type-A in the GI tract with subsequent systemic absorption of dietary amines such as tyramine, the selectivity of selegiline for MAO type-B is diminished as the dose increases. Therefore, specific recommendations for dietary tyramine intake must be followed to minimize the risk of a hypertensive crisis with selegiline, regardless of route or indication for use. In controlled clinical trials of oral selegiline for Parkinson's disease, superiority to placebo was demonstrated on all primary outcome measures including change from baseline in daily levodopa/carbidopa dose, the amount of 'off' time, and patient self-rating of treatment success. Other beneficial effects include end of dose akinesia, decreased tremor and sialorrhea, improved speech and dressing ability and improved overall disability (as assessed by walking or other comparisons to previous physical state). In clinical trials of transdermal selegiline patches for depression, modest efficacy with single episode or recurrent depression was demonstrated in adults 18 to 70 years of age; common adverse reactions include skin irritation and localized application site rash. Due to the dietary restrictions required for MAOI use, as well as their side effect profile and the potential for serious drug-drug and drug-food interactions, MAOIs are primarily considered an option for major depressive disorder (MDD) in adult patients refractory to treatment with other antidepressants (e.g., third-line treatment), and, they may be considered in some patients with combined anxiety/depression resistant to other treatments. All product labels for antidepressants, including traditional MAOI antidepressants, contain a boxed warning related to an increased risk of suicidality in children, adolescents, and young adults during the initial stages of therapy when treating depression or other conditions; therefore, the necessity of pharmacologic therapy versus the potential risks should be carefully considered in these populations. Transdermal selegiline is contraindicated in children less than 12 years of age due to an increased risk of hypertensive crisis.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Specific manufacturer recommendations for dietary tyramine intake must be followed to minimize the risk of a hypertensive crisis.
Oral Solid Formulations
Oral tablet or capsule (e.g., Eldepryl)
-Administer twice daily with breakfast and lunch.
-Do not administer doses greater than 10 mg/day because of the risk of hypertensive crisis.
Orally-disintegrating tablets (e.g., Zelapar)
-Do not push selegiline ODT through the foil backing; peel back the backing of 1 or 2 blisters (as prescribed) with dry hands, and gently remove the tablet(s).
-Immediately place the tablet(s) on top of the patient's tongue where it will disintegrate in seconds. Do not swallow the ODT tablet.
-The patient should avoid ingesting food or liquids for 5 minutes before and after taking selegiline ODT.
-Do not administer doses greater than 2.5 mg/day because of the risk of hypertensive crisis.
Topical Administration
Transdermal Patch Formulations
-Dietary tyramine intake restrictions must be followed to minimize the risk of a hypertensive crisis when using the 9 mg/24 hour or 12 mg/24 hour transdermal patch strengths. Patients should continue to avoid tyramine-rich foods or beverages for 2 weeks after a dose reduction to the 6 mg/24 dose or following discontinuation of the 9 mg/24 hour or 12 mg/24 hour patch.
Transdermal Patch Administration (Emsam)
-Before application, wash the area with soap and warm water, and dry thoroughly.
-Choose an application site of dry, intact skin on the upper chest or back, upper thigh, or the outer surface of the upper arm. The patch should be applied to an area of skin that is not hairy, oily, irritated, broken, scarred, or calloused.
-The patch should be applied immediately after removal from the pouch. Do not store the patch outside of the sealed pouch.
-Remove the transdermal patch from the pouch by tearing at the notches on the pouch. Do not use scissors.
-Do not cut or trim the patch.
-To apply the patch, remove half of the release liner and discard it. Press the sticky side of the transdermal system firmly against the cleaned skin site. Remove the second half of the release liner and press the remaining sticky side firmly against the skin. Ensure that the transdermal system is flat against the skin and is sticking securely. Be sure the edges are stuck to the skin surface.
-After application, hands should be washed with soap and water.
-Advise patients to wear only 1 patch at a time.
-Usual activities, including exercise, bathing, and swimming can be maintained while wearing the patch. Avoid exposing the application site to external sources of direct heat, such as heating pads or electric blankets, heat lamps, saunas, hot tubs, heated water beds, and prolonged direct sunlight.
-If the patch falls off, apply a new patch to a new site and resume the previous dose schedule. In dermal adhesion studies, roughly 6% to 7% of patches applied to the upper torso became detached during a 10-day period.
-Change patch once daily (every 24 hours). Remove the old patch before applying a new one.
-Rotate patch sites between the upper arm, upper chest, upper thigh, and upper back. New patches can be applied to sites near the previous site, but not to the same site.
-Disposal: Once a patch is removed, a used patch should be folded to stick to itself and discarded in a waste receptacle out of the reach of children and pets.
During clinical trials of selegiline orally disintegrating tablet (ODT) as adjunct therapy to levodopa in the treatment of Parkinson's disease, the following centrally-mediated adverse effects occurred in at least 2% of patients in the selegiline/levodopa groups and more frequently than in the placebo/levodopa groups: ataxia (3% vs. 1%), dizziness (11% vs. 8%), dyskinesia (6% vs. 3%), hallucinations (4% vs. 2%), headache (7% vs. 6%), insomnia (7% vs. 4%), drowsiness/somnolence (3% vs. 2%), and tremor (3% vs. 1%). In a parallel, placebo-controlled clinical trial, the following CNS effects occurred more frequently in selegiline-treated patients (n = 49) than placebo-treated patients (n = 50): dizziness (14.3% vs. 2%), confusion (6.1% vs. 0%), hallucinations (6.1% vs. 2%), vivid dreams (4.1% vs. 0%), and headache (4.1% vs. 2%). Other CNS effects reported during clinical trial evaluation of selegiline for Parkinson's disease included abnormal gait, abnormal thinking, agitation, akinesia, anxiety, apathy, aphasia, bradykinesia, chorea, CNS neoplasia, delusions, dementia, disorientation, dystonic reaction, emotional lability, encephalopathy, facial grimace, fall, fatigue, festination, freezing, hollow feeling, hyperkinesis, hypertonia, hypokinesia, hyporeflexia, hypotonia, hypersalivation, incoordination, increased apraxia, increased energy, involuntary movements, irritability, lethargy, lightheadedness, loss of balance, malaise, memory impairment, migraine, muscle twitch, myoclonia, nervousness, neuralgia (neuropathic pain), neuropathy, nightmares, overstimulation, paranoia, peripheral neuritis, personality change, personality disorder, psychosis, restlessness, sleep disorder, stiff neck, subdural hematoma, tardive dyskinesia, transient high, vertigo, and weakness. During clinical trial evaluation of transdermal selegiline in the treatment of major depressive disorder in adults, the following centrally-mediated effects occurred in at least 2% of patients receiving selegiline and with an incidence greater than in those receiving placebo: headache (18% vs. 17%) and insomnia (12% vs. 7%). During other clinical trial evaluation, tremor, twitching, agitation, and amnesia were reported. During a flexible-dose controlled trial in adolescents, insomnia was reported more frequently in the transdermal selegiline group than the placebo group (6% vs. 3%). Postmarketing reports during the use of transdermal selegiline include disorientation (confusion), visual hallucinations, seizures, hypoesthesia, and tension.
Nausea is the most frequently reported adverse effect of selegiline therapy. During clinical trials of oral selegiline as adjunct therapy to levodopa in the treatment of Parkinson's disease, the following adverse gastrointestinal (GI) effects occurred in at least 2% of patients in the selegiline/levodopa groups and more frequently than in the placebo/levodopa groups: nausea (11% vs. 9%), constipation (4% vs. 0%), diarrhea (2% vs. 1%), dysphagia (2% vs. 1%), dyspepsia (5% vs. 3%), flatulence (2% vs. 1%), stomatitis (5% vs. 4%), tooth disorder (2% vs. 1%), vomiting (3% vs. 0%), and xerostomia (4% vs. 2%). In one small, parallel, placebo-controlled clinical trial, the following GI effects occurred more frequently in selegiline-treated patients (n = 49) than placebo-treated patients (n = 50): nausea (20.4% vs. 6%), abdominal pain (8.2% vs. 4%), and xerostomia (6.1% vs. 2%). Other GI effects reported during clinical trial evaluation of selegiline for Parkinson's disease included anorexia, teeth grinding (bruxism), cholecystitis, cholelithiasis, colitis, elevated hepatic enzymes, esophageal ulceration, esophagitis, increased gamma-glutamyl transpeptidase (GGT), gastritis, gastroenteritis, gingivitis, GI bleeding, GI obstruction, hepatitis, peptic ulcer, pyrosis (heartburn), rectal bleeding, and weight loss. During clinical trials evaluating transdermal selegiline in the treatment of major depressive disorder, the following adverse gastrointestinal (GI) effects occurred in at least 2% of patients receiving selegiline and with an incidence greater than in those receiving placebo: diarrhea (9% vs. 7%), dyspepsia (4% vs. 3%), and xerostomia (8% vs. 6%). During other clinical trial evaluation, anorexia was reported. More patients receiving transdermal selegiline experienced at least a 5% weight loss from baseline compared to patients receiving placebo (5% vs. 2.8%) and more patients receiving placebo had at least a 5% weight gain than patients receiving transdermal selegiline (2.4% vs. 2.1%). The mean change in body weight among patients receiving transdermal selegiline was a 1.2 pound weight loss compared to a 0.3 pound weight gain in placebo-treated patients.
MAOIs can predispose patients to a hypertensive crisis due to their inhibition of monoamine oxidase A, an enzyme responsible for the catabolism of dietary amines such as tyramine. Selegiline shows greater selectivity for MAO-B than MAO-A; however, as selegiline concentrations increase, this selectivity is lost with resulting dose-related inhibition of MAO-A. Significant inhibition of intestinal MAO-A activity can impose a cardiovascular safety risk following the ingestion of tyramine-rich foods or beverages (e.g., aged cheese; yeast extract; protein extract; soy sauce; fava bean or broad bean pods; smoked meats; pickled meats; chicken livers, smoked poultry; pickled poultry; smoked fish (lox, smoked salmon); pickled fish (pickled herring); fermented sausage (bologna, pepperoni, salami, summer sausage) or other fermented meat; bananas; avocados; any over-ripe fruit; tap beer and beers that have not been pasteurized). A tyramine-restricted diet is recommended for certain selegiline formulations and dosages. In rare instances, hypertensive crisis associated with dietary influence have occurred at recommended selegiline doses. Hypertensive crisis, which can be fatal, may manifest as occipital headache which may radiate frontally, palpitation, neck stiffness or soreness, nausea, vomiting, sweating with possible fever and cold, clammy skin, dilated pupils, photophobia, tachycardia or bradycardia with possible constricting chest pain, or intracranial bleeding. Patients should be advised to report severe or continuing headache and any other symptoms of hypertension, such as angina, sinus tachycardia, sinus bradycardia, palpitations, mydriasis, profuse sweating, nausea/vomiting, stiff or sore neck, and elevated temperature. During clinical trials of selegiline orally disintegrating tablets (ODT) as adjunct therapy to levodopa in the treatment of Parkinson's disease, the following adverse cardiovascular effects occurred in at least 2% of patients in the selegiline/levodopa groups and more frequently than patients in the placebo/levodopa groups: hypertension (3% vs. 2%) and chest pain (unspecified) (2% vs. 0%). Orthostatic hypotension occurred more frequently with selegiline than placebo, with a peak systolic orthostasis incidence of about 21% in the ODT selegiline group 2 weeks after a dose increase to 2.5 mg (9% incidence in placebo group). The incidence of diastolic orthostatic hypotension was about 12% in the ODT selegiline group and about 4% in the placebo group. Other cardiovascular effects reported during clinical trial evaluation of selegiline for Parkinson's disease included new or worsening angina, arrhythmia, atrial fibrillation, atrial flutter, first degree AV block, bigeminy, cardiomegaly, cardiomyopathy, cerebral ischemia, congestive heart failure, cardiac arrest, hypotension, myocardial infarction, myocardial ischemia, palpitations, peripheral edema, peripheral vasodilation, sinus bradycardia, sinus tachycardia, supraventricular tachycardia (SVT), syncope, and vascular disorder. No clinically meaningful ECG changes have been noted in clinical trials evaluating selegiline. In controlled trials with transdermal selegiline, orthostatic hypotension (defined as a decrease of at least 10 mmHg in mean blood pressure with postural change) occurred more frequently in selegiline-treated patients than placebo-treated patients (10% vs. 7%). Hypotension (defined as 90 mmHg or less with a change from baseline of at least 20 mmHg) occurred more often in the selegiline group than the placebo group (3% vs. 1.5%). In a study which used higher mean doses of transdermal selegiline, a low standing systolic blood pressure was only observed in the selegiline group (6.2% vs. 0%). Other studies have not reported significant clinical effects of orthostatic hypotension. Sinus tachycardia was observed during premarketing evaluation of transdermal selegiline.
During clinical trial evaluation of oral selegiline in Parkinson's disease patients, the following adverse genitourinary (GU) effects were reported: orgasm dysfunction, breast carcinoma, cystitis, decreased penile sensation, epididymitis, nephrolithiasis, ovarian disorder, prostatic carcinoma, increased prostatic specific antigen (PSA), slow urination, increased urinary frequency, impaired urination, nocturia, prostatic hypertrophy, sexual dysfunction (unspecified), urinary hesitancy, urinary incontinence, urinary retention, and urinary urgency. During clinical trial evaluation of transdermal selegiline for major depressive disorder, the following GU effects occurred more frequently in males receiving selegiline than placebo: ejaculation dysfunction (1% vs. 0%), libido decrease (0.7% vs. 0%), impotence (erectile dysfunction) (0.7% vs. 0.4%), orgasm dysfunction (anorgasmia 0.2% vs. 0%). In females, the only reported sexual dysfunction (decreased libido) occurred in the placebo group (0.2%).
Serotonin syndrome has been reported during concomitant administration of MAOIs, including selegiline, and other medications known to increase central serotonin levels such as selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. . Concurrent us of certain medications increases the risk for serotonin syndrome. If serotonin syndrome becomes evident during treatment, selegiline and any serotonergic agents should be discontinued and appropriate medical treatment should be initiated. There has been a fatal case of serotonin syndrome involving oral selegiline.
Application site reaction (e.g., skin irritation, erythema) is the most frequently reported adverse effect of transdermal selegiline. During clinical trials evaluating transdermal selegiline in the treatment of major depressive disorder, the following dermatologic effects occurred in at least 2% of patients receiving selegiline and with an incidence greater than in those receiving placebo: application site reaction (24% vs. 12%) and rash (4% vs. 2%). During other clinical trial evaluation, pruritus was reported. The only adverse event associated with treatment discontinuation in at least 1% of patients and at a rate at least twice that of placebo was application site reaction (2% vs. 0%). Most application site reactions were described as mild or moderate erythema; none were reported as serious. Discontinuation of the transdermal patch typically resolved the skin reaction spontaneously; topical corticosteroids were also used for treatment of events in clinical trials. Higher selegiline patch doses were associated with a higher incidence of application site reactions in one study, although the dose used was not reported. In dermal adhesion studies, roughly 6% to 7% of patches applied to the upper torso became detached during a 10-day period. If this occurs, patients should be instructed to discard the old patch, apply a new patch at another site, and continue with their previous schedule. Application site pruritus has also been reported. Several minor abnormalities of the tongue and oral mucosa occurred during clinical trials with selegiline orally disintegrating tablets (ODT) including swelling and edematous tissue, discrete and multiple areas of focal reddening (erythema), mouth pain, swallowing pain, and oral ulceration. Overall, 10% of subjects receiving selegiline ODT developed these oropharyngeal abnormalities compared to 3% of subjects receiving placebo. Subset analyses revealed that discrete areas of focal reddening developed in 3% of subjects receiving selegiline ODT versus 0% of subjects receiving placebo. Mild ulceration was reported in 2% of those receiving active treatment versus 1% of those receiving placebo. Glossitis was reported during clinical trial evaluation; however, the frequency is unknown.
During clinical trials of selegiline orally disintegrating tablet (ODT) as an adjunct therapy to levodopa in the treatment of Parkinson's disease, depression occurred in 2% of patients in the selegiline/levodopa groups and 1% of patients in the placebo/levodopa groups. Transdermal selegiline is indicated for the treatment of major depressive disorder (MDD) and during clinical trials with the transdermal product, mania occurred in 0.4% of selegiline-treated patients. Monitor all antidepressant-treated patients for any indication for worsening of depression or the condition being treated and the emergence of suicidal behaviors or suicidal ideation, especially during the initial few months of drug therapy and after dosage changes. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in patients 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in the absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. No suicides occurred in any of the pediatric trials. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over 24 years of age; there was a reduction in risk with antidepressant use in patients 65 years and older. Caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation during selegiline treatment.
Some patients receiving medications that increase dopaminergic tone have reported intense and uncontrollable urges to gamble, increased sexual urges, or other intense urges. Causality due to dopaminergic agents has not been established; however, in some cases, the urges stopped after the dose was reduced or the drug was discontinued. Practitioners should inquire periodically about new or worsening impulse control symptoms in patients receiving selegiline. Likewise, patients should be instructed to report such changes while receiving selegiline. Dose reduction or discontinuation should be considered in those who experience these effects.
Ophthalmic, otic, or other reactions affecting the special senses that occurred during clinical trial evaluation of selegiline for Parkinson's disease included abnormal vision (visual impairment), amblyopia, blepharospasm, blindness, blurred vision, cataracts, conjunctivitis, hearing loss, diplopia, xerophthalmia, ocular hemorrhage, glaucoma, otitis externa, retinal artery occlusion, retinal detachment, taste loss, dysgeusia, and tinnitus. The frequencies of these adverse effects are unknown.
During clinical trials of oral selegiline as adjunct therapy to levodopa in the treatment of Parkinson's disease, the following respiratory effects or infections occurred in at least 2% of patients in the selegiline/levodopa groups and more frequently than in the placebo/levodopa groups: dyspnea (3% vs. 0%), pharyngitis (4% vs. 2%), and rhinitis (7% vs. 6%). Other respiratory effects, infections, or related symptoms reported during clinical trial evaluation of selegiline for Parkinson's disease included sinusitis, asthma (bronchospasm), bronchitis, lung carcinoma, hiccups, epistaxis, fever, fungal infection, neoplasm, pulmonary edema, pleural effusion, pneumonia, pneumothorax, superimposed infection, viral infection, and voice alteration. During clinical trials evaluating transdermal selegiline in the treatment of major depressive disorder in adults, the following adverse respiratory effects occurred in at least 2% of patients receiving selegiline and with an incidence greater than in those receiving placebo: pharyngitis (3% vs. 2%) and sinusitis (3% vs. 1%). During a flexible-dose controlled trial in adolescents, upper respiratory tract infection was reported more frequently in the transdermal selegiline group than the placebo group (7% vs. 3%).
General adverse effects not listed elsewhere that were reported during clinical trial evaluation of selegiline for Parkinson's disease included allergic reaction, facial edema, hernia, and cyanosis. The frequencies are unknown and causality to the drug has not been established.
During clinical trials of selegiline as adjunct therapy to levodopa in the treatment of Parkinson's disease, the following adverse dermatologic effects occurred in at least 2% of patients in the selegiline/levodopa groups and more frequently than in the placebo/levodopa groups: rash (unspecified) (4% vs. 1%) and skin disorders (6% vs. 2%). Other dermatologic effects reported during clinical trial evaluation of selegiline for Parkinson's disease included alopecia, atopic dermatitis, cellulitis, contact dermatitis, cyst, diaphoresis, facial hair, fungal dermatitis, hematoma, herpes simplex, herpes zoster, hyperhidrosis, pallor, photosensitivity, pruritus, seborrhea, benign skin neoplasm, skin carcinoma, skin hypertrophy, skin melanoma, skin discoloration, skin ulcer, and xerosis.
During clinical trials of selegiline as adjunct therapy to levodopa in the treatment of Parkinson's disease, the following adverse musculoskeletal effects or pain symptoms occurred in at least 2% of patients in the selegiline/levodopa groups and more frequently than in the placebo/levodopa groups: muscle cramps (3% vs 1%), myalgia (3% vs 0%), back pain (5% vs 3%), and unspecified pain (8% vs 7%). Other musculoskeletal effects, pain symptoms, or altered sensations reported during clinical trial evaluation of selegiline for Parkinson's disease included arthralgia, arthritis, arthrosis (arthropathy), bone pain, bursitis, chills, flank pain, generalized ache, leg pain, neck pain, numbness of toes/fingers, paresthesias, ruptured tendon, supraorbital pain, tenosynovitis, and throat burning.
During clinical trials of selegiline as adjunct therapy to levodopa in the treatment of Parkinson's disease, hypokalemia occurred more frequently in the selegiline/levodopa groups than in the placebo/levodopa groups (2% vs 0%). Other metabolic and nutritional effects reported during clinical trial evaluation of selegiline for Parkinson's disease included hypovitaminosis, dehydration, diabetes mellitus, edema or fluid retention, gout, hypercholesterolemia, hyperglycemia, hyperkalemia, hyperlipidemia, hyperphosphatemia, hypoglycemia, proteinuria, hyponatremia, and hypoproteinemia.
During clinical trials of selegiline as adjunct therapy to levodopa in the treatment of Parkinson's disease, ecchymosis occurred more frequently in patients in the selegiline/levodopa groups than in the placebo/levodopa groups (2% vs 0%). Other hematologic effects that occurred during clinical trial evaluation of selegiline for Parkinson's disease included abnormal platelets, anemia, chronic leukocytosis, eosinophilia, lymphoma-like reaction, new primary malignancy (myelocytic leukemia), and increased sedimentation rate.
Selegiline is contraindicated in patients with a hypersensitivity to selegiline or any inactive ingredients of the formulations.
Selegiline is an irreversible, selective monoamine oxidase (MAO) type B inhibitor. Therefore, selegiline is contraindicated in patients receiving any other MAOI therapy due to the risk for hypertensive crisis.. selegiline transdermal system is contraindicated with selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), St. John's wort, the tricyclic antidepressants (TCAs), cyclobenzaprine, the opiate analgesics meperidine, tramadol, and other opiate agonists, and the antitussive agent dextromethorphan because of a risk of serotonin syndrome or bizarre behaviors when selegiline is used with these agents. Other drugs (e.g., carbamazepine) are contraindicated due to a risk of serious high blood pressure, including crisis. After stopping treatment with drugs contraindicated with selegiline, a time period equal to 4 to 5 half-lives (approximately 1 week) of the drug or any active metabolite should elapse before starting therapy with selegiline. At least 2 weeks should elapse after stopping selegiline before starting therapy with any drug that is contraindicated with selegiline.
The monoamine oxidase (MAO) enzyme system is important in the catabolism of dietary amines (e.g., tyramine), and selegiline acts as an irreversible MAO inhibitor. MAO exists as 2 isoenzymes, referred to as MAO-A and MAO-B. Selegiline shows greater affinity for MAO-B; however, as selegiline concentrations increase, this selectivity is lost with resulting dose-related inhibition of MAO-A. Intestinal MAO is predominantly type A, while in the brain both isoenzymes exist. Significant inhibition of intestinal MAO-A activity can impose a cardiovascular safety risk. MAOIs have been associated with hypertensive crisis caused by the ingestion of foods, beverages, or nutritional supplements with a high concentration of tyramine. Clinical data do not support the need for tyramine dietary modification at the selegiline transdermal dose of 6 mg/24 hour; however, unrestricted dietary tyramine data in clinical trials evaluating the 9 mg/24 hour or 12 mg/24 hour patch are limited and tyramine restrictions should be followed with these higher doses. Study results of selegiline orally disintegrating tablets (ODT) showed that an increase in tyramine sensitivity for blood pressure responses appears to begin at a dose of 5 mg/day; however, hypertensive crisis has also been reported with selegiline ODT use that was not above the recommended dosing. Patients receiving selegiline ODT should be advised to avoid certain foods containing a very large amount of tyramine (e.g., aged cheese) because of the potential for large increases in blood pressure. Oral selegiline tablets and capsules can ordinarily be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day); however, hypertensive reactions at recommended doses associated with dietary influences have been reported. Advise patients of dietary tyramine-restriction recommendations. Selegiline should not be used in patients with alcoholism. Tyramine-rich foods and beverages include: aged cheese; yeast extract; protein extract; soy sauce; fava bean or broad bean pods; smoked meats; pickled meats; chicken livers, smoked poultry; pickled poultry; smoked fish (lox, smoked salmon); pickled fish (pickled herring); fermented sausage (bologna, pepperoni, salami, summer sausage) or other fermented meat; bananas; avocados; any over-ripe fruit; and tap beer and beers that have not been pasteurized. The manufacturer of transdermal selegiline recommends avoiding ethanol ingestion and specifically recommends avoiding tyramine-rich alcoholic beverages such as all varieties of tap beer and beers that have not been pasteurized during use of the 9 mg/24 hour or 12 mg/24 hour patch and for 2 weeks after discontinuation or dose reduction to 6 mg/24 hour due to the risk for hypertensive crisis. Patients receiving any formulation of selegiline should be monitored for new onset hypertension or exacerbation of pre-existing hypertension. Hypertensive crisis, which can be fatal, may manifest as occipital headache which may radiate frontally, palpitation, neck stiffness or soreness, nausea, vomiting, sweating with possible fever and cold, clammy skin, dilated pupils, photophobia, tachycardia or bradycardia with possible constricting chest pain, or intracranial bleeding. A complete drug, food, and dietary supplement history should be obtained in all patients prior to prescribing selegiline. Patients should be instructed on the signs and symptoms of severe hypertension and advised to seek immediate medical attention if these signs or symptoms are present. If a hypertensive crisis occurs, selegiline should be discontinued immediately and the appropriate medical treatment should be initiated to lower blood pressure (e.g., phentolamine, labetalol, nitroprusside) and treat associated symptoms. Patients must be closely monitored until the symptoms have stabilized.
Transdermal selegiline is contraindicated in patients with pheochromocytoma. The associated tumor secretes pressor substances (e.g., norepinephrine) and the metabolism of these pressor substances may be reduced by MAOIs and potentially cause a hypertensive crisis. Oral forms of selegiline should generally also be avoided in these patients, due to similar reasons.
Safety and efficacy of oral selegiline have not been established in pediatric patients less than 18 years of age. Transdermal selegiline, an antidepressant, is contraindicated in children less than 12 years due to the risk of hypertensive crisis. Children younger than 12 years of age appear to have greater drug exposure compared to adolescents and adults with transdermal use, and children may not be able to reliably adhere to the required dietary restrictions. A flexible-dose controlled trial of transdermal selegiline failed to demonstrate efficacy in children adolescents 12 years and older over placebo, although the overall safety profile was similar to adults. A boxed warning in the product label describes the risk of suicidality and suicidal ideation in children, adolescent, and young adult patients receiving antidepressants. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in patients 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. The need for an antidepressant in children, adolescents, or young adults for any use must be weighed against the risk of suicidality; it is unknown if this risk extends to long-term use. All patients should be monitored for symptom worsening or suicidality, especially at treatment initiation or after dose changes. Caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation. A change to the treatment regimen or discontinuation of selegiline may be necessary in patients with emerging suicidality or worsening depression.
Patients should be adequately screened for a personal or family history of bipolar disorder, mania, or hypomania prior to initiating an antidepressant, such as the selegiline transdermal patch. Treatment of a depressive episode with antidepressants, such as transdermal selegiline, has been associated with the precipitation of mania or hypomania in patients with bipolar disorder. Screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. Depression may also be the presenting symptom of a mixed/manic episode of bipolar disorder. Patients with depression or comorbid depression in the setting of other psychiatric illness being treated with an antidepressant should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes. Caregivers should be advised to closely observe the patient on a daily basis and to communicate immediately with the prescriber the emergence of agitation, irritability, unusual changes in behavior, or emergence of suicidality. If a patient develops manic symptoms, transdermal selegiline should be withheld, and appropriate therapy initiated to treat the manic symptoms.
Postmarketing reports indicate that patients may experience new or worsening mental status and behavioral changes, which may be severe, including psychotic-like behavior during oral selegiline treatment or after starting or increasing the dose. Other drugs prescribed to improve the symptoms of Parkinson's disease can have similar effects on thinking and behavior. This abnormal thinking and behavior can consist of 1 or more of a variety of manifestations including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium. Patients with a major psychotic disorder, such as schizophrenia, should generally not be treated with selegiline because the dopamine-enhancing properties of selegiline may cause or exacerbate hallucinations and psychosis. In addition, certain medications used to treat psychosis, such as dopamine antagonists, may exacerbate the symptoms of Parkinson's disease and may decrease the effectiveness of selegiline. Behavioral changes have also 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. Families and caregivers of patients being treated with selegiline, for both psychiatric and nonpsychiatric indications, 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.
Some patients receiving medications for Parkinson's disease that increase dopaminergic tone have reported intense and uncontrollable urges to gamble, increased sexual urges, or other intense urges. Causality due to dopaminergic agents has not been established; however, in some cases the urges stopped after the dose was reduced or the drug was discontinued. Practitioners should inquire periodically about new or worsening impulse control symptoms in Parkinson's patients receiving selegiline. Likewise, patients should be instructed to report such changes while receiving selegiline. Dose reduction or discontinuation should be considered in those who experience these effects.
Patients should be advised that they may develop symptomatic or asymptomatic hypotension while taking oral selegiline, particularly during treatment initiation. Caution patients against rising rapidly after sitting or lying down, especially if they have been doing so for prolonged periods and especially during treatment initiation. The incidence of orthostatic hypotension was higher in elderly adult patients than younger adult patients (3% vs. 0%). Orthostatic hypotension has also occurred with other oral dose forms. During clinical trial evaluation of transdermal selegiline, orthostatic hypotension occurred more frequently with the use of transdermal selegiline than placebo (10% vs. 7%). Patients with a pre-existing tendency towards changes in postural blood pressure should be observed closely for changes in blood pressure throughout treatment, and dose increases should be made carefully.
Caution is advisable in patients with hepatic disease; selegiline undergoes hepatic metabolism to active metabolites. Dosages of selegiline orally disintegrating tablets (ODT) in patients with mild to moderate hepatic impairment (Child-Pugh 5 to 9) are adjusted to clinical response. Selegiline ODT is not recommended in patients with severe hepatic impairment. No adjustment of transdermal selegiline is required in patients with mild or moderate liver impairment (Child-Pugh 5 to 9); transdermal selegiline has not been studied in patients with severe liver impairment (Child-Pugh score 10 to 15). Use oral selegiline tablets or capsules with caution in hepatically impaired patients; no specific recommendations are available.
Caution is advisable in patients with renal impairment; specific manufacturer recommendations should be followed. No dosage adjustment of transdermal selegiline is needed in patients with mild, moderate, or severe renal impairment; however, there are no data in patients with end-stage renal disease (ESRD). No dose adjustment of selegiline orally disintegrating tablets (ODT) is required in patients with mild to moderate renal impairment with a creatinine clearance (CrCl) 30 to 89 mL/minute). Selegiline ODT is not recommended in patients with severe renal impairment or end-stage renal disease (CrCl less than 30 mL/minute). No specific guidance is available for oral selegiline tablets or capsules in patients with renal impairment or renal failure.
Epidemiological studies have shown that patients with Parkinson's disease (PD) have a 2- to 6-fold higher risk of developing melanoma than the general population. It is recommended that a qualified practitioner (e.g., dermatologist) monitor for skin cancer on a regular basis during PD treatment with oral selegiline capsules and tablets. Advise patients to regularly monitor for skin changes and to promptly report these changes to their provider. The orally disintegrating tablets and transdermal selegiline products do not list this precaution in their product labels, since this observation appears to be more related to factors other than selegiline use.
Although selegliline has not been shown to increase the impairment of mental and motor skills caused by alcohol, the concomitant use of selegiline transdermal patch and alcohol in depressed patients is not recommended. Coadministration with other CNS depressants may also increase the risk for psychomotor impairment. All patients taking selegiline (oral and transdermal) should be cautioned about driving or operating machinery until they know how the drug affects them. There have been reports of patients with Parkinson's disease who have experienced sudden sleep onset while performing activities of daily living, including driving. In some cases, excessive drowsiness has resulted in auto accidents or other harmful events in the course of daily living. Symptoms of excessive drowsiness may not be preceded by warning signs such as somnolence. Excessive drowsiness has, in some cases, occurred as late as 1 year after the initiation of treatment. Before initiating treatment with selegiline for Parkinson's disease, advise patients about the potential for drowsiness and specifically assess conditions that may increase this risk, such as the presence of sleep disorders (e.g., narcolepsy, sleep apnea) or coadministration with other CNS depressants. Assessment for somnolence is suggested throughout therapy. Selegiline should generally be discontinued in those who have experienced a sudden episode of sleep while engaged in activities of daily living. If selegiline is continued in these patients, activities requiring mental alertness should be avoided. It is not known if a reduction in dosage will subsequently reduce or eliminate excessive somnolence or sudden episodes of sleep.
Although not reported with selegiline during clinical trials for Parkinson's disease, a symptom complex resembling the neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in antiparkinsonian therapy. Avoid abrupt discontinuation of therapy when possible.
Because there are no adequate and well-controlled studies of selegiline use in pregnant women, oral selegiline should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. The available data on transdermal selegiline in pregnant women are not sufficient to provide information on the risk of drug-associated adverse outcomes during pregnancy. When treating a pregnant woman for depression with transdermal selegiline, the potential risks of taking a monoamine oxidase inhibitor (MAOI), particularly the risk of hypertensive crisis during pregnancy, should be weighed against the established benefits of treating depression with an antidepressant. Selegiline has a low molecular weight and would be expected to cross the placenta. A case report of oral selegiline used in a pregnant woman who continued the drug throughout gestation noted no teratogenic defects or developmental delays in a healthy male infant over a 10-year period. However, animal studies suggest the potential for neurological changes. Decreases in fetal weight, delayed ossification, and embryo-fetal post-implantation lethality have been noted during the period of organogenesis in animal studies at doses up to 60 times the maximum recommended human dose (MRHD). Slight increases in visceral malformations have been seen during the period of embryo-fetal development in animal studies at doses up to 64 times the MRHD. An increase in stillborn pups and post-implantation loss has been seen in rat studies. Throughout lactation and post-weaning periods, decreases in pup weight, retarded pup physical development, and retarded pup neurobehavioral and sexual development were seen at all doses up to 60 times the MRHD. These findings suggest persistent effects on the offspring of treated dams. A no-effect dose was not established for developmental toxicity. It is not known how these animal findings relate to effects in pregnant women. Selegiline has no established use in labor and delivery. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to selegiline; information about the registry can be obtained at womensmentalhealth.org/research/pregnancyregistry or by calling 1-866-961-2388.
It is unknown if selegiline is excreted into human breast milk, effects the breast-fed infant, or effects milk production. Selegiline has a low molecular weight (188 for the free base) and would be expected to cross into human breast milk. During treatment with the oral capsule or tablet formulations of selegiline, a decision should be made whether to discontinue the drug or discontinue breast-feeding, taking into account the importance of the drug to the mother. Consideration should be given to discontinuing the use of all but absolutely essential drug treatments in nursing women. Because of the potential for serious adverse effects in a breast-fed infant, including hypertensive crisis, the manufacturer for the orally disintegrating tablets recommends against breast-feeding during treatment and for 7 days after the final dose. The manufacturer for transdermal selegiline recommends against breast-feeding during treatment with transdermal selegiline and for 5 days after the final dose. A case report describes maternal use of oral selegiline 10 mg/day, levodopa 400 mg, and benserazide 100 mg daily throughout pregnancy and for 3 days while breast-feeding; the child was followed for 10 years and no developmental abnormalities were found. Although rasagiline may be considered as an alternative therapy to selegiline for the adjunct treatment of Parkinson's disease in breast-feeding women, safety data are lacking. In addition, both rasagiline and selegiline can inhibit prolactin secretion, and thus, interference with proper lactation is possible. Psychotropic medications affect neurotransmitter function in the developing central nervous system, and therefore, the accurate prediction of long-term adverse effects may not be possible. Alternatives to selegiline for the treatment of depression may be considered. Because a pooled analysis found that maternal use of sertraline, along with nortriptyline and paroxetine, usually produced undetectable or low drug concentrations in infant serum, these agents may be preferable to other antidepressants when initiating antidepressant therapy in a breast-feeding mother.
Geriatric individuals should be advised that they may develop symptomatic or asymptomatic hypotension or orthostatic hypotension while taking oral selegiline, particularly during treatment initiation and may increase the risk for falls. During clinical trials of transdermal selegiline for depression treatment, effectiveness was not different based on age; however, treated adults 50 years of age and older appeared to be at higher risk for rash than younger adults (4.4% vs. 3.4%). Antidepressant MAOI agents tend not to be first-line options for depression treatment in adults, even when using more selective agents like selegiline, and older adults may be more likely to have MAOI drug interaction concerns or interactions with concomitant diseases or conditions. The U.S. Omnibus Budget Reconciliation Act (OBRA) regulates the use of antidepressants in residents of long-term care facilities (LTCFs). When an antidepressant is being used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt to taper the medication as outlined in the OBRA guidelines, unless a taper is clinically contraindicated. Dosages and durations of treatment used in the geriatric adult should be in accordance with prescribing labels, published literature recommendations, and expert guidelines.
Caution is advised when administering selegiline orally disintegrating tablets to patients with phenylketonuria (PKU). Each selegiline orally disintegrating tablet contains 1.25 mg of phenylalanine (a component of aspartame), which can be harmful to patients with PKU. Before prescribing the orally disintegrating tablets to patients with PKU, consider the combined daily amount of phenylalanine from all sources.
The effect of direct heat applied to the selegiline transdermal patch on the bioavailability of selegiline has not been studied. However, in theory, heat may result in an increase in the amount of selegiline absorbed from the patch and produce elevated serum levels of selegiline. Patients should be advised to avoid exposing the patch application site to external sources of direct heat, such as a heating pad or electric blanket, or any external ambient temperature increase from heat lamps, saunas, hot tubs, heated water beds, and prolonged direct sunlight (UV) exposure.
For the treatment of Parkinson's disease as an adjunct to carbidopa/levodopa:
Oral dosage (tablets and capsules):
Adults: 5 mg PO twice daily.
Oral dosage (orally disintegrating tablets):
Adults: 1.25 mg PO once daily for at least 6 weeks, initially. May increase the dose to 2.5 mg PO once daily based on clinical response and tolerability.
For the treatment of major depression:
Transdermal dosage:
Adults: 6 mg/24 hours transdermally once daily, initially. May increase the dose by 3 mg/24 hours at intervals of 2 weeks or more. Usual dose: 6 to 12 mg/24 hours. Max: 12 mg/24 hours. However, clinical trials were not designed to assess if higher doses are more effective than the lowest effective dose of 6 mg/24 hours.
Maximum Dosage Limits:
-Adults
10 mg/day PO (oral tablets or capsules); 2.5 mg/day PO (orally-disintegrating tablet); Emsam 12 mg/24 hour transdermally.
-Geriatric
10 mg/day PO (oral tablets or capsules); 2.5 mg/day PO (orally-disintegrating tablet); Emsam 12 mg/24 hour transdermally.
-Adolescents
Safety and efficacy have not been established.
-Children
12 years: Safety and efficacy have not been established.
Less than 12 years: Transdermal patch is contraindicated.
-Infants
Not indicated.
Patients with Hepatic Impairment Dosing
Mild to Moderate hepatic impairment (Child-Pugh score 5 to 9): A dose reduction of selegiline orally disintegrating tablets (from 2.5 mg/day to 1.25 mg/day) may be required depending on clinical response. No adjustment of transdermal selegiline is needed. Specific guidelines for dosage adjustments for oral selegiline tablets and capsules are not available.
Severe hepatic impairment (Child-Pugh score greater than 9): Selegiline orally disintegrating tablets are not recommended. Transdermal selegiline has not been studied. Specific guidelines for oral selegiline tablets or capsules in severe hepatic impairment are not available.
Patients with Renal Impairment Dosing
No dose adjustment of selegiline orally disintegrating tablets is required in patients with mild to moderate renal impairment (CrCl 30 to 89 mL/minute). Selegiline orally disintegrating tablets are not recommended in patients with severe renal impairment or end-stage renal disease (CrCl less than 30 mL/minute). No dosage adjustment of transdermal selegiline is needed in patients with mild, moderate, or severe renal impairment; transdermal selegiline has not been studied in patients with end-stage renal disease. Specific guidelines for dosage adjustment of oral selegiline tablets or caspules are not available.
*non-FDA-approved indication
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of diphenhydramine and selegiline due to the risk for additive CNS depression.
Acetaminophen; Caffeine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Avoid use if possible. Dihydrocodeine is closely related to codeine and is usually considered contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with dihydrocodeine. After stopping treatment with dihydrocodeine, a time period equal to 4 to 5 half-lives of the drug or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and pyrilamine. Concurrent use may result in additive CNS depression.
Acetaminophen; Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
Acetaminophen; Codeine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Acetaminophen; Dextromethorphan: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan.
Acetaminophen; Dextromethorphan; Doxylamine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of doxylamine and selegiline due to the risk for additive CNS depression.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Acetaminophen; Dextromethorphan; Phenylephrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Acetaminophen; Diphenhydramine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of diphenhydramine and selegiline due to the risk for additive CNS depression.
Acetaminophen; Guaifenesin; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
Acetaminophen; Hydrocodone: (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
Acetaminophen; Oxycodone: (Major) Avoid concomitant use of oxycodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and pyrilamine. Concurrent use may result in additive CNS depression.
Acetaminophen; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
Acetaminophen; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Acrivastine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. (Major) Avoid coadministration of selegiline with acrivastine due to the risk of additive CNS depression.
Alfentanil: (Moderate) Monitor patients for hypertension and serotonin syndrome and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension, as needed, if alfentanil is administered to patients who have received selegiline within 14 days. Selegiline interactions with alfentanil may also manifest as opioid toxicity. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Almotriptan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant almotriptan and selegiline use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Alprazolam: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Amitriptyline: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
Amobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
Amoxapine: (Contraindicated) Amoxapine, a heterocyclic antidepressant, is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with amoxapine. After stopping treatment with amoxapine, a time period equal to 4 to 5 half-lives of amoxapine or any active metabolite should elapse before starting therapy with selegiline. Hyperpyretic crisis and serotonin syndrome have occurred in patients receiving selective MAO-B inhibitors and cyclic antidepressants simultaneously.
Amphetamine: (Contraindicated) The product labels for amphetamines contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis or serotonin syndrome. Amphetamines should not be used concurrently with MAOIs or within 14 days before or after their use. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Amphetamine; Dextroamphetamine: (Contraindicated) The product labels for amphetamines contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis or serotonin syndrome. Amphetamines should not be used concurrently with MAOIs or within 14 days before or after their use. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Amphetamines: (Contraindicated) The product labels for amphetamines contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis or serotonin syndrome. Amphetamines should not be used concurrently with MAOIs or within 14 days before or after their use. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline with anxiolytics, sedatives, and hypnotics. Concurrent use may result in additive CNS depression.
Apalutamide: (Moderate) Use caution if selegiline and apalutamide are used concomitantly. Although apalutamide is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
Aripiprazole: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Armodafinil: (Moderate) Use caution during concomitant use of selegiline and armodafinil. Armodafinil has not been evaluated for drug interactions with monoamine oxidase inhibitors (MAOIs); however, it is known that many other CNS stimulants may induce severe cardiovascular reactions, such as hypertensive crisis, if administered in combination with drugs with non-selective MAO inhibitor activity.
Articaine; Epinephrine: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as epinephrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
Asenapine: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
Aspirin, ASA; Caffeine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
Aspirin, ASA; Carisoprodol; Codeine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Aspirin, ASA; Oxycodone: (Major) Avoid concomitant use of oxycodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Atomoxetine: (Contraindicated) Selective norepinephrine reuptake inhibitors are contraindicated for use with selegiline because of a possible increased risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a selective norepinephrine reuptake inhibitor. After stopping treatment with the reuptake inhibitor, a time period equal to 4 to 5 half-lives of the reuptake inhibitor or any active metabolite should elapse before starting therapy with selegiline.
Atropine; Difenoxin: (Major) Avoid concomitant use of selegiline and diphenoxylate or difenoxin due to the theoretical risk of hypertensive crisis. The chemical structure of difenoxin and diphenoxylate are similar to opioids that are known to precipitate these events when used with MAO inhibitors.
atypical antipsychotic: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Azelastine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and azelastine. Concurrent use may result in additive CNS depression.
Azelastine; Fluticasone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and azelastine. Concurrent use may result in additive CNS depression.
Barbiturates: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
Belladonna; Opium: (Moderate) Concomitant use of opioid agonists with selegiline may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of opium with selegiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Benzhydrocodone; Acetaminophen: (Major) The use of benzhydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
Benzodiazepines: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Concurrent use of intravenous (IV) methylene blue and MAOIs such as selegiline should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI, it is advisable to discontinue the MAOI and monitor the patient for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, it is advisable to discontinue the MAOI at least 2 weeks prior to methylene blue treatment, but also taking into consideration the half-life of selegiline. Because selegiline is a selective monoamine oxidase-B (MAO-B) inhibitor, an interaction may be less likely to occur than with other traditional MAOIs. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
Benzphetamine: (Contraindicated) The product labels for amphetamines contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis or serotonin syndrome. Amphetamines should not be used concurrently with MAOIs or within 14 days before or after their use. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Bretylium: (Minor) Selegiline, a monoamine oxidase type B inhibitor, might potentiate the effects of the early release of catecholamines from nerve endings produced by bretylium, such as transient hypertension and increased frequency of arrhythmias. Bretylium causes an early release of norepinephrine from the adrenergic nerve terminals.
Brexpiprazole: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Brimonidine: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Brimonidine; Brinzolamide: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Brimonidine; Timolol: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Brompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and brompheniramine. Concurrent use may result in additive CNS depression.
Brompheniramine; Dextromethorphan; Phenylephrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and brompheniramine. Concurrent use may result in additive CNS depression.
Brompheniramine; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and brompheniramine. Concurrent use may result in additive CNS depression.
Brompheniramine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and brompheniramine. Concurrent use may result in additive CNS depression.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and brompheniramine. Concurrent use may result in additive CNS depression.
Bupivacaine; Epinephrine: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as epinephrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
Buprenorphine: (Major) Avoid concomitant use of buprenorphine in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
Buprenorphine; Naloxone: (Major) Avoid concomitant use of buprenorphine in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
Bupropion: (Contraindicated) The manufacturer of bupropion contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with bupropion. After stopping treatment with bupropion, a time period equal to 4 to 5 half-lives of bupropion or any active metabolite should elapse before starting therapy with selegiline.
Bupropion; Naltrexone: (Contraindicated) The manufacturer of bupropion contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with bupropion. After stopping treatment with bupropion, a time period equal to 4 to 5 half-lives of bupropion or any active metabolite should elapse before starting therapy with selegiline.
Buspirone: (Contraindicated) Concomitant use of transdermal selegiline with buspirone or within 14 days after discontinuation of treatment with either agent is contraindicated due to the risk of serotonin syndrome; buspirone has serotonergic activity. The use of buspirone with selegiline may also produce substantial elevations in blood pressure. For selegiline oral formulations, monitor blood pressure for hypertension if use with buspirone is necessary. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
Butalbital; Acetaminophen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
Butalbital; Acetaminophen; Caffeine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
Butalbital; Acetaminophen; Caffeine; Codeine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
Butalbital; Aspirin; Caffeine; Codeine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
Butorphanol: (Major) Avoid coadministration of butorphanol with selegiline due to the risk for serotonin syndrome and additive CNS depression. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Monitor for CNS depression and the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Caffeine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
Caffeine; Sodium Benzoate: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and sodium oxybate. Concurrent use may result in additive CNS depression.
Carbamazepine: (Contraindicated) Carbamazepine is contraindicated for use with selegiline, an inhibitor of monoamine oxidase type B, because of a possible increased risk of serotonin syndrome and/or hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with carbamazepine. After stopping treatment with carbamazepine, a time period equal to 4 to 5 half-lives of carbamazepine or any active metabolite should elapse before starting therapy with selegiline. When used with selegiline transdermal, carbamazepine has been shown to significantly elevate selegiline levels, which may increase the risk of a hypertensive crisis.
Carbidopa; Levodopa: (Moderate) Monitor blood pressure during concomitant use of levodopa and selegiline. Concomitant use of levodopa with selective MAO-B inhibitors may be associated with orthostatic hypotension.
Carbidopa; Levodopa; Entacapone: (Moderate) Monitor blood pressure during concomitant use of levodopa and selegiline. Concomitant use of levodopa with selective MAO-B inhibitors may be associated with orthostatic hypotension.
Carbinoxamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and carbinoxamine. Concurrent use may result in additive CNS depression.
Cariprazine: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Celecoxib; Tramadol: (Contraindicated) Tramadol use is contraindicated in patients who are receiving or who have received selegiline within the previous 14 days. Concomitant use increases the risk for seizures, serotonin syndrome, and opioid toxicity, including respiratory depression.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and selegiline. Concurrent use may result in additive CNS depression.
Cetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and selegiline due to the risk for additive CNS depression.
Cetirizine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and selegiline due to the risk for additive CNS depression.
Chlophedianol; Dexbrompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and dexbrompheniramine. Concurrent use may result in additive CNS depression.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and dexchlorpheniramine. Concurrent use may result in additive CNS depression.
Chlorcyclizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorcyclizine. Concurrent use may result in additive CNS depression.
Chlordiazepoxide: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Chlordiazepoxide; Amitriptyline: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Chlordiazepoxide; Clidinium: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
Chlorpheniramine; Codeine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
Chlorpheniramine; Dextromethorphan: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
Chlorpheniramine; Hydrocodone: (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
Chlorpheniramine; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
Chlorpheniramine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
Chlorpromazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of phenothiazines and selegiline due to the risk for additive CNS depression. It is also possible that dopamine antagonists, such as phenothiazines, could diminish the effectiveness of selegiline.
Citalopram: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. 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 selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
Clemastine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and clemastine. Concurrent use may result in additive CNS depression.
Clomipramine: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
Clonazepam: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Clorazepate: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Clozapine: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Codeine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Codeine; Guaifenesin: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Codeine; Guaifenesin; Pseudoephedrine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Codeine; Phenylephrine; Promethazine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of phenothiazines and selegiline due to the risk for additive CNS depression. It is also possible that dopamine antagonists, such as phenothiazines, could diminish the effectiveness of selegiline.
Codeine; Promethazine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of phenothiazines and selegiline due to the risk for additive CNS depression. It is also possible that dopamine antagonists, such as phenothiazines, could diminish the effectiveness of selegiline.
Cyclobenzaprine: (Contraindicated) Cyclobenzaprine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with cyclobenzaprine. After stopping treatment with cyclobenzaprine, a time period equal to 4 to 5 half-lives of cyclobenzaprine or any active metabolite should elapse before starting therapy with selegiline.
Cyproheptadine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and cyproheptadine. Concurrent use may result in additive CNS depression.
Desflurane: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
Desipramine: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
Desloratadine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Desogestrel; Ethinyl Estradiol: (Moderate) Consider a selegiline dose reduction to minimize the risk for selegiline-related adverse reactions during concomitant ethinyl estradiol use. Concomitant use may increase selegiline exposure.
Desvenlafaxine: (Contraindicated) Serotonin norepinephrine reuptake inhibitors (SNRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SNRI. After stopping treatment with an SNRI, a time period equal to 4 to 5 half-lives of the SNRI or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
Deutetrabenazine: (Contraindicated) Deutetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy, such as selegiline, within the past 14 days. The major metabolites of deutetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
Dexbrompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and dexbrompheniramine. Concurrent use may result in additive CNS depression.
Dexbrompheniramine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and dexbrompheniramine. Concurrent use may result in additive CNS depression.
Dexchlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and dexchlorpheniramine. Concurrent use may result in additive CNS depression.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and dexchlorpheniramine. Concurrent use may result in additive CNS depression.
Dexmethylphenidate: (Contraindicated) The product labels for methylphenidate and its derivatives contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis. Methylphenidate derivatives should not be used concurrently with selegiline or within 14 days before or after selegiline use.
Dextroamphetamine: (Contraindicated) The product labels for amphetamines contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis or serotonin syndrome. Amphetamines should not be used concurrently with MAOIs or within 14 days before or after their use. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Dextromethorphan: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan.
Dextromethorphan; Bupropion: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The manufacturer of bupropion contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with bupropion. After stopping treatment with bupropion, a time period equal to 4 to 5 half-lives of bupropion or any active metabolite should elapse before starting therapy with selegiline.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of diphenhydramine and selegiline due to the risk for additive CNS depression.
Dextromethorphan; Guaifenesin: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan.
Dextromethorphan; Guaifenesin; Phenylephrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Dextromethorphan; Quinidine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan.
Diazepam: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Diethylpropion: (Contraindicated) The product label for diethylpropion contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Diethylpropion should generally not be used concurrently with MAOIs or within 14 days before or after their use.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Dimenhydrinate: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of dimenhydrinate and selegiline due to the risk for additive CNS depression.
Diphenhydramine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of diphenhydramine and selegiline due to the risk for additive CNS depression.
Diphenhydramine; Ibuprofen: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of diphenhydramine and selegiline due to the risk for additive CNS depression.
Diphenhydramine; Naproxen: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of diphenhydramine and selegiline due to the risk for additive CNS depression.
Diphenhydramine; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of diphenhydramine and selegiline due to the risk for additive CNS depression.
Diphenoxylate; Atropine: (Major) Avoid concomitant use of selegiline and diphenoxylate or difenoxin due to the theoretical risk of hypertensive crisis. The chemical structure of difenoxin and diphenoxylate are similar to opioids that are known to precipitate these events when used with MAO inhibitors.
Dobutamine: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as dobutamine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
Dolasetron: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant selegiline and serotonin-receptor antagonist use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dopamine: (Major) Patients who have been treated with monoamine oxidase inhibitors (MAOIs), such as selegiline, within two to three weeks prior to the administration of dopamine should receive initial doses of dopamine no greater than one-tenth of the usual dose. Because dopamine is metabolized by monoamine oxidase, inhibition of this enzyme by MAOIs prolongs and potentiates the effect of dopamine.
Doxapram: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as doxapram. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
Doxepin: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
Doxylamine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of doxylamine and selegiline due to the risk for additive CNS depression.
Doxylamine; Pyridoxine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of doxylamine and selegiline due to the risk for additive CNS depression.
Dronabinol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and dronabinol. Concurrent use may result in additive CNS depression.
Droperidol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and droperidol. Concurrent use may result in additive CNS depression.
Drospirenone; Ethinyl Estradiol: (Moderate) Consider a selegiline dose reduction to minimize the risk for selegiline-related adverse reactions during concomitant ethinyl estradiol use. Concomitant use may increase selegiline exposure.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Consider a selegiline dose reduction to minimize the risk for selegiline-related adverse reactions during concomitant ethinyl estradiol use. Concomitant use may increase selegiline exposure.
Duloxetine: (Contraindicated) Serotonin norepinephrine reuptake inhibitors (SNRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SNRI. After stopping treatment with an SNRI, a time period equal to 4 to 5 half-lives of the SNRI or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
Eletriptan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant eletriptan and selegiline use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Encorafenib: (Moderate) Monitor for a decrease in selegiline efficacy if coadministered with encorafenib. Although adequate studies have not been conducted, concurrent use may decrease selegiline exposure. Selegiline is a CYP3A substrate and encorafenib is a strong CYP3A inducer.
Enzalutamide: (Moderate) Use caution if selegiline and enzalutamide are used concomitantly. Although enzalutamide is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
Ephedrine: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as ephedrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
Ephedrine; Guaifenesin: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as ephedrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
Epinephrine: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as epinephrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
Ergotamine; Caffeine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
Escitalopram: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. 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 selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
Esketamine: (Moderate) Closely monitor patients receiving esketamine and selegiline for sedation and increased blood pressure, including the possibility of hypertensive crisis.
Eslicarbazepine: (Contraindicated) Eslicarbazepine is a prodrug of carbamazepine, which is contraindicated for use with selegiline because of a possible increased risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with eslicarbazepine. After stopping treatment with eslicarbazepine, a time period equal to 4 to 5 half-lives of the active moiety carbamazepine should elapse before starting therapy with selegiline.
Estazolam: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Eszopiclone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline with anxiolytics, sedatives, and hypnotics. Concurrent use may result in additive CNS depression.
Ethanol: (Major) Advise patients to avoid the use of alcohol or alcohol-containing products with selegiline. Use may cause additive CNS depression and some alcohol-containing products may also contain tyramine. Certain alcohol-containing beverages that are tyramine-rich can precipitate a hypertensive reaction if consumed by patients during therapy with selegiline. These include some beers; wines; sherry; hard liquor; or liqueurs. (Major) Advise patients to avoid the use of alcohol or alcohol-containing products with selegiline. Use may cause additive CNS depression and some alcohol-containing products may also contain tyramine. Certain alcohol-containing beverages that are tyramine-rich can precipitate a hypertensive reaction if consumed by patients during therapy with selegiline. These include some beers; wines; sherry; hard liquor; or liqueurs.
Ethinyl Estradiol; Norelgestromin: (Moderate) Consider a selegiline dose reduction to minimize the risk for selegiline-related adverse reactions during concomitant ethinyl estradiol use. Concomitant use may increase selegiline exposure.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Consider a selegiline dose reduction to minimize the risk for selegiline-related adverse reactions during concomitant ethinyl estradiol use. Concomitant use may increase selegiline exposure.
Ethinyl Estradiol; Norgestrel: (Moderate) Consider a selegiline dose reduction to minimize the risk for selegiline-related adverse reactions during concomitant ethinyl estradiol use. Concomitant use may increase selegiline exposure.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Consider a selegiline dose reduction to minimize the risk for selegiline-related adverse reactions during concomitant ethinyl estradiol use. Concomitant use may increase selegiline exposure.
Etomidate: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
Etonogestrel; Ethinyl Estradiol: (Moderate) Consider a selegiline dose reduction to minimize the risk for selegiline-related adverse reactions during concomitant ethinyl estradiol use. Concomitant use may increase selegiline exposure.
Fenfluramine: (Contraindicated) Fenfluramine is contraindicated for use with monoamine oxidase inhibitorsr (MAOIs), such as selegiline, due to the risk of serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with fenfluramine. After stopping treatment with fenfluramine, a time period equal to 4 to 5 half-lives of fenfluramine or any active metabolite should elapse before starting therapy with selegiline.
Fentanyl: (Major) Avoid concomitant use of fentanyl in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
Fexofenadine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Fluoxetine: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. 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 selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
Fluphenazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of phenothiazines and selegiline due to the risk for additive CNS depression. It is also possible that dopamine antagonists, such as phenothiazines, could diminish the effectiveness of selegiline.
Flurazepam: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Fluvoxamine: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. 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 selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
Food: (Major) A diet low in tyramine content may be necessary to avoid this interaction. Patients should be informed not to exceed the recommended selegiline dose, follow dietary instructions, and should generally be instructed to avoid tyramine-rich foods. Selegiline is selective for MAO-B at recommended doses (2.5 to 12 mg/day). However, certain foods may contain very high amounts (i.e., 150 mg or greater) of tyramine and could potentially cause a hypertensive reaction in individual patients with increased sensitivity to tyramine. Food sources considered to be high in tyramine and that may interact with MAO inhibitors in general include Stilton aged cheese, concentrated yeast extracts (e.g., Marmite), aged meats, and sauerkraut. Ethanol ingestion of alcoholic beverages with high tyramine content (e.g., tap beers) also may place patients at risk. If a patient eats foods very rich in tyramine and does not feel well soon after eating, the patient should contact their healthcare provider. Patients should also be instructed to contact their healthcare provider if they experience severe headache, shortness of breath, palpitations, diaphoresis, chest pain or other symptoms suggestive of a significant hypertensive reaction or hypertensive crisis. (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Fosphenytoin: (Moderate) Monitor for a decrease in selegiline efficacy if coadministered with fosphenytoin. Although adequate studies have not been conducted, concurrent use may decrease selegiline exposure. Selegiline is a CYP3A substrate and phenytoin is a strong CYP3A inducer.
Frovatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering frovatriptan with transdermal selegiline, orally disintegrating selegiline tablets, and high doses of oral selegiline capsules and tablets. Since selegiline oral tablets and capsules selectively inhibit MAO-B at recommended doses, no interaction with frovatriptan would be expected with normal prescription use. However, MAO-B selectivity decreases with increasing doses, therefore, an interaction may occur with high dose treatment. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue frovatriptan and selegiline and initiate symptomatic treatment if serotonin syndrome occurs.
Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and gabapentin. Concurrent use may result in additive CNS depression.
General anesthetics: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
Granisetron: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant selegiline and serotonin-receptor antagonist use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Guaifenesin; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
Guaifenesin; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Guanfacine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) such as selegiline are combined with antihypertensives. In addition, when beginning treatment with antihypertensives that initially increase the release of catecholamine stores, such as guanfacine, hypertensive crisis may occur. Because selegiline is a selective MAO-B inhibitor at manufacturer recommended doses, serious reactions with agents affecting catecholamine release are less likely than with non-selective MAOIs. Abrupt cessation of therapy with central alpha-2 adrenergic agonists like guanfacine may be associated with increases (from depressed on-therapy levels) in plasma and urinary catecholamines, symptoms of nervousness and anxiety and, less commonly, increases in blood pressure to levels significantly greater than those prior to therapy, which may affect MAO inhibiting therapy.
Haloperidol: (Major) Due to opposing effects on central dopaminergic activity, selegiline and haloperidol may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Homatropine; Hydrocodone: (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
Hydrocodone: (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
Hydrocodone; Ibuprofen: (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
Hydromorphone: (Major) Avoid concomitant use of hydromorphone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Hydroxyzine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of hydroxyzine and selegiline due to the risk for additive CNS depression.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Concurrent use of intravenous (IV) methylene blue and MAOIs such as selegiline should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI, it is advisable to discontinue the MAOI and monitor the patient for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, it is advisable to discontinue the MAOI at least 2 weeks prior to methylene blue treatment, but also taking into consideration the half-life of selegiline. Because selegiline is a selective monoamine oxidase-B (MAO-B) inhibitor, an interaction may be less likely to occur than with other traditional MAOIs. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
Ibuprofen; Oxycodone: (Major) Avoid concomitant use of oxycodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Ibuprofen; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Iloperidone: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Imipramine: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
Iobenguane I 131: (Major) Discontinue monoamine oxidase inhibitors for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart monoamine oxidase inhibitors until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as monoamine oxidase inhibitors, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy.
Ioflupane I 123: (Moderate) Selegiline may bind to the dopamine transporter and interfere with dopamine transporter (DAT) imaging that utilizes radiolabeled ioflupane.
Isocarboxazid: (Contraindicated) Non-selective monoamine oxidase inhibitors (MAOIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk for hypertensive crisis and a potential risk for serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an MAOI. After stopping treatment with an MAOI, a time period equal to 4 to 5 half-lives of the MAOI or any active metabolite should elapse before starting therapy with selegiline. Hypertensive crisis has occurred in patients receiving selective MAO-B inhibitors and non-selective MAOIs simultaneously.
Isoflurane: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
Isoniazid, INH: (Major) Concurrent use of selegiline and isoniazid may increase the risk of a hypertensive crisis. Isoniazid has monoamine oxidase inhibiting activity and selegiline is a monoamine oxidase inhibitor (MAOI) type B. Monoamine oxidase type A is the primary enzyme in the gastrointestinal tract, and is responsible for the breakdown of dietary amines such as tyramine. When monoamine oxidase is inhibited by an MAOI, tyramine is absorbed systemically and may result in a hypertensive crisis. Although selegiline is a selective monoamine oxidase inhibitor type B, there is a risk of hypertension during ingestion of substances high in tyramine or during concurrent use of other drugs with MAOI activity such as isoniazid, since the MAOI-B selectivity of selegiline decreases with increasing dosages.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Concurrent use of selegiline and isoniazid may increase the risk of a hypertensive crisis. Isoniazid has monoamine oxidase inhibiting activity and selegiline is a monoamine oxidase inhibitor (MAOI) type B. Monoamine oxidase type A is the primary enzyme in the gastrointestinal tract, and is responsible for the breakdown of dietary amines such as tyramine. When monoamine oxidase is inhibited by an MAOI, tyramine is absorbed systemically and may result in a hypertensive crisis. Although selegiline is a selective monoamine oxidase inhibitor type B, there is a risk of hypertension during ingestion of substances high in tyramine or during concurrent use of other drugs with MAOI activity such as isoniazid, since the MAOI-B selectivity of selegiline decreases with increasing dosages. (Moderate) Use caution if selegiline and rifampin are used concomitantly. Although rifampin is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
Isoniazid, INH; Rifampin: (Major) Concurrent use of selegiline and isoniazid may increase the risk of a hypertensive crisis. Isoniazid has monoamine oxidase inhibiting activity and selegiline is a monoamine oxidase inhibitor (MAOI) type B. Monoamine oxidase type A is the primary enzyme in the gastrointestinal tract, and is responsible for the breakdown of dietary amines such as tyramine. When monoamine oxidase is inhibited by an MAOI, tyramine is absorbed systemically and may result in a hypertensive crisis. Although selegiline is a selective monoamine oxidase inhibitor type B, there is a risk of hypertension during ingestion of substances high in tyramine or during concurrent use of other drugs with MAOI activity such as isoniazid, since the MAOI-B selectivity of selegiline decreases with increasing dosages. (Moderate) Use caution if selegiline and rifampin are used concomitantly. Although rifampin is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
Isoproterenol: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as isoproterenol. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
Ketamine: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
Lasmiditan: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and selegiline. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and selegiline. Dosage adjustments of lemborexant and selegiline may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Levocetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and selegiline due to the risk for additive CNS depression.
Levodopa: (Moderate) Monitor blood pressure during concomitant use of levodopa and selegiline. Concomitant use of levodopa with selective MAO-B inhibitors may be associated with orthostatic hypotension.
Levomilnacipran: (Contraindicated) Serotonin norepinephrine reuptake inhibitors (SNRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SNRI. After stopping treatment with an SNRI, a time period equal to 4 to 5 half-lives of the SNRI or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
Levonorgestrel; Ethinyl Estradiol: (Moderate) Consider a selegiline dose reduction to minimize the risk for selegiline-related adverse reactions during concomitant ethinyl estradiol use. Concomitant use may increase selegiline exposure.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Consider a selegiline dose reduction to minimize the risk for selegiline-related adverse reactions during concomitant ethinyl estradiol use. Concomitant use may increase selegiline exposure.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Consider a selegiline dose reduction to minimize the risk for selegiline-related adverse reactions during concomitant ethinyl estradiol use. Concomitant use may increase selegiline exposure.
Levorphanol: (Moderate) Concomitant use of opioid agonists with selegiline may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of levorphanol with selegiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Lidocaine; Epinephrine: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as epinephrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
Linezolid: (Contraindicated) Concurrent use of linezolid with selegiline, a monoamine oxidase inhibitor type B (MAO-B inhibitor), or use of linezolid within 2 weeks of taking selegiline is contraindicated due to the risk of increased blood pressure, including hypertensive crisis. Linezolid is an antibiotic that is also a potent inhibitor of monoamine oxidase. Serotonin syndrome has also been reported when linezolid is given with serotonergic agents, including MAOIs, which can potentiate central serotonin levels.
Lisdexamfetamine: (Contraindicated) The product labels for amphetamines contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis or serotonin syndrome. Amphetamines should not be used concurrently with MAOIs or within 14 days before or after their use. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Lithium: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant selegiline and lithium use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Loratadine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Lorazepam: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Lorcaserin: (Moderate) Concomitant use of selegiline and lorcaserin may increase the risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Loxapine: (Moderate) Due to opposing effects on central dopaminergic activity, loxapine and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible; consider an atypical antipsychotic as an alternative to loxapine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Lumateperone: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Lurasidone: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Maprotiline: (Contraindicated) Concurrent use of selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), and maprotiline, a selective norepinephrine reuptake inhibitor, is contraindicated due to the potential for severe or life-threatening reactions such as hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with maprotiline. After stopping treatment with maprotiline, a time period equal to 4 to 5 half-lives of maprotiline or any active metabolite should elapse before starting therapy with selegiline.
Meperidine: (Contraindicated) Coadministration of meperidine and selegiline is contraindicated due to a risk for serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with meperidine. After stopping treatment with meperidine, a time period equal to 4 to 5 half-lives of meperidine or any active metabolite should elapse before starting therapy with selegiline. Therapeutic doses of meperidine have occasionally precipitated unpredictable, severe, and occasionally fatal reactions in patients who have received MAO inhibiting agents within the past 14 days, and may increase the risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Meprobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline with anxiolytics, sedatives, and hypnotics. Concurrent use may result in additive CNS depression.
Methadone: (Contraindicated) Coadministration of methadone and selegiline is contraindicated due to a risk for serotonin syndrome and opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with methadone. After stopping treatment with methadone, a time period equal to 4 to 5 half-lives of methadone or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of an alternate opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Methamphetamine: (Contraindicated) The product labels for amphetamines contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis or serotonin syndrome. Amphetamines should not be used concurrently with MAOIs or within 14 days before or after their use. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Concurrent use of intravenous (IV) methylene blue and MAOIs such as selegiline should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI, it is advisable to discontinue the MAOI and monitor the patient for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, it is advisable to discontinue the MAOI at least 2 weeks prior to methylene blue treatment, but also taking into consideration the half-life of selegiline. Because selegiline is a selective monoamine oxidase-B (MAO-B) inhibitor, an interaction may be less likely to occur than with other traditional MAOIs. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
Methohexital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
Methyldopa: (Contraindicated) Methyldopa is contraindicated for use with monoamine oxidase inhibitors (MAOIs). Administration of MAOIs with methyldopa has resulted in headaches, severe hypertension, and hallucinations, although data describing the interaction between MAOIs and methyldopa are limited.
Methylene Blue: (Major) Concurrent use of intravenous (IV) methylene blue and MAOIs such as selegiline should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI, it is advisable to discontinue the MAOI and monitor the patient for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, it is advisable to discontinue the MAOI at least 2 weeks prior to methylene blue treatment, but also taking into consideration the half-life of selegiline. Because selegiline is a selective monoamine oxidase-B (MAO-B) inhibitor, an interaction may be less likely to occur than with other traditional MAOIs. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
Methylphenidate Derivatives: (Contraindicated) The product labels for methylphenidate and its derivatives contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis. Methylphenidate derivatives should not be used concurrently with selegiline or within 14 days before or after selegiline use.
Methylphenidate: (Contraindicated) The product labels for methylphenidate and its derivatives contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis. Methylphenidate derivatives should not be used concurrently with selegiline or within 14 days before or after selegiline use.
Metoclopramide: (Major) Close monitoring is advisable if combination therapy is necessary. Metoclopramide is a central dopamine antagonist and may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, or tardive dyskinesia), and rarely, neuroleptic malignant syndrome. The risk of extrapyramidal effects may be increased during concurrent use of metoclopramide and selegiline, and the therapeutic benefits of selegiline in treating Parkinson's disease may be diminished during use of a central dopamine antagonist such as metoclopramide. In addition, because metoclopramide causes release of catecholamines in patients with essential hypertension, it should be administered cautiously to patients receiving MAOIs.
Midazolam: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Midodrine: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as midodrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
Milnacipran: (Contraindicated) Serotonin norepinephrine reuptake inhibitors (SNRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SNRI. After stopping treatment with an SNRI, a time period equal to 4 to 5 half-lives of the SNRI or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
Mirtazapine: (Contraindicated) Mirtazapine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with mirtazapine. After stopping treatment with mirtazapine, a time period of at least 14 days should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonergic antidepressants simultaneously.
Mitotane: (Moderate) Use caution if selegiline and mitotane are used concomitantly. Although mitotane is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
Modafinil: (Moderate) Use caution during concomitant use of selegiline and modafinil. Modafinil has not been evaluated for drug interactions with monoamine oxidase inhibitors (MAOIs); however, it is known that many other CNS stimulants may induce severe cardiovascular reactions, such as hypertensive crisis, if administered in combination with drugs with non-selective MAO inhibitor activity.
Molindone: (Major) Due to opposing effects on central dopaminergic activity, selegiline and molindone may interfere with the effectiveness of each other. If possible, avoid concurrent use and consider an atypical antipsychotic as an alternative to molindone. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Monoamine oxidase inhibitors: (Contraindicated) Non-selective monoamine oxidase inhibitors (MAOIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk for hypertensive crisis and a potential risk for serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an MAOI. After stopping treatment with an MAOI, a time period equal to 4 to 5 half-lives of the MAOI or any active metabolite should elapse before starting therapy with selegiline. Hypertensive crisis has occurred in patients receiving selective MAO-B inhibitors and non-selective MAOIs simultaneously.
Morphine: (Contraindicated) Morphine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If possible, wait 14 days between discontinuation of selegiline and initiation of treatment with morphine. After stopping treatment with morphine, a time period equal to 4 to 5 half-lives of morphine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Morphine; Naltrexone: (Contraindicated) Morphine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If possible, wait 14 days between discontinuation of selegiline and initiation of treatment with morphine. After stopping treatment with morphine, a time period equal to 4 to 5 half-lives of morphine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Nabilone: (Major) Avoid coadministration of selegiline with nabilone due to the risk of additive CNS depression.
Nalbuphine: (Major) Avoid concomitant use of nalbuphine in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Naproxen; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Naratriptan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant naratriptan and selegiline use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Nefazodone: (Contraindicated) Nefazodone is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with nefazodone. After stopping treatment with nefazodone, a time period equal to 4 to 5 half-lives of nefazodone or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and sertonoergic antidepressants simultaneously.
Norepinephrine: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as norepinephrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Consider a selegiline dose reduction to minimize the risk for selegiline-related adverse reactions during concomitant ethinyl estradiol use. Concomitant use may increase selegiline exposure.
Norethindrone; Ethinyl Estradiol: (Moderate) Consider a selegiline dose reduction to minimize the risk for selegiline-related adverse reactions during concomitant ethinyl estradiol use. Concomitant use may increase selegiline exposure.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Consider a selegiline dose reduction to minimize the risk for selegiline-related adverse reactions during concomitant ethinyl estradiol use. Concomitant use may increase selegiline exposure.
Norgestimate; Ethinyl Estradiol: (Moderate) Consider a selegiline dose reduction to minimize the risk for selegiline-related adverse reactions during concomitant ethinyl estradiol use. Concomitant use may increase selegiline exposure.
Nortriptyline: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
Olanzapine: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Olanzapine; Fluoxetine: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. 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 selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions. (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Olanzapine; Samidorphan: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Oliceridine: (Moderate) Concomitant use of oliceridine with selegiline may cause excessive sedation and somnolence. Limit the use of oliceridine with selegiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Ondansetron: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant selegiline and serotonin-receptor antagonist use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Oxazepam: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Oxcarbazepine: (Contraindicated) Oxcarbazepine is the keto-analogue of carbamazepine, which is contraindicated for use with selegiline because of a possible increased risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with oxcarbazepine. After stopping treatment with oxcarbazepine, a time period equal to 4 to 5 half-lives of oxcarbazepine or any active metabolite should elapse before starting therapy with selegiline.
Oxycodone: (Major) Avoid concomitant use of oxycodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Oxymetazoline: (Moderate) Use these drugs together with caution. Monitor blood pressure for hypertension during concomitant use of selegiline and oxymetazoline. Although oxymetazoline is used by nasal or ophthalmic routes, the use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued immediately and therapy to lower blood pressure should be instituted immediately.
Oxymorphone: (Major) Avoid concomitant use of oxymorphone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity.
Ozanimod: (Contraindicated) Coadministration of ozanimod with monoamine oxidase (MAO) inhibitors, like selegiline, is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of treatment with selegiline. Metabolites of ozanimod may inhibit MAO. The potential for a clinical interaction with MAO inhibitors selegiline has not been studied; however, there may be an increased risk of hypertensive crisis.
Paliperidone: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Palonosetron: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant selegiline and serotonin-receptor antagonist use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Paroxetine: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. 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 selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
Pentazocine; Naloxone: (Contraindicated) Coadministration of pentazocine and selegiline is contraindicated due to a risk for serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with pentazocine. After stopping treatment with pentazocine, a time period equal to 4 to 5 half-lives of pentazocine or any active metabolite should elapse before starting therapy with selegiline.
Pentobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
Perampanel: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and perampanel. Concurrent use may result in additive CNS depression.
Perphenazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of phenothiazines and selegiline due to the risk for additive CNS depression. It is also possible that dopamine antagonists, such as phenothiazines, could diminish the effectiveness of selegiline.
Perphenazine; Amitriptyline: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of phenothiazines and selegiline due to the risk for additive CNS depression. It is also possible that dopamine antagonists, such as phenothiazines, could diminish the effectiveness of selegiline.
Phendimetrazine: (Contraindicated) The product label for phendimetrazine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phendimetrazine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
Phenelzine: (Contraindicated) Non-selective monoamine oxidase inhibitors (MAOIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk for hypertensive crisis and a potential risk for serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an MAOI. After stopping treatment with an MAOI, a time period equal to 4 to 5 half-lives of the MAOI or any active metabolite should elapse before starting therapy with selegiline. Hypertensive crisis has occurred in patients receiving selective MAO-B inhibitors and non-selective MAOIs simultaneously.
Phenobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
Phenothiazines: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of phenothiazines and selegiline due to the risk for additive CNS depression. It is also possible that dopamine antagonists, such as phenothiazines, could diminish the effectiveness of selegiline.
Phentermine: (Contraindicated) The product label for phentermine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Phentermine should generally not be used concurrently with MAOIs or within 14 days before or after their use. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Phentermine; Topiramate: (Contraindicated) The product label for phentermine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Phentermine should generally not be used concurrently with MAOIs or within 14 days before or after their use. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
Phenytoin: (Moderate) Monitor for a decrease in selegiline efficacy if coadministered with phenytoin. Although adequate studies have not been conducted, concurrent use may decrease selegiline exposure. Selegiline is a CYP3A substrate and phenytoin is a strong CYP3A inducer.
Pimozide: (Major) Due to opposing effects on central dopaminergic activity, pimozide and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to pimozide. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and pregabalin. Concurrent use may result in additive CNS depression.
Prilocaine; Epinephrine: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as epinephrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
Primidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
Procarbazine: (Major) Avoid use of these drugs together if possible. Concurrent use of selegiline and procarbazine may increase the risk of hypertensive crisis or serotonin syndrome. Procarbazine is an antineoplastic agent which exhibits weak monoamine oxidase (MAO) inhibitor activity and selegiline is a selective monoamine oxidase inhibitor (MAOI) type B. Although selegiline is a selective MAO-B inhibitor, there is a risk of hypertension or serotonin syndrome during concurrent use of other drugs with MAO inhibiting activity such as procarbazine, since the selectivity of selegiline decreases with increasing dosages. Monitoring of blood pressure is advisable if coadministration is medically necessary.
Prochlorperazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of phenothiazines and selegiline due to the risk for additive CNS depression. It is also possible that dopamine antagonists, such as phenothiazines, could diminish the effectiveness of selegiline.
Promethazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of phenothiazines and selegiline due to the risk for additive CNS depression. It is also possible that dopamine antagonists, such as phenothiazines, could diminish the effectiveness of selegiline.
Promethazine; Dextromethorphan: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of phenothiazines and selegiline due to the risk for additive CNS depression. It is also possible that dopamine antagonists, such as phenothiazines, could diminish the effectiveness of selegiline.
Promethazine; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of phenothiazines and selegiline due to the risk for additive CNS depression. It is also possible that dopamine antagonists, such as phenothiazines, could diminish the effectiveness of selegiline.
Propofol: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
Protriptyline: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics.
Pseudoephedrine; Triprolidine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. Uncontrolled hypertension has been reported when taking the recommended dose of oral selegiline and a sympathomimetic medication. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and triprolidine. Concurrent use may result in additive CNS depression.
Quazepam: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Quetiapine: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Racepinephrine: (Contraindicated) The product label for racepinephrine contraindicates use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Racepinephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
Ramelteon: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and ramelteon. Concurrent use may result in additive CNS depression.
Rasagiline: (Contraindicated) Both rasagiline and selegiline are selective monoamine oxidase type B inhibitors (MAO-B inhibitors), and concurrent use is contraindicated. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with rasagiline. After stopping treatment with rasagiline, a time period equal to 4 to 5 half-lives of rasagiline or any active metabolite should elapse before starting therapy with selegiline. Hypertensive crisis has occurred in patients receiving selective MAO-B inhibitors simultaneously. Concurrent use may also represent duplicative therapy.
Remifentanil: (Major) Avoid concomitant use of remifentanil in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
Remimazolam: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Rifampin: (Moderate) Use caution if selegiline and rifampin are used concomitantly. Although rifampin is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
Rifapentine: (Moderate) Use caution if selegiline and rifapentine are used concomitantly. Although rifapentine is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
Risperidone: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Rizatriptan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant rizatriptan and selegiline use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Safinamide: (Contraindicated) Both safinamide and selegiline are selective monoamine oxidase type B inhibitors (MAO-B inhibitors), and concurrent use is contraindicated. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with safinamide. After stopping treatment with safinamide, a time period equal to 4 to 5 half-lives of safinamide or any active metabolite should elapse before starting therapy with selegiline. Hypertensive crisis has occurred in patients receiving selective MAO-B inhibitors simultaneously. Concurrent use may also represent duplicative therapy.
Secobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) Consider a selegiline dose reduction to minimize the risk for selegiline-related adverse reactions during concomitant ethinyl estradiol use. Concomitant use may increase selegiline exposure.
Selective norepinephrine reuptake inhibitors: (Contraindicated) Selective norepinephrine reuptake inhibitors are contraindicated for use with selegiline because of a possible increased risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a selective norepinephrine reuptake inhibitor. After stopping treatment with the reuptake inhibitor, a time period equal to 4 to 5 half-lives of the reuptake inhibitor or any active metabolite should elapse before starting therapy with selegiline.
Selective serotonin reuptake inhibitors: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. 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 selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
Serdexmethylphenidate; Dexmethylphenidate: (Contraindicated) The product labels for methylphenidate and its derivatives contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis. Methylphenidate derivatives should not be used concurrently with selegiline or within 14 days before or after selegiline use.
Serotonin norepinephrine reuptake inhibitors: (Contraindicated) Serotonin norepinephrine reuptake inhibitors (SNRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SNRI. After stopping treatment with an SNRI, a time period equal to 4 to 5 half-lives of the SNRI or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
Serotonin-Receptor Antagonists: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant selegiline and serotonin-receptor antagonist use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Sertraline: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. 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 selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
Sevoflurane: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
Sodium Oxybate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and sodium oxybate. Concurrent use may result in additive CNS depression.
Solriamfetol: (Contraindicated) The concurrent use of noradrenergic drugs, such as solriamfetol, and monoamine oxidase inhibitors (MAOIs), such as selegiline, or use of solriamfetol within 14 days of MAOI therapy is contraindicated due to the increased risk for hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure.
St. John's Wort, Hypericum perforatum: (Contraindicated) Concomitant use of selegiline and St. John's wort is contraindicated due to the risk of serotonin syndrome.
Sufentanil: (Major) Avoid concomitant use of sufentanil in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
Sumatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sumatriptan with transdermal selegiline, orally disintegrating selegiline tablets, and high doses of oral selegiline capsules and tablets. Since selegiline oral tablets and capsules selectively inhibit MAO-B at recommended doses, no interaction with sumatriptan would be expected with normal prescription use. However, MAO-B selectivity decreases with increasing doses, therefore, an interaction may occur with high dose treatment. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue sumatriptan and selegiline and initiate symptomatic treatment if serotonin syndrome occurs.
Sumatriptan; Naproxen: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sumatriptan with transdermal selegiline, orally disintegrating selegiline tablets, and high doses of oral selegiline capsules and tablets. Since selegiline oral tablets and capsules selectively inhibit MAO-B at recommended doses, no interaction with sumatriptan would be expected with normal prescription use. However, MAO-B selectivity decreases with increasing doses, therefore, an interaction may occur with high dose treatment. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue sumatriptan and selegiline and initiate symptomatic treatment if serotonin syndrome occurs.
Suvorexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of suvorexant and selegiline. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants.
Tapentadol: (Contraindicated) Tapentadol use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs), such as selegiline, within the previous 14 days. Concomitant use may result in serious adverse effects including serotonin syndrome, additive CNS depression, or hypotension.
Tedizolid: (Major) Avoid concomitant use of selegiline and tedizolid. Although interactions with monamine oxidase inhibitors (MAOIs) were not evaluated in clinical trials, caution is warranted with the concurrent use of tedizolid and MAOIs due to the potential risk of severe hypertensive crisis and possibly serotonin syndrome. Consider if another antibiotic would be appropriate for the patient. Tedizolid is an oxazolidinone-class antibacterial that is also a weak reversible, non-selective inhibitor of MAO. Serotonin syndrome has been reported when another oxazolidinone-class antibacterial has been administered with certain serotonergic agents.
Temazepam: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Tetrabenazine: (Contraindicated) Tetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy, such as selegiline, within the past 14 days. The major metabolites of tetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
Tetrahydrozoline: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and tetrahydrozoline. Although tetrahydrozoline is only used by ophthalmic and nasal routes, the use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued immediately and therapy to lower blood pressure should be instituted immediately.
Thioridazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of phenothiazines and selegiline due to the risk for additive CNS depression. It is also possible that dopamine antagonists, such as phenothiazines, could diminish the effectiveness of selegiline.
Thiothixene: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Tramadol: (Contraindicated) Tramadol use is contraindicated in patients who are receiving or who have received selegiline within the previous 14 days. Concomitant use increases the risk for seizures, serotonin syndrome, and opioid toxicity, including respiratory depression.
Tramadol; Acetaminophen: (Contraindicated) Tramadol use is contraindicated in patients who are receiving or who have received selegiline within the previous 14 days. Concomitant use increases the risk for seizures, serotonin syndrome, and opioid toxicity, including respiratory depression.
Tranylcypromine: (Contraindicated) Non-selective monoamine oxidase inhibitors (MAOIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk for hypertensive crisis and a potential risk for serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an MAOI. After stopping treatment with an MAOI, a time period equal to 4 to 5 half-lives of the MAOI or any active metabolite should elapse before starting therapy with selegiline. Hypertensive crisis has occurred in patients receiving selective MAO-B inhibitors and non-selective MAOIs simultaneously.
Trazodone: (Contraindicated) Trazodone is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with trazodone. After stopping treatment with trazodone, a time period of at least 14 days should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonergic antidepressants simultaneously.
Triazolam: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of benzodiazepines and selegiline due to the risk for additive CNS depression.
Tricyclic antidepressants: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
Trifluoperazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of phenothiazines and selegiline due to the risk for additive CNS depression. It is also possible that dopamine antagonists, such as phenothiazines, could diminish the effectiveness of selegiline.
Trimipramine: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
Triprolidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and triprolidine. Concurrent use may result in additive CNS depression.
Tryptophan, 5-Hydroxytryptophan: (Major) Avoid use together if possible. The combination of tryptophan supplements and selegiline may lead to increased levels of serotonin and serotonin syndrome. Tryptophan is a serotonin precursor. Selegiline is a MAO-B inhibitor. In the postmarketing period, potentially life-threatening serotonin syndrome has been reported in patients treated with selected serotonergic agents concomitantly with selegiline. There are also reports of tryptophan and MAO inhibitor interactions in the literature.
Valbenazine: (Major) Avoid the use of valbenazine with monoamine oxidase inhibitors (MAOIs), including selegiline. Concomitant use of valbenazine with MAO inhibitors, including selegiline, may result in an increased concentration of monoamine neurotransmitters in synapses, potentially leading to an increased risk of adverse reactions such as serotonin syndrome or an attenuated treatment effect of valbenazine.
Valerian, Valeriana officinalis: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and valerian. Concurrent use may result in additive CNS depression.
Valproic Acid, Divalproex Sodium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and valproic acid. Concurrent use may result in additive CNS depression.
Venlafaxine: (Contraindicated) Serotonin norepinephrine reuptake inhibitors (SNRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SNRI. After stopping treatment with an SNRI, a time period equal to 4 to 5 half-lives of the SNRI or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
Vilazodone: (Contraindicated) Vilazodone is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with vilazodone. After stopping treatment with vilazodone, a time period equal to 4 to 5 half-lives of vilazodone or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonergic antidepressants simultaneously.
Viloxazine: (Contraindicated) Selective norepinephrine reuptake inhibitors are contraindicated for use with selegiline because of a possible increased risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a selective norepinephrine reuptake inhibitor. After stopping treatment with the reuptake inhibitor, a time period equal to 4 to 5 half-lives of the reuptake inhibitor or any active metabolite should elapse before starting therapy with selegiline.
Vortioxetine: (Contraindicated) Vortioxetine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with vortioxetine. After stopping treatment with vortioxetine, a time period equal to 4 to 5 half-lives of vortioxetine or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonergic antidepressants simultaneously.
Zaleplon: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline with anxiolytics, sedatives, and hypnotics. Concurrent use may result in additive CNS depression.
Ziprasidone: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Zolmitriptan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant selegiline and zolmitriptan use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Zolpidem: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline with anxiolytics, sedatives, and hypnotics. Concurrent use may result in additive CNS depression.
Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm.
Selegiline is an irreversible inhibitor of the monoamine oxidase (MAO) enzyme system. MAO exists as 2 catabolic isoenzymes, MAO-A and MAO-B. The neurotransmitters serotonin and norepinephrine are primarily catabolized by MAO-A and dopamine is primarily catabolized by MAO-B. In addition to their role in the catabolism of monoamines in the CNS, MAOs are also important in the catabolism of exogenous amines found in a variety of foods and drugs. MAO in the gastrointestinal tract is primarily type A, and provides protection from systemic absorption of exogenous amines with vasopressor actions, such as tyramine, which can cause hypertensive crisis if absorbed intact. Selegiline is considered a selective MAO-B inhibitor, although selectivity decreases as the dose increases. Restrictions on intake of dietary tyramine during selegiline administration vary according to formulation and dose. Two of the metabolites, amphetamine and methamphetamine, may interfere with neuronal uptake and enhance the release of some neurotransmitters (e.g., norepinephrine, dopamine, serotonin). However, the extent to which these metabolites contribute to the therapeutic effects of selegiline is unknown. Selegiline has demonstrated affinity at the adrenergic alpha 2B receptor. No affinity has been noted at dopamine receptors, adrenergic B3, glutamate, muscarinic, nicotinic, or rolapram receptor/sites.
-Transdermal selegiline: The mechanism of action of transdermal selegiline as an antidepressant is thought to occur from potentiation of monoamine neurotransmitters (e.g., dopamine, serotonin, norepinephrine) in the CNS resulting from its inhibition of MAO-A and MAO-B. When administered in a transdermal patch, targeted inhibition of MAO-A and MAO-B in the CNS is seen. In vitro studies have shown that transdermal selegiline exhibits antidepressant properties only at doses that inhibit both MAO-A and MAO-B activity in brain. Intestinal MAO is predominantly type A, while in the brain both isoenzymes exist. Clinical trials of transdermal selegiline demonstrated a preservation of MAO-A in the intestinal mucosa and liver, allowing for the breakdown of dietary tyramine and the prevention of gastric absorption of dietary tyramine only at a selegiline dose of 6 mg/24 hour. Higher therapeutic doses (i.e., 9 mg/24 hours and 12 mg/24 hours) must be used with tyramine diet restrictions. Effects resulting from transdermal selegiline administration may also occur through its metabolites. However, transdermal dosing results in significantly higher exposure to selegiline with significantly lower exposure for all metabolites relative to oral administration.
-Oral selegiline: At doses used in Parkinson's disease, selegiline typically exhibits a greater affinity for MAO-B. At higher doses, MAO is blocked non-selectively, predisposing patients to the risks (e.g., hypertensive crisis) of traditional MAOIs (e.g., phenelzine) that block both MAO-B and MOA-A. Therefore, the dose limits established for specific oral selegiline products should not be exceeded. An increase in tyramine sensitivity for blood pressure responses appears to begin at a dose of 5 mg/day of selegiline orally disintegrating tablets (ODT); however, the precise dose at which selegiline ODT becomes a non-selective inhibitor of all MAO enzymes in individual patients is unknown. Oral selegiline tablets can ordinarily be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day); however, it should be noted that a few cases of hypertensive reactions have been reported at the recommended dose.
Selegiline is available as an oral tablet, oral capsule, orally disintegrating tablet (ODT), and transdermal patch. Approximately 85% to 90% of plasma selegiline is reversibly bound to plasma proteins. Selegiline rapidly penetrates the blood-brain barrier. Although platelet MAO-B activity returns to the normal range within 5 to 7 days of discontinuation of oral selegiline, the link between platelet and brain MAO-B inhibition is not fully understood nor is the relationship of MAO-B inhibition to the clinical effect. Selegiline is extensively metabolized to N-desmethylselegiline and L-methamphetamine. Both of these metabolites may subsequently be converted to L-amphetamine. The metabolites are further converted to their hydroxymetabolites. Transdermal dosing results in significantly higher exposure to selegiline with significantly lower exposure for all metabolites when compared to oral dosing. In a kinetic evaluation, approximately 10% of a radiolabeled transdermal dose was recovered in the urine and 2% recovered in feces, with at least 63% of the dose unabsorbed. The remaining 25% of the transdermal dose was unaccounted for. Selegiline ODT produces a smaller fraction of the administered dose recoverable as the metabolites than the conventional, swallowed formulation of selegiline. Following a single oral or ODT dose, the mean elimination half-life of selegiline was 1.3 to 2 hours. At steady-state, the elimination half-life increased to 10 hours. After IV administration, the half-lives of selegiline and its 3 metabolites (N-desmethylselegiline, L-amphetamine, and L-methamphetamine) ranged from 18 to 25 hours. Following hepatic metabolism, selegiline is excreted primarily in the urine as metabolites (mainly as L-methamphetamine and L-amphetamine) and as a small amount in the feces.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4, CYP3A5, CYP2B6, CYP2A6, CYP2D6, CYP2C9
Selegiline is a substrate for CYP2B6, CYP2C9 and CYP3A4/5. In vitro studies indicate that CYP2B6, CYP2C9, CYP3A4 and CYP3A5 appear to be the major isoenzymes involved in the formation of L-methamphetamine from selegiline, with CYP2A6 having a minor role. CYP2A6, CYP2B6, CYP3A4, and CYP3A5 appear to contribute to the formation of L-amphetamine from N-desmethylselegiline. A potent CYP3A inhibitor, itraconazole, had no effect on the pharmacokinetics of selegiline (single 10 mg oral, swallowed dose). Although adequate studies to investigate the effect of CYP3A4-inducers on selegiline have not been performed, drugs that induce CYP3A4 (e.g., phenytoin, carbamazepine, nafcillin, phenobarbital, and rifampin) should be used with caution.
In vitro studies have demonstrated that selegiline is not an inhibitor of CYP450 enzymes. Selegiline shows competitive inhibitory action at CYP2D6, CYP3A4/5, CYP2C19, and CYP2B6. However, all inhibitory effects of selegiline occur at concentrations that are several orders of magnitude higher than concentrations seen clinically. Selegiline and two of its metabolites, methamphetamine and desmethylselegiline, have little or no potential to induce CYP1A2 and CYP3A4/5 under clinical conditions.
-Route-Specific Pharmacokinetics
Oral Route
-Oral Tablet or Capsule: Following administration of the tablet or capsule dosage form, selegiline is readily absorbed from the GI tract and crosses the blood/brain barrier; however, the absolute bioavailability is unknown. The extent of systemic exposure to selegiline at a given dose varies significantly among individuals. Peak serum concentrations are found in 0.5 to 2 hours. Mean maximum plasma concentrations of 1.12 ng/mL are reached for the oral 5 mg selegiline tablets (given as 5 mg PO twice daily). The bioavailability of selegiline is increased 3 to 4 fold when it is taken with food. The peak plasma levels of the 3 metabolites (N-desmethylselegiline, L-amphetamine and L-methamphetamine) following a single oral dose of 10 mg are from 4 to almost 20 times greater than that of the maximum plasma concentration (Cmax) of selegiline. The maximum concentrations of amphetamine and methamphetamine, however, are far below those ordinarily expected to produce clinically important effects. The duration of action of selegiline depends on the time required to regenerate MAO type B. Like phenelzine, the effects of selegiline are cumulative, with beneficial effects seen in a few days to several months depending on the condition being treated and individual response.
-Orally Disintegrating Tablet (ODT): Following administration of the orally disintegrating tablet, disintegration and absorption occur rapidly. Detectable levels of selegiline from selegiline ODT have been measured 5 minutes after administration. Selegiline ODT is more rapidly absorbed (time to maximal concentration or Tmax range 10 to 15 minutes) than from the swallowed 5 mg selegiline tablet (Tmax range 40 to 90 minutes). When selegiline ODT is taken with food, the Cmax and AUC of selegiline are about 60% of those seen when selegiline ODT is taken in the fasted state. Since selegiline ODT is placed on the tongue and absorbed through the oral mucosa, the intake of food and liquid should be avoided 5 minutes before and after administration. The pre-gastric absorption from selegiline ODT and the avoidance of first-pass metabolism results in higher concentrations of selegiline and lower concentrations of the metabolites compared to the 5 mg swallowed tablet. Mean maximum plasma concentrations of 3.34 and 4.47 ng/mL are reached after single dose of 1.25 and 2.5 mg selegiline ODT, respectively, compared to 1.12 ng/mL for the swallowed 5 mg selegiline tablets (given as 5 mg bid). Plasma Cmax and AUC of selegiline ODT are dose proportional. Steady state is achieved after 8 days. Following a single dose, the median elimination half-life is 1.3 hours at the 1.25 mg dose. Under steady-state conditions, the median elimination half-life increases to 10 hours. Selegiline ODT produces a smaller fraction of the administered dose recoverable as the metabolites than the conventional swallowed formulation of selegiline.
Other Route(s)
Transdermal Route
With transdermal application, roughly 25 to 30% (range: 10% to 40%) of the selegiline content is delivered systemically over a 24-hour period. The degree of drug absorption may variably be one-third higher than the average amounts of transdermal doses of 6 mg/24 hours to 12 mg/24 hours. Transdermal administration avoids first-pass metabolism and results in much higher bioavailability compared to the oral dose form (74% vs. 4%). Additionally, substantially lower metabolite (L-desmethylselegiline, L-amphetamine, L-methamphetamine) concentrations are seen, compared to oral dosing. Steady-state plasma concentrations are achieved within 5 days. Transdermal selegiline does not accumulate in and is not metabolized in the skin and does not undergo extensive first-pass metabolism. In one study, steady-state selegiline plasma concentrations indicated selegiline concentration-time profiles were comparable when transdermal selegiline is applied to the upper torso or upper thigh, and absorption from these two sites of administration was equivalent.
-Special Populations
Hepatic Impairment
Pharmacokinetic changes in transdermal selegiline have not been noted in patients with mild to moderate hepatic impairment. No pharmacokinetic data are available for oral selegiline or its metabolites in hepatically impaired subjects. In subjects with mild hepatic impairment (Child-Pugh score 5 to 6) receiving selegiline orally disintegrating tablets (ODT) 2.5 mg/day at steady-state, the AUC (exposure) and Cmax (maximal concentration) of selegiline were 1.5-fold higher and the AUC and Cmax of the metabolite desmethylselegiline were 1.4-fold and 1.2-fold higher. In subjects with moderate hepatic impairment (Child-Pugh score 7 to 9), the AUC of selegiline ODT and desmethylselegiline increased 1.5-fold and 1.8-fold, respectively, while the Cmax of selegiline and desmethylselegiline were comparable to healthy subjects. Patients with severe hepatic impairment (Child-Pugh score greater than 9) had a 4-fold increase in the AUC of selegiline, 3-fold increase in the Cmax of selegiline, a 1.25-fold increase in AUC of desmethylselegiline and 50% reduced Cmax of desmethylselegiline. Methamphetamine and amphetamine metabolite AUC values were not affected by liver dysfunction.
Renal Impairment
Pharmacokinetic changes in transdermal selegiline have not been noted in patients with any degree of renal impairment. No pharmacokinetic information is available on oral selegiline or its metabolites in renally impaired subjects. Following steady-state dosing of selegiline orally disintegrating tablets (ODT) 2.5 mg/day in 6 subjects with mild renal impairment (CrCl greater than 50 and up to 89 mL/minute) and in 6 subjects with moderate renal impairment (CrCl greater than 30 up to 50 mL/minute), the AUC and Cmax of selegiline and desmethylselegiline were not significantly different from healthy subjects; however, methamphetamine and amphetamine exposures were increased by 34% to 67% in subjects with moderate renal impairment. Following steady-state dosing of selegiline ODT 1.25 mg/day in end-stage renal disease patients not receiving dialysis (n = 6), selegiline exposure was not significantly different from that in healthy subjects, however methamphetamine and amphetamine exposures were increased approximately 4-fold compared to healthy subjects.
Pediatrics
Limited pharmacokinetic data with transdermal selegiline doses lower than in the commercially available formulations suggest that children less than 12 years of age may experience increased levels of selegiline compared to adolescents and adults. Subsequently, the risk of hypertensive crisis may be increased, even at the lowest recommended dose. Transdermal selegiline is contraindicated in children less than 12 years of age and is not recommended in pediatric patients 12 to 17 years of age.
Geriatric
After administration of a single oral 10 mg dose of selegiline to 12 subjects greater than 60 years of age and 12 subjects between the ages of 18 to 30, systemic exposure was about twice as great in the older subjects compared to the younger subjects; however, the sample size was too small to be conclusive about the effects of age on the pharmacokinetics of selegiline. The effect of age on the pharmacokinetics of selegiline orally disintegrating tablets has not been adequately characterized. The effect of age on the pharmacokinetics of transdermal selegiline has not been adequately studied.
Gender Differences
Females have an approximate 25% decrease in Cmax of selegiline orally disintegrating tablets compared to males. However, since the overall exposure is not different, this pharmacokinetic difference is not likely to be clinically relevant. No information is available on the effects of gender on the pharmacokinetics of oral selegiline tablets or capsules. No gender differences have been observed in the pharmacokinetics or metabolism of transdermal selegiline; therefore, no dosage adjustment of this formulation is needed based on gender.
Ethnic Differences
No studies have been conducted to evaluate the effects of race on the pharmacokinetics of selegiline orally disintegrating tablets. No information is available for the transdermal patches or the selegiline tablets or capsules with regard to race.